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Sample records for postoperative tamoxifen 5-year

  1. Late tamoxifen in patients previously operated for breast cancer without postoperative tamoxifen: 5-year results of a single institution randomised study

    International Nuclear Information System (INIS)

    Veronesi, Andrea; Miolo, GianMaria; Magri, Maria D; Crivellari, Diana; Scalone, Simona; Bidoli, Ettore; Lombardi, Davide

    2010-01-01

    A population of breast cancer patients exists who, for various reasons, never received adjuvant post-operative tamoxifen (TAM). This study was aimed to evaluate the role of late TAM in these patients. From 1997 to 2003, patients aged 35 to 75 years, operated more than 2 years previously for monolateral breast cancer without adjuvant TAM, with no signs of metastases and no contraindication to TAM were randomized to TAM 20 mg/day orally for 2 years or follow-up alone. Events were categorized as locoregional relapse, distant metastases, metachronous breast cancer, tumours other than breast cancer and death from any causes, whichever occurred first. The sample size (197 patients per arm, plus 10% allowance) was based on the assumption of a 30% decrease in the number of events occurring at a rate of 5% annually in the 10 years following randomization. Four hundred and thirty-three patients were randomized in the study (TAM 217, follow-up 216). Patients characteristics (TAM/follow-up) included: median age 55/55 years, median time from surgery 25/25 months (range, 25-288/25-294), in situ carcinoma 18/24, oestrogen receptor (ER) positive in 75/68, negative in 70/57, unknown in 72/91 patients. Previous adjuvant treatment included chemotherapy in 131/120 and an LHRH analogue in 11/13 patients. Thirty-six patients prematurely discontinued TAM after a median of 1 month, mostly because of subjective intolerance. Eighty-three events (TAM 39, follow-up 44) occurred: locoregional relapse in 10/8, distant metastases in 14/16, metachronous breast cancer in 4/10, other tumours in 11/10 patients. Less ER-positive secondary breast cancers occurred in the TAM treated patients than in follow-up patients (1 vs 10, p = 0.005). Event-free survival was similar in both groups of patients. This 5-year analysis revealed significantly less metachronous ER-positive breast cancers in the TAM treated patients. No other statistically significant differences have emerged thus far

  2. Feature of amenorrhea in postoperative tamoxifen users with breast cancer.

    Science.gov (United States)

    Kim, Hoon; Han, Wonshik; Ku, Seung Yup; Suh, Chang Suk; Kim, Seok Hyun; Choi, Young Min

    2017-03-01

    Tamoxifen has been used to prevent the recurrence of breast cancer. However, tamoxifen-users frequently experience amenorrhea and it can be confused from that caused by other hormonal abnormalities. In amenorrheic patients without breast cancer, clinicians usually measure the sex hormone levels that are known to be associated with ovarian or menstrual function. This study aimed to investigate the feature of female sex hormones in premenopausal breast cancer patients undergoing tamoxifen treatment. The medical records of fifty-nine premenopausal breast cancer patients who underwent tamoxifen treatment were reviewed retrospectively. The study population consisted of amenorrheic patients (n=36) and patients with menstruation (n=23). Serum hormone levels were measured either specifically between cycle days 2 and 5 in menstruating patients or at any time in amenorrheic participants. Serum levels of lutenizing hormone and estradiol were not statistically different according to the presence of menstruation. Serum follicle stimulating hormone level was significantly higher in amenorrheic patients (8.1±5.7 mIU/mL) than those in menstruating subjects (5.1±2.2 mIU/mL) (p=0.01). Serum concentration of thyroid stimulating hormone was lower in patients with amenorrhea (1.5±0.9 vs. 2.3±2.2 μIU/mL, p=0.04), although the prevalence of hypo- or hyperthyroidism was not different according to the pattern of menstruation. Menstruation status and hormone levels can be influenced by tamoxifen use in reproductive age breast cancer patients. Physicians should be attentive to the alteration of pituitary hormone levels in addition to sex steroid hormones in this population. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

  3. Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial

    DEFF Research Database (Denmark)

    Rabaglio, M; Sun, Z; Price, K N

    2009-01-01

    of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated......BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years...... with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone...

  4. Post-operative delirium is associated with increased 5-year mortality.

    Science.gov (United States)

    Moskowitz, Eliza E; Overbey, Douglas M; Jones, Teresa S; Jones, Edward L; Arcomano, Todd R; Moore, John T; Robinson, Thomas N

    2017-12-01

    Post-operative delirium is associated with increased short term morbidity and mortality. Limited data exists on long term outcomes for older adults with postoperative delirium. We hypothesize that postoperative delirium is associated with increased 5-year mortality. Patients ≥50 years undergoing elective operations with planned intensive care unit (ICU) admissions were prospectively enrolled. The Confusion Assessment Method ICU (CAM-ICU) was used to diagnose delirium. The primary outcome variable was 5-year mortality. 172 patients were enrolled with an average age of 64 years. The overall incidence of delirium was 44% (75/172). At 5-years post-operatively, mortality was higher (59%, 41/70) in patients with delirium compared to patients without delirium (13%, 12/94, p delirium were 7.35 fold greater (95% CI: 1.49-36.18). Postoperative delirium is associated with increased long term mortality. Published by Elsevier Inc.

  5. 5-year follow-up of a randomized controlled trial of immediate versus delayed zoledronic acid for the prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen: N03CC (Alliance) trial.

    Science.gov (United States)

    Wagner-Johnston, Nina D; Sloan, Jeff A; Liu, Heshan; Kearns, Ann E; Hines, Stephanie L; Puttabasavaiah, Suneetha; Dakhil, Shaker R; Lafky, Jacqueline M; Perez, Edith A; Loprinzi, Charles L

    2015-08-01

    Postmenopausal women with breast cancer receiving aromatase inhibitors are at an increased risk of bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report described the 5-year follow-up results. A total of 551 postmenopausal women with breast cancer who completed tamoxifen treatment and were undergoing daily letrozole treatment were randomized to either upfront (274 patients) or delayed (277 patients) ZA at a dose of 4 mg intravenously every 6 months. In the patients on the delayed treatment arm, ZA was initiated for a postbaseline bone mineral density T-score of prevented bone loss compared with delayed treatment in postmenopausal women receiving letrozole and these differences were maintained at 5 years. The incidence of osteoporosis or fractures was not found to be significantly different between treatment arms. © 2015 American Cancer Society.

  6. Long-term outcomes following laparoscopic adjustable gastric banding: postoperative psychological sequelae predict outcome at 5-year follow-up.

    Science.gov (United States)

    Scholtz, Samantha; Bidlake, Louise; Morgan, John; Fiennes, Alberic; El-Etar, Ashraf; Lacey, John Hubert; McCluskey, Sara

    2007-09-01

    NICE guidelines state that patients with psychological contra-indications should not be considered for bariatric surgery, including Laparoscopic Adjustable Gastric Banding (LAGB) surgery as treatment of morbid obesity, although no consistent correlation between psychiatric illness and long-term outcome in LAGB has been established. This is to our knowledge the first study to evaluate long-term outcomes in LAGB for a full range of DSM-IV defined psychiatric and eating disorders, and forms part of a research portfolio developed by the authors aimed at defining psychological predictors of bariatric surgery in the short-, medium- and long-term. Case notes of 37 subjects operated on between April 1997 and June 2000, who had undergone structured clinical interview during pre-surgical assessment to yield diagnoses of mental and eating disorders according to DSM-IV criteria were analyzed according to a set of operationally defined criteria. Statistical analysis was carried out to compare those with a poor outcome and those considered to have a good outcome in terms of psychiatric profile. In this group of mainly female, Caucasian subjects, ranging in age from 27 to 60 years, one-third were diagnosed with a mental disorder according to DSM-IV criteria. The development of postoperative DSM-IV defined binge eating disorder (BED) or depression strongly predicted poor surgical outcome, but pre-surgical psychiatric factors alone did not. Although pre-surgical psychiatric assessment alone cannot predict outcome, an absence of preoperative psychiatric illness should not reassure surgeons who should be mindful of postoperative psychiatric sequelae, particularly BED. The importance of providing an integrated biopsychosocial model of care in bariatric teams is highlighted.

  7. Persistent tumor-induced osteomalacia confirmed by elevated postoperative levels of serum fibroblast growth factor-23 and 5-year follow-up of bone density changes.

    Science.gov (United States)

    Zimering, Mark B; Caldarella, Felice A; White, Kenneth E; Econs, Michael J

    2005-01-01

    To describe a case of persistent tumor-induced osteomalacia, determine whether serum fibroblast growth factor-23 (FGF-23) levels postoperatively indicate incomplete tumor resection, and report lumbar spine and forearm bone mineral density (BMD) changes during 5 years of follow-up. We present clinical, radiologic, histologic, and bone densitometry data as well as serum FGF-23 levels (determined with use of a novel C-terminal enzyme-linked immunosorbent assay) from the study patient and discuss these findings in the context of previous literature. A 52-year-old man, who presented with muscle weakness and multiple fractures, was found to have low values for serum phosphorus, serum 1,25-dihydroxyvitamin D, and maximal tubular reabsorption of phosphate per glomerular filtration rate, a high level of serum alkaline phosphatase, and a normal serum concentration of parathyroid hormone, characteristic of tumor-induced osteomalacia. Magnetic resonance imaging to evaluate an abnormality of the left foot revealed a soft tissue mass, biopsy of which confirmed the presence of a benign, phosphaturic, mesenchymal tumor. The baseline serum FGF-23 level (2,050 RU/mL) was more than 17 times the upper limit of normal for adults (23 to 118 RU/mL) and decreased substantially within 1 day after partial resection of the tumor but remained above normal postoperatively. BMD changes indicated rapid substantial recovery of vertebral BMD but ongoing loss of forearm bone density. The serum FGF-23 level is high in a substantial proportion of patients with tumor-induced osteomalacia. The postoperative above normal levels of serum FGF-23 correlated with known persistence of tumor in our study patient. In a patient with normal renal function, such as our study patient, levels of serum FGF-23 studied with use of the C-terminal enzyme-linked immunosorbent assay reached their nadir within 24 hours postoperatively. This result suggests that this assay can provide clinicians with rapid prognostic

  8. Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor-Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14.

    Science.gov (United States)

    Wolmark, Norman; Mamounas, Eleftherios P; Baehner, Frederick L; Butler, Steven M; Tang, Gong; Jamshidian, Farid; Sing, Amy P; Shak, Steven; Paik, Soonmyung

    2016-07-10

    We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1-expressing groups. RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) -positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low ( 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis. © 2016 by American Society of Clinical Oncology.

  9. Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor–Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14

    Science.gov (United States)

    Wolmark, Norman; Baehner, Frederick L.; Butler, Steven M.; Tang, Gong; Jamshidian, Farid; Sing, Amy P.; Shak, Steven; Paik, Soonmyung

    2016-01-01

    Purpose We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1–expressing groups. Patients and Methods RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) –positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Results Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low ( 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). Conclusion For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis. PMID:27217450

  10. Tamoxifen- Induced Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Bandyopadhyay Debabrata

    1997-01-01

    Full Text Available A 38 year old woman developed dermatomyositis after radical mastectomy and tamoxifen therapy for metastatic breast carcinoma. The possibility of the drug as the underlying cause of the connective tissue disease is discussed.

  11. Fukushima, 5 years after

    International Nuclear Information System (INIS)

    Perves, Jean-Pierre; Maziere, Maurice

    2016-01-01

    This publication proposes an overview of the situation in Fukushima (in the plant and in its region), 5 years after the accident. As far as the plant is concerned, several issues are addressed: the withdrawal of fuel from decay pools, the management of contaminated waters, and the situation of reactors 1, 2 and 3. The radiological impact for operators is discussed in terms of radioactivity level, of occurrence of leukaemia, and of storage of radioactive wastes. The next part comments the slow return of populations and the recovery of agriculture, notably with respect to decontamination advances, and to waste management. Current perspectives for the Japanese nuclear industry are then addressed: creation of a new and stronger safety authority, and situation of the various other reactors (some are planned to be restarted, some will be dismantled, and new reactors are still being built). The last part addresses the rehabilitation of areas devastated by the tsunami, with temporary housing, urban planning comprising possibilities for the population to quickly find a shelter, and works on the coast for a better protection against tsunamis

  12. Tamoxifen and ovarian function.

    Directory of Open Access Journals (Sweden)

    Martine Berliere

    Full Text Available BACKGROUND: Some studies suggest that the clinical parameter "amenorrhea" is insufficient to define the menopausal status of women treated with chemotherapy or tamoxifen. In this study, we investigated and compared the ovarian function defined either by clinical or biological parameters in pre-menopausal breast cancer patients treated with tamoxifen administered as adjuvant therapy. MATERIALS AND METHODS: Between 1999 and 2003, 138 premenopausal patients consecutively treated for early breast cancer were included. Sixty-eight received tamoxifen in monotherapy as the only adjuvant systemic treatment (Group I and 70 were treated with tamoxifen after adjuvant chemotherapy (Group II. All patients had a confirmed premenopausal status based on clinical parameters and hormonal values at study entry. They were followed prospectively every 3 months for 3 years: menses data, physical examination and blood tests (LH, FSH, 17-beta-estradiol. Vaginal ultrasonography was carried out every 6 months. After 3 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in our institution (1x/year. All data were retrospectively evaluated in 2011. RESULTS: Three patients were excluded from the study in group I and 2 were excluded in group II. Patients were divided into 4 subgroups according to clinical data, i.e. menses patterns. These patterns were assessed by questionnaires. a: Regular menses (>10 cycles/year b: Oligomenorrhea (5 to 9 cycles/year c: Severe oligomenorrhea (1 to 4 cycles/year d: Complete amenorrhea Estrogen levels did not appear to have any impact on disease-free survival rates after 3 or 8 years. FSH values were also documented and analyzed. They exhibited the same profile as estradiol values. CONCLUSIONS: Amenorrhea is an insufficient parameter to define menopausal status in patients receiving tamoxifen. Low estradiol levels must be coupled with other biological parameters to characterize endocrine status

  13. Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic.

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    Donnelly, L S; Evans, D G; Wiseman, J; Fox, J; Greenhalgh, R; Affen, J; Juraskova, I; Stavrinos, P; Dawe, S; Cuzick, J; Howell, A

    2014-04-02

    Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews. All eligible women between 33 and 46 years at ≥17% lifetime risk of breast cancer and undergoing annual mammography in our service were invited to take a 5-year course of tamoxifen. Reasons for accepting (n=15) or declining (n=15) were explored using semi-structured interviews. Of 1279 eligible women, 136 (10.6%) decided to take tamoxifen. Women >40 years (74 out of 553 (13.4%)) and those at higher non-BRCA-associated risk were more likely to accept tamoxifen (129 out of 1109 (11.6%)). Interviews highlighted four themes surrounding decision making: perceived impact of side effects, the impact of others' experience on beliefs about tamoxifen, tamoxifen as a 'cancer drug', and daily reminder of cancer risk. Tamoxifen uptake was similar to previously ascertained uptake in a randomised controlled trial (IBIS-I). Concerns were similar in women who did or did not accept tamoxifen. Decision making appeared to be embedded in the experience of significant others.

  14. The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor-positive early-stage breast cancer

    International Nuclear Information System (INIS)

    Fowble, Barbara; Fein, Douglas A.; Hanlon, Alexandra L.; Eisenberg, Burton L.; Hoffman, John P.; Sigurdson, Elin R.; Daly, Mary B.; Goldstein, Lori J.

    1996-01-01

    Purpose: To evaluate the impact of tamoxifen on breast recurrence, cosmesis, complications, overall and cause-specific survival in women with Stage I-II breast cancer and estrogen receptor positive tumors undergoing conservative surgery and radiation. Methods and Materials: From 1982 to 1991, 491 women with estrogen receptor positive Stage I-II breast cancer underwent excisional biopsy, axillary dissection, and radiation. The median age of the patient population was 60 years with 21% < 50 years of age. The median follow-up was 5.3 years (range 0.1 to 12.8). Sixty-nine percent had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49% and the final margin of resection was negative in 64%. One hundred fifty-four patients received tamoxifen and 337 patients received no adjuvant therapy. None of the patients received adjuvant chemotherapy. Results: There were no significant differences between the two groups for age, race, clinical tumor size, histology, the use of reexcision, or median total dose to the primary. Patients who received tamoxifen were more often axillary node positive (44% tamoxifen vs. 5% no tamoxifen), and, therefore, a greater percentage received treatment to the breast and regional nodes. The tamoxifen patients less often had unknown margins of resection (9% tamoxifen vs. 22% no tamoxifen). The 5-year actuarial breast recurrence rate was 4% for the tamoxifen patients compared to 7% for patients not receiving tamoxifen (p 0.21). Tamoxifen resulted in a modest decrease in the 5-year actuarial risk of a breast recurrence in axillary node-negative patients, in those with unknown or close margins of resection, and in those who underwent a single excision. Axillary node-positive patients had a clinically significant decrease in the 5-year actuarial breast recurrence rate (21 vs. 4%; p 0.08). The 5-year actuarial rate of distant metastasis was not significantly decreased by the addition of adjuvant tamoxifen in all

  15. Menstruation recovery after chemotherapy and luteinizing hormone-releasing hormone agonist plus tamoxifen therapy for premenopausal patients with breast cancer.

    Science.gov (United States)

    Sakurai, Kenichi; Matsuo, Sadanori; Enomoto, Katsuhisa; Amano, Sadao; Shiono, Motomi

    2011-01-01

    Little is known about the period required for menstruation recovery after long-term luteinizing hormone-releasing hormone (LH-RH) agonist plus tamoxifen therapy following chemotherapy. In this study we investigated the period required for menstruation recovery after the therapy. The subjects comprised 105 premenopausal breast cancer patients who had undergone surgery. All patients were administered an LH-RH agonist for 24 months and tamoxifen for 5 years following the postoperative adjuvant chemotherapy, and the status of menstruation recovery was examined. Menstruation resumed in 16 cases (15.2%) after the last LH-RH agonist treatment session. The mean period from the last LH-RH agonist treatment to the recovery of menstruation was 6.9 months. The rate of menstruation recovery was 35.5% in patients aged 40 years or younger and 8.0% in those aged 41 years or older, and it was significantly higher in those aged 40 years or younger. The period until menstruation recovery tended to be longer in older patients at the end of treatment. This study showed that menstruation resumed after treatment at higher rates in younger patients. However, because it is highly likely that ovarian function will be destroyed by the treatment even in young patients, it is considered necessary to explain the risk to patients and obtain informed consent before introducing this treatment modality.

  16. Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early breast cancer

    International Nuclear Information System (INIS)

    Andersson, M.; Storm, H.H.; Mouridsen, H.T.

    1991-01-01

    The incidence of new primary cancers was evaluated in 3538 postmenopausal patients who had received surgical treatment for primary breast cancer. Of these patients, 1828 with a low risk of recurrence received no further treatment. High-risk patients were randomly assigned to one of two groups. The first group (n = 846) received postoperative radiotherapy, while the second group (n = 864) received radiotherapy plus tamoxifen at a dose of 30 mg given daily for 48 weeks. The median observation time was 7.9 years. In comparison with the number of new cancers in the general population, the number of new cancers in the three groups was elevated mostly due to a high number of cancers of the contralateral breast and of colorectal cancers in the high-risk groups. The cumulative risk of nonlymphatic leukemia was increased among patients who received postoperative radiotherapy (P = .04). Cancer incidence in the high-risk tamoxifen-treated group relative to that in the high-risk group not treated with tamoxifen was not significant (1.3). No protective effect of tamoxifen on the opposite breast was seen (rate ratio for breast cancer = 1.1), but a tendency to an elevated risk of endometrial cancer was observed (rate ratio = 3.3; 95% confidence interval = 0.6-32.4). Continued and careful follow-up of women treated with tamoxifen is necessary to clarify the potential cancer-suppressive or cancer-promoting effects of this drug

  17. Phase II Trial of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in Patients With Locally Advanced Rectal Cancer: 5-Year Clinical Outcomes ECOG-ACRIN Cancer Research Group E3204.

    Science.gov (United States)

    Landry, Jerome C; Feng, Yang; Prabhu, Roshan S; Cohen, Steven J; Staley, Charles A; Whittington, Richard; Sigurdson, Elin Ruth; Nimeiri, Halla; Verma, Udit; Benson, Al Bowen

    2015-06-01

    The 5-year oncologic outcomes from the trial regimen were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy.Due to the lack of an improvement in the pathologic complete response rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. The addition of bevacizumab to chemotherapy improves overall survival for metastatic colorectal cancer. We initiated a phase II trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab for locally advanced rectal cancer. The purpose of this report is to describe the 5-year oncologic outcomes of this regimen. In a phase II Simon two-stage design study, we evaluated preoperative treatment with capecitabine (825 mg/m(2) b.i.d. Monday-Friday), oxaliplatin (50 mg/m(2) weekly), bevacizumab (5 mg/kg on days 1, 15, and 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8-12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles). The primary endpoint was a pathologic complete response (path-CR) rate of 30%. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled between 2006 and 2010. Of 57 enrolled patients, 53 were eligible and included in the analysis. Forty-eight (91%) patients completed preoperative therapy, all of whom underwent curative surgical resection. Nine patients (17%) achieved path-CR. There were 29 worst grade 3 events, 8 worst grade 4 events, and 2 patient deaths, 1 of which was attributed to study therapy. Twenty-six patients (54%) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year

  18. Compound list: tamoxifen [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available tamoxifen TMX 00054 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/tam...oxifen.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/tam...oxifen.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/tam...open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/tamoxifen.Rat.in_vivo.Liver.Repeat.zip ...

  19. Is tamoxifen associated with an increased risk for thromboembolic complications in patients undergoing microvascular breast reconstruction? [Ist die Einnahme von Tamoxifen zum Zeitpunkt der mikrovaskulären Brustrekonstruktion mit einer erhöhten Rate an thrombembolischen Komplikationen assoziiert?

    Directory of Open Access Journals (Sweden)

    Krämer, Robert

    2013-02-01

    des hormonrezeptorpen Brustkrebses postmenopausaler Frauen abgelöst. Tamoxifen ist mit einem ca. zweifach erhöhten Risiko für thrombembolische Komplikationen (tiefe Beinvenenthrombose, Lungenembolie assoziiert. Vor dem Hintergrund einer aktuellen und im Februar 2012 im Journal of Plastic and Reconstructive Surgery erschienenen retrospektiven Studie mit Nachweis einer erhöhten Komplikationsrate freier Lappentransplantate zur Brustrekonstruktion unter Tamoxifen-Einnahme haben wir unser Patientenkollektiv nach mikrochirurgischer Brustrekonstruktion retrospektiv auf Minor- und Major-Komplikationen einschließlich thrombembolischer Ereignisse insbesondere vor dem Hintergrund einer perioperativen Tamoxifeneinnahme untersucht. Eingeschlossen wurden insgesamt 29 Patientinnen nach mikrochirurgischer autologer Brustrekonstruktion. Es wurden mikrovaskuläre Lappenkomplikationen und Lappenverluste von Patientinnen ohne und mit Einnahme von Tamoxifen und Aromatasehemmern zum Zeitpunkt der mikrochirurgischen Brustrekonstruktion verglichen. 25 Patientinnen (86,2% erhielten eine DIEP-Lappenplastik und 4 (13,8% eine TRAM-Lappenplastik. Fernerhin verglichen wir die Rate allgemeiner thrombembolischer Ereignisse unter Berücksichtigung sonstiger Nebendiagnosen und Risikofaktoren. Von insgesamt 29 Patientinnen standen zum Zeitpunkt der mikrovaskulären Brustrekonstruktion 3 unter einer Aromatasehemmer-Therapie und 5 unter einer Tamoxifen-Therapie. Insgesamt traten in 11 Fällen (37,9% postoperative Komplikationen auf, in 5 Fällen handelte es sich hierbei um Major-Komplikationen (mit einem Lappenverlust und in um Minorkomplikationen. Unter Tamoxifeneinnahme kam es in einem Fall zu einer Minorkomplikation, und in einem anderen Fall zu einem thrombembolisch bedingten Lappenverlust. Insgesamt kam es postoperativ zu einem thrombembolischen Ereignis in Form einer Lungenembolie ohne Assoziation zur Tamoxifen-Therapie.Die Anzahl thrombembolischer Ereignisse stellten sich mit und ohne

  20. Preoperative psychosocial risk factors for poor outcomes at 1 and 5 years after total knee replacement.

    Science.gov (United States)

    Wylde, Vikki; Trela-Larsen, Lea; Whitehouse, Michael R; Blom, Ashley W

    2017-10-01

    Background and purpose - Psychosocial factors are important risk factors for poor outcomes in the first year after total knee replacement (TKR), however their impact on long-term outcomes is unclear. We aimed to identify preoperative psychosocial risk factors for poor outcomes at 1 year and 5 years after TKR. Patients and methods - 266 patients were recruited prior to TKR surgery. Knee pain and function were assessed preoperatively and at 1 and 5 years postoperative using the WOMAC Pain score, WOMAC Function score and American Knee Society Score (AKSS) Knee score. Preoperative depression, anxiety, catastrophizing, pain self-efficacy and social support were assessed. Statistical analyses involved multiple linear regression and mixed effect linear regression. Results - Higher anxiety was a risk factor for worse pain at 1 year postoperative. No psychosocial factors were associated with any outcomes at 5 years postoperative. Analysis of change over time found that patients with higher pain self-efficacy had lower preoperative pain and experienced less improvement in pain up to 1 year postoperative. Higher pain self-efficacy was associated with less improvement in the AKSS up to 1 year postoperative but more improvement between 1 and 5 years postoperative. Interpretation - Preoperative anxiety was found to influence pain at 1 year after TKR. However, none of the psychosocial variables were risk factors for a poor outcome at 5 years post-operative, suggesting that the negative effects of anxiety on outcome do not persist in the longer-term.

  1. The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress

    International Nuclear Information System (INIS)

    Kim, Hyun-Ah; Ahn, Sei Hyun; Nam, Seok Jin; Park, Seho; Ro, Jungsil

    2016-01-01

    Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy

  2. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial

    DEFF Research Database (Denmark)

    Crivellari, D.; Sun, Z.; Coates, A.S.

    2008-01-01

    PURPOSE: To explore potential differences in efficacy, treatment completion, and adverse events (AEs) in elderly women receiving adjuvant tamoxifen or letrozole for five years in the Breast International Group (BIG) 1-98 trial. METHODS: This report includes the 4,922 patients allocated to 5 years...... of letrozole or tamoxifen in the BIG 1-98 trial. The median follow-up was 40.4 months. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was used to examine the patterns of differences in disease-free survival and incidences of AEs according to age. In addition, three categoric age groups were...... had superior efficacy (DFS) compared with tamoxifen in all age groups. On the basis of a small number of patients older than 75 years (6%), age per se should not unduly affect the choice of adjuvant endocrine therapy Udgivelsesdato: 2008/4/20...

  3. Metabolism and transport of tamoxifen in relation to its effectiveness

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Damkier, Per; Lash, Timothy L

    2014-01-01

    Tamoxifen reduces the rate of breast cancer recurrence by approximately a half. Tamoxifen is metabolized to more active metabolites by enzymes encoded by polymorphic genes, including cytochrome P450 2D6 (CYP2D6). Tamoxifen is a substrate for ATP-binding cassette transporter proteins. We review ta...

  4. Refractive surgery for accommodative esotropia: 5-year follow-up.

    Science.gov (United States)

    Magli, Adriano; Forte, Raimondo; Gallo, Flavio; Carelli, Roberta

    2014-02-01

    To assess the long-term effectiveness and safety of refractive surgery with LASIK or photorefractive keratectomy (PRK) for treating accommodative esotropia in adults. All patients with accommodative esotropia treated with LASIK or PRK until December 2007 and with a minimum follow-up of 5 years were retrospectively included. LASIK was performed on 44 eyes of 22 patients (12 women, 10 men; mean age: 22.7 ± 2.9 years). Mean postoperative follow-up was 62.1 ± 3.2 months. PRK was performed on 16 eyes of 8 patients (4 women, 4 men; mean age: 23.7 ± 1.7 years). Mean postoperative follow-up was 61.3 ± 2.8 months. At the 5-year follow-up, the mean cycloplegic refraction was more hyperopic in the PRK group (0.3 ± 0.8 vs 0.06 ± 0.3 diopters, P = .01). Correction of esotropia to esophoria or orthotropia was present in 21 patients (95.4%) treated with LASIK and in all patients treated with PRK. Both LASIK and PRK were effective in the long-term reduction of accommodative esotropia. Copyright 2014, SLACK Incorporated.

  5. The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Clausen, Mathias Porsmose; Bennetzen, Martin

    2009-01-01

    , the compound is now also recognized as a multitargeting drug with diverse potential applications, for example, it has antiproliferative properties and it can reverse resistance toward antibiotics in bacteria. Furthermore, chlorpromazine can reverse multidrug resistance caused by overexpression of P......Tamoxifen resistance is a major clinical problem in the treatment of estrogen receptor a-positive breast tumors. It is, at present, unclear what exactly causes tamoxifen resistance. For decades, chlorpromazine has been used for treating psychotic diseases, such as schizophrenia. However......-sensitive breast cancer cell line, MCF-7, and in a tamoxifen-resistant cell line, established from the MCF-7 cells. Tamoxifen-sensitive and tamoxifen-resistant cells were killed equally well by combined treatment with chlorpromazine and tamoxifen. This synergistic effect could be prevented by addition of estrogen...

  6. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial

    DEFF Research Database (Denmark)

    Regan, M.M.; Lykkesfeldt, A.E.; Dell'Orto, P.

    2008-01-01

    Background The Breast International Group (BIG) 1-98 trial (a randomised double-blind phase III trial) has shown that letrozole significantly improves disease-free survival (DFS) compared with tamoxifen in postmenopausal women with endocrine-responsive early breast cancer. Our aim was to establish...... whether the benefit of letrozole versus tamoxifen differs according to the ERBB2 status of tumours. Methods The BIG 1-98 trial consists of four treatment groups that compare 5 years of monotherapy with letrozole or tamoxifen, and sequential administration of one drug for 2 years followed by the other drug...... for 3 years. Our study includes data from the 4922 patients randomly assigned to the two monotherapy treatment groups (letrozole or tamoxifen for 5 years; 51 months median follow-up [range

  7. Tamoxifen and CYP2D6

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P.; Damkier, Per

    2018-01-01

    Tamoxifen reduces the rate of breast cancer recurrence by about one-half. It is converted to more active metabolites by enzymes encoded by polymorphic genes, including cytochrome P450 2D6 (CYP2D6) and transported by ATP-binding cassette transporters. Genetic polymorphisms that confer reduced CYP2...

  8. A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients: a retrospective cohort study

    International Nuclear Information System (INIS)

    Gu, Ran; Long, Meijun; Chen, Kai; Chen, Lili; Xiao, Qiaozhen; Wu, Mei; Song, Erwei; Su, Fengxi; Jia, Weijuan; Zeng, Yunjie; Rao, Nanyan; Hu, Yue; Li, Shunrong; Wu, Jiannan; Jin, Liang; Chen, Lijuan

    2012-01-01

    In premenopausal women, endocrine adjuvant therapy for breast cancer primarily consists of tamoxifen alone or with ovarian suppressive strategies. Toremifene is a chlorinated derivative of tamoxifen, but with a superior risk-benefit profile. In this retrospective study, we sought to establish the role of toremifene as an endocrine therapy for premenopausal patients with estrogen and/or progesterone receptor positive breast cancer besides tamoxifen. Patients with early invasive breast cancer were selected from the breast tumor registries at the Sun Yat-Sen Memorial Hospital (China). Premenopausal patients with endocrine responsive breast cancer who underwent standard therapy and adjuvant therapy with toremifene or tamoxifen were considered eligible. Patients with breast sarcoma, carcinosarcoma, concurrent contralateral primary breast cancer, or with distant metastases at diagnosis, or those who had not undergone surgery and endocrine therapy were ineligible. Overall survival and recurrence-free survival were the primary outcomes measured. Toxicity data was also collected and compared between the two groups. Of the 810 patients reviewed, 452 patients were analyzed in the study: 240 received tamoxifen and 212 received toremifene. The median and mean follow up times were 50.8 and 57.3 months, respectively. Toremifene and tamoxifen yielded similar overall survival values, with 5-year overall survival rates of 100% and 98.4%, respectively (p = 0.087). However, recurrence-free survival was significantly better in the toremifene group than in the tamoxifen group (p = 0.022). Multivariate analysis showed that recurrence-free survival improved independently with toremifene (HR = 0.385, 95% CI = 0.154-0.961; p = 0.041). Toxicity was similar in the two treatment groups with no women experiencing severe complications, other than hot flashes, which was more frequent in the toremifene patients (p = 0.049). No patients developed endometrial cancer. Toremifene may be a valid and

  9. Expert systems: A 5-year perspective

    International Nuclear Information System (INIS)

    MacAllister, D.J.; Day, R.; McCormack, M.D.

    1996-01-01

    This paper gives an overview of a major integrated oil company's experience with artificial intelligence (AI) over the last 5 years, with an emphasis on expert systems. The authors chronicle the development of an AI group, including details on development tool selection, project selection strategies, potential pitfalls, and descriptions of several completed expert systems. Small expert systems produced by teams of petroleum technology experts and experienced expert system developers that are focused in well-defined technical areas have produced substantial benefits and accelerated petroleum technology transfer

  10. Postoperative pain

    DEFF Research Database (Denmark)

    Kehlet, H; Dahl, J B

    1993-01-01

    also modify various aspects of the surgical stress response, and nociceptive blockade by regional anesthetic techniques has been demonstrated to improve various parameters of postoperative outcome. It is therefore stressed that effective control of postoperative pain, combined with a high degree......Treatment of postoperative pain has not received sufficient attention by the surgical profession. Recent developments concerned with acute pain physiology and improved techniques for postoperative pain relief should result in more satisfactory treatment of postoperative pain. Such pain relief may...

  11. Genotoxic, epigenetic, and transcriptomic effects of tamoxifen in mouse liver

    International Nuclear Information System (INIS)

    Conti, Aline de; Tryndyak, Volodymyr; Churchwell, Mona I.; Melnyk, Stepan; Latendresse, John R.; Muskhelishvili, Levan; Beland, Frederick A.; Pogribny, Igor P.

    2014-01-01

    Highlights: • Treatment of female mice with tamoxifen caused genotoxic changes in the livers. • Tamoxifen treatment did not affect the hepatic epigenome. • Tamoxifen caused over-expression of hepatic Lcn13 and Pparγ genes. • Mice are resistant to tamoxifen-induced liver carcinogenesis and fatty liver injury. - Abstract: Tamoxifen is a non-steroidal anti-estrogenic drug widely used for the treatment and prevention of breast cancer in women; however, there is evidence that tamoxifen is hepatocarcinogenic in rats, but not in mice. Additionally, it has been reported that tamoxifen may cause non-alcoholic fatty liver disease (NAFLD) in humans and experimental animals. The goals of the present study were to (i) investigate the mechanisms of the resistance of mice to tamoxifen-induced hepatocarcinogenesis, and (ii) clarify effects of tamoxifen on NAFLD-associated liver injury. Feeding female WSB/EiJ mice a 420 p.p.m. tamoxifen-containing diet for 12 weeks resulted in an accumulation of tamoxifen-DNA adducts, (E)-α-(deoxyguanosin-N 2 -yl)-tamoxifen (dG-TAM) and (E)-α-(deoxyguanosin-N 2 -yl)-N-desmethyltamoxifen (dG-DesMeTAM), in the livers. The levels of hepatic dG-TAM and dG-DesMeTAM DNA adducts in tamoxifen-treated mice were 578 and 340 adducts/108 nucleotides, respectively, while the extent of global DNA and repetitive elements methylation and histone modifications did not differ from the values in control mice. Additionally, there was no biochemical or histopathological evidence of NAFLD-associated liver injury in mice treated with tamoxifen. A transcriptomic analysis of differentially expressed genes demonstrated that tamoxifen caused predominantly down-regulation of hepatic lipid metabolism genes accompanied by a distinct over-expression of the lipocalin 13 (Lcn13) and peroxisome proliferator receptor gamma (Pparγ), which may prevent the development of NAFLD. The results of the present study demonstrate that the resistance of mice to tamoxifen

  12. Tumorigenic Effects of Tamoxifen on the Female Genital Tract

    Directory of Open Access Journals (Sweden)

    Kaei Nasu M.D., Ph.D.

    2008-01-01

    Full Text Available Tamoxifen is widely used for endocrine treatment and breast cancer prevention. It acts as both an estrogen antagonist in breast tissue and an estrogen agonist in the female lower genital tract. Tamoxifen causes severe gynecologic side effects, such as endometrial cancer. This review focuses on the effects of prolonged tamoxifen treatment on the human female genital tract and considers its tumorigenicity in the gynecologic organs through clinical data analysis. Tamoxifen is associated with an increased incidence of benign endometrial lesions such as polyps and hyperplasia and a two- to four-fold increased risk of endometrial cancer in postmenopausal patients. Moreover, the incidence of functional ovarian cysts is significantly high in premenopausal tamoxifen users. To prevent tamoxifen from having severe side effects in gynecologic organs, frequent gynecological examination should be performed for both premenopausal and postmenopausal patients with breast cancer who are treated with this drug.

  13. Migration of the Duraloc cup after 5 years.

    Science.gov (United States)

    Stihsen, Christoph; Pabinger, Christof; Radl, Roman; Rehak, Peter; Windhager, Reinhard

    2008-12-01

    The Duraloc cup is a frequently used metal-backed, porous-coated, hemispherical, press-fit acetabular component. Published data on loosening rates are contradictory. In this study we investigated migration patterns with computer-assisted Einzel-Bild-Roentgen-Analyse (EBRA) of 67 Duraloc 100 cups. Cup migration and clinical scores were analysed over a 5-year follow-up period. Median total migration of the Duraloc 100 cup was 1.21 mm at 5 years. Seventy-five percent of implants were radiologically stable at 2 years and 90% at 4 years. One cup loosened aseptically at 60 months, requiring revision. Cup diameters > or = 54 mm migrated significantly more than cups < 54 mm in diameter (p = 0.029 at 4 years). There was a significant correlation between high polyethylene wear and further migrating cups within the first post-operative year (p = 0.035 at 12 months). Our analysis revealed significantly higher wear in males (p = 0.029 at 4 years). Radiological loosening at two years could be calculated using receiver-operating characteristic curve analysis, and 1.2 mm as an adequate threshold value (sensitivity = 100%, specificity = 89%).

  14. TAMOXIFEN RETINOPATHY DURING TREATMENT OF AN INOPERABLE DESMOID TUMOR.

    Science.gov (United States)

    Furst, Meredith; Somogyi, Marie B; Wong, Robert W; Araujo, Dejka; Harper, Clio A

    2017-12-08

    To evaluate the clinical significance and rarity of tamoxifen retinopathy after a long-term tamoxifen treatment for an inoperable desmoid tumor. Case report. Tamoxifen retinopathy is a condition rarely observed in clinical practice. Although tamoxifen is typically a treatment for breast cancer patients, we present a 68-year-old woman taking tamoxifen for an inoperable desmoid tumor, an equally rare condition. She presented with bilaterally deteriorating vision over the course of a year. Fundoscopic examination revealed parafoveal deposits bilaterally. Spectral domain optical coherence tomography exhibited hyperreflective deposits in all layers of the retina. She had a cumulative treatment dose of 292 g of tamoxifen, and the medication was subsequently stopped. Her vision remained stable 3 months after the cessation of tamoxifen. The development of tamoxifen retinopathy in the treatment of a desmoid tumor makes this case a rare entity, and this is the first reported case of these two concomitant conditions to our knowledge. With the use of long-term tamoxifen as a primary treatment, we recommend screening at regular intervals by an ophthalmologist as an integral part of treatment.

  15. Outcome from 5-year live surgical demonstrations in urinary stone treatment: are outcomes compromised?

    NARCIS (Netherlands)

    Legemate, Jaap D.; Zanetti, Stefano P.; Baard, Joyce; Kamphuis, Guido M.; Montanari, Emanuele; Traxer, Olivier; de la Rosette, Jean Jmch

    2017-01-01

    To compare intra- and post-operative outcomes of endourological live surgical demonstrations (LSDs) and routine surgical practice (RSP) for urinary stones. Consecutive ureterorenoscopic (URS) and percutaneous (PNL) urinary stone procedures over a 5-year period were reviewed. Procedures were divided

  16. One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent; Jensen, Maj-Britt; Elversang, Johanna

    2013-01-01

    We report the long-term results of a randomised trial comparing tamoxifen with tamoxifen plus cyclophosphamide, methotrexate and fluorouracil (CMF) in postmenopausal high-risk breast cancer patients. In addition, we analyse the prognostic and predictive value of centrally assessed subtypes....

  17. ATLAS: Adjuvant Tamoxifen Longer Against Shorter

    Science.gov (United States)

    1998-09-01

    largely tunaffected by other these 30 000 women during about 10 years of follow-up patient characteristics or treatments. were 21% (SD 3), 29% (SD 2...for both types of mosted to stop part of the eduon y epatient . most of them did stop, part of the reduction in the The right side of figure 4...patient characteristics (e.g. high/ low-risk, ER+/ER-, pre/post-menopausal) recorded at entry. Other trials of tamoxifen duration The Atlas collaboration

  18. Tamoxifen induces apoptotic neutrophil efferocytosis in horses.

    Science.gov (United States)

    Olave, C; Morales, N; Uberti, B; Henriquez, C; Sarmiento, J; Ortloff, A; Folch, H; Moran, G

    2018-03-01

    Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction of BALF neutrophils, and improvement in animals' clinical status. The aim of this study was to describe if TX induces in vitro efferocytosis of neutrophils by alveolar macrophages. Efferocytosis assay, myeloperoxidase (MPO) detection and translocation phosphatidylserine (PS) were performed on neutrophils isolated from peripheral blood samples from five healthy horses. In in vitro samples from heathy horses, TX treatment increases the phenomenon of efferocytosis of peripheral neutrophils by alveolar macrophages. Similar increases in supernatant MPO concentration and PS translocation were observed in TX-treated neutrophils, compared to control cells. In conclusion, these results confirm that tamoxifen has a direct effect on equine peripheral blood neutrophils, through stimulation of the engulfment of apoptotic neutrophils by alveolar macrophages.

  19. Tamoxifen treatment of bleeding irregularities associated with Norplant use.

    Science.gov (United States)

    Abdel-Aleem, Hany; Shaaban, Omar M; Amin, Ahmed F; Abdel-Aleem, Aly M

    2005-12-01

    To evaluate the possible role of tamoxifen (selective estrogen receptor modulators, SERM) in treating bleeding irregularities associated with Norplant contraceptive use. Randomized clinical trial including 100 Norplant users complaining of vaginal bleeding irregularities. The trial was conducted in the Family Planning Clinic of Assiut University Hospital. Women were assigned at random to receive tamoxifen tablets (10 mg) twice daily for 10 days or similar placebo. Women were followed-up for 3 months. The end points were percentage of women who stopped bleeding during treatment, bleeding/spotting days during the period of follow-up, effect of treatment on their lifestyle, and side effects and discontinuation of contraception. There was good compliance with treatment. At the end of treatment, a significantly higher percentage of tamoxifen users stopped bleeding in comparison to the control group (88% vs. 68%, respectively; p=.016). Women who used tamoxifen had significantly less bleeding and/or spotting days than women who used placebo, during the first and second months. During the third month, there were no significant differences between the two groups. Women who used tamoxifen reported improvement in performing household activities, religious duties and in sexual life, during the first 2 months. In the third month, there were no differences between the two groups. There were no significant differences between tamoxifen and placebo groups in reporting side effects. In the group who used tamoxifen, two women discontinued Norplant use because of bleeding vs. nine women in the placebo group. Tamoxifen use at a dose of 10 mg twice daily orally, for 10 days, has a beneficial effect on vaginal bleeding associated with Norplant use. In addition, the bleeding pattern was better in women who used tamoxifen for the following 2 months after treatment. However, these results have to be confirmed in a larger trial before advocating this line of treatment.

  20. The temporal outcomes of open versus arthroscopic knotted and knotless rotator cuff repair over 5 years

    Science.gov (United States)

    Lucena, Thomas R; Lam, Patrick H; Millar, Neal L

    2015-01-01

    Background The present study aimed to determine how repair technique influenced structural and clinical outcomes at 5 years post-surgery. Methods Three cohorts of patients had repair of a symptomatic rotator cuff tear using (i) an open double-row mattress repair technique (n = 25); (ii) arthroscopic single-row simple suture knotted technique (n = 25); or (iii) arthroscopic single-row inverted mattress knotless technique (n = 36) by one surgeon. Standardized patient- and examiner-determined outcomes were obtained pre-operatively and postoperatively with a validated protocol, ultrasound were also performed at the same time. Results Retear occurred more often after open repair (48%) at 5 years than after arthroscopic knotted (33%) and arthroscopic knotless (26%) repair. Retear was associated with increasing age, pre-operative tear size and weaker pre-operative and 5 years postoperative cuff strength. Between 2 years and 5 years, the open repair group experienced an increase in the frequency of pain during activity, as well as in the difficulty experienced and the severity of pain during overhead activities (p repair group. Conclusions At 5-year follow-up, arthroscopic rotator cuff repair techniques resulted in fewer retears and better outcomes compared to an open double-row technique. PMID:27582985

  1. Thrombosis of digital arteries associated with tamoxifen use: case report.

    Science.gov (United States)

    Hutchison, Richard L; Rayan, Ghazi M

    2012-02-01

    Arterial thrombosis in the upper extremity occurs often at the wrist. We report a unique case of thrombosis that involved multiple digital arteries, without radial or ulnar artery involvement, which developed only after using tamoxifen despite chronic occupational blunt percussive hand use. Revascularization was achieved after thrombectomy. Multiple digital arterial thromboses may complicate the use of tamoxifen. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Tamoxifen for women at high risk of breast cancer

    OpenAIRE

    Nazarali, Safia A; Narod, Steven A

    2014-01-01

    Safia A Nazarali, Steven A Narod Women's College Research Institute, Women's College Hospital, and The University of Toronto, Toronto, Ontario, Canada Abstract: Tamoxifen has been used as a treatment for women who have been diagnosed with breast cancer for roughly four decades and has been approved as chemoprevention for over ten years. Although tamoxifen has been proven to be beneficial in preventing breast cancer in high-risk women, its use has not been widely embraced. To ...

  3. A 5 year prospective study of patient-relevant outcomes after total knee replacement

    DEFF Research Database (Denmark)

    Nilsdotter, A-K; Toksvig-Larsen, S; Roos, E M

    2008-01-01

    men, mean age 71 (51-86) assigned for TKR at the Department of Orthopaedics at Lund University Hospital were included in the study. The self-administered questionnaires Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-36 were mailed preoperatively and 6 months, 12 months and at 5 years......OBJECTIVE: To prospectively describe self-reported outcomes up to 5 years after total knee replacement (TKR) in Osteoarthritis (OA) and to study which patient-relevant factors may predict outcomes for pain and physical function (PF). METHODS: 102 consecutive patients with knee OA, 63 women and 39...... postoperatively. RESULTS: Response rate at 5 years was 86%. At 6 months significant improvement was seen in all KOOS and SF-36 scores (P

  4. Postoperative radiology

    International Nuclear Information System (INIS)

    Burhenne, H.J.

    1989-01-01

    This paper reports on the importance of postoperative radiology. Most surgical procedures on the alimentary tract are successful, but postoperative complications remain a common occurrence. The radiologist must be familiar with a large variety of possible surgical complications, because it is this specialty that is most commonly called on to render a definitive diagnosis. The decision for reoperation, for instance, is usually based on results from radiologic imaging techniques. These now include ultrasonography, CT scanning, needle biopsy, and interventional techniques in addition to contrast studies and nuclear medicine investigation

  5. Discrepancy between ultrasonography and hysteroscopy and histology of endometrium in postmenopausal breast cancer patients using tamoxifen

    NARCIS (Netherlands)

    Mourits, MJE; Van der Zee, AGJ; Willemse, PHB; Ten Hoor, KA; Hollema, H; De Vries, EGE

    Background. The increased risk of endometrial carcinoma following the use of tamoxifen has stimulated studies on endometrial diagnostic screening methods. In tamoxifen users the endometrial thickening observed with transvaginal ultrasonography (TVU) frequently cannot be confirmed by hysteroscopy or

  6. Functional screen for genes responsible for tamoxifen resistance in human breast cancer cells

    NARCIS (Netherlands)

    Meijer, Danielle; van Agthoven, Ton; Bosma, Peter T.; Nooter, Kees; Dorssers, Lambert C. J.

    2006-01-01

    Antiestrogens, such as tamoxifen, are widely used for endocrine treatment of estrogen receptor-positive breast cancer. However, as breast cancer progresses, development of tamoxifen resistance is inevitable. The mechanisms underlying this resistance are not well understood. To identify genes

  7. Adjuvant tamoxifen influences the lipid profile in breast cancer patients.

    Science.gov (United States)

    Lin, Che; Chen, Li-Sheng; Kuo, Shou-Jen; Chen, Dar-Ren

    2014-02-01

    Currently there is a debate regarding whether tamoxifen used in breast cancer has an impact on lipid profiles. The aim of this study was to determine whether tamoxifen has an impact on the serum lipid profile in Taiwanese women. Data of 109 patients were collected from the routine clinical follow-up for women with hormone receptor-positive breast cancer who were treated between July 2005 and March 2008. These patients were divided into 2 subgroups, based on their tumor grade and lymph node status. Subgroup 1 patients had tumor grade I/II and a negative lymph node status. Those patients with tumor grade III or a positive lymph node status were defined as subgroup 2. In the 109 patients, the mean serum total cholesterol (TC) levels after tamoxifen treatment, as well as the serum low-density lipoprotein cholesterol (LDL-C) levels, were lower than the baseline levels, with statistically significant differences. Treatment with tamoxifen lowered the serum TC and LDL-C levels in both subgroups. The results indicate that tamoxifen has an impact on the serum lipid profile of breast cancer patients in Taiwan. Physicians should follow up the lipid profile in these patients.

  8. Augmentation of Endoxifen Exposure in Tamoxifen-Treated Women Following SSRI Switch

    NARCIS (Netherlands)

    L. Binkhorst (Lisette); M. Bannink (Marjolein); P. de Bruijn (Peter); J.B. Ruit (Jos); J. Droogendijk (Jolanda); R.J. van Alphen (Robbert); T.D. den Boer (Tilly D.); M.H. Lam (Mei); A. Jager (Agnes); T. van Gelder (Teun); A.H.J. Mathijssen (Ron)

    2016-01-01

    textabstractBackground and Objective: The anti-oestrogen tamoxifen requires metabolic activation to endoxifen by cytochrome P450 (CYP) enzymes, predominantly CYP2D6. Potent CYP2D6-inhibiting antidepressants can seriously disrupt tamoxifen metabolism, probably influencing the efficacy of tamoxifen.

  9. Epidemiology of rotavirus diarrhea in children under 5 years in ...

    African Journals Online (AJOL)

    Background: Rotavirus still remains the major cause of diarrhea in children below 5 years. No data on rotavirus epidemiology is available in the Northern regions of Cameroon. We aimed to determine the prevalence of group A rotavirus (RVA) in children below 5 years with diarrhea in two regions of Northern Cameroon ...

  10. Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance.

    Directory of Open Access Journals (Sweden)

    John Koren

    Full Text Available MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB. Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family.

  11. Postoperative spinal column; Postoperative Wirbelsaeule

    Energy Technology Data Exchange (ETDEWEB)

    Kaefer, W. [Westpfalzklinikum GmbH, Standort II, Abteilung fuer Wirbelsaeulenchirurgie, Kusel (Germany); Heumueller, I. [Westpfalzklinikum GmbH, Standort II, Institut fuer Radiologie II, Kusel (Germany); Harsch, N.; Kraus, C.; Reith, W. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2016-08-15

    As a rule, postoperative imaging is carried out after spinal interventions to document the exact position of the implant material. Imaging is absolutely necessary when new clinical symptoms occur postoperatively. In this case a rebleeding or an incorrect implant position abutting a root or the spinal cord must be proven. In addition to these immediately occurring postoperative clinical symptoms, there are a number of complications that can occur several days, weeks or even months later. These include the failed back surgery syndrome, implant loosening or breakage of the material and relapse of a disc herniation and spondylodiscitis. In addition to knowledge of the original clinical symptoms, it is also important to know the operation details, such as the access route and the material used. In almost all postoperative cases, imaging with contrast medium administration and corresponding correction of artefacts by the implant material, such as the dual energy technique, correction algorithms and the use of special magnetic resonance (MR) sequences are necessary. In order to correctly assess the postoperative imaging, knowledge of the surgical procedure and the previous clinical symptoms are mandatory besides special computed tomography (CT) techniques and MR sequences. (orig.) [German] In der Regel erfolgt bei spinalen Eingriffen eine postoperative Bildgebung, um die exakte Lage des Implantatmaterials zu dokumentieren. Unbedingt notwendig ist die Bildgebung, wenn postoperativ neue klinische Symptome aufgetreten sind. Hier muessen eine Nachblutung bzw. inkorrekte, eine Wurzel oder das Myelon tangierende Implantatlage nachgewiesen werden. Neben diesen direkt postoperativ auftretenden klinischen Symptomen gibt es eine Reihe von Komplikationen, die erst nach mehreren Tagen, Wochen oder sogar nach Monaten auftreten koennen. Hierzu zaehlen das Failed-back-surgery-Syndrom, die Implantatlockerung oder -bruch, aber auch ein Rezidivvorfall und die Spondylodiszitis. Neben der

  12. Intraoperative Tumor Perforation is Associated with Decreased 5-Year Survival in Colon Cancer

    DEFF Research Database (Denmark)

    Bundgaard, N S; Bendtsen, V O; Ingeholm, P

    2017-01-01

    BACKGROUND: It is a widely held belief that intraoperative tumor perforation in colon cancer impairs survival and causes local recurrence, although the prognostic importance remains unclear. AIM: The aim of this study was to assess the effect of unintended intraoperative tumor perforation...... on postoperative mortality and long-term survival. MATERIAL AND METHODS: This national cohort study was based on data from a prospectively maintained nationwide colorectal cancer database. We included 16,517 colon cancer patients who were resected with curative intent from 2001 to 2012. RESULTS: Intraoperative...... tumor perforation produced a significantly impaired 5-year survival of 40% compared to 64% in non-perforated colon cancer. Intraoperative tumor perforation was an independent risk factor for death, hazard ratio 1.63 (95% confidence interval: 1.4-1.94), with a significantly increased 90-day postoperative...

  13. Are patient-reported outcomes predictive of patient satisfaction 5 years after anterior cervical spine surgery?

    Science.gov (United States)

    Schroeder, Gregory D; Coric, Dom; Kim, Han Jo; Albert, Todd J; Radcliff, Kris E

    2017-07-01

    Patient satisfaction is becoming an increasing common proxy for surgical quality; however, the correlation between patient satisfaction and surgical outcomes 2 and 5 years after anterior cervical surgery has not been evaluated. The study aimed to determine if patient satisfaction is predicted by improvement in patient-reported outcomes (PRO) 2 and 5 years after anterior cervical spine surgery. This is a retrospective analysis of prospectively collected data. The sample included patients enrolled in the Food and Drug Administration investigational device exemption clinical trial comparing total disc replacement with Mobi-C cervical artificial disc and anterior cervical discectomy and fusion. The outcome measures were visual analog scale (VAS) neck pain score, Neck Disability Index (NDI), and Short-Form 12-Item scores, as well as patient satisfaction. Receiver operating characteristic curves were used to determine if improvement in different PRO metrics can accurately identify patient satisfaction. Additionally, a logistic regression analysis was performed on the results at 24 months and 60 months to identify independent predictors of patient satisfaction. This research was supported by LDR (Zimmer Biomet) 13785 Research Boulevard - Suite 200 Austin, TX 78750. Data were available for 512 patients at 60 months. At 24 months postoperatively, NDI score improvement (area under the curve [AUC]=0.806), absolute NDI score (AUC=0.823), and absolute VAS neck pain score (AUC=0.808) were all excellent predictors of patient satisfaction. At 60 months postoperatively, NDI score improvement (AUC=0.815), absolute NDI score (AUC=0.839), VAS neck pain score improvement (AUC=0.803), and absolute VAS neck pain score (AUC=0.861) were all excellent predictors of patient satisfaction. In patients undergoing one- and two-level anterior cervical spine surgery, between 2 and 5 years postoperatively, patient satisfaction is significantly predicted by PROs, including the VAS neck score and the

  14. Cleft maxillary distraction versus orthognathic surgery--which one is more stable in 5 years?

    Science.gov (United States)

    Chua, Hannah Daile P; Hägg, Margareta Bendeus; Cheung, Lim Kwong

    2010-06-01

    The objective of this study was to compare the long-term stability of distraction osteogenesis (DO) and conventional orthognathic surgery (CO) in patients with cleft lip and palate (CLP). CLP patients requiring maxillary advancement of 4 to 10 mm were randomized and assigned to either CO or DO. In the CO group, the maxilla was fully mobilized to the preplanned position and fixed using titanium miniplates. In the DO group, the maxilla was mobilized to a limited extent and distractors were fixed on each side of the maxilla. Serial lateral cephalographs were taken for the assessment of stability at different postoperative periods up to 5 years. In the CO group, the maxilla relapsed backward and upward, whereas in the DO group, it advanced more forward and downward over 5 years. Distraction of the cleft maxilla can achieve better long-term skeletal stability in maintaining its advanced position than CO. Copyright 2010 Mosby, Inc. All rights reserved.

  15. Postoperative hypoparathyroidism

    International Nuclear Information System (INIS)

    Rao, R.S.

    1999-01-01

    It is essential to preserve as many of the parathyroid glands, as possible, during surgery of the thyroid gland. This is achieved by visualizing them and by minimal handling of the glands. Truncal ligation of the inferior thyroid artery is quite safe. Capsular ligation of the branches of the artery is theoretically superior but requires a greater degree of skill and experience in thyroid surgery. It also puts the recurrent laryngeal nerve at a greater risk of injury. Calcitriol or 1.25 dihydroxy vitamin D is a very useful drug in managing patients with severe post-operative hypoparathyroidism

  16. Fitness and Your 4-to 5-Year Old

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Fitness and Your 4- to 5-Year-Old KidsHealth / ... the risk of serious illnesses later in life. Fitness for Preschoolers Physical activity guidelines for preschoolers recommend ...

  17. Medical Care and Your 4- to 5-Year-Old

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Medical Care and Your 4- to 5-Year-Old ... pain, such as from an ear infection Common Medical Problems Problems often found in this age group ...

  18. 75 FR 66724 - Endangered and Threatened Species; 5-Year Review

    Science.gov (United States)

    2010-10-29

    ... extinction throughout its range. Therefore, the 5-year review recommends no change in listing. ADDRESSES... maintained. The list is published at 50 CFR 17.11 (for animals) and 17.12 (for plants). Section 4(c)(2) of...

  19. The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause

    DEFF Research Database (Denmark)

    Chirgwin, Jacquie; Sun, Zhuoxin; Smith, Ian

    2012-01-01

    subclinical ovarian estrogen production), and those with chemotherapy-induced menopause who may experience return of ovarian function. In these situations tamoxifen may be preferable to an aromatase inhibitor. Among 4,922 patients allocated to the monotherapy arms (5 years of letrozole or tamoxifen......) in the BIG 1-98 trial we identified two relevant subpopulations: patients with potential residual ovarian function, defined as having natural menopause, treated without adjuvant or neoadjuvant chemotherapy and age ≤ 55 years (n = 641); and those with chemotherapy-induced menopause (n = 105). Neither...... of the subpopulations examined showed treatment effects differing from the trial population as a whole (interaction P values are 0.23 and 0.62, respectively). Indeed, both among the 641 patients aged ≤ 55 years with natural menopause and no chemotherapy (HR 0.77 [0.51, 1.16]) and among the 105 patients...

  20. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.

    Science.gov (United States)

    Regan, Meredith M; Neven, Patrick; Giobbie-Hurder, Anita; Goldhirsch, Aron; Ejlertsen, Bent; Mauriac, Louis; Forbes, John F; Smith, Ian; Láng, István; Wardley, Andrew; Rabaglio, Manuela; Price, Karen N; Gelber, Richard D; Coates, Alan S; Thürlimann, Beat

    2011-11-01

    Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8·1 years median follow-up. BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years

  1. Adenosarcoma of the uterus following tamoxifen treatment for breast cancer

    NARCIS (Netherlands)

    Mourits, MJE; Hollema, H; Willemse, PHB; De Vries, EGE; Aalders, JG; Van der Zee, AGJ

    1998-01-01

    A 71-year-old patient developed an uterine adenosarcoma two months after two years of tamoxifen adjuvant treatment for early breast cancer. After curettage for postmenopausal bleeding, the patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic

  2. Tamoxifen treatment and gynecologic side effects : A review

    NARCIS (Netherlands)

    Mourits, MJE; De Vries, EGE; Willemse, PHB; Ten Hoor, KA; Hollema, H; Van der Zee, AGJ

    Objective: To review the literature on tamoxifen side effects on the female genital tract and psychosexual function in premenopausal and postmenopausal women. Data Sources: We used the English-language literature in MEDLINE and reference lists from selected articles. Search terms included:

  3. Detection of tamoxifen metabolites by GC-MSD.

    Science.gov (United States)

    Báez, H; Camargo, C; Osorio, H; Umpiérrez, F

    2004-01-01

    Tamoxifen is an antiestrogen used in the adjuvant endocrine therapy of early breast cancer and malignant breast disorders. It is also used in women with anovulatory infertility caused by its stimulating effect on the secretion of the pituitary gonadotrophic hormones. In males it could increase the endogenous production of androgens. Because of these properties tamoxifen may be misused in some sports to treat the androgens suppression caused by the extensive abuse of anabolic androgenic steroids. A method for identification and confirmation of tamoxifen metabolites is described. Hydroxymetoxytamoxifen is detected in urine by gas chromatography and mass spectrometry in a selective ion monitoring method followed by the routine postrun in the screening of anabolic steroids. Once the hydroxymetoxytamoxifen is detected, confirmation of reported metabolites could be performed with a 5973 mass selective detector in the scan mode after solid-phase extraction by cationic exchange. This study also reports an excretion profile for a single dose of tamoxifen equivalent to 40 mg administrated orally to two males volunteers.

  4. Integrative analysis of miRNA and gene expression reveals regulatory networks in tamoxifen-resistant breast cancer

    DEFF Research Database (Denmark)

    Joshi, Tejal; Elias, Daniel; Stenvang, Jan

    2016-01-01

    Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer, however, tamoxifen resistance is frequently observed. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of mi......+ breast cancer patients receiving adjuvant tamoxifen mono-therapy. Our results provide new insight into the molecular mechanisms of tamoxifen resistance and may form the basis for future medical intervention for the large number of women with tamoxifen-resistant ER+ breast cancer.......RNA-mediated gene regulation in three clinically-relevant tamoxifen-resistant breast cancer cell lines (TamRs) compared to their parental tamoxifen-sensitive cell line. Alterations in the expression of 131 miRNAs in tamoxifen-resistant vs. parental cell lines were identified, 22 of which were common to all Tam...

  5. Cancer Care Coordinators to Improve Tamoxifen Persistence in Breast Cancer: How Heterogeneity in Baseline Prognosis Impacts on Cost-Effectiveness.

    Science.gov (United States)

    Nair, Nisha; Kvizhinadze, Giorgi; Blakely, Tony

    2016-12-01

    To assess the cost-effectiveness of a cancer care coordinator (CCC) in helping women with estrogen receptor positive (ER+) early breast cancer persist with tamoxifen for 5 years. We investigated the cost-effectiveness of a CCC across eight breast cancer subtypes, defined by progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and local/regional spread. These subtypes range from excellent to poorer prognoses. The CCC helped in improving tamoxifen persistence by providing information, checking-in by phone, and "troubleshooting" concerns. We constructed a Markov macrosimulation model to estimate health gain (in quality-adjusted life-years or QALYs) and health system costs in New Zealand, compared with no CCC. Participants were modeled until death or till the age of 110 years. Some input parameters (e.g., the impact of a CCC on tamoxifen persistence) had sparse evidence. Therefore, we used estimates with generous uncertainty and conducted sensitivity analyses. The cost-effectiveness of a CCC for regional ER+/PR-/HER2+ breast cancer (worst prognosis) was NZ $23,400 (US $15,800) per QALY gained, compared with NZ $368,500 (US $248,800) for local ER+/PR+/HER2- breast cancer (best prognosis). Using a cost-effectiveness threshold of NZ $45,000 (US $30,400) per QALY, a CCC would be cost-effective only in the four subtypes with the worst prognoses. There is value in investigating cost-effectiveness by different subtypes within a disease. In this example of breast cancer, the poorer the prognosis, the greater the health gains from a CCC and the better the cost-effectiveness. Incorporating heterogeneity in a cost-utility analysis is important and can inform resource allocation decisions. It is also feasible to undertake in practice. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  6. Upper Body Muscular Endurance Among Children 2-5 Years.

    Science.gov (United States)

    Gabbard, Carl P.; And Others

    The upper body muscular endurance of males and females 2-5 years of age was assessed, and relationships relative to sex, age, endurance and selected anthropometric measures were investigated. None of the relationships were found to be of practical predicative value; while upper body muscular strength increased with age, no significant differences…

  7. Malaria Parasitemia in Children Aged less than 5 Years Presenting ...

    African Journals Online (AJOL)

    Fever is the commonest manifestation and Children aged less than 5 years are most vulnerable. An appraisal of this disease among these children is important to reducing the impact of the disease. Objective: To determine the prevalence and identify factors affecting malaria parasitemia in febrile children aged less than 5 ...

  8. Your Child's Development: 2.5 Years (30 Months)

    Science.gov (United States)

    ... 5 Years (30 Months) Print en español El desarrollo de su hijo: 2,5 años (30 meses) ... assistance jumps in place throws a ball overhand Social and Emotional Development enjoys pretend play starts to ...

  9. Your Child's Development: 1.5 Years (18 Months)

    Science.gov (United States)

    ... 5 Years (18 Months) Print en español El desarrollo de su hijo: 1,5 años (18 meses) ... takes off some clothes scribbles with a crayon Social and Emotional Development begins to engage in pretend ...

  10. Clinical prediction of 5-year survival in systemic sclerosis

    DEFF Research Database (Denmark)

    Fransen, Julie Munk; Popa-Diaconu, D; Hesselstrand, R

    2011-01-01

    Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accura...

  11. Evaluating 5 years' NIMART mentoring in South Africa's HIV ...

    African Journals Online (AJOL)

    Evaluating 5 years' NIMART mentoring in South Africa's HIV treatment programme: Successes, challenges and future needs. ... South African Medical Journal ... targeted mentoring was introduced; this increased the percentage of primary nurses eligible for DoH certificates of clinical competence in NIMART from 12%, ...

  12. Free Mediastinal Foreign Bodies: 5-year Experience and Review of ...

    African Journals Online (AJOL)

    Free Mediastinal Foreign Bodies: 5-year Experience and Review of Literature. M O Thomas ... need for public enlightenment against such practice. The evolving world of endoscopic surgery throws a challenge towards the future management of these types of cases. We need to do more in this part of the world. NQJHM Vol.

  13. Change in employment status of 5-year cancer survivors.

    Science.gov (United States)

    Torp, Steffen; Nielsen, Roy A; Fosså, Sophie D; Gudbergsson, Saevar B; Dahl, Alv A

    2013-02-01

    To follow the employment status of 5-year cancer survivors for 5 years after diagnosis with their first lifetime invasive cancer and to identify socio-demographic, work-related and cancer-related predictors of employment status after 5 years. This prospective registry study concerned all 3278 people in Norway (18-61 years old) diagnosed with their first lifetime invasive cancer in 1999 and alive in 2004 and a cancer-free control group (n = 6368) matched by sex, age, educational level and employment status in 1998. The employment rate among male cancer survivors declined steadily every year, from 94% the year before diagnosis (1998) to 77% 5 years after diagnosis (2004). This change did not differ significantly from that of male controls. The employment rate of female survivors also declined steadily, from 87% (1998) to 69% (2004). This decline was greater than that among female controls, and in 2004 survivors had a significantly lower employment rate. For both men and women, the significant pre-diagnosis predictors of being employed in 2004 concerned higher socio-economic position. For both sexes, lung cancer survivors had the highest decline in employment rate, and male skin cancer survivors had a lower decline in employment rate than controls. Socio-demographic and work-related factors explained more of the variance in employment status than did cancer diagnosis. The employment rate among 5-year cancer survivors did not change significantly except for female survivors. Low socio-economic position is a risk factor for decline in employment rate and should be focused on to prevent cancer-related inequity.

  14. MCAM/CD146 promotes tamoxifen resistance in breast cancer cells through induction of epithelial-mesenchymal transition, decreased ER alpha expression and AKT activation

    NARCIS (Netherlands)

    Liang, Yuan-Ke; Zeng, De; Xiao, Ying-Sheng; Wu, Yang; Ouyang, Yan-Xiu; Chen, Min; Li, Yao-Chen; Lin, Hao-Yu; Wei, Xiao-Long; Zhang, Yong-Qu; Kruyt, Frank A. E.; Zhang, Guo-Jun

    2017-01-01

    Tamoxifen resistance presents a prominent clinical challenge in endocrine therapy for hormone sensitive breast cancer. However, the underlying mechanisms that contribute to tamoxifen resistance are not fully understood. In this study, we established a tamoxifen resistant MCF-7 cell line

  15. A Role for Estrogen Receptor Phosphorylation in the Resistance to Tamoxifen

    International Nuclear Information System (INIS)

    De Leeuw, R.; Neefjes, J.; Michalides, R.

    2011-01-01

    About two thirds of all human breast cancer cases are estrogen receptor positive. The drug of first choice for these patients is tamoxifen. However, about half of the recurrences after removal of the primary tumor are or become resistant to this drug. While many mechanisms have been identified for tamoxifen resistance in the lab, at present only a few have been translated to the clinic. This paper highlights the role in tamoxifen resistance of phosphorylation by different kinases on different sites of the estrogen receptor. We will discuss the molecular pathways and kinases that are involved in phosphorylation of ERa and how these affect tamoxifen resistance. Finally, we will elaborate on the clinical translation of these observations and the possibility to predict tamoxifen responses in patient tumor samples before treatment onset. The findings made originally on the bench may translate into a better and personalized treatment of breast cancer patients using an old and safe anticancer drug: tamoxifen

  16. Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat

    Directory of Open Access Journals (Sweden)

    Goldstein Irwin

    2006-09-01

    Full Text Available Abstract Background Tamoxifen, a selective estrogen receptor modulator with both estrogenic and anti-estrogenic activity, is widely used as adjuvant therapy in breast cancer patients. Treatment with tamoxifen is associated with sexual side effects, such as increased vaginal dryness and pain/discomfort during sexual activity. There have been limited investigations of the effect of tamoxifen on estrogen-dependent peripheral genital arousal responses. The objective of this study was to investigate the effects of tamoxifen on vaginal physiology in the rat. Methods Female Sprague-Dawley rats were subjected to sham surgery or bilateral ovariectomy. After 2 weeks, sham-operated rats were implanted with subcutaneous osmotic infusion pumps containing vehicle (control or tamoxifen (150 μg/day. Ovariectomized rats were similarly infused with vehicle. After an additional 2 weeks, vaginal blood flow responses to pelvic nerve stimulation were measured by laser Doppler flowmetry and vaginal tissue was collected for histological and biochemical assay. Results Tamoxifen treatment did not change plasma estradiol concentrations relative to control animals, while ovariectomized rats exhibited a 60% decrease in plasma estradiol. Tamoxifen treatment caused a significant decrease in mean uterine weight, but did not alter mean vaginal weight. Vaginal blood flow was significantly decreased in tamoxifen-infused rats compared to controls. Similar to ovariectomized animals, estrogen receptor binding was increased and arginase enzyme activity was decreased in tamoxifen-infused rats. However, different from control and ovariectomized animals, the vaginal epithelium in tamoxifen-infused rats appeared highly mucified. Periodic acid-Schiff staining confirmed a greater production of carbohydrate-rich compounds (e.g. mucin, glycogen by the vaginal epithelium of tamoxifen-infused rats. Conclusion The observations suggest that tamoxifen exerts both anti-estrogenic and pro

  17. 131I labeling of tamoxifen and biodistribution studies in rats

    International Nuclear Information System (INIS)

    Biber Muftuler, F.Z.; Unak, P.; Teksoz, S.; Acar, C.; Yolcular, S.; Yuerekli, Y.

    2008-01-01

    Tamoxifen [TAM ([Z]-2-[4-(1,2-diphenyl-1-di-butenyl)-phenoxy]-N,N-dimethylethanamine)] has been used as an antiestrogen drug for treatment and prevention of human breast cancer. Tamoxifen was labeled with 131 I using iodogen as an oxidizing agent. Mass spectroscopy of the cold standard showed that the labeling occurs in ortho position to the phenyl ether position of TAM as expected. Quality control, radiochemical yield and stability were established using the radioelectrophoresis method. The radiolabeled compound maintained its stability throughout working period of 24 h. Scintigraphic imaging was performed and tissue distribution was determined in Albino Wistar rats. According to biodistribution and imaging experiments the radiolabeled compound presented estrogen receptor (ER) specificity and it was uptaken by endometrium as well as breast tissue

  18. Dietary predictors of 5-year changes in waist circumference

    DEFF Research Database (Denmark)

    Halkjaer, Jytte; Tjønneland, Anne; Overvad, Kim

    2009-01-01

    the association between intake from 21 food and beverage groups and the subsequent 5-year difference in waist circumference. METHODS: The study population consisted of 22,570 women and 20,126 men, aged 50 to 64 years at baseline, with complete data on baseline and follow-up waist circumference, baseline diet (192...... items food frequency questionnaire), body mass index, and selected potential confounders (eg, smoking status, sport activities, and intake of alcoholic beverages). Multiple linear regression analyses were performed. RESULTS: For women, 5-year difference in waist circumference was inversely related...... intake was positively associated. Sex differences occurred for vegetables, high-fat dairy products, and processed meat. CONCLUSIONS: The results suggest that a diet low in fruits and red meat and high in snack foods was associated with larger waist circumference gains in both sexes. Furthermore, in women...

  19. Undergraduates’ opinion after 5-year experience with rotary endodontic instruments

    OpenAIRE

    Flávia Sens Fagundes Tomazinho; Gisele Aihara Haragushiku; Flares Baratto Filho; Denise Piotto Leonardi; Maria da Graça Kfouri Lopes; Alexandre Moro

    2011-01-01

    Introduction: Dentistry evolution in the past few years has revolutionized daily practice in some specialties. One of these revolutions has occurred in Endodontics due to the advancement of rotary techniques for root canal preparation and its subsequent incorporation into the teaching of Dentistry undergraduates. Objective: The aim of this study was to report a 5-year experience on the undergraduate laboratorial and clinical use of rotary endodontic preparation at a private university. Materi...

  20. Insulin dependent diabetes in under 5 year olds.

    OpenAIRE

    Jefferson, I G; Smith, M A; Baum, J D

    1985-01-01

    Insulin dependent diabetes mellitus presenting in children under five years old exhibits several clinical and management features that differ from diabetes presenting in older children. In this review of the current population of the Oxford children's diabetes clinic, children with diabetes diagnosed aged 0- less than 5 years are compared with those diagnosed aged 5- less than 10 years to illustrate these differences. The mean annual age specific incidence of diabetes for children aged 0- les...

  1. Radiolytic oxidation of tamoxifen using the free radicals .OH and (or) HO2

    International Nuclear Information System (INIS)

    Leguene, C.; Clavere, P.; Jore, D.; Gardes-Albert, M.

    2001-01-01

    Tamoxifen is the most widely used antiestrogen in the treatment of breast cancer. In this work, we have studied its antioxidant properties. We have investigated the ability of tamoxifen to scavenge, in vitro, . OH and (or) HO 2 . free radicals that are produced by water radiolysis. Aqueous solutions of tamoxifen of concentrations ranging between 10 -5 and 2.5 x 10 -5 M have been irradiated (γ 137 Cs) in aerated acidic medium (H 3 PO 4 10 -3 M or HCOOH 10 -1 M). The results show that tamoxifen reacts quantitatively with . OH free radicals but does not react with HO 2 . free radicals under our experimental conditions. (author)

  2. Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma

    International Nuclear Information System (INIS)

    Ma, Ji; Zhang, Jian; Liu, Wenchao; Guo, Yan; Chen, Suning; Zhong, Cuiping; Xue, Yan; Zhang, Yuan; Lai, Xiaofeng; Wei, Yifang; Yu, Shentong

    2014-01-01

    Tamoxifen, an endocrine therapy drug used to treat breast cancer, is designed to interrupt estrogen signaling by blocking the estrogen receptor (ER). However, many ER-positive patients are low reactive or resistant to tamoxifen. Metformin is a widely used anti-diabetic drug with noteworthy anti-cancer effects. We investigated whether metformin has the additive effects with tamoxifen in ER-positive breast cancer therapy. The efficacy of metformin alone and in combination with tamoxifen against ER-positive breast cancer was analyzed by cell survival, DNA replication activity, plate colony formation, soft-agar, flow cytometry, immunohistochemistry, and nude mice model assays. The involved signaling pathways were detected by western blot assay. When metformin was combined with tamoxifen, the concentration of tamoxifen required for growth inhibition was substantially reduced. Moreover, metformin enhanced tamoxifen-mediated inhibition of proliferation, DNA replication activity, colony formation, soft-agar colony formation, and induction of apoptosis in ER-positive breast cancer cells. In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway. Finally, two-drug combination therapy significantly inhibited tumor growth in vivo. The present work shows that metformin and tamoxifen additively inhibited the growth and augmented the apoptosis of ER-positive breast cancer cells. It provides leads for future research on this drug combination for the treatment of ER-positive breast cancer

  3. Survival benefit of tamoxifen and aromatase inhibitor in male and female breast cancer.

    Science.gov (United States)

    Eggemann, Holm; Altmann, Udo; Costa, Serban-Dan; Ignatov, Atanas

    2018-02-01

    Our goal was to compare the survival advantage of tamoxifen (TAM) and aromatase inhibitor (AI) in female (FBC) and male breast cancer (MBC). We performed a retrospective study of 2785 FBC and 257 MBC patients treated with hormonal therapy. The median follow-up was 106 months (range 3-151 months) and 42 months (range 2-115 months) for FBC and MBC, respectively. The patients were divided into two groups according to the hormonal therapy used: TAM-treated and AI-treated. MBC was characterized by older age, advanced tumor stage, and higher rate of lymph node metastases, in comparison with FBC. Matching analysis was performed using six prognostic criteria: patient age, tumor stage, tumor grade, lymph node status, human epidermal growth factor receptor (HER2) status, and administration of chemotherapy. The female and male patients were matched 2:1. In this analysis, 316 women and 158 men treated with TAM, and 60 women and 30 men treated with AI, were included. The overall survival (OS) was estimated by the Kaplan-Meier method and was compared between FBC and MBC. TAM-treated FBC and MBC patients had similar 5-year OS, 85.1 and 89.2%, respectively (p = 0.972). Notably, FBC patients treated with AI had significantly greater 5-year OS (85.0%) in comparison with AI-treated MBC patients (5-year OS of 73.3%; p = 0.028). The OS of TAM-treated patients with MBC was similar to the OS of TAM-treated FBC patients, whereas AI treatment is associated with poorer survival of MBC patients.

  4. Mammographic density changes following discontinuation of tamoxifen in premenopausal women with oestrogen receptor-positive breast cancer.

    Science.gov (United States)

    Kim, Won Hwa; Cho, Nariya; Kim, Young-Seon; Yi, Ann

    2018-04-06

    To evaluate the changes in mammographic density after tamoxifen discontinuation in premenopausal women with oestrogen receptor-positive breast cancers and the underlying factors METHODS: A total of 213 consecutive premenopausal women with breast cancer who received tamoxifen treatment after curative surgery and underwent three mammograms (baseline, after tamoxifen treatment, after tamoxifen discontinuation) were included. Changes in mammographic density after tamoxifen discontinuation were assessed qualitatively (decrease, no change, or increase) by two readers and measured quantitatively by semi-automated software. The association between % density change and clinicopathological factors was evaluated using univariate and multivariate regression analyses. After tamoxifen discontinuation, a mammographic density increase was observed in 31.9% (68/213, reader 1) to 22.1% (47/213, reader 2) by qualitative assessment, with a mean density increase of 1.8% by quantitative assessment compared to density before tamoxifen discontinuation. In multivariate analysis, younger age (≤ 39 years) and greater % density decline after tamoxifen treatment (≥ 17.0%) were independent factors associated with density change after tamoxifen discontinuation (p density change with a mean density increase of 1.8%, which was associated with younger age and greater density change after tamoxifen treatment. • Increased mammographic density after tamoxifen discontinuation can occur in premenopausal women. • Mean density increase after tamoxifen discontinuation was 1.8%. • Density increase is associated with age and density decrease after tamoxifen.

  5. Prone Breast Intensity Modulated Radiation Therapy: 5-Year Results

    International Nuclear Information System (INIS)

    Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Fenton Kerimian, Maria; Goldberg, Judith D.; Formenti, Silvia C.

    2014-01-01

    Purpose: To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. Methods and Materials: Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. Results: Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm 3 , mean 19.65 cm 3 . In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm 3 , mean 1.59 cm 3 . There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. Conclusions: Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and fractionation

  6. Prone Breast Intensity Modulated Radiation Therapy: 5-Year Results

    Energy Technology Data Exchange (ETDEWEB)

    Osa, Etin-Osa O.; DeWyngaert, Keith [Department of Radiation Oncology, New York University School of Medicine, New York, New York (United States); Roses, Daniel [Department of Surgery, New York University School of Medicine, New York, New York (United States); Speyer, James [Department of Medical Oncology, New York University School of Medicine, New York, New York (United States); Guth, Amber; Axelrod, Deborah [Department of Surgery, New York University School of Medicine, New York, New York (United States); Fenton Kerimian, Maria [Department of Radiation Oncology, New York University School of Medicine, New York, New York (United States); Goldberg, Judith D. [Department of Population Health, New York University School of Medicine, New York, New York (United States); Formenti, Silvia C., E-mail: Silvia.formenti@nyumc.org [Department of Radiation Oncology, New York University School of Medicine, New York, New York (United States)

    2014-07-15

    Purpose: To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. Methods and Materials: Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. Results: Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm{sup 3}, mean 19.65 cm{sup 3}. In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm{sup 3}, mean 1.59 cm{sup 3}. There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. Conclusions: Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and

  7. Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial.

    Science.gov (United States)

    Forbes, John F; Sestak, Ivana; Howell, Anthony; Bonanni, Bernardo; Bundred, Nigel; Levy, Christelle; von Minckwitz, Gunter; Eiermann, Wolfgang; Neven, Patrick; Stierer, Michael; Holcombe, Chris; Coleman, Robert E; Jones, Louise; Ellis, Ian; Cuzick, Jack

    2016-02-27

    Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6-8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64-1·23]). The non-inferiority of anastrozole was established (upper 95% CI

  8. Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery.

    Science.gov (United States)

    Newman, M F; Grocott, H P; Mathew, J P; White, W D; Landolfo, K; Reves, J G; Laskowitz, D T; Mark, D B; Blumenthal, J A

    2001-12-01

    The importance of perioperative cognitive decline has long been debated. We recently demonstrated a significant correlation between perioperative cognitive decline and long-term cognitive dysfunction. Despite this association, some still question the importance of these changes in cognitive function to the quality of life of patients and their families. The purpose of our investigation was to determine the association between cognitive dysfunction and long-term quality of life after cardiac surgery. After institutional review board approval and patient informed consent, 261 patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled and followed for 5 years. Cognitive function was measured with a battery of tests at baseline, discharge, and 6 weeks and 5 years postoperatively. Quality of life was assessed with well-validated, standardized assessments at the 5-year end point. Our results demonstrate significant correlations between cognitive function and quality of life in patients after cardiac surgery. Lower 5-year overall cognitive function scores were associated with lower general health and a less productive working status. Multivariable logistic and linear regression controlling for age, sex, education, and diabetes confirmed this strong association in the majority of areas of quality of life. Five years after cardiac surgery, there is a strong relationship between neurocognitive functioning and quality of life. This has important social and financial implications for preoperative evaluation and postoperative care of patients undergoing cardiac surgery.

  9. Failure of siblings to thrive beyond 5 years of age

    Directory of Open Access Journals (Sweden)

    Himanshu Jain

    2013-01-01

    Full Text Available We describe a family in which parents had consanguinity, being children of real sisters. They had given birth to five children. In their family, children remained healthy from birth to pre-school age and then started having symptoms around the age of 5 years and two of them succumbed to this illness. Polyglandular autoimmune syndrome Type-1 is a rare sporadic autosomal recessive disease. It is characterized by the existence of two or more endocrinal disorders. Patients may require lifelong hormone replacement therapy for survival.

  10. 5 years survival after radiotherapy for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kujawska, J; Strzeszynski, J [Instytut Onkologii, Krakow (Poland)

    1973-01-01

    Radiotherapy was applied to 256 patients with lung cancer treated in the Institute of Oncology in Krakow in the years 1959-1967. Malignancy had been confirmed throughout in organs of the chest cavity, and diagnosed by microscopic examination. Eleven patients, i.e. 4%, survived 5 years. Survival rate was related to the stage of the disease and the microscopic pattern. Some patients were cured after irradiation of lung cancer, using nominal doses lower than the lethal dose for squamous cell cancer. The specific physical conditions of radiation absorption in the chest cavity evidently made the effective dose inside the cavity much higher than the nominal dose.

  11. The anticancer estrogen receptor antagonist tamoxifen impairs consolidation of inhibitory avoidance memory through estrogen receptor alpha.

    Science.gov (United States)

    Lichtenfels, Martina; Dornelles, Arethuza da Silva; Petry, Fernanda Dos Santos; Blank, Martina; de Farias, Caroline Brunetto; Roesler, Rafael; Schwartsmann, Gilberto

    2017-11-01

    Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats. In the first experiment, Wistar female rats received a single oral dose of tamoxifen (1, 3, or 10 mg/kg) or saline by gavage immediately after training and were tested for memory consolidation 24 h after training. In the second experiment, rats received a single dose of 1 mg/kg tamoxifen or saline by gavage 3 h after training and were tested 24 h after training for memory consolidation. In the third experiment, rats received a subcutaneous injection with estrogen receptor α agonist or estrogen receptor beta agonist 30 min before the training. After training, rats received a single oral dose of tamoxifen 1 mg/kg or saline and were tested 24 h after training. In the fourth experiment, rats were trained and tested 24 h later. Immediately after test, rats received a single dose of tamoxifen (1 mg/kg) or saline by gavage and were given four additional daily test trials followed by a re-instatement. Tamoxifen at 1 mg/kg impaired memory consolidation when given immediately after training and the estrogen receptor alpha agonist improved the tamoxifen-related memory impairment. Moreover, tamoxifen impairs memory consolidation of the test. These findings indicate that estrogen receptors regulate the early phase of memory consolidation and the effects of tamoxifen on memory consolidation.

  12. Antipsychotic Prescriptions for Children Aged 5 Years or Younger

    Directory of Open Access Journals (Sweden)

    Ana Lòpez-De Fede

    2014-10-01

    Full Text Available The use of antipsychotics in very young children is of concern given the lack of empirical evidence in their efficacy and long-term impact on children’s health. This study examined the prescription of antipsychotics among children aged ≤5 years enrolled in a state Medicaid program. Secondary data analysis was conducted using the Medicaid administrative data of a southeastern state. Using SAS 9.3, descriptive statistics were performed to examine socio-demographic characteristics, psychiatric diagnoses, off-label use, receipt of medications from multiple psychotropic drug classes, and receipt of non-pharmacologic psychiatric services among children aged ≤5 years who received antipsychotic prescriptions in calendar year (CY 2011. A total of 112 children in the target age group received antipsychotics in CY 2011, the most common prescription being risperidone. The most common listed psychiatric diagnosis was attention deficit hyperactivity disorder. Two in five children received antipsychotics for off-label use. Three in four children also received medications from at least one other psychotropic drug class. More than half did not receive adjunct psychiatric services. State-level policies offering specific guidance and recommendations for antipsychotic use among very young children are urgently needed. Future research is warranted to examine long-term impact of such practices on children’s growth and development.

  13. Changing patterns of clinical PET use - 5 years on

    International Nuclear Information System (INIS)

    Binns, D.; Hicks, R.J.

    2002-01-01

    Full text: Increasing clinical awareness and acceptance of the clinical role of positron emission tomography (PET) has the potential to alter patterns of referral. To assess whether patterns of referral are changing in response to greater experience with this technique, we reviewed indications of new referrals to our facility for each of the past 5 years of operation. Of more than 6,183 studies performed since our facility began operation in September 1996, 4,401 were initial referrals. Of these referrals the most common indications were carcinoma of the lung (n = 970, 22.0 %), colorectal cancer (n = 631, 14.3 %), malignant melanoma (n = 506, 11.5 %), genito-urinary tract cancer (n = 427, 9.7 %), epilepsy (n = 366, 8.3 %), and lymphoma (n = 351, 8.0 %). Referrals for all these indications, other than malignant melanoma, continued to grow in absolute terms throughout the 5 year interval but in relative terms only lung cancer maintained a similar proportion of scans reflecting an expansion of other referral indications. Evaluation of intractable partial complex seizures demonstrated the most marked growth in both absolute and relative terms. Conversely, malignant melanoma referrals declined as patients with thick melanoma began to have sentinel lymph node biopsy rather than PET as their initial staging investigation. Our experience suggests that clinical PET referrals reflect the expanding evidence-base regarding both the strengths and weaknesses of PET. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  14. Implementation of a new CT colonography service: 5 Year experience

    International Nuclear Information System (INIS)

    Lung, P.F.C.; Burling, D.; Kallarackel, L.; Muckian, J.; Ilangovan, R.; Gupta, A.; Marshall, M.; Shorvon, P.; Halligan, S.; Bhatnagar, G.; Bassett, P.; Taylor, S.A.

    2014-01-01

    Aim: To describe our experience using a 5 year audit of computed tomography colonography (CTC) practice and identify factors that influence diagnostic performance to guide implementation in other centres. Material and methods: Consecutive patients referred for CTC at a single institution over a 5 year period were identified, and reporting rates and positive predictive value (PPV) calculated for small polyps, large polyps, and colorectal cancer. Diagnostic performance was compared using the Chi-squared test, and trends over time were examined with logistic regression. The effect of faecal tagging and an intravenous spasmolytic were investigated using Fisher's exact test. Results: In total, 4355 CTC examinations were performed. Overall reporting rates and PPV were 17% and 92%, respectively. Negative predictive value (NPV) for cancer was 99.9%. A significant decrease in reporting rate (p < 0.001) was accompanied by an increase in PPV for small polyps (p = 0.02) following the introduction of faecal tagging. Adequacy rates for CTC improved over time (96% to 99%), with improved adequacy rates when using a spasmolytic, 98% versus 96% without. A significant difference in reporting rates, but not PPV, was found between radiologists. Conclusion: Accurate colonic investigation using CTC can be delivered safely to a high-risk patient population at a single centre. Faecal tagging and an intravenous spasmolytic improve diagnostic performance

  15. Clozapine for severe ("kraepelinian" schizophrenia: Sustained improvement over 5 years

    Directory of Open Access Journals (Sweden)

    Ricardo de Oliveira-Souza

    Full Text Available Abstract Clozapine has become a keystone in the treatment of schizophrenia because of its efficacy as an antipsychotic with negligible neuroleptic effects. The long-term stability of its effects, however, is poorly understood, because most studies have probed the usefulness of clozapine over a period of weeks to several months at the most. Knowing whether clozapine's benefits are sustained over the very long-term, i.e., more than 5 years, may be critical for cost-benefit analyses. Objective: To report the results of an open study on the efficacy of clozapine over the very long-term. Methods: Thirty-three adults (26 men with severe (kraepelinian schizophrenia were assessed at regular intervals using a brief neuropsychiatric battery over a 5-year period. Results: A significant improvement was observed between the pre-clozapine and the first "on-clozapine" evaluation. This improvement was paralleled by a remarkable conversion of schizophrenia from "active" (mostly paranoid into "residual" in 70% of all patients. Eight patients became functionally productive to the point of being capable of living an independent life. Roughly one-third of our cases showed no improvement. Conclusions: Clozapine is a safe and effective drug for patients with severe schizophrenia who have failed to improve on other antipsychotic drugs. Clozapine's maximal benefit is established by the end of the first year of treatment and continues unabated for many years thereafter. Clozapine-resistant patients remain a major challenge calling for the discovery of new treatments for schizophrenia.

  16. Oil Sands Regional Aquatics Monitoring Program (RAMP) 5 year report

    International Nuclear Information System (INIS)

    Fawcett, K.

    2003-05-01

    This 5 year report outlined and examined the activities of the Regional Aquatics Monitoring Program (RAMP) from its introduction in 1997 up to 2001. The RAMP is a multi-stakeholder program comprised of industry and government representatives as well as members of aboriginal groups and environmental organizations. The objectives of RAMP are to monitor aquatic environments in the oil sands region in order to allow for assessment of regional trends and cumulative effects, as well as to provide baseline data against which impact predictions of recent environmental impact assessments can be verified. Scientific programs conducted as part of RAMP during the 5-year period included water quality and sediment quality analyses; fish monitoring; benthic communities monitoring; water quality and aquatic vegetation analyses of wetlands; and hydrology and climate monitoring. RAMP's programs have expanded annually in scope as a result of increased oil sands development in the region. This report provided outlines of RAMP's individual program objectives and organizational structures, as well as details of all studies conducted for each year. Data were collected for all major study areas were presented, and program methodologies for assessing and identifying trends were outlined. refs., tabs., figs

  17. CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen

    Energy Technology Data Exchange (ETDEWEB)

    Prather, Paul L. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M. [Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); Ford, Benjamin M.; Franks, Lirit N. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); Radominska-Pandya, Anna, E-mail: RadominskaAnna@uams.edu [Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States)

    2013-11-15

    Highlights: •Tamoxifen produces cytotoxicity via estrogen-receptor (ER) independent mechanisms. •Tamoxifen binds to CB1 and CB2 cannabinoid receptors and acts as an inverse agonist. •CB1 and CB2 receptors are novel molecular targets for Tamoxifen. •ER-independent effects for Tamoxifen may be mediated via CB1 and/or CB2 receptors. -- Abstract: Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9–3 μM). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs. Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel

  18. CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen

    International Nuclear Information System (INIS)

    Prather, Paul L.; FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M.; Ford, Benjamin M.; Franks, Lirit N.; Radominska-Pandya, Anna

    2013-01-01

    Highlights: •Tamoxifen produces cytotoxicity via estrogen-receptor (ER) independent mechanisms. •Tamoxifen binds to CB1 and CB2 cannabinoid receptors and acts as an inverse agonist. •CB1 and CB2 receptors are novel molecular targets for Tamoxifen. •ER-independent effects for Tamoxifen may be mediated via CB1 and/or CB2 receptors. -- Abstract: Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9–3 μM). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs. Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel

  19. CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer

    DEFF Research Database (Denmark)

    Regan, Meredith M; Leyland-Jones, Brian; Bouzyk, Mark

    2012-01-01

    Adjuvant tamoxifen therapy is effective for postmenopausal women with endocrine-responsive breast cancer. Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. In this study, we investigated...

  20. Identification of a putative protein-profile associating with tamoxifen therapy-resistance in breast cancer

    NARCIS (Netherlands)

    A. Umar (Arzu); J.W.M. Martens (John); J.A. Foekens (John); L. Paša-Tolić (Ljiljana); H. Kang; A.M. Timmermans (Mieke); M.P. Look (Maxime); M.E. Meijer van Gelder (Marion); N. Jaitly (Navdeep); M.A. den Bakker (Michael)

    2009-01-01

    textabstractTamoxifen-resistance is a major cause of death in patients with recurrent breast cancer. Current clinical parameters can correctly predict therapy response in only half of the treated patients. Identification of proteins that associate with tamoxifen-resistance is a first step towards

  1. Tamoxifen therapy for the management of pubertal gynecomastia: a systematic review

    NARCIS (Netherlands)

    Lapid, Oren; van Wingerden, Jan J.; Perlemuter, Leon

    2013-01-01

    Objective: A systematic review to assess the efficacy of tamoxifen in the management of idiopathic pubertal gynecomastia. Data sources: Searches were conducted using the databases of Medline (search engine PubMed) and Web of Science (R). Study selection: Studies reporting the use of Tamoxifen for

  2. Fibroblast growth factor receptor 4 predicts failure on tamoxifen therapy in patients with recurrent breast cancer

    NARCIS (Netherlands)

    Meijer, Danielle; Sieuwerts, Anieta M.; Look, Maxime P.; van Agthoven, Ton; Foekens, John A.; Dorssers, Lambert C. J.

    2008-01-01

    Tamoxifen treatment of estrogen-dependent breast cancer ultimately loses its effectiveness due to the development of resistance. From a functional screen for identifying genes responsible for tamoxifen resistance in human ZR-75-1 breast cancer cells, fibroblast growth factor (FGF) 17 was recovered.

  3. Mitotically Active Leiomyoma of the Uterus in a Postmenopausal Breast Cancer Patient Receiving Tamoxifen

    Directory of Open Access Journals (Sweden)

    I-Feng Liu

    2006-06-01

    Conclusion: Endometrial cancer is rarely noted in breast cancer patients taking tamoxifen. Further, none have reported mitotically active leiomyoma of the uterus. From this case, endometrial proliferation and mitotically active leiomyoma of the uterus may be related to tamoxifen therapy, and should not be neglected in breast cancer patients.

  4. Dextromethorphan as a phenotyping test to predict endoxifen exposure in patients on tamoxifen treatment

    NARCIS (Netherlands)

    Graan, A.J. de; Teunissen, S.F.; Vos, F.Y. de; Loos, W.J.; Schaik, R.H. van; Jongh, F.E. de; Vos, A.I. de; Alphen, R.J. van; Holt, B. van der; Verweij, J.; Seynaeve, C.; Beijnen, J.H.; Mathijssen, R.H.

    2011-01-01

    PURPOSE: Tamoxifen, a widely used agent for the prevention and treatment of breast cancer, is mainly metabolized by CYP2D6 and CYP3A to form its most abundant active metabolite, endoxifen. Interpatient variability in toxicity and efficacy of tamoxifen is substantial. Contradictory results on the

  5. Dextromethorphan as a phenotyping test to predict endoxifen exposure in patients on tamoxifen treatment.

    Science.gov (United States)

    de Graan, Anne-Joy M; Teunissen, Sebastiaan F; de Vos, Filip Y F L; Loos, Walter J; van Schaik, Ron H N; de Jongh, Felix E; de Vos, Aad I; van Alphen, Robbert J; van der Holt, Bronno; Verweij, Jaap; Seynaeve, Caroline; Beijnen, Jos H; Mathijssen, Ron H J

    2011-08-20

    Tamoxifen, a widely used agent for the prevention and treatment of breast cancer, is mainly metabolized by CYP2D6 and CYP3A to form its most abundant active metabolite, endoxifen. Interpatient variability in toxicity and efficacy of tamoxifen is substantial. Contradictory results on the value of CYP2D6 genotyping to reduce the variable efficacy have been reported. In this pharmacokinetic study, we investigated the value of dextromethorphan, a known probe drug for both CYP2D6 and CYP3A enzymatic activity, as a potential phenotyping probe for tamoxifen pharmacokinetics. In this prospective study, 40 women using tamoxifen for invasive breast cancer received a single dose of dextromethorphan 2 hours after tamoxifen intake. Dextromethorphan, tamoxifen, and their respective metabolites were quantified. Exposure parameters of all compounds were estimated, log transformed, and subsequently correlated. A strong and highly significant correlation (r = -0.72; P dextromethorphan (0 to 6 hours) and endoxifen (0 to 24 hours). Also, the area under the plasma concentration-time curve of dextromethorphan (0 to 6 hours) and daily trough endoxifen concentration was strongly correlated (r = -0.70; P dextromethorphan exposure. Dextromethorphan exposure after a single administration adequately predicted endoxifen exposure in individual patients with breast cancer taking tamoxifen. This test could contribute to the personalization and optimization of tamoxifen treatment, but it needs additional validation and simplification before being applicable in future dosing strategies.

  6. The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy.

    Science.gov (United States)

    Dorchies, Olivier M; Reutenauer-Patte, Julie; Dahmane, Elyes; Ismail, Heham M; Petermann, Olivier; Patthey- Vuadens, Ophélie; Comyn, Sophie A; Gayi, Elinam; Piacenza, Tony; Handa, Robert J; Décosterd, Laurent A; Ruegg, Urs T

    2013-02-01

    Duchenne muscular dystrophy (DMD) is a severe disorder characterized by progressive muscle wasting,respiratory and cardiac impairments, and premature death. No treatment exists so far, and the identification of active substances to fight DMD is urgently needed. We found that tamoxifen, a drug used to treat estrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx(5Cv) mouse model of DMD. Oral tamoxifen treatment from 3 weeks of age for 15 months at a dose of 10 mg/kg/day stabilized myofiber membranes, normalized whole body force, and increased force production and resistance to repeated contractions of the triceps muscle above normal values. Tamoxifen improved the structure of leg muscles and diminished cardiac fibrosis by~ 50%. Tamoxifen also reduced fibrosis in the diaphragm, while increasing its thickness,myofiber count, and myofiber diameter, thereby augmenting by 72% the amount of contractile tissue available for respiratory function. Tamoxifen conferred a markedly slower phenotype to the muscles.Tamoxifen and its metabolites were present in nanomolar concentrations in plasma and muscles,suggesting signaling through high-affinity targets. Interestingly, the estrogen receptors ERa and ERb were several times more abundant in dystrophic than in normal muscles, and tamoxifen normalized the relative abundance of ERb isoforms. Our findings suggest that tamoxifen might be a useful therapy for DMD.

  7. Antiarrhythmic effect of tamoxifen on the vulnerability induced by hyperthyroidism to heart ischemia/reperfusion damage.

    Science.gov (United States)

    Pavón, Natalia; Hernández-Esquivel, Luz; Buelna-Chontal, Mabel; Chávez, Edmundo

    2014-09-01

    Hyperthyroidism, known to have deleterious effects on heart function, and is associated with an enhanced metabolic state, implying an increased production of reactive oxygen species. Tamoxifen is a selective antagonist of estrogen receptors. These receptors make the hyperthyroid heart more susceptible to ischemia/reperfusion. Tamoxifen is also well-known as an antioxidant. The aim of the present study was to explore the possible protective effect of tamoxifen on heart function in hyperthyroid rats. Rats were injected daily with 3,5,3'-triiodothyronine at 2mg/kg body weight during 5 days to induce hyperthyroidism. One group was treated with 10mg/kg tamoxifen and another was not. The protective effect of the drug on heart rhythm was analyzed after 5 min of coronary occlusion followed by 5 min reperfusion. In hyperthyroid rats not treated with tamoxifen, ECG tracings showed post-reperfusion arrhythmias, and heart mitochondria isolated from the ventricular free wall lost the ability to accumulate and retain matrix Ca(2+) and to form a high electric gradient. Both of these adverse effects were avoided with tamoxifen treatment. Hyperthyroidism-induced oxidative stress caused inhibition of cis-aconitase and disruption of mitochondrial DNA, effects which were also avoided by tamoxifen treatment. The current results support the idea that tamoxifen inhibits the hypersensitivity of hyperthyroid rat myocardium to reperfusion damage, probably because its antioxidant activity inhibits the mitochondrial permeability transition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Dried blood spots voor het bepalen van de serumconcentratie van tamoxifen en zijn actieve metaboliet endoxifen

    NARCIS (Netherlands)

    Jager, Nynke G L; Rosing, Hilde; Schellens, Jan H M; Beijnen, Jos H.; Linn, Sabine C.

    2016-01-01

    OBJECTIVE To establish the relationship between dried blood spot (DBS) and serum concentrations of tamoxifen and endoxifen in order to allow the use of DBS sampling, a simple and patient-friendly alternative to venous sampling, in clinical practice. The antiestrogenic effect of tamoxifen is

  9. Approaches for predicting effects of unintended environmental exposure to an endocrine active pharmaceutical, tamoxifen

    Science.gov (United States)

    Tamoxifen is an endocrine-active pharmaceutical (EAP) that is used world-wide. Because tamoxifen is a ubiquitous pharmaceutical and interacts with estrogen receptors, a case study was conducted with this compound to (1) determine effects on reproductive endpoints in a nontarget s...

  10. Quality of life in cancer survivors 5 years or more after total gastrectomy: a case-control study.

    Science.gov (United States)

    Lee, Seung Soo; Chung, Ho Young; Kwon, Oh Kyoung; Yu, Wansik

    2014-01-01

    This study investigated how total gastrectomy (TG), along with memories of cancer, affect the subjective wellness of survivors long after surgery. Rational approaches for effectively improving the quality of life (QoL) of these survivors were suggested. Between 2008 and 2013, QoL data of gastric cancer patients who underwent a curative TG, were obtained at 5-year postoperative follow-up visits (5-year survivors) and at visits beyond 5 years (long-term survivors). The control groups for these survivor groups were constructed from volunteers who visited our health-examination center for annual medical checkups. The Korean versions of the European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and the gastric cancer specific module, the EORTC QLQ-STO22, were used to assess QoL. Five-year survivors showed worse QoL compared to the control group in role functioning, social functioning, nausea/vomiting, appetite loss, financial difficulties, reflux, eating restrictions, taste, and body image, and better QoL in the emotional and cognitive functioning scales. In long-term survivors, deterioration in QoL were still apparent in financial difficulties, reflux, and eating restrictions, while QoL differences in the remaining scales had diminished. Surviving 5 years after TG does not result in living in a carefree state in terms of QoL. After 5 postoperative years, survivors still need extended care for deteriorated QoL indicators due to symptomatic, behavioral, and financial consequences of surgery. While relevant clinical and institutional approaches are required for corresponding declines in QoL, such efforts must extend beyond 5 postoperative years. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  11. Postoperative radiation therapy for adenoid cystic carcinoma

    International Nuclear Information System (INIS)

    Oguchi, Masahiko; Shikama, Naoto; Gomi, Koutarou; Shinoda, Atsunori; Nishikawa, Atsushi; Arakawa, Kazukiyo; Sasaki, Shigeru; Takei, Kazuyoshi; Sone, Syusuke

    2000-01-01

    The authors retrospectively assessed the usefulness of postoperative radiation therapy after local resection of adenoid cystic carcinoma, with emphasis on organ-conserving treatment and the cosmetic results. Between 1985 and 1995, 32 patients underwent local resection followed by postoperative radiation therapy with curative and organ-conserving intent. None of patients received any form of chemotherapy as part of their initial treatment. Radiation therapy was carried out by techniques that were appropriate for the site and extension of each tumor. The 5-year local control, disease-free, and overall survival rates of all patients were 76%, 68%, and 86%, respectively. The 5-year local control rate and disease-free survival rate of patients with microscopically positive margins were 89% and 75%, respectively, and higher than in patients with macroscopically residual disease, but no significant difference in 5-year overall survival rate was observed. The postoperative cosmetic results in 29 patients with head and neck lesions were evaluated. No difference was documented between the cosmetic results postoperatively setting and after postoperative radiotherapy, and no significant differences in cosmetic results were observed according to radiation dose. The combination of local resection with organ-conserving intent and postoperative radiation therapy provided good cosmetic results in patients with T1 or T2 lesions. Postoperative radiation therapy with smaller fractions is useful, because good local control can be achieved in patients with adenoid cystic carcinoma having microscopically positive margins without inducing any late adverse reactions. However, the number of patients was too small and the follow-up period was too short to draw any definite conclusion in regard to fraction size. A much longer follow-up study with a larger number patients will be required to accurately determine the optimal treatment intensity and duration of treatment. (K.H.)

  12. Achalasia 5 years following Roux-en-y gastric bypass

    Directory of Open Access Journals (Sweden)

    Mehyar Hefazi Torghabeh

    2015-01-01

    Full Text Available Oesophageal achalasia is a rare, but serious condition in which the motility of the lower oesophageal sphincter (LES is inhibited. This disorder of idiopathic aetiology complicates the peristaltic function and relaxation of the LES that may cause symptoms such as dysphagia, epigastric pain, and regurgitation of an obstructed food. The following case describes achalasia in a patient 5 years following a laparoscopic Roux-en-Y gastric bypass (RYGB. The patient underwent a laparoscopic Heller myotomy without a fundoplication. Although achalasia seems to be a rare occurrence in obese patients, this is the third case documented in a patient who previously had an RYGB. The role of performing a fundoplication in these patients remains to be elucidated.

  13. Pineal gliosarcoma in a 5-year-old girl

    Directory of Open Access Journals (Sweden)

    Ana María Granados, PhD

    2018-02-01

    Full Text Available The purpose of this paper is to report a rare case of a pediatric pineal gliosarcoma. Gliomas on the pineal region are uncommon, representing 0.4%-1% of all brain tumors. Furthermore, pediatric gliosarcomas are a very rare entity. We present a case of a 5-year-old girl, with a history of headache, vomiting, diplopia, and gait disturbances. A pineal tumor was found with pathology results consistent with a gliosarcoma. A total of 25 cases of pediatric gliosarcomas have been reported, none of them in pineal topography. Only 3 gliosarcomas were found in the pineal region, but these were found in adults. To our knowledge, this is the first pediatric pineal gliosarcoma reported in the literature.

  14. How to reduce scientific irreproducibility: the 5-year reflection.

    Science.gov (United States)

    Fiala, Clare; Diamandis, Eleftherios P

    2017-10-26

    We discuss in depth six causes of scientific irreproducibility and their ramifications for the clinical sciences: fraud, unfounded papers published by prominent authorities, bias, technical deficiencies, fragmented science and problems with big data. Some proposed methods to combat this problem are briefly described, including an effort to replicate results from some high impact papers and a proposal that authors include detailed preclinical data in papers with supposedly high translational value. We here advocate for a 5-year reflection on papers with seemingly high clinical/translational potential, published alongside the original paper where authors reflect on the quality, reproducibility and impact of their findings. These reflections can be used as a benchmark for credibility, and begin a virtuous cycle of improving the quality of published findings in the literature.

  15. 5 years prognostic value of dipyridamole-thallium myocardial imaging

    International Nuclear Information System (INIS)

    Yang Yifeng; Qian Zhonghao; Jiang Changying

    1993-01-01

    A prognostic study of dipyridamole-thallium myocardial imaging was conducted with the use of logistic regression. Over a 5 years follow-up period, cardiac events occurred in 13 patients within the 41 patients tested, death in 5 and myocardial infarction in 8. The results of this study indicates that dipyridamole-thallium imaging has significant prognostic utility and that an abnormal scan increased the relative risk for the development of subsequent myocardial infarction or cardiac death (O.R. 18.54). The presence of transient multiple thallium defects further increased the risk of a cardiac event. In conclusion , intravenous dipyridamole thallium imaging is a potentially useful diagnostic test to determine the presence and severity of coronary diseases, and this noninvasive method is also beneficial for prognosis

  16. How do 5-year-olds understand questions?

    DEFF Research Database (Denmark)

    Sauerland, Uli; Grohmann, Kleanthes; Teresa Guasti, Maria

    2016-01-01

    developing children across 19 European countries, 18 different languages, and 7 language (sub-)families. The study investigated the effects of two factors on question formation: (a) whether the question contains a simple interrogative word like ‘who’ or a complex one like ‘which princess’, and (b) whether......The comprehension of constituent questions is an important topic for language acquisition research and for applications in the diagnosis of language impairment. This article presents the results of a study investigating the comprehension of different types of questions by 5-year-old, typically...... the question word was related to the sentential subject or object position of the verb. The findings show that there is considerable variation among languages, but the two factors mentioned consistently affect children’s performance. The cross-linguistic variation shows that three linguistic factors facilitate...

  17. Poly(amidoamine-Cholesterol Conjugate Nanoparticles Obtained by Electrospraying as Novel Tamoxifen Delivery System

    Directory of Open Access Journals (Sweden)

    R. Cavalli

    2011-01-01

    Full Text Available A new poly(amidoamine-cholesterol (PAA-cholesterol conjugate was synthesized, characterized and used to produce nanoparticles by the electrospraying technique. The electrospraying is a method of liquid atomization that consists in the dispersion of a solution into small charged droplets by an electric field. Tuning the electrospraying process parameters spherical PAA-chol nanoparticles formed. The PAA-cholesterol nanoparticles showed sizes lower than 500 nm and spherical shape. The drug incorporation capacity was investigated using tamoxifen, a lipophilic anticancer drug, as model drug. The incorporation of the tamoxifen did not affect the shape and sizes of nanoparticles showing a drug loading of 40%. Tamoxifen-loaded nanoparticles exhibited a higher dose-dependent cytotoxicity than free tamoxifen, while blank nanoparticles did not show any cytotoxic effect at the same concentrations. The electrospray technique might be proposed to produce tamoxifen-loaded PAA-chol nanoparticle in powder form without any excipient in a single step.

  18. Production and Investigation of Controlled Drug Release Properties of Tamoxifen Loaded Alginate-Gum Arabic Microbeads

    Directory of Open Access Journals (Sweden)

    Rukiye Yavaşer

    2016-08-01

    Full Text Available The entrapment of tamoxifen onto alginate-gum arabic beads and the production of controlled drug release was investigated in this study. The polymeric system that would provide the controlled release of tamoxifen was formed using alginate and gum arabic. In the first phase of the study, the optimization of the alginate-gum arabic beads production was conducted; then the study continued with drug entrapment experiments. Tamoxifen entrapment yield was found to be approximately 90% of initial tamoxifen concentration. In vitro drug release experiments were performed in simulated gastric juice and intestinal fluid where the tamoxifen release was 20% and 53% of the initial drug present, respectively. As a result of this study, it is expected that a valuable contribution to the field of controlled drug release system production is realized.

  19. Risk of skin cancer following tamoxifen treatment in more than 16,000 breast cancer patients

    DEFF Research Database (Denmark)

    Præstegaard, Camilla; Kjaer, Susanne K.; Andersson, Michael

    2016-01-01

    Background: Women with breast cancer are at increased risk of developing skin cancer. Little is known about how tamoxifen affects this risk. We aimed to investigate whether tamoxifen treatment following breast cancer is associated with skin cancer. Methods: A cohort consisting of 44,589 women...... diagnosed with breast cancer during 1977–2007 from the nationwide clinical database of the Danish Breast Cancer Cooperative Group, was followed for a primary skin cancer [basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or melanoma] in the Danish Cancer Registry supplemented by data on BCC and SCC...... from the Danish Pathology Register. We investigated incidence of skin cancer among 16,214 women treated with tamoxifen compared to 28,375 women not treated with tamoxifen by calculating incidence rate ratios (IRRs) in Cox regression models. Results: Tamoxifen users were followed for a median of 2...

  20. Evaluation of Nutritional Status Post Laparoscopic Sleeve Gastrectomy-5-Year Outcomes.

    Science.gov (United States)

    Al-Mutawa, Aliaa; Al-Sabah, Salman; Anderson, Alfred Kojo; Al-Mutawa, Mohammad

    2017-12-01

    Obesity is considered a public health problem and has led to advancements in bariatric surgery. Laparoscopic sleeve gastrectomy (LSG) had become the most performed procedure worldwide; however, its consequences on nutritional status in the short and long term are of concern. A retrospective analysis of medical records and bariatric database of patients who underwent LSG from October 2008-September 2015 at Al-Amiri Hospital, Kuwait, was performed. Data regarding nutritional status along with demographic data were collected over a 5-year follow-up period. One thousand seven hundred ninety-three patients comprising of 74% females and 26% males were included. The greatest % total body weight loss (%TBWL) was at 18 months post-LSG (33%), corresponding to a % excess weight loss (%EWL) of 73.8%. With regard to nutritional status, vitamin B1 showed a significant drop at 3-5 years post-op in comparison to pre-op value, but stayed within the normal range throughout the study. Red blood cells count, hemoglobin, and hematocrit also showed a significant drop starting from 6 months post-op until the fifth year of follow-up. On the other hand, vitamins B6 and B12 showed a significant increase at 6 months post-op and decreased afterwards, but did not reach pre-op values. Vitamin D also showed a significant increase throughout the study period from deficient value at the pre-op time, but remained insufficient. Albumin, transferrin, folate, ferritin, iron, and vitamin B2 showed no significant changes at 5 years post-LSG compared to pre-op values. Little is known about the nutritional status and optimal nutritional care plan post-LSG, especially in the longer term. Nutritional deficiencies were prevalent prior and post-LSG. Some of the nutritional parameters improved and even reached the abnormal high level post-LSG. These observations highlight the importance of pre- and post-operative nutritional assessment and tailored supplementation to ensure optimal nutritional status.

  1. Accidental head injuries in children under 5 years of age

    International Nuclear Information System (INIS)

    Johnson, K.; Fischer, T.; Chapman, S.; Wilson, B.

    2005-01-01

    AIM: To evaluate the type and nature of head injuries sustained by children under the age of 5 years who present to a busy accident and emergency (A and E) department following an accidental fall. MATERIALS AND METHODS: This study included all children under the age of 5 years, who over an 8-month period were referred to our A and E Department with head injury following an accidental fall. Data were collected regarding the height of the fall, whether or not stairs were involved, the type of surface that the child landed on and the height of the child. This was correlated with any soft-tissue injury or skull fracture. RESULTS: A total of 72 children (aged 4 months to 4.75 years) fulfilled all the criteria for an accidental fall. The heights of the falls ranged from less than 50 cm to over 3 m, with the majority below 1 m. Of the falls, 49 were onto a hard surface and 23 were onto a soft surface. Of the 72 children, 52 had visible evidence of head injury, 35 (71%) of 49 being the result of falls onto hard surfaces and 17 (74%) of 23 onto soft (carpeted) surfaces. There was no significant difference in the type of surface that resulted in a visible head injury. A visible head injury was seen in all children who fell from a height of over 1.5 m and in 95% of children who fell over 1 m. Of the 72 children, 32 (44%) had skull radiographs performed in accordance with established guidelines and 4 (12.5%) were identified as having a fracture. Of the 3 linear parietal fractures 2 were inflicted by falls of just over 1 m (from a work surface) and 1 by a fall of 80 to 90 cm onto the hard-edged surface of a stone fire surround. The 4th was a fracture of the base of skull following a fall from more than 3 m (from a first-storey window). CONCLUSIONS: In the vast majority of domestic accidents children do not suffer significant harm. Skull fractures are rare and probably occur in less than 5% of cases. To cause a skull fracture the fall needs to be from over 1 m or, if from a

  2. A randomized trial of tamoxifen with or without breast radiation in women over 50 years of age with T1/2 N0 disease

    International Nuclear Information System (INIS)

    Fyles, A.; Manchul, L.; McCready, D.; Merante, P.; Pintilie, M.; Trudeuau, M.; Olivotto, I.; Weir, L.

    2003-01-01

    To determine the effect of breast radiation (RT) on disease-free survival (DFS) and ipsilateral breast relapse (IBR) in women over 50 with T1 and T2 node negative breast cancer. Between December 1992 and June 2000, 769 women were randomized to RT and Tamoxifen (Tam) 20 mg daily for 5 years or Tam alone. Median age was 68 years, 639 patients had pT1 lesions and ER/PR were positive in 700 patients. Six hundred and thirty-four patients had pathologically negative nodes and 135 over age 65 were clinically node negative. Median follow-up was 5.6 years and patient and tumour characteristics were well balanced between the two arms. Overall, there were 54 relapses from breast cancer in the Tam arm and 27 in the Tam + RT arm. IBR at 5 years was 7.7% in the Tam arm compared to 0.6% in the Tam + RT group (p<0.0001). Significant factors for breast relapse and DFS at 5 years included tumour size (p=0.02 and 0.0001 respectively), hormone-receptor status (p=0.0008 and 0.0001), grade (p=0.001 and 0.003) and treatment arm (p=0.0001 and 0.004). Four-hundred and nineteen patients with low-risk features (T1, receptor-positive and grade 1/2) treated with Tam alone had a 5% risk of IBR at 5 years, increasing to 10% at 8 years. There was no difference in relapse at regional or distant sites, or in the contralateral breast. No difference was seen in the number of deaths due to breast cancer (13 and 11 for Tam + RT and Tam, respectively), nor in OS (93% at 5 years in both arms). Tamoxifen and breast RT results in a significantly lower rate of breast relapse than Tam alone in women over 50 with node-negative breast cancer. There does not appear to be a low-risk group who can be treated with Tamoxifen without breast radiation

  3. Salt repository sealing materials development program: 5-year work plan

    International Nuclear Information System (INIS)

    Myers, L.B.

    1986-06-01

    This plan covers 5 years (fiscal years 1986 through 1990) of work in the repository sealing materials program to support design decisions and licensing activities for a salt repository. The plan covers a development activity, not a research activity. There are firm deliverables as the end points of each part of the work. The major deliverables are: development plans for code development and materials testing; seal system components models; seal system performance specifications; seal materials specifications; and seal materials properties ''handbook.'' The work described in this plan is divided into three general tasks as follows: mathematical modeling; materials studies (salt, cementitious materials, and earthen materials); and large-scale testing. Each of the sections presents an overview, status, planned activities, and summary of program milestones. This plan will be the starting point for preparing the development plans described above, but is subject to change if preparation of the work plan indicates that a different approach or sequence is preferable to achieve the ultimate goal, i.e., support of design and licensing

  4. CB1 and CB2 Receptors are Novel Molecular Targets for Tamoxifen and 4OH-Tamoxifen

    OpenAIRE

    Prather, Paul L.; FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M.; Ford, Benjamin M.; Franks, Lirit N.; Radominska-Pandya, Anna

    2013-01-01

    Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for t...

  5. Postoperative radiotherapy for intracranial meningioma

    International Nuclear Information System (INIS)

    Chun, Ha Chung; Lee, Myung Za

    2001-01-01

    To evaluate the effectiveness and tolerance of postoperative external radiotherapy for patients with intracranial meningiomas. The records of thirty three patients with intracranial meningiomas who were treated with postoperative external irradiation at our institution between Feb, 1988 and Nov, 1999 were retrospectively analyzed. Median age of patients at diagnosis was 53 years with range of 17 to 68 years. Sites of involvement were parasagital, cerebral convexity, sphenoid ridge, parasellar and tentorium cerebella. Of 33 evaluated patients, 15 transitional, 10 meningotheliomatous, 4 hemangiopericytic, 3 atypical and 1 malignant meningioma were identified. Four patients underwent biopsy alone and remaining 29 patients underwent total tumor resection. A dose of 50 to 60 Gy was delivered in 28-35 daily fractions over a period of 5 to 7 weeks. Follow-up period ranged from 12 months to 8 years. The actuarial survival rates at 5 and 7 years for entire group of patients were 78% and 67%, respectively. The corresponding disease free survival rates were 73% and 61 %, respectively. The overall local control rate at 5 years was 83%. One out of 25 patients in benign group developed local failure, while 4 out of 8 patients in malignant group did local failure (p <0.05), Of 4 patients who underwent biopsy alone, 2 developed local failure. There was no significant difference in 5 year actuarial survival between patients who underwent total tumor resection and those who did biopsy alone. Patients whose age is under 60 showed slightly better survival than those whose age is 60 or older, although this was not statistically significant. There was no documented late complications in any patients. Based on our study, we might conclude that postoperative external beam radiotherapy tends to improve survival of patients with intracranial meningiomas comparing with surgery alone

  6. Novel Carbonyl Analogs of Tamoxifen: Design, Synthesis, and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Konstantinos M. Kasiotis

    2017-09-01

    Full Text Available Aim of this work was to provide tamoxifen analogs with enhanced estrogen receptor (ER binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known ER inhibitor ICI182,780. Theoretical calculations and molecular modeling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

  7. A misdiagnosed Riedel's thyroiditis successfully treated by thyroidectomy and tamoxifen.

    Science.gov (United States)

    Wang, Chih-Jung; Wu, Ta-Jen; Lee, Chung-Ta; Huang, Shih-Ming

    2012-12-01

    Riedel's thyroiditis, known as invasive fibrous thyroiditis, is a very rare form of chronic thyroiditis. It is hard to make the diagnosis without surgical biopsy. We present a case of Riedel's thyroiditis in a 52-year-old female with past history of Hashimoto's thyroiditis. She suffered from bilateral neck pain, which radiated to both lower jaws. The erythrocyte sedimentation rate was 125 mm/hour. Subacute thyroiditis superimposed on Hashimoto's thyroiditis was diagnosed and treated with steroid. However the response was poor and she had a history of severe peptic ulcer. To avoid inducing the peptic ulcer by steroid, she received bilateral subtotal thyroidectomy. During surgery, the thyroid had severe adhesion to surrounding soft tissue and the pathology showed Riedel's thyroiditis. The neck pain improved after thyroidectomy. Tamoxifen has been given for 8 months and the size of remnant thyroid decreased to 8 mm. We concluded that combined thyroidectomy and tamoxifen successfully cured a patient with Riedel's thyroiditis. Copyright © 2012. Published by Elsevier B.V.

  8. Novel Carbonyl Analogues of Tamoxifen: Design, Synthesis, and Biological Evaluation

    Science.gov (United States)

    Kasiotis, Konstantinos M.; Lambrinidis, George; Fokialakis, Nikolas; Tzanetou, Evangelia N.; Mikros, Emmanuel; Haroutounian, Serkos A.

    2017-09-01

    Aim of this work was to provide tamoxifen analogues with enhanced estrogen receptor binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known estrogen receptor inhibitor ICI182,780. Theoretical calculations and molecular modelling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

  9. Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: Proteomic characterization

    International Nuclear Information System (INIS)

    Wang Ying; He Qingyu; Chen Hongming; Chiu Jenfu

    2007-01-01

    The anti-estrogen tamoxifen and vitamin A-related compound, all-trans retinoic acid (RA), in combination act synergistically to inhibit the growth of MCF-7 human breast cancer cells. In the present study, we applied two-dimensional gel electrophoresis based proteomic approach to globally analyze this synergistic effect of RA and tamoxifen. Proteomic study revealed that multiple clusters of proteins were involved in RA and tamoxifen-induced apoptosis in MCF-7 breast cancer cells, including post-transcriptional and splicing factors, proteins related to cellular proliferation or differentiation, and proteins related to energy production and internal degradation systems. The negative growth factor-transforming growth factor β (TGFβ) was secreted by RA and/or tamoxifen treatment and was studies as a potential mediator of the synergistic effects of RA and tamoxifen in apoptosis. By comparing protein alterations in treatments of RA and tamoxifen alone or in combination to those of TGFβ treatment, or co-treatment with TGFβ inhibitor SB 431542, proteomic results showed that a number of proteins were involved in TGFβ signaling pathway. These results provide valuable insights into the mechanisms of RA and tamoxifen-induced TGFβ signaling pathway in breast cancer cells

  10. Bioanalytical methods for determination of tamoxifen and its phase I metabolites: A review

    International Nuclear Information System (INIS)

    Teunissen, S.F.; Rosing, H.; Schinkel, A.H.; Schellens, J.H.M.; Beijnen, J.H.

    2010-01-01

    The selective estrogen receptor modulator tamoxifen is used in the treatment of early and advanced breast cancer and in selected cases for breast cancer prevention in high-risk subjects. The cytochrome P450 enzyme system and flavin-containing monooxygenase are responsible for the extensive metabolism of tamoxifen into several phase I metabolites that vary in toxicity and potencies towards estrogen receptor (ER) alpha and ER beta. An extensive overview of publications on the determination of tamoxifen and its phase I metabolites in biological samples is presented. In these publications techniques were used such as capillary electrophoresis, liquid, gas and thin layer chromatography coupled with various detection techniques (mass spectrometry, ultraviolet or fluorescence detection, liquid scintillation counting and nuclear magnetic resonance spectroscopy). A trend is seen towards the use of liquid chromatography coupled to mass spectrometry (LC-MS). State-of-the-art LC-MS equipment allowed for identification of unknown metabolites and quantification of known metabolites reaching lower limit of quantification levels in the sub pg mL -1 range. Although tamoxifen is also metabolized into phase II metabolites, the number of publications reporting on phase II metabolism of tamoxifen is scarce. Therefore the focus of this review is on phase I metabolites of tamoxifen. We conclude that in the past decades tamoxifen metabolism has been studied extensively and numerous metabolites have been identified. Assays have been developed for both the identification and quantification of tamoxifen and its metabolites in an array of biological samples. This review can be used as a resource for method transfer and development of analytical methods used to support pharmacokinetic and pharmacodynamic studies of tamoxifen and its phase I metabolites.

  11. Global surgery in a postconflict setting - 5-year results of implementation in the Russian North Caucasus

    Directory of Open Access Journals (Sweden)

    Fatima I. Lunze

    2015-10-01

    Full Text Available Background: Collaborations for global surgery face many challenges to achieve fair and safe patient care and to build sustainable capacity. The 2004 terrorist attack on a school in Beslan in North Ossetia in the Russian North Caucasus left many victims with complex otologic barotrauma. In response, we implemented a global surgery partnership between the Vladikavkaz Children's Hospital, international surgical teams, the North Ossetian Health Ministry, and civil society organizations. This study's aim was to describe the implementation and 5-year results of capacity building for complex surgery in a postconflict, mid-income setting. Design: We conducted an observational study at the Children's Hospital in Vladikavkaz in the autonomous Republic of North Ossetia-Alania, part of the Russian Federation. We assessed the outcomes of 15 initial patients who received otologic surgeries for complex barotrauma resulting from the Beslan terrorism attack and for other indications, and report the incidence of intra- and postoperative complications. Results: Patients were treated for trauma related to terrorism (53% and for indications not related to violence (47%. None of the patients developed peri- or postoperative complications. Three patients (two victims of terrorism who underwent repair of tympanic perforations presented with re-perforations. Four junior and senior surgeons were trained on-site and in Germany to perform and teach similar procedures autonomously. Conclusions: In mid-income, postconflict settings, complex surgery can be safely implemented and achieve patient outcomes comparable to global standards. Capacity building can build on existing resources, such as operation room management, nursing, and anesthesia services. In postconflict environments, substantial surgical burden is not directly attributable to conflict-related injury and disease, but to health systems weakened by conflicts. Extending training and safe surgical care to include

  12. Clinical spectrum and outcome of pulmonary nocardiosis: 5-year experience

    Directory of Open Access Journals (Sweden)

    Akashdeep Singh

    2016-01-01

    Full Text Available Background: Pulmonary nocardiosis is a rare but a life-threatening infection caused by Nocardia spp. The diagnosis is often missed and delayed resulting in delay in appropriate treatment and thus higher mortality. Aim: In this study, we aim to evaluate the clinical spectrum and outcome of patients with pulmonary nocardiosis. Methods: A retrospective, 5-year (2009-2014 review of demographic profile, risk factors, clinical manifestations, imaging findings, treatment, and outcome of patients with pulmonary nocardiosis admitted to a tertiary care hospital. Results: The median age of the study subjects was 54 years (range, 16-76 and majority of them (75% were males. The risk factors for pulmonary nocardiosis identified in our study were long-term steroid use (55.6%, chronic lung disease (52.8%, diabetes (27.8%, and solid-organ transplantation (22.2%. All the patients were symptomatic, and the most common symptoms were cough (91.7%, fever (78%, and expectoration (72%. Almost two-third of the patients were initially misdiagnosed and the alternative diagnosis included pulmonary tuberculosis (n = 7, community-acquired pneumonia (n = 5, lung abscess (n = 4, invasive fungal infection (n = 3, lung cancer (n = 2, and Wegener′s granulomatosis (n = 2. The most common radiographic features were consolidation (77.8% and nodules (56%. The mortality rate for indoor patients was 33% despite treatment. Higher mortality rate was observed among those who had brain abscess (100.0%, HIV positivity (100%, need for mechanical ventilation (87.5%, solid-organ transplantation (50%, and elderly (age > 60 years patients (43%. Conclusion: The diagnosis of pulmonary nocardiosis is often missed and delayed resulting in delay in appropriate treatment and thus high mortality. A lower threshold for diagnosing pulmonary nocardiosis needs to be exercised, in chest symptomatic patients with underlying chronic lung diseases or systemic immunosuppression, for the early diagnosis, and

  13. Gamma knife thalamotomy for Parkinson's tremor: A 5-year experience

    International Nuclear Information System (INIS)

    Duma, Christopher M.; Jacques, Deane B.; Kopyov, Oleg V.; Mark, Rufus J.; Copcutt, Brian G.

    1996-01-01

    Purpose: Elderly, high-risk surgical patients, may be unfit for radiofrequency thalamotomy for Parkinson's tremor. We have performed gamma knife radiosurgery in this select patient population, in lieu of open surgery, in an attempt at amelioration of disabling tremor. Materials and Methods: Radiosurgical nucleus ventralis intermedalis thalamotomy using gamma unit technique was performed on 38 patients (median age, 72 years; range: 50-88 years) over a period of 5 years. A median dose of 155 Gy (range: 110-160 Gy) was delivered using a single 4-mm collimator to 40 nuclei (2 patients underwent bilateral thalamotomy) using only anatomical atlas landmarks. The number of males and females were evenly divided, and their ages ranged from 50 to 88 years (median: 72 years). Two-thirds of the patients underwent left thalamotomy for right-sided trmor. Patients were followed-up for a median of 14 months (range: 6 to 43 months). Independent neurological evaluation of tremor as well as subjective patient evaluation were based on a 4-tiered scale: no improvement, mild improvement (0-33% effect), good improvement (33-66% effect), and excellent improvement (66-100%). Results: Eight thalamotomies (20%) failed, four (10%) gave mild improvement, and 28 (70%) gave good to excellent improvement of tremor (median time of onset of improvement was 3 months; range: 1-11 months). In 12 patients (32%) the tremor was eliminated completely. Concordance between independent neurologist evaluation and that of the patient was significant (p<0.001). Two patients in the failure group had an initial transient improvement. Two patients who underwent unilateral thalamotomy had bilateral improvement of their tremor. A permanent 5-6 mm lesion was seen on all follow-up MRIs and there were no radiological complications. A worsening of hand strength was seen in only patient. Conclusion: The safety and efficacy of gamma unit radiosurgical thalamotomy is on par with that of radiofrequency thalamotomy, and in a

  14. Tamoxifen-Containing Eye Drops Successfully Trigger Cre-Mediated Recombination in the Entire Eye.

    Science.gov (United States)

    Schlecht, Anja; Leimbeck, Sarah V; Tamm, Ernst R; Braunger, Barbara M

    2016-01-01

    Embryonic lethality in mice with targeted gene deletion is a major issue that can be circumvented by using Cre-loxP-based animal models. Various inducible Cre systems are available, e.g. such that are activated following tamoxifen treatment, and allow deletion of a specific target gene at any desired time point during the life span of the animal. In this study, we describe the efficiency of topical tamoxifen administration by eye drops using a Cre- reporter mouse strain (R26R). We report that tamoxifen-responsive CAGGCre-ER (TM) mice show a robust Cre- mediated recombination throughout the entire eye.

  15. C-Cbl reverses HER2-mediated tamoxifen resistance in human breast cancer cells.

    Science.gov (United States)

    Li, Wei; Xu, Ling; Che, Xiaofang; Li, Haizhou; Zhang, Ye; Song, Na; Wen, Ti; Hou, Kezuo; Yang, Yi; Zhou, Lu; Xin, Xing; Xu, Lu; Zeng, Xue; Shi, Sha; Liu, Yunpeng; Qu, Xiujuan; Teng, Yuee

    2018-05-02

    Tamoxifen is a frontline therapy for estrogen receptor (ER)-positive breast cancer in premenopausal women. However, many patients develop resistance to tamoxifen, and the mechanism underlying tamoxifen resistance is not well understood. Here we examined whether ER-c-Src-HER2 complex formation is involved in tamoxifen resistance. MTT and colony formation assays were used to measure cell viability and proliferation. Western blot was used to detect protein expression and protein complex formations were detected by immunoprecipitation and immunofluorescence. SiRNA was used to examine the function of HER2 in of BT474 cells. An in vivo xenograft animal model was established to examine the role of c-Cbl in tumor growth. MTT and colony formation assay showed that BT474 cells are resistant to tamoxifen and T47D cells are sensitive to tamoxifen. Immunoprecipitation experiments revealed ER-c-Src-HER2 complex formation in BT474 cells but not in T47D cells. However, ER-c-Src-HER2 complex formation was detected after overexpressing HER2 in T47D cells and these cells were more resistant to tamoxifen. HER2 knockdown by siRNA in BT474 cells reduced ER-c-Src-HER2 complex formation and reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was also disrupted and tamoxifen resistance was reversed in BT474 cells by the c-Src inhibitor PP2 and HER2 antibody trastuzumab. Nystatin, a lipid raft inhibitor, reduced ER-c-Src-HER2 complex formation and partially reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was disrupted by overexpression of c-Cbl but not by the c-Cbl ubiquitin ligase mutant. In addition, c-Cbl could reverse tamoxifen resistance in BT474 cells, but the ubiquitin ligase mutant had no effect. The effect of c-Cbl was validated in BT474 tumor-bearing nude mice in vivo. Immunofluorescence also revealed ER-c-Src-HER2 complex formation was reduced in tumor tissues of nude mice with c-Cbl overexpression. Our results suggested that c-Cbl can reverse tamoxifen

  16. Assessing HITECH Implementation and Lessons: 5 Years Later.

    Science.gov (United States)

    Gold, Marsha; McLAUGHLIN, Catherine

    2016-09-01

    The expansive goals of the Health Information Technology for Economic and Clinical Health (HITECH) Act required the simultaneous development of a complex and interdependent infrastructure and a wide range of relationships, generating points of vulnerability. While federal legislation can be a powerful stimulus for change, its effectiveness also depends on its ability to accommodate state and local policies and private health care markets. Ambitious goals require support over a long time horizon, which can be challenging to maintain. The future of health information technology (health IT) support nationally is likely to depend on the ability of the technology to satisfy its users that its functionalities address the interests policymakers and other stakeholders have in using technology to promote better care, improved outcomes, and reduced costs. The Health Information Technology for Economic and Clinical Health (HITECH) Act set ambitious goals for developing electronic health information as one tool to reform health care delivery and improve health outcomes. With HITECH's grant funding now mostly exhausted but statutory authority for standards remaining, this article looks back at HITECH's experience in the first 5 years to assess its implementation, remaining challenges, and lessons learned. This review derives from a global assessment of the HITECH Act. Earlier, we examined the logic of HITECH and identified interdependencies critical to its ultimate success. In this article, we build on that framework to review what has and has not been accomplished in building the infrastructure authorized by HITECH since it was enacted. The review incorporates quantitative and qualitative evidence of progress from the global assessment and from the evaluations funded by the Office of the National Coordinator for Health Information Technology (ONC) of individual programs authorized by the HITECH Act. Our review of the evidence provides a mixed picture. Despite HITECH

  17. Results of proximal gastric vagotomy over 1-5 years in a district general hospital.

    Science.gov (United States)

    Makey, D A; Tovey, F I; Heald, R J

    1979-01-01

    One hundred and seventy-three underwent proximal gastric vagotomy for duodenal ulceration over a 6-year period. One hundred and fifteen of these have been followed up for 1-5 years. The operative mortality was nil and the result was satisfactory in 91 per cent. The incidence of side effects was small, notably that of dumping being 2.4 per cent and of diarrhoea, 3.6 per cent. Incidence of postoperative heartburn was reduced from 13 per cent to 4 per cent by the introduction of hepatic interposition. The incidence of recurrent ulceration was 5.1 per cent after an average interval of 2 years and that of new gastric ulceration 2.6 per cent after an average of 4 years. There were no recurrent ulcers in those who had peroperative Burge tests, although secretory studies showed no difference between those tested and those not tested. Most recurrences occurred in the earliest cases operated on before Burge testing was introduced and when only 2 cm of the lower oesophagus were exposed.

  18. Spectral domain optical coherence tomography findings in tamoxifen retinopathy--a case report.

    Science.gov (United States)

    Nair, Sandhya Narayanan; Anantharaman, Giridhar; Gopalakrishnan, Mahesh; Vyas, Jyothiprakash

    2013-01-01

    To report spectral domain optical coherence tomography findings in a case of typical tamoxifen retinopathy. In this observational case report, a patient with tamoxifen retinopathy was imaged with spectral domain optical coherence tomography and fundus auto fluorescence. Spectral domain optical coherence tomography showed numerous hyperreflective spots within the retina, mainly in the inner retinal layers in both the eyes. The external limiting membrane, the Inner Segment-Outer Segment junction, and the photoreceptors were not discernable at the fovea in the right eye. In the left eye, there was foveal atrophy with total loss of photoreceptors. The autofluorescent images showed macular hypofluorescence with foveal hyperfluorescence. Spectral domain optical coherence tomography demonstrated abnormalities in the outer retinal layers in tamoxifen retinopathy. There were also characteristic alterations in the autofluorescence pattern at the macula in tamoxifen retinopathy.

  19. Tool Weighs Benefits, Risks of Raloxifene or Tamoxifen to Prevent Breast Cancer

    Science.gov (United States)

    Researchers have developed a benefit-risk index to help guide decisions on whether postmenopausal women at increased risk of developing breast cancer should take raloxifene or tamoxifen to reduce that risk.

  20. Fasting Plasma Insulin at 5 Years of Age Predicted Subsequent Weight Increase in Early Childhood over a 5-Year Period—The Da Qing Children Cohort Study

    Science.gov (United States)

    Chen, Yan Yan; Wang, Jin Ping; Jiang, Ya Yun; Li, Hui; Hu, Ying Hua; Lee, Kok Onn; Li, Guang Wei

    2015-01-01

    Background The association between hyperinsulinemia and obesity is well known. However, it is uncertain especially in childhood obesity, if initial fasting hyperinsulinemia predicts obesity, or obesity leads to hyperinsulinemia through insulin resistance. Objective To investigate the predictive effect of fasting plasma insulin on subsequent weight change after a 5-year interval in childhood. Methods 424 Children from Da Qing city, China, were recruited at 5 years of age and followed up for 5 years. Blood pressure, anthropometric measurements, fasting plasma insulin, glucose and triglycerides were measured at baseline and 5 years later. Results Fasting plasma insulin at 5 years of age was significantly correlated with change of weight from 5 to 10 years (ΔWeight). Children in the lowest insulin quartile had ΔWeight of 13.08±0.73 kg compare to 18.39±0.86 in the highest insulin quartile (P<0.0001) in boys, and similarly 12.03±0.71 vs 15.80±0.60 kg (P<0.0001) in girls. Multivariate analysis showed that the predictive effect of insulin at 5 years of age on subsequent weight gain over 5 years remained statistically significant even after the adjustment for age, sex, birth weight, TV-viewing time and weight (or body mass index) at baseline. By contrast, the initial weight at 5 years of age did not predict subsequent changes in insulin level 5 years later. Children who had both higher fasting insulin and weight at 5 years of age showed much higher levels of systolic blood pressures, fasting plasma glucose, the homeostasis model assessment for insulin resistance (HOMA-IR) and triglycerides at 10 years of age. Conclusions Fasting plasma insulin at 5 years of age predicts weight gain and cardiovascular risk factors 5 year later in Chinese children of early childhood, but the absolute weight at 5 years of age did not predict subsequent change in fasting insulin. PMID:26047327

  1. Fasting Plasma Insulin at 5 Years of Age Predicted Subsequent Weight Increase in Early Childhood over a 5-Year Period-The Da Qing Children Cohort Study.

    Directory of Open Access Journals (Sweden)

    Yan Yan Chen

    Full Text Available The association between hyperinsulinemia and obesity is well known. However, it is uncertain especially in childhood obesity, if initial fasting hyperinsulinemia predicts obesity, or obesity leads to hyperinsulinemia through insulin resistance.To investigate the predictive effect of fasting plasma insulin on subsequent weight change after a 5-year interval in childhood.424 Children from Da Qing city, China, were recruited at 5 years of age and followed up for 5 years. Blood pressure, anthropometric measurements, fasting plasma insulin, glucose and triglycerides were measured at baseline and 5 years later.Fasting plasma insulin at 5 years of age was significantly correlated with change of weight from 5 to 10 years (ΔWeight. Children in the lowest insulin quartile had ΔWeight of 13.08±0.73 kg compare to 18.39±0.86 in the highest insulin quartile (P<0.0001 in boys, and similarly 12.03±0.71 vs 15.80±0.60 kg (P<0.0001 in girls. Multivariate analysis showed that the predictive effect of insulin at 5 years of age on subsequent weight gain over 5 years remained statistically significant even after the adjustment for age, sex, birth weight, TV-viewing time and weight (or body mass index at baseline. By contrast, the initial weight at 5 years of age did not predict subsequent changes in insulin level 5 years later. Children who had both higher fasting insulin and weight at 5 years of age showed much higher levels of systolic blood pressures, fasting plasma glucose, the homeostasis model assessment for insulin resistance (HOMA-IR and triglycerides at 10 years of age.Fasting plasma insulin at 5 years of age predicts weight gain and cardiovascular risk factors 5 year later in Chinese children of early childhood, but the absolute weight at 5 years of age did not predict subsequent change in fasting insulin.

  2. Tamoxifen treatment in hamsters induces protection during taeniosis by Taenia solium.

    Science.gov (United States)

    Escobedo, Galileo; Palacios-Arreola, M Isabel; Olivos, Alfonso; López-Griego, Lorena; Morales-Montor, Jorge

    2013-01-01

    Human neurocysticercosis by Taenia solium is considered an emergent severe brain disorder in developing and developed countries. Discovery of new antiparasitic drugs has been recently aimed to restrain differentiation and establishment of the T. solium adult tapeworm, for being considered a central node in the disease propagation to both pigs and humans. Tamoxifen is an antiestrogenic drug with cysticidal action on Taenia crassiceps, a close relative of T. solium. Thus, we evaluated the effect of tamoxifen on the in vitro evagination and the in vivo establishment of T. solium. In vitro, tamoxifen inhibited evagination of T. solium cysticerci in a dose-time dependent manner. In vivo, administration of tamoxifen to hamsters decreased the intestinal establishment of the parasite by 70%, while recovered tapeworms showed an 80% reduction in length, appearing as scolices without strobilar development. Since tamoxifen did not show any significant effect on the proliferation of antigen-specific immune cells, intestinal inflammation, and expression of Th1/Th2 cytokines in spleen and duodenum, this drug could exert its antiparasite actions by having direct detrimental effects upon the adult tapeworm. These results demonstrate that tamoxifen exhibits a strong cysticidal and antitaeniasic effect on T. solium that should be further explored in humans and livestock.

  3. Tamoxifen with and without radiation after partial mastectomy in patients with involved nodes

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, Andrew L; Perera, Francisco; Fisher, Barbara; Opeitum, Abiola; Yu, Norman

    1995-02-15

    Purpose: To determine the effect of tamoxifen on local control after partial mastectomy with and without adjuvant breast irradiation. Methods and Materials: A retrospective study of 97 node positive patients identified from the records of the London Regional Cancer Center included 44 patients who received tamoxifen and breast irradiation (40 or 50 Gy plus booster dose) after partial mastectomy, and 53 patients who received tamoxifen only after partial mastectomy. Base line characteristics of the two groups were similar. Results: At 39 months actuarial follow-up there was a breast tumor recurrence (BTR) in 5% vs. 21% of patients when radiation was omitted (p = 0.0388), but there was no difference in the cause-specific mortality of the two treatment groups. Cox Regression analysis (on only 10 BTR) showed age and adjuvant radiation as significant predictors of BTR. In patients not receiving radiation, no BTR was seen in 22 patients {>=}70 years of age at diagnosis vs. 8 BTR in 31 patients <70 years (p = 0.0130). All BTR occurred while patients were receiving tamoxifen. Conclusion: Tamoxifen alone with omission of radiation after partial mastectomy provides inferior breast tumor control in node positive patients. This is especially true for patients under 70 years of age. Patients aged 70 years or older at the time of diagnosis of breast cancer who receive tamoxifen have a low rate of breast tumor recurrence when radiation is omitted. These patients represent a group for whom radiation might not be necessary.

  4. Therapeutic Effects of a Traditional Chinese Medicine Formula Plus Tamoxifen vs. Tamoxifen for the Treatment of Mammary Gland Hyperplasia: A Meta-Analysis of Randomized Trials

    Science.gov (United States)

    Li, Hao-Tian; Liu, Hong-Hong; Yang, Yu-Xue; Wang, Tao; Zhou, Xue-Lin; Yu, Yang; Li, Su-Na; Zheng, Yi; Zhang, Ping; Wang, Rui-Lin; Li, Jian-Yu; Wei, Shi-Zhang; Li, Kun; Li, Peng-Yan; Qian, Li-Qi

    2018-01-01

    As a common disorder that accounts for over 70% of all breast disease cases, mammary gland hyperplasia (MGH) causes a severe problem for the quality of patients' life, and confers an increased risk of breast carcinoma. However, the etiology and pathogenesis of MGH remain unclear, and the safety and efficacy of current western drug therapy for MGH still need to be improved. Therefore, a meta-analysis was conducted by our team to determine whether a TCM formula named Ru-Pi-Xiao in combination with tamoxifen or Ru-Pi-Xiao treated alone can show more prominent therapeutic effects against MGH with fewer adverse reactions than that of tamoxifen. Studies published before June 2017 were searched based on standardized searching rules in several mainstream medical databases. A total of 27 articles with 4,368 patients were enrolled in this meta-analysis. The results showed that the combination of Ru-Pi-Xiao and tamoxifen could exhibit better therapeutic effects against MGH than that of tamoxifen (OR: 3.79; 95% CI: 3.09–4.65; P < 0.00001) with a lower incidence of adverse reactions (OR: 0.35; 95% CI: 0.28–0.43; P < 0.00001). The results also suggested that this combination could improve the level of progesterone (MD: 2.22; 95% CI: 1.72–2.71; P < 0.00001) and decrease the size of breast lump (MD: −0.67; 95% CI: −0.86 to −0.49; P < 0.00001) to a greater extent, which might provide a possible explanation for the pharmacodynamic mechanism of Ru-Pi-Xiao plus tamoxifen. In conclusion, Ru-Pi-Xiao and related preparations could be recommended as auxiliary therapy combined tamoxifen for the treatment of MGH. PMID:29456506

  5. Physiologically-based pharmacokinetic modeling of tamoxifen and its metabolites in women of different CYP2D6 phenotypes provides new insight into the tamoxifen mass balance

    Directory of Open Access Journals (Sweden)

    Kristin eDickschen

    2012-05-01

    Full Text Available Tamoxifen is a first-line endocrine agent in the mechanism-based treatment of estrogen receptor positive (ER+ mammary carcinoma and applied to breast cancer patients all over the world. Endoxifen is a secondary and highly active metabolite of tamoxifen that is formed among others by the polymorphic cytochrome P450 2D6 (CYP2D6. It is widely accepted that CYP2D6 poor metabolizers (PM exert a pronounced decrease in endoxifen steady-state plasma concentrations compared to CYP2D6 extensive metabolizers (EM. Nevertheless, an in-depth understanding of the chain of cause and effect between CYP2D6 genotype, endoxifen steady-state plasma concentration, and subsequent tamoxifen treatment benefit still remains to be evolved.In this context, physiologically-based pharmacokinetic (PBPK-modeling provides a useful tool to mechanistically investigate the impact of CYP2D6 phenotype on endoxifen formation in female breast cancer patients undergoing tamoxifen therapy.It has long been thought that only a minor percentage of endoxifen is formed via 4-hydroxytamoxifen. However, the current investigation supports very recently published data that postulates a contribution of 4-hydroxytamoxifen above 20 % to total endoxifen formation. The developed PBPK-model describes tamoxifen PK in rats and humans. Moreover, tamoxifen metabolism in dependence of CYP2D6 phenotype in populations of European female individuals is well described, thus providing a good basis to further investigate the linkage of PK, mode of action, and treatment outcome in dependence of factors such as phenotype, ethnicity or co-treatment with CYP2D6 inhibitors.

  6. Tamoxifen with ovarian function suppression versus tamoxifen alone as an adjuvant treatment for premenopausal breast cancer: a meta-analysis of published randomized controlled trials

    Science.gov (United States)

    Yan, Shunchao; Li, Kai; Jiao, Xin; Zou, Huawei

    2015-01-01

    Background Ovarian function suppression (OFS) significantly downregulates the concentration of plasma estrogens. However, it is unclear whether it offers any survival benefits if combined with adjuvant tamoxifen treatment in premenopausal women. This meta-analysis was designed to assess data from previous studies involving adjuvant tamoxifen treatment plus OFS in premenopausal breast cancer. Methods Electronic literature databases (PubMed, Embase, the Web of Science, and the Cochrane Library) were searched for relevant randomized controlled trials published prior to February 1, 2015. Only randomized controlled trials that compared tamoxifen alone with tamoxifen plus OFS for premenopausal women with breast cancer were selected. The evaluated endpoints were disease-free survival and overall survival. Results Four randomized controlled trials comprising 6,279 patients (OFS combination, n=3,133; tamoxifen alone, n=3,146) were included in the meta-analysis. There was no significant improvement in disease-free survival or overall survival with addition of OFS in either the whole population or the hormone receptor-positive subgroup. The risk of distant recurrence was not reduced with the addition of OFS in the whole population. A subgroup analysis showed that addition of OFS significantly improved overall survival in patients who were administered chemotherapy. Conclusion Based on the available studies, concurrent administration of OFS and adjuvant tamoxifen treatment for premenopausal women with breast cancer has no effect on prolonging disease-free survival and overall survival, excluding patients who were administered chemotherapy. It should not be widely recommended, except perhaps for women who were hormone-receptor positive and who were also administered adjuvant chemotherapy. PMID:26109867

  7. Integrative analysis of miRNA and gene expression reveals regulatory networks in tamoxifen-resistant breast cancer

    DEFF Research Database (Denmark)

    Joshi, Tejal; Elias, Daniel; Stenvang, Jan

    2016-01-01

    and 14-3-3 family genes. Integrating the inferred miRNA-target relationships, we investigated the functional importance of 2 central genes, SNAI2 and FYN, which showed increased expression in TamR cells, while their corresponding regulatory miRNA were downregulated. Using specific chemical inhibitors......Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer, however, tamoxifen resistance is frequently observed. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of miRNA......-mediated gene regulation in three clinically-relevant tamoxifen-resistant breast cancer cell lines (TamRs) compared to their parental tamoxifen-sensitive cell line. Alterations in the expression of 131 miRNAs in tamoxifen-resistant vs. parental cell lines were identified, 22 of which were common to all Tam...

  8. The formation of estrogen-like tamoxifen metabolites and their influence on enzyme activity and gene expression of ADME genes.

    Science.gov (United States)

    Johänning, Janina; Kröner, Patrick; Thomas, Maria; Zanger, Ulrich M; Nörenberg, Astrid; Eichelbaum, Michel; Schwab, Matthias; Brauch, Hiltrud; Schroth, Werner; Mürdter, Thomas E

    2018-03-01

    Tamoxifen, a standard therapy for breast cancer, is metabolized to compounds with anti-estrogenic as well as estrogen-like action at the estrogen receptor. Little is known about the formation of estrogen-like metabolites and their biological impact. Thus, we characterized the estrogen-like metabolites tamoxifen bisphenol and metabolite E for their metabolic pathway and their influence on cytochrome P450 activity and ADME gene expression. The formation of tamoxifen bisphenol and metabolite E was studied in human liver microsomes and Supersomes™. Cellular metabolism and impact on CYP enzymes was analyzed in upcyte® hepatocytes. The influence of 5 µM of tamoxifen, anti-estrogenic and estrogen-like metabolites on CYP activity was measured by HPLC MS/MS and on ADME gene expression using RT-PCR analyses. Metabolite E was formed from tamoxifen by CYP2C19, 3A and 1A2 and from desmethyltamoxifen by CYP2D6, 1A2 and 3A. Tamoxifen bisphenol was mainly formed from (E)- and (Z)-metabolite E by CYP2B6 and CYP2C19, respectively. Regarding phase II metabolism, UGT2B7, 1A8 and 1A3 showed highest activity in glucuronidation of tamoxifen bisphenol and metabolite E. Anti-estrogenic metabolites (Z)-4-hydroxytamoxifen, (Z)-endoxifen and (Z)-norendoxifen inhibited the activity of CYP2C enzymes while tamoxifen bisphenol consistently induced CYPs similar to rifampicin and phenobarbital. On the transcript level, highest induction up to 5.6-fold was observed for CYP3A4 by tamoxifen, (Z)-4-hydroxytamoxifen, tamoxifen bisphenol and (E)-metabolite E. Estrogen-like tamoxifen metabolites are formed in CYP-dependent reactions and are further metabolized by glucuronidation. The induction of CYP activity by tamoxifen bisphenol and the inhibition of CYP2C enzymes by anti-estrogenic metabolites may lead to drug-drug-interactions.

  9. Two years of tamoxifen or no adjuvant systemic therapy for patients with high-risk breast cancer

    DEFF Research Database (Denmark)

    Jensen, Maj-Britt; Krarup, Jens Fabricius; Palshof, Torben

    2018-01-01

    randomly assigned to two years of daily placebo or tamoxifen. Survival statistics was collected from the Danish Civil Registration System. RESULTS: The five-year invasive breast cancer recurrence (BCR) rate was 43.2% in the placebo arm and 31.9% in the tamoxifen arm. Compared with the placebo arm...... the hazard ratio for a BCR event was 0.73 in the tamoxifen arm (p = .07). With an estimated median follow-up on overall survival of 40.9 years, 154 and 145 patients had died in the placebo and tamoxifen arm, respectively. After adjustment for baseline characteristics a significant reduction in mortality...

  10. Evaluation of nutrient status after laparoscopic sleeve gastrectomy 1, 3, and 5 years after surgery.

    Science.gov (United States)

    Saif, Taha; Strain, Gladys W; Dakin, Gregory; Gagner, Michel; Costa, Ricardo; Pomp, Alfons

    2012-01-01

    Laparoscopic sleeve gastrectomy evolved as a primary bariatric procedure with little information on its nutritional effects. Our objective was to assess the longer term micronutrient and vitamin status after laparoscopic sleeve gastrectomy at a university hospital. Measurements of ferritin, iron, total iron binding capacity, hemoglobin, hematocrit, parathyroid hormone, albumin, calcium, magnesium, phosphorus, zinc, folate, and vitamins A, B1, B12, and D were obtained at baseline and 1, 3, and 5 years after surgery. Two-sample t tests with multiple adjusted comparisons and Fisher's exact test were used to determine deficiency. A total of 82 patients (67% women), with a mean age of 46.4 years and a baseline body mass index 55.7 kg/m2 were included in the present study (35 at 1, 27 at 3, and 30 at 5 years postoperatively). The percentage of excess body mass index loss was 58.5% at year 1 in 35 patients, 63.1% at year 3 in 27 patients, and 46.1% at year 5 in 30 patients. The parathyroid hormone level decreased from 75.0 to 49.6 ng/mL in year 1 to 40.7 ng/mL in year 3. The year 5 levels increased to 99.6 ng/mL. The mean vitamin D level increased from 23.6 ng/mL to 35.0, 32.1 and 34.8 at years 1, 3, and 5 (P = .05 for baseline to year 1). The vitamin D level was less than normal in 42% of the patients at year 5. After normalization from baseline, by year 5, parathyroid hormone had increased in 58.3% of patients. At year 5, vitamin B1 was less than normal in 30.8% of patients, and hemoglobin and hematocrit were less than normal in for 28.6% and 25% of patients, respectively. Finally, 28.9% of patients reported taking supplements in year 1, 42.9% in year 3, and 63.3% in year 5. The other variables were not significantly different. Laparoscopic sleeve gastrectomy resulted in health improvements through year 3. At year 5, the nutrient levels had reverted toward the baseline values. These observations provide focus for necessary clinical monitoring. Copyright © 2012 American

  11. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial.

    Science.gov (United States)

    Cuzick, Jack; Sestak, Ivana; Cawthorn, Simon; Hamed, Hisham; Holli, Kaija; Howell, Anthony; Forbes, John F

    2015-01-01

    Four previously published randomised clinical trials have shown that tamoxifen can reduce the risk of breast cancer in healthy women at increased risk of breast cancer in the first 10 years of follow-up. We report the long-term follow-up of the IBIS-I trial, in which the participants and investigators remain largely masked to treatment allocation. In the IBIS-I randomised controlled trial, premenopausal and postmenopausal women 35-70 years of age deemed to be at an increased risk of developing breast cancer were randomly assigned (1:1) to receive oral tamoxifen 20 mg daily or matching placebo for 5 years. Patients were randomly assigned to the two treatment groups by telephone or fax according to a block randomisation schedule (permuted block sizes of six or ten). Patients and investigators were masked to treatment assignment by use of central randomisation and coded drug supply. The primary endpoint was the occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analysed by intention to treat. Cox proportional hazard models were used to assess breast cancer occurrence and mortality. The trial is closed to recruitment and active treatment is completed, but long-term follow-up is ongoing. This trial is registered with controlledtrials.com, number ISRCTN91879928. Between April 14, 1992, and March 30, 2001, 7154 eligible women recruited from genetics clinics and breast care clinics in eight countries were enrolled into the IBIS-I trial and were randomly allocated to the two treatment groups: 3579 to tamoxifen and 3575 to placebo. After a median follow up of 16.0 years (IQR 14.1-17.6), 601 breast cancers have been reported (251 [7.0%] in 3579 patients in the tamoxifen group vs 350 [9.8%] in 3575 women in the placebo group; hazard ratio [HR] 0.71 [95% CI 0.60-0.83], pbreast cancer was similar between years 0-10 (226 [6.3%] in 3575 women in the placebo group vs 163 [4.6%] in 3579 women in the tamoxifen group; hazard ratio [HR] 0.72 [95% CI 0

  12. Tamoxifen dosing for Cre-mediated recombination in experimental bronchopulmonary dysplasia.

    Science.gov (United States)

    Ruiz-Camp, Jordi; Rodríguez-Castillo, José Alberto; Herold, Susanne; Mayer, Konstantin; Vadász, István; Tallquist, Michelle D; Seeger, Werner; Ahlbrecht, Katrin; Morty, Rory E

    2017-02-01

    Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth characterized by blunted post-natal lung development. BPD can be modelled in mice by exposure of newborn mouse pups to elevated oxygen levels. Little is known about the mechanisms of perturbed lung development associated with BPD. The advent of transgenic mice, where genetic rearrangements can be induced in particular cell-types at particular time-points during organogenesis, have great potential to explore the pathogenic mechanisms at play during arrested lung development. Many inducible, conditional transgenic technologies available rely on the application of the estrogen-receptor modulator, tamoxifen. While tamoxifen is well-tolerated and has been widely employed in adult mice, or in healthy developing mice; tamoxifen is not well-tolerated in combination with hyperoxia, in the most widely-used mouse model of BPD. To address this, we set out to establish a safe and effective tamoxifen dosing regimen that can be used in newborn mouse pups subjected to injurious stimuli, such as exposure to elevated levels of environmental oxygen. Our data reveal that a single intraperitoneal dose of tamoxifen of 0.2 mg applied to newborn mouse pups in 10 μl Miglyol vehicle was adequate to successfully drive Cre recombinase-mediated genome rearrangements by the fifth day of life, in a murine model of BPD. The number of recombined cells was comparable to that observed in regular tamoxifen administration protocols. These findings will be useful to investigators where tamoxifen dosing is problematic in the background of injurious stimuli and mouse models of human and veterinary disease.

  13. Tamoxifen-loaded polymeric micelles: preparation, physico-chemical characterization and in vitro evaluation studies.

    Science.gov (United States)

    Cavallaro, Gennara; Maniscalco, Laura; Licciardi, Mariano; Giammona, Gaetano

    2004-11-20

    Several samples of polymeric micelles, formed by amphiphilic derivatives of PHEA, obtained by grafting into polymeric backbone of PEGs and/or hexadecylamine groups (PHEA-PEG-C(16) and PHEA-C(16)) and containing different amount of Tamoxifen, were prepared. All Tamoxifen-loaded polymeric micelles showed to increase drug water solubility. TEM studies provided evidence of the formation of supramolecular core/shell architectures containing drug, in the nanoscopic range and with spherical shape. Samples with different amount of encapsulated Tamoxifen were subjected to in vitro cytotoxic studies in order to evaluate the effect of Tamoxifen micellization on cell growth inhibition. All samples of Tamoxifen-loaded polymeric micelles showed a significantly higher antiproliferative activity in comparison with free drug, probably attributable to fluidification of cellular membranes, caused by amphiphilic copolymers, that allows a higher penetration of the drug into tumoral cells. To gain preliminary information about the potential use of prepared micelles as Tamoxifen drug delivery systems, studies evaluating drug release ability of micelle systems in media mimicking biological fluids (buffer solutions at pH 7.4 and 5.5) and in human plasma were carried out. These studies, performed evaluating the amount of Tamoxifen that remains in solution as a function of time, showed that at pH 7.4, as well as in plasma, PHEA-C(16) polymeric micelles were able to release lower drug amounts than PHEA-PEG(5000)-C(16) ones, while at pH 5.5, the behavior difference between two kind of micelles was less pronounced.

  14. Effect of tamoxifen on the coronary vascular reactivity of spontaneously hypertensive female rats

    Directory of Open Access Journals (Sweden)

    M.V. Borgo

    2011-08-01

    Full Text Available Tamoxifen has been associated with a reduction in the incidence of myocardial infarction. However, the effects of tamoxifen on coronary reactivity have not been fully elucidated. The objective of this study was to determine the effects of chronic treatment with tamoxifen on coronary vascular reactivity in spontaneously hypertensive rats (SHR. Female SHR were divided into four groups (N = 7 each: sham-operated (SHAM, sham-operated and treated with tamoxifen (10 mg/kg by gavage for 90 days (TAMOX, ovariectomized (OVX, and ovariectomized and treated with tamoxifen (OVX+TAMOX. Mean arterial pressure (MAP, heart rate (HR, coronary perfusion pressure (CPP, and coronary vascular reactivity were measured. MAP and HR were reduced (9.42 and 11.67%, respectively in the OVX+TAMOX group compared to the OVX group (P < 0.01. The coronary vascular reactivity of the OVX+TAMOX group presented smaller vasoconstrictor responses to acetylcholine (2-64 µg when compared to the OVX group (P < 0.01 and this response was similar to that of the SHAM group. The adenosine-induced vasodilator response was greater in the TAMOX group compared to the SHAM and OVX groups (P < 0.05. Baseline CPP was higher in OVX+TAMOX and TAMOX groups (136 ± 3.6 and 130 ± 1.5 mmHg than in OVX and SHAM groups (96 ± 2 and 119 ± 2.3 mmHg; P < 0.01. Tamoxifen, when combined with OVX, attenuated the vasoconstriction induced by acetylcholine and increased the adenosine-induced vasodilatory response, as well as reducing the MAP, suggesting beneficial effects of tamoxifen therapy on coronary vascular reactivity after menopause.

  15. Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

    International Nuclear Information System (INIS)

    Zheng, Kai; Chen, Maoyun; Xiang, Yangfei; Ma, Kaiqi; Jin, Fujun; Wang, Xiao; Wang, Xiaoyan; Wang, Shaoxiang; Wang, Yifei

    2014-01-01

    Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections

  16. Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients

    International Nuclear Information System (INIS)

    Wegman, Pia; Vainikka, Linda; Stål, Olle; Nordenskjöld, Bo; Skoog, Lambert; Rutqvist, Lars-Erik; Wingren, Sten

    2005-01-01

    Tamoxifen is widely used as endocrine therapy for oestrogen-receptor-positive breast cancer. However, many of these patients experience recurrence despite tamoxifen therapy by incompletely understood mechanisms. In the present report we propose that tamoxifen resistance may be due to differences in activity of metabolic enzymes as a result of genetic polymorphism. Cytochrome P450 2D6 (CYP2D6) and sulfotransferase 1A1 (SULT1A1) are polymorphic and are involved in the metabolism of tamoxifen. The CYP2D6*4 and SULT1A1*2 genotypes result in decreased enzyme activity. We therefore investigated the genotypes of CYP2D6 and SULT1A1 in 226 breast cancer patients participating in a trial of adjuvant tamoxifen treatment in order to validate the benefit from the therapy. The patients were genotyped using PCR followed by cleavage with restriction enzymes. Carriers of the CYP2D6*4 allele demonstrated a decreased risk of recurrence when treated with tamoxifen (relative risk = 0.28, 95% confidence interval = 0.11–0.74, P = 0.0089). A similar pattern was seen among the SULT1A1*1 homozygotes (relative risk = 0.48, 95% confidence interval = 0.21–1.12, P = 0.074). The combination of CYP2D6*4 and/or SULT1A1*1/*1 genotypes comprised 60% of the patients and showed a 62% decreased risk of distant recurrence with tamoxifen (relative risk = 0.38, 95% confidence interval = 0.19–0.74, P = 0.0041). The present study suggests that genotype of metabolic enzymes might be useful as a guide for adjuvant endocrine treatment of postmenopausal breast cancer patients. However, results are in contradiction to prior hypotheses and the present sample size is relatively small. Findings therefore need to be confirmed in a larger cohort

  17. Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Kai [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of Life Science and Technology, Jinan University, Guangzhou (China); Chen, Maoyun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Xiang, Yangfei; Ma, Kaiqi [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Jin, Fujun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Wang, Xiao [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Wang, Xiaoyan; Wang, Shaoxiang [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Wang, Yifei, E-mail: twang-yf@163.com [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China)

    2014-04-18

    Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections.

  18. Long-term outcomes of Botulinum toxin in the treatment of chronic anal fissure: 5 years of follow-up.

    Science.gov (United States)

    Barbeiro, Sandra; Atalaia-Martins, Catarina; Marcos, Pedro; Gonçalves, Cláudia; Canhoto, Manuela; Arroja, Bruno; Silva, Filipe; Cotrim, Isabel; Eliseu, Liliana; Santos, Antonieta; Vasconcelos, Helena

    2017-03-01

    Chronic anal fissure is a frequent and disabling disease, often affecting young adults. Botulinum toxin and lateral internal sphincterotomy are the main therapeutic options for refractory cases. Botulinum toxin is minimally invasive and safer compared with surgery, which carries a difficult post-operative recovery and fecal incontinence risk. The long-term efficacy of Botulinum toxin is not well known. The aim of this study was to evaluate the long-term efficacy and safety of Botulinum toxin in the treatment of chronic anal fissure. This was a retrospective study at a single center, including patients treated with Botulinum toxin from 2005 to 2010, followed over at least a period of 5 years. All patients were treated with injection of 25U of Botulinum toxin in the intersphincteric groove. The response was registered as complete, partial, refractory and relapse. Botulinum toxin was administered to 126 patients, 69.8% ( n  = 88) were followed over a period of 5 years. After 3 months, 46.6% ( n  = 41) had complete response, 23.9% ( n  = 21) had partial response and 29.5% ( n  = 26) were refractory. Relapse was observed in 1.2% ( n  = 1) at 6 months, 11.4% ( n  = 10) at 1 year, 2.3% ( n  = 2) at 3 years; no relapse at 5 years. The overall success rate was 64.8% at 5 years of follow-up. Botulinum toxin was well tolerated by all patients and there were no complications. The use of Botulinum toxin to treat patients with chronic anal fissure was safe and effective in long-term follow-up.

  19. Understanding postoperative fatigue.

    Science.gov (United States)

    Rose, E A; King, T C

    1978-07-01

    Performance characteristics of the central nervous, cardiovascular, respiratory and muscular systems in man postoperatively have received little investigative attention, despite the well known syndrome of postoperative fatigue. The impairmen in perception and psychomotor skills that has been shown to result from caloric restriction, bedrest, sedation and sleep deprivation suggests that a similar deficit may occur after surgical procedures. After a simple elective surgical procedure, maximal oxygen uptake decreases and the adaptability of heart rate to submaximal workloads is impaired. Similar deleterious effects on cardiorespiratory performance have been documented with starvation and bedrest; an understanding of cardiorespiratory performance postoperatively awaits further investigation. Maximal muscular force of contraction is also impaired by caloric restriction and bedrest, suggesting that similar effects may be seen in the postoperative state, although this has not been studied. A better understanding of the syndrome of postoperative fatigue could be achieved by a descriptive analysis of physiologic performance postoperatively. Such descriptive data could form the basis for objective evaluation of therapeutic measures intended to improve performance, such as nutritional supplementation and pharmacologic intervention. The observation that exercise with the patient in the supine position may decrease the impairment in maximal aerobic power otherwise expected in immobilized patients suggests that controlled exercise therapy may be of value in reducing physiologic impairment postoperatively.

  20. Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence

    DEFF Research Database (Denmark)

    Chirgwin, Jacquie H; Giobbie-Hurder, Anita; Coates, Alan S

    2016-01-01

    PURPOSE: To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. METHODS: The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor......-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards......). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age...

  1. [Characteristics of postoperative peritonitis].

    Science.gov (United States)

    Lock, J F; Eckmann, C; Germer, C-T

    2016-01-01

    Postoperative peritonitis is still a life-threatening complication after abdominal surgery and approximately 10,000 patients annually develop postoperative peritonitis in Germany. Early recognition and diagnosis before the onset of sepsis has remained a clinical challenge as no single specific screening test is available. The aim of therapy is a rapid and effective control of the source of infection and antimicrobial therapy. After diagnosis of diffuse postoperative peritonitis surgical revision is usually inevitable after intestinal interventions. Peritonitis after liver, biliary or pancreatic surgery is managed as a rule by means of differentiated therapy approaches depending on the severity.

  2. Memory enhancement by Tamoxifen on amyloidosis mouse model.

    Science.gov (United States)

    Pandey, Deepika; Banerjee, Sugato; Basu, Mahua; Mishra, Nibha

    2016-03-01

    Tamoxifen (TMX) is a selective estrogen receptor modulator (SERM) used in the treatment of breast cancer. Earlier studies show its neuroprotection via regulating apoptosis, microglial functions, and synaptic plasticity. TMX also showed memory enhancement in ovariectomized mice, and protection from amyloid induced damage in hippocampal cell line. These reports encouraged us to explore the role of TMX in relevance to Alzheimer's disease (AD). We report here, the effect of TMX treatment a) on memory, and b) levels of neurotransmitters (acetylcholine (ACh) and dopamine (DA)) in breeding-retired-female mice injected with beta amyloid1-42 (Aβ1-42). Mice were treated with TMX (10mg/kg, i.p.) for 15 days. In Morris water maze test, the TMX treated mice escape latency decreased during training trials. They also spent longer time in the platform quadrant on probe trial, compared to controls. In Passive avoidance test, TMX treated mice avoided stepping on the shock chamber. This suggests that TMX protects memory from Aβ induced toxicity. In frontal cortex, ACh was moderately increased, with TMX treatment. In striatum, dopamine was significantly increased, 3,4-dihydroxyphenylacetic acid (DOPAC) level and DOPAC/DA ratio was decreased post TMX treatment. Therefore, TMX enhances spatial and contextual memory by reducing dopamine metabolism and increasing ACh level in Aβ1-42 injected-breeding-retired-female mice. Copyright © 2015. Published by Elsevier Inc.

  3. Paradoxical action of fulvestrant in estradiol-induced regression of tamoxifen-stimulated breast cancer.

    Science.gov (United States)

    Osipo, Clodia; Gajdos, Csaba; Liu, Hong; Chen, Bin; Jordan, V Craig

    2003-11-05

    Long-term tamoxifen treatment of breast cancer can result in tamoxifen-stimulated breast cancer, in which estrogen inhibits tumor growth after tamoxifen withdrawal. We investigated the molecular mechanism(s) of estradiol-induced tumor regression by using an in vivo model of tamoxifen-stimulated human breast cancer. Growth of parental estradiol-stimulated MCF-7E2 and long-term tamoxifen-stimulated MCF-7TAMLT xenografts in athymic mice was measured during treatment with vehicle, estradiol, estradiol plus tamoxifen, tamoxifen alone, estradiol plus fulvestrant, or fulvestrant alone. Apoptosis was detected by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Protein expression was assessed by western blot analysis. mRNA expression was assessed by real-time reverse transcription-polymerase chain reaction. All statistical tests were two-sided. MCF-7E2 tumor growth was stimulated by estradiol (cross-sectional area at week 13 = 1.06 cm2, 95% confidence interval [CI] = 0.82 to 1.30 cm2; Pestradiol-induced regression to 0.18 cm2 (95% CI = 0.15 to 0.21 cm2; P<.001), and tamoxifen or estradiol plus fulvestrant enhanced tumor growth to 1.00 cm2 (95% CI = 0.88 to 1.22 cm2). Estradiol increased the number of apoptotic cells in tumors by 23% (95% CI = 20% to 26%; P<.001) compared with all other treatments, decreased estrogen receptor alpha(ERalpha) protein expression, increased the expression of Fas mRNA and protein, decreased the expression of HER2/neu mRNA and protein and nuclear factor kappaB (NF-kappaB) protein but did not affect Fas ligand protein expression compared with control. Paradoxically, fulvestrant reversed this effect and stimulated MCF-7TAMLT tumor growth apparently through ERalpha-mediated regulation of Fas, HER2/neu, and NF-kappaB. Physiologic levels of estradiol induced regression of tamoxifen-stimulated breast cancer tumors, apparently by inducing the death receptor Fas and suppressing the antiapoptotic

  4. Effect of Tamoxifen on Seminiferous Tubules Structure during Pregnancy in Adult Mice

    Directory of Open Access Journals (Sweden)

    J Soleimani Rad

    2016-03-01

    Full Text Available Introduction: Tamoxifen is a nonsteroidal drug which mainly treats breast cancer. It is also applied for stimulation of ovulation and remedy of infertility. Regarding the tamoxifen binding to estrogen receptors and the possible role of estrogens in spermatogenesis, the present study aimed to histologically evaluate spermatogenesis in the seminiferous ducts of mice, whose mothers had received tamoxifen during pregnancy. Methods: In the present study, 30 female and 15 male mice of NMRI race were selected for mating. Since 13th day of pregnancy, the experimental group received tamoxifen with the dosage of 5 mg/kg intra-peritoneally for 7 days, wherease the control group received normal saline. After childbirth of the mated mice, male infants were selected and monitored in the standard laboratory conditions. After reaching the age of puberty (6-8Weeks, adult mice were sacrificed by the cervical dislocation, and the testes were removed for histological evaluation of spermatogenesis. After routine histological processing, the samples were studied by the light microscope. Results: Histological studies showed that spermatogenic and Sertoli cells in the seminiferous tubules in control and experimental groups were significantly different, though no difference was observed in the number of Leydig cells in the both groups. Conclusion: The findings of the present study showed that tamoxifen exposure during development can cause histological changes in the seminiferous tubules, which can lead to infertility in the male rat.

  5. Tamoxifen: an FDA approved drug with neuroprotective effects for spinal cord injury recovery

    Directory of Open Access Journals (Sweden)

    Jennifer M Colón

    2016-01-01

    Full Text Available Spinal cord injury (SCI is a condition without a cure, affecting sensory and/or motor functions. The physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal regeneration. Among these complex set of events are damage of the blood-brain barrier, edema formation, inflammation, oxidative stress, demyelination, reactive gliosis and apoptosis. The multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival, regeneration, vascular reorganization and synaptic formation. Tamoxifen, a selective estrogen receptor modulator, is an FDA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating condition. Various investigators using different animal models and injury parameters have demonstrated the beneficial effects of this drug to improve functional locomotor recovery after SCI. Results suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant, anti-inflammatory and anti-gliotic responses. A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this treatment. In addition, the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be investigated. This review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the field.

  6. Smart coumarin-tagged imprinted polymers for the rapid detection of tamoxifen.

    Science.gov (United States)

    Ray, Judith V; Mirata, Fosca; Pérollier, Celine; Arotcarena, Michel; Bayoudh, Sami; Resmini, Marina

    2016-03-01

    A signalling molecularly imprinted polymer was synthesised for easy detection of tamoxifen and its metabolites. 6-Vinylcoumarin-4-carboxylic acid (VCC) was synthesised from 4-bromophenol to give a fluorescent monomer, designed to switch off upon binding of tamoxifen. Clomiphene, a chlorinated analogue, was used as the template for the imprinting, and its ability to quench the coumarin fluorescence when used in a 1:1 ratio was demonstrated. Tamoxifen and 4-hydroxytamoxifen were also shown to quench coumarin fluorescence. Imprinted and non-imprinted polymers were synthesised using VCC, methacrylic acid as a backbone monomer and ethylene glycol dimethacrylate as cross-linker, and were ground and sieved to particle sizes ranging between 45 and 25 μm. Rebinding experiments demonstrate that the imprinted polymer shows very strong affinity for both clomiphene and tamoxifen, while the non-imprinted polymer shows negligible rebinding. The fluorescence of the imprinted polymer is quenched by clomiphene, tamoxifen and 4-hydroxytamoxifen. The switch off in fluorescence of the imprinted polymer under these conditions could also be detected under a UV lamp with the naked eye, making this matrix suitable for applications when coupled with a sample preparation system.

  7. Tamoxifen treatment for pubertal gynecomastia in two siblings with partial androgen insensitivity syndrome.

    Science.gov (United States)

    Saito, Reiko; Yamamoto, Yukiyo; Goto, Motohide; Araki, Shunsuke; Kubo, Kazuyasu; Kawagoe, Rinko; Kawada, Yasusada; Kusuhara, Koichi; Igarashi, Maki; Fukami, Maki

    2014-01-01

    Although tamoxifen has been shown to be fairly safe and effective for idiopathic pubertal gynecomastia, it remains unknown whether it is also beneficial for gynecomastia associated with endocrine disorders. Here, we report the effect of tamoxifen on pubertal gynecomastia in 2 siblings with partial androgen insensitivity syndrome (PAIS). Cases 1 and 2 presented with persistent pubertal gynecomastia at 13 and 16 years of age, respectively. Physical examinations revealed breast of Tanner stage 3 and normal male-type external genitalia in both cases. Clinical features such as female-type pubic hair and borderline small testis indicated mildly impaired masculinization. Molecular analysis identified a previously reported p.Arg789Ser mutation in the androgen receptor gene (AR) in the 2 cases. Two months of oral administration of tamoxifen ameliorated gynecomastia to Tanner stage 2 with no adverse events. Additional treatment with testosterone enanthate showed negligible effects on body hair and penile length. Hormone values of the 2 cases during tamoxifen treatment remained similar to those in previously reported untreated patients with PAIS. The results indicate that tamoxifen was effective in treating pubertal gynecomastia in these 2 patients with PAIS and may be considered as a therapeutic option in this situation pending further studies.

  8. Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

    International Nuclear Information System (INIS)

    Moreira, Paula I.; Custodio, Jose B.A.; Nunes, Elsa; Moreno, Antonio; Seica, Raquel; Oliveira, Catarina R.; Santos, Maria S.

    2007-01-01

    Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17β-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca 2+ delaying the opening of the permeability transition pore. The presence of 25 μM E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H 2 O 2 in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered

  9. Mullerian adenosarcoma of the uterus associated with tamoxifen treatment for breast cancer

    Directory of Open Access Journals (Sweden)

    Yasin Ceylan

    2015-12-01

    Full Text Available Mullerian adenosarcoma following tamoxifen therapy is a rare condition. Our aim was to report the youngest patient in the literature with uterine mullerian adenosarcoma who was undergoing tamoxifen therapy for breast cancer. A premenopausal woman aged 38 years who was undergoing tamoxifen therapy for breast cancer, was admitted with symptoms of lower abdominal pain and irregular vaginal bleeding and malodorous vaginal discharge that had continued for at least 6 months. A pelvic examination revealed a large and malodorous polypoid mass protruding through the cervix and an enlarged uterus. A biopsy from the protruding polypoid mass was reported as a large area of necrosis with neoplastic mesenchymal cells. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oopherectomy, pelvic-paraaortic lymph node dissection, and omentectomie. The histologic diagnosis was Mullerian adenosarcoma. As a result, she was discharged to the oncology department. The woman is alive and her chemoradiotherapy treatment is ongoing. The role of tamoxifen therapy in the development of endometrial neoplasms remains unclear, but all cases of endometrial thickening and vaginal bleeding must be investigated for Mullerian adenosarcoma in tamoxifen users.

  10. Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells.

    Science.gov (United States)

    Ambrosio, Maria Rosaria; D'Esposito, Vittoria; Costa, Valerio; Liguoro, Domenico; Collina, Francesca; Cantile, Monica; Prevete, Nella; Passaro, Carmela; Mosca, Giusy; De Laurentiis, Michelino; Di Bonito, Maurizio; Botti, Gerardo; Franco, Renato; Beguinot, Francesco; Ciccodicola, Alfredo; Formisano, Pietro

    2017-12-12

    Type 2 diabetes and obesity are negative prognostic factors in patients with breast cancer (BC). We found that sensitivity to tamoxifen was reduced by 2-fold by 25 mM glucose (High Glucose; HG) compared to 5.5 mM glucose (Low Glucose; LG) in MCF7 BC cells. Shifting from HG to LG ameliorated MCF7 cell responsiveness to tamoxifen. RNA-Sequencing of MCF7 BC cells revealed that cell cycle-related genes were mainly affected by glucose. Connective Tissue Growth Factor (CTGF) was identified as a glucose-induced modulator of cell sensitivity to tamoxifen. Co-culturing MCF7 cells with human adipocytes exposed to HG, enhanced CTGF mRNA levels and reduced tamoxifen responsiveness of BC cells. Inhibition of adipocyte-released IL8 reverted these effects. Interestingly, CTGF immuno-detection in bioptic specimens from women with estrogen receptor positive (ER + ) BC correlated with hormone therapy resistance, distant metastases, reduced overall and disease-free survival. Thus, glucose affects tamoxifen responsiveness directly modulating CTGF in BC cells, and indirectly promoting IL8 release by adipocytes.

  11. Analysis of the Ki-67 index in the vaginal epithelium of castrated rats treated with tamoxifen

    Directory of Open Access Journals (Sweden)

    Afif Rieth Nery-Aguiar

    2016-02-01

    Full Text Available OBJECTIVES: Vaginal atrophy and breast cancer are common conditions in postmenopausal women and tamoxifen is the standard endocrine treatment for hormone-sensitive tumors. The present study aimed to assess the effect of tamoxifen on Ki-67 protein expression in the vaginal epithelium of castrated rats. MATERIAL AND METHODS: Forty Wistar-Hannover adult, virgin, castrated rats were randomly divided into two groups, group I (control, n=20 and group II (tamoxifen, n=20, receiving 0.5 ml of propylene glycol and 250 µg of tamoxifen diluted in 0.5 ml of propylene glycol, respectively, daily by gavage for 30 days. On the 31st day, the rats were euthanized and their vaginas were removed and fixed in 10% buffered formalin for the immunohistochemical study of Ki-67 protein expression. Data were analyzed by the Levene and Student’s t tests (p<0.05. RESULTS: The mean index of Ki-67 expression in the rat vagina of groups I and II was 4.04±0.96 and 26.86±2.19, respectively (p<0.001. CONCLUSIONS: According to the results of the present study, tamoxifen, at the dose and treatment length used, induced a significant increase in the cell proliferation of the vaginal mucosa in castrated rats, as evaluated by Ki-67 protein expression.

  12. Gene expression profiling identifies FYN as an important molecule in tamoxifen resistance and a predictor of early recurrence in patients treated with endocrine therapy

    DEFF Research Database (Denmark)

    Elias, D; (Hansen) Vever, Henriette; Lænkholm, A-V

    2015-01-01

    To elucidate the molecular mechanisms of tamoxifen resistance in breast cancer, we performed gene array analyses and identified 366 genes with altered expression in four unique tamoxifen-resistant (TamR) cell lines vs the parental tamoxifen-sensitive MCF-7/S0.5 cell line. Most of these genes were...

  13. The postoperative stomach

    Energy Technology Data Exchange (ETDEWEB)

    Woodfield, Courtney A. [Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104 (United States); Levine, Marc S. [Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104 (United States)]. E-mail: marc.levine@uphs.upenn.edu

    2005-03-01

    Gastric surgery may be performed for the treatment of a variety of benign and malignant diseases of the upper gastrointestinal tract, including peptic ulcers and gastric carcinoma. Radiographic studies with water-soluble contrast agents often are obtained to rule out leaks, obstruction, or other acute complications during the early postoperative period. Barium studies may also be obtained to evaluate for anastomotic strictures or ulcers, bile reflux gastritis, recurrent tumor, or other chronic complications during the late postoperative period. Cross-sectional imaging studies such as CT are also helpful for detecting abscesses or other postoperative collections, recurrent or metastatic tumor, or less common complications such as afferent loop syndrome or gastrojejunal intussusception. It is important for radiologists to be familiar not only with the radiographic findings associated with these various abnormalities but also with the normal appearances of the postoperative stomach on radiographic examinations, so that such appearances are not mistaken for pseudoleaks or other postoperative complications. The purpose of this article is to describe the normal postsurgical anatomy after the most commonly performed operations (including partial gastrectomy, esophagogastrectomy and gastric pull-through, and total gastrectomy and esophagojejunostomy) and to review the acute and chronic complications, normal postoperative findings, and major abnormalities detected on radiographic examinations in these patients.

  14. The postoperative stomach

    International Nuclear Information System (INIS)

    Woodfield, Courtney A.; Levine, Marc S.

    2005-01-01

    Gastric surgery may be performed for the treatment of a variety of benign and malignant diseases of the upper gastrointestinal tract, including peptic ulcers and gastric carcinoma. Radiographic studies with water-soluble contrast agents often are obtained to rule out leaks, obstruction, or other acute complications during the early postoperative period. Barium studies may also be obtained to evaluate for anastomotic strictures or ulcers, bile reflux gastritis, recurrent tumor, or other chronic complications during the late postoperative period. Cross-sectional imaging studies such as CT are also helpful for detecting abscesses or other postoperative collections, recurrent or metastatic tumor, or less common complications such as afferent loop syndrome or gastrojejunal intussusception. It is important for radiologists to be familiar not only with the radiographic findings associated with these various abnormalities but also with the normal appearances of the postoperative stomach on radiographic examinations, so that such appearances are not mistaken for pseudoleaks or other postoperative complications. The purpose of this article is to describe the normal postsurgical anatomy after the most commonly performed operations (including partial gastrectomy, esophagogastrectomy and gastric pull-through, and total gastrectomy and esophagojejunostomy) and to review the acute and chronic complications, normal postoperative findings, and major abnormalities detected on radiographic examinations in these patients

  15. [Thyroid status peculiarities of elderly patients 5 years after operation depending on the volume of surgical intervention].

    Science.gov (United States)

    Aristarhov, V G; Danilov, N V; Aristarkhov, R V; Puzin, D A; Birykov, C V

    2016-01-01

    Long-term results of treatment of 180 patients operated 5 years ago for benign thyroid nodular pathology have been analyzed in the present paper, the results being analyzed depending on the volume of surgical intervention. The rate of postoperative hypothyrodism is lower in patients who had undergone limited thyroid resection, recurrent cases are more frequent, but they are not clinically significant and seldom require reoperation. It should also be noted that those patients have fewer cardiac complaints as the dose of hormone replacement therapy preparations is small. Elder patients who had undergone functionally significant thyroidectomy and need to take great doses of Thyroxin (107-150 mcg/day) have cardiac complaints more often (43 %) comparing to those who had undergone limited resections (35 %).

  16. The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fowble, B; Fein, D A; Hanlon, A L; Eisenberg, B L; Hoffman, J P; Sigurdson, E R; Daly, M B; Goldstein, L J

    1995-07-01

    Purpose: In the NSABP B14 trial evaluating tamoxifen (tam) in axillary node negative, estrogen receptor positive tumors fewer breast recurrences were observed in patients treated with conservative surgery and radiation who received tam compared to the observation arm. An additional series, however, has suggested that tam adversely impacts on the cosmetic result. To further address these issues we compared the outcome of estrogen receptor positive tumors treated with conservative surgery and radiation with or without tam. Materials and Methods: From 1982 to 1991, 491 women with estrogen receptor positive stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. The median age of the patient population was 60 years (range 39-85). The median followup was 5.3 years (range .1-12.8). 69% had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49%. The final margin of resection was negative in 64%, unknown in 18%, and close or positive in 19%. None of the patients received adjuvant chemotherapy. 154 patients received tam and 337 received no adjuvant therapy. Patients who received tam were more often axillary node positive (44% tam vs 5% no tam) and less often had unknown margins (9% tam vs 22% no tam). There were no significant differences for the 2 groups for median age, primary tumor size, histology, race, or use of reexcision. Results: The 5 yr act rate of breast recurrence was 4% for the tam patients compared to 7% for patients not receiving tam (p=.21). At 8 yrs, the breast recurrence rates were 4% for the tam patients compared to 11% for the no tam patients (p=.05). However, at 9 years the rates were 17% tam vs 14% no tam (p=.21). The benefit from tam in terms of a decreased 5 year actuarial breast recurrence rate was most evident for patients who did not have a reexcision (3% tam vs 10% no tam, p=.15), had unknown margins (7% tam vs 13% no tam, p=.37) or close margins (0% tam vs 11% no tam, p=.34

  17. The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer

    International Nuclear Information System (INIS)

    Fowble, B.; Fein, D.A.; Hanlon, A.L.; Eisenberg, B.L.; Hoffman, J.P.; Sigurdson, E.R.; Daly, M.B.; Goldstein, L.J.

    1995-01-01

    Purpose: In the NSABP B14 trial evaluating tamoxifen (tam) in axillary node negative, estrogen receptor positive tumors fewer breast recurrences were observed in patients treated with conservative surgery and radiation who received tam compared to the observation arm. An additional series, however, has suggested that tam adversely impacts on the cosmetic result. To further address these issues we compared the outcome of estrogen receptor positive tumors treated with conservative surgery and radiation with or without tam. Materials and Methods: From 1982 to 1991, 491 women with estrogen receptor positive stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. The median age of the patient population was 60 years (range 39-85). The median followup was 5.3 years (range .1-12.8). 69% had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49%. The final margin of resection was negative in 64%, unknown in 18%, and close or positive in 19%. None of the patients received adjuvant chemotherapy. 154 patients received tam and 337 received no adjuvant therapy. Patients who received tam were more often axillary node positive (44% tam vs 5% no tam) and less often had unknown margins (9% tam vs 22% no tam). There were no significant differences for the 2 groups for median age, primary tumor size, histology, race, or use of reexcision. Results: The 5 yr act rate of breast recurrence was 4% for the tam patients compared to 7% for patients not receiving tam (p=.21). At 8 yrs, the breast recurrence rates were 4% for the tam patients compared to 11% for the no tam patients (p=.05). However, at 9 years the rates were 17% tam vs 14% no tam (p=.21). The benefit from tam in terms of a decreased 5 year actuarial breast recurrence rate was most evident for patients who did not have a reexcision (3% tam vs 10% no tam, p=.15), had unknown margins (7% tam vs 13% no tam, p=.37) or close margins (0% tam vs 11% no tam, p=.34

  18. Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in Breast Cancer.

    Science.gov (United States)

    Choi, Hee-Joo; Joo, Hyeong-Seok; Won, Hee-Young; Min, Kyueng-Whan; Kim, Hyung-Yong; Son, Taekwon; Oh, Young-Ha; Lee, Jeong-Yeon; Kong, Gu

    2018-04-01

    Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764). RBP2-mediated tamoxifen resistance was confirmed by invitro sulforhodamine B (SRB) colorimetric, colony-forming assays, and invivo xenograft models (n = 8 per group). RNA-seq analysis and receptor tyrosine kinase assay were performed to identify the tamoxifen resistance mechanism by RBP2. All statistical tests were two-sided. RBP2 was associated with poor prognosis to tamoxifen therapy in ER-positive breast cancer (P = .04 in HYU cohort, P = .02 in KM plotter, P = .007 in METABRIC, log-rank test). Furthermore, RBP2 expression was elevated in patients with tamoxifen-resistant breast cancer (P = .04, chi-square test). Knockdown of RBP2 conferred tamoxifen sensitivity, whereas overexpression of RBP2 induced tamoxifen resistance invitro and invivo (MCF7 xenograft: tamoxifen-treated control, mean [SD] tumor volume = 70.8 [27.9] mm3, vs tamoxifen-treated RBP2, mean [SD] tumor volume = 387.9 [85.1] mm3, P < .001). Mechanistically, RBP2 cooperated with ER co-activators and corepressors and regulated several tamoxifen resistance-associated genes, including NRIP1, CCND1, and IGFBP4 and IGFBP5. Furthermore, epigenetic silencing of IGFBP4/5 by RBP2-ER-NRIP1-HDAC1 complex led to insulin-like growth factor-1 receptor (IGF1R) activation. RBP2 also increased IGF1R-ErbB crosstalk and subsequent PI3K-AKT activation via demethylase activity-independent ErbB protein stabilization. Combinational treatment with tamoxifen and PI3K inhibitor could overcome RBP2-mediated tamoxifen

  19. Postoperative analgesia in children when using clonidine in addition ...

    African Journals Online (AJOL)

    The aim of the study was to evaluate the efficacy of clonidine in association with fentanyl as an additive to bupivacaine 0.25% given via single shot caudal epidural in pediatric patients for postoperative pain relief. In the present prospective randomized double blind study, 40 children of ASA-I-II aged 1-5 years scheduled for ...

  20. The effect of tamoxifen on pubertal bone development in adolescents with pubertal gynecomastia.

    Science.gov (United States)

    Akgül, Sinem; Derman, Orhan; Kanbur, Nuray

    2016-01-01

    During puberty, estrogen has a biphasic effect on epiphyses; at low levels, it leads to an increase in height and bone mass, whereas at high levels, it leads to closure of the epiphysis. Tamoxifen is a selective estrogen receptor modulator that has been used in the treatment of pubertal gynecomastia. Although it has not been approved for this indication, studies have shown it to be both successful and safe. In males, the peak of pubertal bone development occurs during Tanner stage 3-4, which is also when pubertal gynecomastia reaches its highest prevalence. Thus tamoxifen treatment could potentially effect pubertal bone development. The aim of this study was to assess the effects of tamoxifen on bone mineral density (BMD) and skeletal maturation when used for pubertal gynecomastia. We evaluated 20 boys with pubertal gynecomastia receiving tamoxifen for at least 4 months. BMD was measured with dual-energy X-ray absorptiometry. Z-score and absolute BMD (g/cm(2)) was determined at baseline and 2 months after completing tamoxifen treatment. Bone age and height was evaluated before treatment and again one year later. Using absolute BMD (g/cm(2)), the mean difference from baseline was significant between the two groups both at spine (p=0.002) and femur (p=0.001), but not with the Z-score. This result was attributed to the expected increase during puberty according to sex and age. No significant effect on skeletal maturation was found (p=1.112). We conclude that when pubertal bone development is concerned, tamoxifen is safe for the treatment of pubertal gynecomastia as neither bone mineralization nor growth potential was affected.

  1. Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials.

    Science.gov (United States)

    Brentnall, Adam R; Cuzick, Jack; Byers, Helen; Segal, Corrinne; Reuter, Caroline; Detre, Simone; Sestak, Ivana; Howell, Anthony; Powles, Trevor J; Newman, William G; Dowsett, Mitchell

    2016-08-01

    A case-control study from two randomised breast cancer prevention trials of tamoxifen and raloxifene (P-1 and P-2) identified single-nucleotide polymorphisms (SNPs) in or near genes ZNF423 and CTSO as factors which predict which women will derive most anti-cancer benefit from selective oestrogen receptor modulator (SERM) therapy. In this article, we further examine this question using blood samples from two randomised tamoxifen prevention trials: the International Breast Cancer Intervention Study I (IBIS-I) and the Royal Marsden trial (Marsden). A nested case-control study was designed with 2:1 matching in IBIS-I and 1:1 matching in Marsden. The OncoArray was used for genotyping and included two SNPs previously identified (rs8060157 in ZNF423 and rs10030044 near CTSO), and 102 further SNPs within the same regions. Overall, there were 369 cases and 662 controls, with 148 cases and 268 controls from the tamoxifen arms. Odds ratios were estimated by conditional logistic regression, with Wald 95 % confidence intervals. In the tamoxifen arms, the per-allele odds ratio for rs8060157 was 0.99 (95 %CI 0.73-1.34) and 1.00 (95 %CI 0.76-1.33) for rs10030044. In the placebo arm, the odds ratio was 1.10 (95 %CI 0.87-1.40) for rs8060157 and 1.01 (95 %CI 0.79-1.29) for rs10030044. There was no evidence to suggest that other SNPs in the surrounding regions of these SNPs might predict response to tamoxifen. Results from these two prevention trials do not support the earlier findings. rs8060157 in ZNF423 and rs10030044 near CTSO do not appear to predict response to tamoxifen.

  2. Gene expression profiling reveals underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis

    International Nuclear Information System (INIS)

    Pogribny, Igor P.; Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.; Muskhelishvili, Levan; Rodriguez-Juarez, Rocio; Kovalchuk, Olga; Han Tao; Fuscoe, James C.; Ross, Sharon A.; Beland, Frederick A.

    2007-01-01

    Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the molecular mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. In the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during early stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that early stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during early stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G 1 to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt1/2, Akt3, and cyclin B, D1, and D3 proteins. The early appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen

  3. Internal fixation of mandibular angle fractures using one miniplate in Greek children: a 5-year retrospective study.

    Science.gov (United States)

    Iatrou, Ioannis; Theologie-Lygidakis, Nadia; Tzermpos, Fotios; Kamperos, Georgios

    2015-01-01

    Treatment modalities of mandibular angle fractures (MAFs) have been analyzed in several studies mainly referring to adult populations. The aim of this study was to retrospectively present and discuss our experience and literature findings regarding the treatment of MAFs in children. Data were retrieved from the files of the Oral and Maxillofacial department, at the Children's Hospital ''P. & A. Kyriakou'' of Athens, during a 5 years period (2009-2013). Demographic features, treatment methods, outcome and follow-up of all patients with mandibular angle fractures were recorded. 6 boys, 5-14 years old (mean age 10 years), were included in the study. They were all treated intraorally with open reduction and fixation via one monocortical titanium plate osteosynthesis at the external oblique line of the mandible, followed by 1 week of intermaxillary fixation (IMF). Plates were removed 3-12 months post-operatively. Follow-up period ranged from 12 to 18 months (mean 14.7 months). All fractures healed uneventfully and the patients tolerated well both the operation and the post-operative period. Osteosynthesis via intraoral approach combined with short duration IMF is adequate in treating MAFs in children. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  4. Principles of management of recurrence of breast cancer after tamoxifen therapy (abstract)

    International Nuclear Information System (INIS)

    Rasool, I.

    1999-01-01

    The management of recurrence of breast cancer after Tamoxifen therapy needs special attention. The recurrence can be local or distant. The patient, should be thoroughly investigated to find out exact sites of recurrences. Local recurrence is managed by excision, skin grafting or various types of flaps. If extensive radiation is administrated or if not given previously. The distant recurrence in patients who have had adjuvant menopausal status, sites of recurrence while life threatening or not and previous response. The patients who are post menopausal have responded to previous Tamoxifen therapy, long DFI and soft tissues and bony metastasis are best managed by Aromatase inhibitors i.e. Letrozole. (author)

  5. Postoperative spine infections

    Directory of Open Access Journals (Sweden)

    Paolo Domenico Parchi

    2015-09-01

    Full Text Available Postoperative spinal wound infection is a potentially devastating complication after operative spinal procedures. Despite the utilization of perioperative prophylactic antibiotics in recent years and improvements in surgical technique and postoperative care, wound infection continues to compromise patients’ outcome after spinal surgery. In the modern era of pending health care reform with increasing financial constraints, the financial burden of post-operative spinal infections also deserves consideration. The aim of our work is to give to the reader an updated review of the latest achievements in prevention, risk factors, diagnosis, microbiology and treatment of post-operative spinal wound infections. A review of the scientific literature was carried out using electronic medical databases Pubmed, Google Scholar, Web of Science and Scopus for the years 1973-2012 to obtain access to all publications involving the incidence, risk factors, prevention, diagnosis, treatment of postoperative spinal wound infections. We initially identified 119 studies; of these 60 were selected. Despite all the measures intended to reduce the incidence of surgical site infections in spine surgery, these remain a common and potentially dangerous complication.

  6. Partial Breast Radiation Therapy With Proton Beam: 5-Year Results With Cosmetic Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Bush, David A., E-mail: dbush@llu.edu [Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, California (United States); Do, Sharon [Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, California (United States); Lum, Sharon; Garberoglio, Carlos [Department of Surgical Oncology, Loma Linda University Medical Center, Loma Linda, California (United States); Mirshahidi, Hamid [Department of Medical Oncology, Loma Linda University Medical Center, Loma Linda, California (United States); Patyal, Baldev; Grove, Roger; Slater, Jerry D. [Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, California (United States)

    2014-11-01

    Purpose: We updated our previous report of a phase 2 trial using proton beam radiation therapy to deliver partial breast irradiation (PBI) in patients with early stage breast cancer. Methods and Materials: Eligible subjects had invasive nonlobular carcinoma with a maximal dimension of 3 cm. Patients underwent partial mastectomy with negative margins; axillary lymph nodes were negative on sampling. Subjects received postoperative proton beam radiation therapy to the surgical bed. The dose delivered was 40 Gy in 10 fractions, once daily over 2 weeks. Multiple fields were treated daily, and skin-sparing techniques were used. Following treatment, patients were evaluated with clinical assessments and annual mammograms to monitor toxicity, tumor recurrence, and cosmesis. Results: One hundred subjects were enrolled and treated. All patients completed the assigned treatment and were available for post-treatment analysis. The median follow-up was 60 months. Patients had a mean age of 63 years; 90% had ductal histology; the average tumor size was 1.3 cm. Actuarial data at 5 years included ipsilateral breast tumor recurrence-free survival of 97% (95% confidence interval: 100%-93%); disease-free survival of 94%; and overall survival of 95%. There were no cases of grade 3 or higher acute skin reactions, and late skin reactions included 7 cases of grade 1 telangiectasia. Patient- and physician-reported cosmesis was good to excellent in 90% of responses, was not changed from baseline measurements, and was well maintained throughout the entire 5-year follow-up period. Conclusions: Proton beam radiation therapy for PBI produced excellent ipsilateral breast recurrence-free survival with minimal toxicity. The treatment proved to be adaptable to all breast sizes and lumpectomy cavity configurations. Cosmetic results appear to be excellent and unchanged from baseline out to 5 years following treatment. Cosmetic results may be improved over those reported with photon

  7. Tamoxifen in the Mouse Brain: Implications for Fate-Mapping Studies Using the Tamoxifen-Inducible Cre-loxP System

    Czech Academy of Sciences Publication Activity Database

    Valný, Martin; Honsa, Pavel; Kirdajová, Denisa; Kameník, Zdeněk; Anděrová, Miroslava

    2016-01-01

    Roč. 10, ost (2016), s. 243 ISSN 1662-5102 R&D Projects: GA ČR(CZ) GA16-10214S; GA ČR(CZ) GA15-02760S Institutional support: RVO:68378041 ; RVO:61388971 Keywords : tamoxifen * brain metabolism * fate-mapping Subject RIV: FH - Neurology; EE - Microbiology, Virology (MBU-M) Impact factor: 4.555, year: 2016

  8. The EPOS-CC Score: An Integration of Independent, Tumor- and Patient-Associated Risk Factors to Predict 5-years Overall Survival Following Colorectal Cancer Surgery.

    Science.gov (United States)

    Haga, Yoshio; Ikejiri, Koji; Wada, Yasuo; Ikenaga, Masakazu; Koike, Shoichiro; Nakamura, Seiji; Koseki, Masato

    2015-06-01

    Surgical audit is an essential task for the estimation of postoperative outcome and comparison of quality of care. Previous studies on surgical audits focused on short-term outcomes, such as postoperative mortality. We propose a surgical audit evaluating long-term outcome following colorectal cancer surgery. The predictive model for this audit is designated as 'Estimation of Postoperative Overall Survival for Colorectal Cancer (EPOS-CC)'. Thirty-one tumor-related and physiological variables were prospectively collected in 889 patients undergoing elective resection for colorectal cancer between April 2005 and April 2007 in 16 Japanese hospitals. Postoperative overall survival was assessed over a 5-years period. The EPOS-CC score was established by selecting significant variables in a uni- and multivariate analysis and allocating a risk-adjusted multiplication factor to each variable using Cox regression analysis. For validation, the EPOS-CC score was compared to the predictive power of UICC stage. Inter-hospital variability of the observed-to-estimated 5-years survival was assessed to estimate quality of care. Among the 889 patients, 804 (90%) completed the 5-years follow-up. Univariate analysis displayed a significant correlation with 5-years survival for 14 physiological and nine tumor-related variables (p model for the prediction of survival. Risk-adjusted multiplication factors between 1.5 (distant metastasis) and 0.16 (serum sodium level) were accorded to the different variables. The predictive power of EPOS-CC was superior to the one of UICC stage; area under the curve 0.87, 95% CI 0.85-0.90 for EPOS-CC, and 0.80, 0.76-0.83 for UICC stage, p < 0.001. Quality of care did not differ between hospitals. The EPOS-CC score including the independent variables age, performance status, serum sodium level, TNM stage, and lymphatic invasion is superior to the UICC stage in the prediction of 5-years overall survival. This higher accuracy might be explained by the

  9. AIB1 is required for the acquisition of epithelial growth factor receptor-mediated tamoxifen resistance in breast cancer cells

    International Nuclear Information System (INIS)

    Zhao Wenhui; Zhang Qingyuan; Kang Xinmei; Jin Shi; Lou Changjie

    2009-01-01

    Acquired resistance to tamoxifen has become a serious obstacle in breast cancer treatment. The underlying mechanism responsible for this condition has not been completely elucidated. In this study, a tamoxifen-resistant (Tam-R) MCF-7 breast cancer cell line was developed to mimic the occurrence of acquired tamoxifen resistance as seen in clinical practice. Increased expression levels of HER1, HER2 and the estrogen receptor (ER)-AIB1 complex were found in tamoxifen-resistant cells. EGF stimulation and gefitinib inhibition experiments further demonstrated that HER1/HER2 signaling and AIB1 were involved in the proliferation of cells that had acquired Tam resistance. However, when AIB1 was silenced with AIB1-siRNA in Tam-R cells, the cell growth stimulated by the HER1/HER2 signaling pathway was significantly reduced, and the cells were again found to be inhibited by tamoxifen. These results suggest that the AIB1 protein could be a limiting factor in the HER1/HER2-mediated hormone-independent growth of Tam-R cells. Thus, AIB1 may be a new therapeutic target, and the removal of AIB1 may decrease the crosstalk between ER and the HER1/HER2 pathway, resulting in the restoration of tamoxifen sensitivity in tamoxifen-resistant cells.

  10. Lack of evidence from HPLC 32P-post-labelling for tamoxifen-DNA adducts in the human endometrium.

    Science.gov (United States)

    Carmichael, P L; Sardar, S; Crooks, N; Neven, P; Van Hoof, I; Ugwumadu, A; Bourne, T; Tomas, E; Hellberg, P; Hewer, A J; Phillips, D H

    1999-02-01

    Tamoxifen is associated with an increased incidence of endometrial cancer in women. It is also a potent carcinogen in rat liver and forms covalent DNA adducts in this tissue. A previous study exploring DNA adducts in human endometria, utilizing thin layer chromatography 32P-postlabelling, found no evidence for adducts in tamoxifen-treated women [Carmichael,P.L., Ugwumadu,A.H.N., Neven,P., Hewer,A.J., Poon,G.K. and Phillips,D.H. (1996) Cancer Res., 56, 1475-1479]. However, subsequent work utilizing HPLC 32P-post-labelling [Hemminki,K., Ranjaniemi,H., Lindahl,B. and Moberger,B. (1996) Cancer Res., 56, 4374-4377] suggested that very low levels could be detected. We have sought to investigate this question further by reproducing the HPLC methodology at two centres, and analysing endometrial DNA from 20 patients treated with 20 mg/day tamoxifen for between 22 and 65 months. Liver DNA isolated from tamoxifen-treated rats was used as a positive control. We found no convincing evidence for tamoxifen-derived DNA adducts in human endometrium. HPLC elution profiles of post-labelled DNA from tamoxifen-treated women were indistinguishable from those obtained with DNA from 14 untreated women and from six women taking toremifene, an analogue of tamoxifen.

  11. [Effect evaluation of over 5 year follow up of unilateral pedicle screw fixation with transforaminal lumbar interbody fusion for lumbar degenerative diseases].

    Science.gov (United States)

    Wang, Chong; Ying, Jin-He; Xie, Pan-Pan; Wu, Xiao-Guang

    2016-07-25

    To evaluate the clinical effects of over 5 year follow up of unilateral pedicle screw fixation with transforaminal lumbar interbody fusion(TLIF) in treating lumbar degenerative diseases. The clinical data of 24 patients with lumbar degenerative disease underwent unilateral pedicle screw fixation with transforaminal lumbar interbody fusion from March 2007 to October 2009, were retrospectively analyzed. There were 13 males and 11 females, aged from 34 to 68 years old with an average of 52 years. Postoperative pain and functional results were analyzed by the visual analogue scale(VAS) and Oswestry Disability Index(ODI). Radiological examination was obtained for each patient to assess the height of intervertebral space, postoperative intervertebral fusion conditions and general complications. All patients were followed up from 5 to 8 years with an average of 6.7 years. VAS scores of low back pain and leg pain decreased from preoperative 7.82±0.71, 8.42±1.24 to postoperative 1.87±0.81, 2.23±1.62, respectively( P degenerative diseases according to over 5 year follow up, however, its indications should be well considered. But the problems such as intervertebral space height of operated side loss and adjacent segment degeneration after unilateral pedicle screw fixation need further clinical study.

  12. [Postoperative cognitive deficits].

    Science.gov (United States)

    Kalezić, Nevena; Dimitrijević, Ivan; Leposavić, Ljubica; Kocica, Mladen; Bumbasirević, Vesna; Vucetić, Cedomir; Paunović, Ivan; Slavković, Nemanja; Filimonović, Jelena

    2006-01-01

    Cognitive dysfunctions are relatively common in postoperative and critically ill patients. This complication not only compromises recovery after surgery, but, if persistent, it minimizes and compromises surgery itself. Risk factors of postoperative cognitive disorders can be divided into age and comorbidity dependent, and those related to anesthesia and surgery. Cardiovascular, orthopedic and urologic surgery carries high risk of postoperative cognitive dysfunction. It can also occur in other types of surgical treatment, especially in elderly. Among risk factors of cognitive disorders, associated with comorbidity, underlying psychiatric and neurological disorders, substance abuse and conditions with elevation of intracranial pressure are in the first place in postoperative patients. Preoperative and perioperative predisposing conditions for cognitive dysfunction and their incidence were described in our paper. These are: geriatric patients, patients with substance abuse, preexisting psychiatric or cognitive disorders, neurologic disease with high intracranial pressure, cerebrovascular insufficiency, epilepsia, preeclampsia, acute intermittent porphyria, operation type, brain hypoxia, changes in blood glucose level, electrolyte imbalance, anesthetic agents, adjuvant medication and intraoperative awareness. For each of these factors, evaluation, prevention and treatment strategies were suggested, with special regard on anesthetic technique.

  13. Postoperative Chemotherapy for Medulloblastoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-03-01

    Full Text Available The survival rate and cognitive function of 43 children, age <3 years, with medulloblastoma treated with intensive postoperative chemotherapy alone, without radiotherapy, were determined at the University of Wurzburg and other centers in Germany Chemotherapy consisted of three two-month cycles of cyclophosphamide, methotrexate, vincristine, carboplatin, and etoposide.

  14. Construction of a Nanodiamond–Tamoxifen Complex as a Breast Cancer Drug Delivery Vehicle

    Directory of Open Access Journals (Sweden)

    Linda-Lucila Landeros-Martínez

    2016-01-01

    Full Text Available According to the World Health Organization, breast cancer represents 16% of all cancer cases in women and is the second most common cancer. In the past decades, the mortality among patients with metastasis breast cancer has been reduced significantly via drug delivery by means of nanodiamond therapies, which are both biocompatible and scalable. In this study, we determined a theoretical pathway for the construction of a nanodiamond–tamoxifen complex that will act as a drug delivery vehicle for targeting tumor tissues of breast cancer. The tamoxifen pharmacophore was defined and the binding zone was identified for the electrostatic interaction between tamoxifen and a functionalized site of a nanodiamond particle allowing for attachment of the payload (this drug to the surface of the nanodiamond particle. In addition, an analysis of the intermolecular interaction between the nanodiamond and tamoxifen was conducted, showing three hydrogen bonds complying fully with Lipinski’s rule of five, which states that a compound should have five or fewer hydrogen bonds to be permeating and easily absorbed by the body (qualitative prediction. All calculations were performed using the conceptual Density Functional Theory with the M06 functional and the basis set 6-31G(d. The solvent effect has been taken into account by an implicit model, the conductor like polarizable continuum model.

  15. Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells.

    Science.gov (United States)

    Kim, Sangmin; Lee, Jeongmin; Oh, Soo Jin; Nam, Seok Jin; Lee, Jeong Eon

    2015-09-01

    Although tamoxifen is the most common and effective therapy for treatment of estrogen receptor-α (ER-α) breast cancer patients, resistance of endocrine therapy occurs, either de novo or acquired during therapy. Here, we investigated the clinical value of epidermal growth factor receptor (EGFR) in tamoxifen-resistant (TamR) patients and the differential effect of EGFR inhibitors, neratinib and gefitinib, on TamR breast cancer cell model. The morphology of TamR MCF7 cells showed mesenchymal phenotypes and did not induce cell death by tamoxifen treatment compared with tamoxifen‑sensitive (TamS) MCF7 cells. In addition, mesenchymal marker proteins, including N-cadherin (N-cad), fibronectin (FN), and Slug, significantly increased in TamR cells. In contrast, ER-α and E-cadherin (E-cad) were greatly decreased. We also found that the levels of EGFR and HER2 expression were increased in TamR cells. Furthermore, we observed that EGFR expression was directly involved with poor prognosis of tamoxifen-treated breast cancer patients using the GSE1378 date set. Thus, we treated TamR and TamS cells with EGFR inhibitors, neratinib and gefitinib, respectively. Interestingly, neratinib induced apoptotic cell death of TamR but not gefitinib. Cleaved PARP-1 expression was also increased by neratinib treatment in TamR cells. Therefore, we suggest that neratinib may be a potential therapeutic drug for treating TamR breast cancer.

  16. FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Lukasz Turczyk

    2017-10-01

    Full Text Available Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa. Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy.

  17. Polypoid endometriosis mimicking invasive cancer in an obese, postmenopausal tamoxifen user

    Directory of Open Access Journals (Sweden)

    William T. Jaegle

    2017-11-01

    Précis: Endometriosis is a benign estrogen dependent condition rarely problematic in a postmenopausal patient. Tamoxifen use in the setting of an obese patient may contribute to a proliferation of pre-existing endometriosis which resembles an aggressive late-stage gynecological malignancy.

  18. Use of dried blood spots for the determination of serum concentrations of tamoxifen and endoxifen

    NARCIS (Netherlands)

    Jager, N G L; Rosing, H; Schellens, J H M; Beijnen, J H; Linn, S C

    The anti-estrogenic effect of tamoxifen is suggested to be mainly attributable to its metabolite (Z)-endoxifen, and a minimum therapeutic threshold for (Z)-endoxifen in serum has been proposed. The objective of this research was to establish the relationship between dried blood spot (DBS) and serum

  19. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

    NARCIS (Netherlands)

    Pan, Hongchao; Gray, Richard; Braybrooke, Jeremy; Davies, Christina; Taylor, Carolyn; McGale, Paul; Peto, Richard; Pritchard, Kathleen I.; Bergh, Jonas; Dowsett, Mitch; Hayes, Daniel F.; Albain, K.; Anderson, S.; Arriagada, R.; Barlow, W.; Bartlett, J.; Bergsten‐Nordström, E.; Bliss, J.; Boccardo, F.; Bradley, R.; Brain, E.; Cameron, D.; Clarke, M.; Coates, A.; Coleman, R.; Correa, C.; Costantino, J.; Cuzick, J.; Davidson, N.; Dodwell, D.; Di Leo, A.; Ewertz, M.; Forbes, J.; Gelber, R.; Gnant, M.; Goldhirsch, A.; Goodwin, P.; Hill, C.; Ingle, J.; Jagsi, R.; Janni, W.; Loibl, S.; MacKinnon, E.; Martin, M.; Mukai, H.; Norton, L.; Ohashi, Y.; Paik, S.; Perez, E.; Bijker, N.

    2017-01-01

    The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining

  20. Anxiety and depression after prostate cancer diagnosis and treatment: 5-year follow-up

    NARCIS (Netherlands)

    Korfage, I. J.; Essink-Bot, M.-L.; Janssens, A. C. J. W.; Schröder, F. H.; de Koning, H. J.

    2006-01-01

    To document anxiety and depression from pretreatment till 5-year follow-up in 299 men with localized prostate cancer. To assess, if baseline scores were predictive for anxiety and depression at 1-year follow-up. Respondents completed four assessments (pretreatment, at 6 and 12 months, and at 5-year

  1. Hypomineralized second primary molars: prevalence data in Dutch 5-year-olds

    NARCIS (Netherlands)

    Elfrink, M.E.C.; Schuller, A.A.; Weerheijm, K.L.; Veerkamp, J.S.J.

    2008-01-01

    The aim of this cross-sectional observational study was to report on the prevalence of hypomineralizations in second primary molars in 5-year-old Dutch children. In the study 386 (45% girls) 5-year-old Dutch children, all insured by a Health Insurance Fund, participated. Scoring criteria for molar

  2. Reprogramming of the ERRα and ERα target gene landscape triggers tamoxifen resistance in breast cancer.

    Science.gov (United States)

    Thewes, Verena; Simon, Ronald; Schroeter, Petra; Schlotter, Magdalena; Anzeneder, Tobias; Büttner, Reinhard; Benes, Vladimir; Sauter, Guido; Burwinkel, Barbara; Nicholson, Robert I; Sinn, Hans-Peter; Schneeweiss, Andreas; Deuschle, Ulrich; Zapatka, Marc; Heck, Stefanie; Lichter, Peter

    2015-02-15

    Endocrine treatment regimens for breast cancer that target the estrogen receptor-α (ERα) are effective, but acquired resistance remains a limiting drawback. One mechanism of acquired resistance that has been hypothesized is functional substitution of the orphan receptor estrogen-related receptor-α (ERRα) for ERα. To examine this hypothesis, we analyzed ERRα and ERα in recurrent tamoxifen-resistant breast tumors and conducted a genome-wide target gene profiling analysis of MCF-7 breast cancer cell populations that were sensitive or resistant to tamoxifen treatment. This analysis uncovered a global redirection in the target genes controlled by ERα, ERRα, and their coactivator AIB1, defining a novel set of target genes in tamoxifen-resistant cells. Beyond differences in the ERα and ERRα target gene repertoires, both factors were engaged in similar pathobiologic processes relevant to acquired resistance. Functional analyses confirmed a requirement for ERRα in tamoxifen- and fulvestrant-resistant MCF-7 cells, with pharmacologic inhibition of ERRα sufficient to partly restore sensitivity to antiestrogens. In clinical specimens (n = 1041), increased expression of ERRα was associated with enhanced proliferation and aggressive disease parameters, including increased levels of p53 in ERα-positive cases. In addition, increased ERRα expression was linked to reduced overall survival in independent tamoxifen-treated patient cohorts. Taken together, our results suggest that ERα and ERRα cooperate to promote endocrine resistance, and they provide a rationale for the exploration of ERRα as a candidate drug target to treat endocrine-resistant breast cancer. ©2015 American Association for Cancer Research.

  3. Management of Postoperative Respiratory Failure.

    Science.gov (United States)

    Mulligan, Michael S; Berfield, Kathleen S; Abbaszadeh, Ryan V

    2015-11-01

    Despite best efforts, postoperative complications such as postoperative respiratory failure may occur and prompt recognition of the process and management is required. Postoperative respiratory failure, such as postoperative pneumonia, postpneumonectomy pulmonary edema, acute respiratory distress-like syndromes, and pulmonary embolism, are associated with high morbidity and mortality. The causes of these complications are multifactorial and depend on preoperative, intraoperative, and postoperative factors, some of which are modifiable. The article identifies some of the risk factors, causes, and treatment strategies for successful management of the patient with postoperative respiratory failure. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. 25-Hydroxy vitamin-D, obesity, and associated variables as predictors of breast cancer risk and tamoxifen benefit in NSABP-P1.

    Science.gov (United States)

    Amir, Eitan; Cecchini, Reena S; Ganz, Patricia A; Costantino, Joseph P; Beddows, Samantha; Hood, Nicola; Goodwin, Pamela J

    2012-06-01

    Observational studies suggest that host factors are associated with breast cancer risk. The influence of obesity, vitamin-D status, insulin resistance, inflammation, and elevated adipocytokines in women at high risk of breast cancer is unknown. The NSABP-P1 trial population was used for a nested case-control study. Cases were drawn from those who developed invasive breast cancer and controls selected from unaffected participants (≤4 per case) matched for age, race, 5 year Gail score, and geographic location of clinical center as a surrogate for latitude. Fasting serum banked at trial enrolment was assayed for 25-hydroxy vitamin-D (25OHD), insulin, leptin (adipocytokine), and C-reactive protein (CRP, marker of inflammation). Logistic regression was used to test for associations between study variables and the risk of invasive breast cancer. Two hundred and thirty-one cases were matched with 856 controls. Mean age was 54, and 49% were premenopausal. There were negative correlations for 25OHD with body mass index (BMI), insulin, CRP, and leptin. BMI ≥ 25 kg/m(2) was associated with higher breast cancer risk (odds ratio [OR] 1.45, p = 0.02) and tamoxifen treatment was associated with lower risk (OR = 0.44, p continuous variables, 25OHD, insulin, CRP, and leptin levels were not associated with breast cancer risk (all p > 0.34). In this high risk population, higher BMI was associated with a greater breast cancer risk. Serum levels of 25OHD, insulin, CRP, and leptin were not independent predictors of either breast cancer risk or tamoxifen benefit.

  5. Radiolytic oxidation of tamoxifen using the free radicals {sup .}OH and (or) HO{sub 2}{sup .}; Oxydation radiolytique du tamoxifene par les radicaux libres {sup .}OH et (ou) HO{sub 2}{sup .}

    Energy Technology Data Exchange (ETDEWEB)

    Leguene, C. [Lab. de Chimie-Physique, Centre national de la recherche scientifique, CNRS, Univ. Rene Descartes, Paris (France); Clavere, P. [Service de Radiotherapie et d' Oncologie, Centre hospitalier universitaire, CHU, Dupuytren, Limoges (France); Jore, D.; Gardes-Albert, M. [Lab. de Chimie-Physique, Centre national de la recherche scientifique, CNRS, Univ. Rene Descartes, Paris (France)

    2001-02-01

    Tamoxifen is the most widely used antiestrogen in the treatment of breast cancer. In this work, we have studied its antioxidant properties. We have investigated the ability of tamoxifen to scavenge, in vitro, {sup .}OH and (or) HO{sub 2}{sup .} free radicals that are produced by water radiolysis. Aqueous solutions of tamoxifen of concentrations ranging between 10{sup -5} and 2.5 x 10{sup -5} M have been irradiated ({gamma} {sup 137}Cs) in aerated acidic medium (H{sub 3}PO{sub 4} 10{sup -3} M or HCOOH 10{sup -1} M). The results show that tamoxifen reacts quantitatively with {sup .}OH free radicals but does not react with HO{sub 2}{sup .} free radicals under our experimental conditions. (author)

  6. Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells.

    Science.gov (United States)

    Cheng, Ran; Liu, Ya-Jing; Cui, Jun-Wei; Yang, Man; Liu, Xiao-Ling; Li, Peng; Wang, Zhan; Zhu, Li-Zhang; Lu, Si-Yi; Zou, Li; Wu, Xiao-Qin; Li, Yu-Xia; Zhou, You; Fang, Zheng-Yu; Wei, Wei

    2017-05-02

    Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

  7. Pediatric cardiac postoperative care

    Directory of Open Access Journals (Sweden)

    Auler Jr. José Otávio Costa

    2002-01-01

    Full Text Available The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

  8. A prospective 5-year study of fixed partial prostheses supported by implants with machined and TiO2-blasted surface

    DEFF Research Database (Denmark)

    Gotfredsen, K; Karlsson, U

    2001-01-01

    PURPOSE: The aim of the present study was to evaluate whether there was a difference between machined and TiO(2)-blasted implants regarding survival rate and marginal bone loss during a 5-year observation period. MATERIALS AND METHODS: A total of 133 implants (Astra Tech Dental Implants; Astra Tech...... AB, Mölndal, Sweden) were placed in 50 patients at 6 centers in 4 Scandinavian countries. Forty-eight implants were installed in the maxilla and 85 implants in the mandible. A randomization and a stratification were done, so that each fixed partial prosthesis was supported by at least 1 machined...... and 1 TiO(2)-blasted implant. The implant-supported fixed partial prostheses (ISFPP) were fabricated within 2 months after postoperative healing. A total of 52 ISFPP (17 maxillary, 35 mandibular) were inserted. The patients were clinically examined once a year for 5 years. At the annual follow...

  9. Accelerated partial breast irradiation in the elderly: 5-year results of high-dose rate multi-catheter brachytherapy

    International Nuclear Information System (INIS)

    Genebes, Caroline; Hannoun-Levi, Jean-Michel; Chand, Marie-Eve; Gal, Jocelyn; Gautier, Mathieu; Raoust, Ines; Ihrai, Tarik; Courdi, Adel; Ferrero, Jean-Marc; Peyrottes, Isabelle

    2014-01-01

    To evaluate clinical outcome after accelerated partial breast irradiation (APBI) in the elderly after high-dose-rate interstitial multi-catheter brachytherapy (HIBT). Between 2005 and 2013, 70 patients underwent APBI using HIBT. Catheter implant was performed intra or post-operatively (referred patients) after lumpectomy and axillary sentinel lymph node dissection. Once the pathological results confirmed the indication of APBI, planification CT-scan was performed to deliver 34 Gy/10f/5d or 32 Gy/8f/4d. Dose-volume adaptation was manually achieved (graphical optimization). Dosimetric results and clinical outcome were retrospectively analyzed. Physician cosmetic evaluation was reported. With a median follow-up of 60.9 months [4.6 – 90.1], median age was 80.7 years [62 – 93.1]. Regarding APBI ASTRO criteria, 61.4%, 18.6% and 20% were classified as suitable, cautionary and non-suitable respectively. Axillary sentinel lymph node dissection was performed in 94.3%; 8 pts (11.5%) presented an axillary involvement. A median dose of 34 Gy [32 – 35] in 8 to 10 fractions was delivered. Median CTV was 75.2 cc [16.9 – 210], median D90 EQD2 was 43.3 Gy [35 – 72.6] and median DHI was 0.54 [0.19 – 0.74]. One patient experienced ipsilateral recurrence (5-year local free recurrence rate: 97.6%. Five-year specific and overall survival rates were 97.9% and 93.2% respectively. Thirty-four patients (48%) presented 47 late complications classified grade 1 (80.8%) and grade 2 (19.2%) with no grade ≥ 3. Cosmetic results were considered excellent/good for 67 pts (95.7%). APBI using HIBT and respecting strict rules of implantation and planification, represents a smart alternative between no post-operative irradiation and whole breast irradiation delivered over 6 consecutive weeks

  10. Early endoscopic realignment of traumatic anterior and posterior urethral disruptions under caudal anaesthesia - a 5-year review.

    Science.gov (United States)

    Olapade-Olaopa, E O; Atalabi, O M; Adekanye, A O; Adebayo, S A; Onawola, K A

    2010-01-01

    We recently described early rigid retrograde endoscopic realignment of the disrupted urethra under caudal anaesthesia in the outpatient setting. This retrospective study was performed to evaluate our medium-term results. A retrospective review of patients who had early rigid retrograde endoscopic realignment of traumatic urethral disruptions in our institution over a 5-year period was done and the relevant data extracted and analyzed. Fourteen acutely ruptured urethras (10 posterior and four anterior) were endoscopically realigned early in the study period. Nine (90%) of the posterior disruptions occurred at bulbo-membranous urethra (distal to the external sphincter mechanism). Thirteen of the ruptured urethras (93%) were successfully realigned (nine posterior and four anterior) and postoperative clean intermittent self-calibration (CIC) was instituted in 10 patients. The mean follow-up period was 36.6 months (range 18-54 months). The mean operating time and the median hospital stay were 22 min (range 8-68 min) and 3 days (range 1-10 days), respectively, and were shorter in patients with injuries of the anterior urethra than those with posterior urethral tears (p < or = 0.0001). Post-realignment, all 13 patients were potent and continent. Two patients required additional procedures (direct vision internal urethrotomy or urethral dilation) and one patient has remained on CIC i.e. a stricture rate of 21%. Early retrograde endoscopic realignment under caudal analgesia is suitable and cost-effective for patients with acute traumatic urethral disruptions and has good medium-term results. In addition, an early postoperative regimen of CIC significantly reduced stricture-formation in our series.

  11. Brain Function, Structure, and Neurochemistry After Tamoxifen/Chemotherapy Assessed by Neuropsychologic Testing and H Magnetic Resonance Spectroscopy

    National Research Council Canada - National Science Library

    Ernst, Thomas

    2000-01-01

    ...). On magnetic resonance spectroscopy (1H MRS), women who received tamoxifen (average 4.4 years) had no statistically significant differences in brain metabolite ratios compared to the negative control group...

  12. Management of stage III thymoma with postoperative radiation therapy

    International Nuclear Information System (INIS)

    Krueger, J.B.; Sagerman, R.H.; King, G.A.

    1987-01-01

    The results of postoperative radiation therapy in 12 patients with Stage III thymoma treated during the period 1966-1986 were reviewed. Surgical therapy consisted of total resection in one, subtotal resection in seven, and biopsy only in four. Megavoltage irradiation in the dose range of 3,000-5,600 cGy was employed, with the majority receiving a dose of at least 5,000 cGy. The local control rate was 67%. The actuarial 5-year observed and adjusted survival rates were 57% and 75%, respectively. These results indicate that postoperative radiation therapy is an effective therapeutic modality in the control of Stage III thymoma

  13. Cardiovascular disease risk factors in 5-year-old urban South ...

    African Journals Online (AJOL)

    Cardiovascular disease risk factors in 5-year-old urban South African children the birth to ten study. Krisela Steyn, Thea de Wet, Linda Richter, Noel Cameron, Naomi S Levitt, Christopher Morrell ...

  14. Tamoxifen induces regression of estradiol-induced mammary cancer in ACI.COP-Ept2 rat model

    OpenAIRE

    Ruhlen, Rachel L.; Willbrand, Dana M.; Besch-Williford, Cynthia L.; Ma, Lixin; Shull, James D.; Sauter, Edward R.

    2008-01-01

    The ACI rat is a unique model of human breast cancer in that mammary cancers are induced by estrogen without carcinogens, irradiation, xenografts or transgenic manipulations. We sought to characterize mammary cancers in a congenic variant of the ACI rat, the ACI.COP-Ept2. All rats with estradiol implants developed mammary cancers in 5–7 months. Rats bearing estradiol-induced mammary cancers were treated with tamoxifen for three weeks. Tamoxifen reduced tumor mass, measured by magnetic resonan...

  15. The Effect of Tamoxifen Administration and γ-Irradiation on Thyroid Hormones Levels in Rats Bearing Mammary Tumours

    International Nuclear Information System (INIS)

    Abdelgawad, M.R.

    2013-01-01

    Breast Cancer is the most common malignancy among women in most developed and developing regions of the world, in female, tamoxifen acting as an oestrogen antagonist on the breast. Thyroid hormones can stimulate the proliferation in vitro of certain tumor cell lines. The aim of the present study is to evaluate the effect of tamoxifen and/ or irradiation treatment on thyroid hormones in rats' mammary tumours. Forty-two female Sprague-Dawely rats randomly divided into seven groups' proliferation (6 rats each). Control group, normal rats supplemented with tamoxifen for 3 weeks, normal rats exposed to a single dose 3Gy γ-rays, rats treated with Dimethylbenz (a) anthracene (DMBA) dissolved in corn oil (30ppm) sc and followed for 6 months until breast cancer occurrence, breast cancer bearing rats supplemented with tamoxifen for 3 weeks twice a day, breast cancer bearing rats exposed to a single dose 3Gy γ-rays, breast cancer bearing rats exposed to a single dose 3Gy γ-rays and supplemented with tamoxifen for 3 weeks twice a day. At the end of the experiment, mammary tumours and control rats were sacrificed after 3 weeks from different treatments and serum thyroid hormones and estradiol (E2) levels were assayed using commercial kits. Results show T4 and E2 levels not triiodothyronine (T3) were altered in different experimental groups. It could be concluded that γ-irradiation promote the expression of neoplastic potential by affecting both E2 and thyroid hormones and tamoxifen may alter the thyroid hormones. Tamoxifen administration and γ-irradiation may have worth effects on thyroxin (T4) and E2 levels. It is recommended to further studies towards the bystander effect of γ-rays exposure and tamoxifen treatment on the tissue culture and molecular biology scale.

  16. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single [14C]-Labeled Therapeutic Dose.

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K; Tompkins, E M; Boocock, D J; Martin, E A; Farmer, P B; Turteltaub, K W; Ubick, E; Hemingway, D; Horner-Glister, E; White, I H

    2007-05-23

    Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the U.S. for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated but much interest has focussed on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to ten women as a single [{sup 14}C]-labeled therapeutic (20 mg) dose, {approx}18 h prior to undergoing colon resections. Using the sensitive technique of accelerator mass spectrometry, coupled with HPLC separation of enzymatically digested DNA, a peak corresponding to authentic dG-N{sup 2}-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/10{sup 9} nucleotides. No [{sup 14}C]-radiolabel associated with tamoxifen or its major metabolites was detected. The presence of detectable CYP3A4 protein in all colon samples suggests this tissue has the potential to activate tamoxifen to {alpha}-hydroxytamoxifen, in addition to that occurring in the systemic circulation, and direct interaction of this metabolite with DNA could account for the binding observed. Although the level of tamoxifeninduced damage displayed a degree of inter-individual variability, when present it was {approx}10-100 times higher than that reported for other suspect human colon carcinogens such as PhIP. These findings provide a mechanistic basis through which tamoxifen could increase the incidence of colon cancers in women.

  17. Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial

    DEFF Research Database (Denmark)

    Thomson, Neil C; Rubin, Adalberto S; Niven, Robert M

    2011-01-01

    Bronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure.......Bronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure....

  18. Tamoxifen enhances stemness and promotes metastasis of ERα36+ breast cancer by upregulating ALDH1A1 in cancer cells

    Science.gov (United States)

    Wang, Qiang; Jiang, Jun; Ying, Guoguang; Xie, Xiao-Qing; Zhang, Xia; Xu, Wei; Zhang, Xuemin; Song, Erwei; Bu, Hong; Ping, Yi-Fang; Yao, Xiao-Hong; Wang, Bin; Xu, Shilei; Yan, Ze-Xuan; Tai, Yanhong; Hu, Baoquan; Qi, Xiaowei; Wang, Yan-Xia; He, Zhi-Cheng; Wang, Yan; Wang, Ji Ming; Cui, You-Hong; Chen, Feng; Meng, Kun; Wang, Zhaoyi; Bian, Xiu-Wu

    2018-01-01

    The 66 kDa estrogen receptor alpha (ERα66) is the main molecular target for endocrine therapy such as tamoxifen treatment. However, many patients develop resistance with unclear mechanisms. In a large cohort study of breast cancer patients who underwent surgery followed by tamoxifen treatment, we demonstrate that ERα36, a variant of ERα66, correlates with poor prognosis. Mechanistically, tamoxifen directly binds and activates ERα36 to enhance the stemness and metastasis of breast cancer cells via transcriptional stimulation of aldehyde dehydrogenase 1A1 (ALDH1A1). Consistently, the tamoxifen-induced stemness and metastasis can be attenuated by either ALDH1 inhibitors or a specific ERα36 antibody. Thus, tamoxifen acts as an agonist on ERα36 in breast cancer cells, which accounts for hormone therapy resistance and metastasis of breast cancer. Our study not only reveals ERα36 as a stratifying marker for endocrine therapy but also provides a promising therapeutic avenue for tamoxifen-resistant breast cancer. PMID:29393296

  19. Effects of 13- cis-retinoic acid on the tamoxifen induced uterine histological changes in the rabbit

    International Nuclear Information System (INIS)

    Hamid, S.; Minhas, L.A.; Khan, M.Y.

    2013-01-01

    Objective: To study the effects of 13-cis-retinoic acid on the tamoxifen induced uterine histological changes in the rabbit. Study Design: Experimental - randomized controlled trial. Place and Duration of study: The study was conducted for 4 months at the department of Anatomy, Army Medical College and National Institute of Health in 2007. Material and Methods: The animals were randomly divided into three groups, a control group A, and two experimental groups B and C, consisting of thirty rabbits each. The experimental groups were treated with tamoxifen only and tamoxifen plus retinoic acid, respectively. The animals were sacrificed after three months. The uteri were then processed for paraffin embedding. Sections were then assessed for the luminal epithelial height, endometrial area and percentage of mitotic figures. Results: The results obtained were suggestive of uterine proliferation by tamoxifen. The adjuvant administration of 13-cis-retinoic acid produced a statistically significant (p = 0.002) inhibitory effect on the tamoxifen induced increase in the area of endometrium, whereas no significant suppressive effect of this drug has been observed on the other parameters when compared with Group B. Conclusion: 13-cis Retinoic acid has not shown a significant role in the reversal of tamoxifen induced changes in the uterine tissue after a short term administration of three months. (author)

  20. Prescribing tamoxifen in primary care for the prevention of breast cancer: a national online survey of GPs' attitudes.

    Science.gov (United States)

    Smith, Samuel G; Foy, Robbie; McGowan, Jennifer A; Kobayashi, Lindsay C; DeCensi, Andrea; Brown, Karen; Side, Lucy; Cuzick, Jack

    2017-06-01

    The cancer strategy for England (2015-2020) recommends GPs prescribe tamoxifen for breast cancer primary prevention among women at increased risk. To investigate GPs' attitudes towards prescribing tamoxifen. In an online survey, GPs in England, Northern Ireland, and Wales ( n = 928) were randomised using a 2 × 2 between-subjects design to read one of four vignettes describing a healthy patient seeking a tamoxifen prescription. In the vignette, the hypothetical patient's breast cancer risk (moderate versus high) and the clinician initiating the prescription (GP prescriber versus secondary care clinician [SCC] prescriber) were manipulated in a 1:1:1:1 ratio. Outcomes were willingness to prescribe, comfort discussing harms and benefits, comfort managing the patient, factors affecting the prescribing decision, and awareness of tamoxifen and the National Institute for Health and Care Excellence (NICE) guideline CG164. Half (51.7%) of the GPs knew tamoxifen can reduce breast cancer risk, and one-quarter (24.1%) were aware of NICE guideline CG164. Responders asked to initiate prescribing (GP prescriber) were less willing to prescribe tamoxifen than those continuing a prescription initiated in secondary care (SCC prescriber) (68.9% versus 84.6%, P preventive therapy in secondary care before asking GPs to continue the patient's care may overcome some prescribing barriers. © British Journal of General Practice 2017.

  1. Endoscopic Gluteus Medius Repair With Concomitant Arthroscopy for Labral Tears: A Case Series With Minimum 5-Year Outcomes.

    Science.gov (United States)

    Perets, Itay; Mansor, Yosif; Yuen, Leslie C; Chen, Austin W; Chaharbakhshi, Edwin O; Domb, Benjamin G

    2017-12-01

    To report the minimum 5-year outcomes of endoscopic gluteus medius repair for partial- and full-thickness tears with concomitant hip arthroscopy. Data for all patients who underwent hip arthroscopy between February 2009 and September 2011 were prospectively collected. We included patients who underwent endoscopic gluteus medius repair with concomitant arthroscopic labral treatment and for whom the following measures were obtained preoperatively and at a minimum of 5 years' follow-up: modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome Score-Sports Specific Subscale, and visual analog scale score for pain. For included patients, the International Hip Outcome Tool-12 (iHOT-12) score and satisfaction rating were also available at latest follow-up. Patients with at least 1 of the following criteria were excluded: preoperative Tönnis osteoarthritis grade of 2 or greater, previous hip conditions, severe dysplasia, and Workers' Compensation claims. There were 16 patients eligible for inclusion, 14 (87.5%) of whom had minimum 5-year follow-up, with a mean of 68.8 months (range, 60.1-79.6 months). The study group consisted of 13 women (92.9%) and 1 man (7.1%) with a mean age at surgery of 57.4 years (range, 46.3-74.8 years). Outcome scores improved as follows: modified Harris Hip Score, from 52.4 to 81.2 (P = .004); Non-Arthritic Hip Score, from 48.0 to 82.5 (P = .002); Hip Outcome Score-Sports Specific Subscale, from 30.1 to 66.4 (P arthroscopy for labral tears is safe and shows favorable outcomes at minimum 5-year follow-up. Patient outcomes were as favorable at 5 years as they were at 2 years postoperatively. Level IV, therapeutic case series. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  2. Tumor specific HMG-CoA reductase expression in primary pre-menopausal breast cancer predicts response to tamoxifen

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2011-01-31

    Abstract Introduction We previously reported an association between tumor-specific 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) expression and a good prognosis in breast cancer. Here, the predictive value of HMG-CoAR expression in relation to tamoxifen response was examined. Methods HMG-CoAR protein and RNA expression was analyzed in a cell line model of tamoxifen resistance using western blotting and PCR. HMG-CoAR mRNA expression was examined in 155 tamoxifen-treated breast tumors obtained from a previously published gene expression study (Cohort I). HMG-CoAR protein expression was examined in 422 stage II premenopausal breast cancer patients, who had previously participated in a randomized control trial comparing 2 years of tamoxifen with no systemic adjuvant treatment (Cohort II). Kaplan-Meier analysis and Cox proportional hazards modeling were used to estimate the risk of recurrence-free survival (RFS) and the effect of HMG-CoAR expression on tamoxifen response. Results HMG-CoAR protein and RNA expression were decreased in tamoxifen-resistant MCF7-LCC9 cells compared with their tamoxifen-sensitive parental cell line. HMG-CoAR mRNA expression was decreased in tumors that recurred following tamoxifen treatment (P < 0.001) and was an independent predictor of RFS in Cohort I (hazard ratio = 0.63, P = 0.009). In Cohort II, adjuvant tamoxifen increased RFS in HMG-CoAR-positive tumors (P = 0.008). Multivariate Cox regression analysis demonstrated that HMG-CoAR was an independent predictor of improved RFS in Cohort II (hazard ratio = 0.67, P = 0.010), and subset analysis revealed that this was maintained in estrogen receptor (ER)-positive patients (hazard ratio = 0.65, P = 0.029). Multivariate interaction analysis demonstrated a difference in tamoxifen efficacy relative to HMG-CoAR expression (P = 0.05). Analysis of tamoxifen response revealed that patients with ER-positive\\/HMG-CoAR tumors had a significant response to tamoxifen (P = 0.010) as well as

  3. Postoperative radiation therapy for major salivary gland cancer

    International Nuclear Information System (INIS)

    Kato, Fumio; Yahara, Katsuya; Ohguri, Takayuki

    2003-01-01

    A retrospective study was performed on 29 patients with major salivary gland cancer treated with postoperative irradiation between 1981 and 2002. Univariate and multivariate analyses of age, gender, cancer grade, T stage, N stage, surgical resectability, concomitant chemotherapy, and neoadjuvant or adjuvant chemotherapy were performed for disease-free survival. The 5-year survival rates and 5-year disease-free survival rate were 61.6% and 41.4%, respectively. Both univariate and multivariate analyses showed that cancer grade and surgical resectability influenced survival rates. Chemotherapy did not influence the disease-free survival. The total dose of postoperative radiation was 47.6±8.8 Gy in the complete excision group as planned, but was 56.1±7.9 Gy in the incomplete excision group, which may be insufficient and lead to poor treatment outcome. (author)

  4. Postoperative care in geriatrics

    Directory of Open Access Journals (Sweden)

    Grzegorz Ulenberg

    2017-08-01

    Full Text Available Treatment of the elderly is becoming increasingly common problem and is of interest, because in the future this phenomenon will affect most of us. For many years, he observed in different countries increasingly rapid aging of the population, including in Poland. The operation in such a patient poses a high risk of complications and life-threatening conditions. Their age makes in the postoperative period there are many medical problems. Many factors can affect the scope of a different self-care nursing with such a patient.

  5. Postoperative conversion disorder.

    Science.gov (United States)

    Afolabi, Kola; Ali, Sameer; Gahtan, Vivian; Gorji, Reza; Li, Fenghua; Nussmeier, Nancy A

    2016-05-01

    Conversion disorder is a psychiatric disorder in which psychological stress causes neurologic deficits. A 28-year-old female surgical patient had uneventful general anesthesia and emergence but developed conversion disorder 1 hour postoperatively. She reported difficulty speaking, right-hand numbness and weakness, and right-leg paralysis. Neurologic examination and imaging revealed no neuronal damage, herniation, hemorrhage, or stroke. The patient mentioned failing examinations the day before surgery and discontinuing her prescribed antidepressant medication, leading us to diagnose conversion disorder, with eventual confirmation by neuroimaging and follow-up examinations. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Tamoxifen affects glucose and lipid metabolism parameters, causes browning of subcutaneous adipose tissue and transient body composition changes in C57BL/6NTac mice

    International Nuclear Information System (INIS)

    Hesselbarth, Nico; Pettinelli, Chiara; Gericke, Martin; Berger, Claudia; Kunath, Anne; Stumvoll, Michael; Blüher, Matthias; Klöting, Nora

    2015-01-01

    Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to generate inducible conditional transgenic mouse models. Activation of ER signaling plays an important role in the regulation of adipose tissue (AT) metabolism. We therefore tested the hypothesis that tamoxifen administration causes changes in AT biology in vivo. 12 weeks old male C57BL/6NTac mice were treated with either tamoxifen (n = 18) or vehicle (n = 18) for 5 consecutive days. Tamoxifen treatment effects on body composition, energy homeostasis, parameters of AT biology, glucose and lipid metabolism were investigated up to an age of 18 weeks. We found that tamoxifen treatment causes: I) significantly increased HbA 1c , triglyceride and free fatty acid serum concentrations (p < 0.01), II) browning of subcutaneous AT and increased UCP-1 expression, III) increased AT proliferation marker Ki67 mRNA expression, IV) changes in adipocyte size distribution, and V) transient body composition changes. Tamoxifen may induce changes in body composition, whole body glucose and lipid metabolism and has significant effects on AT biology, which need to be considered when using Tamoxifen as a tool to induce conditional transgenic mouse models. Our data further suggest that tamoxifen-treated wildtype mice should be characterized in parallel to experimental transgenic models to control for tamoxifen administration effects. - Highlights: • Tamoxifen treatment causes significantly increased HbA 1c , triglyceride and free fatty acid serum concentrations. • Tamoxifen induces browning of subcutaneous AT and increased UCP-1 expression. • Tamoxifen changes adipocyte size distribution, and transient body composition

  7. Tamoxifen affects glucose and lipid metabolism parameters, causes browning of subcutaneous adipose tissue and transient body composition changes in C57BL/6NTac mice

    Energy Technology Data Exchange (ETDEWEB)

    Hesselbarth, Nico; Pettinelli, Chiara [Department of Medicine, University of Leipzig, D-04103 Leipzig (Germany); Gericke, Martin [Institute of Anatomy, University of Leipzig, D-04103 Leipzig (Germany); Berger, Claudia [IFB Adiposity Disease, Core Unit Animal Models, University of Leipzig, D-04103 Leipzig (Germany); Kunath, Anne [German Center for Diabetes Research (DZD), Leipzig (Germany); Stumvoll, Michael; Blüher, Matthias [Department of Medicine, University of Leipzig, D-04103 Leipzig (Germany); Klöting, Nora, E-mail: nora.kloeting@medizin.uni-leipzig.de [IFB Adiposity Disease, Core Unit Animal Models, University of Leipzig, D-04103 Leipzig (Germany)

    2015-08-28

    Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to generate inducible conditional transgenic mouse models. Activation of ER signaling plays an important role in the regulation of adipose tissue (AT) metabolism. We therefore tested the hypothesis that tamoxifen administration causes changes in AT biology in vivo. 12 weeks old male C57BL/6NTac mice were treated with either tamoxifen (n = 18) or vehicle (n = 18) for 5 consecutive days. Tamoxifen treatment effects on body composition, energy homeostasis, parameters of AT biology, glucose and lipid metabolism were investigated up to an age of 18 weeks. We found that tamoxifen treatment causes: I) significantly increased HbA{sub 1c}, triglyceride and free fatty acid serum concentrations (p < 0.01), II) browning of subcutaneous AT and increased UCP-1 expression, III) increased AT proliferation marker Ki67 mRNA expression, IV) changes in adipocyte size distribution, and V) transient body composition changes. Tamoxifen may induce changes in body composition, whole body glucose and lipid metabolism and has significant effects on AT biology, which need to be considered when using Tamoxifen as a tool to induce conditional transgenic mouse models. Our data further suggest that tamoxifen-treated wildtype mice should be characterized in parallel to experimental transgenic models to control for tamoxifen administration effects. - Highlights: • Tamoxifen treatment causes significantly increased HbA{sub 1c}, triglyceride and free fatty acid serum concentrations. • Tamoxifen induces browning of subcutaneous AT and increased UCP-1 expression. • Tamoxifen changes adipocyte size distribution, and transient body composition.

  8. Global characterization of signalling networks associated with tamoxifen resistance in breast cancer

    DEFF Research Database (Denmark)

    Browne, Brigid C.; Hochgräfe, Falko; Wu, Jianmin

    2013-01-01

    R cells. Phosphorylation of the tyrosine kinase Yes and expression of the actin‐binding protein myristoylated alanine‐rich C‐kinase substrate (MARCKS) were increased two‐ and eightfold in TamR cells respectively, and these proteins were selected for further analysis. Knockdown of either protein in Tam......Acquired resistance to the anti‐estrogen tamoxifen remains a significant challenge in breast cancer management. In this study, we used an integrative approach to characterize global protein expression and tyrosine phosphorylation events in tamoxifen‐resistant MCF7 breast cancer cells (Tam...... was perturbed in TamR cells, together with pathways enriched for proteins associated with growth factor, cell–cell and cell matrix‐initiated signalling. Consistent with known roles for Ras/MAPK and PI3‐kinase signalling in tamoxifen resistance, tyrosine‐phosphorylated MAPK1, SHC1 and PIK3R2 were elevated in Tam...

  9. CNS tumors: postoperative evaluation

    International Nuclear Information System (INIS)

    Dayanir, Y.

    2012-01-01

    Full text: Imaging assessment of brain tumors following surgery is complex and depends upon several factors, including the location of the tumor, the surgical procedure and the disease process for which it was performed. Depending upon these factors, one or a combination of complementary imaging modalities may be required to demonstrate any clinically relevant situation, to assist the surgeon in deciding if repeat surgery is necessary. Conventional magnetic resonance imaging (MRI) can show the shape, size, signal intensity, and enhancement of a brain tumor. It has been widely used to diagnose and differentiate brain tumors and to assess the surgery outcomes. Longitudinal MRI scans have also been applied for the assessment of treatment and response to surgery. The newly developed MRI techniques, including diffusion weighted imaging (DWI), perfusion weighted imaging (PWI) and magnetic resonance spectroscopy (MRS), have the potential to provide the molecular, functional and metabolic information of preoperative and postoperative brain tumors. Postoperative diffusion and perfusion magnetic resonance imaging are especially useful in predicting early functional recovery from new deficits after brain tumor surgery.This lecture will stress the principles, applications, and pitfalls of conventional as well as newly developing functional imaging techniques following operation of brain tumors

  10. Study of Sperm Parameters and Sperm Fertility in Mice were Exposed to Tamoxifen during Embryonic Development

    Directory of Open Access Journals (Sweden)

    J Soleimanirad

    2017-05-01

    Full Text Available Introduction: Tamoxifen is steroidal drug, which mainly treats breast cancer and also used to stimulate ovulation. The purpose of the present study was the evaluation of sperm parameters and fertility of mice whose mothers had received tamoxifen during pregnancy. Methods: In this study, 30 female and 15 male mice of NMRI were selected for mating. After mating female mice were randomly divided into two groups, the first group (control and second group (experimental. All of which contained 15 mice. From the day 13th day of pregnancy, experimental group has received tamoxifen with the dosage of 5 mg/kg for 7 days. After childbirth of the mated mice, male infants were selected. After reaching the age of puberty (6-8Weeks, adult mice were sacrificed by the cervical dislocation. After take sperm, sperm parameters (count, normality and motility, and sperm fertility was performed. In this study SPSS software and statistical t-test was used (p <0.001. Results: Studies showed that sperm parameters and sperm fertilization were significantly different. The number of sperm in the control group was 83.50±28.20 million, and in the experimental group was 60±14.14 million. There was a decrease in average sperm count in the experimental group compared with the control group (p <0.001. Our findings from in vitro fertilization culture media showed that embryos formation and oocyte disruption between control and experimental groups significantly different (p <0.001. Conclusion: The results showed that tamoxifen exposure during development can cause histological changes in the seminiferous tubules, which can lead to infertility.

  11. THE PROFILE OF TAMOXIFEN USER DUE TO GYNECOMASTIA INDUCED BY ANABOLIC STEROIDS FOR BODYBUILDERS OR BODYBUILDING

    Directory of Open Access Journals (Sweden)

    E. Santos

    2016-09-01

    Full Text Available Due to valorization of body appearance, the seek for a good physic body gets a central importance in externalization of subjectivity and in the construction the identities of the people. Because of this, them invest time to look for devices to streamline results to get a perfect body, between mechanisms used there is the use of anabolic steroids (AS. With the rapid response this kind of treatment, there are aware concerns their side effects such as gynecomastia which is characterized by breast enlargement of man. In an attempt to prevent this effect aesthetically uncomfortable, the users seek take medicines such as tamoxifen to reverse or prevent this situation without proper prescription or monitoring of a pharmacist professional, as well as almost all treatments with EA which are made clandestinely. This work aimed to describe profile among consumers seeking the tamoxifen therapy to prevent or treat gynecomastia induced using EA. The target audience was composed of bodybuilders men that were making anabolic cycles, aiming fast muscular hypertrophy. Two questionnaires were applied, one to the drugstores that sell these drugs and one for bodybuilders who buy these drugs. Tamoxifen user profile found in this study shows that they are young people aged 18 to 35 years old, seeking muscle hypertrophy strength. As the natural results are slow, influenced by training friends, start using EA, even declaring know about the risks to health. Use along with these steroids, tamoxifen, in an attempt to prevent or treat gynecomastia, get the medication in drugstores without a prescription and without the pharmacist questioning, demonstrating that pharmaceutical care is still not fully deployed and functioning

  12. The Wnt signalling pathway is upregulated in an in vitro model of acquired tamoxifen resistant breast cancer

    International Nuclear Information System (INIS)

    Loh, Yan Ni; Hedditch, Ellen L; Baker, Laura A; Jary, Eve; Ward, Robyn L; Ford, Caroline E

    2013-01-01

    Acquired resistance to Tamoxifen remains a critical problem in breast cancer patient treatment, yet the underlying causes of resistance have not been fully elucidated. Abberations in the Wnt signalling pathway have been linked to many human cancers, including breast cancer, and appear to be associated with more metastatic and aggressive types of cancer. Here, our aim was to investigate if this key pathway was involved in acquired Tamoxifen resistance, and could be targeted therapeutically. An in vitro model of acquired Tamoxifen resistance (named TamR) was generated by growing the estrogen receptor alpha (ER) positive MCF7 breast cancer cell line in increasing concentrations of Tamoxifen (up to 5 uM). Alterations in the Wnt signalling pathway and epithelial to mesenchymal transition (EMT) in response to Tamoxifen and treatment with the Wnt inhibitor, IWP-2 were measured via quantitative RT-PCR (qPCR) and TOP/FOP Wnt reporter assays. Resistance to Tamoxifen, and effects of IWP-2 treatment were determined by MTT proliferation assays. TamR cells exhibited increased Wnt signalling as measured via the TOP/FOP Wnt luciferase reporter assays. Genes associated with both the β-catenin dependent (AXIN2, MYC, CSNK1A1) and independent arms (ROR2, JUN), as well as general Wnt secretion (PORCN) of the Wnt signalling pathway were upregulated in the TamR cells compared to the parental MCF7 cell line. Treatment of the TamR cell line with human recombinant Wnt3a (rWnt3a) further increased the resistance of both MCF7 and TamR cells to the anti-proliferative effects of Tamoxifen treatment. TamR cells demonstrated increased expression of EMT markers (VIM, TWIST1, SNAI2) and decreased CDH1, which may contribute to their resistance to Tamoxifen. Treatment with the Wnt inhibitor, IWP-2 inhibited cell proliferation and markers of EMT. These data support the role of the Wnt signalling pathway in acquired resistance to Tamoxifen. Further research into the mechanism by which activated Wnt

  13. Tamoxifen up-regulates catalase production, inhibits vessel wall neutrophil infiltration, and attenuates development of experimental abdominal aortic aneurysms.

    Science.gov (United States)

    Grigoryants, Vladimir; Hannawa, Kevin K; Pearce, Charles G; Sinha, Indranil; Roelofs, Karen J; Ailawadi, Gorav; Deatrick, Kristopher B; Woodrum, Derek T; Cho, Brenda S; Henke, Peter K; Stanley, James C; Eagleton, Matthew J; Upchurch, Gilbert R

    2005-01-01

    Selective estrogen receptor modulators (SERMs), similar to estrogens, possess vasoprotective effects by reducing release of reactive oxygen species. Little is known about the potential effects of SERMs on the pathogenesis of abdominal aortic aneurysms (AAAs). This study's objective was to investigate the growth of experimental AAAs in the setting of the SERM tamoxifen. In the first set of experiments, adult male rats underwent subcutaneous tamoxifen pellet (delivering 10 mg/kg/day) implantation (n = 14) or sham operation (n = 16). Seven days later, all animals underwent pancreatic elastase perfusion of the abdominal aorta. Aortic diameters were determined at that time, and aortas were harvested 7 and 14 days after elastase perfusion for immunohistochemistry, real-time polymerase chain reaction, Western blot analysis, and zymography. In the second set of experiments, a direct irreversible catalase inhibitor, 3-amino-1,2,4-triazole (AT), was administered intraperitoneally (1 mg/kg) daily to tamoxifen-treated (n = 6) and control rats (n = 6), starting on day 7 after elastase perfusion. Aortic diameters were measured on day 14. In a third set of experiments, rats were perfused with catalase (150 mg/kg) after the elastase (n = 5), followed by daily intravenous injections of catalase (150 mg/kg/day) administered for 10 days. A control group of rats (n = 7) received 0.9% NaCl instead of catalase. Mean AAA diameters were approximately 50% smaller in tamoxifen-treated rats compared with sham rats 14 days after elastase perfusion (P = .002). The tamoxifen-treated group's aortas had a five-fold increase in catalase mRNA expression (P = .02) on day 7 and an eight-fold increase in catalase protein on day 14 (P = .04). Matrix metalloprotroteinase-9 activity was 2.4-fold higher (P = .01) on day 7 in the aortas of the controls compared to the tamoxifen-treated group's aortas. Tamoxifen-treated rats had approximately 40% fewer aortic polymorphonuclear neutrophils compared to

  14. Clinical impact of and contributing factors to urinary incontinence in women 5 years after first delivery.

    Science.gov (United States)

    Liang, Ching-Chung; Wu, Ming-Ping; Lin, Shu-Jen; Lin, Yu-Jr; Chang, Shuenn-Dhy; Wang, Hui-Hsuan

    2013-01-01

    This study was conducted to investigate the prevalence of and contributing factors to urinary incontinence (UI) in women 5 years after their first birth and to evaluate the associations of UI with delivery mode and quality of life. Between 2005 July and 2006 March, primiparous women who delivered at term in a tertiary hospital were recruited into this cohort study. Immediately postpartum, the women completed a structured urogynecological questionnaire regarding lower urinary tract symptoms. Then the same urogynecological questionnaire, the Incontinence Impact Questionnaire (IIQ-7), and the Urinary Distress Inventory (UDI-6) were mailed to them 5 years later to follow up on UI. Three hundred and twelve women responding to the mailed questionnaires were included in the analyses. The prevalence 5 years after first delivery of stress (SUI) and urge (UUI) UI were 43.6 % and 19.2 %, respectively. Women with UI during their first pregnancy were more likely to develop UI 5 years postpartum than those without it; women who delivered their first child vaginally had a greater incidence of UI than those having cesarean birth; UUI in women following cesarean delivery more negatively impacted emotional health than it did following vaginal birth, whereas the impact of SUI did not significantly differ between delivery groups. UI during the first pregnancy and vaginal delivery in primiparous women may predict an increased risk of having UI 5 years after delivery. UUI adversely affected women's emotional health, especially in those undergoing cesarean section.

  15. Social influence on 5-year survival in a longitudinal chemotherapy ward co-presence network.

    Science.gov (United States)

    Lienert, Jeffrey; Marcum, Christopher Steven; Finney, John; Reed-Tsochas, Felix; Koehly, Laura

    2017-09-01

    Chemotherapy is often administered in openly designed hospital wards, where the possibility of patient-patient social influence on health exists. Previous research found that social relationships influence cancer patient's health; however, we have yet to understand social influence among patients receiving chemotherapy in the hospital. We investigate the influence of co-presence in a chemotherapy ward. We use data on 4,691 cancer patients undergoing chemotherapy in Oxfordshire, United Kingdom who average 59.8 years of age, and 44% are Male. We construct a network of patients where edges exist when patients are co-present in the ward, weighted by both patients' time in the ward. Social influence is based on total weighted co-presence with focal patients' immediate neighbors, considering neighbors' 5-year mortality. Generalized estimating equations evaluated the effect of neighbors' 5-year mortality on focal patient's 5-year mortality. Each 1,000-unit increase in weighted co-presence with a patient who dies within 5 years increases a patient's mortality odds by 42% ( β = 0.357, CI:0.204,0.510). Each 1,000-unit increase in co-presence with a patient surviving 5 years reduces a patient's odds of dying by 30% ( β = -0.344, CI:-0.538,0.149). Our results suggest that social influence occurs in chemotherapy wards, and thus may need to be considered in chemotherapy delivery.

  16. Generation of NSE-MerCreMer transgenic mice with tamoxifen inducible Cre activity in neurons.

    Directory of Open Access Journals (Sweden)

    Mandy Ka Man Kam

    Full Text Available To establish a genetic tool for conditional deletion or expression of gene in neurons in a temporally controlled manner, we generated a transgenic mouse (NSE-MerCreMer, which expressed a tamoxifen inducible type of Cre recombinase specifically in neurons. The tamoxifen inducible Cre recombinase (MerCreMer is a fusion protein containing Cre recombinase with two modified estrogen receptor ligand binding domains at both ends, and is driven by the neural-specific rat neural specific enolase (NSE promoter. A total of two transgenic lines were established, and expression of MerCreMer in neurons of the central and enteric nervous systems was confirmed. Transcript of MerCreMer was detected in several non-neural tissues such as heart, liver, and kidney in these lines. In the background of the Cre reporter mouse strain Rosa26R, Cre recombinase activity was inducible in neurons of adult NSE-MerCreMer mice treated with tamoxifen by intragastric gavage, but not in those fed with corn oil only. We conclude that NSE-MerCreMer lines will be useful for studying gene functions in neurons for the conditions that Cre-mediated recombination resulting in embryonic lethality, which precludes investigation of gene functions in neurons through later stages of development and in adult.

  17. Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines.

    Science.gov (United States)

    Attia, Yasmin M; El-Abhar, Hanan S; Al Marzabani, Mahmoud M; Shouman, Samia A

    2015-11-03

    Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate. An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor. Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well. 3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment.

  18. Tamoxifen-independent recombination in the RIP-CreER mouse.

    Directory of Open Access Journals (Sweden)

    Yanmei Liu

    Full Text Available BACKGROUND: The inducible Cre-lox system is a valuable tool to study gene function in a spatial and time restricted fashion in mouse models. This strategy relies on the limited background activity of the modified Cre recombinase (CreER in the absence of its inducer, the competitive estrogen receptor ligand, tamoxifen. The RIP-CreER mouse (Tg (Ins2-cre/Esr1 1Dam is among the few available β-cell specific CreER mouse lines and thus it has been often used to manipulate gene expression in the insulin-producing cells of the endocrine pancreas. PRINCIPAL FINDINGS: Here, we report the detection of tamoxifen-independent Cre activity as early as 2 months of age in RIP-CreER mice crossed with three distinct reporter strains. SIGNIFICANCE: Evidence of Cre-mediated recombination of floxed alleles even in the absence of tamoxifen administration should warrant cautious use of this mouse for the study of pancreatic β-cells.

  19. The biochemical effects of nano tamoxifen and some bioactive components in experimental breast cancer.

    Science.gov (United States)

    Ezzat, Afaf; Abdelhamid, Abdou Osman; El Awady, Mostafa K; Abd El Azeem, Amal S; Mohammed, Dina Mostafa

    2017-11-01

    The effect of nano tamoxifen and some bioactive components such as yeast, isoflavone, and silymarin on the level of resistance and prevention of breast cancer progression in experimental animals is the target of this study. Thirty female Sprague-Dawley rats received a single medication dosage of 7,12-dimethylbenz[a]anthracene (DMBA) intragastrically. After fourteen days of DMBA admission, the procedure protocol started out. Finally, all the experimental results evaluated, tabulated and statistically analyzed. The results demonstrated a highly significant elevation in the 8-OHdG level in group 1 (nano yeast) and 3 (nano silymarin) while the results demonstrated a highly significant reduction in group 2 (nano tamoxifen). The apoptosis results demonstrated a significant elevation in group 3 (nano silymarin) where appeared significant reduction in group 4 (nano isoflavone). ErbB-2 results demonstrated a significant elevation in group 2 (nano tamoxifen) and a significant reduction in each of group 3 (nano silymarin) and 4 (nano isoflavone). The lipid peroxide level demonstrated an extremely significant reduction in group 4 (nano isoflavone). And a significant reduction of total antioxidant was observed in group 3 (nano silymarin) in comparison to injected animals control. This may be considered a new vision and strategy to resist breast cancer disease or prevent progression. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines

    International Nuclear Information System (INIS)

    Attia, Yasmin M.; EL-Abhar, Hanan S.; Al Marzabani, Mahmoud M.; Shouman, Samia A.

    2015-01-01

    Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate. An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor. Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well. 3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment

  1. Serum-dependent effects of tamoxifen and cannabinoids upon C6 glioma cell viability.

    Science.gov (United States)

    Jacobsson, S O; Rongård, E; Stridh, M; Tiger, G; Fowler, C J

    2000-12-15

    In the present study, the effects of the combination of tamoxifen ((Z)-2[p-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylamine citrate) and three cannabinoids (Delta(9)-tetrahydrocannabinol [Delta(9)-THC], cannabidiol, and anandamide [AEA]) upon the viability of C6 rat glioma cells was assessed at different incubation times and using different culturing concentrations of foetal bovine serum (FBS). Consistent with previous data for human glioblastoma cells, the tamoxifen sensitivity of the cells was increased as the FBS content of the culture medium was reduced from 10 to 0.4 and 0%. The cells expressed protein kinase C alpha and calmodulin (the concentration of which did not change significantly as the FBS concentration was reduced), but did not express estrogen receptors. Delta(9)-THC and cannabidiol, but not AEA, produced a modest reduction in cell viability after 6 days of incubation in serum-free medium, whereas no effects were seen in 10% FBS-containing medium. There was no observed synergy between the effects of tamoxifen and the cannabinoids upon cell viability.

  2. Tamoxifen Promotes Axonal Preservation and Gait Locomotion Recovery after Spinal Cord Injury in Cats

    Directory of Open Access Journals (Sweden)

    Braniff de la Torre Valdovinos

    2016-01-01

    Full Text Available We performed experiments in cats with a spinal cord penetrating hemisection at T13-L1 level, with and without tamoxifen treatment. The results showed that the numbers of the ipsilateral and contralateral ventral horn neurons were reduced to less than half in the nontreated animals compared with the treated ones. Also, axons myelin sheet was preserved to almost normal values in treated cats. On the contrary, in the untreated animals, their myelin sheet was reduced to 28% at 30 days after injury (DAI, in both the ipsilateral and contralateral regions of the spinal cord. Additionally, we made hindlimb kinematics experiments to study the effects of tamoxifen on cat locomotion after the injury: at 4, 16, and 30 DAI. We observed that the ipsilateral hindlimb angular displacement (AD of the pendulum-like movements (PLM during gait locomotion was recovered to almost normal values in treated cats. Contralateral PLM acquired similar values to those obtained in intact cats. At 4 DAI, untreated animals showed a compensatory increment of PLM occurring in the contralateral hindlimb, which was partially recovered at 30 DAI. Our findings indicate that tamoxifen exerts a neuroprotective effect and preserves or produces myelinated axons, which could benefit the locomotion recovery in injured cats.

  3. [Effect of the estrogen antagonist tamoxifen in the treatment of advanced mastocarcinoma (author's transl)].

    Science.gov (United States)

    Szepesi, T; Kärcher, K H

    1977-12-01

    Today the endocrin therapy of the advanced mastocarcinoma is in common use. Besides the already known therapy by estrogens, androgens, gestagens, and steroids, Tamoxifen, and estrogen antagonist, is a very promising therapeutic drug. In the presented study, Tamoxifen was submitted to a critical clinical control during a period of one year from 1st October 1975 until 1st October 1976. After a three months' treatment, a rate of 41% of objective remissions could be obtained. The criteria of success were estimated according to the scheme of Karnofsky. The average remission time is 5,5 months. By a determination of the estrogen receptors it would be possible to realize a therapeutic selection and to achieve a higher remission rate. The authors made an interesting observation, i.e. a probably immuno-stimulating effect which, however, still has to be submitted to further examinations. The side effects are described in detail and the indications are established. Its is astonishing that the subjective ameliorations, i.e. cessation of pains in case of generalized formation of metastases in the bones are much more frequent than the objective remissions. We came to the conclusion that the treatment by Tamoxifen is a valuable alternative in the therapy of the mastocarcinoma, above all in the postmenopausal period if the disease is advanced and incurable.

  4. National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial: advancing the science of recruitment and breast cancer risk assessment in minority communities.

    Science.gov (United States)

    McCaskill-Stevens, Worta; Wilson, John W; Cook, Elise D; Edwards, Cora L; Gibson, Regina V; McElwain, Diane L; Figueroa-Moseley, Colmar D; Paskett, Electra D; Roberson, Noma L; Wickerham, D Lawrence; Wolmark, Norman

    2013-04-01

    One of the first chemoprevention trials conducted in the western hemisphere, the National Surgical Adjuvant Breast and Bowel Project's (NSABP) Breast Cancer Prevention Trial (BCPT), demonstrated the need to evaluate all aspects of recruitment in real time and to implement strategies to enroll racial and ethnic minority women. The purpose of this report is to review various patient recruitment efforts the NSABP developed to enhance the participation of racial and ethnic minority women in the Study of Tamoxifen and Raloxifene (STAR) trial and to describe the role that the recruitment process played in the implementation and understanding of breast cancer risk assessment in minority communities. The NSABP STAR trial was a randomized, double-blinded study comparing the use of tamoxifen 20 mg/day to raloxifene 60 mg/day, for a 5-year period, to reduce the risk of developing invasive breast cancer. Eligible postmenopausal women were required to have a 5-year predicted breast cancer risk of 1.66% based on the modified Gail Model. For the current report, eligibility and enrollment data were tabulated by race/ethnicity for women who submitted STAR risk assessment forms (RAFs). A total of 184,460 RAFs were received, 145,550 (78.9%) from white women and 38,910 (21.1%) from minority women. Of the latter group, 21,444 (11.6%) were from African Americans/blacks, 7913 (4.5%) from Hispanics/Latinas, and 9553 (5.2%) from other racial or ethnic groups. The percentages of risk-eligible women among African Americans, Hispanics/Latinas, others, and whites were 14.2%, 23.3%, 13.7%, and 57.4%, respectively. Programs targeting minority enrollment submitted large numbers of RAFs, but the eligibility rates of the women referred from those groups tended to be lower than the rates among women referred outside of those programs. The average number of completed risk assessments increased among minority women over the course of the recruitment period compared to those from whites. We have not

  5. Postoperative radiotherapy for stage II and III rectal cancer

    International Nuclear Information System (INIS)

    Qian Liting; Song Yongwen; Liu Xinfan; Yu Zihao; Qian Tunan; Li Yexiong

    2003-01-01

    Objective: To evaluate the impact of postoperative adjuvant radiotherapy, compared with surgery alone for rectal cancer. Methods: From January 1994 to October 1997, 192 patients with stage II or III rectal cancer were treated by radical resection and postoperative radiotherapy (Group S + R) and 51 patients with the same stage lesions underwent surgery alone (Group S). The median dose of radiation was 50(32-62) Gy. Kaplan-Meier method and Log-rank test were used for analysis. Results: The 5-year overall and disease-free survival rates were 60.3% and 58.3%, respectively. The overall 5-year survival rate was 59.4% in Group S + R and 64.7% in Group S, and the 5-year disease-free survival rates were 57.0% and 66.4%, respectively. There were no significant differences between either group (P=0.601 and P=0.424). The disease-free survival was not significantly prolonged in Group S + R as compared with that of Group S. The local recurrence rate was evidently reduced in Group S + R (15.8% v 26.8%, P=0.043). Conclusion: Local recurrence is a major cause of morbidity and mortality in rectal cancer. Postoperative radiotherapy, though reduces the incidence of local recurrence, does not improve the survival in the treatment of stage II and III diseases

  6. Clubfoot Does Not Impair Gross Motor Development in 5-Year-Olds.

    Science.gov (United States)

    Zapata, Karina A; Karol, Lori A; Jeans, Kelly A; Jo, Chan-Hee

    2018-04-01

    To evaluate the gross motor development of 5-year-olds using the Peabody Developmental Motor Scales, 2nd Edition (PDMS-2), test after initial nonoperative management of clubfoot as infants. The PDMS-2 Stationary, Locomotion, and Object Manipulation subtests were assessed on 128 children with idiopathic clubfeet at the age of 5 years. Children were categorized by their initial clubfoot severity as greater than 13, unilateral or bilateral involvement, and required surgery. Children with treated clubfeet had average gross motor scores (99 Gross Motor Quotient) compared with age-matched normative scores. Children with more severe clubfeet required surgery significantly more than children with less severe scores (P < .01). Peabody scores were not significantly different according to initial clubfoot severity, unilateral versus bilateral involvement, and surgical versus nonsurgical outcomes. Clubfoot does not significantly impair gross motor development in 5-year-olds.

  7. The effects of oil pollution on Antarctic benthic diatom communities over 5 years.

    Science.gov (United States)

    Polmear, R; Stark, J S; Roberts, D; McMinn, A

    2015-01-15

    Although considered pristine, Antarctica has not been impervious to hydrocarbon pollution. Antarctica's history is peppered with oil spills and numerous abandoned waste disposal sites. Both spill events and constant leakages contribute to previous and current sources of pollution into marine sediments. Here we compare the response of the benthic diatom communities over 5 years to exposure to a commonly used standard synthetic lubricant oil, an alternative lubricant marketed as more biodegradable, in comparison to a control treatment. Community composition varied significantly over time and between treatments with some high variability within contaminated treatments suggesting community stress. Both lubricants showed evidence of significant effects on community composition after 5 years even though total petroleum hydrocarbon reduction reached approximately 80% over this time period. It appears that even after 5 years toxicity remains high for both the standard and biodegradable lubricants revealing the temporal scale at which pollutants persist in Antarctica. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Essure transcervical tubal sterilization: a 5-year x-ray follow up.

    Science.gov (United States)

    Franchini, Mario; Boeri, Cecilia; Calzolari, Stefano; Imperatore, Alberto; Cianferoni, Luciano; Litta, Pietro; Giarrè, Giovanna; Zerbetto, Irene; Moncini, Irene; Florio, Pasquale

    2011-05-01

    To evaluate the x-ray appearance of Essure microinserts 5 years after their insertion. Prospective controlled study. Tertiary referral centers for gynecologic care. Forty-five consecutive women with successful hysteroscopic bilateral placement of the Essure devices and postprocedure satisfactory hysterosalpingography confirmation test. Pelvic anteroposterior x-ray. Stability and and symmetric appearance of Essure microinsert positions; measurement of the intrauterine distance between the two devices. After 5 years from their placement, no detachment nor fracture of devices was observed. x-Ray recognition of the device after 5 years showed findings similar to those recorded at 3 months' follow-through hysterosalpingography. x-Ray evaluation of findings related to stability of position, symmetric appearance, and distance between the two Essure microinserts corroborates the irreversibility and the reliability of the fibrotic reaction that ensured tubal occlusion after devices placement. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Postoperative chemoradiotherapy in high risk locally advanced gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Song, Sang Hyuk; Chie, Eui Kyu; Kim, Kyu Bo; Lee, Hyuk Joon; Yang, Han Kwang; Han, Sae Won; Oh, Do Youn; Im, Seok Ah; Bang, Yung Jue; Ha, Sung W. [Seoul National University College of Medicine, Seoul(Korea, Republic of)

    2012-12-15

    To evaluate treatment outcome of patients with high risk locally advanced gastric cancer after postoperative chemoradiotherapy. Between May 2003 and May 2012, thirteen patients who underwent postoperative chemoradiotherapy for gastric cancer with resection margin involvement or adjacent structure invasion were retrospectively analyzed. Concurrent chemotherapy was administered in 10 patients. Median dose of radiation was 50.4 Gy (range, 45 to 55.8 Gy). The median follow-up duration for surviving patients was 48 months (range, 5 to 108 months). The 5-year overall survival rate was 42% and the 5-year disease-free survival rate was 28%. Major pattern of failure was peritoneal seeding with 46%. Loco-regional recurrence was reported in only one patient. Grade 2 or higher gastrointestinal toxicity occurred in 54% of the patients. However, there was only one patient with higher than grade 3 toxicity. Despite reported suggested role of adjuvant radiotherapy with combination chemotherapy in gastric cancer, only very small portion of the patients underwent the treatment. Results from this study show that postoperative chemoradiotherapy provided excellent locoregional control with acceptable and manageable treatment related toxicity in patients with high risk locally advanced gastric cancer. Thus, postoperative chemoradiotherapy may improve treatment result in terms of locoregional control in these high risk patients. However, as these findings are based on small series, validation with larger cohort is suggested.

  10. Identification of urine metabolites associated with 5-year changes in biomarkers of glucose homoeostasis

    DEFF Research Database (Denmark)

    Friedrich, N.; Skaaby, T.; Pietzner, M.

    2017-01-01

    of insulin resistance (HOMA-IR) index values. Methods: Urine metabolites in 3986 participants at both baseline and 5-year follow-up of the population-based Inter99 study were analyzed by 1H-NMR spectroscopy. Linear regression and analyses of covariance models were used to detect associations between urine...... associated with a decrease in HbA1c over time. Analyses of 5-year changes in fasting glucose and HOMA-IR index showed similar findings, with high baseline levels of lactic acid, beta-d-glucose, creatinine, alanine and 1-methylnicotinamide associated with increases in both parameters. Conclusion: Several...

  11. The effect of postoperative radiotherapy on leukocyte zinc, serum trace elements and nutritional status of breast cancer patients

    International Nuclear Information System (INIS)

    Antila, H.M.J.; Salo, M.S.; Kirvelae, O.; Nikkanen, V.

    1992-01-01

    Mononuclear (MNC) and polymorphonuclear cell (PMNC) zinc content was determined together with serum zinc, copper, selenium and iron concentrations in 24 operable breast cancer patients during and after postoperative radiotherapy. Anthropometric and biochemical indices of nutritional status were measured as background data. The measurements were carried out in the years 1987-1988. Nine patients used unconventional multivitamin or trace element preparations. A steady but statistically insignificant decrease in PMNC zinc was seen during treatment. No changes occurred in MNC zinc. Serum copper levels increased in five patients possibly due to tamoxifen treatment, but no other alterations occurred in serum trace element levels. Appetite was well maintained and nutritional status remained unaltered. Postoperative radiotherapy for breast carcinoma had thus no effect on either trace element or nutritional status. Patient-initiated alternative treatments did not significantly affect their trace element levels. This was probably due to small supplementation doses or irregular use of the preparations. (orig.)

  12. Transanal pull-through procedure for Hirschsprung's disease: a 5-year experience.

    Science.gov (United States)

    Jester, I; Holland-Cunz, S; Loff, S; Hosie, S; Reinshagen, K; Wirth, H; Ali, M; Waag, K-L

    2009-04-01

    Transanal endorectal pull-through (TEPT) has become a widely used approach for the treatment of Hirschsprung's Disease. The technique is safe and, according to previous reports, it has a good clinical outcome. In this study our experience with TEPT in the early postoperative period is evaluated. The clinical course of 34 children (28 boys and 6 girls) who underwent one-stage pull-through operation according to De la Torre for Hirschsprung's disease from January 2003 to December 2007 was reviewed. Their ages ranged from 2 months to 4 years. Complications occurring within the first four weeks after operation were analyzed. Eight of 34 children (24 %) had early complications in the form of dehiscences of the anastomosis. Two children (6 %) had symptomatic anastomotic dehiscences. One child had an almost full retraction of the colon that had to be pulled down and resutured. One child developed a retrorectal abscess three weeks postoperatively due to anastomotic leakage. The dehiscences of 6 children (18 %) were asymptomatic. These dehiscences were detected only with standardized routine examination. The dehiscences healed uneventfully after resuturing. Two other patients (6 %) developed an anastomotic stricture that could be treated with rectal dilatations. Four children (12 %) showed a single episode of postoperative enterocolitis. The rate of early clinical and particularly subclinical complications such as anastomotic dehiscences after TEPT is higher than previously estimated. Patients should be monitored carefully during the early postoperative period. Severe complications can only be avoided with a thorough examination. Early resuturing of dehiscences might be helpful to prevent hazardous sequelae.

  13. Risk factors for atopic dermatitis in New Zealand children at 3.5 years of age.

    Science.gov (United States)

    Purvis, D J; Thompson, J M D; Clark, P M; Robinson, E; Black, P N; Wild, C J; Mitchell, E A

    2005-04-01

    The prevalence of atopic dermatitis (AD) is increasing in Western societies. The hygiene hypothesis proposes that this is due to reduced exposure to environmental allergens and infections during early life. To examine factors associated with a diagnosis of AD at 3.5 years of age, especially those factors implicated by the hygiene hypothesis. The Auckland Birthweight Collaborative study is a case-control study of risk factors for small for gestational age babies. Cases were born at term with birthweight 10th centile. The infants were assessed at birth, 1 year and 3.5 years of age. Data were collected by parental interview and examination of the child. AD was defined as the presence of an itchy rash in the past 12 months with three or more of the following: history of flexural involvement; history of generally dry skin; history of atopic disease in parents or siblings; and visible flexural dermatitis as per photographic protocol. Statistical analyses took into account the disproportionate sampling of the study population. Analysis was restricted to European subjects. Eight hundred and seventy-one children were enrolled at birth, 744 (85.4%) participated at 1 year, and 550 (63.2%) at 3.5 years. AD was diagnosed in 87 (15.8%) children seen at 3.5 years. The prevalence of AD did not differ by birthweight. AD at 3.5 years was associated with raised serum IgE > 200 kU L(-1), and wheezing, asthma, rash or eczema at 1 year. In multivariate analysis, adjusted for parental atopy and breastfeeding, AD at 3.5 years was associated with atopic disease in the parents: maternal atopy only, adjusted odds ratio (OR) 3.83, 95% confidence interval (CI) 1.20-12.23; paternal atopy only, adjusted OR 3.59, 95% CI 1.09-11.75; both parents atopic, adjusted OR 6.12, 95% CI 2.02-18.50. There was a higher risk of AD with longer duration of breastfeeding: or = 6 months, adjusted OR 9.70, 95% CI 2.47-38.15 compared with never breastfed. These findings remained significant after adjusting for

  14. Thrombolysis in Postoperative Stroke.

    Science.gov (United States)

    Voelkel, Nicolas; Hubert, Nikolai Dominik; Backhaus, Roland; Haberl, Roman Ludwig; Hubert, Gordian Jan

    2017-11-01

    Intravenous thrombolysis (IVT) is beneficial in reducing disability in selected patients with acute ischemic stroke. There are numerous contraindications to IVT. One is recent surgery. The aim of this study was to analyze the safety of IVT in patients with postoperative stroke. Data of consecutive IVT patients from the Telemedical Project for Integrative Stroke Care thrombolysis registry (February 2003 to October 2014; n=4848) were retrospectively searched for keywords indicating preceding surgery. Patients were included if surgery was performed within the last 90 days before stroke. The primary outcome was defined as surgical site hemorrhage. Subgroups with major/minor surgery and recent/nonrecent surgery (within 10 days before IVT) were analyzed separately. One hundred thirty-four patients underwent surgical intervention before IVT. Surgery had been performed recently (days 1-10) in 49 (37%) and nonrecently (days 11-90) in 85 patients (63%). In 86 patients (64%), surgery was classified as major, and in 48 (36%) as minor. Nine patients (7%) developed surgical site hemorrhage after IVT, of whom 4 (3%) were serious, but none was fatal. One fatal bleeding occurred remotely from surgical area. Rate of surgical site hemorrhage was significantly higher in recent than in nonrecent surgery (14.3% versus 2.4%, respectively, odds ratio adjusted 10.73; 95% confidence interval, 1.88-61.27). Difference between patients with major and minor surgeries was less distinct (8.1% and 4.2%, respectively; odds ratio adjusted 4.03; 95% confidence interval, 0.65-25.04). Overall in-hospital mortality was 8.2%. Intracranial hemorrhage occurred in 9.7% and was asymptomatic in all cases. IVT may be administered safely in postoperative patients as off-label use after appropriate risk-benefit assessment. However, bleeding risk in surgical area should be taken into account particularly in patients who have undergone surgery shortly before stroke onset. © 2017 American Heart Association, Inc.

  15. A 5-year evaluation of a smoking cessation incentive program for chemical employees.

    Science.gov (United States)

    Olsen, G W; Lacy, S E; Sprafka, J M; Arceneaux, T G; Potts, T A; Kravat, B A; Gondek, M R; Bond, G G

    1991-11-01

    This 5-year study of the Dow Chemical Texas Operations 1984-1985 Smoking Cessation Incentive Program (SCIP) evaluated the smoking habits of 1,097 participants and 1,174 nonparticipants. We observed, via questionnaire and saliva cotinine data, that participants were 2.3 times more likely to be long-term (greater than or equal to 5 years) nonusers of tobacco than nonparticipants (10.2% vs 4.4%, P less than or equal to 0.01). However, smoking cessation rates for 3-4 years, 1-2 years, and less than 1 year were similar for participants who remained smokers at the conclusion of SCIP and nonparticipants. Age and the interaction between the management job category and having quit smoking for at least 30 days sometime prior to the worksite program were important predictors of smoking cessation among participants. Thirty-six percent of the participants who were considered exsmokers of 6 months duration at the conclusion of the program in 1985 remained long-term quitters 5 years later. Stress and enjoyment of smoking were the two most important reasons provided by participants for recidivism. The results of this 5-year evaluation demonstrate the heterogeneity of employee participation and success with a worksite smoking cessation program.

  16. A 5-year review of physical and verbal aggression in a psychiatric ...

    African Journals Online (AJOL)

    A 5-year review of physical and verbal aggression in a psychiatric ward in Ilorin, Nigeria. ... p=0.6) and previous episode of mental illness in patient (÷=00; p=1.0). ... of ward culture, staff-to-staff and staff-to-patient dynamics and environment.

  17. Integrated cognitive remediation and standard rehabilitation therapy in patients of schizophrenia: persistence after 5years.

    Science.gov (United States)

    Buonocore, Mariachiara; Spangaro, Marco; Bechi, Margherita; Baraldi, Maria Alice; Cocchi, Federica; Guglielmino, Carmelo; Bianchi, Laura; Mastromatteo, Antonella; Bosia, Marta; Cavallaro, Roberto

    2018-02-01

    Cognitive remediation, often used in combination with standard rehabilitation programs, represents the best available tool to treat cognitive impairments in patients with schizophrenia. However, there are still open questions about durability of effects and generalization of cognitive improvements to functional outcome. This study aims to investigate the persistence of both cognitive and functional effects of combined cognitive remediation plus standard rehabilitation interventions, 5years after completion of the intervention, also comparing different durations of the standard rehabilitation. Sixty patients diagnosed with schizophrenia and previously treated with a 6months intervention, consisting of standard rehabilitation plus 3-months of cognitive remediation, either followed by another year of standard rehabilitation or routine psychiatric treatment, were reassessed with neuropsychological and functional measures 5years after the intervention. Results show that cognitive abilities remained stable after 5years in both groups, while functional performance significantly decreased in patients treated with the 6months intervention only. Data thus suggest that cognitive effects persist even after 5years, while a longer standard rehabilitation following the cognitive remediation program may be needed to achieve a stable functional gain. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Neurocognitive development in first episode psychosis 5 years follow-up

    DEFF Research Database (Denmark)

    Barder, Helene Eidsmo; Sundet, Kjetil; Rund, Bjørn Rishovd

    2013-01-01

    , as measured by relapses and diagnostic subgroups. The study is an extension of previous findings from the TIPS-project, reporting stability over the first two years. Sixty-two FEP patients (53% male, age 28 ± 9 years) were neuropsychologically examined at baseline and at 1, 2, and 5 year follow-ups. The test...

  19. Predictors of ADHD Persistence in Girls at 5-Year Follow-Up

    Science.gov (United States)

    Mick, Eric; Byrne, Deirdre; Fried, Ronna; Monuteaux, Michael; Faraone, Stephen V.; Biederman, Joseph

    2011-01-01

    Objective: The main aim of this study was to examine the age-dependent remission from ADHD in girls transitioning through childhood into adolescence and early adulthood. Method: We conducted a 5-year prospective follow-up study of 123 girls with ADHD and 106 non-ADHD control girls aged between 6 and 17 years at ascertainment. ADHD was considered…

  20. Determinants of acute diarrhoea in children aged 0 – 5 years in ...

    African Journals Online (AJOL)

    Objective: To establish the prevalence and determinants of acute diarrhoea in children aged 0 – 5 years in Uganda. Design: Cross-sectional study using the 2000/2001 Uganda Demographic and Health Survey (UDHS) dataset. Subjects: Information was derived from the women's questionnaire done on sampled mothers ...

  1. Speaking a Tone Language Enhances Musical Pitch Perception in 3-5-Year-Olds

    Science.gov (United States)

    Creel, Sarah C.; Weng, Mengxing; Fu, Genyue; Heyman, Gail D.; Lee, Kang

    2018-01-01

    Young children learn multiple cognitive skills concurrently (e.g., language and music). Evidence is limited as to whether and how learning in one domain affects that in another during early development. Here we assessed whether exposure to a tone language benefits musical pitch processing among 3-5-year-old children. More specifically, we compared…

  2. a 5-year evaluation of the effect of introduction of subspecialty

    African Journals Online (AJOL)

    2016. Spine/knee. Paediatrics. Arthroplasty. Pelvis/Acetabulum. Over the 5 year study period, the hospital realized an increase in the number of orthopaedic surgeons from six to fourteen. The number of trainees from. Moi University also increased, gradually increasing the total number of work force in the department of.

  3. Care for overweight children attending the 5-year preventive child health examination in general practice.

    Science.gov (United States)

    Andersen, Merethe Kousgaard; Christensen, Bo; Søndergaard, Jens

    2013-02-01

    The purpose of this study was to analyse general practitioners' (GPs) care for children with a weight-for-height above normal based on the GPs' clinical evaluation, that is, 'GP-assessed overweight'. This study is a cross-sectional survey targeting GPs' care for children with GP-assessed overweight at the 5-year preventive child health examination (PCHE). Out of 1135 children attending the 5-year PCHE, 171 were assessed overweight by the GP. According to the Danish body mass index (kg/m(2)) growth charts, 147 children were overweight. The GPs addressed their concern about the child's weight to the parents in 58% of the 171 cases with GP-assessed overweight. The national guideline was reported consulted in 6% of the cases. Diet, physical activity and dispositions were evaluated by the GPs in 68%, 57% and 34% of cases, respectively. An appointment for a follow-up was made in 12% of cases. Various care activities were carried out for most children with GP-assessed overweight at the 5-year PCHE. However, the GP did not raise concern about the child's weight with the parents in almost one third of the children. It seems that there is a potential for improving the overweight care at the 5-year PCHE beginning with the involvement of the parents.

  4. Nutrition and mental development of 4-5-year old children on macrobiotic diets.

    NARCIS (Netherlands)

    Herens, M.C.; Dagnelie, P.C.; Kleber, R.J.; Mol, M.C.; Staveren, van W.A.

    1992-01-01

    Mental development of 4–5-year old children on macrobiotic diets (almost devoid of animal foods and fat) with long-term growth deficits, was studied using the Snijders-Oomen Non-verbal Intelligence (SON) scale. In addition, food consumption and behavioural style of the children, and family and

  5. Performance of a Press-Lam bridge : a 5-year load-testing and monitoring program

    Science.gov (United States)

    D. S. Gromala; R. C. Moody; M. M. Sprinkel

    1985-01-01

    This paper summarizes the results of load tests on an experimental highway bridge erected and put into service on the George Washington National Forest in Virginia in 1977. The bridge, made entirely of Press-Lam, a laminated veneer lumber (LVL) product, was load tested 1 month, 1 year, and 5 years after erection. The bridge continues to perform quite well and,...

  6. The introduction of the 5-year impact factor : does it benefit statistics journals?

    NARCIS (Netherlands)

    van Nierop, Erjen

    In this paper, we investigate the effects of the introduction of 5-year impact factors. We collect impact factor data for all disciplines available in the Journal Citation Reports. For all these categories, we give insights into the relationship between the traditional 2-year impact factor and the

  7. Introducing Engineering in Elementary Education: A 5-Year Study of Teachers and Students

    Science.gov (United States)

    Diefes-Dux, Heidi A.

    2015-01-01

    Engineering, when integrated into K-12 education, may offer a number of potential student learning and future success benefits. In a 5-year study, four cohorts of elementary teachers of grades 2 to 4 in a single US school district were provided with teacher professional development with engineering education. Teachers were prepared to teach…

  8. Balanitis xerotica obliterans in children and its incidence under the age of 5 years.

    Science.gov (United States)

    Jayakumar, S; Antao, B; Bevington, O; Furness, P; Ninan, G K

    2012-06-01

    To analyse the incidence of BXO among paediatric circumcisions for preputial pathology, in particular in children under the age of 5 years. Retrospective review revealed 1769 paediatric circumcisions performed between 1997 and 2008 at our institution. Data were collected on patient's age, date when sample received by pathology department and histological findings for all the foreskin samples received and examined during the study period. Epidemiological data were obtained from the Office for National Statistics, UK. A total of 346 foreskin samples were received and BXO was found in 182 (52.6%). There were 31 children under the age of 5 years circumcised for preputial pathology. BXO was reported in 6 (19.3%) and chronic inflammation in 16 (51.6%) of these patients. The foreskin was reported normal in 2 (6.5%) and the remaining 7 (22.6%) patients had preputial cysts or other pathology. Epidemiological population data analysis revealed the incidence of BXO per year to be 3.01 cases/1000 boys under 15 years of age and 0.322 cases/1000 boys under 5 years. The incidence of BXO in boys noted in our study is higher than previously reported. BXO can result in significant complications and should be considered in children even under 5 years. Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  9. Urethro-vaso-cutaneous fistula in a 5-year-old child

    International Nuclear Information System (INIS)

    Arat, A.; Midia, M.; Oeztuerk, H.; Uenal, B.; Aydingoez, Ue.; Uensal, M.

    1997-01-01

    A 5-year-old boy with a 4-year history of urethro-vaso-cutaneous fistula is presented. This is the youngest patient reported to have an acquired urethro-vaso-cutaneous fistula. Fistulography is a convenient method for the demonstration of such entities. (orig.). With 1 fig

  10. Verbal Competence in Narrative Retelling in 5-Year-Olds with Unilateral Cleft Lip and Palate

    Science.gov (United States)

    Klintö, Kristina; Salameh, Eva-Kristina; Lohmander, Anette

    2015-01-01

    Background: Research regarding expressive language performance in children born with cleft palate is sparse. The relationship between articulation/phonology and expressive language skills also needs to be further explored. Aims: To investigate verbal competence in narrative retelling in 5-year-old children born with unilateral cleft lip and palate…

  11. Effect of Psychological Intervention on Marital Satisfaction of Mothers with Slow Pace Under 5 Years Children

    Directory of Open Access Journals (Sweden)

    Mehran Soleymani

    2012-04-01

    Full Text Available Objectives: Objective of this study was investigating impact of early psychological interventions on marital satisfaction of mothers with slow pace under 5 years children. Considering variables of the research, that is, early psychological interventions and marital satisfaction, research hypotheses was as follows: "early psychological interventions affect marital satisfaction of mothers with slow pace under 5 years children" and it was examined. Methods: This research is of experimental type and pretest-posttest plan with control groups was used. Statistical population included all mothers with slow pace under 5 years children in Urmia. To this end, 40 mothers with slow pace children were selected as the sample in a non-random manner by convenience sampling. They were assigned randomly into two groups of 20 (20 test group and 20 control group, and finally psychological interventions were conducted on one of groups randomly. In order to evaluate marital satisfaction, Enrich marital satisfaction questionnaire with 47 items was used. Data were analyzed by univariate analysis of covariance. Results: findings showed that there is significant difference between two groups in posttest in overall score of marital satisfaction as well as in some elements such as conventional responses, marital satisfaction, personality issues, marital relationships, conflict resolution, leisure, parenting, family and friends, and ideological orientation and sexual relations (P<0.005, and no significant difference was observed in financial supervision and roles related to gender equality. Discusion: Psychological interventions were effective in promoting marital satisfaction in mothers with slow pace under 5 years children.

  12. Child development at 5 years of age predicted mathematics ability and schooling outcomes in Malawian adolescents.

    Science.gov (United States)

    Gandhi, Mihir; Teivaanmaki, Tiina; Maleta, Kenneth; Duan, Xiaolian; Ashorn, Per; Cheung, Yin Bun

    2013-01-01

    This study aimed to examine the association between child development at 5 years of age and mathematics ability and schooling outcomes at 12 years of age in Malawian children. A prospective cohort study looking at 609 rural Malawian children. Outcome measures were percentage of correctly answered mathematics questions, highest school grade completed and number of times repeating school grades at 12 years of age. A child development summary score obtained at 5 years of age was the main exposure variable. Regression analyses were used to estimate the association and adjust for confounders. Sensitivity analysis was performed by handling losses to follow-up with multiple imputation (MI) method. The summary score was positively associated with percentage of correctly answered mathematics questions (p = 0.057; p = 0.031 MI) and with highest school grade completed (p = 0.096; p = 0.070 MI), and negatively associated with number of times repeating school grades (p = 0.834; p = 0.339 MI). Fine motor score at 5 years was independently associated with the mathematic score (p = 0.032; p = 0.011 MI). The association between child development and mathematics ability did not depend on school attendance. Child development at 5 years of age showed signs of positive association with mathematics ability and possibly with highest school grade completed at 12 years of age. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

  13. Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies

    DEFF Research Database (Denmark)

    Eron, Joseph J; Cooper, David A; Steigbigel, Roy T

    2013-01-01

    Two randomised, placebo-controlled trials-BENCHMRK-1 and BENCHMRK-2-investigated the efficacy and safety of raltegravir, an HIV-1 integrase strand-transfer inhibitor. We report final results of BENCHMRK-1 and BENCHMRK-2 combined at 3 years (the end of the double-blind phase) and 5 years (the end ...

  14. Episodic Memory and Episodic Foresight in 3- and 5-Year-Old Children

    Science.gov (United States)

    Hayne, Harlene; Gross, Julien; McNamee, Stephanie; Fitzgibbon, Olivia; Tustin, Karen

    2011-01-01

    In the present study, we examined the development of episodic memory and episodic foresight. Three- and 5-year-olds were interviewed individually using a personalised timeline that included photographs of them at different points in their life. After constructing the timeline with the experimenter, each child was asked to discuss a number of…

  15. Parental Verbal Strategies and Children's Capacities at 3 and 5 Years during a Memory Task

    Science.gov (United States)

    Labrell, Florence; Ubersfeld, Guillaume

    2004-01-01

    In order to study the influence on memorization of external inputs as well as children's own strategies, we examined both parental discourses in terms of distancing (Sigel, 1970) and spontaneous rehearsal by children during a memory task. Our aim was to assess the influence of each factor for children between 3 and 5 years of age. In our study of…

  16. Anterior single implants with different neck designs : 5 Year results of a randomized clinical trial

    NARCIS (Netherlands)

    den Hartog, Laurens; Meijer, Henny J A; Vissink, Arjan; Raghoebar, Gerry M

    BACKGROUND: The design of the implant neck might be significant for preservation of marginal bone. PURPOSE: To compare the 5-year radiographic and clinical outcome of single anterior implants provided with a smooth neck, a rough neck or a scalloped rough neck. MATERIALS AND METHODS: 93 Patients with

  17. The effects of oil pollution on Antarctic benthic diatom communities over 5 years

    International Nuclear Information System (INIS)

    Polmear, R.; Stark, J.S.; Roberts, D.; McMinn, A.

    2015-01-01

    Highlights: • We examine the impact of hydrocarbon pollution on Antarctic benthic diatoms. • The effect of standard synthetic lubricant oil and a biodegradable oil were examined. • There were significant effects from both treatments for over 5 years. • There was little difference between the different types of oil. - Abstract: Although considered pristine, Antarctica has not been impervious to hydrocarbon pollution. Antarctica’s history is peppered with oil spills and numerous abandoned waste disposal sites. Both spill events and constant leakages contribute to previous and current sources of pollution into marine sediments. Here we compare the response of the benthic diatom communities over 5 years to exposure to a commonly used standard synthetic lubricant oil, an alternative lubricant marketed as more biodegradable, in comparison to a control treatment. Community composition varied significantly over time and between treatments with some high variability within contaminated treatments suggesting community stress. Both lubricants showed evidence of significant effects on community composition after 5 years even though total petroleum hydrocarbon reduction reached approximately 80% over this time period. It appears that even after 5 years toxicity remains high for both the standard and biodegradable lubricants revealing the temporal scale at which pollutants persist in Antarctica

  18. Haematoma-like primary intracranial malignant fibrous histiocytoma in a 5-year-old girl

    International Nuclear Information System (INIS)

    Oezhan, S.; Tali, E.T.; Isik, S.; Saygili, M.R.; Baykaner, K.

    1999-01-01

    We present CT and MRI of an intracranial malignant fibrous histiocytoma in a 5-year-old girl with headache and vomiting. This case is unusual particular by virtue of its radiological appearances and the young age of the patient. (orig.)

  19. HRCT features in a 5-year-old child with follicular bronchiolitis

    International Nuclear Information System (INIS)

    Reittner, P.; Fotter, R.; Lindbichler, F.; Tillich, M.; Varga, E.M.; Zach, M.; Popper, H.

    1997-01-01

    High-resolution CT (HRCT) is the most sensitive radiographic method to image small airways disease. We discuss the HRCT features of follicular bronchiolitis in a 5-year-old boy and correlate them with the histopathological findings. The changes described include centrilobular nodules, bronchiectasis and bronchiolectasis, branching opacities and areas of reduced lung attenuation. (orig.)

  20. HRCT features in a 5-year-old child with follicular bronchiolitis

    Energy Technology Data Exchange (ETDEWEB)

    Reittner, P.; Fotter, R.; Lindbichler, F.; Tillich, M. [Department of Radiology, Karl-Franzens University and University Hospital Graz, Auenbruggerplatz 9, A-8036 Graz (Austria); Varga, E.M.; Zach, M. [Department of Pediatrics, Karl-Franzens University and University Hospital Graz, Graz (Austria); Popper, H. [Department of Pathology, Karl-Franzens University and University Hospital Graz, Graz (Austria)

    1997-11-01

    High-resolution CT (HRCT) is the most sensitive radiographic method to image small airways disease. We discuss the HRCT features of follicular bronchiolitis in a 5-year-old boy and correlate them with the histopathological findings. The changes described include centrilobular nodules, bronchiectasis and bronchiolectasis, branching opacities and areas of reduced lung attenuation. (orig.) With 2 figs., 5 refs.

  1. A Case Series of Marijuana Exposures in Pediatric Patients Less than 5 Years of Age

    Science.gov (United States)

    Wang, George Sam; Narang, Sandeep K.; Wells, Kathryn; Chuang, Ryan

    2011-01-01

    Objective: In Colorado, there has been a large increase in medical marijuana dispensaries and licenses for the use of medical marijuana over the past year. This is a retrospective case series of marijuana exposures that have presented to the emergency department (ED) in children less than 5 years of age. Methods: We performed a retrospective chart…

  2. Low-energy house in Arctic climate - 5 years of experience

    DEFF Research Database (Denmark)

    Vladyková, Petra; Rode, Carsten; Kragh, J.

    2011-01-01

    The aim of this article is to present and disseminate the experience gained from a low‐energy house in Sisimiut, Greenland, over the 5 years of operation since its inauguration in April 2005. The house was designed to test and present new low‐energy technologies in the Arctic climate and to impro...

  3. Therapeutic Community in a California Prison: Treatment Outcomes after 5 Years

    Science.gov (United States)

    Zhang, Sheldon X.; Roberts, Robert E. L.; McCollister, Kathryn E.

    2011-01-01

    Therapeutic communities have become increasingly popular among correctional agencies with drug-involved offenders. This quasi-experimental study followed a group of inmates who participated in a prison-based therapeutic community in a California state prison, with a comparison group of matched offenders, for more than 5 years after their initial…

  4. Prognosis of teeth in the line of mandibular fracture: 5 - year clinical ...

    African Journals Online (AJOL)

    The focus was on 96 teeth in the line of mandibular fracture retained after reduction and immobilization of the fracture by closed reduction technique. The clinical and radiological follow-up period of patients ranged between six months and 3.5 years. RESULTS: Majority of the patients 33 (53.2%) were in their third decade of ...

  5. Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Zielen, Stefen; Garcia-Garcia, María Luz

    2005-01-01

    The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parall...

  6. Lessons learned from 15 years of KIMS and 5 years of ACROSTUDY

    DEFF Research Database (Denmark)

    Luger, Anton; Feldt-Rasmussen, Ulla; Abs, Roger

    2011-01-01

    -deficient adults for 15 years. Approximately 5 years ago, the ACROSTUDY database was established to monitor the long-term safety and effectiveness of pegvisomant in patients with acromegaly. CONCLUSIONS: By collecting data on the treatment of relatively rare conditions in routine clinical practice...

  7. Clinical Evaluation of Small Diameter Straumann Implants in Partially Edentulous Patients: A 5-Year Retrospective Study

    Directory of Open Access Journals (Sweden)

    S. OZER

    2011-06-01

    Full Text Available Objective: The aim of the present study was to retrospectively evaluate small-diameter (3.3 mm Straumann® dental implants placed in the maxilla or the mandible over a period of 5 years in function.Materials and Methods: Twenty- eight partially edentulous patients received a total of 48 implants over a 5-year period. After the standard healing period (3 to 6 months, the implants were restored with single-tooth prostheses or fixed partial dentures. All patients were followed according to a strict maintenance program with regular recalls. The cumulative survival rates of implants were analyzed and prosthetic complications were assessed.Results: After 5 years of function, one single 10-mm-long implant in the maxillary premolar region was lost because of recurrent peri-implant infection in a female patient. Two single 10-mm-long maxillary implants placed in the posterior region were lost due to body fracture. The cumulative 5-year survival rate of the implants was 93.75 %. The most common prosthetic complication was loosening of the occlusal screw.Conclusion: Within the limited observation period and the number of patients included in this study, it may be concluded that the use of small-diameter implants appears to be predictable if clinical guidelines are followed and appropriate prosthetic restorations are provided. However, it should be noted that fatigue fracture may occur.

  8. How Do 5-Year-Olds Understand Questions? Differences in Languages across Europe

    Science.gov (United States)

    Sauerland, Uli; Grohmann, Kleanthes K.; Guasti, Maria Teresa; Andelkovic, Darinka; Argus, Reili; Armon-Lotem, Sharon; Arosio, Fabrizio; Avram, Larisa; Costa, João; Dabašinskiene, Ineta; de López, Kristine; Gatt, Daniela; Grech, Helen; Haman, Ewa; van Hout, Angeliek; Hrzica, Gordana; Kainhofer, Judith; Kamandulyte-Merfeldiene, Laura; Kunnari, Sari; Kovacevic, Melita; Kuvac Kraljevic, Jelena; Lipowska, Katarzyna; Mejias, Sandrine; Popovic, Maša; Ruzaite, Jurate; Savic, Maja; Sevcenco, Anca; Varlokosta, Spyridoula; Varnava, Marina; Yatsushiro, Kazuko

    2016-01-01

    The comprehension of constituent questions is an important topic for language acquisition research and for applications in the diagnosis of language impairment. This article presents the results of a study investigating the comprehension of different types of questions by 5-year-old, typically developing children across 19 European countries, 18…

  9. Jejunal Intramural Hematoma with Bowel Obstruction in a 5-year-old Boy: A Case Report

    International Nuclear Information System (INIS)

    Kim, Seung Soo; Kim, Young Tong

    2009-01-01

    Intramural hematoma of the jejunum is rare and can be classified as trauma-related or occurring spontaneously. Spontaneous intramural hematoma commonly occurs in patients treated with warfarin. We report a case of intramural hematoma of the jejunum with intestinal obstruction in a 5-year-old boy who had neither a definite history of trauma nor the tendency to bleed

  10. Jejunal Intramural Hematoma with Bowel Obstruction in a 5-year-old Boy: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Soo; Kim, Young Tong [Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of)

    2009-12-15

    Intramural hematoma of the jejunum is rare and can be classified as trauma-related or occurring spontaneously. Spontaneous intramural hematoma commonly occurs in patients treated with warfarin. We report a case of intramural hematoma of the jejunum with intestinal obstruction in a 5-year-old boy who had neither a definite history of trauma nor the tendency to bleed.

  11. Immediate restoration of single tapered implants with nonoccluding provisional crowns: a 5-year clinical prospective study.

    Science.gov (United States)

    Lang, Lisa A; Turkyilmaz, Ilser; Edgin, Wendell A; Verrett, Ronald; Garcia, Lily T

    2014-04-01

    Dental literature has limited number of publications regarding long-term outcome data of immediate restoration of single missing teeth with an implant-supported provisional crown. This 5-year study evaluated hard and soft tissue responses to the immediate placement of single implant-supported provisional crowns. Twenty patients received one dental implant restored immediately with a provisional acrylic resin screw-retained crown. Crestal bone loss was evaluated from standardized periapical radiographs collected at 3-month intervals for the first 21 months followed by a 5-year evaluation. Historical controls acquired from available dental literature were used for comparison. One implant failed within 2 months of surgical placement, presenting with pain and mobility. The remaining implants demonstrated no infection, pain, or radiolucencies. Nineteen implants were clinically immobile, osseointegrated, and asymptomatic at 21 months. At 5 years, one patient died, three patients were noncompliant, and 15 implants were evaluated as functional. Mean bone loss (MBL) at 1 year and 21 months was approximately 0.5 ± 0.5 mm and 0.70 ± 0.26 mm at 5 years. There was no statistically significant difference between MBLs at p provisionalization of single dental implants compares favorably with conventional loading protocols. Long-term data suggest that immediate provisionalization of single dental implants is a viable treatment option. © 2012 Wiley Periodicals, Inc.

  12. 77 FR 64959 - Endangered and Threatened Species; Initiation of 5-Year Review for the Southern Distinct...

    Science.gov (United States)

    2012-10-24

    ... listing classification for this species. A 5-year review is based on the best scientific and commercial... on this document, identified by NOAA-NMFS-2012-0198, by any of the following methods: Electronic... resulting list and click on the ``Submit a Comment'' icon on the right of that line. Mail or hand-delivery...

  13. Influence of Emotional Facial Expressions on 3-5-Year-Olds' Face Recognition

    Science.gov (United States)

    Freitag, Claudia; Schwarzer, Gudrun

    2011-01-01

    Three experiments examined 3- and 5-year-olds' recognition of faces in constant and varied emotional expressions. Children were asked to identify repeatedly presented target faces, distinguishing them from distractor faces, during an immediate recognition test and during delayed assessments after 10 min and one week. Emotional facial expression…

  14. Effect of breastfeeding on common pediatric infections: a 5-year prospective cohort study.

    Science.gov (United States)

    Ardiç, Cüneyt; Yavuz, Erdinç

    2018-04-01

    The studies conducted revealed that breastfeeding duration has a reducing effect on common infectious diseases in the children during breastfeeding period. The aim of the present study was to address the association between breastfeeding duration and common infectious diseases in the children until 5 years of age to show long-term protective effects of the breast milk. The study included 411 infants who were born in Rize (Turkey) between January 2011 and December 2011. The present prospective-cohort study lasted for 5 years and 11 interviews were conducted with each mother of the infants during this period. The infants were divided into two groups as those who were breastfed more and less than 12 months and the association between breastfeeding and infections such as acute otitis media, acute gastroenteritis, acute respiratory tract infections and acute urinary system infections was investigated. Of 270 infants 193 (71.5%) were breastfed longer than 12 months and 77 (28.5%) were breastfed less than 12 months. Infants in the first group had less acute otitis media and acute gastroenteritis (n= 77, 28.52%) when compared with the infants breastfed less than 12 months during 5-year period (p <0.05). The present study detected that breastfeeding duration longer than 12 months significantly reduces the common childhood infections such as otitis media and gastroenteritis during the first 5 years of life. Sociedad Argentina de Pediatría.

  15. Pancreas transplantation with grafts from donors deceased after circulatory death (DCD) : 5 years single center experience

    NARCIS (Netherlands)

    Kopp, Wouter H; Lam, Hwai-Ding; Schaapherder, Alexander F M; Huurman, Volkert A L; van der Boog, Paul; de Koning, Eelco; de Fijter, Johan W; Baranski, Andrzej; Braat, Andries E

    2017-01-01

    INTRODUCTION: Donation after circulatory death (DCD) pancreas transplantation has been shown to be an additional way to deal with donor organ shortages. The results of 5-year DCD pancreas transplantation are presented. METHODS: A retrospective, single center analysis (2011 - 2015) was performed to

  16. Gastroesophageal Acid Reflux Control 5 Years After Antireflux Surgery, Compared With Long-term Esomeprazole Therapy.

    Science.gov (United States)

    Hatlebakk, Jan G; Zerbib, Frank; Bruley des Varannes, Stanislas; Attwood, Stephen E; Ell, Christian; Fiocca, Roberto; Galmiche, Jean-Paul; Eklund, Stefan; Långström, Göran; Lind, Tore; Lundell, Lars R

    2016-05-01

    We compared the ability of laparoscopic antireflux surgery (LARS) and esomeprazole to control esophageal acid exposure, over a 5-year period, in patients with chronic gastroesophageal reflux disease (GERD). We also studied whether intraesophageal and intragastric pH parameters off and on therapy were associated with long-term outcomes. We analyzed data from a prospective, randomized, open-label trial comparing the efficacy and safety of LARS vs esomeprazole (20 or 40 mg/d) over 5 years in patients with chronic GERD. Ambulatory intraesophageal and intragastric 24-hour pH monitoring data were compared between groups before LARS or the start of esomeprazole treatment, and 6 months and 5 years afterward. A secondary aim was to evaluate the association between baseline and 6-month pH parameters and esomeprazole dose escalation, reappearance of GERD symptoms, and treatment failure over 5 years in patients receiving LARS or esomeprazole. In the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P acidity was stable in both groups. Patients who required a dose increase to 40 mg/d had more severe supine reflux at baseline, and decreased esophageal acid exposure (P acidity after dose escalation. Esophageal and intragastric pH parameters, off and on therapy, did not predict long-term symptom breakthrough. In a prospective study of patients with chronic GERD, esophageal acid reflux was reduced greatly by LARS or esomeprazole therapy. However, patients receiving LARS had significantly greater reductions in 24-hour esophageal acid exposure after 6 months and 5 years. Esophageal and gastric pH, off and on therapy, did not predict long-term outcomes of patients. Abnormal supine acid exposure predicted esomeprazole dose escalation. ClinicalTrials.Gov identifier: NCT00251927 (available: http://clinicaltrials.gov/ct2/show

  17. Risk Factors of Pneumonia Among Children Under 5 Years at a Pediatric Hospital in Sudan

    Directory of Open Access Journals (Sweden)

    Siham M.O. Gritly

    2018-04-01

    Full Text Available Introduction: Pneumonia is major cause of mortality among acute respiratory infections, killing up to 5 million of children below the age of 5 years annually in developing countries. Total 50% out-patients cases in Sudan are children while 30% of children admissions are due to pneumonia. Every year, the number of deaths in infant and children below the age of 5 years is reported to be 12 million. Objectives: The aim of this study is to find out the pneumonia risks in Sudan among children <5 years and to establish a baseline data and statistical information about pneumonia in the age group for future use. Study design and Setting: A hospital based descriptive study was conducted among children <5 years at Mohamed Al-Amin Hamid Pediatric Hospital in February 2017. Methods: Parents of 40 children <5 years admitted to the hospital during the study period completed the constructed questionnaire after obtaining informed consents from each of them. Data was then analyzed. Results: Children in this study consisted of 27 (57.50% males and 13 (42.5% females. Factors found to have association with pneumonia include low socio-economic status and low educational level of mothers. Conclusion and Recommendations: The study concluded that the pneumonia is more prevalent in children less than one year. Factors found to have association with pneumonia include low socioeconomic status and low educational level of mothers admitted to Mohamed Al-Amin pediatric hospital in Omdurman locality. It was recommended to have an early diagnosis and treatment of pneumonia. Community health education and completion of the immunization program are recommended to decrease the infection.

  18. Significance of postoperative irradiation for breast cancer

    International Nuclear Information System (INIS)

    Murai, Nobuko; Ogami, Koji; Nishikawa, Kiyoshi; Koga, Kenji; Waki, Norio; Higashi, Hidefumi; Hayashi, Asami; Shibata, Koichiro; Watanabe, Katsuji

    1986-01-01

    From 1978 through 1983, 27 patients were treated with surgery followed by irradiation (irradiated group) and 29 with surery alone (non-irradiated group). In the irradiated group, 10 had stage II and 17 stage III; in the non-irradiated group, 25 had stage II and 4 stage III. The most common histology was medullary tubular carcinoma (MTC). There was no significant difference in survivals at 3 years and 5 years between the groups. Similarly, no significant difference was seen among stage II patients. Patients with MTC tended to have worse survivals in the irradiated group than in the non-irradiated group, with no statistically significant difference. Among stage II patients, no major differences in local recurrence were seen between the groups; the incidence of distant metastases tended to be high in the irradiated group. The incidence of both local recurrence and distant metastases for stage III patients showed a tendency to be higher in the irradiated group than in the non-irradiated group. The results indicated no apparent benifit of postoperative irradiation for breast cancer. A randomized clinical trial is needed for the evaluation of postoperative irradiation for breast cancer. (Namekawa, K.)

  19. Postoperative US of leg tendon reconstruction

    International Nuclear Information System (INIS)

    Draghi, F.; Calliada, F.; Fulle, I.; Madonia, L.; Bottinelli, O.; Campani, R.

    1999-01-01

    The role of ultrasound (US) in the postoperative assessment of tendon reconstruction is not clearly defined and there is non systematic arrangement of US patterns. The authors examined 34 patients submitted to surgery or conservative treatment for total/partial tear or musculotendinous detachment of patellar or Achilles tendon in the last 5 years. All patients underwent physical and US examinations. The surgical tendon exhibited the same US patterns in 23/28 patients: it was markedly enlarged (three-/fourfold the normal diameter) and more rounded, with inhomogeneous and hypoechoic appearance not only at the tear/surgical site but also above and below it, for some cm. Small hyperechoic images, mainly dots, were seen in 19 cases, which were referable to small calcifications and stitches. More and larger calcifications were found in 8 patients, where they were associated with anechoic degeneration areas. Color Doppler US showed moderate or strong hypervascularization around the tear in the first months post injury. US patterns did not correlate with physical findings, but color Doppler patterns did. In 6 cases of musculotendinous detachment submitted to conservative treatment, US showed enlargement and hypoechogenicity in the injury site only, with no involvement of the remaining tendon. US was also used to time and guide drainage of perilesional hematomas, which were often quite large. US is the method of choice in the postoperative follow-up of tendon tears and musculotendinous detachments because it shows abnormal signs which are missed at clinics and provides additional information needed for treatment planning [it

  20. Steroid receptor coactivators, HER-2 and HER-3 expression is stimulated by tamoxifen treatment in DMBA-induced breast cancer

    International Nuclear Information System (INIS)

    Moi, Line L Haugan; Flågeng, Marianne Hauglid; Gjerde, Jennifer; Madsen, Andre; Røst, Therese Halvorsen; Gudbrandsen, Oddrun Anita; Lien, Ernst A; Mellgren, Gunnar

    2012-01-01

    Steroid receptor coactivators (SRCs) may modulate estrogen receptor (ER) activity and the response to endocrine treatment in breast cancer, in part through interaction with growth factor receptor signaling pathways. In the present study the effects of tamoxifen treatment on the expression of SRCs and human epidermal growth factor receptors (HERs) were examined in an animal model of ER positive breast cancer. Sprague-Dawley rats with DMBA-induced breast cancer were randomized to 14 days of oral tamoxifen 40 mg/kg bodyweight/day or vehicle only (controls). Tumors were measured throughout the study period. Blood samples and tumor tissue were collected at sacrifice and tamoxifen and its main metabolites were quantified using LC-MS/MS. The gene expression in tumor of SRC-1, SRC-2/transcription intermediary factor-2 (TIF-2), SRC-3/amplified in breast cancer 1 (AIB1), ER, HER-1, -2, -3 and HER-4, as well as the transcription factor Ets-2, was measured by real-time RT-PCR. Protein levels were further assessed by Western blotting. Tamoxifen and its main metabolites were detected at high concentrations in serum and accumulated in tumor tissue in up to tenfolds the concentration in serum. Mean tumor volume/rat decreased in the tamoxifen treated group, but continued to increase in controls. The mRNA expression levels of SRC-1 (P = 0.035), SRC-2/TIF-2 (P = 0.002), HER-2 (P = 0.035) and HER-3 (P = 0.006) were significantly higher in tamoxifen treated tumors compared to controls, and the results were confirmed at the protein level using Western blotting. SRC-3/AIB1 protein was also higher in tamoxifen treated tumors. SRC-1 and SRC-2/TIF-2 mRNA levels were positively correlated with each other and with HER-2 (P ≤ 0.001), and the HER-2 mRNA expression correlated with the levels of the other three HER family members (P < 0.05). Furthermore, SRC-3/AIB1 and HER-4 were positively correlated with each other and Ets-2 (P < 0.001). The expression of SRCs and HER-2 and -3 is stimulated

  1. A pooled analysis of CYP2D6 genotype in breast cancer prevention trials of low-dose tamoxifen.

    Science.gov (United States)

    Johansson, Harriet; Gandini, Sara; Serrano, Davide; Gjerde, Jennifer; Lattanzi, Monia; Macis, Debora; Guerrieri-Gonzaga, Aliana; Aristarco, Valentina; Mellgren, Gunnar; Lien, Ernst; DeCensi, Andrea; Bonanni, Bernardo

    2016-08-01

    Decreased CYP2D6 activity is associated with lower levels of active tamoxifen metabolites. We examined the impact of CYP2D6 genotype on tamoxifen pharmacokinetics, biomarker activity, and efficacy in a pooled analysis of low-dose tamoxifen. Four randomized breast cancer prevention trials of very-low-dose (1 mg/day, n = 52 or 10 mg/week, n = 152) or low-dose tamoxifen (5 mg/day, n = 171) were pooled. DNA from 367 subjects was genotyped for CYP2D6 alleles associated with absent (PM allele: *3, *4, *5, *6, *7, *8, *12, and *14), reduced (IM allele: *9, *10, *17, *29, *41), normal (EM allele), or increased (UM: *XN) enzyme activity. Associations of tamoxifen, metabolites, activity biomarkers, and event-free survival with rapid (UM/EM, UM/IM, EM/EM, EM/IM, or EM/PM alleles) versus slow metabolizers (PM/IM or PM/PM) were investigated through random effects models, with 'study' as the random factor, and Cox regression models, adjusting for confounders. Rapid metabolizers had higher endoxifen levels than slow metabolizers: 15.3 versus 12.2 ng/mL (P = 0.018) with 5 mg/day, and 3.8 versus 2.8 ng/mL (P = 0.004) with 1 mg/day or 10 mg/week tamoxifen. The IGF-I decrease correlated with endoxifen (P = 0.002) and 4-hydroxytamoxifen levels, demonstrating steeper decreases at higher metabolite levels (P = 0.001). After a median follow-up of 12 years, rapid metabolizers with prior history of breast neoplasms allocated to tamoxifen 5 mg/day had a 60 % reduction of risk of recurrences (HR = 0.40, 95 % CI: 0.16-0.99) compared to slow metabolizers. CYP2D6 genotype may have an impact on tamoxifen efficacy at low doses. Trials investigating tamoxifen dose adjustments based on the woman's hormonal context and CYP2D6 genotype are warranted.

  2. Postoperative radiotherapy for parotid gland malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Keun Yong; Wu, Hong Gyun; Kim, Jae Sung; Park, Charn Il; Kim, Kwang Hyun; Lee, Chae Seo [Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, In Ah [Bundang Seoul National University Hospital, Seongnam (Korea, Republic of)

    2005-09-15

    The aim of this study was to evaluate the clinical results of postoperative radiotherapy for parotid gland malignancy, and determine prognostic factors for locoregional control and survival. Between 1980 and 2002, 130 patients with parotid malignancy were registered in the database of the Department of Radiation Oncology, Seoul National University Hospital. The subjects of this analysis were the 72 of these 130 patients who underwent postoperative irradiation. There were 42 males and 30 females, with a median age of 46.5 years. The most common histological type was a mucoepidermoid carcinoma. There were 6, 23, 23 and 20 patients in Stages I, II, III and IV, respectively. The median dose to the tumor bed was 60 Gy, with a median fraction size of 1.8 Gy. The overall 5 and 10 year survival rates were 85 and 76%, respectively. The five-year locoregional control rate was 85%, which reached a plateau phase after 6 years. Sex and histological type were found to be statistically significant for overall survival from a multivariate analysis. No other factors, including age, facial nerve palsy and stage, were related to overall survival. For locoregional control, nodal involvement and positive resection margin were associated with poor local control. Histological type, tumor size, perineural invasion and type of surgery were not significant for locoregional control. A high survival rate of parotid gland malignancies, with surgery and postoperative radiotherapy, was confirmed. Sex and histological type were significant prognostic factors for overall survival. Nodal involvement and a positive resection margin were associated with poor locoregional control.

  3. Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice.

    Science.gov (United States)

    Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki

    2016-07-29

    Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes.

  4. Tamoxifen for one year versus two years versus 6 months of Tamoxifen and 6 months of megestrol acetate: A randomized comparison in postmenopausal patients with high-risk breast cancer (DBCG 89C)

    DEFF Research Database (Denmark)

    Andersen, Jørn; Kamby, C.; Ejlertsen, B.

    2008-01-01

    From January 1, 1990 to December 31, 1994, DBCG conducted a randomised trial in 1 615 postmenopausal women with operable, high-risk, receptor-positive or -unknown breast cancer. The patients were after surgery randomised to Tamoxifen for 1 year (TAM1), Tamoxifen for 2 years (TAM 2) or Tamoxifen...... for 6 months followed by megestrol acetate for 6 months (TAM/MA). When the preplanned sample size of 1 500 patients was reached it was decided to continue randomisation to TAM1 or TAM2 and the study was finally closed December 31, 1996. With a median follow-up of more than 10 years...... in hazard ratios for DFS or OS among the three arms. Sideeffects were rare but more common in the TAM2 and TAM/MA arms Udgivelsesdato: 2008...

  5. Minimally invasive transforaminal lumbar interbody fusion for spondylolisthesis and degenerative spondylosis: 5-year results.

    Science.gov (United States)

    Park, Yung; Ha, Joong Won; Lee, Yun Tae; Sung, Na Young

    2014-06-01

    Multiple studies have reported favorable short-term results after treatment of spondylolisthesis and other degenerative lumbar diseases with minimally invasive transforaminal lumbar interbody fusion. However, to our knowledge, results at a minimum of 5 years have not been reported. We determined (1) changes to the Oswestry Disability Index, (2) frequency of radiographic fusion, (3) complications and reoperations, and (4) the learning curve associated with minimally invasive transforaminal lumbar interbody fusion at minimum 5-year followup. We reviewed our first 124 patients who underwent minimally invasive transforaminal lumbar interbody fusion to treat low-grade spondylolisthesis and degenerative lumbar diseases and did not need a major deformity correction. This represented 63% (124 of 198) of the transforaminal lumbar interbody fusion procedures we performed for those indications during the study period (2003-2007). Eighty-three (67%) patients had complete 5-year followup. Plain radiographs and CT scans were evaluated by two reviewers. Trends of surgical time, blood loss, and hospital stay over time were examined by logarithmic curve fit-regression analysis to evaluate the learning curve. At 5 years, mean Oswestry Disability Index improved from 60 points preoperatively to 24 points and 79 of 83 patients (95%) had improvement of greater than 10 points. At 5 years, 67 of 83 (81%) achieved radiographic fusion, including 64 of 72 patients (89%) who had single-level surgery. Perioperative complications occurred in 11 of 124 patients (9%), and another surgical procedure was performed in eight of 124 patients (6.5%) involving the index level and seven of 124 patients (5.6%) at adjacent levels. There were slowly decreasing trends of surgical time and hospital stay only in single-level surgery and almost no change in intraoperative blood loss over time, suggesting a challenging learning curve. Oswestry Disability Index scores improved for patients with spondylolisthesis

  6. Minimal impact of adjuvant exemestane or tamoxifen treatment on mammographic breast density in postmenopausal breast cancer patients: A Dutch TEAM trial analysis

    NARCIS (Netherlands)

    J.G.H. van Nes; L.V. Beex (Louk); C.M. Seynaeve (Caroline); H. Putter (Hein); A. Sramek (Alexandr); S. Lardenoije (Susanne); M.D.-D.E. Carpentier (Marjolijn Duijm-D.E.); I. Van Rongen (Inge); J.W.R. Nortier (Johan W. R.); H.M. Zonderland (Harmine); C.J.H. van de Velde (Cornelis)

    2015-01-01

    textabstractBackground. Mammographic breast density is one of the strongest independent risk factors for developing breast cancer. We examined the effect of exemestane and tamoxifen on breast density in Dutch postmenopausal early breast cancer patients participating in the Tamoxifen Exemestane

  7. Tamoxifen effects on subjective and psychosexual well-being, in a randomised breast cancer study comparing high-dose and standard-dose chemotherapy

    NARCIS (Netherlands)

    Mourits, MJ; Bockermann, [No Value; de Vries, EG; van der Zee, AG; ten Hoor, KA; van der Graaf, WT; Sluiter, WJ; Willemse, PH

    2002-01-01

    To evaluate the impact of tamoxifen on subjective and psychosexual well-being in breast cancer patients in relation to type of prior chemotherapy and menopausal status. Longitudinal interview study in breast cancer patients during and after adjuvant tamoxifen use. Menopausal status was defined by

  8. The postoperative spine

    International Nuclear Information System (INIS)

    Anon.

    1985-01-01

    The failed back surgery syndrome (FBSS) is one of the most perplexing medical and medicoeconomic problems facing our health system today. In many studies reoperation rates tend to be between 10 and 20%, but as many as 20-45% 3 of patients may have persistent back or radicular pain following what was to have been definitive therapy. The causes for the FBSS are very complex. The Workmen's Compensation system and medicolegal trends toward very high settlements of litigation for injury have provided serious incentive for patients to remain symptomatic. It is difficult to analyze any statistical survey of symptomatic back patients without serious bias from this group of patients. Others suggest that patients with severe psychological problems, drug abuse, and alcoholism are inappropriately selected as surgical candidates. They believe that careful psychological evaluation of patients minimizes FBSS. Even if all extrinsic factors could be eliminated, the problem of failed back surgery would still be a major one. This chapter is based on a review of 300 postoperative lumbar spine multiplanar CT scans performed over a 15-month period. All patients had a complete set of axial images, with sagittal and coronal reformations photographed twice: optimized once for bone definition and once for soft-tissue contrast resolution

  9. Preoperative alcoholism and postoperative morbidity

    DEFF Research Database (Denmark)

    Tonnesen, H; Kehlet, H

    1999-01-01

    BACKGROUND: Preoperative risk assessment has become part of daily clinical practice, but preoperative alcohol abuse has not received much attention. METHODS: A Medline search was carried out to identify original papers published from 1967 to 1998. Relevant articles on postoperative morbidity...... in alcohol abusers were used to evaluate the evidence. RESULTS: Prospective and retrospective studies demonstrate a twofold to threefold increase in postoperative morbidity in alcohol abusers, the most frequent complications being infections, bleeding and cardiopulmonary insufficiency. Wound complications...... to postoperative morbidity. CONCLUSION: Alcohol consumption should be included in the preoperative assessment of likely postoperative outcome. Reduction of postoperative morbidity in alcohol abusers may include preoperative alcohol abstinence to improve organ function, or perioperative alcohol administration...

  10. Chest wall stabilization and reconstruction: short and long-term results 5 years after the introduction of a new titanium plates system.

    Science.gov (United States)

    De Palma, Angela; Sollitto, Francesco; Loizzi, Domenico; Di Gennaro, Francesco; Scarascia, Daniele; Carlucci, Annalisa; Giudice, Giuseppe; Armenio, Andrea; Ludovico, Rossana; Loizzi, Michele

    2016-03-01

    We report short and long-term results with the dedicated Synthes(®) titanium plates system, introduced 5 years ago, for chest wall stabilization and reconstruction. We retrospectively analyzed (January 2010 to December 2014) 27 consecutive patients (22 males, 5 females; range 16-83 years, median age 60 years), treated with this system: primary [3] and secondary [8] chest wall tumor; flail chest [5]; multiple ribs fractures [5]; sternal dehiscence-diastasis [3]; sternal fracture [1]; sternoclavicular joint dislocation [1]; Poland syndrome [1]. Short-term results were evaluated as: operating time, post-operative morbidity, mortality, hospital stay; long-term results as: survival, plates-related morbidity, spirometric values, chest pain [measured with Verbal Rating Scale (VRS) and SF12 standard V1 questionnaire]. Each patient received from 1 to 10 (median 2) titanium plates/splints; median operating time was 150 min (range: 115-430 min). Post-operative course: 15 patients (55.6%) uneventful, 10 (37%) minor complications, 2 (7.4%) major complications; no post-operative mortality. Median post-operative hospital stay was 13 days (range: 5-129 days). At a median follow-up of 20 months (range: 1-59 months), 21 patients (78%) were alive, 6 (22%) died. Three patients presented long-term plates-related morbidity: plates rupture [2], pin plate dislodgment [1]; two required a second surgical look. One-year from surgery median spirometric values were: FVC 3.31 L (90%), FEV1 2.46 L (78%), DLCO 20.9 mL/mmHg/min (76%). On 21 alive patients, 7 (33.3%) reported no pain (VRS score 0), 10 (47.6%) mild (score 2), 4 (19.1%) moderate (score 4), no-one severe (score >4); 15 (71.5%) reported none or mild, 6 (28.5%) moderate pain influencing quality of life. An optimal chest wall stabilization and reconstruction was achieved with the Synthes(®) titanium plates system, with minimal morbidity, no post-operative mortality, acceptable operating time and post-operative hospital stay. Long

  11. Bone marrow cytology in Hiroshima atomic bomb survivors 5 years following exposure

    International Nuclear Information System (INIS)

    Oesterle, S.N.; Finch, S.C.

    1978-11-01

    Bone marrow aspiration smears obtained from 35 individuals, 5 years following exposure to the Hiroshima atomic bomb, were intensively evaluated for radiation related cytologic abnormalities. No definite radiation related changes were observed, but some findings were very suggestive. The most interesting of these was the occurrence of internuclear bridges joining erythroid precursors in the marrow smears of seven (20%) of the heavily exposed survivors. Although not specific it is likely that this lesion is indicative of residual stem cell damage and some degree of ineffectual erythropoiesis. The bone marrow morphologic lesions may be good markers of residual radiation damage but they are too infrequent in their occurrence to be of value as a biologic dosimeter. The findings in this study also suggest that a gradual disappearance of radiation induced late bone marrow changes continues for periods of 3 to 5 years or more following high dose acute radiation exposure. (author)

  12. Short-course chemotherapy for paediatric respiratory tuberculosis: 5-year report.

    Science.gov (United States)

    Swaminathan, S; Raghavan, A; Duraipandian, M; Kripasankar, A S; Ramachandran, P

    2005-06-01

    This report presents the 5-year follow-up of 137 children with respiratory tuberculosis enrolled in a randomised clinical trial of two different anti-tuberculosis regimens 9HR and 2HRZ3/4RH2. Both regimens had similar cure rates, with low relapse rates and mortality. Of 134 children followed up to 5 years, 86% had normal radiographs, with more sequelae in the 9HR group (15% vs. 1.5%, P < 0.01). One patient relapsed and there was one accidental death. Short-course chemotherapy in children is safe, effective and well tolerated, and leads to excellent long-term results, with a small proportion of children left with radiological sequelae.

  13. The longitudinal impact of partner coping in couples following 5 years of unsuccessful fertility treatments

    DEFF Research Database (Denmark)

    Peterson, B D; Pirritano, M; Christensen, Ulla

    2009-01-01

    BACKGROUND Because there is a lack of longitudinal research examining the impact of partner coping in couples experiencing infertility, we know very little about the long-term nature of coping with infertility and how partner coping strategies impact personal, marital and social distress. METHODS...... Participants were Danish men and women about to start a cycle of assisted reproduction treatment who were followed for a 5 year period of unsuccessful treatments. Multilevel modeling using the actor-partner interdependence model was used to examine the couple as the unit of analysis. RESULTS Active and passive...... have a significant impact on the other member of the couple over time in men and women undergoing infertility treatments over a 5 year period. Physicians and mental health professionals can educate men and women regarding the ineffectiveness of avoidance coping strategies as well as the beneficial...

  14. A prospective 4- to 5-year study of DSM-III-R hypochondriasis.

    Science.gov (United States)

    Barsky, A J; Fama, J M; Bailey, E D; Ahern, D K

    1998-08-01

    Although hypochondriasis is generally thought to be a chronic and stable condition with a relatively low remission rate, this disorder remains understudied. This is a 4- to 5-year prospective case-control study of DSM-III-R hypochondriasis. Medical outpatients meeting DSM diagnostic criteria for hypochondriasis completed an extensive research battery assessing hypochondriacal symptoms, medical and psychiatric comorbidity, functional status and role impairment, and medical care. A comparison group of nonhypochondriacal patients from the same setting underwent the same battery. Four to 5 years later, both cohorts were re-interviewed. One hundred twenty hypochondriacal and 133 nonhypochondriacal comparison patients were originally studied. Follow-up was obtained on 73.5% (n = 186) of all patients. At follow-up, the hypochondriacal sample was significantly (Psomatization (Psomatization (PHypochondriasis, therefore, carries a very substantial, long-term burden of morbidity, functional impairment, and personal distress.

  15. SCANDCLEFT RANDOMIZED TRIALS: SPEECH OUTCOMES IN 5-YEAR-OLDS WITH UCLP - velopharyngeal competency and hypernasality

    DEFF Research Database (Denmark)

    Lohmander, Anette; Persson, Christina; Willadsen, Elisabeth

    2017-01-01

    Background and aim: Adequate velopharyngeal function and speech are main goals in the treatment of cleft palate. The objective was to investigate if there were differences in velopharyngeal competency (VPC) and hypernasality at age 5 years in children with unilateral cleft lip and palate (UCLP...... (136 girls, 255 boys) were available and perceptually analysed. The main outcome measures were VPC and hypernasality from blinded assessments. Results: There were no statistically significant differences between the prevalences in the arms in any of the trials. VPC: Trial 1, A: 58%, B: 61%; Trial 2, A......: 57%, C: 54%; Trial 3, A: 35%, D: 51%. No hypernasality: Trial 1, A: 54%, B: 44%; Trial 2, A: 47%, C: 51%; Trial 3, A: 34%, D: 49%. Conclusions: No differences were found regarding VPC and hypernasality at age 5 years after different methods for primary palatal repair. The burden of care in terms...

  16. Measles Antibody Titres In 0-5 Years Children At Aligarh

    Directory of Open Access Journals (Sweden)

    Kandpal S D

    1999-01-01

    Full Text Available Research Question: What is the level of measles antibodies in 0-5 year children? Objectives: 1.To assess the pattern of decline of maternal antibodies in 0-9 months infants. 2. To estimate the seropositivity for measles antibodies in vaccinated 9 months infants. Study design: Cross- sectional. Setting: Rural areas of District Aligarh, U.P. Participants: 456 children in the age group of 0-5 years. Statistical analysis: Percentages, correlation coefficient. Results: 1. In all the study subjects below 9 months of age, the transplacentally acquired maternal measles antibodies showed a linear decline with increase in age. Out of 202 study subjects who had been immunized against measles 195(96.50% were seropositive and 7(3.5% were seronegative for measles antibodies.

  17. Predicting an asthma exacerbation in children 2 to 5 years of age

    DEFF Research Database (Denmark)

    Swern, A.S.; Tozzi, C.A.; Knorr, B.

    2008-01-01

    BACKGROUND: Asthma exacerbations in young children are prevalent. Identification of symptoms or other factors that are precursors of asthma exacerbations would be useful for early treatment and prevention. OBJECTIVES: To determine whether diary symptoms and beta2-agonist use before an exacerbation...... could predict an asthma exacerbation in children 2 to 5 years of age. METHODS: Post hoc analyses were conducted on data collected in a study of 689 patients 2 to 5 years of age with asthma symptoms, randomly assigned to montelukast, 4 mg, or placebo daily for 12 weeks. During the study, 196 patients had...... of an exacerbation. These methods predicted 149 (66.8%) of the exacerbations with a very low false-positive rate of 14.2%. CONCLUSIONS: No individual symptom was predictive of an imminent asthma exacerbation, but a combination of increased daytime cough, daytime wheeze, and nighttime beta2-agonist use 1 day before...

  18. Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Heilmann, Carsten; Weihe, Pal

    2017-01-01

    Perfluorinated alkylate substances (PFASs) are highly persistent and may cause immunotoxic effects. PFAS-associated attenuated antibody responses to childhood vaccines may be affected by PFAS exposures during infancy, where breastfeeding adds to PFAS exposures. Of 490 members of a Faroese birth...... cohort, 275 and 349 participated in clinical examinations and provided blood samples at ages 18 months and 5 years. PFAS concentrations were measured at birth and at the clinical examinations. Using information on duration of breastfeeding, serum-PFAS concentration profiles during infancy were estimated......, with decreases by up to about 20% for each two-fold higher exposure, while associations for serum concentrations at ages 18 months and 5 years were weaker. Modeling of serum-PFAS concentration showed levels for age 18 months that were similar to those measured. Concentrations estimated for ages 3 and 6 months...

  19. Clinical Case Report on Treatment of Generalized Aggressive Periodontitis: 5-Year Follow-up.

    Science.gov (United States)

    Hu, Kai-Fang; Ho, Ya-Ping; Ho, Kun-Yen; Wu, Yi-Min; Wang, Wen-Chen; Chou, Yu-Hsiang

    2015-01-01

    Generalized aggressive periodontitis (GAgP) is a distinct type of periodontal disease associated with considerably more rapid periodontal tissue destruction than chronic periodontitis. This study presents the 5-year follow-up of a patient with GAgP. A 29-year-old man reported experiencing increasing gingival recession. He was treated using cause-related therapy, provisional splints, and flap surgery combined with allograft grafting and was followed up for 5 years. This case study shows that elimination of infectious microorganisms and meticulous long-term maintenance provide an effective treatment modality for aggressive periodontitis cases. This treatment modality can restore the masticatory function and provide the GAgP patient with improved quality of life.

  20. Air Travel Safety in Postoperative Breast Cancer Patients: A Systematic Review.

    Science.gov (United States)

    Co, Michael; Ng, Judy; Kwong, Ava

    2018-05-17

    Air travel has long been a dilemma in post-breast cancer surgery patients. Anecdotal reports have described adverse outcomes on surgical wound, implants, and lymphedema during air travel. This review aims to evaluate the best evidence from the literature concerning the air travel safety in breast cancer patients. A comprehensive review was performed of the Medline, Embase, CINAHL, and Cochrane databases using a predefined strategy. Retrieved studies were independently screened and rated for relevance. Data were extracted by 2 researchers. We reviewed the best evidence on air travel safety in postoperative breast cancer patients. Evidence was limited in the current literature to suggest adverse effects on postoperative mastectomy wounds and drains by high-altitude travel. Similarly, adverse effects on breast implants were limited to case reports and ex vivo experiments. A systematic review of 12 studies concluded that air travel is not associated with upper limb lymphedema after breast cancer surgery. Deep-vein thrombosis (DVT) is a known complication after air travel; in addition, malignancy itself is a known risk factor for DVT. Evidence of safety to continue tamoxifen during the period of air travel is lacking in the literature. Evidence to support the use of systemic DVT prophylaxis in general postoperative breast cancer patients is also limited. Best evidence from a large retrospective study suggested that mechanical antiembolism devices and early mobilization are the only measures required. Air travel is generally safe in patients after breast cancer surgery. Copyright © 2018. Published by Elsevier Inc.

  1. Cartilaginous avulsion fracture of the tibial spine in a 5-year-old girl

    International Nuclear Information System (INIS)

    Kim, Jung Ryul; Song, Ji Hun; Lee, Ju Hong; Lee, Sang Yong; Yoo, Wan Hee

    2008-01-01

    Fractures of the tibial spine usually occur in children aged 8 to 14 years. Usually, radiographs will demonstrate a tibial spine fracture, with the degree of displacement. Tibial spine fractures in younger children have not been reported in the previously published literature. We report a tibial spine fracture that occurred in 5-year-old girl. The cartilaginous avulsion fracture of the tibial spine was not revealed by radiographs because it was limited to the cartilaginous portion of the proximal tibia. (orig.)

  2. Development and verification of child observation sheet for 5-year-old children.

    Science.gov (United States)

    Fujimoto, Keiko; Nagai, Toshisaburo; Okazaki, Shin; Kawajiri, Mie; Tomiwa, Kiyotaka

    2014-02-01

    The aim of the study was to develop a newly devised child observation sheet (COS-5) as a scoring sheet, based on the Childhood Autism Rating Scale (CARS), for use in the developmental evaluation of 5-year-old children, especially focusing on children with autistic features, and to verify its validity. Seventy-six children were studied. The children were recruited among participants of the Japan Children's Cohort Study, a research program implemented by the Research Institute of Science and Technology for Society (RISTEX) from 2004 to 2009. The developmental evaluation procedure was performed by doctors, clinical psychologists, and public health nurses. The COS-5 was also partly based on the Kyoto Scale of Psychological Development 2001 (Kyoto Scale 2001). Further, the Developmental Disorders Screening Questionnaire for 5-Years-Olds, PDD-Autism Society Japan Rating Scale (PARS), doctor interview questions and neurological examination for 5-year-old children, and the Draw-a-Man Test (DAM) were used as evaluation scales. Eighteen (25.4%) children were rated as Suspected, including Suspected PDD, Suspected ADHD and Suspected MR. The COS-5 was suggested to be valid with favorable reliability (α=0.89) and correlation with other evaluation scales. The COS-5 may be useful, with the following advantages: it can be performed within a shorter time frame; it facilitates the maintenance of observation quality; it facilitates sharing information with other professions; and it is reliable to identify the autistic features of 5-year-old children. In order to verify its wider applications including the screening of infants (18months to 3years old) by adjusting the items of younger age, additional study is needed. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  3. Australian children with cleft palate achieve age-appropriate speech by 5 years of age.

    Science.gov (United States)

    Chacon, Antonia; Parkin, Melissa; Broome, Kate; Purcell, Alison

    2017-12-01

    Children with cleft palate demonstrate atypical speech sound development, which can influence their intelligibility, literacy and learning. There is limited documentation regarding how speech sound errors change over time in cleft palate speech and the effect that these errors have upon mono-versus polysyllabic word production. The objective of this study was to examine the phonetic and phonological speech skills of children with cleft palate at ages 3 and 5. A cross-sectional observational design was used. Eligible participants were aged 3 or 5 years with a repaired cleft palate. The Diagnostic Evaluation of Articulation and Phonology (DEAP) Articulation subtest and a non-standardised list of mono- and polysyllabic words were administered once for each child. The Profile of Phonology (PROPH) was used to analyse each child's speech. N = 51 children with cleft palate participated in the study. Three-year-old children with cleft palate produced significantly more speech errors than their typically-developing peers, but no difference was apparent at 5 years. The 5-year-olds demonstrated greater phonetic and phonological accuracy than the 3-year-old children. Polysyllabic words were more affected by errors than monosyllables in the 3-year-old group only. Children with cleft palate are prone to phonetic and phonological speech errors in their preschool years. Most of these speech errors approximate typically-developing children by 5 years. At 3 years, word shape has an influence upon phonological speech accuracy. Speech pathology intervention is indicated to support the intelligibility of these children from their earliest stages of development. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Intraindividual variability in reaction time predicts cognitive outcomes 5 years later.

    Science.gov (United States)

    Bielak, Allison A M; Hultsch, David F; Strauss, Esther; Macdonald, Stuart W S; Hunter, Michael A

    2010-11-01

    Building on results suggesting that intraindividual variability in reaction time (inconsistency) is highly sensitive to even subtle changes in cognitive ability, this study addressed the capacity of inconsistency to predict change in cognitive status (i.e., cognitive impairment, no dementia [CIND] classification) and attrition 5 years later. Two hundred twelve community-dwelling older adults, initially aged 64-92 years, remained in the study after 5 years. Inconsistency was calculated from baseline reaction time performance. Participants were assigned to groups on the basis of their fluctuations in CIND classification over time. Logistic and Cox regressions were used. Baseline inconsistency significantly distinguished among those who remained or transitioned into CIND over the 5 years and those who were consistently intact (e.g., stable intact vs. stable CIND, Wald (1) = 7.91, p < .01, Exp(β) = 1.49). Average level of inconsistency over time was also predictive of study attrition, for example, Wald (1) = 11.31, p < .01, Exp(β) = 1.24. For both outcomes, greater inconsistency was associated with a greater likelihood of being in a maladaptive group 5 years later. Variability based on moderately cognitively challenging tasks appeared to be particularly sensitive to longitudinal changes in cognitive ability. Mean rate of responding was a comparable predictor of change in most instances, but individuals were at greater relative risk of being in a maladaptive outcome group if they were more inconsistent rather than if they were slower in responding. Implications for the potential utility of intraindividual variability in reaction time as an early marker of cognitive decline are discussed. (c) 2010 APA, all rights reserved

  5. Thinning cherry-maple stands in West Virginia: 5-year results

    Science.gov (United States)

    Neil I. Lamson; H. Clay. Smith; H. Clay. Smith

    1988-01-01

    In northern West Virginia, 60-year-old cherry-maple stands were thinned to 75,60, and 45 percent relative stand density. Analysis of 5-year growth data showed that basal-area growth was not reduced by thinning. Cubic-foot and board-foot volume growth decreased slightly. Individual-tree growth of all trees, dominant/codominant trees, and the 50 largest diameter trees...

  6. Low antibiotic resistance among anaerobic Gram-negative bacteria in periodontitis 5 years following metronidazole therapy.

    Science.gov (United States)

    Dahlen, G; Preus, H R

    2017-02-01

    The objective of this study was to assess antibiotic susceptibility among predominant Gram-negative anaerobic bacteria isolated from periodontitis patients who 5 years prior had been subject to mechanical therapy with or without adjunctive metronidazole. One pooled sample was taken from the 5 deepest sites of each of 161 patients that completed the 5 year follow-up after therapy. The samples were analyzed by culture. A total number of 85 anaerobic strains were isolated from the predominant subgingival flora of 65/161 patient samples, identified, and tested for antibiotic susceptibility by MIC determination. E-tests against metronidazole, penicillin, amoxicillin, amoxicillin + clavulanic acid and clindamycin were employed. The 73/85 strains were Gram-negative rods (21 Porphyromonas spp., 22 Prevotella/Bacteroides spp., 23 Fusobacterium/Filifactor spp., 3 Campylobacter spp. and 4 Tannerella forsythia). These were all isolated from the treated patients irrespective of therapy procedures (+/-metronidazole) 5 years prior. Three strains (Bifidobacterium spp., Propionibacterium propionicum, Parvimonas micra) showed MIC values for metronidazole over the European Committee on Antimicrobial Susceptibility Testing break point of >4 μg/mL. All Porphyromonas and Tannerella strains were highly susceptible. Metronidazole resistant Gram-negative strains were not found, while a few showed resistance against beta-lactam antibiotics. In this population of 161 patients who had been subject to mechanical periodontal therapy with or without adjunct metronidazole 5 years prior, no cultivable antibiotic resistant anaerobes were found in the predominant subgingival microbiota. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Influence of subject-role games on interpersonal communication of 4–5 yeared children

    Directory of Open Access Journals (Sweden)

    Liudmyla Matsuk

    2017-03-01

    Full Text Available The article describes the impact of subject-role games on interpersonal communicationof 4–5-yeared children. It is outlined that need to communicate forms intensively in preschoolyears. Accordingly learning efficiency increases when the child is in conditions close to real.In preschool childhood it is a play activity, which is built with support on the motivationalsphere of children’s personality.Key words: game, game activity, speech culture, communication, interpersonalcommunication, subject-role game.

  8. Orthodontic Treatment of Binder Syndrome: A Case Report With 5 Years of Follow-up.

    Science.gov (United States)

    Cossellu, Gianguido; Biagi, Roberto; Faggioni, Giulia; Farronato, Giampietro

    2015-07-01

    We report here the case of orthodontic nonsurgical treatment in a patient with Binder syndrome. This rare syndrome (orthodontic-surgical protocol, which includes several invasive interventions such as LeFort I or II. In this patient and early diagnosis made it possible to intervene on an orthodontic level only, thus avoiding highly invasive surgical procedures (as of a 5-year follow-up).

  9. Cognitive impairment at age 5 years in very preterm infants born following premature rupture of membranes.

    Science.gov (United States)

    Mura, Thibault; Picaud, Jean-Charles; Larroque, Béatrice; Galtier, Florence; Marret, Stephane; Roze, Jean-Christophe; Truffert, Patrick; Kuhn, Pierre; Fresson, Jeanne; Thiriez, Gérard; Arnaud, Catherine; Mercier, Gregoire; Picot, Marie-Christine; Ancel, Pierre-Yves; Ledesert, Bernard

    2013-08-01

    To evaluate the relationship between preterm premature rupture of membranes (PPROM) and cognitive impairment in 5-year-old children born very preterm. The Etude Epidémiologique sur les Petits Ages Gestationnels Study is a population-based cohort of children followed up from birth to age 5 years recruited in 9 French regions in 1997. We analyzed data from singletons born between 24 and 32 weeks gestation categorized into 4 groups according to etiology of prematurity: infants born after PPROM, after idiopathic preterm labor, in a vascular context (Vasc), and to women with other complications (Other). Cognitive development at age 5 years was assessed using the Mental Processing Composite score of the Kaufman-Assessment Battery for Children. Among the 1051 children followed up to age 5 years, the mean Mental Processing Composite score was 93.6 ± 19.7, and 13.3% of the children (140 of 1051) had cognitive impairment. After adjustment for potential confounders, the risk of cognitive impairment among infants in the PPROM group was not significantly different than that in the idiopathic preterm labor group (OR, 1.09; 95% CI, 0.62-1.92) and the Other group (OR, 1.36; 95% CI, 0.75-2.47), but was lower than that in the Vasc group (OR, 1.86; 95% CI, 1.16-2.97). In the PPROM group, the risk of cognitive impairment was greater when the latency period (ie, time from rupture to delivery) was <3 days (OR, 2.32; 95% CI, 1.07-5.02). Preterm infants born after PPROM are not at increased risk for cognitive impairment in childhood, but the time between PPROM and birth may influence that risk. Copyright © 2013 Mosby, Inc. All rights reserved.

  10. Learn from the burn: The High Park Fire 5 years later

    Science.gov (United States)

    Sue Miller; Charles Rhodes; Pete Robichaud; Sandra Ryan; Jen Kovecses; Carl Chambers; Sara Rathburn; Jared Heath; Stephanie Kampf; Codie Wilson; Dan Brogan; Brad Piehl; Mary Ellen Miller; John Giordanengo; Erin Berryman; Monique Rocca

    2017-01-01

    It has been 5 years since the High Park Fire burned over 85,000 acres in Northern Colorado, causing extensive property damage, loss of life, and severe impacts to the water quality of the Poudre River. In the fall of 2016, a conference was organized by the USFS Rocky Mountain Research Station and the Coalition for the Poudre River Watershed to discuss what has been...

  11. Community-wide intervention and population-level physical activity: a 5-year cluster randomized trial

    Science.gov (United States)

    Kamada, Masamitsu; Kitayuguchi, Jun; Abe, Takafumi; Taguri, Masataka; Inoue, Shigeru; Ishikawa, Yoshiki; Bauman, Adrian; Lee, I-Min; Miyachi, Motohiko; Kawachi, Ichiro

    2018-01-01

    Abstract Background Evidence from a limited number of short-term trials indicates the difficulty in achieving population-level improvements in physical activity (PA) through community-wide interventions (CWIs). We sought to evaluate the effectiveness of a 5-year CWI for promoting PA in middle-aged and older adults using a cluster randomized design. Methods We randomized 12 communities in Unnan, Japan, to either intervention (9) or control (3). Additionally, intervention communities were randomly allocated to three subgroups by different PA types promoted. Randomly sampled residents aged 40–79 years responded to the baseline survey (n = 4414; 74%) and were followed at 1, 3 and 5 years (78–83% response rate). The intervention was a 5-year CWI using social marketing to promote PA. The primary outcome was a change in recommended levels of PA. Results Compared with control communities, adults achieving recommended levels of PA increased in intervention communities [adjusted change difference = 4.6 percentage points (95% confidence interval: 0.4, 8.8)]. The intervention was effective for promoting all types of recommended PAs, i.e. aerobic (walking, 6.4%), flexibility (6.1%) and muscle-strengthening activities (5.7%). However, a bundled approach, which attempted to promote all forms of PAs above simultaneously, was not effective (1.3–3.4%, P ≥ 0.138). Linear dose–response relationships between the CWI awareness and changes in PA were observed (P ≤ 0.02). Pain intensity decreased in shoulder (intervention and control) and lower back (intervention only) but there was little change difference in all musculoskeletal pain outcomes between the groups. Conclusions The 5-year CWI using the focused social marketing strategy increased the population-level of PA. PMID:29228255

  12. Equatorial annual oscillation with QBO-driven 5-year modulation in NCEP data

    Directory of Open Access Journals (Sweden)

    H. G. Mayr

    2007-02-01

    Full Text Available An analysis is presented of the stratospheric zonal wind and temperature variations supplied by the National Center for Environmental Prediction (NCEP. The derived zonal-mean variations are employed. Stimulated by modeling studies, the data are separated into the hemispherically symmetric and anti-symmetric components, and spectral analysis is applied to study the 12-month annual oscillation (AO and the quasi-biennial oscillation (QBO. For data samples that cover as much as 40 years, the zonal wind results reveal a pronounced 5-year modulation of the symmetric AO in the lower stratosphere, which is confined to equatorial latitudes. This modulation is also seen in the temperature variations but extends to high latitudes, qualitatively consistent with published model results. A comparison between different time intervals of the data indicates that the signature of the 5-year oscillation is larger when the QBO of 30 months is more pronounced. Thus there is circumstantial evidence that this particular QBO period is involved in generating the oscillation as was shown in a modeling study (Mayr et al., 2000. In agreement with the model, the spectral analysis also reveals a weak anti-symmetric 5-year oscillation in the zonal wind data, which could interact with the strong anti-symmetric AO to produce the modulation of the symmetric AO. The 30-month QBO is well suited to be synchronized by, and phase-locked to, the equatorial semi-annual oscillation (SAO, and this may explain why this QBO periodicity and its 5-year spin-off are observed to persist for many cycles.

  13. Equatorial Annual Oscillation with QBO-driven 5-year Modulation in NCEP Data

    Science.gov (United States)

    Mayr, H. G.; Mengel, J. G.; Huang, F. T.; Nash, E. R.

    2007-01-01

    An analysis is presented of the zonal wind and temperature variations supplied by the National Center for Environmental Prediction (NCEP), which have been assimilated in the Reanalysis and the Climate Prediction Center (CCP) data sets. The derived zonal-mean variations are employed. Stimulated by modeling studies, the data are separated into the hemispherically symmetric and anti-symmetric components, and spectral analysis is applied to study the annual 12-month oscillation and Quasi-biennial Oscillation (QBO). For data samples that cover as much as 40 years, the results reveal a pronounced 5-year modulation of the symmetric AO in the lower stratosphere, which is confined to equatorial latitudes. This modulation is also inferred for the temperature variations but extends to high latitudes, qualitatively consistent with published model results. A comparison between different data samples indicates that the signature of the 5-year oscillation is larger when the QBO of 30 months is more pronounced. Thus there is circumstantial evidence that this periodicity of the QBO is involved in generating the oscillation. The spectral analysis shows that there is a weak anti-symmetric 5-year oscillation in the zonal winds, which could interact with the large antisymmetric A0 to produce the modulation of the symmetric AO as was shown in earlier modeling studies. According to these studies, the 30-month QBO tends to be synchronized by the equatorial Semi-annual Oscillation (SAO), and this would explain why the inferred 5-year modulation is observed to persist and is phase locked over several cycles.

  14. Childhood leukaemia incidence below the age of 5 years near French nuclear power plants

    International Nuclear Information System (INIS)

    Laurier, D; Hemon, D; Clavel, J

    2008-01-01

    A recent study indicated an excess risk of leukaemia among children under the age of 5 years living in the vicinity of nuclear power plants in Germany. We present results relating to the incidence of childhood leukaemia in the vicinity of nuclear power plants in France for the same age range. These results do not indicate an excess risk of leukaemia in young children living near French nuclear power plants. (note)

  15. Antenatal and postnatal growth and 5-year cognitive outcome in very preterm infants.

    Science.gov (United States)

    Leppänen, Marika; Lapinleimu, Helena; Lind, Annika; Matomäki, Jaakko; Lehtonen, Liisa; Haataja, Leena; Rautava, Päivi

    2014-01-01

    To study how antenatal growth affects cognitive outcome in very preterm infants and to determine whether there is an association between growth in any particular time period between birth and 5 years of age and cognitive outcome. Small for gestational age (SGA) and non-SGA infants were analyzed separately, because antenatal growth may affect postnatal growth. Very low birth weight (growth was determined as a z score change between measurement points. Cognitive development was assessed at 5 years of age with the Wechsler Preschool and Primary Scales of Intelligence-Revised. The association between growth and full-scale IQ (FSIQ) was studied. Growth in length and height was not associated with 5-year cognitive outcome. However, weight (r = 0.18, P = .04) and HC growth (r = 0.25, P = .01) between birth and 2 years of corrected age correlated to FSIQ in non-SGA children. In SGA children, HC growth (r = 0.33, P = .03) around term age correlated to FSIQ. Cognitive outcome was similar in SGA and non-SGA very preterm infants. Growth affected cognition positively in both subgroups, but the critical time period was different.

  16. Juvenile osteochondritis dissecans: a 5-year review of the natural history using clinical and MRI evaluation

    International Nuclear Information System (INIS)

    Hughes, Jacqueline A.; Cook, Jane V.; Warren, Mary E.; Churchill, Mark A.

    2003-01-01

    Although MRI prognostic features for juvenile osteochondritis dissecans (JOCD) have been determined, the natural history of JOCD on serial MRI has not been fully documented. To document the natural history of JOCD on serial MRI and to correlate this with arthroscopy and clinical outcome over a 5-year follow-up. Twenty-one knees in 19 patients (15 boys, 4 girls; age range 5-15 years) with JOCD underwent MRI and clinical follow-up over 5 years. Lesions were classified as stable or unstable on MRI and compared with clinical and arthroscopic data. On 5-year follow-up, 17 of 19 patients were asymptomatic and 2 of 19 had minimal pain. Fourteen arthroscopies were performed on 11/21 knees. One of twenty-one had fragment fixation. On initial MRI, eight knees had marked fragmentation, high signal at the fragment/bone interface and incomplete defects in the hyaline cartilage (MRI stage III-stable), but no tear. Of these, five had arthroscopy, all confirming intact cartilage. One of twenty-one knees was unstable (MRI stage IVb) with a detached osteochondral fragment, requiring surgery. Despite extensive subchondral bone changes on MRI, all cases with intact cartilage (95%) improved with conservative treatment. Early MRI allows prompt diagnosis and institution of conservative treatment. This results in healing and avoidance of surgery in most patients. (orig.)

  17. Life prolongation and 5-year survival by intensive irradiation of inoperable lung cancer

    International Nuclear Information System (INIS)

    Eichhorn, H.-J.

    1982-01-01

    The effect of intensive radiotherapy on 1-5 year survival rates of patients with inoperable lung cancer is investigated. Some 123 cases were treated with 200 kV X-rays (> 3500 cGy tumour dose) and 1046 with cobalt-60 ν-rays (> 5000 cGy tumour dose). All patients had inoperable, histologically confirmed tumours, limited to one side of the thorax. Survival rates for 1 year were 22% and 37% respectively; for 3 years 1% and 5%; and for 5 years 0 and 2.5%. In all highly differentiated tumours the authors obtained a 5-year survival with telecobalt therapy of 6.5%, and for all oat-cell cases, 2.5%. By comparing the total result with their own control group of 'untreated', but prognostically more favourable patients (122 thoracotomized cases without resection) the increase of survival rates achieved by Cobalt-60 therapy is convincing (2.5 times for 1 year, 5 times for 2 years). Nevertheless, the very unfavourable prognosis for more than half of the cases justifies trials with systemic therapy. To date chemotherapy does not appear to influence survival times (except for small-cell tumours). Therefore randomized trials with two half-body irradiations (800 cGy each, 'Toronto method') are recommended. (Auth.)

  18. Progressive Tinnitus Management Level 3 Skills Education: A 5-Year Clinical Retrospective.

    Science.gov (United States)

    Edmonds, Catherine M; Ribbe, Cheri; Thielman, Emily J; Henry, James A

    2017-09-18

    The primary purpose of this study was to determine whether progressive tinnitus management Level 3 skills education workshops conducted at the Bay Pines and Boston Veterans Affairs hospitals result in consistent use of the presented tinnitus management strategies by patients 1-5 years after completing the workshops. In fiscal year (FY) 2015, the tinnitus workshop follow-up form was mailed to all veterans who completed the Level 3 workshops between FY 2010 and FY 2014. Data were compiled to determine which, if any, of the skills taught in the workshops were being used 1-5 years after completion of the workshops and the impact on quality-of-life indicators. All self-management skills were being utilized up to 5 years postcompletion; therapeutic sound was utilized the most. The majority of patients reported an improved ability to manage reactions to tinnitus and improved quality-of-life indicators. Over 90% of patients from both sites recommended the program to others with tinnitus. The self-management skills taught in the progressive tinnitus management Level 3 workshops are sustained over time even when limited resources prevent the full complement of workshops or the involvement of mental health services. The workshops can also be successfully implemented through remote delivery via videoconferencing (telehealth). https://doi.org/10.23641/asha.5370883.

  19. The prevalence of dental erosion in 5-year-old preschoolers in Sharjah, United Arab Emirates.

    Science.gov (United States)

    Gopinath, Vellore Kannan

    2016-01-01

    The aim of this study was to determine the percentage of 5-year-old preschoolers in Sharjah, affected by dental erosion and to assess the predictors. A total of 403 5-year-old children were examined of which 48.14% (n = 194) were boys and 51.86% (n = 209) were girls; 31.27% (n = 126) were Emirati and 68.73% (n = 277) were non-Emirati Arabs. Examination of dental erosion was confined to palatal surfaces of maxillary incisors using the erosion index described in the UK National Survey of Children's Dental Health, 1993. Dental caries was charted using the World Health Organization 1997 criteria. In the sample of 403 5-year-old preschoolers examined, dental erosion was apparent in 237 (58.80%) children, with 55.09% showing the dissolution of enamel and 3.72% exhibiting exposed dentin. Predictors of dental erosion as determined by logistic regression concluded that compared to Emirati citizens other Arab nationalities have 0.27 times the odds (95% confidence interval [CI] =0.18-0.42) of having tooth erosion (P United Arab Emirates, were affected by dental erosion. Caries experience and consumption of acidic drinks were associated with dental erosion.

  20. HIV Rapid Testing in a VA Emergency Department Setting: Cost Analysis at 5 Years.

    Science.gov (United States)

    Knapp, Herschel; Chan, Kee

    2015-07-01

    To conduct a comprehensive cost-minimization analysis to comprehend the financial attributes of the first 5 years of an implementation wherein emergency department (ED) registered nurses administered HIV oral rapid tests to patients. A health science research implementation team coordinated with ED stakeholders and staff to provide training, implementation guidelines, and support to launch ED registered nurse-administered HIV oral rapid testing. Deidentified quantitative data were gathered from the electronic medical records detailing quarterly HIV rapid test rates in the ED setting spanning the first 5 years. Comprehensive cost analyses were conducted to evaluate the financial impact of this implementation. At 5 years, a total of 2,620 tests were conducted with a quarterly mean of 131 ± 81. Despite quarterly variability in testing rates, regression analysis revealed an average increase of 3.58 tests per quarter. Over the course of this implementation, Veterans Health Administration policy transitioned from written to verbal consent for HIV testing, serving to reduce the time and cost(s) associated with the testing process. Our data indicated salient health outcome benefits for patients with respect to the potential for earlier detection, and associated long-run cost savings. Copyright © 2015. Published by Elsevier Inc.

  1. Long-term life and partnership satisfaction in infertile patients: a 5-year longitudinal study.

    Science.gov (United States)

    Schanz, Stefan; Reimer, Thorisa; Eichner, Martin; Hautzinger, Martin; Häfner, Hans-Martin; Fierlbeck, Gerhard

    2011-08-01

    To describe the long-term effects of infertility on life and partnership satisfaction. Longitudinal cohort study. A university outpatient andrology and gynecology infertility clinic. 275 men and 272 women treated for infertility between August 2000 and December 2001. None. The Life Satisfaction Questionnaire (FLZ), the Partnership Questionnaire (PFB), and sociodemographic items at baseline (T1) and 5 years later (T2). Compared with a representative sample, our male and female participants had higher Finance and Partnership scores and lower Health scores on the FLZ at T1. They also had markedly higher PFB scores, with the exception of Conflict Behavior. After 5 years (T2), 101 men and 113 women rated the Partnership and Sexuality FLZ subscales as well as all the PFB subscales statistically significantly lower than at baseline. Only the women rated the Self-esteem FLZ subscale lower than at baseline (T1). Participants who became parents had lower Leisure and Partnership FLZ subscale scores, and fathers had lower Finance FLZ subscale scores. Satisfaction declined over 5 years for both men and women, but only in the partnership-related domains. Women were more affected than men. The success of infertility treatment had only a minor influence on a couple's future satisfaction. Copyright © 2011. Published by Elsevier Inc.

  2. Impact of functional determinants on 5.5-year mortality in Amazon riparian elderly

    Directory of Open Access Journals (Sweden)

    Tiago C. Antonini

    Full Text Available ABSTRACT Objective To ascertain whether modifiable physical performance–based measurements predicted 5.5-year mortality in a riparian elderly cohort in the Amazon rainforest region. Methods A longitudinal study evaluating the impact of functional determinants on 5.5-year mortality in a riparian elderly cohort from Maués City in the state of Amazonas, Brazil, was performed. The study was a follow-up of a previous observational investigation that evaluated various fitness tests in 630 Amazonian riparian elderly (291 males and 339 females aged 72.3 ± 8.0 (60–99 years old. The cohort was selected for its adverse environmental conditions, which increased the risk of falls yet required maintenance of good physical condition for carrying out relatively rigorous daily activities, and restricted access to specialized health services. Official death records were obtained from the Maués Municipal Health Department. Results A total of 80 study participants (12.7% died over the 5.5-year study period. Kaplan-Meier regression analysis showed significant association between Timed Up and Go (TUG test scores ≥ 14 seconds and mortality risk, independent of sex, age, and other health variables. Conclusions The study results suggest that the TUG test can be used as an indicator for initiating therapeutic and preventive actions, including conducting exercises or physical activities adapted to the health and functional conditions of the elderly, by identifying elderly people with a higher relative risk of mortality.

  3. Outcome and Prognostic Factors for Traumatic Endophthalmitis over a 5-Year Period

    Directory of Open Access Journals (Sweden)

    Simona Delia Nicoară

    2014-01-01

    Full Text Available Purpose. To evaluate the outcome and identify the prognostic factors of traumatic endophthalmitis over a 5-year period. Methods. We reviewed the medical records of all the traumatic endophthalmities that we treated in our department over the last 5 years (2009–2013. We extracted the following parameters: age, gender, wound anatomy, associated ocular lesions, treatment, and initial and final visual acuities. We used the program SPSS version 20.0.0. for the statistical analysis of our data. Results. During the last 5 years, we treated 14 traumatic endophthalmities, representing 46.66% of all types of endophthalmities. The infection rate in open globe injuries was 8.13% and 34.78%, if an intraocular foreign body (IOFB was associated. All the patients were males with the median age of 37 years. Initial visual acuities varied between light perception and 0.4 and the timing of treatment from a few hours to 10 days. We administered antibiotic and anti-inflammatory drugs, systemically and intravitreally, in all cases. We performed pars plana vitrectomy in 64.28% of cases. In 57.14% of cases, the final visual acuity was 0.1 or more. Conclusions. IOFBs increased significantly the risk for endophthalmitis. The worse prognostic factors were retinal detachment at presentation and delayed treatment. This trial is registered with IRCT2014082918966N1.

  4. Shigella infection in children under 5 years old in western French Guiana.

    Science.gov (United States)

    Parisot, M; Parez, N; Boukhari, R; Breurec, S; Jolivet, A

    2018-04-15

    French Guiana, a tropical country, is characterised by a young and multi-ethnic population. Difficulties in accessing safe water sources lead to outbreaks of gastroenteritis. The objectives of this study were (1) to describe the microbiological profile of shigella strains isolated in western French Guiana, including antimicrobial susceptibility and the distribution of strains in terms of species and serotypes and (2) to estimate the incidence of shigellosis in children under 5 years old. A retrospective observational study was conducted of 213 cases of shigellosis diagnosed in the biology department of the hospital centre for western French Guiana between 2000 and 2012 in children under 5 years old. The serogroups (formerly known as species) that predominates in French Guiana was Shigella flexneri. No resistance was observed to fluoroquinolones or to third-generation cephalosporins. The average incidence of shigellosis in children under 5 years old in western French Guiana was estimated at 189.6 cases per 100 000 inhabitants per year. Shigellosis is a public health problem in western French Guiana. These infections suggest the difficulties in accessing safe water sources and the lack of public sanitation. A quadrivalent vaccine containing Shigella sonnei and three serotypes of S. flexneri (S. flexneri 2a, 3a and 6) could provide broad coverage against shigella infections.

  5. Gross Motor Development in Children Aged 3-5 Years, United States 2012.

    Science.gov (United States)

    Kit, Brian K; Akinbami, Lara J; Isfahani, Neda Sarafrazi; Ulrich, Dale A

    2017-07-01

    Objective Gross motor development in early childhood is important in fostering greater interaction with the environment. The purpose of this study is to describe gross motor skills among US children aged 3-5 years using the Test of Gross Motor Development (TGMD-2). Methods We used 2012 NHANES National Youth Fitness Survey (NNYFS) data, which included TGMD-2 scores obtained according to an established protocol. Outcome measures included locomotor and object control raw and age-standardized scores. Means and standard errors were calculated for demographic and weight status with SUDAAN using sample weights to calculate nationally representative estimates, and survey design variables to account for the complex sampling methods. Results The sample included 339 children aged 3-5 years. As expected, locomotor and object control raw scores increased with age. Overall mean standardized scores for locomotor and object control were similar to the mean value previously determined using a normative sample. Girls had a higher mean locomotor, but not mean object control, standardized score than boys (p  0.05). Conclusions In a nationally representative sample of US children aged 3-5 years, TGMD-2 mean locomotor and object control standardized scores were similar to the established mean. These results suggest that standardized gross motor development among young children generally did not differ by demographic or weight status.

  6. Juvenile osteochondritis dissecans: a 5-year review of the natural history using clinical and MRI evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, Jacqueline A.; Cook, Jane V.; Warren, Mary E. [Radiology Department, Queen Mary' s Hospital for Children, Epsom and St Helier NHS Trust, Carshalton, Surrey SM5 1AA (United Kingdom); Churchill, Mark A. [Orthopaedic Department, Queen Mary' s Hospital for Children, Epsom and St Helier NHS Trust, Carshalton (United Kingdom)

    2003-06-01

    Although MRI prognostic features for juvenile osteochondritis dissecans (JOCD) have been determined, the natural history of JOCD on serial MRI has not been fully documented. To document the natural history of JOCD on serial MRI and to correlate this with arthroscopy and clinical outcome over a 5-year follow-up. Twenty-one knees in 19 patients (15 boys, 4 girls; age range 5-15 years) with JOCD underwent MRI and clinical follow-up over 5 years. Lesions were classified as stable or unstable on MRI and compared with clinical and arthroscopic data. On 5-year follow-up, 17 of 19 patients were asymptomatic and 2 of 19 had minimal pain. Fourteen arthroscopies were performed on 11/21 knees. One of twenty-one had fragment fixation. On initial MRI, eight knees had marked fragmentation, high signal at the fragment/bone interface and incomplete defects in the hyaline cartilage (MRI stage III-stable), but no tear. Of these, five had arthroscopy, all confirming intact cartilage. One of twenty-one knees was unstable (MRI stage IVb) with a detached osteochondral fragment, requiring surgery. Despite extensive subchondral bone changes on MRI, all cases with intact cartilage (95%) improved with conservative treatment. Early MRI allows prompt diagnosis and institution of conservative treatment. This results in healing and avoidance of surgery in most patients. (orig.)

  7. Bilateral Macular Edema in a Patient Treated with Tamoxifen: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Paraskevas Zafeiropoulos

    2014-12-01

    Full Text Available We present a case of a 41-year-old female patient with progressive bilateral visual loss. On examination, her best corrected visual acuity (BCVA in her right eye was 3/10 and her BCVA in her left eye was 2/10. Fundus and optical coherence tomography examination revealed severe bilateral macular edema. She had been diagnosed with breast cancer 6 years ago and was receiving tamoxifen at a dosage of 20 mg/day ever since. Tamoxifen therapy was discontinued, and the patient received 250 mg of acetazolamide three times a day for a period of 1 month. Both foveae regained their normal contour within 2 months, and her vision was restored to 10/10 BCVA 3 months later. To our knowledge, this is the first case reported where bilateral intraretinal macular edema is the only retinal manifestation in a patient on oral tamoxifen.

  8. Bilateral macular edema in a patient treated with tamoxifen: a case report and review of the literature.

    Science.gov (United States)

    Zafeiropoulos, Paraskevas; Nanos, Panagiotis; Tsigkoulis, Evangelos; Stefaniotou, Maria

    2014-01-01

    We present a case of a 41-year-old female patient with progressive bilateral visual loss. On examination, her best corrected visual acuity (BCVA) in her right eye was 3/10 and her BCVA in her left eye was 2/10. Fundus and optical coherence tomography examination revealed severe bilateral macular edema. She had been diagnosed with breast cancer 6 years ago and was receiving tamoxifen at a dosage of 20 mg/day ever since. Tamoxifen therapy was discontinued, and the patient received 250 mg of acetazolamide three times a day for a period of 1 month. Both foveae regained their normal contour within 2 months, and her vision was restored to 10/10 BCVA 3 months later. To our knowledge, this is the first case reported where bilateral intraretinal macular edema is the only retinal manifestation in a patient on oral tamoxifen.

  9. Safety and efficacy of immediate postoperative feeding and bowel stimulation to prevent ileus after major gynecologic surgical procedures.

    Science.gov (United States)

    Fanning, James; Hojat, Rod

    2011-08-01

    Postoperative ileus is a major complication of abdominal surgical procedures To evaluate the incidence of ileus and gastrointestinal morbidity in patients who received immediate postoperative feeding and bowel stimulation after undergoing major gynecologic surgical procedures. During a 5-year period, the authors tracked demographic, surgical outcome, and follow-up information for 707 patients who underwent major gynecologic operations. All patients received the same postoperative orders, including immediate feeding of a diet of choice and bowel stimulation with 30 mL of magnesium hydroxide (milk of magnesia) twice daily until bowel movements occurred. Of 707 patients, 6 (<1%) had postoperative ileus. No patients experienced postoperative bowel obstruction and 2 patients (0.3%) had postoperative intestinal leak. No serious adverse effects associated with bowel stimulation were reported. Immediate postoperative feeding and bowel stimulation is a safe and effective approach to preventing ileus in patients who undergo major gynecologic surgical procedures.

  10. POSTOPERATIVE NAUSEA AND VOMITING | Yusufu | Annals of ...

    African Journals Online (AJOL)

    Antiemetics, acupuncture and other drugs are used to prevent and treat postoperative nausea and vomiting. Those that manage patients in the postoperative period should endeavour to make postoperative nausea and vomiting as unacceptable as postoperative pain. Key words: Postoperative, Nausea, Vomiting, Narcotics, ...

  11. Development of the Intrinsic Language Network in Preschool Children from Ages 3 to 5 Years.

    Science.gov (United States)

    Xiao, Yaqiong; Brauer, Jens; Lauckner, Mark; Zhai, Hongchang; Jia, Fucang; Margulies, Daniel S; Friederici, Angela D

    2016-01-01

    Resting state studies of spontaneous fluctuations in the functional magnetic resonance imaging (fMRI) blood oxygen level dependent signal have shown great potential in mapping the intrinsic functional connectivity of the human brain underlying cognitive functions. The aim of the present study was to explore the developmental changes in functional networks of the developing human brain exemplified with the language network in typically developing preschool children. To this end, resting-sate fMRI data were obtained from native Chinese children at ages of 3 and 5 years, 15 in each age group. Resting-state functional connectivity (RSFC) was analyzed for four regions of interest; these are the left and right anterior superior temporal gyrus (aSTG), left posterior superior temporal gyrus (pSTG), and left inferior frontal gyrus (IFG). The comparison of these RSFC maps between 3- and 5-year-olds revealed that RSFC decreases in the right aSTG and increases in the left hemisphere between aSTG seed and IFG, between pSTG seed and IFG, as well as between IFG seed and posterior superior temporal sulcus. In a subsequent analysis, functional asymmetry of the language network seeding in aSTG, pSTG and IFG was further investigated. The results showed an increase of left lateralization in both RSFC of pSTG and of IFG from ages 3 to 5 years. The IFG showed a leftward lateralized trend in 3-year-olds, while pSTG demonstrated rightward asymmetry in 5-year-olds. These findings suggest clear developmental trajectories of the language network between 3- and 5-year-olds revealed as a function of age, characterized by increasing long-range connections and dynamic hemispheric lateralization with age. Our study provides new insights into the developmental changes of a well-established functional network in young children and also offers a basis for future cross-culture and cross-age studies of the resting-state language network.

  12. Development of the Intrinsic Language Network in Preschool Children from Ages 3 to 5 Years.

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    Yaqiong Xiao

    Full Text Available Resting state studies of spontaneous fluctuations in the functional magnetic resonance imaging (fMRI blood oxygen level dependent signal have shown great potential in mapping the intrinsic functional connectivity of the human brain underlying cognitive functions. The aim of the present study was to explore the developmental changes in functional networks of the developing human brain exemplified with the language network in typically developing preschool children. To this end, resting-sate fMRI data were obtained from native Chinese children at ages of 3 and 5 years, 15 in each age group. Resting-state functional connectivity (RSFC was analyzed for four regions of interest; these are the left and right anterior superior temporal gyrus (aSTG, left posterior superior temporal gyrus (pSTG, and left inferior frontal gyrus (IFG. The comparison of these RSFC maps between 3- and 5-year-olds revealed that RSFC decreases in the right aSTG and increases in the left hemisphere between aSTG seed and IFG, between pSTG seed and IFG, as well as between IFG seed and posterior superior temporal sulcus. In a subsequent analysis, functional asymmetry of the language network seeding in aSTG, pSTG and IFG was further investigated. The results showed an increase of left lateralization in both RSFC of pSTG and of IFG from ages 3 to 5 years. The IFG showed a leftward lateralized trend in 3-year-olds, while pSTG demonstrated rightward asymmetry in 5-year-olds. These findings suggest clear developmental trajectories of the language network between 3- and 5-year-olds revealed as a function of age, characterized by increasing long-range connections and dynamic hemispheric lateralization with age. Our study provides new insights into the developmental changes of a well-established functional network in young children and also offers a basis for future cross-culture and cross-age studies of the resting-state language network.

  13. Phase I Clinical Trial Assessing Temozolomide and Tamoxifen With Concomitant Radiotherapy for Treatment of High-Grade Glioma

    International Nuclear Information System (INIS)

    Patel, Shilpen; DiBiase, Steven; Meisenberg, Barry; Flannery, Todd; Patel, Ashish; Dhople, Anil; Cheston, Sally; Amin, Pradip

    2012-01-01

    Purpose: The new standard treatment of glioblastoma multiforme is concurrent radiotherapy (RT) and temozolomide. The proliferation of high-grade gliomas might be partly dependent on protein kinase C-mediated pathways. Tamoxifen has been shown in vitro to inhibit protein kinase C through estrogen receptor-independent antineoplastic effects. This Phase I trial was designed to determine the maximal tolerated dose (MTD) of tamoxifen when given with temozolomide and concurrent RT to patients with high-grade gliomas. Methods and Materials: A total of 17 consecutive patients in four cohorts with World Health Organization Grade 3 (n = 2) and 4 (n = 15) gliomas were given tamoxifen twice daily during 6 weeks of concurrent RT and temozolomide. Eligibility included histologic diagnosis, age >18 years old, Karnofsky performance status ≥60, and no previous brain RT or chemotherapy. The starting dose was 50 mg/m 2 divided twice daily. If no dose-limiting toxicities (DLTs) occurred in 3 patients, the dose was escalated in 25-mg/m 2 increments until the MTD was reached. When ≥2 patients within a cohort experienced a DLT, the MTD had been exceeded. Temozolomide was given with RT at 75 mg/m 2 . A dose of 60 Gy in 2 Gy/d fractions to a partial brain field was delivered. Results: A total of 6 patients in Cohort 4 had received tamoxifen at 125 mg/m 2 . One patient was excluded, and the fourth patient developed Grade 4 thrombocytopenia (DLT). Thus, 3 more patients needed to be enrolled. A deep venous thrombosis (DLT) occurred in the sixth patient. Thus, the MTD was 100 mg/m 2 . Conclusions: The MTD of tamoxifen was 100 mg/m 2 when given concurrently with temozolomide 75 mg/m 2 and RT. Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy.

  14. Clinical evidence on the magnitude of change in growth pathway activity in relation to Tamoxifen resistance is required.

    Science.gov (United States)

    Mansouri, Sepideh; Farahmand, Leila; Teymourzadeh, Azin; Majidzadeh-A, Keivan

    2017-08-08

    Despite prolonged disease-free survival and overall survival rates in estrogen receptor (ER)-positive patients undergoing adjuvant treatment, Tamoxifen therapy tends to fail due to eventual acquisition of resistance. Although numerous studies have emphasized the role of receptor tyrosine kinases (RTKs) in the development of Tamoxifen resistance, inadequate clinical evidence is available regarding the alteration of biomarker expression during acquired resistance, thus undermining the validity of the findings. Results of two meta-analyses investigating the effect of HER2 status on the prognosis of Tamoxifen-receiving patients have demonstrated that despite HER2-negative patients having longer disease-free survival; there is no difference in overhaul survival between the two groups. Furthermore, due to the intricate molecular interactions among estrogen receptors including ERα36, ERα66, and also RTKs, it is not surprising that RTK suppression does not restore Tamoxifen sensitivity. In considering such a complex network, we speculate that by the time HER2/EGFR is suppressed via targeted therapies, activation of ERα66 and ERα36 initiate molecular signaling pathways downstream of RTKs, thereby enhancing cell proliferation even in the presence of both Tamoxifen and RTK inhibitors. Although clinical findings regarding the molecular pathways downstream of RTKs have been thoroughly discussed in this review, further clinical studies are required in determining a consistency between preclinical and clinical findings. Discovering the best targets in preventing tumor progression requires thorough comprehension of estrogen-dependent and estrogen-independent pathways during Tamoxifen resistance development. Indeed, exploring additional clinically-proven targets would allow for better characterized treatments being available for breast cancer patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Toxicidade ocular causada pelo tamoxifeno: relato de caso Ocular toxicity caused by tamoxifen: case report

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    Eliane Terumi Inada

    2005-08-01

    Full Text Available O objetivo desse trabalho é relatar um caso de toxicidade ocular pelo tamoxifeno. Para isso, aferiu-se a melhor acuidade visual corrigida de ambos os olhos em tabela de Snellen. Foram realizados biomicroscopia do segmento anterior, refração, oftalmoscopia, angiofluoresceinografia e retinografia numa paciente de 63 anos, sexo feminino, cor branca, em uso de tamoxifeno 20 mg/dia há 4 anos, com acuidade visual corrigida de 20/70 e 20/40. A biomicroscopia do segmento anterior apresentava ceratopatia verticilata e catarata nuclear e cortical posterior de 1+/4 em ambos os olhos. À oftalmoscopia, foi verificado alteração do brilho macular de ambos os olhos. E a angiofluoresceinografia mostrou hiperfluorescência na área macular em fase precoce (defeito em janela. Relata-se um caso de ceratopatia e maculopatia causadas pelo tamoxifeno.To report tamoxifen ocular toxicity. The best visual acuity was measured in both eyes with Snellen chart, slit-lamp examination of anterior segment, refraction, dilated fundus examination, fluorescein angiography and retinography in a 63-year-old patient, female, white, using tamoxifen 20 mg/day for 4 years, with 20/70 and 20/40 corrected visual acuity. The anterior segment examination showed corneal linear subepithelial opacity inferior to the visual axis and nuclear and posterior cortical cataract (1+/4 in both eyes. Fundus examination showed alteration of macular color in both eyes. Fluorescein angiography presented hyperfluorescence in the macular area at an early phase (window defect. Report of keratopathy and maculopathy caused by tamoxifen.

  16. Transgenic mice for a tamoxifen-induced, conditional expression of the Cre recombinase in osteoclasts.

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    Maria Arantzazu Sanchez-Fernandez

    Full Text Available BACKGROUND: Studies on osteoclasts, the bone resorbing cells, have remained limited due to the lack of transgenic mice allowing the conditional knockout of genes in osteoclasts at any time during development or adulthood. METHODOLOGY/PRINCIPAL FINDING: We report here on the generation of transgenic mice which specifically express a tamoxifen-inducible Cre recombinase in osteoclasts. These mice, generated on C57BL/6 and FVB background, express a fusion Cre recombinase-ERT2 protein whose expression is driven by the promoter of cathepsin K (CtsK, a gene highly expressed in osteoclasts. We tested the cellular specificity of Cre activity in CtsKCreERT2 strains by breeding with Rosa26LacZ reporter mice. PCR and histological analyses of the CtsKCreERT2LacZ positive adult mice and E17.5 embryos show that Cre activity is restricted largely to bone tissue. In vitro, primary osteoclasts derived from the bone marrow of CtsKCreERT2+/-LacZ+/- adult mice show a Cre-dependent β-galactosidase activity after tamoxifen stimulation. CONCLUSIONS/SIGNIFICANCE: We have generated transgenic lines that enable the tamoxifen-induced, conditional deletion of loxP-flanked genes in osteoclasts, thus circumventing embryonic and postnatal gene lethality and avoiding gene deletion in other cell types. Such CtsKCreERT2 mice provide a convenient tool to study in vivo the different facets of osteoclast function in bone physiology during different developmental stages and adulthood of mice.

  17. The effects of soy and tamoxifen on apoptosis in the hippocampus and dentate gyrus in a pentylenetetrazole-induced seizure model of ovariectomized rats.

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    Ebrahimzadeh-Bideskan, Ali Reza; Mansouri, Somaieh; Ataei, Mariam Lale; Jahanshahi, Mehrdad; Hosseini, Mahmoud

    2018-03-01

    The effects of tamoxifen and soy on apoptosis of the hippocampus and dentate gyrus of ovariectomized rats after repeated seizures were investigated. Female rats were divided into: (1) Control, (2) Sham, (3) Sham-Tamoxifen (Sham-T), (4) Ovariectomized (OVX), (5) OVX-Tamoxifen (OVX-T), (6)OVX-Soy(OVX-S) and (7) OVX-S-T. The animals in the OVX-S, OVX-T and OVX-S-T groups received soy extract (60 mg/kg; i.p.), tamoxifen (10 mg/kg) or both for 2 weeks before induction of seizures. The animals in these groups additionally received the mentioned treatments before each injection of pentylenetetrazole (PTZ; 40 mg/kg) for 6 days. The animals in the Sham and OVX groups received a vehicle of tamoxifen and soy. A significant decrease in the seizure score and TUNEL-positive neurons was seen in the OVX group compared to the Sham (P < 0.001). The animals in both the OVX-T and OVX-S groups had a significantly higher seizure score as well as number of TUNEL-positive neurons compared to the OVX group (P < 0.01-P < 0.001). Co-treatment of the OVX rats by the extract and tamoxifen decreased the seizure score and number of TUNEL-positive neurons compared to OVX-S (P < 0.001). Treatment of the OVX rats by either soy or tamoxifen increased the seizure score as well as the number of TUNEL-positive neurons in the hippocampal formation. Co-administration of tamoxifen and soy extract inhibited the effects of the soy extract and tamoxifen when they were administered alone. It might be suggested that both soy and tamoxifen have agonistic effects on estrogen receptors by changing the seizure severity.

  18. Tamoxifen therapy improves overall survival in luminal A subtype of ductal carcinoma in situ: a study based on nationwide Korean Breast Cancer Registry database.

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    Hwang, Ki-Tae; Kim, Eun-Kyu; Jung, Sung Hoo; Lee, Eun Sook; Kim, Seung Il; Lee, Seokwon; Park, Heung Kyu; Kim, Jongjin; Oh, Sohee; Kim, Young A

    2018-06-01

    To determine the prognostic role of tamoxifen therapy for patients with ductal carcinoma in situ (DCIS) according to molecular subtypes. Data of 14,944 patients with DCIS were analyzed. Molecular subtypes were classified into four categories based on expression of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Kaplan-Meier estimator was used for overall survival analysis while Cox proportional hazards model was used for univariate and multivariate analyses. Luminal A subtype (ER/PR+, HER2-) showed higher (P = .009) survival rate than triple-negative (TN) subtype. Tamoxifen therapy group showed superior (P < .001) survival than no-tamoxifen therapy group. It had survival benefit only for luminal A subtype (P = .001). Tamoxifen therapy resulted in higher survival rate in subgroups with positive ER (P = .006), positive PR (P = .009), and negative HER2 (P < .001). In luminal A subtype, tamoxifen therapy showed lower hazard ratio (HR) compared to no-tamoxifen therapy (HR, 0.420; 95% CI 0.250-0.705; P = .001). Tamoxifen therapy was a significant independent factor by multivariate analysis (HR, 0.538; 95% CI 0.306-0.946; P = .031) as well as univariate analysis. Tamoxifen therapy group showed superior prognosis than the no-tamoxifen therapy group. Its prognostic influence was only effective for luminal A subtype. Patients with luminal A subtype showed higher survival rate than those with TN subtype. Active tamoxifen therapy is recommended for DCIS patients with luminal A subtype, and routine tests for ER, PR, and HER2 should be considered for DCIS.

  19. Estrogen receptor (ESR1) mRNA expression and benefit from tamoxifen in the treatment and prevention of estrogen receptor-positive breast cancer.

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    Kim, Chungyeul; Tang, Gong; Pogue-Geile, Katherine L; Costantino, Joseph P; Baehner, Frederick L; Baker, Joffre; Cronin, Maureen T; Watson, Drew; Shak, Steven; Bohn, Olga L; Fumagalli, Debora; Taniyama, Yusuke; Lee, Ahwon; Reilly, Megan L; Vogel, Victor G; McCaskill-Stevens, Worta; Ford, Leslie G; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman; Paik, Soonmyung

    2011-11-01

    Several mechanisms have been proposed to explain tamoxifen resistance of estrogen receptor (ER) -positive tumors, but a clinically useful explanation for such resistance has not been described. Because the ER is the treatment target for tamoxifen, a linear association between ER expression levels and the degree of benefit from tamoxifen might be expected. However, such an association has never been demonstrated with conventional clinical ER assays, and the ER is currently used clinically as a dichotomous marker. We used gene expression profiling and ER protein assays to help elucidate molecular mechanism(s) responsible for tamoxifen resistance in breast tumors. We performed gene expression profiling of paraffin-embedded tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) trials that tested the worth of tamoxifen as an adjuvant systemic therapy (B-14) and as a preventive agent (P-1). This was a retrospective subset analysis based on available materials. In B-14, ESR1 was the strongest linear predictor of tamoxifen benefit among 16 genes examined, including PGR and ERBB2. On the basis of these data, we hypothesized that, in the P-1 trial, a lower level of ESR1 mRNA in the tamoxifen arm was the main difference between the two study arms. Only ESR1 was downregulated by more than two-fold in ER-positive cancer events in the tamoxifen arm (P < .001). Tamoxifen did not prevent ER-positive tumors with low levels of ESR1 expression. These data suggest that low-level expression of ESR1 is a determinant of tamoxifen resistance in ER-positive breast cancer. Strategies should be developed to identify, treat, and prevent such tumors.

  20. Estrogen Receptor (ESR1) mRNA Expression and Benefit From Tamoxifen in the Treatment and Prevention of Estrogen Receptor–Positive Breast Cancer

    Science.gov (United States)

    Kim, Chungyeul; Tang, Gong; Pogue-Geile, Katherine L.; Costantino, Joseph P.; Baehner, Frederick L.; Baker, Joffre; Cronin, Maureen T.; Watson, Drew; Shak, Steven; Bohn, Olga L.; Fumagalli, Debora; Taniyama, Yusuke; Lee, Ahwon; Reilly, Megan L.; Vogel, Victor G.; McCaskill-Stevens, Worta; Ford, Leslie G.; Geyer, Charles E.; Wickerham, D. Lawrence; Wolmark, Norman; Paik, Soonmyung

    2011-01-01

    Purpose Several mechanisms have been proposed to explain tamoxifen resistance of estrogen receptor (ER) –positive tumors, but a clinically useful explanation for such resistance has not been described. Because the ER is the treatment target for tamoxifen, a linear association between ER expression levels and the degree of benefit from tamoxifen might be expected. However, such an association has never been demonstrated with conventional clinical ER assays, and the ER is currently used clinically as a dichotomous marker. We used gene expression profiling and ER protein assays to help elucidate molecular mechanism(s) responsible for tamoxifen resistance in breast tumors. Patients and Methods We performed gene expression profiling of paraffin-embedded tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) trials that tested the worth of tamoxifen as an adjuvant systemic therapy (B-14) and as a preventive agent (P-1). This was a retrospective subset analysis based on available materials. Results In B-14, ESR1 was the strongest linear predictor of tamoxifen benefit among 16 genes examined, including PGR and ERBB2. On the basis of these data, we hypothesized that, in the P-1 trial, a lower level of ESR1 mRNA in the tamoxifen arm was the main difference between the two study arms. Only ESR1 was downregulated by more than two-fold in ER-positive cancer events in the tamoxifen arm (P < .001). Tamoxifen did not prevent ER-positive tumors with low levels of ESR1 expression. Conclusion These data suggest that low-level expression of ESR1 is a determinant of tamoxifen resistance in ER-positive breast cancer. Strategies should be developed to identify, treat, and prevent such tumors. PMID:21947828

  1. Gene expression changes induced by estrogen and selective estrogen receptor modulators in primary-cultured human endometrial cells: signals that distinguish the human carcinogen tamoxifen

    International Nuclear Information System (INIS)

    Pole, Jessica C.M.; Gold, Leslie I.; Orton, Terry; Huby, Russell; Carmichael, Paul L.

    2005-01-01

    Tamoxifen has long been the endocrine treatment of choice for women with breast cancer and is now employed for prophylactic use in women at high risk from breast cancer. Other selective estrogen receptor modulators (SERMs), such as raloxifene, mimic some of tamoxifen's beneficial effects and, like tamoxifen, exhibit a complex mixture of organ-specific estrogen agonist and antagonistic properties. However, accompanying the positive effects of tamoxifen has been the emergence of evidence for an increased risk of endometrial cancer associated with its use. A more complete understanding of the mechanism(s) of SERM carcinogenicity and endometrial effects is therefore required. We have sought to compare and characterise the transcript profile of tamoxifen, raloxifene and the agonist estradiol in human endometrial cells. Using primary cultures of human endometria, to best emulate the in vivo responses in a manageable in vitro system, we have shown 230 significant changes in gene expression for epithelial cultures and 83 in stromal cultures, either specific to 17β-estradiol, tamoxifen or raloxifene, or changed across more than one of the treatments. Considering the transcriptome as a whole, the endometrial responses to raloxifene or tamoxifen were more similar than either drug was to 17β-estradiol. Treatment of endometrial cultures with tamoxifen resulted in the largest number of gene changes relative to control cultures and a high proportion of genes associated with regulation of gene transcription, cell-cycle control and signal transduction. Tamoxifen-specific changes that might point towards mechanisms for its proliferative response in the endometrium included changes in retinoblastoma and c-myc binding proteins, the APCL, dihydrofolate reductase (DHFR) and E2F1 genes and other transcription factors. Tamoxifen was also found to give rise to the highest number of gene expression changes common to those that characterise malignant endometria. It is anticipated that this

  2. Tamoxifen and the Rafoxifene analog LY117018: their effects on arachidonic acid release from cells in culture and on prostaglandin I2 production by rat liver cells

    International Nuclear Information System (INIS)

    Levine, Lawrence

    2004-01-01

    Tamoxifen is being used successfully to treat breast cancer. However, tamoxifen also increases the risk of developing endometrial cancer in postmenopausal women. Raloxifene also decreases breast cancer in women at high risk and may have a lower risk at developing cancer of the uterus. Tamoxifen has been shown to stimulate arachidonic acid release from rat liver cells. I have postulated that arachidonic acid release from cells may be associated with cancer chemoprevention. Rat liver, rat glial, human colon carcinoma and human breast carcinoma cells were labelled with [ 3 H] arachidonic acid. The release of the radiolabel from these cells during incubation with tamoxifen and the raloxifene analog LY117018 was measured. The prostaglandin I 2 produced during incubation of the rat liver cells with μM concentrations of tamoxifen and the raloxifene analog was quantitatively estimated. Tamoxifen is about 5 times more effective than LY117018 at releasing arachidonic acid from all the cells tested. In rat liver cells only tamoxifen stimulates basal prostaglandin I 2 production and that induced by lactacystin and 12-O-tetradecanoyl-phorbol-13-acetate. LY117018, however, blocks the tamoxifen stimulated prostaglandin production. The stimulated prostaglandin I 2 production is rapid and not affected either by preincubation of the cells with actinomycin or by incubation with the estrogen antagonist ICI-182,780. Tamoxifen and the raloxifene analog, LY117018, may prevent estrogen-independent as well as estrogen-dependent breast cancer by stimulating phospholipase activity and initiating arachidonic acid release. The release of arachidonic acid and/or molecular reactions that accompany that release may initiate pathways that prevent tumor growth. Oxygenation of the intracellularly released arachidonic acid and its metabolic products may mediate some of the pharmacological actions of tamoxifen and raloxifene

  3. Postoperative Ileus in the Elderly

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    Chih-Peng Tu

    2014-03-01

    Full Text Available Postoperative ileus is among the most common complications after surgery. Aging is associated with an increased colonic transit time, and anesthetic disturbance to colonic motility is often aggravated in the elderly. Postoperative ileus increases morbidity, prolongs the length of hospital stay, and constitutes a significant economic burden on the healthcare system. Multimodal enhanced recovery protocols, or fast-track surgeries, have been developed to improve postoperative recovery. Patient education, avoidance of perioperative fluid overload, selective use of nasogastric decompression, early ambulation, adopting a minimally invasive approach, early initiation of clear fluids, and gum chewing are all possible measures to reduce postoperative ileus. Thoracic epidural anesthesia is a well-established technique to hasten recovery, whereas insufficient data are available to ascertain the safety and efficacy of opioid-sparing analgesia in the elderly. The evidence is clear that traditional prokinetic medications are not helpful in the treatment or prevention of postoperative ileus. Early results suggest that alvimopan is a promising agent to reverse opioid-induced ileus. Since postoperative ileus is a multifactorial condition, a concerted effort is therefore necessary to prevent or decrease the duration of postoperative ileus using multimodal strategies.

  4. A tamoxifen inducible knock-in allele for investigation of E2A function

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    Kondo Motonari

    2009-10-01

    Full Text Available Abstract Background E-proteins are transcription factors important for the development of a variety of cell types, including neural, muscle and lymphocytes of the immune system. E2A, the best characterized E-protein family member in mammals, has been shown to have stage specific roles in cell differentiation, lineage commitment, proliferation, and survival. However, due to the complexity of E2A function, it is often difficult to separate these roles using conventional genetic approaches. Here, we have developed a new genetic model for reversible control of E2A protein activity at physiological levels. This system was created by inserting a tamoxifen-responsive region of the estrogen receptor (ER at the carboxyl end of the tcfe2a gene to generate E2AER fusion proteins. We have characterized and analyzed the efficiency and kinetics of this inducible E2AER system in the context of B cell development. Results B cell development has been shown previously to be blocked at an early stage in E2A deficient animals. Our E2AER/ER mice demonstrated this predicted block in B cell development, and E2AER DNA binding activity was not detected in the absence of ligand. In vitro studies verified rapid induction of E2AER DNA binding activity upon tamoxifen treatment. While tamoxifen treatment of E2AER/ER mice showed inefficient rescue of B cell development in live animals, direct exposure of bone marrow cells to tamoxifen in an ex vivo culture was sufficient to rescue and support early B cell development from the pre-proB cell stage. Conclusion The E2AER system provides inducible and reversible regulation of E2A function at the protein level. Many previous studies have utilized over-expression systems to induce E2A function, which are complicated by the toxicity often resulting from high levels of E2A. The E2AER model instead restores E2A activity at an endogenous level and in addition, allows for tight regulation of the timing of induction. These features make

  5. Effect of chronic administration of Tamoxifen on fertility in male bonnet monkeys (Macaca radiata).

    Science.gov (United States)

    Rao, A J; Ramachandra, S G; Ramesh, V; Krishnamurthy, H N; Jayaraman, S; Gopalakrishnan, K; Juneja, H S

    1998-01-01

    Administration of Tamoxifen via the Alzet pump at a rate of 50 micrograms hr-1 for 90 days in the adult male bonnet monkeys Macaca radiata had no effect on the serum testosterone concentration determined at 10 AM and 10 PM as well as total sperm count determined at 15-day intervals over a period of 260 days. However, a significant reduction in sperm motility was observed beyond 90 days up until the 225th day. Breeding studies conducted from day 90 to 260 revealed that these males were infertile.

  6. Postoperative imaging of the shoulder

    International Nuclear Information System (INIS)

    Woertler, K.; Rummeny, E.J.

    2004-01-01

    Correct interpretation of imaging findings in the postoperative shoulder is impaired by surgical distortion of normal anatomy and possible artifacts. Advanced postoperative imaging of the shoulder in addition to the selection of the best suited modality necessitates familiarity with the surgical procedure that has been performed and its consecutive morphological changes. This article reviews the most common arthroscopic and open techniques used for treatment of shoulder instability, lesions of the superior labral-bicipital complex, primery impingement, and rotator cuff tears, their typical postoperative imaging findings, as well as the diagnostic performance of cross sectional imaging techniques in the detection of recurrent lesions and complications. (orig.) [de

  7. Postoperative MRI of the ankle; Postoperative Magnetresonanztomographie des Sprunggelenks

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    Sharabianlou Korth, M.; Fritz, L.B. [Rheinlandaerzte, Willich (Germany)

    2017-11-15

    Postoperative imaging of the ankle can be challenging, even for the experienced radiologist. Pathological and postoperative changes to the primarily complex anatomy of the ankle with its great variety of bone structures, tendons, ligaments, and soft tissue in a very limited space may cause great difficulty in differentiating underlying pathology from expected postoperative changes and artifacts, especially in magnetic resonance imaging (MRI). Selecting the appropriate radiological modality is key to making the correct diagnosis. Therefore, knowledge of the initial and current symptoms is just as important as familiarity with the most frequently performed operations in the ankle. This article aims to give its reader a summary of the most important and frequently performed operation techniques of the ankle and discusses the expected appearance and possible complications in postoperative imaging. (orig.) [German] Die postoperative radiologische Bildgebung des Sprunggelenks kann auch fuer den erfahrenen Radiologen eine besondere Herausforderung darstellen. Die komplex aufgebaute Anatomie des Sprunggelenks, mit seinen multiplen Gelenkflaechen, Sehnen, Baendern und neurovaskulaeren Strukturen auf engstem Raum, kann durch Operationen signifikant veraendert und insbesondere in der Magnetresonanztomographie (MRT) verfaelscht dargestellt werden. Fuer eine fundierte Befundung und Beurteilung der Operationsergebnisse ist die Kenntnis der praeoperativen Diagnose, Zeitpunkt und Technik der durchgefuehrten Operation(en) sowie der aktuellen klinischen Symptomatik von grosser Bedeutung. Dieser Artikel konzentriert sich auf zu erwartende radiologische Veraenderungen und gibt Tipps zur Befundung der postoperativen MRT des Sprunggelenks bei einer Auswahl relevanter operativer Eingriffe. Zudem wird auf moegliche postoperative Komplikationen und ihre radiologische Darstellung hingewiesen. (orig.)

  8. Prognostic significance of postoperative pneumonia after curative resection for patients with gastric cancer.

    Science.gov (United States)

    Tu, Ru-Hong; Lin, Jian-Xian; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Lu, Jun; Chen, Qi-Yue; Cao, Long-Long; Lin, Mi; Zheng, Chao-Hui; Huang, Chang-Ming

    2017-12-01

    Few studies have been designed to investigate the incidence of postoperative pneumonia after radical gastrectomy and its effect on prognosis of these patients. Incidences of postoperative pneumonia after radical gastrectomy in our department between January 1996 and December 2014 were summarized. Their effects on prognosis were retrospectively analyzed using survival curves and Cox regression. A total of 5237 patients were included in this study, 767 (14.4%) of them had complications, including 383 cases of postoperative pneumonia (7.2%). The 5-year overall and disease-specific survival of patients with postoperative pneumonia were both lower than those without this complication (P pneumonia were independent risk factors for disease-specific survival. Postoperative pneumonia after radical gastrectomy is an independent risk factor for prognosis of gastric cancer patients, especially in stage III. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  9. Postoperative radiation therapy for grade II and III intracranial ependymoma

    International Nuclear Information System (INIS)

    Mansur, David B.; Perry, Arie; Rajaram, Veena; Michalski, Jeff M.; Park, T.S.; Leonard, Jeffrey R.; Luchtman-Jones, Lori; Rich, Keith M.; Grigsby, Perry W.; Lockett, Mary Ann; Wahab, Sasha H.; Simpson, Joseph

    2005-01-01

    Purpose: To retrospectively determine the long-term outcome of intracranial ependymoma patients treated with surgery and postoperative radiation therapy. Methods and materials: Sixty patients were treated at our institution between 1964 and 2000. Forty patients had World Health Organization Grade II ependymoma, and 20 patients had Grade III ependymoma. The median patient age was 10.7 years. The majority of patients were male (55%), had infratentorial tumors (80%), and had subtotal resections (72%). Postoperative radiation therapy was delivered to all patients to a median total dose of 50.4 Gy. Craniospinal radiation therapy was used in the earlier era in only 12 patients (20%). Results: The median follow-up of surviving patients was 12.5 years. The 5-year and 10-year disease-free survival rates for all patients were 58.4% and 49.5%, respectively. The 5-year and 10-year overall survival rates for all patients were 71.2% and 55.0%, respectively. Supratentorial tumor location was independently associated with a worse disease-free survival. Subtotal resection and supratentorial location predicted a worse overall survival, but this failed to reach statistical significance. No statistically significant effect on prognosis was observed with tumor grade, patient age, or radiation dose or volume. Conclusion: Our long-term follow-up indicates that half of ependymoma patients will have disease recurrences, indicating the need for more effective treatments

  10. Association between depression in carers and malnutrition in children aged 6 months to 5 years.

    Science.gov (United States)

    Motlhatlhedi, Keneilwe; Setlhare, Vincent; Ganiyu, Adewale; Firth, Jacqueline

    2017-01-30

     Childhood malnutrition is an important risk factor for child mortality and underlies close to 50% of child deaths worldwide. Previous studies have found an association between maternal depression and child malnutrition, but it is not known whether this association exists in Botswana. In addition, previous studies excluded non-maternal primary caregivers (PCGs). It is unclear whether the association between primary caregiver depression and child malnutrition remains when non-maternal PCGs are included. The aim of this study was to determine if there is an association between PCG depression and malnutrition in children aged between 6 months and 5 years in Mahalapye, Botswana. The study was conducted in the child welfare clinics of Xhosa and Airstrip clinics, two primary health care facilities in Mahalapye, Botswana. This was a case control study. Cases were malnourished children aged between 6 months and 5 years, and controls were non-malnourished children matched for age and gender. The outcome of interest was depression in the PCGs of the cases and controls, which was assessed using the Patient Health Questionnaire 9 (PHQ 9), a depression screening tool. From a sample of 171 children, 84 of whom were malnourished, we found that the malnourished children were significantly more likely to have depressed PCGs (odds ratio = 4.33; 95% CI: 1.89, 9.89) than non-malnourished children in the 6-month to 5-year age group; the PCGs of malnourished children also had lower educational status. This study found a significant association between PCG depression and child malnutrition.

  11. Arthroscopic Labral Base Repair in the Hip: 5-Year Minimum Clinical Outcomes.

    Science.gov (United States)

    Domb, Benjamin G; Yuen, Leslie C; Ortiz-Declet, Victor; Litrenta, Jody; Perets, Itay; Chen, Austin W

    2017-10-01

    Arthroscopic labral base repair (LBR) in the hip is a previously described technique designed to restore the native functional anatomy of the labrum by reproducing its seal against the femoral head. LBR has been shown to have good short-term outcomes. Hypothesis/Purpose: The purpose was to evaluate clinical outcomes of an LBR cohort with a minimum 5-year follow-up. It was hypothesized that patients who underwent LBR would continue to have significant improvement from their preoperative scores and maintain scores similar to their 2-year outcomes. Case series; Level of evidence, 4. Data for patients undergoing primary hip arthroscopic surgery with LBR from February 2008 to May 2011 with a minimum 5-year follow-up were prospectively collected and retrospectively reviewed. Patients with preoperative Tonnis osteoarthritis grade ≥2, previous hip conditions (slipped capital femoral epiphysis, avascular necrosis, Legg-Calv-Perthes disease), severe dysplasia (lateral center-edge angle hip surgery were excluded. Statistical equivalence tests evaluated patient-reported outcomes (PROs) including the modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), Hip Outcome Score-Sport-Specific Subscale (HOS-SSS), visual analog scale (VAS) for pain, and patient satisfaction (0-10 scale; 10 = very satisfied). Of the 70 patients (74 hips) who met inclusion and exclusion criteria, 60 (85.7%) patients (64 hips) were available at a minimum 5-year follow-up. All PRO scores significantly improved from preoperative values with a mean follow-up of 67.8 ± 7.4 months (range, 60.0-89.7 months). The mean mHHS increased from 64.4 ±13.8 to 85.3 ± 17.7 ( P hip arthroscopic surgery has yet to be determined; however, these midterm results demonstrate the rates of additional procedures (both secondary arthroscopic surgery and conversion to total hip arthroplasty), that may be necessary after 2 years.

  12. Changes in asthma control, work productivity, and impairment with omalizumab: 5-year EXCELS study results.

    Science.gov (United States)

    Zazzali, James L; Raimundo, Karina P; Trzaskoma, Benjamin; Rosén, Karin E; Schatz, Michael

    2015-01-01

    Asthma poses a significant disease burden worldwide. Current guidelines emphasize achieving and maintaining asthma control. To describe longitudinal changes of asthma control and asthma-related work, school, and activity impairment for patients with moderate-to-severe asthma treated with omalizumab and those who did not receive omalizumab in a real-world setting. This study used 5 years of data from patients ages ≥12 years old with moderate-to-severe persistent allergic asthma who were enrolled in the Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma observational study. Asthma control was assessed with the Asthma Control Test for 5 years, and asthma-related work, school, and activity impairment was measured with the Work Productivity/Activity Impairment-Asthma questionnaire for the first 2 years. The percentage of patients treated with omalizumab (n = 4930) and with well-controlled asthma (Asthma Control Test score, >20) increased from 45% at baseline to 61% at month 60, and it was 49% (baseline) and 67% (month 60) for the non-omalizumab-treated cohort (n = 2779). For new starters to omalizumab (n = 576), the percentage with well-controlled asthma increased from 25% at baseline to 51% at month 6, and to 60% at month 60. Patients in the omalizumab-treated cohort and those in the non-omalizumab-treated cohort experienced a reduction in asthma-related work, school, and activity impairment. The amount of improvement in asthma control achieved and the reduction in asthma-related work, school, and activity impairment were similar, regardless of asthma severity. On average, patients in the Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma observational study who initiated omalizumab experienced clinically significant improvement in asthma control, which was observed within 6 months and persisted for 5 years.

  13. Annual Papanicolaou screening for 5 years among human papillomavirus-negative women

    International Nuclear Information System (INIS)

    Petry, Karl Ulrich; Rinnau, Franziska; Böhmer, Gerd; Hollwitz, Bettina; Luyten, Alexander; Buttmann, Nina; Brünger, Martin; Iftner, Thomas

    2013-01-01

    Primary human papilloma virus (HPV) screening is more effective than cytology in reducing the risk of cervical cancer, but screening intervals should be extended in HPV-negative women. However, some Markov models predicted that long intervals are associated with an excess risk of cervical cancer. The aim of this analysis was to estimate the real-life risks and benefits of annual Papanicolaou (Pap) screening in HPV-negative women with normal cytology. Women with negative Hybrid Capture 2 (HC2) results and normal cytology at the time of inclusion in the Hannover HPV screening trial underwent annual Pap smears for 5 years. A subgroup was randomly selected for retesting with cytology, HC2, and colposcopy 60–68 months after recruitment. Of 4236 women included, 3406 had at least one Pap smear, but only 1185 attended all five annual screening visits. The proportion of women with at least one abnormal smear was 14.4% in 60 months. The probability of abnormal smears increased continuously over time. No case of ≥ CIN2+ was observed during 5 years. Of 605 women selected for subgroup analysis, 292 agreed to be retested (48.3%). The rate of high-risk HPV at 60–68 months was 3.0% (9/296). The long-term risk of high-grade neoplasia after an initial negative HC2 test and normal cytology result was low, while the rate of false-positive abnormal Pap smears was significant and increased constantly over time. Pap smear screening of HPV-negative women more frequently than every 5 years could be potentially harmful and seems to be of little clinical value

  14. Do very preterm twins and singletons differ in their neurodevelopment at 5 years of age?

    Science.gov (United States)

    Bodeau-Livinec, Florence; Zeitlin, Jennifer; Blondel, Béatrice; Arnaud, Catherine; Fresson, Jeanne; Burguet, Antoine; Subtil, Damien; Marret, Stéphane; Rozé, Jean-Christophe; Marchand-Martin, Laetitia; Ancel, Pierre-Yves; Kaminski, Monique

    2013-11-01

    Twins have inconsistently shown poorer outcomes than singletons. Although a high proportion of twins are born very preterm, data are sparse on the long-term outcomes in very preterm twins. The objective of this study was to compare mortality and neurodevelopmental outcomes of very preterm singletons and twins and to study outcomes in relation to factors specific to twins. Birth cohort study Etude Epidemiologique sur les Petits Ages Gestationnels (EPIPAGE). Nine regions in France. All very preterm live births occurring from 22 to 32 weeks of gestation in all maternity wards of nine French regions in 1997 (n=2773). Neurodevelopmental status, including cerebral palsy, and a cognitive assessment with the Kaufman Assessment Battery for Children, with scores on the Mental Processing Composite (MPC) scale, was available for 1732 and 1473 children at 5 years of age, respectively. Among live births, twins had higher hospital mortality than singletons (adjusted (a)OR: 1.4 (95% CI 1.1 to 1.9)). Among survivors, there was no crude difference at 5 years between twins and singletons in the prevalence of cerebral palsy (8.0% vs 9.1%, respectively), MPC <70 (9.5% vs 11.1%) and mean MPC (94.6 vs 94.4). However, after adjustment for sex, gestational age, intrauterine growth restriction and social factors, twins were more likely to have lower MPC scores (mean difference: -2.4 (95% CI-4.8 to 0.01)). Live born twins had a higher risk of mortality when birth weight discordance was present (aOR:2.9 (95% CI 1.7 to 4.8)), but there were no differences in long-term outcomes. Compared with very preterm singletons, twins had higher mortality, no difference with respect to severe deficiencies, but slightly lower MPC scores at 5 years.

  15. Assessment of Iron Overload in Homozygous and Heterozygous Beta Thalassemic Children below 5 Years of Age

    Directory of Open Access Journals (Sweden)

    Dhiraj J. Trivedi

    2014-07-01

    Full Text Available Background: Thalassemia is a genetic disease having 3-7% carrier rate in Indians. It is transfusion dependent anemia having high risk of iron overloading. A clinical symptom of iron overload becomes detectable in second decade causing progressive liver, heart and endocrine glands damage. There is a need to assess iron overload in thalassemics below 5 years of age to protect them from complications at later age of life. Aims and objectives: Present study was undertaken to estimate serum iron status and evaluate serum transferrin saturation in both homozygous & heterozygous form of thalassemia as an index of iron overload among children of one to five years of age. Materials and Methods: Clinically diagnosed thirty cases of β thalassemia major & thirty cases of β thalassemia minor having severe anemia, hepatospleenomegaly and between 1 year to 5 years of age were included in study group and same age matched healthy controls were included in the study. RBC indices and HbA, HbA2 and HbF were estimated along with serum iron & serum Total Iron Binding Capacity (TIBC and serum transferrin levels. Results: Significant difference was observed in hemoglobin levels between control and both beta thalassemia groups. Mean Corpuscular Volume (MCV and Mean Corpuscular Hemoglobin (MCH values were reduced. Hemoglobin electrophoresis showed the elevated levels of HbF and HbA2 in both beta thalassemia groups. Among serum iron parameters, serum iron, TIBC and transferrin saturation were elevated whereas serum transferrin levels were low in thalassemia major in children below 5 years of age. Conclusion: Although clinical symptoms of iron overload have been absent in thalassemic children below five years of age, biochemical iron overloading has started at much lower age which is of great concern.

  16. Brain reserve against physical disability progression over 5 years in multiple sclerosis.

    Science.gov (United States)

    Sumowski, James F; Rocca, Maria A; Leavitt, Victoria M; Meani, Alessandro; Mesaros, Sarlota; Drulovic, Jelena; Preziosa, Paolo; Habeck, Christian G; Filippi, Massimo

    2016-05-24

    The brain reserve hypothesis links larger maximal lifetime brain growth (MLBG, estimated with intracranial volume [ICV]) with lower risk for cognitive decline/dementia. We examined whether larger MLBG is also linked to less physical disability progression over 5 years in a prospective sample of treatment-naive patients with multiple sclerosis (MS). Physical disability was measured with the Expanded Disability Status Scale (EDSS) at baseline and 5-year follow-up in 52 treatment-naive Serbian patients with MS. MRI measured disease burden (cerebral atrophy, T2 lesion volume) and MLBG: a genetically determined, premorbid (established during adolescence, stable thereafter) patient characteristic estimated with ICV (adjusted for sex). Logistic regression tested whether MLBG (smaller vs larger) predicts disability progression (stable vs worsened) independently of disease burden. Disability progression was observed in 29 (55.8%) patients. Larger MLBG predicted lower risk for progression (odds ratio 0.13, 95% confidence interval 0.02-0.78), independently of disease burden. We also calculated absolute change in EDSS scores, and observed that patients with smaller MLBG showed worse EDSS change (0.91 ± 0.71) than patients with larger MLBG (0.42 ± 0.87). Larger MLBG was linked to lower risk for disability progression in patients with MS over 5 years, which is the first extension of the brain reserve hypothesis to physical disability. MLBG (ICV) represents a clinically available metric that may help gauge risk for future disability in patients with MS, which may advance the science and practice of early intervention. Potential avenues for future research are discussed. © 2016 American Academy of Neurology.

  17. CLINICAL PROFILE OF ACUTE LOWER RESPIRATORY TRACT INFECTIONS IN CHILDREN BETWEEN 2MONTHS TO 5 YEARS

    Directory of Open Access Journals (Sweden)

    Amitoj Singh Chhina

    2015-08-01

    Full Text Available BACKGROUND : Acute respiratory infections are a leading cause of morbidity and mortality in under - five children in developing countries. Hence, the present study was undertaken to study the various risk factors, clinical profile and outcome of acute lower respiratory tract infections (ALRI in children aged 2 month to 5 years. OBJECTIVE : clinical features, laborato ry assessment and morbidity and mortality pattern associated with acute lower respiratory tract infections in children aged 2 months to 5 years. METHODS: 100 ALRI cases fulfilling WHO criteria for pneumonia, in the age group of 2 month to 5 years were evaluated for clinical profile as per a predesigned proforma in a rural medical college. RESULTS : Of cases 61% were infants and remaining 39%12 - 60 months age group, males outnumbered females with sex ratio of 1.3;1. Elevated total leukocyte counts for age were observed in only 22% of cases, of these 3% were having pneumonia, 9% severe pneumonia and 10% very severe pneumonia. Significant association was found between leukocytosis and ALRI severity (p= 0.0001 Positive blood culture was obtained in 8% of cases and was significantly associated with ALRI severity (p=. 0.027. Among the ALRI cases, 84% required oxygen supplementation at any time during the hospital stay and 8% required mechanical ventilation. The mortality rate was 1%; with 99% of cases recovering and getting discharged uneventfully. CONCLUSION : Among the clinical variables, the signs and symptoms of ALRI as per the WHO ARI Control Programme were found in almost all cases. Regarding the laboratory profile, leukocytosis and blood culture positivity w ere observed in a small percentage, but significant association with ALRI severity was observed for both. Thus, clinical signs, and not invasive blood tests are a better diagnostic tools, though the latter may provide additional therapeutic and prognostic information in severe disease

  18. Development of allocentric spatial memory abilities in children from 18 months to 5 years of age.

    Science.gov (United States)

    Ribordy, Farfalla; Jabès, Adeline; Banta Lavenex, Pamela; Lavenex, Pierre

    2013-02-01

    Episodic memories for autobiographical events that happen in unique spatiotemporal contexts are central to defining who we are. Yet, before 2 years of age, children are unable to form or store episodic memories for recall later in life, a phenomenon known as infantile amnesia. Here, we studied the development of allocentric spatial memory, a fundamental component of episodic memory, in two versions of a real-world memory task requiring 18 month- to 5-year-old children to search for rewards hidden beneath cups distributed in an open-field arena. Whereas children 25-42-months-old were not capable of discriminating three reward locations among 18 possible locations in absence of local cues marking these locations, children older than 43 months found the reward locations reliably. These results support previous findings suggesting that allocentric spatial memory, if present, is only rudimentary in children under 3.5 years of age. However, when tested with only one reward location among four possible locations, children 25-39-months-old found the reward reliably in absence of local cues, whereas 18-23-month-olds did not. Our findings thus show that the ability to form a basic allocentric representation of the environment is present by 2 years of age, and its emergence coincides temporally with the offset of infantile amnesia. However, the ability of children to distinguish and remember closely related spatial locations improves from 2 to 3.5 years of age, a developmental period marked by persistent deficits in long-term episodic memory known as childhood amnesia. These findings support the hypothesis that the differential maturation of distinct hippocampal circuits contributes to the emergence of specific memory processes during early childhood. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. CYP2D6 polymorphisms may predict occurrence of adverse effects to tamoxifen: a preliminary retrospective study

    Directory of Open Access Journals (Sweden)

    Wickramage I

    2017-03-01

    Full Text Available Ishani Wickramage,1 Kamani Hemamala Tennekoon,1 Merenchi Arachchige Yasantha Ariyaratne,2 Asanka Sudeshini Hewage,1 Tharmini Sundralingam,1 1Institute of Biochemistry, Molecular Biology and Biotechnology (IBMBB, University of Colombo, Colombo, Sri Lanka; 2National Cancer Institute, Maharagama, Sri Lanka Introduction and aims: Tamoxifen is an adjuvant drug effective in treating hormone ­receptor – positive breast cancer. However, 30%–50% of patients relapse and many develop adverse effects, such as hot flashes and fatty liver. Allelic variations altering the activity of cytochrome P450-2D6 enzyme affect response to tamoxifen by modulating metabolism of tamoxifen into its pharmacologically active metabolite endoxifen. Although association between CYP2D6 polymorphisms and recurrence of breast cancer in patients on tamoxifen had been reported, little evidence exists on association between these polymorphisms and adverse effects to tamoxifen. This study explored the association between CYP2D6 polymorphisms and tamoxifen effects, hitherto not studied in Sri Lanka. Methods: A retrospective preliminary study was carried out on 24 breast cancer patients on tamoxifen for minimally 3 months attending National Cancer Institute, Maharagama, Sri Lanka. They were not on CYP2D6-inhibiting drugs, chemotherapy or other endocrine therapy, and had no conditions that could occur as adverse effects to tamoxifen before starting the therapy. Their blood samples were collected, DNA was extracted and genotyped using SNaPshot Multiplex sequencing based single-nucleotide polymorphism (SNP assay. Results: SNP/allele frequencies detected: 1846G>A (confirmatory of *4 null allele=8.3%; 2549delA (confirmatory of *3 null allele=50%; 100C>T (suggestive of *10 reduced functional allele, in addition to other alleles=0%; combination of 2988G>A, -1584C and 2850C>T (strongly suggestive of *41 or other reduced functional allele=4.8%. Occurrence of heterozygous 2988G>A SNP with

  20. Posttraumatic stress disorder among Danish soldiers 2.5 years after military deployment in Afghanistan

    DEFF Research Database (Denmark)

    Hellerup, Janne; Andersen, Søren Bo; Høgh (Hogh), Annie

    2015-01-01

    Understanding the development of posttraumatic stress disorder (PTSD) implicates research regarding factors besides the preceding traumatic event. This study investigated the influence of predisposing personality traits on development of PTSD in a group of Danish Soldiers deployed to Afghanistan (N...... = 445). Using a prospective design data was collected using questionnaires including the NEO Five Factor Inventory and the Posttraumatic Stress Disorder Checklist. The results showed a PTSD-prevalence of 9.2% in the total sample 2.5 years after homecoming. Using Kruskal-Wallis, Mann-Whitney U...

  1. Sexual function in multiple sclerosis. A 5-year follow-up study

    DEFF Research Database (Denmark)

    Stenager, E; Stenager, E N; Jensen, K

    1996-01-01

    Sexual dysfunction is known to occur in multiple sclerosis (MS). The purpose of the study is to describe the change in sexual function and symptoms in a longitudinal study. Forty-nine patients (27 females, 22 males) with definite MS were interviewed and examined with 5 years interval. The number...... of patients with sexual dysfunction increased significantly (p = 0.009) and involved females and males equally. Males usually had 1 or two symptoms of sexual dysfunction, while females frequently had 2 or more symptoms. It is concluded that the risk of sexual dysfunction increases over time. Further studies...

  2. Malnutrition Among Children Younger Than 5 Years-Old in Conflict Zones of Chiapas, Mexico

    Science.gov (United States)

    Sánchez-Pérez, Héctor Javier; Hernán, Miguel A.; Ríos-González, Adriana; Arana-Cedeño, Marcos; Navarro, Albert; Ford, Douglas; Micek, Mark A.; Brentlinger, Paula

    2007-01-01

    We performed a cross-sectional, community-based survey, supplemented by interviews with community leaders in Chiapas, Mexico, to examine the prevalence and predictors of child malnutrition in regions affected by the Zapatista conflict. The prevalence rates of stunting, wasting, and underweight were 54.1%, 2.9%, and 20.3%, respectively, in 2666 children aged younger than 5 years. Stunting was associated with indigenous ethnicity, poverty, region of residence, and intracommunity division. The results indicate that malnutrition is a serious public health problem in the studied regions. PMID:17194868

  3. Analysis of 5 year survival of esophageal cancer treated by radiotherapy

    International Nuclear Information System (INIS)

    Takegawa, Yoshihiro; Ohgushi, Ikuyo; Hiraki, Yoshio; Honke, Yoshifumi; Matsuki, Tsutomu; Yokoyama, Takashi; Yoshida, Mineo.

    1987-01-01

    Since 1984, a total of 1,419 patients with carcinoma of the esophagus were treated at the Department of Radiology of 17 hospitals in Chugoku-Shikoku province. The five year survival rate was 7.3 % (42/578 cases). Thirty-nine out of the forty-two cases were analyzed according to the tumor extent, localization and types of the X-ray findings. In addition, 95 patients (67 had been reported in other journals and 28 in this report) who have survived more than 5 years after radical radiotherapy were analyzed. (author)

  4. 5 year Survey of Carcinoma Breast at No.(2) Military Hospital (1987 to 1991)

    Energy Technology Data Exchange (ETDEWEB)

    Pe, Aye; Saw, Kaythi; Mon, Shu; Aung, Yin Yin [Department of Medical Oncology, Yangon, (Myanmar)

    1993-03-15

    Over 250 cases of carcinoma of Breast in different stages, treated by Joint Cancer Clinic (JCC) of No (2) Military Hospital over 5 years (1987 to 1991) were analysed. Different combination of drugs CMF, CMF(P),CMFVP and COFA regimes were given either alone on in combination with local radiation therapy after surgery- lumpectomy or extended simple mastectomy. Hormonal therapy was also added to the standard method of treatment in most of the cases. Results were evaluated in different arms of treatment. The value of immunotherapy and neochemotherapy were also studied.

  5. Family orientation for the development and formation table maners in 4 to 5 years old children

    Directory of Open Access Journals (Sweden)

    Lidielys González Tamayo

    2014-03-01

    Full Text Available The Cuban family should obtain an elevated preparation for the formation of table manners or habits in children. The formative activities to take place should have to contribute priorities for all. Departing from the study which had taken place in reference to the preparation of the families about the formation of table manners or habits and a bibliographical study related with the problem. As a result of work, a manual is offered to orient and direct the family on how to develop table habits in 4-5 years old children and orientations for its effective use in any center.

  6. Hyperventilation with cold versus dry air in 2- to 5-year-old children with asthma

    DEFF Research Database (Denmark)

    Nielsen, Kim G; Bisgaard, Hans

    2005-01-01

    UNLABELLED: Cold air challenge (CACh) has been shown to discriminate between children with asthma and healthy young children. Hyperventilation with dry room-temperature air is a simplified alternative. We compared responsiveness in young children with asthma between two standardized, single......-subject SDs (SDw). The challenge sequence was randomly assigned. A comparator challenge was performed 1 hour later if the first challenge gave a change of 3 SDw or more. Forty 2- to 5-year-old children with asthma were included. Responsiveness to cold versus dry air showed significant, but weak, correlation...

  7. 5 year Survey of Carcinoma Breast at No.(2) Military Hospital (1987 to 1991)

    International Nuclear Information System (INIS)

    Aye Pe; Kaythi Saw; Shu Mon; Yin Yin Aung

    1993-03-01

    Over 250 cases of carcinoma of Breast in different stages, treated by Joint Cancer Clinic (JCC) of No (2) Military Hospital over 5 years (1987 to 1991) were analysed. Different combination of drugs CMF, CMF(P),CMFVP and COFA regimes were given either alone on in combination with local radiation therapy after surgery- lumpectomy or extended simple mastectomy. Hormonal therapy was also added to the standard method of treatment in most of the cases. Results were evaluated in different arms of treatment. The value of immunotherapy and neochemotherapy were also studied

  8. Total pancreatectomy and autoislet transplant for chronic recurrent pancreatitis in a 5-year-old boy

    Directory of Open Access Journals (Sweden)

    Shaheed Merani

    2016-10-01

    Full Text Available Childhood chronic pancreatitis is a rare disorder, which can lead to a chronically debilitating condition. The etiology of recurrent hereditary pancreatitis, which previously was classified as idiopathic, has now been attributed in certain cases to specific genetic mutations including abnormalities in the PRSS gene. We describe here the use of total pancreatectomy and autoislet transplant in a 5-year-old with chronic pancreatitis. This represents the youngest patient undergoing the procedure at our institution. The early successful outcomes for this patient, both of symptom relief and glycemic control are detailed.

  9. Study visit carbon sinks Peugeot. Evaluation after 5 years and perspectives

    International Nuclear Information System (INIS)

    Grosso, M.; Sao Nicolau, F.

    2005-01-01

    In the framework of its project of the climatic change control, PSA Peugeot Citroen, decided to involve in the decrease of the carbon dioxide emissions. In parallel to the vehicles consumption decrease and the biofuels utilization, the group developed since 5 years a pilot project of carbon sink. This project aims to study the impact of a trees plantation, at a big scale, on the atmospheric carbon dioxide fixation. This document is a first evaluation after the phase of trees plantation. (A.L.B.)

  10. Early Eruption of Maxillary Pre Molar with Turner's Hypoplasia in a 5-Year-Old Boy.

    Science.gov (United States)

    Rai, Nitya; Mathur, Shivani; Sandhu, Meera; Sachdev, Vinod

    2016-08-01

    Early eruption of permanent maxillary premolar appears to be a unique finding, at such an early chronological age. Untimely eruption of permanent maxillary premolar is discussed in a 5-year-old male patient. On intra oral examination grossly carious primary maxillary first molar (tooth number 54,64) were reported. The erupting teeth presented with a hypomineralized cusp tip. Extraction following space maintainer in 64 region was given. Pediatric dentist should consider these kinds of rarities in eruption pattern while examining a pediatric patient.

  11. Postoperative MRI of the ankle

    International Nuclear Information System (INIS)

    Sharabianlou Korth, M.; Fritz, L.B.

    2017-01-01

    Postoperative imaging of the ankle can be challenging, even for the experienced radiologist. Pathological and postoperative changes to the primarily complex anatomy of the ankle with its great variety of bone structures, tendons, ligaments, and soft tissue in a very limited space may cause great difficulty in differentiating underlying pathology from expected postoperative changes and artifacts, especially in magnetic resonance imaging (MRI). Selecting the appropriate radiological modality is key to making the correct diagnosis. Therefore, knowledge of the initial and current symptoms is just as important as familiarity with the most frequently performed operations in the ankle. This article aims to give its reader a summary of the most important and frequently performed operation techniques of the ankle and discusses the expected appearance and possible complications in postoperative imaging. (orig.) [de

  12. Association of CYP2D6 and CYP2C19 polymorphisms and disease-free survival of Thai post-menopausal breast cancer patients who received adjuvant tamoxifen

    Directory of Open Access Journals (Sweden)

    Chamnanphon M

    2013-05-01

    Full Text Available Montri Chamnanphon,1 Khunthong Pechatanan,2 Ekapob Sirachainan,3 Narumol Trachu,4 Wasun Chantratita,5 Ekawat Pasomsub,5 Wilai Noonpakdee,6 Insee Sensorn,1,7 Chonlaphat Sukasem11Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 2Department of Medicine, Phramongkutklao College of Medicine, 3Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 4Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 5Division of Virology, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 6Department of Biochemistry, Faculty of Science, Mahidol University, 7Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, ThailandPurpose: To investigate the impact of CYP2D6 and CYP2C19 polymorphisms in predicting tamoxifen efficacy and clinical outcomes in Thai breast cancer patients.Methods: Polymorphisms of CYP2D6 and CYP2C19 were genotyped by the AmpliChip™ CYP450 Test (Roche Molecular Diagnostics, Branchburg, NJ, USA for 57 patients, who were matched as recurrent versus nonrecurrent breast cancers (n = 33 versus n = 24, respectively, with a 5-year follow-up.Results: Based on the genotype data, five CYP2D6 predicted phenotype groups were identified in this study including homozygous extensive metabolizer (13 of 57, 22.80%, extensive/intermediate metabolizer (23 of 57, 40.40%, extensive/poor metabolizer (3 of 57, 5.30%, homozygous intermediate metabolizer (14 of 57, 24.50%, and intermediate/poor metabolizer (4 of 57, 7.00%, and three CYP2C19 genotype groups including homozygous extensive metabolizer (27 of 57, 47.40%, extensive/intermediate metabolizer (27 of 57, 47.40%, and homozygous poor metabolizer (3 of 57, 5.30%. The CYP2D6 variant alleles were *10 (52 of 114, 45.60%, *5 (5 of 114, 4.40%, *41 (2 of 114, 1.80%, *4 (1 of 114, 0

  13. Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen.

    Science.gov (United States)

    Dominick, Sally; Hickey, Martha; Chin, Jason; Su, H Irene

    2015-12-09

    Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer. To determine the effectiveness and safety of levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events. We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Specialised Register (MDSG), Cochrane Breast Cancer Group Specialised Register (CBCG), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Abstracts of Reviews of Effects (DARE), The Cochrane Library, clinicaltrials.gov, The World Health Organisation International Trials Registry, ProQuest Dissertations & Theses, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science, OpenGrey, LILACS, PubMed, and Google. The final search was performed in October 2015. Randomised controlled trials of women with breast cancer on adjuvant tamoxifen that compared endometrial surveillance alone (control condition) versus the LNG-IUS with endometrial surveillance (experimental condition) on the incidence of endometrial pathology. Study selection, risk of bias assessment and data extraction were performed independently by two review authors. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer) diagnosed at hysteroscopy or

  14. The relation of hearing loss degrees and oral stereognosis in 5-year-old children

    Directory of Open Access Journals (Sweden)

    Seyede Zohre Mousavi

    2012-12-01

    Full Text Available Background and Aim: Oral stereognosis is the ability to recognize the objects placed in the mouth; this plays a significant role in speech sounds production. Since the children with hearing loss have articulation disorders, this study aimed to clear the relation of hearing loss degrees and oral stereognosis in 5-year-old children.Methods: In this cross-sectional non-invasive study, 40 children of 5-year-old (30 children with different degrees of hearing loss and 10 normal children were involved. Oral steriognostic test was done for all of them and the Mann-Whitney U was used for statistical analysis.Results: There were significant differences between the mean of oral stereognostic ability between the normal children and the children with severe (p<0.01 or profound hearing loss (p=0.05. There was no significant difference between the mean of oral stereognostic ability among the children with moderate, severe and profound hearing loss compared with together. Besides, there was no significant difference between the mean of the time of diagnosis among all of hearing loss and normal children.Conclusion: The study shows that the children with moderate, severe and profound hearing loss have inefficient oral stereognosis in comparison with the normal children.

  15. HIV rapid testing in a Veterans Affairs hospital ED setting: a 5-year sustainability evaluation.

    Science.gov (United States)

    Knapp, Herschel; Hagedorn, Hildi; Anaya, Henry D

    2014-08-01

    Routine HIV testing in primary care settings is now recommended in the United States. The US Department of Veterans Affairs (VA) has increased the number of patients tested for HIV, but overall HIV testing rates in VA remain low. A proven strategy for increasing such testing involves nurse-initiated HIV rapid testing (HIV RT). The purpose of this work was to use a mixed methodology approach to evaluate the 5-year sustainability of an intervention that implemented HIV RT in a VA emergency department setting in a large, urban VA medical center to reduce missed diagnostic and treatment opportunities in this vulnerable patient population. In-person semistructured interviews were conducted with providers and stakeholders. Interview notes were qualitatively coded for emerging themes. Quarterly testing rates were evaluated for a 5-year time span starting from the launch in July 2008. Findings indicate that HIV RT was sustained by the enthusiasm of 2 clinical champions who oversaw the registered nurses responsible for conducting the testing. The departure of the clinical champions was correlated with a substantial drop-off in testing. Findings also indicate potential strategies for improving sustainability including engaging senior leadership in the project, engaging line staff in the implementation planning from the start to increase ownership over the innovation, incorporating information into initial training explaining the importance of the innovation to quality patient care, providing ongoing training to maintain skills, and providing routine progress reports to staff to demonstrate the ongoing impact of their efforts. Published by Elsevier Inc.

  16. Pattern of Energy and Protein Intake among Stunted Children Aged 3–5 Years in Jatinangor

    Directory of Open Access Journals (Sweden)

    Geraldo Laurus

    2016-09-01

    Full Text Available Background: A child’s optimal growth can be indicated by many factors, among them is body height, therefore stunting is one of the evidences of undergrowth. Nutrition, on the other hand, is one of variables affecting growth. This study aimed to examine the nutrition intake, in the form of energy, carbohydrate, protein, and fat in stunted children aged 3–5 years in Jatinangor. Methods: This cross sectional study was carried out in September to October 2014 using the random sampling method. Dietary data from 70 stunted children aged 3–5 years in pre–school and kindegarten located in 9 urban areas in Jatinangor were collected through 3x24 Recall and Food Frequency Questionaire and analyzed. Results: Mean energy intake was 1113.6 kcal and mean carbohydrate intake was 137.4 grams. Mean protein intake was 38.4 gram and mean fat intake was 38.2 gram. Types of food highly consumed as the source of carbohydrate were white rice and biscuit, and as the source of protein were meatball, sausage, and egg. Highest consumed vegetables, fruits and snack were water spinach, cabbage, watermelon, banana, and milk respectively. Conclusions: Mean energy intake, mean carbohydrate intake, and mean fat intake are all below the recommended dietary allowance (RDA 2013 with individual value of mean energy intake is below RDA 2013 for all subjects. Mean protein intake is slightly above RDA 2013.

  17. Analysis of the 5-year final dataset of the Supernova Legacy Survey project

    International Nuclear Information System (INIS)

    Fourmanoit, N.

    2010-01-01

    The Supernova Legacy Survey (SNLS) is a program that aims at discovering and photometrically following hundreds of Type Ia supernovae (SNe Ia). Its goal is to measure the expansion history of the Universe in order to constrain the nature of the dark energy, namely its equation of state w DE . The survey completed its data taking during summer 2008 after 5 years of program. This thesis work consists in the analysis of these 5 years of SNLS data and the photometry of the 419 Type Ia supernovae discovered and spectroscopically identified. For each supernova, the light-curves are produced in the g M r M i M z M bands, calibrated and fitted with a spectrophotometric model. A new photometric method which does not make use of any pixel re-sampling has also been implemented and tested. This method preserves the pixels statistical properties, and produces this way more accurate flux measurement statistical uncertainties, that can be propagated to cosmological measurements. Both photometry results were checked and compared using calibration stars and supernovae, proving that the accuracy of the new method flux measurement uncertainty is indeed better, and that the photometric accuracy and stability of both techniques are similar. A sample of supernovae with unprecedented statistics and quality is now available for cosmological analysis. With the complement of an external nearby supernovae sample, a measurement within 5% of the dark energy equation of state of dark energy is thus for the first time within reach. (author)

  18. A 5-year comparison of ED visits by homeless and nonhomeless patients.

    Science.gov (United States)

    Tadros, Allison; Layman, Shelley M; Brewer, Marissa Pantaleone; Davis, Stephen M

    2016-05-01

    A 2005 study examined emergency department (ED) utilization by homeless patients in the United States. Within the following 5 years, unemployment increased by 5%. The objective was to analyze changes in ED utilization between 2005 and 2010 by homeless patients and compare with nonhomeless visits. Data from the 2010 National Hospital Ambulatory Medical Care Survey were evaluated. Approximately 679854 visits were made by homeless patients, the majority of which were made by men (72.3%) and patients between the ages of 45 and 64 (50.5%). Homeless patients were twice as likely to be uninsured. ED visits by homeless patients had increased by 44% during the 5-year period. Arrival to the ED by ambulance increased by 14% between the study years, and homeless patients were less likely to be admitted. The number of visits by homeless patients in the ED increased proportionally to an overall increase in ED visits between 2005 and 2010. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Psychological recovery 5 years after the 2004 Niigata-Chuetsu earthquake in Yamakoshi, Japan.

    Science.gov (United States)

    Nakamura, Kazutoshi; Kitamura, Kaori; Someya, Toshiyuki

    2014-01-01

    The 2004 Niigata-Chuetsu earthquake of Japan caused considerable damage. We assessed long-term changes in psychological distress among earthquake victims during the period 5 years after the earthquake. The participants were people aged 18 years or older living in Yamakoshi, a community in Niigata Prefecture near the epicenter. A self-administered questionnaire survey was conducted annually for 5 consecutive years after the earthquake. Response rates were 1316/1841 (71.5%) in 2005, 667/1381 (48.3%) in 2006, 753/1451 (51.9%) in 2007, 541/1243 (43.5%) in 2008, and 814/1158 (70.3%) in 2009. The questionnaire asked about demographic characteristics, including sex, age, employment status, social network, and psychological status. Psychological distress was assessed using the 12-item General Health Questionnaire and was defined as a total score of 4 or higher. The overall prevalence of psychological distress decreased (P 1590). Subgroup analyses showed that prevalence did not decrease over the 5-year study period among participants with poor social contact (P = 0.0659). From 2008 to 2009 prevalence increased in women (+7.5%, P = 0.0403) and participants aged 65 years or older (+7.2%, P = 0.0400). The prevalence of psychological distress in Yamakoshi people decreased steadily during the 4 years immediately after the earthquake but appeared to increase thereafter. The earthquake victims are still reestablishing their lives. Thus, continued attention should be focused on maintaining and further assessing their mental health.

  20. Gross motor skill development of 5-year-old Kindergarten children in Myanmar.

    Science.gov (United States)

    Aye, Thanda; Oo, Khin Saw; Khin, Myo Thuzar; Kuramoto-Ahuja, Tsugumi; Maruyama, Hitoshi

    2017-10-01

    [Purpose] The purpose of this study was to examine the gross motor skill development of 5-year-old Kindergarten children in Myanmar. [Subjects and Methods] Total 472 healthy Kindergarten children (237 males, 235 females) of 2016-2017 academic year from four schools in urban area and four schools in rural area of Myanmar were recruited. The gross motor skill development of all subjects was assessed with the test of gross motor development second edition (TGMD-2). All subjects performed two trials for each gross motor skill and the performance was video recorded and scored. The assessment procedures were done according to the standardized guidelines of TGMD-2. [Results] The majority of subjects had average level of gross motor skill rank. The significant differences were found on the run and gallop of locomotor skills and the most of object control skills except the catch between males and females. The significant differences were also found between subjects from urban and rural areas. [Conclusion] Gross motor skill development of 5-year-old Kindergarten children in Myanmar had gender-based and region-based differences on both locomotor and object control skills. This study added a valuable information to the establishment of a normative reference of Kindergarten aged children for future studies.

  1. Body composition during early infancy and developmental progression from 1 to 5 years of age

    DEFF Research Database (Denmark)

    Abera, Mubarek; Tesfaye, Markos; Admassu, Bitiya

    2018-01-01

    aimed to examine the relation between fat mass (FM) or fat-free mass (FFM) tissues at birth and their accretion during early infancy, and later developmental progression. In a birth cohort from Ethiopia, 455 children who have BC measurement at birth and 416 who have standardised rate of BC growth during...... variables was examined using linear-mixed regression model. The finding revealed that FFM at birth was positively associated with global developmental progression from 1 to 5 years (β=1·75; 95 % CI 0·11, 3·39) and from 4 to 5 years (β=1·34; 95 % CI 0·23, 2·44) in the adjusted model. Furthermore, the rate...... of postnatal FFM tissue accretion was positively associated with development at 1 year of age (β=0·50; 95 % CI 0·01, 0·99). Neither fetal nor postnatal FM showed a significant association. In conclusion, fetal, rather than postnatal, FFM tissue accretion was associated with developmental progression...

  2. A 5-year prospective observational study of the outcomes of international treatment guidelines for Crohn's disease.

    LENUS (Irish Health Repository)

    Cullen, Garret

    2012-02-01

    BACKGROUND & AIMS: Therapeutic strategies for patients with Crohn\\'s disease are based on American and European guidelines. High rates of corticosteroid dependency and low remission rates are identified as weaknesses of this therapy and as justification for early introduction of biologic agents (top-down treatment) in moderate\\/severe Crohn\\'s disease. We reviewed outcomes and corticosteroid-dependency rates of patients with moderate-to-severe disease who were treated according to the international guidelines. METHODS: Consecutive patients (102) newly diagnosed with Crohn\\'s disease in 2000-2002 were identified from a prospectively maintained database. Severity of disease was scored using the Harvey-Bradshaw Index (HBI). Disease was classified by Montreal classification. Five-year follow-up data were recorded. RESULTS: Seventy-two patients had moderate\\/severe disease at diagnosis (HBI >8). Fifty-four (75%) had nonstricturing, nonpenetrating disease (B1). Sixty-four (89%) received corticosteroids, and 44 (61%) received immunomodulators. Twenty-one patients (29%) received infliximab. Thirty-nine patients (54%) required resection surgery. At a median of 5 years, 66 of 72 (92%) patients with moderate\\/severe disease were in remission (median HBI, 1). Twenty-five patients (35%) required neither surgery nor biologic therapy. CONCLUSIONS: When international treatment guidelines are strictly followed, Crohn\\'s disease patients can achieve high rates of remission and low rates of morbidity at 5 years. Indiscriminate use of biologic agents therefore is not appropriate for all patients with moderate-to-severe disease.

  3. Psychosocial Development of 5-year-old Children with Hearing Loss: Risks and protective factors

    Science.gov (United States)

    Wong, Cara L.; Ching, Teresa YC; Leigh, Greg; Cupples, Linda; Button, Laura; Marnane, Vivienne; Whitfield, Jessica; Gunnourie, Miriam; Martin, Louise

    2016-01-01

    Objective The aims of this paper were to report on the global psychosocial functioning of 5-year-old DHH children and examine the risk and protective factors that predict outcomes. Design A cross-sectional analysis of data collected from a prospective, population-based longitudinal study. Study Sample Parents/caregivers of 356 children completed questionnaires on psychosocial development (CDI, SDQ), functional communication (PEACH) and demographic information. Children completed standardised assessments of non-verbal cognitive ability (WNV) and language (PLS-4). Results On average, global psychosocial functioning was within the range of typically developing children; however, variability was high and 12% of children had scores that were more than 2 SDs below the norm. Non-verbal cognitive ability, presence of additional disabilities, language and functional communication significantly predicted outcomes. In contrast, type of hearing device, severity of hearing loss and age at intervention did not. Conclusion The global psychosocial functioning of this cohort of 5-year-old DHH children fell within the range of typically developing children. . The findings suggest that spoken language ability and functional communication skills are vital for healthy psychosocial development. PMID:27541363

  4. A 5-year follow-up case of multiple intrusive luxative injuries

    Directory of Open Access Journals (Sweden)

    Seema Thakur

    2012-01-01

    Full Text Available Introduction: Traumatic intrusive luxation is one of the most severe forms of dental injuries, usually affecting the maxillary incisors. The consequence of such an occurrence is a high risk of healing complications such as pulp necrosis, external inflammatory resorption, and external replacement resorption (ankylosis. Case Report: This report presents a case of severe intrusive luxation of multiple anterior teeth in an 11-year-old girl. The teeth were repositioned successfully by endodontic and orthodontic management. The case was monitored for 5 years. Discussion: Depending on the severity of the injury, different clinical approaches for treatment of intrusive luxation may be used. Despite the variety of treatment modalities, rehabilitation of intruded teeth is always a challenge and a multidisciplinary approach is important to achieve a successful result. In this case, intruded teeth were endodontically treated with multiple calcium hydroxide dressings and repositioned orthodontically. The follow-up of such cases is very important as the repair process after intrusion is complex. After 5 years, no clinical or radiographic pathology was detected.

  5. Maxillary Arch Dimension Changes of 3-5 Years Old Filipino Children

    Directory of Open Access Journals (Sweden)

    Abdol Hamid Zafarmand

    2014-11-01

    Full Text Available Background: The purpose of this study was to assess the dental arch dimensions in primary dentition of 3-5 years old Filipino children and determining the existence of sexual dimorphism.Materials and Methods: In this descriptive study, 60 Filipino preschool children aged 3-5 years old were selected from Manila city. Study casts were used for measurements of 3 arch dimensions: bicanine width, bimolar width, and arch length. The analyses were performed to compare values within age-groups and within gender-groups, besides reporting mean and standard deviations. The data were subjected to One-way ANOVA and Student t-test.Results: Significant differences were observed regarding dental arch dimensions among different ages and genders (p<0.05. Comparison between genders showed a statistically significant difference in bicanine width at the age of 4 (p=0.04, in bimolar width at age of 5 (p=0.006, and in arch length at age of 4 (p=0.03 and 5 (p=0.02. Differences within male group for different ages showed only arch length dimension was statistically significant (p=0.021. In females, however the comparison between age-groups also revealed a statistically significant difference in bicanine (p= 0.016 and bimolar widths (p=0.027 dimensions.Conclusion: The present study showed that dental arch dimensions, vary among different ages and genders of children. It also showed that a sexual dimorphism does exist between the gender groups.

  6. Efficacy of Essure hysteroscopic sterilization--5 years follow up of 1200 women.

    Science.gov (United States)

    Ríos-Castillo, José E; Velasco, Esther; Arjona-Berral, José E; Monserrat Jordán, José A; Povedano-Cañizares, Balbino; Castelo-Branco, Camil

    2013-06-01

    To assess the efficacy of the Essure hysteroscopic birth control device after 5 years follow up. Retrospective analysis of case series. Outpatient hysteroscopy facility in a large teaching hospital. One-thousand three-hundred and twenty-one women who underwent hysteroscopic sterilization with Essure device (Conceptus, Inc., Mountain View, CA) between January 2003 and May 2005. Hysteroscopic tubal sterilization using Essure system. Efficacy/effectiveness, failure rate. Satisfactory insertion was accomplished in the first attempt in 1166 women (97.16%). After the second attempt, successful insertion rate rise to 98.6%. (n = 31, 2.6%). Three pregnancies had been reported after 5 years follow up, which implies an overall absolute rate of 0.25%. This represents a Pearl index of 0.05 after 72,000 months of surveillance. All of them occurred in the first year of use of the microinsert. There has been no unintended pregnancy in the next 4 years. Essure has the lowest Pearl index never published being the most effective permanent birth control system to date. Unintended pregnancies tend to occur in the first year after the insertion, and can be avoided encouraging women to accomplish the protocol.

  7. A 5-Year Investigation of Children's Adaptive Functioning Following Conformal Radiation Therapy for Localized Ependymoma

    International Nuclear Information System (INIS)

    Netson, Kelli L.; Conklin, Heather M.; Wu Shengjie; Xiong Xiaoping; Merchant, Thomas E.

    2012-01-01

    Purpose: Conformal and intensity modulated radiation therapies have the potential to preserve cognitive outcomes in children with ependymoma; however, functional behavior remains uninvestigated. This longitudinal investigation prospectively examined intelligence quotient (IQ) and adaptive functioning during the first 5 years after irradiation in children diagnosed with ependymoma. Methods and Materials: The study cohort consisted of 123 children with intracranial ependymoma. Mean age at irradiation was 4.60 years (95% confidence interval [CI], 3.85-5.35). Serial neurocognitive evaluations, including an age-appropriate IQ measure and the Vineland Adaptive Behavior Scales (VABS), were completed before irradiation, 6 months after treatment, and annually for 5 years. A total of 579 neurocognitive evaluations were included in these analyses. Results: Baseline IQ and VABS were below normative means (P<.05), although within the average range. Linear mixed models revealed stable IQ and VABS across the follow-up period, except for the VABS Communication Index, which declined significantly (P=.015). Annual change in IQ (−.04 points) did not correlate with annual change in VABS (−.90 to +.44 points). Clinical factors associated with poorer baseline performance (P<.05) included preirradiation chemotherapy, cerebrospinal fluid shunt placement, number and extent of surgical resections, and younger age at treatment. No clinical factors significantly affected the rate of change in scores. Conclusions: Conformal and intensity modulated radiation therapies provided relative sparing of functional outcomes including IQ and adaptive behaviors, even in very young children. Communication skills remained vulnerable and should be the target of preventive and rehabilitative interventions.

  8. EXPOSE-E: an ESA astrobiology mission 1.5 years in space.

    Science.gov (United States)

    Rabbow, Elke; Rettberg, Petra; Barczyk, Simon; Bohmeier, Maria; Parpart, André; Panitz, Corinna; Horneck, Gerda; von Heise-Rotenburg, Ralf; Hoppenbrouwers, Tom; Willnecker, Rainer; Baglioni, Pietro; Demets, René; Dettmann, Jan; Reitz, Guenther

    2012-05-01

    The multi-user facility EXPOSE-E was designed by the European Space Agency to enable astrobiology research in space (low-Earth orbit). On 7 February 2008, EXPOSE-E was carried to the International Space Station (ISS) on the European Technology Exposure Facility (EuTEF) platform in the cargo bay of Space Shuttle STS-122 Atlantis. The facility was installed at the starboard cone of the Columbus module by extravehicular activity, where it remained in space for 1.5 years. EXPOSE-E was returned to Earth with STS-128 Discovery on 12 September 2009 for subsequent sample analysis. EXPOSE-E provided accommodation in three exposure trays for a variety of astrobiological test samples that were exposed to selected space conditions: either to space vacuum, solar electromagnetic radiation at >110 nm and cosmic radiation (trays 1 and 3) or to simulated martian surface conditions (tray 2). Data on UV radiation, cosmic radiation, and temperature were measured every 10 s and downlinked by telemetry. A parallel mission ground reference (MGR) experiment was performed on ground with a parallel set of hardware and samples under simulated space conditions. EXPOSE-E performed a successful 1.5-year mission in space.

  9. Non-surgical approach to advanced chronic periodontitis: a 17.5-year case report.

    Science.gov (United States)

    Kawamura, M; Sadamori, S; Okada, M; Sasahara, H; Hamada, T

    2004-03-01

    This 17.5-year longitudinal case report details the treatment of advanced chronic periodontitis in a female patient commencing at 34 years of age. The woman was provided with periodontal care comprising of temporary fixation, scaling and root planing, intra-pocket irrigation using a root canal syringe and regular supervised maintenance. The patient presented with a 10-year history of bleeding gums. Therapy conducted in general practice had included simple curettage and irrigation. However, these treatments proved unsuccessful and the patient often changed dentists seeking better treatment. She presented to the University Dental Hospital, for diagnosis and treatment of her periodontal conditions after her mandibular lateral incisor had exfoliated. On presentation a purulent exudate could be expressed from all of the pockets. All anterior teeth, excluding the maxillary canines, demonstrated +2 to +3 mobility. The patient did not want any surgical treatment or her teeth extracted. It was decided to treat the patient conservatively without surgery. By postponing extraction, the authors were in a better position to determine the prognosis of the remaining teeth after the infection was under control. Although six teeth were extracted during the 17.5 years, this case report suggests that a non-surgical approach is a viable option while maintaining regular visits for periodontal care.

  10. Factors associated with vaccination coverage in children < 5 years in Angola

    Directory of Open Access Journals (Sweden)

    Manuel Falcão Saturnino de Oliveira

    2014-12-01

    Full Text Available OBJECTIVE To analyze vaccination coverage and factors associated with a complete immunization scheme in children < 5 years old. METHODS This cross-sectional household census survey evaluated 1,209 children < 5 years old living in Bom Jesus, Angola, in 2010. Data were obtained from interviews, questionnaires, child immunization histories, and maternal health histories. The statistical analysis used generalized linear models, in which the dependent variable followed a binary distribution (vaccinated, unvaccinated and the association function was logarithmic and had the children’s individual, familial, and socioeconomic factors as independent variables. RESULTS Vaccination coverage was 37.0%, higher in children < 1 year (55.0% and heterogeneous across neighborhoods; 52.0% of children of both sexes had no immunization records. The prevalence rate of vaccination significantly varied according to child age, mother’s level of education, family size, ownership of household appliances, and destination of domestic waste. CONCLUSIONS Vulnerable groups with vaccination coverage below recommended levels continue to be present. Some factors indicate inequalities that represent barriers to full immunization, indicating the need to implement more equitable policies. The knowledge of these factors contributes to planning immunization promotion measures that focus on the most vulnerable groups.

  11. Cre recombinase expression or topical tamoxifen treatment do not affect retinal structure and function, neuronal vulnerability or glial reactivity in the mouse eye.

    Science.gov (United States)

    Boneva, S K; Groß, T R; Schlecht, A; Schmitt, S I; Sippl, C; Jägle, H; Volz, C; Neueder, A; Tamm, E R; Braunger, B M

    2016-06-14

    Mice with a constitutive or tamoxifen-induced Cre recombinase (Cre) expression are frequently used research tools to allow the conditional deletion of target genes via the Cre-loxP system. Here we analyzed for the first time in a comprehensive and comparative way, whether retinal Cre expression or topical tamoxifen treatment itself would cause structural or functional changes, including changes in the expression profiles of molecular markers, glial reactivity and photoreceptor vulnerability. To this end, we characterized the transgenic α-Cre, Lmop-Cre and the tamoxifen-inducible CAGG-CreER™ mouse lines, all having robust Cre expression in the neuronal retina. In addition, we characterized the effects of topical tamoxifen treatment itself in wildtype mice. We performed morphometric analyses, immunohistochemical staining, in vivo ERG and angiography analyses and realtime RT-PCR analyses. Furthermore, the influence of Cre recombinase or topical tamoxifen exposure on neuronal vulnerability was studied by using light damage as a model for photoreceptor degeneration. Taken together, neither the expression of Cre, nor topical tamoxifen treatment caused detectable changes in retinal structure and function, the expression profiles of investigated molecular markers, glial reactivity and photoreceptor vulnerability. We conclude that the Cre-loxP system and its induction through tamoxifen is a safe and reliable method to delete desired target genes in the neural retina. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Development of biodegradable polymer based tamoxifen citrate loaded nanoparticles and effect of some manufacturing process parameters on them: a physicochemical and in-vitro evaluation

    Directory of Open Access Journals (Sweden)

    Basudev Sahana

    2010-08-01

    Full Text Available Basudev Sahana, Kousik Santra, Sumit Basu, Biswajit MukherjeeDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata, IndiaAbstract: The aim of the present study was to develop nanoparticles of tamoxifen citrate, a non-steroidal antiestrogenic drug used for the treatment of breast cancer. Biodegradable poly (D, L- lactide-co-glycolide-85:15 (PLGA was used to develop nanoparticles of tamoxifen citrate by multiple emulsification (w/o/w and solvent evaporation technique. Drug-polymer ratio, polyvinyl alcohol concentrations, and homogenizing speeds were varied at different stages of preparation to optimize the desired size and release profile of drug. The characterization of particle morphology and shape was performed by field emission scanning electron microscope (FE-SEM and particle size distribution patterns were studied by direct light scattering method using zeta sizer. In vitro drug release study showed that release profile of tamoxifen from biodegradable nanoparticles varied due to the change in speed of centrifugation for separation. Drug loading efficiency varied from 18.60% to 71.98%. The FE-SEM study showed that biodegradable nanoparticles were smooth and spherical in shape. The stability studies of tamoxifen citrate in the experimental nanoparticles showed the structural integrity of tamoxifen citrate in PLGA nanoparticles up to 60°C in the tested temperatures. Nanoparticles containing tamoxifen citrate could be useful for the controlled delivery of the drug for a prolonged period.Keywords: biodegradable, nanoparticles, PLGA, stability, tamoxifen citrate

  13. Segmental correction of adolescent idiopathic scoliosis by all-screw fixation method in adolescents and young adults. minimum 5 years follow-up with SF-36 questionnaire

    Directory of Open Access Journals (Sweden)

    Yu Ching-Hsiao

    2012-02-01

    Full Text Available Abstract Background In our institution, the fixation technique in treating idiopathic scoliosis was shifted from hybrid fixation to the all-screw method beginning in 2000. We conducted this study to assess the intermediate -term outcome of all-screw method in treating adolescent idiopathic scoliosis (AIS. Methods Forty-nine consecutive patients were retrospectively included with minimum of 5-year follow-up (mean, 6.1; range, 5.1-7.3 years. The average age of surgery was 18.5 ± 5.0 years. We assessed radiographic measurements at preoperative (Preop, postoperative (PO and final follow-up (FFU period. Curve correction rate, correction loss rate, complications, accuracy of pedicle screws and SF-36 scores were analyzed. Results The average major curve was corrected from 58.0 ± 13.0° Preop to 16.0 ± 9.0° PO(p p = 0.12 FFU. This revealed a 72.7% correction rate and a correction loss of 2.4° (3.92%. The thoracic kyphosis decreased little at FFU (22 ± 12° to 20 ± 6°, (p = 0.25. Apical vertebral rotation decreased from 2.1 ± 0.8 PreOP to 0.8 ± 0.8 at FFU (Nash-Moe grading, p Conclusion Follow-up more than 5 years, the authors suggest that all-screw method is an efficient and safe method.

  14. Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen + triptorelin in premenopausal patients with early breast cancer.

    Science.gov (United States)

    Rossi, Emanuela; Morabito, Alessandro; De Maio, Ermelinda; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; Piccirillo, Maria Carmela; D'Aiuto, Giuseppe; D'Aiuto, Massimiliano; Rinaldo, Massimo; Botti, Gerardo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

    2008-01-10

    To compare the endocrine effects of 6 months of adjuvant treatment with letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with early breast cancer within an ongoing phase 3 trial (Hormonal Adjuvant Treatment Bone Effects study). Prospectively collected hormonal data were available for 81 premenopausal women, of whom 30 were assigned to receive tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin +/- zoledronate. Serum 17-beta-estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), Delta4-androstenedione, testosterone, dehydroepiandrosterone-sulfate, progesterone, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline and after 6 months of treatment. For each hormone, 6-month values were compared between treatment groups by the Wilcoxon-Mann-Whitney exact test. Median age was 44 years for both groups of patients. Letrozole + triptorelin (+/- zoledronate) induced a stronger suppression of median E2 serum levels (P = .0008), LH levels (P = .0005), and cortisol serum levels (P < .0001) compared with tamoxifen + triptorelin. Median FSH serum levels were suppressed in both groups, but such suppression was lower among patients receiving letrozole, who showed significantly higher median FSH serum levels (P < .0001). No significant differences were observed for testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone between the two groups of patients. Letrozole in combination with triptorelin induces a more intense estrogen suppression than tamoxifen + triptorelin in premenopausal patients with early breast cancer.

  15. Implication of protein tyrosine phosphatase 1B in MCF-7 cell proliferation and resistance to 4-OH tamoxifen

    International Nuclear Information System (INIS)

    Blanquart, Christophe; Karouri, Salah-Eddine; Issad, Tarik

    2009-01-01

    The protein tyrosine phosphatase 1B (PTP1B) and the T-cell protein tyrosine phosphatase (TC-PTP) were initially thought to be mainly anti-oncogenic. However, overexpression of PTP1B and TC-PTP has been observed in human tumors, and recent studies have demonstrated that PTP1B contributes to the appearance of breast tumors by modulating ERK pathway. In the present work, we observed that decreasing the expression of TC-PTP or PTP1B in MCF-7 cells using siRNA reduced cell proliferation without affecting cell death. This reduction in proliferation was associated with decreased ERK phosphorylation. Moreover, selection of tamoxifen-resistant MCF-7 cells, by long-term culture in presence of 4-OH tamoxifen, resulted in cells that display overexpression of PTP1B and TC-PTP, and concomitant increase in ERK and STAT3 phosphorylation. siRNA experiments showed that PTP1B, but not TC-PTP, is necessary for resistance to 4-OH tamoxifen. Therefore, our work indicates that PTP1B could be a relevant therapeutic target for treatment of tamoxifen-resistant breast cancers.

  16. Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Chiu, Hsien-Chun; Syu, Jhan-Jhang; Jian, Yi-Jun; Chen, Chien-Yu; Jian, Yun-Ting; Huang, Yi-Jhen; Wo, Ting-Yu; Lin, Yun-Wei

    2014-03-01

    Tamoxifen is a triphenylethylene nonsteroidal estrogen receptor (ER) antagonist used worldwide as an adjuvant hormone therapeutic agent in the treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Thymidine phosphorylase (TP) is an enzyme of the pyrimidine salvage pathway which is upregulated in cancers. In this study, tamoxifen treatment inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with tamoxifen decreased TP mRNA and protein levels through AKT inactivation. Furthermore, expression of constitutively active AKT (AKT-CA) vectors significantly rescued the decreased TP protein and mRNA levels in tamoxifen-treated NSCLC cells. In contrast, combination treatment with PI3K inhibitors (LY294002 or wortmannin) and tamoxifen further decreased the TP expression and cell viability of NSCLC cells. Knocking down TP expression by transfection with small interfering RNA of TP enhanced the cytotoxicity and cell growth inhibition of tamoxifen. Erlotinib (Tarceva, OSI-774), an orally available small molecular inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is approved for clinical treatment of NSCLC. Compared to a single agent alone, tamoxifen combined with erlotinib resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-AKT and phospho-ERK1/2, and reduced TP protein levels. These findings may have implications for the rational design of future drug regimens incorporating tamoxifen and erlotinib for the treatment of NSCLC. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. The Working Memory and Dorsolateral Prefrontal-Hippocampal Functional Connectivity Changes in Long-Term Survival Breast Cancer Patients Treated with Tamoxifen

    Science.gov (United States)

    Chen, Xingui; Tao, Longxiang; Li, Jingjing; Wu, Jiaonan; Zhu, Chunyan; Yu, Fengqiong; Zhang, Lei; Zhang, Jingjie; Qiu, Bensheng; Yu, Yongqiang; He, Xiaoxuan

    2017-01-01

    Abstract Background: Tamoxifen is the most widely used drug for treating patients with estrogen receptor-sensitive breast cancer. There is evidence that breast cancer patients treated with tamoxifen exhibit cognitive dysfunction. However, the underlying neural mechanism remains unclear. The present study aimed to investigate the neural mechanisms underlying working memory deficits in combination with functional connectivity changes in premenopausal women with breast cancer who received long-term tamoxifen treatment. Methods: A total of 31 premenopausal women with breast cancer who received tamoxifen and 32 matched healthy control participants were included. The participants completed n-back tasks and underwent resting-state functional magnetic resonance imaging, which measure working memory performance and brain functional connectivity, respectively. A seed-based functional connectivity analysis within the whole brain was conducted, for which the dorsolateral prefrontal cortex was chosen as the seed region. Results: Our results indicated that the tamoxifen group had significant deficits in working memory and general executive function performance and significantly lower functional connectivity of the right dorsolateral prefrontal cortex with the right hippocampus compared with the healthy controls. There were no significant changes in functional connectivity in the left dorsolateral prefrontal cortex within the whole brain between the tamoxifen group and healthy controls. Moreover, significant correlations were found in the tamoxifen group between the functional connectivity strength of the dorsolateral prefrontal cortex with the right hippocampus and decreased working memory performance. Conclusion: This study demonstrates that the prefrontal cortex and hippocampus may be affected by tamoxifen treatment, supporting an antagonistic role of tamoxifen in the long-term treatment of breast cancer patients. PMID:28177081

  18. Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial.

    Science.gov (United States)

    Rossi, Emanuela; Morabito, Alessandro; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; De Maio, Ermelinda; Di Maio, Massimo; Piccirillo, Maria Carmela; De Feo, Gianfranco; D'Aiuto, Giuseppe; Botti, Gerardo; Chiodini, Paolo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

    2009-07-01

    PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

  19. Hormone therapy with tamoxifen reduces plasma levels of NT-B-type natriuretic peptide but does not change ventricular ejection fraction after chemotherapy in women with breast cancer

    Directory of Open Access Journals (Sweden)

    F.B. Silva

    2015-02-01

    Full Text Available The objective of this study was to evaluate the effect of tamoxifen on the plasma concentration of NT-pro-B-type natriuretic peptide (NT-proBNP in women undergoing chemotherapy for breast cancer and to correlate changes in NT-proBNP with the left ventricular ejection fraction (LVEF. Over a period of 12 months, we followed 60 women with a diagnosis of breast cancer. The patients were separated into a group that received only chemotherapy (n=23, a group that received chemotherapy + tamoxifen (n=21, and a group that received only tamoxifen (n=16. Plasma levels of NT-proBNP were assessed at 0 (T0, 6 (T6, and 12 (T12 months of treatment, and echocardiography data were assessed at T0 and T12. Plasma NT-proBNP levels were increased in the chemotherapy-only group at T6 and T12, whereas elevated NT-proBNP levels were only found at T6 in the chemotherapy + tamoxifen group. At T12, the chemotherapy + tamoxifen group exhibited a significant reduction in the peptide to levels similar to the group that received tamoxifen alone. The chemotherapy-only group exhibited a significant decrease in LVEF at T12, whereas the chemotherapy + tamoxifen and tamoxifen-only groups maintained levels similar to those at the beginning of treatment. Treatment with tamoxifen for 6 months after chemotherapy significantly reduced the plasma levels of NT-proBNP and did not change LVEF in women with breast cancer.

  20. Clinical Presentation of Uterine Fibroids in Nnewi, Nigeria: A 5-year Review.

    Science.gov (United States)

    Ezeama, Co; Ikechebelu, Ji; Obiechina, Nj; Ezeama, Nn

    2012-07-01

    Uterine leiomyomas are the commonest benign tumors in women, with a higher preponderance amongst Africans. Several etiological factors have been suggested, with subtle variations in clinical presentation being reported in different studies. This may constitute a determinant for the management measures undertaken. To review the clinical presentation and management measures undertaken for uterine leiomyoma. A retrospective study was conducted at Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, from January 2002 to December 2006. A review of case records of patients with a diagnosis of uterine leiomyoma was done. The data were analyzed and presented in tables using comparative percentages. Uterine leiomyoma constituted 117 of the 1094 gynecological admissions during this study period (10.7%, 117/1094). The mean (SD) age of presentation was 35.7 (6.1) years. Most of the patients were nulliparous (76.7%, 79/103) and 51.5% (53/103) were married. The commonest mode of presentation was lower abdominal mass (66.9%, 67/103) and the least was recurrent abortion (1%, 1/103). Surgery was employed in all cases, with myomectomy being the commonest modality used in 90.3% (93/103) of cases. The common postoperative complications were prolonged pain (49.5%, 51/103) and postoperative pyrexia (34.9%, 36/103). The symptom of lower abdominal mass correlates with late presentations in our setting. This makes the application of newer therapies like laparoscopic myomectomy difficult even when they are available. Other therapies which are independent of fibroid size (like uterine artery embolization) are not readily available in our environment. This further emphasizes the importance of myomectomy as the most important treatment modality in our environment.

  1. Optimizing tamoxifen-inducible Cre/loxp system to reduce tamoxifen effect on bone turnover in long bones of young mice.

    Science.gov (United States)

    Zhong, Zhendong A; Sun, Weihua; Chen, Haiyan; Zhang, Hongliang; Lay, Yu-An E; Lane, Nancy E; Yao, Wei

    2015-12-01

    For tamoxifen-dependent Cre recombinase, also known as CreER recombinase, tamoxifen (TAM) is used to activate the Cre to generate time- and tissue-specific mouse mutants. TAM is a potent CreER system inducer; however, TAM is also an active selective estrogen receptor modulator (SERM) that can influence bone homeostasis. The purpose of this study was to optimize the TAM dose for Cre recombinase activation while minimizing the effects of TAM on bone turnover in young growing mice. To evaluate the effects of TAM on bone turnover and bone mass, 1-month-old wild-type male and female mice were intraperitoneally injected with TAM at 0, 1, 10 or 100mg/kg/day for four consecutive days, or 100, 300 mg/kg/day for one day. The distal femurs were analyzed one month after the last TAM injection by microCT, mechanical test, and surface-based bone histomorphometry. Similar doses of TAM were used in Col1 (2.3 kb)-CreERT2; mT/mG reporter male mice to evaluate the dose-dependent efficacy of Cre-ER activation in bone tissue. A TAM dose of 100 mg/kg × 4 days significantly increased trabecular bone volume/total volume (BV/TV) of the distal femur, femur length, bone strength, and serum bone turnover markers compared to the 0mg control group. In contrast, TAM doses ≤ 10 mg/kg did not significantly change any of these parameters compared to the 0mg group, although a higher bone strength was observed in the 10mg group. Surface-based histomorphometry revealed that the 100mg/kg dose of TAM dose significantly increased trabecular bone formation and decreased periosteal bone formation at 1-week post-TAM treatment. Using the reporter mouse model Col1-CreERT2; mT/mG, we found that 10mg/kg TAM induced Col1-CreERT2 activity in bone at a comparable level to the 100mg/kg dose. TAM treatment at 100mg/kg/day × 4 days significantly affects bone homeostasis, resulting in an anabolic bone effect on trabecular bone in 1-month-old male mice. However, a lower dose of TAM at 10 mg/kg/day × 4 days can

  2. Treatment of selective mutism: a 5-year follow-up study.

    Science.gov (United States)

    Oerbeck, Beate; Overgaard, Kristin Romvig; Stein, Murray B; Pripp, Are Hugo; Kristensen, Hanne

    2018-01-22

    Selective mutism (SM) has been defined as an anxiety disorder in the diagnostic and statistical manual of mental disorders (DSM-5). Cognitive behavioral therapy (CBT) is the recommended approach for SM, but prospective long-term outcome studies are lacking. Reports from the children themselves, and the use of more global quality of life measures, are also missing in the literature. We have developed a school-based CBT intervention previously found to increase speech in a pilot efficacy study and a randomized controlled treatment study. Continued progress was found in our 1-year follow-up studies, where older age and more severe SM had a significant negative effect upon outcome. In the present study, we provide 5-year outcome data for 30 of these 32 children with SM who completed the same CBT for mean 21 weeks (sd 5, range 8-24) at mean age 6 years (10 boys). Mean age at the 5-year follow-up was 11 years (range 8-14). Outcome measures were diagnostic status, the teacher- and parent-rated selective mutism questionnaires, and child rated quality of life and speaking behavior. At the 5-year follow-up, 21 children were in full remission, five were in partial remission and four fulfilled diagnostic criteria for SM. Seven children (23%) fulfilled criteria for social phobia, and separation anxiety disorder, specific phobia and/or enuresis nocturna were found in a total of five children (17%). Older age and severity at baseline and familial SM were significant negative predictors of outcome. Treatment gains were maintained on the teacher- and parent questionnaires. The children rated their overall quality of life as good. Although most of them talked outside of home, 50% still experienced it as somewhat challenging. These results point to the long-term effectiveness of CBT for SM, but also highlight the need to develop more effective interventions for the subset of children with persistent symptoms.Clinical trials registration NCT01002196.

  3. [Child malnutrition in children under 5 years of age in Peru: trends and determinants].

    Science.gov (United States)

    Sobrino, Manuel; Gutiérrez, César; Cunha, Antonio J; Dávila, Miguel; Alarcón, Jorge

    2014-02-01

    Analyze malnutrition and anemia trends in Peruvian children under 5 years of age and their association with determinants in the 2000-2011 period. Nutritional indicators for children under 5 years of age from the 2011 Demographic and Family Health Survey (ENDES), and their evolution based on data from the 2000, 2005, and 2008 ENDES, were analyzed. Chronic malnutrition (CM) (height/age ≤ 2 SD), acute malnutrition (AM), (height/weight ≤ 2 SD), and anemia trends were estimated. Associations were found with factors such as sex, age, area of residence (urban or rural), region of residence, mother's education, wealth quintile, availability of public water system, sewer availability, altitude, presence of other children in household, birth order, presence of diarrhea in previous 15 days, and presence of cough in previous 15 days. AM, CM, and anemia in Peruvian children under 5 years of age decreased from 2000-2011. This reduction was not uniform for the three conditions, with decreases of 1.1% to 0.4% recorded for AM, 31.6% to 19.6% for CM, and 50.4% to 30.7% for anemia. Although the factors analyzed were related to the prevalence of these three illnesses, calculation of the adjusted odds ratios showed significant differences for CM (mother's education, Sierra region, altitude greater than 2 500 m above sea level, presence of two or more children in household, and being the third or successive child) and anemia (child sex [higher in males], children under 2 years of age, Resto de costa region and Selva region, altitude greater than 2 500 m above sea level, availability of public water system, sewer availability, presence of two or more children in household, and presence of diarrhea within 15 days prior to the survey). For AM, differences were observed according to some factors but they were not significant in the adjusted model. In the 2000-2011 period, Peru achieved reduction of its CM, AM, and anemia rates. AM rates decreased to almost one-third, with overall

  4. Basis for new strategies in postoperative radiotherapy of bronchogenic carcinoma

    International Nuclear Information System (INIS)

    Choi, N.C.H.; Grillo, H.C.; Gardiello, M.; Scannel, J.G.; Wilkins, E.W. Jr.

    1980-01-01

    In order to improve our understanding of the role of postoperative radiotherapy and to search for new strategies in the management of N 1 , N 2 , T 3 stage carcinoma of the lung, we analyzed results of treatment in 148 of 166 patients who were registered at the Massachusetts General Hospital Tumor Registry from 1971 to 1977 with a pathological diagnosis of N 1 , N 2 , T 3 carcinoma of the lung after pulmonary resection. Ninety-three patients received postoperative radiotherapy and another 55 were followed without further treatment. Patients with adenocarcinoma showed significant improvement of survival by postoperative radiotherapy; actuarial NED (no evidence of disease) survival rates were 85% and 51% at 1 year, and 43% and 8% at 5 years for S + RT (patients treated with surgery plus postoperative radiotherapy) and S (patients treated with surgery only) groups, respectively, (P 2 , T 3 stages. Regional recurrence was the most common failure in squamous cell carcinoma; 76% (13/17) and 45% (10/22) of all failures were in the regional area in S and S + RT groups. Regional failure in S + RT group was noted with radiation dose up to 5000 rad (TDF 82) which suggests radiation dose higher than 5000 rad in future trial

  5. Midfacial rejuvenation via a minimal-incision brow-lift approach: critical evaluation of a 5-year experience.

    Science.gov (United States)

    Williams, Edwin F; Vargas, Hannah; Dahiya, Ravinder; Hove, Christopher R; Rodgers, Bret J; Lam, Samuel M

    2003-01-01

    To evaluate the surgical technique, cosmetic results, and complications of patients who underwent a midface-lift via a minimal-incision brow-lift performed by the senior author (E.F.W.). Private, ambulatory surgical center. A retrospective review of 325 midface-lifts performed over a 5-year period by a single surgeon. Patients A total of 325 consecutive patients who underwent a midface-lift, with or without concurrent rhytidectomy and other adjunctive procedures, and who completed 3 months of follow-up were reviewed for perioperative complications. One hundred patients who had complete photographic and chart records and who had a minimum of 6 months of follow-up were randomly selected for photographic rating and chart review. Of the patients who had a minimum of 1 year of follow-up, 50 were randomly selected to determine if midfacial elevation led to any evidence of lateral-canthal distortion. Midfacial elevation was assessed in 3 facial zones by 3 independent evaluators. Zone I represents the malar-infraorbital complex; zone II, the nasolabial sulcus; and zone III, the jawline. The zones were rated on a scale from 0 to 2 (0, no improvement; 1, mild improvement; and 2, marked improvement). Change in the lateral-canthal position was measured in the vertical and horizontal axis for each eye. All complications were recorded. The 3 independent evaluators correlated well in their scores (kappa = 0.643) and found that most patients showed the best improvements in zone I, with 70% of patients showing marked improvement (Pjawline (zone III). Although the postoperative lateral-canthal position revealed statistically significant vertical elevation of the lateral canthus on the right side, this finding did not correlate with any perceived clinical significance by the reviewer or patient (P<.01). Temporary morbidity included 2 subperiosteal abscesses and 3 frontal and 1 buccal facial nerve neuropraxias that resolved by 6 months. Permanent complications included 1 case of

  6. Multicenter Analysis of Midterm Clinical Outcomes of Arthroscopic Labral Repair in the Hip: Minimum 5-Year Follow-up.

    Science.gov (United States)

    Hevesi, Mario; Krych, Aaron J; Johnson, Nick R; Redmond, John M; Hartigan, David E; Levy, Bruce A; Domb, Benjamin G

    2018-02-01

    The technique of hip arthroscopic surgery is advancing and becoming more commonly performed. However, most current reported results are limited to short-term follow-up, and therefore, the durability of the procedure is largely unknown. To perform a multicenter analysis of mid-term clinical outcomes of arthroscopic hip labral repair and determine the risk factors for patient outcomes. Cohort study; Level of evidence, 3. Prospectively collected data of primary hip arthroscopic labral repair performed at 4 high-volume centers between 2008 and 2011 were reviewed retrospectively. Patients were assessed preoperatively and postoperatively with the visual analog scale (VAS), modified Harris Hip Score (mHHS), and Hip Outcome Score-Sports-Specific Subscale (HOS-SSS) at a minimum of 5 years' follow-up. Factors including age, body mass index (BMI), Tönnis grade, and cartilage grade were analyzed in relation to outcome scores, and revision rates were determined. Failure was defined as subsequent ipsilateral hip surgery, including revision arthroscopic surgery and open hip surgery. A total of 303 patients (101 male, 202 female) with a mean age of 32.0 years (range, 10.7-58.9 years) were followed for a mean of 5.7 years (range, 5.0-7.9 years). Patients achieved mean improvements in VAS of 3.5 points, mHHS of 20.1 points, and HOS-SSS of 29.3 points. Thirty-seven patients (12.2%) underwent revision arthroscopic surgery, and 12 (4.0%) underwent periacetabular osteotomy, resurfacing, or total hip arthroplasty during the study period. Patients with a BMI >30 kg/m 2 had a mean mHHS score 9.5 points lower and a mean HOS-SSS score 15.9 points lower than those with a BMI ≤30 kg/m 2 ( P 35 years at surgery had a mean mHHS score 4.5 points lower and a HOS-SSS score 6.7 points lower than those aged ≤35 years ( P = .03). Patients with Tönnis grade 2 radiographs demonstrated a 12.5-point worse mHHS score ( P = .02) and a 23.0-point worse HOS-SSS score ( P SSS scores after arthroscopic

  7. The anticancer drug tamoxifen is active against Trypanosoma cruzi in vitro but ineffective in the treatment of the acute phase of Chagas disease in mice

    Directory of Open Access Journals (Sweden)

    Danilo Ciccone Miguel

    2010-11-01

    Full Text Available The activity of the antineoplastic drug tamoxifen was evaluated against Trypanosoma cruzi. In vitro activity was determined against epimastigote, trypomastigote and amastigote forms of CL14, Y and Y benznidazole resistant T. cruzi strains. Regardless of the strain used, the drug was active against all life-cycle stages of the parasite with a half maximal effective concentration ranging from 0.7-17.9 µM. Two experimental models of acute Chagas disease were used to evaluate the in vivo efficacy of treatment with tamoxifen. No differences in parasitemia and mortality were observed between control mock-treated and tamoxifen-treated mice.

  8. Cardiovascular Risk Factors and 5-year Mortality in the Copenhagen Stroke Study

    DEFF Research Database (Denmark)

    Kammersgaard, Lars Peter; Olsen, Tom Skyhøj

    2005-01-01

    population. METHODS: We studied 905 ischemic stroke patients from the community-based Copenhagen Stroke Study. Patients had a CT scan and stroke severity was measured by the Scandinavian Stroke Scale on admission. A comprehensive evaluation was performed by a standardized medical examination...... and questionnaire for cardiovascular risk factors, age, and sex. Follow-up was performed 5 years after stroke, and data on mortality were obtained for all, except 6, who had left the country. Five-year mortality was calculated by the Kaplan-Meier procedure and the influence of multiple predictors was analyzed...... by Cox proportional hazards analyses adjusted for age, gender, stroke severity, and risk factor profile. RESULTS: In Kaplan-Meier analyses atrial fibrillation (AF), ischemic heart disease, diabetes, and previous stroke were associated with increased mortality, while smoking and alcohol intake were...

  9. Cardiovascular risk factors and 5-year mortality in the Copenhagen Stroke Study

    DEFF Research Database (Denmark)

    Kammersgaard, Lars Peter; Olsen, Tom Skyhøj

    2005-01-01

    population. METHODS: We studied 905 ischemic stroke patients from the community-based Copenhagen Stroke Study. Patients had a CT scan and stroke severity was measured by the Scandinavian Stroke Scale on admission. A comprehensive evaluation was performed by a standardized medical examination...... and questionnaire for cardiovascular risk factors, age, and sex. Follow-up was performed 5 years after stroke, and data on mortality were obtained for all, except 6, who had left the country. Five-year mortality was calculated by the Kaplan-Meier procedure and the influence of multiple predictors was analyzed...... by Cox proportional hazards analyses adjusted for age, gender, stroke severity, and risk factor profile. RESULTS: In Kaplan-Meier analyses atrial fibrillation (AF), ischemic heart disease, diabetes, and previous stroke were associated with increased mortality, while smoking and alcohol intake were...

  10. Stable glomerular filtration rate in normotensive IDDM patients with stable microalbuminuria. A 5-year prospective study

    DEFF Research Database (Denmark)

    Mathiesen, E R; Feldt-Rasmussen, B; Hommel, E

    1997-01-01

    patients with persistent microalbuminuria (mean urinary albumin excretion [UAE] 84 mg/24 h [range 30-300]) were followed prospectively for 5 years of clinical examinations that included the measurement of GFR (51Cr-labeled EDTA clearance) at least once a year. The mean GFR at baseline was 120 +/- 18 ml x....... Out of 40 patients, 14 progressed to diabetic nephropathy (UAE > 300 mg/24 h). These patients had a significant reduction in GFR (mean -2.2 +/- 3.8 ml x min-1 x year-1; P = 0.05), while GFR remained stable in the remaining 26 patients with nonprogressive microalbuminuria (change in GFR 0.5 +/- 2.1 ml...

  11. Radium retention in mature beagles injected at 5 years of age

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Bruenger, F.W.; Jones, C.W.; Taylor, G.N.; Mays, C.W.

    1982-01-01

    Retention of 226 Ra was substantially lower in mature beagles injected at 5 years of age compared to corresponding values for 1 1/2-year-old young adult beagles. As with young adults, average retention in mature dogs given about 10 μCi/kg exceeded that of mature dogs given 4 μCi/kg or less. Measured 222 Rn/ 226 Ra ratios in bone were similar in mature and young adults. About 66% of the injected radium was excreted by mature dogs during the first 3 weeks, about 2/3 of the total excretion appearing in the feces. Distribution of 226 Ra within the skeleton was similar in mature and young adult beagles

  12. Urinary phthalates from 168 girls and boys measured twice a year during a 5-year period

    DEFF Research Database (Denmark)

    Mouritsen, A; Frederiksen, H; Sørensen, K

    2013-01-01

    Background: Little is known about the possible deleterious effects of phthalate exposure on endogenous sex steroid levels in children. Objective: Our objective was to investigate whether urinary phthalate metabolite levels are associated with circulating adrenal androgen levels and age at puberty....... Methods: This was a longitudinal study of 168 healthy children (84 girls) examined every 6 months for 5 years. Serum levels of dehydroepiandrostenedione sulfate (DHEAS), Δ4-androstenedione, testosterone, and urinary morning excretion of 14 phthalate metabolites, corresponding to 7 different phthalate...... diesters were determined. A variation in urinary excretion of phthalates was evident in each child, which made a mean of repetitive samples more representative for long-term excretion than a single determination. Results: We found that girls with excretion of monobutyl phthalate isomers (MBP) and di(2...

  13. Coral reefs in Saudi Arabia: 3.5 years after the Gulf War oil spill

    Science.gov (United States)

    Vogt, I. P.

    1995-11-01

    As a consequence of the 1991 Gulf War, 6-8 million barrels of oil were released into the marine environment and a total of 1.12 billion barrels were burned in the Kuwaiti oil fields. In order to detect delayed effects of the Gulf War pollution, six permanent transect lines were placed on Saudi Arabian offshore and inshore reefs. A comparison of three sets of video recordings taken between 1992 and 1994 indicated a significant increase in live coral cover. Therefore, it has been concluded that corals in Saudi Arabia survived the largest oil spill on record remarkably unscathed, with no visible signs of immediate or late effects up to 3.5 years after the Gulf War.

  14. 5 years of experience with a large-scale mentoring program for medical students

    Directory of Open Access Journals (Sweden)

    Pinilla, Severin

    2015-02-01

    Full Text Available In this paper we present our 5-year-experience with a large-scale mentoring program for undergraduate medical students at the Ludwig Maximilians-Universität Munich (LMU. We implemented a two-tiered program with a peer-mentoring concept for preclinical students and a 1:1-mentoring concept for clinical students aided by a fully automated online-based matching algorithm. Approximately 20-30% of each student cohort participates in our voluntary mentoring program. Defining ideal program evaluation strategies, recruiting mentors from beyond the academic environment and accounting for the mentoring network reality remain challenging. We conclude that a two-tiered program is well accepted by students and faculty. In addition the online-based matching seems to be effective for large-scale mentoring programs.

  15. Mandatory presuit mediation: 5-year results of a medical malpractice resolution program.

    Science.gov (United States)

    Jenkins, Randall C; Smillov, Arlene E; Goodwin, Matthew A

    2014-01-01

    The Florida Patient Safety and Presuit Mediation Program (FLPSMP) is a mandatory mediation program designed to provide deserving patients with fast, fair compensation while limiting the healthcare provider expenses incurred during traditional litigation. Mediation occurs before litigation begins; therefore, patients with meritorious claims receive compensation often years earlier than they would with extended litigation. This early mediation fosters confidential and candid communication between doctors and patients, which promotes early fact-finding and candid discussion. The program went into effect across the University of Florida (UF) Health system on January 1, 2008. In an article previously published in this journal, we discussed the positive trend observed 2 years after the implementation of the FLPSMP. This article incorporates 5 years of data, which includes new benchmarks with state and national data, to demonstrate that the program can be used successfully as a medical malpractice solution. © 2014 American Society for Healthcare Risk Management of the American Hospital Association.

  16. Animal livestock and the risk of hospitalized diarrhoea in children under 5 years in Vietnam.

    Science.gov (United States)

    Thiem, Vu Dinh; Schmidt, Wolf-Peter; Suzuki, Motoi; Tho, Le Huu; Yanai, Hideki; Ariyoshi, Koya; Anh, Dang Duc; Yoshida, Lay-Myint

    2012-05-01

    To investigate the association between environmental exposure to livestock and incidence of diarrhoea among Vietnamese children. A population-based cohort of 353,525 individuals, living in 75,828 households in Khanh Hoa Province, Vietnam, with baseline data covering geo-referenced information on demography, socio-economic status and household animals was investigated. Geographic information system was applied to calculate the density of livestock. The data were linked to hospitalized diarrhoea cases of children under 5 years recorded at two hospitals treating patients from the area as inpatients in the study area. Overall, 3116 children with diarrhoea were hospitalized during the study period. The incidence of diarrhoea hospitalization was 60.8/1000 child-years. Male gender, age Vietnam. Public health interventions to reduce childhood diarrhoea burden should focus on well-recognized causes such as sanitation, personal hygiene, access to adequate clean water supply and vaccination. © 2012 Blackwell Publishing Ltd.

  17. Increased risk of stroke and transient ischemic attack in 5-year survivors of Hodgkin lymphoma

    DEFF Research Database (Denmark)

    De Bruin, Marie L; Dorresteijn, Lucille D A; van't Veer, Mars B

    2009-01-01

    BACKGROUND: Information on clinically verified stroke and transient ischemic attack (TIA) following Hodgkin lymphoma is scarce. We quantified the long-term risk of cerebrovascular disease associated with the use of radiotherapy and chemotherapy in survivors of Hodgkin lymphoma and explored...... Cox regression techniques to study treatment-related factors and other risk factors. All statistical tests were two-sided. RESULTS: After a median follow-up of 17.5 years, 96 patients developed cerebrovascular disease (55 strokes, 31 TIAs, and 10 with both TIA and stroke; median age = 52 years). Most...... ischemic events were from large-artery atherosclerosis (36%) or cardioembolisms (24%). The standardized incidence ratio for stroke was 2.2 (95% confidence interval [CI] = 1.7 to 2.8), and for TIA, it was 3.1 (95% CI = 2.2 to 4.2). The risks remained elevated, compared with those in the general population...

  18. Including persistency of impairment in mild cognitive impairment classification enhances prediction of 5-year decline.

    Science.gov (United States)

    Vandermorris, Susan; Hultsch, David F; Hunter, Michael A; MacDonald, Stuart W S; Strauss, Esther

    2011-02-01

    Although older adults with Mild Cognitive Impairment (MCI) show elevated rates of conversion to dementia as a group, heterogeneity of outcomes is common at the individual level. Using data from a prospective 5-year longitudinal investigation of cognitive change in healthy older adults (N = 262, aged 64-92 years), this study addressed limitations in contemporary MCI identification procedures which rely on single occasion assessment ("Single-Assessment [SA] MCI") by evaluating an alternate operational definition of MCI requiring evidence of persistent cognitive impairment over multiple-testing sessions ("Multiple-Assessment [MA] MCI"). As hypothesized, prevalence of SA-MCI exceeded that of MA-MCI. Further, the MA-MCI groups showed lower baseline cognitive and functional performance and steeper cognitive decline compared with Control and SA-MCI group. Results are discussed with reference to retest effects and clinical implications.

  19. Risk factors of diarrhea in children under 5 years in Al-Mukalla, Yemen.

    Science.gov (United States)

    Bahartha, Ali S; AlEzzi, Jalil I

    2015-06-01

    To assess the risk factors associated with diarrhea among children below 5-years-old in Mukalla, Yemen, and compare with other studies.   We conducted a case-control study on 200 children (100 cases and 100 controls) who attended the Maternity and Child Hospital, outpatient-clinics, and the Primary Health Care Centers in Al-Mukalla, Hadhramout, Yemen between February and April 2013.   We found that the significant risk factors associated with diarrhea were crowded housing (odds ratio [OR] 2.02; p=0.02; confidence interval [CI] 1.03-4.01), incomplete vaccination of the child (OR=2.02; p=0.027; CI: 1.08-3.8), and recurrent diarrheal illness during the last 3 months (OR=6.61; p=0.001; CI: 3.41-12.90).   Diarrheal diseases are strongly associated with incomplete vaccination, recurrent diarrheal disease, and crowded housing.

  20. Clinical characteristics and outcome of patients diagnosed with psychogenic nonepileptic seizures: a 5-year review.

    LENUS (Irish Health Repository)

    O'Sullivan, S S

    2012-02-03

    OBJECTIVE: The goal of this article was to describe the clinical characteristics and outcomes of patients diagnosed with psychogenic nonepileptic seizures (PNES). METHODS: We conducted a retrospective review of patients diagnosed with PNES in a 5-year period. RESULTS: Fifty patients with PNES were identified, giving an estimated incidence of 0.91\\/100,000 per annum. Thirty-eight were included for review, 15 of whom were male (39%). Eighteen patients had been diagnosed with epilepsy as well as PNES (47%). We demonstrated a gender difference in our patients, with males having higher seizure frequencies, more antiepileptic drug use, and a longer interval before diagnosis of PNES. Females were diagnosed with other conversion disorders more often than males. Impaired social function was observed in PNES, as was resistance to psychological interventions with a subsequent poor response to treatments. CONCLUSIONS: PNES remains a difficult condition to treat, and may affect males in proportions higher than those described in previous studies.

  1. A case of ocular thelaziasis in a 2.5 years old Holstein heifer

    Directory of Open Access Journals (Sweden)

    Mousa Daradka

    2014-09-01

    Full Text Available A 2.5-years-old, Holstein lactating dairy cow was presented to the Veterinary Health Center with severe conjunctivitis and exuberant granulation tissue formation of the left eye. Upon close examination of the eye, a 2-cm long slender-shaped nematode was found in the conjunctival sac. The nematode was examined by a veterinary parasitologist and determined to be Thelazia species. The exuberant granulation tissue was surgically removed and a total of 0.5 mL of 1% levamisole was injected subconjunctivally. Levamesole was also injected subcutaneously at a dose of 10 mg/kg of body weight and repeated after 15 days. The cow made a complete recovery within 25 days following treatment. This is the first case report of ocular thelaziasis in dairy cattle in Jordan.

  2. Quality assurance of approved out of programme psychiatry training and research over the past 5 years

    Science.gov (United States)

    Osman-Hicks, Victoria; Graham, Hannah; Leadbetter, Peter; Brittlebank, Andrew

    2015-01-01

    Aims and method This paper intends to analyse the number of applications, trainee demographic and approval rate of those applying for out of programme training (OOPT) or out of programme research (OOPR) between January 2008 and April 2013 using the committee’s anonymised database. We also describe the process of application and approval by the Quality Assurance Committee. Results There were 90 applications, including 10 resubmissions during the 64-month period. Most applicants (77%) were higher trainees; 53% of applicants were from the London deanery; 60% of applications were for research posts and higher degrees (OOPR). Overall, 64% were approved by the committee: 70% for OOPRs and 53% for OOPTs. Clinical implications This paper shows with transparency the breakdown of applications to the Quality Assurance Committee. Around two-thirds of applications to the committee are supported (64%). Relatively few psychiatry trainees (2.5%) have applied for an OOPT or an OOPR over the past 5 years. PMID:26191450

  3. Advanced paternal age and mortality of offspring under 5 years of age

    DEFF Research Database (Denmark)

    Urhoj, S K; Jespersen, Louise Norman; Nissen, Marie

    2014-01-01

    Study question: Do children born to fathers of advanced age have an increased risk of dying before the age of 5 years? Summary answer: Children born to fathers aged 40 years or more have an increased risk of dying in early childhood due to an excess risk of fatal congenital anomalies, malignancies...... and external causes. What is known already: Advanced paternal age has previously been associated with adverse reproductive outcomes and some long term health problems in the offspring. This is possibly due to specific point mutations, a condition known to increase in the sperm with increasing paternal age....... Study design, size, duration: A Danish population-based register study, designed as a prospective cohort study, of 1 575 521 live born children born from 1978 to 2004. The age of the child (in days) was used as the underlying time and the children entered the cohort the day they were born and were...

  4. 5-YEAR SURVIVAL OF PATIENTS WITH STAGE II UTERINE CANCER DEPENDING ON MORPHOLOGIC FEATURES OF TUMOR

    Directory of Open Access Journals (Sweden)

    Ye. A. Mustafina

    2008-01-01

    Full Text Available Retrospective data of treatment results of 109 patients with rarely observed stage II uterine cancer, admitted to N.N. Blokhin Russian Cancer Research Center from 1980 to 2000 is analyzed. Correlation of overall 5-year survival rates of stage IIA and IIB uterine can- cer patients with a number of tumor morphologic features is studied. The influence of some non-elucidated morphologic features of stage IIA and IIB uterine cancer such as the degree of cellular anaplasia, the depth of tumor invasion into the uterine neck, lymho- vascular invasion into the myometrium and uterine neck, microscopic vessels density in the area of the most extensive invasion, the presence of necrotic areas in the tumor tissue on long-term treatment results are analyzed.

  5. Separable sustained and selective attention factors are apparent in 5-year-old children

    DEFF Research Database (Denmark)

    Underbjerg, Mette; George, Melanie S; Thorsen, Poul

    2013-01-01

    In adults and older children, evidence consistent with relative separation between selective and sustained attention, superimposed upon generally positive inter-test correlations, has been reported. Here we examine whether this pattern is detectable in 5-year-old children from the healthy...... and auditory stimuli were good. In a factor analysis, the two TEA-Ch(J) selective attention tasks (one visual, one auditory) loaded onto a common factor and diverged from the two sustained attention tasks (one auditory, one motor), which shared a common loading on the second factor. This pattern, which...... suggests that the tests are indeed sensitive to underlying attentional capacities, was supported by the relationships between the TEA-Ch(J) factors and Test of Everyday Attention for Children subtests in the older children in the sample. It is possible to gain convincing performance-based estimates...

  6. Intranasal LH-RH treatment of cryptorchidism. A clinical trial and 5 years follow-up

    DEFF Research Database (Denmark)

    Thorup, Jørgen Mogens; Mauritzen, K; Skakkebaek, N E

    1987-01-01

    The effect of intranasal LH-RH on cryptorchidism was investigated in 45 prepubertal boys with 68 undescended testes. A daily dose of 1.2 mg LH-RH was given for 4 weeks. A total of 16 testes (24%) descended. Follow-up examination 5 years later showed that relapse had occurred in two cases. Fifty......-two testes did not descend during the LH-RH treatment. However, seven of these testes descended spontaneously during puberty. So far surgical treatment has been carried out in 39 of the remaining 45 testes. Anatomical anomalies (ectopic position of the testis, open processus vaginalis, abnormal epididymis......) explained the failure of LH-RH to cause descent in the majority of the surgically treated cases....

  7. Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS.

    Science.gov (United States)

    Sumowski, James F; Rocca, Maria A; Leavitt, Victoria M; Dackovic, Jelena; Mesaros, Sarlota; Drulovic, Jelena; DeLuca, John; Filippi, Massimo

    2014-05-20

    Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time. Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression. Patients with MS declined in cognitive efficiency and memory (p improve prediction of future cognitive decline in patients with MS. © 2014 American Academy of Neurology.

  8. Renal stone associated with the ketogenic diet in a 5-year old girl with intractable epilepsy.

    Science.gov (United States)

    Choi, Ji Na; Song, Ji Eun; Shin, Jae Il; Kim, Heung Dong; Kim, Myung Joon; Lee, Jae Seung

    2010-05-01

    In this paper, we report on a 5-year-old girl who developed a renal stone while following the ketogenic diet to treat refractory seizure disorder. Three months after initiating the ketogenic diet, she developed severe abdominal pain and vomiting. The spot urine calcium-to-creatinine (Ca/Cr) ratio and 24-hour urine evaluation showed hypercalciuria. Computed tomography (CT) imaging revealed a stone in the right ureteropelvic junction, resulting in hydronephrosis of the right kidney. The renal stone disappeared 5 days after conservative treatment; the patient's microscopic hematuria resolved concurrently. In light of this case report, we recommend regularly monitoring the urine Ca/Cr ratio with ultrasonography for further development of renal stones in patients following the ketogenic diet. If these patients exhibit evidence of symptomatic hypercalciuria or cyristalluria, liberalization of fluid restriction and urine alkalization using oral potassium citrate should be considered.

  9. Global strategy for the diagnosis and management of asthma in children 5 years and younger

    DEFF Research Database (Denmark)

    Hurd, Suzanne S; Lemanske, Robert F; Becker, Allan

    2011-01-01

    in this age group. For this reason, to aid in the diagnosis of asthma in young children, a symptoms-only descriptive approach that includes the definition of various wheezing phenotypes has been recommended. In 1993, the Global Initiative for Asthma (GINA) was implemented to develop a network of individuals...... and our ability to manage and control it effectively. However, in children 5 years and younger, the clinical symptoms of asthma are variable and non-specific. Furthermore, neither airflow limitation nor airway inflammation, the main pathologic hallmarks of the condition, can be assessed routinely......, organizations, and public health officials to disseminate information about the care of patients with asthma while at the same time assuring a mechanism to incorporate the results of scientific investigations into asthma care. Since then, GINA has developed and regularly revised a Global Strategy for Asthma...

  10. Programmatic Impact of 5 Years of Mortality Surveillance of New York City Homeless Populations

    Science.gov (United States)

    Marder, Dova; Begier, Elizabeth; Gutkovich, Alexander; Mos, Robert; Griffin, Angela; Zimmerman, Regina; Madsen, Ann

    2013-01-01

    A homeless mortality surveillance system identifies emerging trends in the health of the homeless population and provides this information to key stakeholders in a timely and ongoing manner to effect evidence-based, programmatic change. We describe the first 5 years of the New York City homeless mortality surveillance system and, for the first time in peer-reviewed literature, illustrate the impact of key elements of sustained surveillance (i.e., timely dissemination of aggregate mortality data and real-time sharing of information on individual homeless decedents) on the programs of New York City’s Department of Homeless Services. These key elements had a positive impact on the department’s programs that target sleep-related infant deaths and hypothermia, drug overdose, and alcohol-related deaths among homeless persons. PMID:24148068

  11. Torpedo maculopathy with an anisometropic amblyopia in a 5-year-old Caucasian girl: case report

    Directory of Open Access Journals (Sweden)

    Marco Dutra-Medeiros

    2013-08-01

    Full Text Available The aim of this study is to report a clinical case of asymptomatic female Caucasian children with torpedo maculopathy. A 5-year-old girl was referred to our clinic for routine evaluation. The ophthalmic examination revealed best-corrected visual acuity of 20/20 in both eyes, without any changes in the biomicroscopy. Fundus examination showed normal findings in one eye, whereas in the contralateral eye it disclosed, in the temporal sector of the macular region, a whitish, atrophic, oval chorioretinal lesion with clearly defined margins. Posterior evaluations documented the stability of the lesion. Torpedo maculopathy diagnosis is based on its characteristic shape and peculiar location. The differential diagnosis has to be estabilished versus choroidal lesions (melanoma and nevus, congenital or iatrogenic hyperplasia of the retinal pigment epithelium (RPE and particularly versus the congenital pigmented lesions associated with Gardner's syndrome.

  12. Care for overweight children attending the 5-year preventive child health examination in general practice

    DEFF Research Database (Denmark)

    Andersen, Merethe Kousgaard; Christensen, Bo; Søndergaard, Jens

    2013-01-01

    's weight to the parents in 58% of the 171 cases with GP-assessed overweight. The national guideline was reported consulted in 6% of the cases. Diet, physical activity and dispositions were evaluated by the GPs in 68%, 57% and 34% of cases, respectively. An appointment for a follow-up was made in 12......% of cases.Conclusion. Various care activities were carried out for most children with GP-assessed overweight at the 5-year PCHE. However, the GP did not raise concern about the child's weight with the parents in almost one third of the children. It seems that there is a potential for improving......OBJECTIVE: The purpose of this study was to analyse general practitioners' (GPs) care for children with a weight-for-height above normal based on the GPs' clinical evaluation, that is, 'GP-assessed overweight'.Design. This study is a cross-sectional survey targeting GPs' care for children with GP...

  13. 5-years APAP adherence in OSA patients--do first impressions matter?

    Science.gov (United States)

    van Zeller, Mafalda; Severo, Milton; Santos, Ana Cristina; Drummond, Marta

    2013-12-01

    Although continuous positive airway pressure (CPAP) is effective in treating obstructive sleep apnoea (OSA), inadequate adherence remains a major cause of treatment failure. This study aimed to determine long term adherence to auto adjusting-CPAP (APAP) and its influencing factors including the role of initial compliance. Eighty-eight male patients with newly diagnosed moderate/severe OSA were included. After initiation of APAP treatment, patients had periodic follow-up appointments at 2 weeks, 6 months and then annually for at least 5 years. Patient's compliance to therapy was assessed in each appointment and predictors to treatment abandonment and poor compliance were evaluated. The studied population had a mean age of 53.8 years and mean apnoea-hypopnoea index of 52.71/h. The mean time of follow-up was 5.2 (± 1.6) years, during that time 22 (25%) patients abandoned APAP, those who maintained treatment had good compliance to it since 94% of them used it more than 4 h/day for at least 70% of days. A significant negative association was found between age, % of days and mean time of APAP use on 12th day and 6th month and the risk of abandoning. APAP use lower than 33% and 57% of days at 12th day and 6th month, respectively had high specificity (≈ 100%) to detect treatment abandonment. the majority of patients adheres to long term APAP treatment and has good compliance after 5-years of follow-up. Age and initial compliance (% days of use and mean hour/day) have the ability to predict future adherence, as soon as 12 days and 6 months after initiation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Plantar Pressures After Nonoperative Treatment for Clubfoot: Intermediate Follow-up at Age 5 Years.

    Science.gov (United States)

    Jeans, Kelly A; Erdman, Ashley L; Karol, Lori A

    2017-01-01

    Worldwide, a nonoperative approach in the treatment of idiopathic clubfoot has been taken in an attempt to reduce the incidence of surgical outcomes. Although both the Ponseti casting (Ponseti) and the French physiotherapy (PT) methods have shown gait and pedobarograph differences at age 2 years, improved gait results have been reported by age 5 years. The purpose of this study was to assess plantar pressures in feet treated with the Ponseti versus the PT methods at this intermediate stage. Clubfoot patients treated nonoperatively (Ponseti or PT) underwent pedobarograph data collection at age 5 years. The foot was subdivided into the medial/lateral hindfoot, midfoot, and forefoot regions. Variables included Peak Pressure, Maximum Force, Contact Area%, Contact Time%, Pressure Time Integral, the hindfoot-forefoot angle, and displacement of the center of pressure (COP) line. Twenty controls were used for comparison. Pedobarograph data from 164 patients (238 feet; 122 Ponseti and 116 PT) showed no significant differences between the Ponseti and the PT feet, except the PT feet had a significantly less medial movement of the COP than the Ponseti feet (P=0.0379). Compared with controls, both groups had decreased plantar pressures in the hindfoot and first metatarsal regions, whereas the midfoot and lateral forefoot experienced significant increases compared with controls. This lateralization was also reflected in the hindfoot-forefoot angle and the COP. Feet that remain nonoperative and avoid surgical intervention are considered a good clinical result. However, pedobarograph results indicate mild residual deformity in these feet despite clinically successful outcomes. Level II-therapeutic.

  15. Colorectal cancer screening: results of a 5-year program in asymptomatic subjects at increased risk.

    Science.gov (United States)

    Pezzoli, A; Matarese, V; Rubini, M; Simoni, M; Caravelli, G C; Stockbrugger, R; Cifalà, V; Boccia, S; Feo, C; Simone, L; Trevisani, L; Liboni, A; Gullini, S

    2007-01-01

    The province of Ferrara has one of the highest incidences of colorectal cancer (CRC) in Italy. In January 2000, we set up a colonoscopy screening program focussing on first-degree relatives of CRC patients. We now report the results 5 years after the beginning of the project. SCREENEES AND METHODS: In October 1999, we started a campaign stressing the usefulness of colonoscopy for the first-degree relatives of CRC patients. Subjects included in the screening program were aged between 45 and 75 years with at least one first-degree relative affected by CRC. They were invited to an interview where a physician suggested colonoscopy as a screening option. In 5 years, 776 subjects were interviewed and 733 (94.4%) agreed to an endoscopic examination (M/F:375/401; mean age 55 years): 562 colonoscopies were performed. Adenomas and cancers were found in 122 (21.7%) and 12 (2.1%) subjects, respectively. Histological examination in 181 persons with lesions (32.8%) showed (most serious lesion quoted) 47 hyperplastic polyps (26% of all lesions), 2 serrated adenomas (1.1%), 68 tubular adenomas (48%), 24 tubulovillous adenomas (13.3%), 9 adenomas with high grade dysplasia (5%) and 12 adenocarcinomas (6.6%). The majority of the cancers were at an early stage (8 Dukes A and 3 Dukes B). Sedation was used in only 42 colonoscopies (7.5%). A colonoscopy-based screening in this selected high-risk population is feasible. Even without sedation subjects readily agreed to the endoscopic procedure. We identified a significant number of advanced neoplasms and cancers at an early stage suggesting that this could be a useful tool in early identification of CRC.

  16. Henoch schonlein purpura--a 5-year review and proposed pathway.

    Directory of Open Access Journals (Sweden)

    Louise Watson

    Full Text Available Henoch Schonlein Purpura (HSP is the commonest systemic vasculitis of childhood typically presenting with a palpable purpuric rash and frequently involving the renal system. We are the first group to clinically assess, critically analyse and subsequently revise a nurse led monitoring pathway for this condition.A cohort of 102 children presenting with HSP to a secondary/tertiary level UK paediatric hospital over a five year period, were monitored using a nurse led care pathway. Using this cohort, the incidence (6.21 cases per 100,000 children per year and natural disease course of HSP nephritis (46% initial renal inflammation; 9% subsequent renal referral; 1% renal biopsy and immunosuppression was determined. Older patients were at higher risk of requiring a renal referral (renal referral 12.3 (8.4-13.5 years vs. normal outcome 6.0 (3.7-8.5 years; p<0.01. A normal urinalysis on day 7 had a 97% (confidence interval 90 to 99% negative predictive value in predicting a normal renal outcome.Using this data and existing literature base, The Alder Hey Henoch Schonlein Purpura Pathway was developed, a revised pathway for the screening of poor renal outcome in HSP. This is based on a six-month monitoring period for all patients presenting with HSP, which importantly prioritises patients according to the urine findings on day 7 and thus intensively monitors those at higher risk of developing nephritis. The pathway could be easily adapted for use in different settings and resources.The introduction of a standardised pathway for the monitoring of HSP will facilitate the implementation of disease registries to further our understanding of the condition and permit future clinical trials.

  17. A 5-year scientometric analysis of research centers affiliated to Tehran University of Medical Sciences

    Science.gov (United States)

    Yazdani, Kamran; Rahimi-Movaghar, Afarin; Nedjat, Saharnaz; Ghalichi, Leila; Khalili, Malahat

    2015-01-01

    Background: Since Tehran University of Medical Sciences (TUMS) has the oldest and highest number of research centers among all Iranian medical universities, this study was conducted to evaluate scientific output of research centers affiliated to Tehran University of Medical Sciences (TUMS) using scientometric indices and the affecting factors. Moreover, a number of scientometric indicators were introduced. Methods: This cross-sectional study was performed to evaluate a 5-year scientific performance of research centers of TUMS. Data were collected through questionnaires, annual evaluation reports of the Ministry of Health, and also from Scopus database. We used appropriate measures of central tendency and variation for descriptive analyses. Moreover, uni-and multi-variable linear regression were used to evaluate the effect of independent factors on the scientific output of the centers. Results: The medians of the numbers of papers and books during a 5-year period were 150.5 and 2.5 respectively. The median of the "articles per researcher" was 19.1. Based on multiple linear regression, younger age centers (p=0.001), having a separate budget line (p=0.016), and number of research personnel (p<0.001) had a direct significant correlation with the number of articles while real properties had a reverse significant correlation with it (p=0.004). Conclusion: The results can help policy makers and research managers to allocate sufficient resources to improve current situation of the centers. Newly adopted and effective scientometric indices are is suggested to be used to evaluate scientific outputs and functions of these centers. PMID:26157724

  18. Vitamin supplementation and related nutritional status in Thai children, aged 1-5 years.

    Science.gov (United States)

    Ratanachu-ek, Suntaree

    2014-06-01

    To evaluate the prevalence of vitamin supplementation in Thai children aged 1-5 years at Queen Sirikit National Institute of Child Health (QSNICH), parental knowledge of vitamins, practices, and related factors such as nutritional status in vitamin supplementation. A cross-sectional study was performed at the Well Child Clinic, QSNICH, from 1-31 May 2005. Five hundred parents of young children, aged 1-5 years were interviewed by using the questionnaire to obtain information regarding knowledge and practices of vitamin supplementation. Weight and length/height were measured and nutritional status was assessed using the Thai growth reference. The relationships among vitamin supplement, nutritional status, and other related factors were analyzed using Chi-square test. The p-value vitamin supplementation was 76%, including vitamin C 62%, multi-vitamin (MTV) 35%, and cod-liver oil 20%. Regarding parental knowledge of vitamins, 57% of them knew the health benefits but 74% did not know the toxic effects of vitamins. The reasons for vitamin supplementation were poor feeding 63%, under-weight 23% and unhealthy status 14%. Vitamins were obtained from over-the-counter 59%, health services 40%, and friends 1%. Vitamin supplementation was significantly higher in children over 2 years of age, whose parents knew the benefits of vitamins, and in those children with malnutrition. The prevalence of vitamin supplementation was high in malnourished children, over 2 years of age whose parents had knowledge about benefits of vitamins. Parents should be warned about the dangers of high dose of vitamin consumption.

  19. A case of recurrent delayed radiation myelopathy with 5-year remission interval

    International Nuclear Information System (INIS)

    Tsukagoshi, Setsuki; Ikeda, Masaki; Tano, Shinobu; Obayashi, Kai; Fujita, Yukio; Okamoto, Koichi

    2010-01-01

    We report a 47-year-old woman with relapsed delayed radiation myelopathy (DRM), occurring 5 years and 10 years after radiation therapy for nasopharyngeal carcinoma at 37 years old. Sensations of pain and temperature had been disturbed in the right leg since 42 years old. MRI showed Gadolinium-enhanced lesion as a ring-like-enhancement of the spinal cord at C1-2 on T 1 -weighted image (T 1 WI), with high signal area and swelling of the spinal cord at the upper C1 to C6 areas on T 2 -weighted image. We diagnosed her as having DRM after considering the differential diagnosis, e.g., multiple sclerosis, spinal tumor and other neurological diseases. Her sensory symptoms quickly improved following therapy with prednisolone and warfarin. Although she remained healthy for a few years, dysesthesia of the neck on the right side appeared 5 years later after the first clinical occurrence. At this time, MRI demonstrated Gadolinium-enhanced lesion as a ring-like enhancement of the spinal cord at C2 on T 1 WI, but the area also differed from that of previous lesion; a high signal area and swelling of the spinal cord was also seen on fluid attenuated inversion recovery (FLAIR) image of the medulla and upper C1 to C6. For recurrence of DRM, we administered prednisolone and warfarin. Thereafter, the patient recovered and the spinal cord lesion on MRI decreased markedly. The clinical course demonstrated that administration of prednisolone and warfarin might be effective for relapsed DRM. (author)

  20. Parenting style and family meals: cross-sectional and 5-year longitudinal associations.

    Science.gov (United States)

    Berge, Jerica M; Wall, Melanie; Neumark-Sztainer, Dianne; Larson, Nicole; Story, Mary

    2010-07-01

    Research on family meals in the past decade has shown a positive association between family meal frequency and adolescent healthy dietary intake. However, less is known about factors within the home environment, such as parenting style, that may be associated with family meal patterns. The purpose of this study is to test cross-sectional and 5-year longitudinal associations between parenting styles (authoritative, authoritarian, permissive, and neglectful) and the frequency of family meals among adolescents. Data were from Project Eating Among Teens, a population-based study comprised of youth from diverse ethnic/racial and socioeconomic backgrounds. Two cohorts of adolescents (middle school and high school) completed in-class surveys in 1999 (Time 1) and mailed surveys in 2004 (Time 2). Multiple linear regression models were used to predict mean frequency of family meals at Time 1 and Time 2 from adolescent report of parenting style (both mother and father) at Time 1. Cross-sectional analyses included both adolescent cohorts (n=4,746) and longitudinal analyses included only the younger cohort (n=806) because family meal frequency was not assessed in the older cohort at Time 2. Cross-sectional results for adolescent girls indicated a positive association between maternal and paternal authoritative parenting style and frequency of family meals. For adolescent boys, maternal authoritative parenting style was associated with more frequent family meals. Longitudinal results indicated that authoritative parenting style predicted higher frequency of family meals 5 years later, but only between opposite sex parent/adolescent dyads. Future research should identify additional factors within the home environment that are associated with family meal frequency to develop effective interventions that result in increased family meals for youth. Also, future research should investigate the mealtime behaviors of authoritative parents and identify specific behaviors that dietetics

  1. Seminar program for postgraduate specialty training in general practice: proposal for a 5-year thematic catalogue

    Directory of Open Access Journals (Sweden)

    Sommer, Susanne

    2017-11-01

    Full Text Available Introduction: In different German regions, seminar programs have been conducted for General practice residents. In each region, selection and teaching of learning content is conducted in a different manner. So far, no structured, standardized curriculum has been implemented nationwide. We have investigated, if the development of a common 5-year program of learning topics is conceivable between the different university departments of General practice in Germany.Method: The seminar program working group of the DEGAM (German College of General Practitioners and Family Physicians has conducted an online survey based on information gathered via preliminary telephone conference (n=7; physicians with postgraduate teaching experience among all German university departments of General Practice and two non-university teaching institutions, identified via the internet. 884 topics were extracted from 14 Seminar programs. The topics were entered in a database, discussed and categorized: Practice management/practice work flow/standardized documentation forms/quality management (n=33 topics, common acute and chronic diseases, including disease management programs (n=29 topics, communication, neurological, psychological and psychiatric consultations (n=24 topics, common medical problems, including eye, ear, nose, throat, skin and pediatric problems (n=99 Topics family physicians general approach, including epidemiology, shared decision making, test of time (n=42 Topics. These topics have been rated for priority and desirable number of teaching-units.Results: A catalogue of 111 topics was designed, encompassing 160 teaching units. There is a suggestion of wide topics collections plus an add-on catalogue.Conclusion: A proposal for a 5-year-thematic catalogue for postgraduate training of general practice residents in Germany has been developed. This newly developed curriculum has the potential to improve knowledge and skills that have not been covered during in

  2. Environmental restoration and waste management: Robotics technology development program: Robotics 5-year program plan

    International Nuclear Information System (INIS)

    1991-01-01

    This plan covers robotics Research, Development, Demonstration, Testing, activities in the Program for the next five years. These activities range from bench-scale R ampersand D to fullscale hot demonstrations at DOE sites. This plan outlines applications of existing technology to near-term needs, the development and application of enhanced technology for longer-term needs, and an initiation of advanced technology development to meet those needs beyond the five-year plan. The objective of the Robotic Technology Development (RTDP) is to develop and apply robotics technologies that will enable Environmental Restoration and Waste Management operations at DOE sites to be safer, faster and cheaper. Five priority DOE sites were visited in March 1990 to identify needs for robotics technology in ER ampersand WM operations. This 5-Year Program Plan for the RTDP detailed annual plans for robotics technology development based on identified needs. This 5-Year Program Plan discusses the overall approach to be adopted by the RTDP to aggressively develop robotics technology and contains discussions of the Program Management Plan, Site Visit and Needs Summary, Approach to Needs-Directed Technical Development, Application-Specific Technical Development, and Cross-Cutting and Advanced Technology. Integrating application-specific ER ampersand WM needs, the current state of robotics technology, and the potential benefits (in terms of faster, safer, and cheaper) of new technology, the Plan develops application-specific road maps for robotics RDDT ampersand E for the period FY 1991 through FY 1995. In addition, the Plan identifies areas where longer-term research in robotics will have a high payoff in the 5- to 20-year time frame. 12 figs

  3. Evaluation of Laparoscopic Curricula in American Urology Residency Training: A 5-Year Update.

    Science.gov (United States)

    Clements, Matthew B; Morrison, Kasey Y; Schenkman, Noah S

    2016-03-01

    Medical simulation offers the advantage of improving resident skill and comfort without impacting patient care. Five years ago, we identified trends in the use of robotic and laparoscopic simulation in 2008 and 2009 at American urology residency training programs. We seek to identify the changes in the use of simulators and the presence of formal curricula in the wake of technological advances and changes in graduate medical education. Attendees of the American Urological Association (AUA) Basic Sciences Course, mostly in their second or third year of residency, were surveyed on the availability and use of laparoscopic/robotic simulators at their program, the presence of a formal curriculum, and a Likert scale questionnaire regarding face and content validity. Over a 5-year period, the availability of virtual reality robotic simulators substantially increased from 14% to nearly 60% availability in 2013. Despite this increase, the frequency of simulator use remained unchanged (p = 0.40) and the reported presence of formal curricula decreased from 41% to 34.8%. There was no significant difference in simulator use between residents in programs with or without laparoscopic/robotic curricula (p = 0.95). There was also a decrease in the percentage of residents who felt official laparoscopic curricula (93%-81%) and simulators (82%-74%) should be involved in resident education. In the past 5 years, despite evidence supporting benefits from simulator use and increasing availability, self-reported resident use has remained unchanged and the reporting of presence of laparoscopic/robotic curricula has decreased. With more dedicated investment in formal curricula, residency training programs may receive greater returns on their simulator investments, improve resident skills and comfort, and ultimately improve the quality of patient care.

  4. Status of medical education reform at Saga Medical School 5 years after introducing PBL.

    Science.gov (United States)

    Oda, Yasutomo; Koizumi, Shunzo

    2008-03-01

    In Japan, problem-based learning (PBL) is a relatively new method of educating medical students that is reforming the face of medical education throughout the world, including Asia. It shifts from teacher-centered learning strategies (for example, lectures in large auditoriums) to student-centered, self-directed learning methods (for example, active discussions and problem-solving by students in small groups under the guidance of faculty tutors). Upon a recommendation by the Japan Model Core Curriculum, Saga Medical School introduced a PBL curriculum 5 years ago. A full PBL curriculum was adopted from the McMaster model through Hawaii. A description of how PBL was implemented into the 3rd and 4th year (Phase III curriculum) is given. The overall result has been good. Students who experienced PBL had increased scores on the National Medical License Exam, and Saga increased its ranking from 56th to 19th of the 80 medical schools in Japan. A key step was introduction of the educational scaffolding in PBL Step 0. Students were allowed to see page one of the PBL case, containing the chief complaint, on the weekend before meeting in small groups. Despite a perceived overall benefit to student learning, symptoms of superficial discussions by students have been observed recently. How this may be caused by poor case design is discussed. Other problems, including "silent tutors" and increased faculty workload, are discussed. It is concluded that after 5 years, Saga's implementation of a PBL curriculum has been successful. However, many additional issues, including motivation of students and preparation for PBL in the first 2 years, must still be resolved in the future. This is the first description of the positive and negative outcomes associated with the reform of medical education and the introduction of PBL to a traditional medical school curriculum in Japan.

  5. Status of Medical Education Reform at Saga Medical School 5 Years After Introducing PBL

    Directory of Open Access Journals (Sweden)

    Yasutomo Oda

    2008-03-01

    Full Text Available In Japan, problem-based learning (PBL is a relatively new method of educating medical students that is reforming the face of medical education throughout the world, including Asia. It shifts from teacher-centered learning strategies (for example, lectures in large auditoriums to student-centered, self-directed learning methods (for example, active discussions and problem-solving by students in small groups under the guidance of faculty tutors. Upon a recommendation by the Japan Model Core Curriculum, Saga Medical School introduced a PBL curriculum 5 years ago. A full PBL curriculum was adopted from the McMaster model through Hawaii. A description of how PBL was implemented into the 3rd and 4th year (Phase III curriculum is given. The overall result has been good. Students who experienced PBL had increased scores on the National Medical License Exam, and Saga increased its ranking from 56th to 19th of the 80 medical schools in Japan. A key step was introduction of the educational scaffolding in PBL Step 0. Students were allowed to see page one of the PBL case, containing the chief complaint, on the weekend before meeting in small groups. Despite a perceived overall benefit to student learning, symptoms of superficial discussions by students have been observed recently. How this may be caused by poor case design is discussed. Other problems, including “silent tutors” and increased faculty workload, are discussed. It is concluded that after 5 years, Saga's implementation of a PBL curriculum has been successful. However, many additional issues, including motivation of students and preparation for PBL in the first 2 years, must still be resolved in the future. This is the first description of the positive and negative outcomes associated with the reform of medical education and the introduction of PBL to a traditional medical school curriculum in Japan.

  6. Antenatal hydronephrosis: Negative predictive value of normal postnatal ultrasound - a 5-year study

    Energy Technology Data Exchange (ETDEWEB)

    Moorthy, I.; Joshi, N.; Cook, J.V. E-mail: jcook@epsom-sthelier.nhs.uk; Warren, M

    2003-12-01

    AIM: To determine whether normal postnatal ultrasound, as part of a strict screening protocol for the detection and follow-up of antenatal hydronephrosis, effectively excludes the majority of babies with congenital urinary tract abnormalities that would otherwise present with a urinary tract infection. MATERIALS AND METHODS: We retrospectively reviewed all babies who had postnatal follow-up of antenatally detected hydronephrosis over a 5-year period at our institution, a district general Trust with a specialist paediatric unit. We then studied all babies presenting with urinary tract infection before their first birthday to our institution over the same period. By cross-referencing these two study groups we were able to determine which babies developed a urinary tract infection having been previously discharged after normal postnatal ultrasound. RESULTS: Four hundred and twenty-five babies had postnatal follow-up of antenatal hydronephrosis. Of these, 284 were investigated with ultrasound alone. In the same 5-year period, 230 babies presented with urinary tract infection before their first birthday. Only three of these babies had been previously discharged after normal postnatal ultrasound. The negative predictive value of a normal postnatal ultrasound was therefore 98.9% (281/284) for babies who subsequently presented with a urinary tract infection before their first birthday. CONCLUSION: Careful antenatal and postnatal ultrasound with strict protocols is effective in detecting congenital renal tract abnormalities. Infants discharged after normal postnatal ultrasound are highly unlikely to still have an undetected urinary tract abnormality. We suggest that all babies with antenatal hydronephrosis are started on prophylactic antibiotics at birth, pending further investigation. All babies without features of severe obstruction antenatally should have their postnatal ultrasound delayed for a month. We recommend selective use of micturating cystourethrogram (MCUG

  7. Antenatal hydronephrosis: Negative predictive value of normal postnatal ultrasound - a 5-year study

    International Nuclear Information System (INIS)

    Moorthy, I.; Joshi, N.; Cook, J.V.; Warren, M.

    2003-01-01

    AIM: To determine whether normal postnatal ultrasound, as part of a strict screening protocol for the detection and follow-up of antenatal hydronephrosis, effectively excludes the majority of babies with congenital urinary tract abnormalities that would otherwise present with a urinary tract infection. MATERIALS AND METHODS: We retrospectively reviewed all babies who had postnatal follow-up of antenatally detected hydronephrosis over a 5-year period at our institution, a district general Trust with a specialist paediatric unit. We then studied all babies presenting with urinary tract infection before their first birthday to our institution over the same period. By cross-referencing these two study groups we were able to determine which babies developed a urinary tract infection having been previously discharged after normal postnatal ultrasound. RESULTS: Four hundred and twenty-five babies had postnatal follow-up of antenatal hydronephrosis. Of these, 284 were investigated with ultrasound alone. In the same 5-year period, 230 babies presented with urinary tract infection before their first birthday. Only three of these babies had been previously discharged after normal postnatal ultrasound. The negative predictive value of a normal postnatal ultrasound was therefore 98.9% (281/284) for babies who subsequently presented with a urinary tract infection before their first birthday. CONCLUSION: Careful antenatal and postnatal ultrasound with strict protocols is effective in detecting congenital renal tract abnormalities. Infants discharged after normal postnatal ultrasound are highly unlikely to still have an undetected urinary tract abnormality. We suggest that all babies with antenatal hydronephrosis are started on prophylactic antibiotics at birth, pending further investigation. All babies without features of severe obstruction antenatally should have their postnatal ultrasound delayed for a month. We recommend selective use of micturating cystourethrogram (MCUG

  8. Direct Costs of Very Old Persons with Subsyndromal Depression: A 5-Year Prospective Study.

    Science.gov (United States)

    Ludvigsson, Mikael; Bernfort, Lars; Marcusson, Jan; Wressle, Ewa; Milberg, Anna

    2018-03-15

    This study aimed to compare, over a 5-year period, the prospective direct healthcare costs and service utilization of persons with subsyndromal depression (SSD) and non-depressive persons (ND), in a population of very old persons. A second aim was to develop a model that predicts direct healthcare costs in very old persons with SSD. A prospective population-based study was undertaken on 85-year-old persons in Sweden. Depressiveness was screened with the Geriatric Depression Scale at baseline and at 1-year follow-up, and the results were classified into ND, SSD, and syndromal depression. Data on individual healthcare costs and service use from a 5-year period were derived from national database registers. Direct costs were compared between categories using Mann-Whitney U tests, and a prediction model was identified with linear regression. For persons with SSD, the direct healthcare costs per month of survival exceeded those of persons with ND by a ratio 1.45 (€634 versus €436), a difference that was significant even after controlling for somatic multimorbidity. The final regression model consisted of five independent variables predicting direct healthcare costs: male sex, activities of daily living functions, loneliness, presence of SSD, and somatic multimorbidity. SSD among very old persons is associated with increased direct healthcare costs independently of somatic multimorbidity. The associations between SSD, somatic multimorbidity, and healthcare costs in the very old need to be analyzed further in order to better guide allocation of resources in health policy. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. [The Octabaix study. Baseline assessment and 5 years of follow-up].

    Science.gov (United States)

    Ferrer, Assumpta; Formiga, Francesc; Padrós, Gloria; Badia, Teresa; Almeda, Jesús; Octabaix, Grupo Estudio

    This is a review of a prospective, community-based study with a follow-up period of 5years. It is a study of 328 participants aged 85 at baseline, of which 62% were female, 53% widows, and a third of them living alone. High blood pressure was observed in 75.9%, dyslipidaemia in 51.2%, and diabetes in 17.7%. At baseline the median Barthel Index was 95, the Spanish version of the Mini-Mental State Examination was 28, the Charlson index 1, the Mini Nutritional Assessment 25, the Gijón test 10, the visual analogue scale of the Quality of Life Test was 60, and with a mean of 6.1 prescription drugs. A lower quality of life was also associated with female gender, a phenotype of frailty, heart failure, and a high level of social risk. At 5years of follow-up, the mortality rate was high, with 138 (42.1%) of the population sample dying at the end of the period. It represents an annual mortality rate of 8.4%. Thus, a common denominator of this review has been the high importance of functionality and overall comorbidity factors associated with mortality in this very old age group, compared to other more traditional factors in younger populations. Several studies of frailty have also been assessed in this group, as well as falls, nutritional risk, diabetes and successful aging, including important aspects to better understand this population group. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Radiologically isolated syndrome: 5-year risk for an initial clinical event.

    Directory of Open Access Journals (Sweden)

    Darin T Okuda

    Full Text Available OBJECTIVE: To report the 5-year risk and to identify risk factors for the development of a seminal acute or progressive clinical event in a multi-national cohort of asymptomatic subjects meeting 2009 RIS Criteria. METHODS: Retrospectively identified RIS subjects from 22 databases within 5 countries were evaluated. Time to the first clinical event related to demyelination (acute or 12-month progression of neurological deficits was compared across different groups by univariate and multivariate analyses utilizing a Cox regression model. RESULTS: Data were available in 451 RIS subjects (F: 354 (78.5%. The mean age at from the time of the first brain MRI revealing anomalies suggestive of MS was 37.2 years (y (median: 37.1 y, range: 11-74 y with mean clinical follow-up time of 4.4 y (median: 2.8 y, range: 0.01-21.1 y. Clinical events were identified in 34% (standard error=3% of individuals within a 5-year period from the first brain MRI study. Of those who developed symptoms, 9.6% fulfilled criteria for primary progressive MS. In the multivariate model, age [hazard ratio (HR: 0.98 (95% CI: 0.96-0.99; p=0.03], sex (male [HR: 1.93 (1.24-2.99; p=0.004], and lesions within the cervical or thoracic spinal cord [HR: 3.08 (2.06-4.62; p=<0.001] were identified as significant predictors for the development of a first clinical event. INTERPRETATION: These data provide supportive evidence that a meaningful number of RIS subjects evolve to a first clinical symptom. An age <37 y, male sex, and spinal cord involvement appear to be the most important independent predictors of symptom onset.

  11. Missed Immunization Opportunities Among Children Under 5 Years Of Age Dwelling In Karachi City.

    Science.gov (United States)

    Khaliq, Asif; Sayed, Sayeeda Amber; Hussaini, Syed Abdullah; Azam, Kiran; Qamar, Mehak

    2017-01-01

    Immunization is the safest and effective measure for preventing and eradicating various communicable diseases. A glaring immunization gap exists between developing and industrialized countries towards immunization, because the developing countries including Pakistan are still striving to provide basic immunization to their children. The purpose of this study was to access the prevalence and factors of missing immunization among under 5-year children of Karachi.. A cross sectional study was conducted from June 2015 to October 2015 among different outpatient clinics of Karachi. Parents who had child less than 5 year of age were approached by non-probability purposive sampling. Data was analysed by using Statistical Package of Social Sciences. There were around 59.09% (n=156) and 64.43% (n=165) parents who have correctly responded regarding the number of essential immunization visit during the first and second year of their child life respectively. About 28.12% (n=108) parents responded that they do not know about the name and number of missed doses of vaccines. 31.78% (n=122) parents responded that their children have missed either one or more than one doses of routine immunization vaccines. Of which 34.42% (n=42) children have missed more than one vaccine. Lack of knowledge regarding immunization schedule 28.68% (n=34), concern about vaccine side effects 21.31%, (n=26), child sickness 17.21% (n=21), and lack of trust about government 10.65%, (n=13) were the major barriers identified by parents for missed immunization opportunities. Parents have inadequate knowledge regarding routine immunization visits, immunization schedule and vaccine doses. The practices of parents for routine childhood immunization are also poor. Parents refuse to immunize their child because of lack of immunization visit knowledge and also because of their doubts regarding vaccine potency and side effects. A proper system of immunization promotion, advocacy and reminder systems with proper

  12. Characteristics and Costs of Disability Pensions in Finnish Agriculture Based on 5-Year Insurance Records.

    Science.gov (United States)

    Karttunen, Janne P; Rautiainen, Risto H; Leppälä, Jarkko

    2015-01-01

    The characteristics and costs of disability pensions in Finnish farmers were investigated. The data included a total of 4,088 permanent or temporary disability pensions of the self-employed Finnish farming population over a 5-year period (2008-2012), an annual rate of 1.04 new cases per 100 person-years (males 0.94/100 and females 1.24/100). These cases resulted in the loss of almost 6,800 person-years and 60.2 million Euros in pension costs in the 5-year period. Almost half of the outcomes (44.6%) were primarily related to diseases of the musculoskeletal system (MSDs). Other common outcomes were mental and behavioral disorders (17.5%), injuries (9.8%), diseases of the circulatory system (7.8%), and diseases of the nervous system (6.6%). Relative proportions of these outcomes and their costs were similar with few exceptions. Although farmers have high risk of acute traumatic injuries, they also have a high risk of chronic conditions that affect their work ability. Particularly MSDs were common primary reasons for disability pension among farmers in general and among female farmers in particular. In addition to healthy lifestyle choices, improvements in the working environment and methods to reduce heavy or repetitive manual labor should be emphasized in vocational and extension education of farmers. Modern working conditions with meaningful and varied work tasks could enhance both physical and mental well-being of farmers and thus reinforce and extend their careers.

  13. Etiology of Diarrhea in Children Younger Than 5 Years Attending the Bengo General Hospital in Angola.

    Science.gov (United States)

    Gasparinho, Carolina; Mirante, Maria Clara; Centeno-Lima, Sónia; Istrate, Claudia; Mayer, António Carlos; Tavira, Luis; Nery, Susana Vaz; Brito, Miguel

    2016-02-01

    Diarrheal disease is among the leading causes of death in children younger than 5 years, especially in developing countries. The aim of this study was to investigate the most frequent etiological agents of diarrhea and its associated factors in children younger than 5 years attending the Bengo General Hospital in Angola. From September 2012 through December 2013, stool samples were collected from 344 children presenting with diarrhea to investigate the presence of viral, bacterial and parasitic agents. Relevant sociodemographic and clinical data were obtained from parents and caregivers. An enteric pathogen was detected in 66.6% of stool samples: Cryptosporidium spp. (30.0%), rotavirus (25.1%), Giardia lamblia (21.6%), diarrheagenic Escherichia coli (6.3%), Ascaris lumbricoides (4.1%), adenovirus (3.8%), Strongyloides stercoralis (3.5%), astrovirus (2.6%), Hymenolepis nana (1.7%), Entamoeba histolytica/dispar (0.9%), Taenia spp. (0.6%), Trichuris trichiura (0.3%) and Entamoeba histolytica (0.3%). Children younger than 12 months were more frequently infected with Cryptosporidium spp. compared with older children (age: 12-59 months), independently of sex, season, lethargy and wasting [odds ratio (OR): 3.5, 95% confidence interval (95% CI): 2.0-6.2]. Age (OR: 5.0, 95% CI: 2.6-9.3), vomiting (OR: 2.7, 95% CI: 1.5-4.8) and type of admission (inpatients, OR: 0.5, 95% CI: 0.3-0.9) were significantly associated with rotavirus infection. This study demonstrates high rates of infection with an enteric pathogen, particularly in children younger than 12 months, emphasizing the need to address diarrheal disease in this age group.

  14. Histopathological report of colorectal carcinoma resections: A 5-year audit in Lagos.

    Science.gov (United States)

    Badmos, Kabir Bolarinwa; Rotimi, Olorunda; Lawal, Abdulrazzaq Oluwagbemiga; Osinowo, Adedapo O; Habeebu, Mohammed Y; Abdulkareem, Fatimah Biade

    2018-01-01

    Complete and accurate pathology reporting of colorectal carcinoma (CRC) resection specimen is critical to clinical management of individual patients. The study aims to audit colorectal cancer histopathology reporting in Lagos between 2011 and 2015 before the adoption of the Society for Gastroenterology and Hepatology in Nigeria pro forma in 2016. All resected CRC cases were identified from the Histopathology record of our Department and that of a private Laboratory in Lagos over a 5-year from 2011 to 2015. The dataset as contained in the pro forma was extracted from the reports and analysed using SPSS version 16 software. A total of 92 colorectal resections were received during the 5-year period consisting of 90 colonic and 2 rectal tumours. Data inclusiveness on tumour differentiation, extent of primary tumour, total lymph node and lymph node involvement were 96.7%, 91.3%, 83.7% and 92.4%, respectively. Tumour perforation, level of venous involvement and distant metastasis were reported in 73.9%, 21.7% and 96.7% respectively. The circumferential resection margin (CRM) in the 2 rectal tumours had 100% inclusiveness. Tumour node metastasis staging was complete in 87% of cases while Dukes staging was documented in 8.7% of the reports. None of the data items was 100% complete except the CRM for rectal carcinoma. Free text reporting results in incomplete data resulting in improper staging, especially the lymph node status. This highlights the need for pro forma reporting to ensure and maintain consistent reporting of important parameters required for proper staging and management of patients with colorectal cancer.

  15. The T 380A intrauterine device: a retrospective 5-year evaluation.

    Science.gov (United States)

    de Araujo, Fabio Fernando; Barbieri, Márcia; Guazzelli, Cristina Aparecida Falho; Lindsey, Prescilla Chow

    2008-12-01

    The undue resistance to intrauterine device (IUD) use seen in several settings does not seem to occur in the Family Planning Unit of UNIFESP-EPM (São Paulo Federal University, Brazil). In fact, the Copper T 380A IUD in this clinic has reached an outstanding importance and this motivated us to present our differing experience. The prevalence of this method in this clinic is as high as 40%. This contrasts to the low use in the rest of the country, where tubal ligation is by far the most used contraceptive method (40%) and where IUD is inexpressive (1.1%). This is a retrospective study of the records of 118 users of Copper T 380A IUD inserted at the clinic and who were followed during 5 years. The cumulative pregnancy rate was 0.8%. The main cause for discontinuation of the study was loss to follow-up (21.3%). Other reasons for the withdrawal of the device were personal option (13.6%), dislocation (11.7%) and pregnancy wish (3.4%). There was no withdrawal by pelvic inflammatory disease. Bleeding (0.8%) was not an important cause for withdrawal, and there were no withdrawals due to pain. The continuation rate at 5 years was 46.7%. The structured service and an adequate educative program perhaps could explain at least partially the good performance of IUD use in this clinic. There was an amazing prevalence of the components of the metabolic syndrome. This could represent contraindications for hormonal contraception, and, in consequence, it could influence the increased option for and continuation of the IUD. These data show a good performance of the IUD for long duration, in relation to other studies, and this should be considered as a reliable alternative to the high prevalence of female sterilization in this country.

  16. Retinal and Optic Nerve Degeneration in Patients with Multiple Sclerosis Followed up for 5 Years.

    Science.gov (United States)

    Garcia-Martin, Elena; Ara, Jose R; Martin, Jesus; Almarcegui, Carmen; Dolz, Isabel; Vilades, Elisa; Gil-Arribas, Laura; Fernandez, Francisco J; Polo, Vicente; Larrosa, Jose M; Pablo, Luis E; Satue, Maria

    2017-05-01

    To quantify retinal nerve fiber layer (RNFL) changes in patients with multiple sclerosis (MS) and healthy controls with a 5-year follow-up and to analyze correlations between disability progression and RNFL degeneration. Observational and longitudinal study. One hundred patients with relapsing-remitting MS and 50 healthy controls. All participants underwent a complete ophthalmic and electrophysiologic exploration and were re-evaluated annually for 5 years. Visual acuity (Snellen chart), color vision (Ishihara pseudoisochromatic plates), visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (SLP), and visual evoked potentials. Expanded Disability Status Scale (EDSS) scores, disease duration, treatments, prior optic neuritis episodes, and quality of life (QOL; based on the 54-item Multiple Sclerosis Quality of Life Scale score). Optical coherence tomography (OCT) revealed changes in all RNFL thicknesses in both groups. In the MS group, changes were detected in average thickness and in the mean deviation using the GDx-VCC nerve fiber analyzer (Laser Diagnostic Technologies, San Diego, CA) and in the P100 latency of visual evoked potentials; no changes were detected in visual acuity, color vision, or visual fields. Optical coherence tomography showed greater differences in the inferior and temporal RNFL thicknesses in both groups. In MS patients only, OCT revealed a moderate correlation between the increase in EDSS and temporal and superior RNFL thinning. Temporal RNFL thinning based on OCT results was correlated moderately with decreased QOL. Multiple sclerosis patients exhibit a progressive axonal loss in the optic nerve fiber layer. Retinal nerve fiber layer thinning based on OCT results is a useful marker for assessing MS progression and correlates with increased disability and reduced QOL. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  17. Tamoxifen from Failed Contraceptive Pill to Best-Selling Breast Cancer Medicine: A Case-Study in Pharmaceutical Innovation

    Directory of Open Access Journals (Sweden)

    Viviane M. Quirke

    2017-09-01

    Full Text Available Today, tamoxifen is one of the world's best-selling hormonal breast cancer drugs. However, it was not always so. Compound ICI 46,474 (as it was first known was synthesized in 1962 within a project to develop a contraceptive pill in the pharmaceutical laboratories of ICI (now part of AstraZeneca. Although designed to act as an anti-estrogen, the compound stimulated, rather than suppressed ovulation in women. This, and the fact that it could not be patented in the USA, its largest potential market, meant that ICI nearly stopped the project. It was saved partly because the team's leader, Arthur Walpole, threatened to resign, and pressed on with another project: to develop tamoxifen as a treatment for breast cancer. Even then, its market appeared small, because at first it was mainly used as a palliative treatment for advanced breast cancer. An important turning point in tamoxifen's journey from orphan drug to best-selling medicine occurred in the 1980s, when clinical trials showed that it was also useful as an adjuvant to surgery and chemotherapy in the early stages of the disease. Later, trials demonstrated that it could prevent its occurrence or re-occurrence in women at high risk of breast cancer. Thus, it became the first preventive for any cancer, helping to establish the broader principles of chemoprevention, and extending the market for tamoxifen and similar drugs further still. Using tamoxifen as a case study, this paper discusses the limits of the rational approach to drug design, the role of human actors, and the series of feedback loops between bench and bedside that underpins pharmaceutical innovation. The paper also highlights the complex evaluation and management of risk that are involved in all therapies, but more especially perhaps in life-threatening and emotion-laden diseases like cancer.

  18. National Prociency Testing Result of CYP2D6*10 Genotyping for Adjuvant Tamoxifen Therapy in China.

    Directory of Open Access Journals (Sweden)

    Guigao Lin

    Full Text Available Tamoxifen has been successfully used for treating breast cancer and preventing cancer recurrence. Cytochrome P450 2D6 (CYP2D6 plays a key role in the process of metabolizing tamoxifen to its active moiety, endoxifen. Patients with variants of the CYP2D6 gene may not receive the full benefit of tamoxifen treatment. The CYP2D6*10 variant (the most common variant in Asians was analyzed to optimize the prescription of tamoxifen in China. To ensure referring clinicians have accurate information for genotype-guided tamoxifen treatment, the Chinese National Center for Clinical Laboratories (NCCL organized a national proficiency testing (PT to evaluate the performance of laboratories providing CYP2D6*10 genotyping. Ten genomic DNA samples with CYP2D6 wild-type or CYP2D6*10 variants were validated by PCR-sequencing and sent to 28 participant laboratories. The genotyping results and pharmacogenomic test reports were submitted and evaluated by NCCL experts. Additional information regarding the number of samples tested, the accreditation/certification status, and detecting technology was also requested. Thirty-one data sets were received, with a corresponding analytical sensitivity of 98.2% (548/558 challenges; 95% confidence interval: 96.7-99.1% and an analytic specificity of 96.5% (675/682; 95% confidence interval: 97.9-99.5%. Overall, 25/28 participants correctly identified CYP2D6*10 status in 10 samples; however, two laboratories made serious genotyping errors. Most of the essential information was included in the 20 submitted CYP2D6*10 test reports. The majority of Chinese laboratories are reliable for detecting the CYP2D6*10 variant; however, several issues revealed in this study underline the importance of PT schemes in continued external assessment and provision of guidelines.

  19. Inhibition of MAP kinase promotes the recruitment of corepressor SMRT by tamoxifen-bound estrogen receptor alpha and potentiates tamoxifen action in MCF-7 cells

    International Nuclear Information System (INIS)

    Hong, Wei; Chen, Linfeng; Li, Juan; Yao, Zhi

    2010-01-01

    Estrogen receptor alpha (ERα), a ligand controlled transcription factor, plays an important role in breast cancer growth and endocrine therapy. Tamoxifen (TAM) antagonizes ERα activity and has been applied in breast cancer treatment. TAM-bound ERα associates with nuclear receptor-corepressors. Mitogen-activated protein kinase (MAPK) has been elucidated to result in cross-talk between growth factor and ERα mediated signaling. We show that activated MAPK represses interaction of TAM-bound ERα with silencing mediator for retinoid and thyroid hormone receptors (SMRT) and inhibits the recruitment of SMRT by ERα to certain estrogen target genes. Blockade of MAPK signaling cascade with MEK inhibitor U0126 promotes the interaction and subsequently inhibits ERα activity via enhanced recruitment of SMRT, leading to reduced expression of ERα target genes. The growth rate of MCF-7 cells was decelerated when treated with both TAM and U0126. Moreover, the growth of MCF-7 cells stably expressing SMRT showed a robust repression in the presence of TAM and U0126. These results suggest that activated MAPK signaling cascade attenuates antagonist-induced recruitment of SMRT to ERα, suggesting corepressor mediates inhibition of ERα transactivation and breast cancer cell growth by antagonist. Taken together, our finding indicates combination of antagonist and MAPK inhibitor could be a helpful approach for breast cancer therapy.

  20. Postoperative ileus: a preventable event

    DEFF Research Database (Denmark)

    Holte, Kathrine; Kehlet, H

    2000-01-01

    BACKGROUND: Postoperative ileus has traditionally been accepted as a normal response to tissue injury. No data support any beneficial effect of ileus and indeed it may contribute to delayed recovery and prolonged hospital stay. Efforts should, therefore, be made to reduce such ileus. METHODS......: Material was identified from a Medline search of the literature, previous review articles and references cited in original papers. This paper updates knowledge on the pathophysiology and treatment of postoperative ileus. RESULTS AND CONCLUSION: Pathogenesis mainly involves inhibitory neural reflexes...... only cisapride is proven beneficial; the effect of early enteral feeding remains unclear. However, postoperative ileus may be greatly reduced when all of the above are combined in a multimodal rehabilitation strategy....

  1. Alcohol abuse and postoperative morbidity

    DEFF Research Database (Denmark)

    Tønnesen, Hanne

    2003-01-01

    Patients who drink too much have more complications after surgery. The aim of this thesis was to evaluate the evidence, possible mechanisms, and prevention of the increased postoperative morbidity in alcohol abusers, defined by a consumption of at least five drinks per day. The literature could...... be criticised for several methodological flaws. Nevertheless, the results are in agreement showing moderate to strong evidence of increased postoperative morbidity after surgical procedures on alcohol abusers. There is weak to moderate evidence of increased postoperative mortality, hospital stay, and re......-operation. The personal and economic consequences are tremendous. The incidence of alcohol abusers undergoing surgery was 7% to 49%, according to gender and diagnosis. They have been identified by a self-reported alcohol intake, which implies the possibility of underestimation. Alcohol markers could be used for a more...

  2. Oxygen therapy reduces postoperative tachycardia

    DEFF Research Database (Denmark)

    Stausholm, K; Kehlet, H; Rosenberg, J

    1995-01-01

    Concomitant hypoxaemia and tachycardia in the postoperative period is unfavourable for the myocardium. Since hypoxaemia per se may be involved in the pathogenesis of postoperative tachycardia, we have studied the effect of oxygen therapy on tachycardia in 12 patients randomly allocated to blinded...... air or oxygen by facemask on the second or third day after major surgery. Inclusion criteria were arterial hypoxaemia (oxygen saturation 90 beat.min-1). Each patient responded similarly to oxygen therapy: an increase in arterial oxygen saturation and a decrease...... in heart rate (p oxygen has a positive effect on the cardiac oxygen delivery and demand balance....

  3. The efficacy of postoperative radiotherapy in localized primary soft tissue sarcoma treated with conservative surgery

    International Nuclear Information System (INIS)

    Zhao, Ru-Ping; Yu, Xiao-Li; Zhang, Zhen; Jia, Li-Juan; Feng, Yan; Yang, Zhao-Zhi; Chen, Xing-Xing; Wang, Jian; Ma, Sheng-Lin; Guo, Xiao-Mao

    2016-01-01

    To evaluate the efficacy of postoperative radiotherapy (RT) on local failure-free survival (LFFS), distant metastasis-free survival (DMFS) and overall survival (OS) in patients with localized primary soft tissue sarcoma (STS) and to identify prognostic factors. Between January 2000 and July 2010, 220 consecutive patients with localized primary STS, who received conservative surgery with or without postoperative RT, were enrolled in the study. Survival curves were constructed by the Kaplan-Meier method and log-rank test was used to assess statistical significance. Multivariate analysis was applied to identify the prognostic factors. After a median follow-up of 68 months (range, 5–127 months), the 5-year LFFS, DMFS and OS were 70.0, 78.2 and 71.2 %, respectively. Tumor size, histological subtypes, margin status and postoperative RT were independent predictors for OS. Postoperative RT was associated with a significant reduced local recurrence risk versus surgery alone (hazard ratio [HR] = 0.408, 95 % confidence interval [CI] 0.235–0.707, P = 0.001), with 5-year LFFS of 81.1 and 63.6 %, respectively (log-rank, P = 0.004). The log-rank test showed that postoperative RT had a tendency of improving OS compared with surgery alone, with 5-year OS of 74.8 and 65.0 %, respectively (P = 0.089). Multivariate analysis demonstrated that postoperative RT significantly reduced mortality rate compared with surgery alone (HR = 0.512, 95 % CI 0.296–0.886, p = 0.017), especially in patients with liposarcoma (p = 0.034). Postoperative radiotherapy reduce both local recurrence and STS mortality in patients with localized primary STS. The efficacy of RT on survival warrants further prospective study. The online version of this article (doi:10.1186/s13014-016-0605-y) contains supplementary material, which is available to authorized users

  4. [Therapeutic education of elderly patients under antivitamin - K treatment: evaluation of the program after 5 years].

    Science.gov (United States)

    Thiriat, N; Peyron, I; Bernard-Charrière, S; Monti, A; Pariel, S; Pautas, E

    2014-09-01

    Elderly people with vitamin K antagonists (VKA) have a higher risk of potentially serious hemorrhagic complications. An education program for patients (EPP) aged > or = 75 years with VKA was set up in 2008 in a French geriatric hospital. It includes individual and group sessions conducted by a nurse and a geriatrician. The aim of this study was to assess this EPP after 5 years. Strengths, weaknesses and difficulties of implementation were highlighted, and some improvements were proposed. This study is an external audit conducted by a pharmacist trained in EPP. Files of consecutive patients included in the program between may 2008 and March 2013 were reviewed allowing the data collection of patients characteristics and results of the different sessions. The educational objectives were assessed by the rate of correct responses to the questionnaires during the program. The results are presented taking into account the changes made during the 5 years of the program. One hundred forty-three patients, mean age 83.3 +/- 6.5 years, were included in the EPP. 51 sessions were conducted (2.8 patients/session on average). 58% of selected patients were hospitalized. The mean time between the start of anticoagulant treatment and the incLusion in the program was 48.9 +/- 71 months. For 95 patients (66.4%) the medication management at home required a caregiver who was present for sessions in 82 cases (57.3%). The questionnaires form and the organisation of the sessions were gradually improved between 2008 and the end of 2010. Thus, the impact of the EPP has been estimated from November 2010 to March 2013. The correct responses rates before and after the sessions were respectively: 47.8% vs 91.3% for knowledge of INR target values, 25.4% vs 91.3% for knowledge of hemorrhagic signs, 14.9% vs 87.0% for knowledge of the situations or the medications that may disturb the INR equilibrium. Furthermore, the mean number of correct responses, for the 23 patients participating in the entire

  5. 5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials.

    Science.gov (United States)

    Reddy, Vivek Y; Doshi, Shephal K; Kar, Saibal; Gibson, Douglas N; Price, Matthew J; Huber, Kenneth; Horton, Rodney P; Buchbinder, Maurice; Neuzil, Petr; Gordon, Nicole T; Holmes, David R

    2017-12-19

    The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, St. Paul, Minnesota) was equivalent to warfarin for preventing stroke in atrial fibrillation, but had a high rate of complications. In a second randomized trial, PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), the complication rate was low. The warfarin cohort experienced an unexpectedly low ischemic stroke rate, rendering the efficacy endpoints inconclusive. However, these outcomes were based on relatively few patients followed for a relatively short time. The final results of the PREVAIL trial, both alone and as part of a patient-level meta-analysis with the PROTECT AF trial, are reported with patients in both trials followed for 5 years. PREVAIL and PROTECT AF are prospective randomized clinical trials with patients randomized 2:1 to LAAC or warfarin; together, they enrolled 1,114 patients for 4,343 patient-years. Analys