[The roles of otolith organs in the recurrence primary benign paroxysmal positional vertigo].

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Zhou, Xiaowei; Yu, Youjun; Wu, Ziming; Liu, Xinjian; Chen, Xianbing

2015-09-01

To explore the roles of otolith organs in the occurrence and recurrence of primary benign paroxysmal positional vertigo (BPPV) by vestibular evoked myogenic potential (VEMP) test. We enrolled 17 recurrent primary BPPV patients and 42 non-recurrent primary BPPV patients between September 2014 and November 2014. All patients underwent VEMP tests, including cervical vestibular evoked myogenic potential (cVEMP and ocular vestibular evoked myogenic potential (oVEMP) tests. The abnormal case was defined as non-elicitation or asymmetry rate between bilateral sides is larger than 29%. Significant difference was found in abnormal rate between cVEMP and oVEMP (P 0.05). No significant difference was found in sex and age between recurrent and non-recurrent groups (P > 0.05). The impairment of otolith organs, especially the utricle, is related to primary BPPV. Dysfunction of utricle may play a role in recurrence of BPPV. Recurrence of BPPV is not correlated with sex and age.

Analysis of perfusion weighted image of CNS lymphoma

International Nuclear Information System (INIS)

Lee, In Ho; Kim, Sung Tae; Kim, Hyung-Jin; Kim, Keon Ha; Jeon, Pyoung; Byun, Hong Sik

2010-01-01

Purpose: It is difficult to differentiate CNS lymphoma from other tumors such as malignant gliomas, metastases, or meningiomas with conventional MR imaging, because the imaging findings are overlapped between these tumors. The purpose of this study is to investigate the perfusion weighted MR imaging findings of CNS lymphomas and to compare the relative cerebral blood volume ratios between CNS lymphomas and other tumors such as high grade gliomas, metastases, or meningiomas. Materials and methods: We retrospectively reviewed MRI findings and clinical records in 13 patients with pathologically proven CNS lymphoma between January 2006 and November 2008. We evaluated the relative cerebral blood volume ratios of tumor, which were obtained by dividing the values obtained from the normal white matter on MRI. Results: Total 13 patients (M:F = 8:5; age range 46-67 years, mean age 52.3 years) were included. The CNS lymphomas showed relatively low values of maximum relative CBV ratio in most patients regardless of primary or secondary CNS lymphoma. Conclusion: Perfusion weighted image may be helpful in the diagnosis of CNS lymphoma in spite of primary or secondary or B cell or T cell.

Recurrent Primary Spinal Hydatid Cyst

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Okan Turk

2015-03-01

Full Text Available Primary hydatid disease of spine is rare and spinal hydatitosis constitute only 1% of all hydatitosis. We report a case of recurrent primary intraspinal extradural hydatid cyst of the thoracic region causing progressive paraparesis. The patient was operated 16 years ago for primary spinal hydatid disease involvement and was instrumented dorsally for stabilization. The magnetic resonance imaging (MRI of thoracic spine showed a cystic lesion at T11-12 level and compressed spinal cord posterolaterally. Intraspinal cyst was excised through T11-12 laminectomy which made formerly. The early postoperative period showed a progressive improvement of his neurological deficit and he was discharged with antihelmintic treatment consisting of albendazole and amoxicillin-sulbactam combination. [Cukurova Med J 2015; 40(Suppl 1: 84-89

Radiation therapy in recurrence of carcinoma of the uterine cervix after primary surgery

International Nuclear Information System (INIS)

Kim, Jin Hee; Kim, Ok Bae

2003-01-01

The purpose of this study was to evaluate treatment results in terms of the survival and failure patterns subsequent to radiation therapy in recurrent cervical cancer, following primary surgery. Between January 1990 and December 1999, 27 patients, with recurrent cervical cancer following primary surgery, were subsequently treated with radiation in the Department of Radiation Oncology, at the Keimyung University Dongsan Medical Center. Their median age was 48, ranging from 31 to 70 years old. With regard to the initial FIGO stage on presentation, 20 and 7 patients were stages I and II, respectively. Twenty three patients had squamous ceH carcinomas and 4 had adenocarcinomas. The time interval from the primary surgery to the recurrence ranged from 2 to 90 months with a median of 29 months. The recurrent sites were the vaginal cuff alone, the pelvic cavity and combined recurrence in 14, 9 and 4 patients, respectively. Radiation was performed, with external and vaginal intracavitary radiation in 13 patients, external radiation alone in 13 and vaginal intracavitary radiation alone in another one. The median follow-up period was 55 months, ranging from 6 to 128 months. The five year disease free survival (5y DFS) and five year overall survival (5y OS) rates were 68.2 and 71.9%, respectively. There was a marginal statistically significant difference in the 5y DFS in relation to the recurrent site (5y DFS, 85.7% in vaginal cuff recurrence alone, 53.3% in pelvic cavity recurrence, p=0.09). There was no difference in the survival according to the time interval between the primary surgery and a recurrence. There was only a 7% local failure rate in the patients with a vaginal cuff recurrence. The major failure patterns were local failure in the patients with pelvic cavity recurrence, and distant failure in the patients with a combined recurrence. There were no complications above grade 3 after the radiation therapy. Radiation therapy was safe and effective treatment for a

Recurrent Primary Spontaneous Pneumothorax is Common Following Chest Tube and Conservative Treatment.

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Olesen, Winnie Hedevang; Lindahl-Jacobsen, Rune; Katballe, Niels; Sindby, Jesper Eske; Titlestad, Ingrid Louise; Andersen, Poul Erik; Licht, Peter Bjørn

2016-09-01

Previous studies on primary spontaneous pneumothorax reported variable recurrence rates, but they were based on heterogeneous patient populations including secondary pneumothorax. We investigated young patients with primary spontaneous pneumothorax exclusively and used a national registry to track readmissions and calculate independent predictors of recurrence. A prospective cohort study of consecutive young patients who were admitted over a 5-year period with their first episode of primary spontaneous pneumothorax and treated conservatively with a chest tube. Baseline characteristics were obtained from questionnaires presented on admittance. All patients were discharged with fully expanded lungs on chest radiography. Patient charts were identified in the national electronic patient registry for detailed information on readmissions due to recurrent spontaneous pneumothorax. We included 234 patients. Male/female = ratio 5/1. After a median observation period of 3.6 years (range 1-6 years), recurrent pneumothorax was observed in 54 %. Ipsilateral recurrence was the most common (79 %) but 30 % also experienced contralateral pneumothorax during the study period. Females had a significantly higher age at debut (p pneumothorax in younger patients with their first episode had a much higher recurrence rate than previously reported. Every doctor who treats patients with primary spontaneous pneumothorax should be aware and patients informed.

High-dose rate brachytherapy (HDRB) for primary or recurrent cancer in the vagina

International Nuclear Information System (INIS)

Beriwal, Sushil; Heron, Dwight E; Mogus, Robert; Edwards, Robert P; Kelley, Joseph L; Sukumvanich, Paniti

2008-01-01

The purpose of this study was to evaluate the efficacy of HDR brachytherapy for primary or recurrent vaginal cancer. Between the years 2000 to 2006, 18 patients with primary or recurrent vaginal cancer were treated with brachytherapy (HDRB). Six patients had primary vaginal cancer (stage II to IVA) while 12 were treated for isolated vaginal recurrence (primary cervix = 4, vulva = 1 and endometrium = 7). Five patients had previous pelvic radiation therapy. All except one patient received external beam radiation therapy to a median dose of 45 Gy (range 31.2–55.8 Gy). The HDRB was intracavitary using a vaginal cylinder in 5 patients and interstitial using a modified Syed-Nesblett template in 13 patients. The dose of interstitial brachytherapy was 18.75 Gy in 5 fractions delivered twice daily. The median follow-up was 18 months (range 6–66 months). Complete response (CR) was achieved in all but one patient (94%). Of these 17 patients achieving a CR, 1 had local recurrence and 3 had systemic recurrence at a median time of 6 months (range 6–22 months). The 2-year actuarial local control and cause-specific survival for the entire group were 88% and 82.5%, respectively. In subset analysis, the crude local control was 100% for primary vaginal cancer, 100% for the group with recurrence without any prior radiation and 67% for group with recurrence and prior radiation therapy. Two patients had late grade 3 or higher morbidity (rectovaginal fistula in one patient and chronic vaginal ulcer resulting in bleeding in one patient). Both these patients had prior radiation therapy. Our small series suggests that HDRB is efficacious for primary or recurrent vaginal cancer. Patients treated with primary disease and those with recurrent disease without prior irradiation have the greatest benefit from HDRB in this setting. The salvage rate for patients with prior radiation therapy is lower with a higher risk of significant complications. Additional patients and follow-up are ongoing

Actuarial risk of isolated CNS involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate

International Nuclear Information System (INIS)

Trigg, M.E.; Makuch, R.; Glaubiger, D.

1985-01-01

Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolate CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving DNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to CNS

Diagnostic value of kinetic analysis using dynamic FDG PET in immunocompetent patients with primary CNS lymphoma

International Nuclear Information System (INIS)

Nishiyama, Yoshihiro; Yamamoto, Yuka; Monden, Toshihide; Sasakawa, Yasuhiro; Satoh, Katashi; Ohkawa, Motoomi; Kawai, Nobuyuki

2007-01-01

The purpose of this study was to investigate the accumulation of FDG in immunocompetent patients with primary central nervous system (CNS) lymphoma using qualitative and quantitative PET images and to compare baseline with follow-up PET after therapy. Twelve immunocompetent patients with CNS lymphoma were examined. Dynamic emission data were acquired for 60 min immediately following injection of FDG. In seven patients, repeated PET studies were performed after treatment. Applying a three-compartment five-parameter model, K 1 , k 2 , k 3 , k 4 , vascular fraction (V B ) and cerebral metabolic rate of glucose (CMR Glc ) were obtained. We evaluated the FDG uptake visually using qualitative and parametric images and quantitatively using parametric images. A total of 12 lesions were identified in ten patients with newly diagnosed CNS lymphoma. On visual analysis, ten lesions showed an increase on qualitative images, eight showed an increase on K 1 images, 12 showed an increase on k 3 images and ten showed an increase on CMR Glc images. On quantitative analysis, k 2 , k 3 and CMR Glc values of the lesion were significantly different from those of the normal grey matter (p 3 and CMR Glc images. The K 1 , k 2 , k 3 and CMR Glc values after treatment were significantly different from those obtained before treatment (p 3 , using dynamic FDG PET might be helpful for diagnosis of CNS lymphoma and for monitoring therapeutic assessment. (orig.)

Stage IE Primary Bone Lymphoma:Limb Salvage for Local Recurrence

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Khodamorad Jamshidi

2015-01-01

Full Text Available Background:   Primary bone lymphoma or non-Hodgkin lymphoma of bone is a rare disease. There are only a few case series of stage IE of this condition in medical literature. The aim of this study is to determine the rate of survival   for stage IE after combined modality treatment, the rate of local recurrence, and the results of limb salvage in cases   of local recurrence.     Methods:   We collected data from 61 patients with histologically confirmed PBL treated at the Musculoskeletal   Oncology Department of our hospital from 2000 to 2010. Retrospective evaluation included demographics, symptoms, tumor locations, outcomes of surgical treatment for local recurrence and survival rates. Results:   All patients received Combined Modality Therapy. Overall,five year survival was 89% and five year disease free survival rate was 78%. Local recurrence occurred in 6 patients during follow up period, which was treated surgically     by wide excision and reconstruction. The mean follow-up for the local recurrence group was 36(24-54 months and mortality rate in this group was 17%. Conclusions:   Combined Modality Therapy for stage IE primary bone lymphomaresults in good survival rate. In case   of local recurrence, wide excision and reconstruction improves the outcomes.

Recurrent Primary Spontaneous Pneumothorax is Common Following Chest Tube and Conservative Treatment

DEFF Research Database (Denmark)

Olesen, Winnie Hedevang; Lindahl-Jacobsen, Rune; Katballe, Niels

2016-01-01

INTRODUCTION: Previous studies on primary spontaneous pneumothorax reported variable recurrence rates, but they were based on heterogeneous patient populations including secondary pneumothorax. We investigated young patients with primary spontaneous pneumothorax exclusively and used a national...... registry to track readmissions and calculate independent predictors of recurrence. METHODS: A prospective cohort study of consecutive young patients who were admitted over a 5-year period with their first episode of primary spontaneous pneumothorax and treated conservatively with a chest tube. Baseline...... characteristics were obtained from questionnaires presented on admittance. All patients were discharged with fully expanded lungs on chest radiography. Patient charts were identified in the national electronic patient registry for detailed information on readmissions due to recurrent spontaneous pneumothorax...

Testicular regulation of neuronal glucose and monocarboxylate transporter gene expression profiles in CNS metabolic sensing sites during acute and recurrent insulin-induced hypoglycemia.

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Vavaiya, Kamlesh V; Paranjape, Sachin A; Briski, Karen P

2007-01-01

Recurrent insulin-induced hypoglycemia (RIIH) impairs glucose counter-regulatory function in male humans and rodents and, in the latter, diminishes neuronal activation in CNS structures that monitor metabolic homeostasis, including the lateral hypothalamic area (LHA) and dorsal vagal complex (DVC). We investigated whether habituated neuronal reactivity in CNS sensing sites to hypoglycemia is correlated with modified monocarboxylate and/or glucose uptake by using quantitative real-time RT-PCR to analyze neuronal monocarboxylate transporter (MCT2) and glucose transporter variant (GLUT and GLUT4) gene expression profiles in the microdissected LHA, ventromedial nucleus hypothalamus (VMH), and DVC after one or multiple insulin injections. Because orchidectomy (ORDX) maintains uniform glycemic responses to RIIH in male rats, we also examined whether regional gene response patterns are testes dependent. In the intact male rat DVC, MCT2, GLUT3, and GLUT4 gene expression was not altered by acute hypoglycemia but was enhanced by RIIH. MCT2 and GLUT3 mRNA levels in the ORDX rat DVC did not differ among groups, but GLUT4 transcripts were progressively increased by acute and recurrent hypoglycemia. Precedent hypoglycemia decreased or increased basal MCT2 and GLUT4 gene expression, respectively, in the intact rat LHA; LHA GLUT3 transcription was augmented by RIIH in intact rats only. Acute hypoglycemia suppressed MCT2, GLUT3, and GLUT4 gene expression in the intact rat VMH, a response that was abolished by RIIH. In ORDX rats, VMH gene transcript levels were unchanged in response to one dose of insulin but were selectively diminished during RIIH. These data demonstrate site-specific, testes-dependent effects of acute and recurrent hypoglycemia on neuronal metabolic substrate transporter gene expression in characterized rat brain metabolic sensing loci and emphasize the need to assess the impact of potential alterations in glucose and lactate uptake during RIIH on general and

Association Between BMI and Recurrence of Primary Spontaneous Pneumothorax.

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Tan, Juntao; Yang, Yang; Zhong, Jianhong; Zuo, Chuantian; Tang, Huamin; Zhao, Huimin; Zeng, Guang; Zhang, Jianfeng; Guo, Jianji; Yang, Nuo

2017-05-01

Whether body mass index (BMI) is a significant risk factor for recurrence of primary spontaneous pneumothorax (PSP) remains controversial. The purpose of this study was to examine whether BMI and other factors are linked to risk of PSP recurrence. A consecutive cohort of 273 patients was retrospectively evaluated. Patients were divided into those who experienced recurrence (n = 81) and those who did not (n = 192), as well as into those who had low BMI (n = 75) and those who had normal or elevated BMI (n = 198). The two pairs of groups were compared in terms of baseline data, and Cox proportional hazards modeling was used to identify predictors of PSP recurrence. Rates of recurrence among all 273 patients were 20.9% at 1 year, 23.8% at 2 years, and 28.7% at 5 years. Univariate analysis identified the following significant predictors of PSP recurrence: height, weight, BMI, size of pneumothorax, and treatment modality. Multivariate analyses identified several risk factors for PSP recurrence: low BMI, pneumothorax size ≥50%, and non-surgical treatment. Kaplan-Meier survival analysis indicated that patients with low BMI showed significantly lower recurrence-free survival than patients with normal or elevated BMI (P pneumothorax size ≥50%, and non-surgical treatment were risk factors for PSP recurrence in our cohort. Low BMI may be a clinically useful predictor of PSP recurrence.

Mammographic Features of Local Recurrence after Conservative Surgery and Radiation Therapy: Comparison with that of the Primary Tumor

International Nuclear Information System (INIS)

Guenhan-Bilgen, I.; Oktay, A.

2007-01-01

Purpose: To compare the mammographic features of recurrent breast cancer with those of the primary tumor and to determine whether certain mammographic features are associated with a higher risk of local recurrence after breast-conserving therapy. Material and Methods: A retrospective review of mammograms of 421 patients who were treated with conservative surgery and radiotherapy revealed 41 recurrent tumors. Mammographic findings, location, and histopathologic characteristics were retrospectively compared between primary and recurrent tumors. Results: Recurrent tumors were similar in mammographic appearance to primary tumors in 27 (66%) cases. Of 27 primary tumors that occurred as masses without calcifications, 19 (70%) recurred as a mass, and of the six isolated calcifications, five (83%) recurred with calcifications. Ten (53%) of the 19 recurrent masses and five (100%) of the five recurrent calcifications had morphologic features that were similar to those of the primary tumor. Ninety-two percent (11/12) of the recurrences containing microcalcifications (isolated or associated with a mass) had microcalcifications in their primary tumor. Of 27 masses that recurred, the morphology of the primary tumor was obscured in 13 (48%), ill defined in 10 (37%), and spiculated in four (15%) of the masses. Seventy-six percent (31/41) of recurrences were within the lumpectomy quadrant. In 25 (61%) cases, the histologic findings from the primary tumor and the recurrence were identical. Conclusion: The majority of recurrent tumors appear to be mammographically similar to primary tumors. Therefore, it is important to review preoperative mammograms during follow-up of these patients. Although the study population is small, it was noted that mass with spiculated contour is associated with a lower risk for local recurrence

CNS effects following the treatment of malignancy

International Nuclear Information System (INIS)

Rane, N.; Quaghebeur, G.

2012-01-01

Corporeal and central nervous system (CNS) axis chemotherapy and radiotherapy have long been used for the effective treatment and prophylaxis of CNS, body malignancies, and leukaemias. However, they are not without their problems. Following the proliferation of magnetic resonance neuroimaging in recent years it has become clear that the spectrum of toxicity that these therapies produce ranges from subclinical white matter changes to overt brain necrosis. The effects are both direct and indirect and via different pathological mechanisms. Chronic and progressive changes can be detected many years after the initial intervention. In addition to leucoencephalopathic changes, grey matter changes are now well described. Changes may be difficult to distinguish from tumour recurrence, though may be reversible and remediable, and are thus very important to differentiate. In this review toxic effects are classified and their imaging appearances discussed, with reference to specific syndromes.

Computed tomography-guided cryoablation of local recurrence after primary resection of pancreatic adenocarcinoma

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Claudio Pusceddu

2015-06-01

Full Text Available The optimal management of local recurrences after primary resection of pancreatic cancer still remains to be clarified. A 58-yearold woman developed an isolated recurrence of pancreatic cancer six year after distal pancreatectomy. Re-resection was attempted but the lesion was deemed unresectable at surgery. Then chemotherapy was administrated without obtaining a reduction of the tumor size nor an improvement of the patient’s symptoms. Thus the patient underwent percutaneous cryoablation under computed tomography (CT-guidance obtaining tumor necrosis and a significant improvement in the quality of life. A CT scan one month later showed a stable lesion with no contrast enhancement. While the use of percutaneous cryoblation has widened its applications in patients with unresectable pancreatic cancer, it has never been described for the treatment of local pancreatic cancer recurrence after primary resection. Percutaneous cryoablation deserves further studies in the multimodality treatment of local recurrence after primary pancreatic surgery.

Management and Outcome of Patients With Langerhans Cell Histiocytosis and Single-Bone CNS-Risk Lesions: A Multi-Institutional Retrospective Study

NARCIS (Netherlands)

Chellapandian, Deepak; Shaikh, Furqan; van den Bos, Cor; Somers, Gino R.; Astigarraga, Itziar; Jubran, Rima; Degar, Barbara; Carret, Anne-Sophie; Mandel, Karen; Belletrutti, Mark; Dix, David; Visser, Johannes; Abuhadra, Nour; Chang, Tiffany; Rollins, Barret; Whitlock, James; Weitzman, Sheila; Abla, Oussama

2015-01-01

Children with Langerhans cell histiocytosis (LCH) and single-bone CNS-risk lesions have been reported to be at increased risk of diabetes insipidus (DI), central nervous system neurodegeneration (CNS-ND), and recurrence of disease. However, it is unknown whether the addition of chemotherapy or

Which is worse? Comparison of ART outcome between women with primary or recurrent endometriomas.

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Ata, Baris; Mumusoglu, Sezcan; Aslan, Kiper; Seyhan, Ayse; Kasapoglu, Isil; Avci, Berrin; Urman, Bulent; Bozdag, Gurkan; Uncu, Gurkan

2017-07-01

Are live birth rates (LBR) different after ART cycles between women with primary or recurrent endometrioma? Women with recurrent endometrioma have similar LBR as compared to patients with primary endometrioma. Recurrence rate can be as high as 29% after endometrioma excision. Prior studies on management of endometrioma before ART involve primary endometriomas. There is limited information regarding the prognosis of women with recurrent endometriomas. A multicenter retrospective cohort study, including 76 women with primary and 82 women with recurrent endometriomas treated at the participating centers over a 6-year period. Women with endometrioma who underwent ART at three academic ART centers. Couples with another indication for ART were excluded. Female age, median number of prior failed ART cycles, proportion of patients with bilateral endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total gonadotropin consumption were similar between the study groups. Numbers of metaphase two oocytes (5 versus 6), number of embryos transferred, and the proportion of patients undergoing blastocyst transfer were similar across the study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference 2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent and primary endometrioma were similar. Comparable success rates were also confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P = 2.3). The retrospective design has inherent limitations. Some women with severely decreased ovarian reserve after primary endometrioma excision may not have pursued further treatment. The management of endometrioma prior to ART is controversial but a different management strategy is not required for recurrent endometriomas. Since recurrent endometriomas do not have a worse impact on ART outcome than primary endometriomas, and repeat surgery has a higher

Can metabolic tumor parameters on primary staging 18F-FDG PET/CT aid in risk stratification of primary central nervous system lymphomas for patient management as a prognostic model?

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Okuyucu, K; Alagoz, E; Ince, S; Ozaydin, S; Arslan, N

Primary central nervous system (CNS) lymphoma is an aggressive and fatal extranodal non-Hodgkin lymphoma jailed in CNS at initial diagnosis. Its prognosis is poor and the disease has a fatal outcome when compared with systemic non-Hodgkin lymphoma. A few baseline risk stratification scoring systems have been suggested to estimate the prognosis mainly based on serum lactate dehydrogenase level,age, Karnofsky performance score, involvement of deep brain structures and cerebrospinal fluid protein concentration. 18 F-FDG PET/CT has a high prognostic value with respect to overall survival and disease-free survival in many cancers and lymphomas. We aimed to investigate metabolic tumor indexes on primary staging 18 F-FDG PET/CT as prognostic markers in primary CNS lymphoma. Fourteen patients with primary CNS diffuse large B-cell lymphoma (stage i) were enrolled in this retrospective cohort study. Primary staging 18 F-FDG PET/CT was performed and quantitative parameters like maximum standardized uptake value, average standardized uptake value, metabolic tumor volume and total lesion glycolysis (TLG) were calculated for all patients before the treatment. Cox regression models were performed to determine their relation with survival time. In the evaluation of all potential risk factors impacting recurrence/metastases (age, sex, serum lactate dehydrogenase, involvement of deep brain structures, maximum standardized uptake value, average standardized uptake value, metabolic tumor volume, and TLG) with univariate analysis, TLG remained statistically significant (P=.02). Metabolic tumor parameters are useful in prognosis estimation of primary CNS lymphomas, especially TLG, which is the most important one and may play a role in patient management. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Economic burden of primary compared with recurrent Clostridium difficile infection in hospitalized patients: a prospective cohort study.

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Shah, D N; Aitken, S L; Barragan, L F; Bozorgui, S; Goddu, S; Navarro, M E; Xie, Y; DuPont, H L; Garey, K W

2016-07-01

Few studies have investigated the additional healthcare costs of recurrent C. difficile infection (CDI). To quantify inpatient treatment costs for CDI and length of stay among hospitalized patients with primary CDI only, compared with CDI patients who experienced recurrent CDI. This was a prospective, observational cohort study of hospitalized adult patients with primary CDI followed for three months to assess for recurrent CDI episodes. Total and CDI-attributable hospital length of stay (LOS) and hospitalization costs were compared among patients who did or did not experience at least one recurrent CDI episode. In all, 540 hospitalized patients aged 62±17 years (42% males) with primary CDI were enrolled, of whom 95 patients (18%) experienced 101 recurrent CDI episodes. CDI-attributable median (interquartile range) LOS and costs (in US$) increased from 7 (4-13) days and $13,168 (7,525-24,456) for patients with primary CDI only versus 15 (8-25) days and $28,218 (15,050-47,030) for patients with recurrent CDI (Pcosts increased from 11 (6-22) days and $20,693 (11,287-41,386) for patients with primary CDI only versus 24 (11-48) days and $45,148 (20,693-82,772) for patients with recurrent CDI (Pcost of pharmacological treatment while hospitalized was $60 (23-200) for patients with primary CDI only (N=445) and $140 (30-260) for patients with recurrent CDI (P=0.0013). This study demonstrated that patients with CDI experience a significant healthcare economic burden attributed to CDI. Economic costs and healthcare burden increased significantly for patients with recurrent CDI. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Primary spontaneous pneumothorax in menstruating females has high recurrence

Science.gov (United States)

Mehta, Christopher K.; Stanifer, Bryan P.; Fore-Kosterski, Susan; Gillespie, Colin; Yeldandi, Anjana; Meyerson, Shari; Odell, David D.; DeCamp, Malcolm M.; Bharat, Ankit

2016-01-01

Background Primary spontaneous pneumothorax (PSP) is treated based on studies that have predominantly consisted of tall male subjects. Here we determined recurrence of PSP in average-statured menstruating women and studied prevalence of catamenial pneumothorax (CP) in this population. Methods Males and menstruating females, aged 18-55 years, without underlying lung disease or substance abuse were retrospectively studied between 2009-2015. A chest pathologist reviewed all specimens for thoracic endometriosis. Kaplan-Meier curves were constructed to determine recurrence. Results The median age of females (n=33) and males (n=183) was 33.4 and 31.6 years, respectively. In females, nine (27%) had left-sided and 24 (73%) had right-sided PSP, treated with tube thoracostomy. Recurrence occurred in 21 (64%) females with median follow up of 14 months and was treated with thoracoscopic pleurodesis. Right PSP had higher recurrence (70%) compared to left (56%, p=0.02). Four females (12%) presented with recurrent tension pneumothorax within six months. Eight (24%) patients had PSP within 72 hours of menses, meeting clinical criteria of CP. All these were placed on hormonal suppression after initial episode but went on to develop recurrence that was treated with pleurodesis. However, classic endometrial glands were not found in any biopsy specimens obtained during the thoracoscopy. In contrast to female subjects, only 8 (4.4%) average-statured males had recurrence (p<0.001) with a median follow up of 16 months. Conclusions PSP in healthy average-statured menstruating women has high recurrence compared to male counterparts. CP is a clinical diagnosis and often recurs despite hormonal suppression therapy. PMID:27345097

Primary Spontaneous Pneumothorax in Menstruating Women Has High Recurrence.

Science.gov (United States)

Mehta, Christopher K; Stanifer, Bryan P; Fore-Kosterski, Susan; Gillespie, Colin; Yeldandi, Anjana; Meyerson, Shari; Odell, David D; DeCamp, Malcolm M; Bharat, Ankit

2016-10-01

Primary spontaneous pneumothorax (PSP) is treated on the basis of studies that have predominantly consisted of tall male subjects. Here, we determined recurrence of PSP in average-statured menstruating women and studied prevalence of catamenial pneumothorax (CP) in this population. Men and menstruating women, aged 18 to 55 years, without underlying lung disease or substance abuse were retrospectively studied between 2009 and 2015. A chest pathologist reviewed all specimens for thoracic endometriosis. Kaplan-Meier curves were constructed to determine recurrence. The median age of women (n = 33) and men (n = 183) was 33.4 and 31.6 years, respectively. In women, 9 (27%) had left-sided and 24 (73%) had right-sided PSP, treated with tube thoracostomy. Recurrence occurred in 21 women (64%) with median follow-up of 14 months, and they were treated with thoracoscopic pleurodesis. Right PSP had higher recurrence (70%) than left PSP (56%, p = 0.02). Four women (12%) presented with recurrent tension pneumothorax within 6 months. Eight patients (24%) had PSP within 72 hours of menses, meeting clinical criteria of CP. All these were placed on hormonal suppression after initial episode but went on to experience recurrence that was treated with pleurodesis. Classical endometrial glands were not found in any biopsy specimens obtained during the thoracoscopy. In contrast to female subjects, only 8 average-statured men (4.4%) had recurrence (p < 0.001) with a median follow-up of 16 months. PSP in healthy average-statured menstruating women has high recurrence compared with male counterparts. CP is a clinical diagnosis and often recurs despite hormonal suppression therapy. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Recurrent rates and risk factors associated with recurrent painful bullous keratopathy after primary phototherapeutic keratectomy

Directory of Open Access Journals (Sweden)

Kasetsuwan N

2015-09-01

Full Text Available Ngamjit Kasetsuwan, Kanokorn Sakpisuttivanit, Usanee Reinprayoon, Vilavun Puangsricharern Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand Objective: To assess the recurrent rate, mean survival time, and risk factors associated with recurrent painful bullous keratopathy (BK after primary treatment with phototherapeutic keratectomy.Methods: Medical records from 72 patients (72 eyes who had phototherapeutic keratectomy for painful BK were evaluated. Data for sex, age, duration of BK, associated ocular and systemic diseases (hypertension, diabetes mellitus, ischemic heart disease, asthma, dyslipidemia, and rheumatoid arthritis, frequency and degree of pain (grade 1–3, visual acuity, corneal thickness, intraocular pressure, and laser setting were extracted and analyzed.Results: The mean age of the patients was 64.2±11.4 years. The mean preoperative duration of BK was 15.0±11.0 months. Most patients had pseudophakic BK (69.40%. Majority of the cases had grade 3 degree of pain (48.60%. Glaucoma and hypertension were markedly found among these patients (51.40% and 19.40%, respectively. Preoperative mean intraocular pressure and corneal thickness were 13.70±4.95 mmHg and 734.1±83.80 µm, respectively. The mean laser diameter and depth were 8.36±1.22 mm and 38.89±8.81 µm, respectively. Systemic disease was significantly associated with the risk for developing recurrent painful BK (P=0.022, hazard ratio [HR] 1.673, 95% confidence interval [CI] 1.08–2.58. The overall recurrent rate was 51%. The average duration time of recurrent painful BK was 17.3±12.9 months (range 1–50 months. The median survival time before recurrence was 29.0±6.6 months.Conclusion: Systemic disease was found to be the only risk factor significantly associated with the development of recurrent painful BK. Low recurrent rate and long mean survival time showed that phototherapeutic

Definitive chemoradiation for locoregional recurrences of esophageal cancer after primary curative treatment.

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Jeene, P M; Versteijne, E; van Berge Henegouwen, M I; Bergmann, J J G H M; Geijsen, E D; Muller, K; van Laarhoven, H W M; Hulshof, M C C M

2017-02-01

The aim of this study was to determine the outcome of salvage definitive chemoradiation (dCRT) for a locoregional recurrence after any prior curative treatment outside previously irradiated areas. Thirty-nine patients treated between January 2005 and December 2014 were reviewed for locoregional recurrent esophageal cancer outside previously irradiated areas. All patients received salvage treatment with external beam radiotherapy (50.4 Gy in 28 fractions) combined with weekly concurrent paclitaxel and carboplatin. The median follow-up period was 15 months (range 1.7-120). The median overall survival (OS) for all patients after salvage dCRT was 22 months (95% CI 6.2-37.6). The 1-, 3-, and 5-year OS was 72%, 31%, and 28%, respectively. Median survival after salvage dCRT for a regional lymph node recurrence was 33 months (95% CI 5.8-60.3) versus 14 months (95% CI 6.8-21.6) for a recurrence at the anastomosis (P = 0.022, logrank). Median OS was 35 months for the squamous cell carcinoma group and 19 months for the adenocarcinoma group (P = 0.67). Sixteen of 39 patients developed a locoregional recurrence after salvaged dCRT. The median locoregional recurrence-free survival (LRFS) was 24 months. The 1-, 3-, and 5-year LRFS was 79%, 36%, and 36%, respectively. Median disease-free survival (DFS) was 15 months. The 1-, 3-, and 5-year DFS was 66%, 27%, and 27%, respectively. Of 16 patients, 8 (50%) with a primary failure at the site of the anastomosis developed a local recurrence after salvaged dCRT compared to 7 of 22 patients (32%) with a primary recurrence in a lymph node. Definitive chemoradiation is a feasible and effective treatment for locoregional recurrent esophageal cancer outside a previously irradiated area, and should be given with a curative intent. This holds true for recurrence of both squamous cell carcinoma and adenocarcinoma. Lymph node recurrences have a markedly better prognosis than recurrences at the site of the anastomosis. © 2016

Recurrent parotitis as a first manifestation in a child with primary Sjogren's syndrome.

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Alp, H; Orbak, Z; Erdogan, T; Karabag, K; Gursan, N

2011-12-01

Recurrent parotitis is an acute, severe inflammation of one or both parotid glands, the major salivary glands in young children. We report the case of a seven-year old boy with Primary Sjogrens syndrome (PSS) who presented with 15 episodes of painful recurrent bilateral swellings of the parotid glands over a four-year period.

Molecular characteristics of Clostridium difficile strains from patients with a first recurrence more than 8 weeks after the primary infection.

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Chen, Yijian; Rashid, Mamun Ur; Huang, Haihui; Fang, Hong; Nord, Carl Erik; Wang, Minggui; Weintraub, Andrej

2017-08-01

Nearly all published studies of recurrent Clostridium difficile infections (CDI) report recurrent CDI within 8 weeks after the primary infection. This study explored the molecular characteristics of C. difficile isolates from the first recurrent CDI more than 8 weeks after the primary infection. Consecutive hospitalized patients with a recurrent CDI more than 8 weeks after a primary infection were enrolled prospectively from January 2008 to February 2011. All C. difficile isolates of the primary and recurrent infections were collected and subjected to polymerase chain reaction ribotyping and antimicrobial susceptibility testing. There were 62 cases of CDI in this study, which included 32 cases (51.6%) of recurrence due to the same ribotype of C. difficile, 26 (41.9%) cases due to a different ribotype, and four (6.5%) cases with 2-4 recurrences due to the same or different strains. One hundred and forty C. difficile isolates were obtained, which included 62 primary CDI isolates and 78 recurrent isolates. Ribotype 020 was the most common C. difficile strain in primary and recurrent infections. Ribotype 001 accounted for 15.4% (10/78) of recurrent infections and 3.2% (2/62) of primary infections (p = 0.0447). The minimum inhibitory concentration at 90% (MIC 90 ) values of linezolid, moxifloxacin, and clindamycin against type 001 strains were much higher, compared to the three other common ribotypes. Recurrent CDI more than 8 weeks after a primary infection can be caused by the same or different C. difficile ribotype at similar percentages. Ribotype 001 C. difficile strains, which have a lower susceptibility to antimicrobials, were isolated more frequently in patients with a recurrent CDI. Copyright © 2015. Published by Elsevier B.V.

Apex-to-Cupola Distance Following VATS Predicts Recurrence in Patients With Primary Spontaneous Pneumothorax

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Chang, Jia-Ming; Lai, Wu-Wei; Yen, Yi-Ting; Tseng, Yau-Lin; Chen, Ying-Yuan; Wu, Ming-Ho; Chen, Wei; Light, Richard W.

2015-01-01

Abstract Our study sought to determine whether the size of the residual apical pleural space in young patients with primary spontaneous pneumothorax (PSP) following video-assisted thoracoscopic surgery is associated with the risk of recurrence. We retrospectively reviewed patients (≤30 years’ old) with primary spontaneous pneumothorax following thoracoscopic surgery (2002–2010) in a university-affiliated hospital. The size of residual apical pleural space was estimated by measuring the apex-to-cupola distance on a postoperative chest radiograph at 2 time windows: first between postoperative day (POD) 0 and 3, and second between POD 4 and 14. A total of 149 patients were enrolled with a median follow-up of 11.2 months (interquartile range, 0.95–29.5 months), of whom 141 (94.6%) were male with a mean age of 20 years. The postoperative recurrence rate was 11.4%. Comparing the characteristics between the patients with and without recurrent pneumothorax, the patients with recurrence were younger (18.2 + 2.4 vs 20.7 + 3.7 years, P = 0.008), with a lower rate of pleurodesis (35% vs1 69%, P = 0.037), longer apex-to-cupola distance at POD 0 to 3 (22.41 ± 19.56 vs 10.07 ± 10.83 mm, P pneumothorax, age 10 mm (P = 0.027, OR: 5.319), and no pleurodesis during VATS (P = 0.022, OR: 5.042) were independent risk factors for recurrent pneumothorax. The recurrence rate was not low (11.4%) in young patients with PSP following VATS. Residual apical pleural space with apex-to-cupola distance of 10 mm or greater at POD 0 to 3, younger age, and no pleurodesis would increase postoperative recurrence of primary spontaneous pneumothorax. PMID:26376396

Endoscopic repair of primary versus recurrent male unilateral inguinal hernias: Are there differences in the outcome?

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Köckerling, F; Jacob, D; Wiegank, W; Hukauf, M; Schug-Pass, C; Kuthe, A; Bittner, R

2016-03-01

To date, there are no prospective randomized studies that compare the outcome of endoscopic repair of primary versus recurrent inguinal hernias. It is therefore now attempted to answer that key question on the basis of registry data. In total, 20,624 patients were enrolled between September 1, 2009, and April 31, 2013. Of these patients, 18,142 (88.0%) had a primary and 2482 (12.0%) had a recurrent endoscopic repair. Only patients with male unilateral inguinal hernia and with a 1-year follow-up were included. The dependent variables were intra- and postoperative complications, reoperations, recurrence, and chronic pain rates. The results of unadjusted analyses were verified via multivariable analyses. Unadjusted analysis did not reveal any significant differences in the intraoperative complications (1.28 vs 1.33%; p = 0.849); however, there were significant differences in the postoperative complications (3.20 vs 4.03%; p = 0.036), the reoperation rate due to complications (0.84 vs 1.33%; p = 0.023), pain at rest (4.08 vs 6.16%; p primary versus recurrent male unilateral inguinal hernia showed significant differences to the disadvantage of the recurrent operation. Therefore, endoscopic repair of recurrent inguinal hernias calls for particular competence on the part of the hernia surgeon.

Primary CNS lymphoma in nonimmunocompromised patients magnetic resonance study

International Nuclear Information System (INIS)

Pena, J.; Fernandez, J.M.; Galarraga, M.I.; Pozo, A.; Montes, A.; Ablanedo, P.

1995-01-01

Prymary lymphoma of the CNS (PLCNS) is a relatively infrequent malignant tumor that has become increasingly common over the past decade. The radiological signs, although not pathognomonic, are quite specific and suggestive of the correct diagnosis, thus facilitating therapeutic management. We present six cases of PLCNS in nonimmunocopromised patients studied by MR in our hospital over the past two and a half years. We describe theradiological findings, correlating them with those mentioned in the literature. 14 refs

Late Recurrent Post-Transplant Primary Biliary Cirrhosis in British Columbia

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Eric M Yoshida

1997-01-01

Full Text Available Late recurrent primary biliary cirrhosis (PBC following orthotopic liver transplant remains a controversial topic. The first documented case of recurrence occurring in 16 patients transplanted for PBC and followed at the authors' institution for longer than one year is presented. A 54-year-old man transplanted for PBC developed a cholestatic pattern of enzyme elevation on post-transplant day (PTD 1305. Repeat antimitochondrial antibody was strongly positive (1:300 to 1:400. A liver biopsy revealed severe bile duct damage, lymphocytic cholangitis, focal periductal noncaseating granuloma and minimal endotheliitis. Recurrent PBC was diagnosed. At the time of orthotopic liver transplant this patient received induction immunosuppression with OKT3 crossed over to cyclosporine (CsA, azathioprine (AZA and prednisone. AZA was discontinued early and maintenance CsA tapered to a target trough level of 150 to 200 ng/mL by PTD 365. Prednisone was withdrawn by PTD 664. CsA levels during PTDs 1225 to 1305 (before elevation of hepatobiliary enzymes were below target at 114 to 166 ng/mL. Of the 16 patients, all but three were maintained on CsA, AZA and prednisone. One was on CsA (trough levels on target and AZA; the other two, including the patient with recurrent PBC, were on CsA only. The trough CsA level of the patient without recurrent PBC has been within the target range. The authors speculate that the underlying defect in immunoregulation in PBC persists post-transplant and that in the patient without recurrent PBC this defect was unmasked by lowered maintenance immunosuppression - allowing recurrence of PBC in a previously stable liver allograft.

Locoregional Recurrent or Second Primary Head and Neck Cancer: Management Strategies and Challenges.

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Wong, Stuart J; Heron, Dwight E; Stenson, Kerstin; Ling, Diane C; Vargo, John A

2016-01-01

Treatment of patients with locoregional recurrent or second primary head and neck squamous cell cancer (HNSCC) has been guided by well-reasoned principles and informed by carefully tested chemotherapy and radiation regimens. However, clinical decision making for this population is complicated by many factors. Although surgery is generally considered the treatment of choice for patients with HNSCC with recurrent disease or new second primary disease in a previously irradiated field, operability of cases is not always straightforward. Postoperative treatment is frequently warranted but carries significant risk. In addition, the rapid rise in the incidence of HPV-associated HNSCC raises the question of whether established treatment paradigms should be re-examined in this population of patients with a much better prognosis than the non-HPV population. Furthermore, new radiation techniques and new systemic agents show early promising results in recent clinical studies, suggesting potential for practice-changing effects in the future management of this disease. This article examines each of the treatment modalities used in the care of patients with HNSCC with recurrent or new second primary disease and provides a perspective to aid clinicians in the management of this disease.

Non-psychogenic polydipsia in 45-year-old man with primary hyperparathyroidism and recurrent bilateral nephrolithiasis

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Rahmat Cahyanur

2012-11-01

Full Text Available Non-psychogenic polydipsia with hyponatremia is a rare clinical presentation. Primary hyperparathyroidism is a disorder of calcium, phosphate, and bone metabolism caused by increased level of parathyroid hormone (PTH. It is estimated the incidence of primary hyperparathyroidism are 21.6 per 100,000 person a year. This case report describe a 45-year-old man presented with non-psychogenic polydipsia. This patient drank a lot of water out of the fear of recurrent kidney stones. He had history of recurrent nephrolithiasis with hypercalcemia. We investigate further the cause of hypercalcemia and we diagnosed primary hyperparathryoidism as the cause. (Med J Indones. 2012;21:230-4Keywords: Hyponatremia, non-psychogenic polydipsia, primary hyperparathyroidism

Excision and primary closure of pilonidal sinus disease: worthwhile option with an acceptable recurrence rate.

LENUS (Irish Health Repository)

Gilani, S N S

2012-01-31

BACKGROUND: Treatment of pilonidal sinus disease is controversial. Many claim policy of marsupialisation and healing by secondary intention. This is demanding in terms of nursing care and time lost from work. AIMS: To examine outcome of excision and primary closure of chronic pilonidal disease on recurrence rate and patient\\'s daily activities. PATIENTS AND METHODS: One hundred and fourteen consecutive elective patients who had excision and primary closure of pilonidal sinus disease were reviewed. The demographic data and the post-operative outcome were studied. RESULTS: The recurrence of pilonidal sinus was noted in 9% of patients, wound breakdown occasioning delayed healing in 9%, patients able to drive by day 16 on average. The mean time to return to work was 20.5 days; duration of analgesia, 2.4 days; and duration of antibiotic treatment, 4.7 days. CONCLUSION: Excision and primary closure of chronic pilonidal sinus has low recurrence rate with early return to activities. Primary closure appears to be a cost-effective option for uncomplicated pilonidal sinus disease.

Factors influencing survival and recurrence-free intervals after treatment of primary breast cancer

International Nuclear Information System (INIS)

O'Higgins, N.; Brady, H.R.; Clark, C.G.

1984-01-01

A retrospective analysis of 739 patients with breast cancer is presented. Factors influencing overall survival, recurrence-free interval and survival after first recurrence are analysed and discussed. None of the factors was affected by age or menopausal status at the time of presentation. Overall survival and recurrence-free intervals varied significantly with tumour size, extent of nodal spread and tumour site. Medially situated tumours, large tumours and extensive nodal spread were associated with earlier first recurrence and poor prognosis. No difference in survival or recurrence-free interval was observed between different surgical operations. Although overall survival was longer in patients who received post-operative radiotherapy, no significant differences in survival or disease-free intervals were noted when patients were standardised for operation or tumour stage. Survival after local recurrence was longer than survival after distant metastases, although the time of onset of local and distant disease followed an identical pattern. These results suggest that the tumour characteristics of size, site and nodal spread are important determinants of survival and recurrence-free interval in primary breast cancer. Local recurrence should be regarded as a manifestation of systemic disease. (author)

Prospective evaluation of delayed central nervous system (CNS) toxicity of hyperfractionated total body irradiation (TBI)

International Nuclear Information System (INIS)

Wenz, Frederik; Steinvorth, Sarah; Lohr, Frank; Fruehauf, Stefan; Wildermuth, Susanne; Kampen, Michael van; Wannenmacher, Michael

2000-01-01

Purpose: Prospective evaluation of chronic radiation effects on the healthy adult brain using neuropsychological testing of intelligence, attention, and memory. Methods and Materials: 58 patients (43 ± 10 yr) undergoing hyperfractionated total body irradiation (TBI) (TBI, 14.4 Gy, 12 x 1.2 Gy in 4 days) before bone marrow or peripheral blood stem cell transplantation were prospectively included. Twenty-one recurrence-free long-term survivors were re-examined 6-36 months (median 27 months) after completion of TBI. Neuropsychological testing included assessment of general intelligence, attention, and memory using normative, standardized psychometric tests. Mood status was controlled, as well. Test results are given as IQ scores (population mean 100) or percentiles for attention and memory (population mean 50). Results: The 21 patients showed normal baseline test results of IQ (101 ± 13) and attention (53 ± 28), with memory test scores below average (35 ± 21). Test results of IQ (98 ± 17), attention (58 ± 27), and memory (43 ± 28) showed no signs of clinically measurable radiation damage to higher CNS (central nervous system) functions during the follow-up. The mood status was improved. Conclusion: The investigation of CNS toxicity after hyperfractionated TBI showed no deterioration of test results in adult recurrence-free patients with tumor-free CNS. The median follow-up of 27 months will be extended.

Recurrence-free survival, but not surgical therapy per se, determines 583 patients' long-term satisfaction following primary pilonidal sinus surgery.

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Doll, Dietrich; Luedi, Markus M; Evers, Theo; Kauf, Peter; Matevossian, Edouard

2015-05-01

With pilonidal sinus disease (PSD) incidence increasing and patients freely choosing their surgeon, patients' interest issues have been brought forward estimating patient satisfaction following pilonidal sinus surgery. The influence of wound healing time and long-term recurrence rate on patient satisfaction in primary PSD surgery has not been investigated yet. Five hundred eighty-three patients (German military cohort) were interviewed, compiling wound healing time, aesthetic satisfaction, long-term recurrence-free survival and patient satisfaction having undergone primary open (PO) treatment, marsupialization (MARS) or primary midline closure (PMC) treatment. Recurrence rate was determined by Kaplan-Meier calculation following up to 20 years after primary PSD surgery. Patient satisfaction ranking from 1 to 10 (10 = max. satisfied) showed an average satisfaction of 8.2 (range 0-10; 95% confidence interval (CI) 7891-8250). In-hospital stay time was significantly longer in primary open (PO) and marsupialization (MARS) group as compared to primary midline closure (PMC; p < 0.0001, Kruskal-Wallis test). Satisfaction was comparable between treatment groups, and was neither linked to in-hospital stay time nor to longer outpatient wound care period or total treatment time. Recurrence-free survival, as seen in the PO and PMC treatment group, revealed a highly significant difference for all patients. Improvement in MARS patients with versus without recurrence was low, as satisfaction with primary treatment was lower as the other groups. Neither choice of surgical treatment nor treatment duration within hospital or after hospital influences patient satisfaction, as long as recurrence-free survival can be provided. Marsupialization was ranked lower in both groups (with or without recurrence), and should be abandoned, as patients are significantly less satisfied with either results, independent of recurrence.

Renal papillary attenuation differences between primary and recurrent idiopathic calcium stone disease patients.

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Cakiroglu, B; Eyyupoglu, S E; Tas, T; Esen, T; Acar, O; Aksoy, S H

2014-06-01

The aim of this paper was to investigate whether renal papillae of patients with nephrolithiasis are more radiodense than that of control patients and to evaluate the predictability of urolithiasis using papillary density differences between stone and non-stone formers. Renal papillary Hounsfield Unit (HU) measurements were conducted at the level of upper pole, middle region and lower pole of both kidneys in a total of 126 primary (group 1), 133 recurrent (group 2) stone disease patients and 108 controls (group 3). Mean patient age did not differ significantly between groups (P>0.05). Mean stone diameters (±SD) were 5.0±3.1 mm (3-9 mm) and 6.1±3.3 mm (3-15 mm) for primary and recurrent groups, respectively and group distributions and variances were similar (P>0.05). Mean papillary attenuation values (±SD) were 27.26±9.30 (4.00-56.00) in group 1, 30.42±9.88 (12.00-64.00) in group 2 and 25.83±2.72 (20.30-32.56) in the control group. The difference between the mean papillary attenuation value of the primary stone disease group and the control group was statistically insignificant (P=0.104). When the control group and the recurrent stone group was compared without variances, in terms of the mean renal papillary attenuation value, a statistical significance was achieved (P=0.000). With increasing renal papillary HU values, the risk of recurrent calcium stone disease is increased.

NI-60RECURRENT PATTERNS OF BEVACIZUMAB MONOTHERAPY FOR RECURRENT PRIMARY GLIOBLASTOMA AND PERSPECTIVES ON BEVACIZUMAB-BASED THERAPIES

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Nagane, Motoo; Kobayashi, Keiichi; Saito, Kuniaki; Shiokawa, Yoshiaki

2014-01-01

BACKGROUND. Prognosis of patients with recurrent glioblastoma (GBM) remains dismal, their median overall survival (mOS) ranging from 7 to 10 months. Currently, bevacizumab (BEV), a monoclonal antibody against VEGF, has been widely used since it prolonged progression-free survival (PFS) accompanied with symptom relief in BEV trials. However, improvement of OS seems modest at most, and issues regarding short survival after BEV failure, invasive relapse, and difficulty in determining true progression remain unsolved. Here we examined the patterns of radiological BEV failure in relationship with survival of several post-treatment periods. METHODS. Twenty-five patients with primary GBM who were treated with BEV monotherapy at recurrence in Kyorin University hospital since August 2009 were included in this study. Mean age was 53 yo, 13 males/12 females, median KPS was 60 (30-100), and mOS from the initial surgery was 23.2 months. MRI patterns at BEV progression were determined using modified classification by Nowosielsky et al. (Neurology 2014) as follows: 1) T2-diffuse, 2) cT1-flare up, 3) Primary non-responders, 4) T2-circumscribed, and 5) Remote metastasis. RESULTS. mPFS and mOS of BEV monotherapy were 3.4 and 7.6 months, respectively, and post-BEV mOS was 4.7 months. Frequency and BEV-PFS/post-BEV OS were 1) 20%, 3.8/0.8 months; 2) 40%, 3.4/7.1 months, 3) 24%, 0.9/3.3 months, 4) 8%, 3.7/3.9 months, 5) 8%, 2.0/4.2 months. The cT1-flare up recurrent pattern was found most frequently with relatively better survivals, whereas the T2-diffuse recurrence included fatal brain stem invasion in two cases, resulting in poorer prognosis. CONCLUSIONS. BEV monotherapy showed limited survival benefit and the clinical course after BEV failure may differ by patterns of relapse. Although RANO criteria have been a standard method to determine progression, measurement of T2/FLAIR hyperintensity remains critically controversial. Efforts to improve BEV-based therapy for recurrent GBM

Concurrent Stereotactic Radiosurgery and Bevacizumab in Recurrent Malignant Gliomas: A Prospective Trial

International Nuclear Information System (INIS)

Cabrera, Alvin R.; Cuneo, Kyle C.; Desjardins, Annick; Sampson, John H.; McSherry, Frances; Herndon, James E.; Peters, Katherine B.; Allen, Karen; Hoang, Jenny K.; Chang, Zheng; Craciunescu, Oana; Vredenburgh, James J.; Friedman, Henry S.; Kirkpatrick, John P.

2013-01-01

Purpose: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. Methods and Materials: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. Results: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. Conclusions: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach

Recurrent Candida albicans Ventriculitis Treated with Intraventricular Liposomal Amphotericin B

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Demet Toprak

2015-01-01

Full Text Available Central nervous system (CNS infection with Candida is rare but significant because of its high morbidity and mortality. When present, it is commonly seen among immunocompromised and hospitalized patients. Herein, we describe a case of a four-year-old boy with acute lymphoblastic leukemia (ALL who experienced recurrent Candida albicans meningitis. The patient was treated successfully with intravenous liposomal amphotericin B at first attack, but 25 days after discharge he was readmitted to hospital with symptoms of meningitis. Candida albicans was grown in CFS culture again and cranial magnetic resonance imaging (MRI showed ventriculitis. We administered liposomal amphotericin B both intravenously and intraventricularly and favorable result was achieved without any adverse effects. Intraventricular amphotericin B may be considered for the treatment of recurrent CNS Candida infections in addition to intravenous administration.

CNS role evolution.

Science.gov (United States)

Payne, J L; Baumgartner, R G

1996-01-01

THE CNS ROLE has been actualized in a variety of ways. Flexibility-inherent in the role-and the revolution in health care consciousness tend to place the CNS at risk for criticism regarding value to the organization. At Vanderbilt University Medical Center, a CNS task force evaluated the current reality of CNS practice and recommended role changes to include the financial analysis of patient care. After incorporating a financial perspective into our present practice, we have embarked on an interesting journey of post-Master's degree study, that of the tertiary care nurse practitioner. This practice option could elevated the clinical and financial aspects of providing cost-effective health care to a more autonomous role form; however, the transition has been challenging. Since 1990, the American Nurses Association has recommended that nursing school curricula change to meet the needs of the health care environment and provide increased career flexibility through creating one advanced degree incorporating both CNS and NP functions. Swiftly moving past differences and toward similarities will bridge the gap for advanced practice nurses in the future.

Diabetes due to recurrent pancreatitis secondary to hypercalcemia due to primary hyperparathyroidism

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Sumit Kumar Chakrabarti

2013-01-01

Full Text Available Acute pancreatitis due to hypercalcemia associated with hyperparathyroidism (HPT is not very common. We herein report a case of a 21-year-old woman, who presented with acute pancreatitis. She had a past history of recurrent nephrolithiasis. Subsequent evaluation revealed hypercalcemia (serum calcium: 12.6 mg/dL; low phosphate (2.9 mg/dL with elevated parathyroid hormone (PTH, 156.7 pg/mL and HbA1c (6.9%. Diagnosis of primary HPT (PHPT was made. Recurrent pancreatitis due to hypercalcemia may have resulted in diabetes mellitus.

Definitive radiotherapy for primary vaginal cancer. Correlation between treatment patterns and recurrence rate

International Nuclear Information System (INIS)

Kanayama, Naoyuki; Isohashi, Fumiaki; Yoshioka, Yasuo

2015-01-01

The purpose of this study was to determine the outcomes and optimal practice patterns of definitive radiotherapy for primary vaginal cancer. Between 1993 and 2012, 49 patients were treated with definitive radiotherapy for primary vaginal cancer in three hospitals. Of these, 15 patients (31%) had clinically positive regional lymph node metastasis. A total of 34 patients (70%) received external beam radiotherapy with high-dose-rate brachytherapy (interstitial or intracavitary), and 8 (16%) (with small superficial Stage I tumors) were treated with local radiotherapy. The median follow-up was 33 months (range: 1–169 months). The 3-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 83%, 59% and 71%, respectively. In multivariate analysis, the histological type (P = 0.044) was significant risk factors for LRC. In Federation of Gynecology and Obstetrics (FIGO) Stage I cases, 3 of 8 patients (38%) who did not undergo prophylactic lymph node irradiation had lymph node recurrence, compared with 2 of 12 patients (17%) who underwent prophylactic pelvic irradiation. For Stage III–IV tumors, the local recurrence rate was 50% and the lymph node recurrence rate was 40%. Patients with FIGO Stage I/II or clinical Stage N1 had a higher recurrence rate with treatment using a single modality compared with the recurrence rate using combined modalities. In conclusion, our treatment outcomes for vaginal cancer were acceptable, but external beam radiotherapy with brachytherapy (interstitial or intracavitary) was needed regardless of FIGO stage. Improvement of treatment outcomes in cases of FIGO Stage III or IV remains a significant challenge. (author)

Primary patellar dislocations without surgical stabilization or recurrence: how well are these patients really doing?

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Magnussen, Robert A; Verlage, Megan; Stock, Elizabeth; Zurek, Lauren; Flanigan, David C; Tompkins, Marc; Agel, Julie; Arendt, Elizabeth A

2017-08-01

While a significant research has gone into identifying patients at highest risk of recurrence following primary patellar dislocation, there has been little work exploring the outcomes of patients who do not have a recurrent patellar dislocation. We hypothesize that patients without recurrent dislocation episodes will exhibit significantly higher KOOSs than those who suffer recurrent dislocations, but lower scores than published age-matched normative data. A retrospective review of patients with nonoperatively treated primary lateral patellar dislocations was carried out, and patients were contacted at a mean of 3.4 years (range 1.3-5.5 years) post-injury. Information regarding subsequent treatment and recurrent dislocations along with patient-reported outcome scores and activity level was collected. One hundred and eleven patients (29.8 %) of 373 eligible patients agreed to study participation, seven of whom were excluded because they underwent subsequent patellar stabilization surgery on the index knee. Seventy-six patients (73.1 %) reported no further dislocation events, and the mean KOOS subscales at follow-up were: symptoms-80.2 ± 18.8, pain-81.8 ± 16.2, ADL-88.7 ± 15.9, sport/recreation-72.1 ± 24.4, and QOL-63.9 ± 23.8 at a mean follow-up of 3.3 years (range 1.3-5.5 years). No significant differences in any of the KOOS subscales were noted between these patients and the group that reported recurrent patellar dislocations. Only 26.4 % of the patients without further dislocations reported they were able to return to desired sport activities without limitations following their dislocation. Patients who do not report recurrent patellar dislocations following nonoperative treatment of primary patellar dislocations are in many cases limited by this injury 3 years following the initial dislocation event. Retrospective cohort study, Level III.

Primary Hyperaldosteronism As A Risk Factor For Recurrent Nephrolithiasis

Directory of Open Access Journals (Sweden)

Ekamol Tantisattamo

2012-06-01

Hyperaldosteronism can cause hypercalciuria, phosphaturia, and hypocitraturia, all of which are risk factors for nephrolithiasis. Additionally, hyperaldosteronism and deoxycorticosterone mediated hypertension have been associated with hypocalcemia and secondary hyperparathyroidism. Our case augments earlier literature suggesting increased risk for nephrolithiasis in patients with hyperaldosteronism and suggests that hyperaldosteronism should be considered as a risk factor for patient with nephrolithiasis. It remains unclear if both primary and secondary hyperaldosteronism increase the relative risk for nephrolithiasis and the role of aldosterone receptor antagonist therapy for recurrent nephrolithiasis associated with hyperaldosteronism.

Recurrent primary hyperparathyroidism due to Type 1 parathyromatosis.

Science.gov (United States)

Jain, Monica; Krasne, David L; Singer, Frederick R; Giuliano, Armando E

2017-02-01

Parathyromatosis is a rare condition consisting of multiple nodules of benign hyperfunctioning parathyroid tissue scattered throughout the neck and superior mediastinum. As a potential cause of recurrent or persistent hyperparathyroidism, parathyromatosis is a challenging condition to diagnose and treat. The optimal evaluation and management of patients with parathyromatosis is not well established. The reported case involves a patient who was initially diagnosed with primary hyperparathyroidism. The diagnosis of Type 1 parathyromatosis was made after the patient developed recurrent hyperparathyroidism with hypercalcemia and osteoporosis 17 years after the initial operation and underwent two additional operations. The majority of parathyromatosis cases are diagnosed in the setting of secondary hyperparathyroidism. Consensus regarding the preoperative diagnosis and evaluation is lacking due to the paucity of cases of this rare clinical entity. Management involves complete surgical extirpation of all identifiable rests of parathyroid tissue. Intra-operative parathyroid hormone level monitoring and frozen section examination are excellent tools that could increase the rates of initial operative success. Despite this, long-term disease remission is rare, and medical therapy, including calcimimetics and bisphosphonates, may be required for postoperative or non-operative management.

Detecting recurrent major depressive disorder within primary care rapidly and reliably using short questionnaire measures.

Science.gov (United States)

Thapar, Ajay; Hammerton, Gemma; Collishaw, Stephan; Potter, Robert; Rice, Frances; Harold, Gordon; Craddock, Nicholas; Thapar, Anita; Smith, Daniel J

2014-01-01

Major depressive disorder (MDD) is often a chronic disorder with relapses usually detected and managed in primary care using a validated depression symptom questionnaire. However, for individuals with recurrent depression the choice of which questionnaire to use and whether a shorter measure could suffice is not established. To compare the nine-item Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory, and the Hospital Anxiety and Depression Scale against shorter PHQ-derived measures for detecting episodes of DSM-IV major depression in primary care patients with recurrent MDD. Diagnostic accuracy study of adults with recurrent depression in primary care predominantly from Wales Scores on each of the depression questionnaire measures were compared with the results of a semi-structured clinical diagnostic interview using Receiver Operating Characteristic curve analysis for 337 adults with recurrent MDD. Concurrent questionnaire and interview data were available for 272 participants. The one-month prevalence rate of depression was 22.2%. The area under the curve (AUC) and positive predictive value (PPV) at the derived optimal cut-off value for the three longer questionnaires were comparable (AUC = 0.86-0.90, PPV = 49.4-58.4%) but the AUC for the PHQ-9 was significantly greater than for the PHQ-2. However, by supplementing the PHQ-2 score with items on problems concentrating and feeling slowed down or restless, the AUC (0.91) and the PPV (55.3%) were comparable with those for the PHQ-9. A novel four-item PHQ-based questionnaire measure of depression performs equivalently to three longer depression questionnaires in identifying depression relapse in patients with recurrent MDD.

Magnetic resonance imaging guided reirradiation of recurrent and second primary head and neck cancer

OpenAIRE

Chen, Allen M.; Cao, Minsong; Hsu, Sophia; Lamb, James; Mikaeilian, Argin; Yang, Yingli; Agazaryan, Nzhde; Low, Daniel A.; Steinberg, Michael L.

2017-01-01

Purpose: To report a single-institutional experience using magnetic resonance imaging (MRI) guided radiation therapy for the reirradiation of recurrent and second cancers of the head and neck. Methods and materials: Between October 2014 and August 2016, 13 consecutive patients with recurrent or new primary cancers of the head and neck that occurred in a previously irradiated field were prospectively enrolled in an institutional registry trial to investigate the feasibility and efficacy of ...

Herpes simplex virus specific T cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences.

Science.gov (United States)

Franzen-Röhl, Elisabeth; Schepis, Danika; Atterfelt, Fredrik; Franck, Kristina; Wikström, Arne; Liljeqvist, Jan-Åke; Bergström, Tomas; Aurelius, Elisabeth; Kärre, Klas; Berg, Louise; Gaines, Hans

2017-05-01

During the last decades, a changing epidemiological pattern of genital herpes simplex virus (HSV) infection has emerged. Primary infection is now caused as often by HSV-1 as by HSV-2. Once established, HSV can be reactivated leading to recurrent mucocutaneous lesions as well as meningitis. Why some otherwise immune-competent individuals experience severe and frequent recurrences is not known, and the immunological mechanism underlying recurrent symptomatic HSV infection is not fully understood. In this study, we investigate and characterise the immune response of patients with first episode of HSV genital infection and its relation to the frequency of symptomatic recurrences. In this cohort study, clinical and immunological data were collected from 29 patients who were followed 1 year after presenting with a first episode of genital or meningeal HSV infection. They were classified by PCR and serology as those with primary HSV-1, primary HSV-2 and non-primary HSV-2 infection. HSV-specific interleukin(Il)-4 and Il-10 responses at first visit were higher in primary infected HSV-2 infected patients experiencing lower numbers of recurrences during subsequent year. The median number of recurrences following primary HSV-2 genital infection may partly be predicted by the strength of an early HSV-specific IL-4 and IL-10 response. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Chemoradiotherapy response in recurrent rectal cancer

International Nuclear Information System (INIS)

Yu, Stanley K T; Bhangu, Aneel; Tait, Diana M; Tekkis, Paris; Wotherspoon, Andrew; Brown, Gina

2014-01-01

The efficacy of response to preoperative chemoradiotherapy (CRT) in recurrent versus primary rectal cancer has not been investigated. We compared radiological downsizing between primary and recurrent rectal cancers following CRT and determined the optimal size reduction threshold for response validated by survival outcomes. The proportional change in tumor length for primary and recurrent rectal cancers following CRT was compared using the independent sample t-test. Overall survival (OS) was calculated using the Kaplan–Meier product limit method and differences between survival for tumor size reduction thresholds of 30% (response evaluation criteria in solid tumors [RECIST]), 40%, and 50% after CRT in primary and recurrent rectal cancer groups. A total of 385 patients undergoing CRT were analyzed, 99 with recurrent rectal cancer and 286 with primary rectal cancer. The mean proportional reduction in maximum craniocaudal length was significantly higher for primary rectal tumors (33%) compared with recurrent rectal cancer (11%) (P < 0.01). There was no difference in OS for either primary or recurrent rectal cancer when ≤30% or ≤40% definitions were used. However, for both primary and recurrent tumors, significant differences in median 3-year OS were observed when a RECIST cut-off of 50% was used. OS was 99% versus 77% in primary and 100% versus 42% in recurrent rectal cancer (P = 0.002 and P = 0.03, respectively). Only patients that demonstrated >50% size reduction showed a survival benefit. Recurrent rectal cancer appears radioresistant compared with primary tumors for tumor size after CRT. Further investigation into improving/intensifying chemotherapy and radiotherapy for locally recurrent rectal cancer is justified

Primary Cystic Pleuropulmonary Synovial Sarcoma Presenting as Recurrent Pneumothorax

Directory of Open Access Journals (Sweden)

Eric D. Johnson

2017-07-01

Full Text Available Primary pleuropulmonary synovial sarcomas are quite rare, representing 0.1–0.5% of all pulmonary malignancies. We report an entirely cystic monophasic synovial sarcoma in a 25-year-old male who presented with recurrent pneumothorax and no evidence of a mass lesion on imaging. The purpose of this case report is to increase awareness of neoplasms clinically presenting as a pneumothorax with no imagining evidence of a mass-forming lesion and emphasize the significance of fluorescent in situ hybridization testing in nontypical synovial sarcoma cases.

Isolated vasculitis of the CNS

International Nuclear Information System (INIS)

Block, F.; Reith, W.

2000-01-01

Vasculitis is a rare cause for disease of the CNS. The isolated vasculitis of the CNS is restricted to the CNS whereas other forms of vasculitis affect various organs including the CNS. Headache, encephalopathy, focal deficits and epileptic seizures are the major symptoms suggestive for vasculitis. One major criterion of the isolated vasculitis of the CNS is the lack of evidence for other vasculitis forms or for pathology of other organs. Angiography displays multifocal segmental stenosis of intracranial vessels. MRI demonstrates multiple lesions which in part show enhancement after gadolinium. A definite diagnosis can only be made on the grounds of biopsy from leptomeninges and parenchyma. Therapy consists of corticosteroids and cyclophosphamid. (orig.) [de

Adjuvant VHF therapy in locally recurrent and primary unresectable rectal cancer

International Nuclear Information System (INIS)

Trotter, J.M.; Lamb, M.H.; Bayliss, E.J.; Edis, A.J.; Blackwell, J.B.; Shepherd, J.M.; Cassidy, B.

1996-01-01

In a prospective randomized study, 434 MHz microwave therapy combined with external beam radiotherapy (VHF+RT) was compared with standard external beam radiotherapy (RT) in controlling locally recurrent or unresectable primary adenocarcinoma of the rectum. Independent assessors documented quality of life scores, performance status, toxicities local response to treatment, and systemic disease progression before treatment and after treatment and every 8 week thereafter. Of 75 patients randomized, 73 were eligible for inclusion in the study. Forty-three of these patients had local pelvic tumour recurrence only and 21 also had distant metastases. In addition, nine patients had primary inoperable carcinomas, two of whom also had metastases. Thirty-seven patients were randomized to RT and 36 to VHF+RT. Th median dose of radiation in the VHF+RT arm was 4275 cGy with a median fraction size of 150 cGy and median duration of therapy of 48.5 days versus 4500 cGy in the RT-only arm with a median fraction size of 180 cGy and median duration of therapy of 38 days. These doses are unlikely to be significantly different in biological effect. No significant difference between the two groups was observed in extent and duration of local control, measures of toxicity or quality of life scores. Additionally, survival and cumulative incidence of pelvic site of first progression did not differ significantly between the groups. It is concluded that VHF microwave therapy in conjunction with radiotherapy produces no therapeutic advantage over conventional radiation therapy alone in the treatment of locally recurrent rectal carcinoma. 35 refs., 8 tabs., 3 figs

Surgical management of secondary hyperparathyroidism: how to effectively reduce recurrence at the time of primary surgery.

Science.gov (United States)

Xu, D; Yin, Y; Hou, L; Dai, W

2016-05-01

Successful parathyroidectomy (PTX) often results in a dramatic drop in the parathyroid hormone (PTH) levels, relieves the patient from clinical symptoms, and reduces mortality. Although PTX is generally a successful treatment for progressive secondary hyperparathyroidism (SHPT) patients subjected to surgery, a significant proportion develops recurrent SHPT following PTX. SHPT requiring PTX occurs more commonly in progressive chronic kidney disease and in long-term lithium therapy. Operative approaches include subtotal PTX, total PTX with or without autotransplantation, and possible thymectomy. Each approach has its proponents, advantages, and disadvantages. Although PTX offers the highest percentage cure for SHPT, compared to all other medical and surgical treatment, recurrent hyperparathyroidism can be observed in some patients dependent on follow-up time. A literature review and analysis of recent data regarding how to reduce recurrence of SHPT at the time of primary surgery was performed. The current literature and our own experience in the field have confirmed that pre-operative imaging, thymectomy, stereo magnifier, and surgical procedure may effectively reduce recurrence of SHPT at the time of primary surgery.

SPECIFIC FEATURE OF HORMONAL PROFILE IN PATIENTS WITH PRIMARY AND RECURRENT BREAST CANCER AND THEIR ROLE IN THE EFFICIENCY OF CHEMOTHERAPY

Directory of Open Access Journals (Sweden)

M. B. Kozlova

2009-01-01

Full Text Available The hormonal background was studied in 32 menopausal patients who had primary breast cancer (Stage III or its recurrence in the postoperative scar. The patients with the primary process, unlike those with a recurrence, were found to have increased adrenocortical cortisol-forming activity and changed thyroid homeostasis. In both types of the neoplastic process, the blood concentrations of estradi- ol, testosterone, prolactin, follicle-stimulating and luteinizing hormones were disturbed in a substantial number of cases; the distinc- tive feature of the primary process and its recurrence lies in the opposite direction. An association of individual differences in the con- centrations of estradiol and testosterone with the efficiency of neoadjuvant chemotherapy was analyzed in patients with recurrent can- cer.

Results of primary versus recurrent surgery to treat stress urinary incontinence in women

NARCIS (Netherlands)

van der Doelen, Maarten J; Withagen, Mariëlla I J; Vierhout, Mark E; Heesakkers, John P F A

INTRODUCTION AND HYPOTHESIS: We compared cure rates and complication rates in patients who had undergone primary or recurrent (secondary) surgery for stress urinary incontinence (SUI). METHODS: A retrospective cohort study that included patients who underwent surgery to treat SUI in a tertiary

Results of primary versus recurrent surgery to treat stress urinary incontinence in women

NARCIS (Netherlands)

Doelen, M.J. van der; Withagen, M.I.J.; Vierhout, M.E.; Heesakkers, J.P.F.A.

2015-01-01

INTRODUCTION AND HYPOTHESIS: We compared cure rates and complication rates in patients who had undergone primary or recurrent (secondary) surgery for stress urinary incontinence (SUI). METHODS: A retrospective cohort study that included patients who underwent surgery to treat SUI in a tertiary

Imaging aspects of neurologic emergencies in children treated for non-CNS malignancies

International Nuclear Information System (INIS)

Kaste, S.C.; Langston, J.; Rodriguez-Galindo, C.; Furman, W.L.; Thompson, S.J.

2000-01-01

There is a paucity of radiologic literature addressing neurologic emergencies in children receiving therapy for non-CNS primary malignancies. In the acute setting, many of these children present to local community hospitals. This pictorial is from a single institutional experience describing the spectrum of neurologic emergencies seen in children with non-CNS cancers. We hope to familiarize pediatric radiologists with these entities in order to expedite diagnosis, facilitate treatment, and minimize morbity and mortality that may be associated with these complications. (orig.)

Chemoradiotherapy response in recurrent rectal cancer.

Science.gov (United States)

Yu, Stanley K T; Bhangu, Aneel; Tait, Diana M; Tekkis, Paris; Wotherspoon, Andrew; Brown, Gina

2014-02-01

The efficacy of response to preoperative chemoradiotherapy (CRT) in recurrent versus primary rectal cancer has not been investigated. We compared radiological downsizing between primary and recurrent rectal cancers following CRT and determined the optimal size reduction threshold for response validated by survival outcomes. The proportional change in tumor length for primary and recurrent rectal cancers following CRT was compared using the independent sample t-test. Overall survival (OS) was calculated using the Kaplan-Meier product limit method and differences between survival for tumor size reduction thresholds of 30% (response evaluation criteria in solid tumors [RECIST]), 40%, and 50% after CRT in primary and recurrent rectal cancer groups. A total of 385 patients undergoing CRT were analyzed, 99 with recurrent rectal cancer and 286 with primary rectal cancer. The mean proportional reduction in maximum craniocaudal length was significantly higher for primary rectal tumors (33%) compared with recurrent rectal cancer (11%) (P rectal cancer when ≤30% or ≤40% definitions were used. However, for both primary and recurrent tumors, significant differences in median 3-year OS were observed when a RECIST cut-off of 50% was used. OS was 99% versus 77% in primary and 100% versus 42% in recurrent rectal cancer (P = 0.002 and P = 0.03, respectively). Only patients that demonstrated >50% size reduction showed a survival benefit. Recurrent rectal cancer appears radioresistant compared with primary tumors for tumor size after CRT. Further investigation into improving/intensifying chemotherapy and radiotherapy for locally recurrent rectal cancer is justified. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Results of postoperative reirradiation for recurrent or second primary head and neck carcinoma

NARCIS (Netherlands)

Kasperts, N; Slotman, BJ; Leemans, CR; de Bree, R; Doornaert, P; Langendijk, JA

2006-01-01

BACKGROUND. In this prospective study, the effects of a second course of postoperative radiation therapy on locoregional control, survival, toxicity, and quality of life were investigated in patients who underwent resection of a second primary or locoregional recurrent head and neck tumor in a

Endoscopic Endonasal Transsphenoidal Surgery, A Reliable Method for Treating Primary and Recurrent/Residual Craniopharyngiomas: Nine Years of Experience.

Science.gov (United States)

Bal, Ercan; Öge, Kamil; Berker, Mustafa

2016-10-01

Craniopharyngioma resection is one of the most challenging surgical procedures. Herein, we describe our extended endoscopic endonasal transsphenoidal surgery (EETS) technique, and the results of 9 years of use on primary and recurrent/residual craniopharyngiomas. This study reviewed 28 EETSs in 25 patients with craniopharyngiomas between January 2006 and September 2015. The patients were divided into 2 groups, newly diagnosed patients (group A, n = 15), and patients having residual or recurrent tumors (group B, n = 10). There was no significant difference between the groups in terms of the largest tumor diameter (P = 0.495), and all patients underwent EETS. The clinical and ophthalmologic examinations, imaging studies, endocrinologic studies, and operative findings for these cases were reviewed retrospectively. The number of gross total resections in group A was 13/15, and 7/10 in group B. Three of the patients developed postoperative cerebrospinal fluid leakage (all in group A). There were no neurovascular or ophthalmologic complications, and no meningitis or mortality was observed. There has been a notable increase in the use of EETS in the treatment of craniopharyngiomas during the last decade. Despite its increased use in the treatment of primary craniopharyngiomas, its implementation for recurrent or residual craniopharyngiomas has been viewed with suspicion. In this study, the results have been presented separately for primary and recurrent/residual craniopharyngiomas, so that the results can be compared. Overall, EETS is a reliable and successful surgical treatment method for primary and recurrent/residual craniopharyngiomas. Copyright © 2016 Elsevier Inc. All rights reserved.

Magnetic resonance imaging guided reirradiation of recurrent and second primary head and neck cancer.

Science.gov (United States)

Chen, Allen M; Cao, Minsong; Hsu, Sophia; Lamb, James; Mikaeilian, Argin; Yang, Yingli; Agazaryan, Nzhde; Low, Daniel A; Steinberg, Michael L

2017-01-01

To report a single-institutional experience using magnetic resonance imaging (MRI) guided radiation therapy for the reirradiation of recurrent and second cancers of the head and neck. Between October 2014 and August 2016, 13 consecutive patients with recurrent or new primary cancers of the head and neck that occurred in a previously irradiated field were prospectively enrolled in an institutional registry trial to investigate the feasibility and efficacy of MRI guided radiation therapy using a 0.35-T MRI scanner with a cobalt-60 radiation therapy source called the ViewRay system (ViewRay Inc., Cleveland, OH). Eligibility criteria included biopsy-proven evidence of recurrent or new primary squamous cell carcinoma of the head and neck, measurable disease, and previous radiation to >60 Gy. MRI guided reirradiation was delivered either using intensity modulated radiation therapy with conventional fractionation to a median dose of 66 Gy or stereotactic body radiation therapy (SBRT) using 7 to 8 Gy fractions on nonconsecutive days to a median dose of 40 Gy. Two patients (17%) received concurrent chemotherapy. The 1- and 2-year estimates of in-field control were 72% and 72%, respectively. A total of 227 daily MRI scans were obtained to guide reirradiation. The 2-year estimates of overall survival and progression-free survival were 53% and 59%, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis and/or conjunctivitis, and 1 case of aspiration pneumonia. Our preliminary findings show that reirradiation with MRI guided radiation therapy results in effective disease control with relatively low morbidity for patients with recurrent and second primary cancers of the head and neck. The superior soft tissue resolution of the MRI scans that were used for planning and delivery has the potential to improve the therapeutic ratio.

The therapeutic efficacy of propranolol in children with recurrent primary epistaxis

Science.gov (United States)

Bjelakovic, Bojko; Bojanovic, Mila; Lukic, Stevo; Saranac, Ljiljana; Vukomanovic, Vladislav; Prijic, Sergej; Zivkovic, Nikola; Randjelovic, Dusica

2013-01-01

We hypothesized that some characteristics of beta-blockers, including negative inotropic, peripheral vasoconstrictor, and antiangiogenic effects, might be potentially useful in treating children with epistaxis. From June 2010 to March 2012, a total of seven children with recurrent primary epistaxis resistant to conventional management were observed at our institution. An overall effectiveness of propranolol was noted in all seven children when given a dose of 1.5–2 mg/kg/day (divided into three doses) as a second line therapy for terminating epistaxis. Based on our first experience, we believe that propranolol could be a favorable treatment option for patients with primary epistaxis. PMID:23467483

Attributable Healthcare Resource Utilization and Costs for Patients With Primary and Recurrent Clostridium difficile Infection in the United States.

Science.gov (United States)

Zhang, Dongmu; Prabhu, Vimalanand S; Marcella, Stephen W

2018-04-17

The economic burden of Clostridium difficile infection (CDI), the leading cause of nosocomial infectious diarrhea, is not well understood. The objective of this study was to estimate the healthcare resource utilization (HCRU) and costs attributable to primary CDI and recurrent CDI (rCDI). This is a database (MarketScan) study. Patients without CDI were matched 1:1 by propensity score to those with primary CDI but no recurrences to obtain HCRU and costs attributable to primary CDI. Patients with primary CDI but no recurrences were matched 1:1 by propensity score to those with primary CDI plus 1 recurrence in order to obtain HCRU and costs attributable to rCDI. Adjusted estimates for incremental cumulative hospitalized days and healthcare costs over a 6-month follow-up period were obtained by generalized linear models with a Poisson or gamma distribution and a log link. Bootstrapping was used to obtain 95% confidence intervals (CIs). A total of 55504 eligible CDI patients were identified. Approximately 25% of these CDI patients had rCDI. The cumulative hospitalized days attributable to primary CDI and rCDI over the 6-month follow-up period were 5.20 days (95% CI, 5.01-5.39) and 1.95 days (95% CI, 1.48-2.43), respectively. The healthcare costs attributable to primary CDI and rCDI over the 6-month follow-up period were $24205 (95% CI, $23436-$25013) and $10580 (95% CI, $8849-$12446), respectively. The HCRU and costs attributable to primary CDI and rCDI are quite substantial. It is necessary to reduce the burden of CDI, especially rCDI.

Nanomedicines for the Treatment of CNS Diseases.

Science.gov (United States)

Reynolds, Jessica L; Mahato, Ram I

2017-03-01

Targeting and delivering macromolecular therapeutics to the central nervous system (CNS) has been a major challenge. The blood-brain barrier (BBB) is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Therefore, much effort has been channelled into improving transport of therapeutics across the BBB and into the CNS including the use of nanoparticles. In this thematic issue, several reviews and original research are presented that address "Nanomedicines for CNS Diseases." The articles in this issue are concentrated on either CNS-HIV disease or CNS tumors. In regards to CNS-HIV disease, there are two reviews that discuss the role of nanoparticles for improving the delivery of HIV therapeutics to the CNS. In addition, there are two original articles focusing on therapies for CNS-HIV, one of them uses nanoparticles for delivery of siRNA specific to a key protein in autophagy to microglia, and another discusses nanoparticle delivery of a soluble mediator to suppress neuroinflammation. Furthermore, a comprehensive review about gene therapy for CNS neurological diseases is also included. Finally, this issue also includes review articles on enhanced drug targeting to CNS tumors. These articles include a review on the use of nanoparticles for CNS tumors, a review on functionalization (ligands) of nanoparticles for drug targeting to the brain tumor by overcoming BBB, and the final review discusses the use of macrophages as a delivery vehicle to CNS tumors. This thematic issue provides a wealth of knowledge on using nanomedicines for CNS diseases.

Problems of prophylactic CNS radiotherapy in acute children's leukemia

International Nuclear Information System (INIS)

Bek, V.; Pribylova, O.; Abrahamova, J.; Hynieova, H.; Hrodek, O.

1980-01-01

The prophylactic treatment of the CNS was conducted by cobalt teletherapy of the cranium and by intrathecal application of MTX after the induction of primary remission in 70 children with acute leukemia throughout 5 years up to the end of 1978. The method of the combined radio- and chemoprophylaxis of the CNS was being changed during the years, especially as far as the radiation dose for the cranium was concerned. A detailed analysis made in a group of 59 children with the minimum interval of 18 months from the beginning of the treatment showed the best results after the application of a dose of 24 Gy/3 weeks. Following this procedure the relapse of leukemia in the CNS occurred in 9% only, whereas on the application of doses of 20 Gy and lower it occurred in 35 to 40%. On the whole 24 out of 59 children, i.e. 41%, are surviving, 35 children, i.e. 59%, died. Mostly complete, but only temporary, epilation was an invariable consequence of the irradiation of the cranium. The somnolence syndrome was only sporadically observed. It cannot be excluded, however, that some of its forms in patients discharged from hospital escaped attention. No case was recorded of serious impairment of the CNS of the leukoencephalopathic type. Up to now the psychomotor, intellectual and emotional development of the surviving children has been normal. (author)

Impact on regional recurrence and survival of axillary surgery in women with node-negative primary breast cancer

DEFF Research Database (Denmark)

Axelsson, C K; Düring, M; Christiansen, P M

2009-01-01

-negative primary breast cancer treated solely by surgery. Median follow-up was 9 years. RESULTS: The number of lymph nodes removed correlated with a reduction in the rate of subsequent axillary recurrence (from 2.1 to 0.4 per cent; P = 0.037), local recurrence (from 7.4 to 3.8 per cent; P

Management of CNS tumors

International Nuclear Information System (INIS)

Griem, M.L.

1987-01-01

The treatment of tumors of the CNS has undergone a number of changes based on the impact of CT. The use of intraoperative US for the establishment of tumor location and tumor histology is demonstrated. MR imaging also is beginning to make an impact on the diagnosis and treatment of tumors of the CNS. Examples of MR images are shown. The authors then discuss the important aspects of tumor histology as it affects management and newer concepts in surgery, radiation, and chemotherapy on tumor treatment. The role of intraoperative placement of radioactive sources, the utilization of heavy particle radiation therapy, and the potential role of other experimental radiation therapy techniques are discussed. The role of hyperfractionated radiation and of neutrons and x-ray in a mixed-beam treatment are discussed in perspective with standard radiation therapy. Current chemotherapy techniques, including intraarterial chemotherapy, are discussed. The complications of radiation therapy alone and in combination with chemotherapy in the management of primary brain tumors, brain metastases, and leukemia are reviewed. A summary of the current management of pituitary tumors, including secreting pituitary adenomas and chromophobe adenomas, are discussed. The treatment with heavy particle radiation, transsphenoidal microsurgical removal, and combined radiotherapeutic and surgical management are considered. Tumor metastasis management of lesions of the brain and spinal cord are considered

Self-expandable metallic stents for patients with recurrent esophageal carcinoma after failure of primary chemoradiotherapy

Energy Technology Data Exchange (ETDEWEB)

Muto, Manabu; Ohtsu, Atsushi; Boku, Narikazu; Yoshida, Shigeaki [National Cancer Center, Kashiwa, Chiba (Japan). Hospital East; Miyata, Yoshinori; Shioyama, Yasukazu

2001-06-01

Recent advances in chemoradiotherapy for esophageal carcinoma have resulted in improved survival rates. However, there are few options for recurrent dysphagia due to refractory carcinoma after failure of primary chemoradiotherapy. The aim of this study was to evaluate the safety and efficacy of self-expandable metallic stent placement for patients with recurrent esophageal carcinoma where definitive chemoradiotherapy has failed. Thirteen consecutive patients with recurrent squamous cell carcinoma of the esophagus, in whom self-expandable metallic stents were placed after failure of primary chemoradiotherapy, were studied retrospectively. All patients had esophageal obstruction or malignant fistula. The oral alimentation status of nine of 13 patients (69%) improved after successful placement of the stent. Following placement of the stent, fever (>38 deg C) and severe chest pain occurred in 85% (11/13) of the patients. In all patients examined, C-reactive protein was elevated within 1 week of the operation. Esophageal perforation occurred in three patients. Stent-related mediastinitis and pneumonia developed in six (46%) and three (23%) patients, respectively. Seven of the 13 patients (54%) died of stent-related pulmonary complications. Although the placement of a self-expandable metallic stent for patients with recurrent esophageal carcinoma after failure of chemoradiotherapy improved their oral alimentation status, we found that this treatment increases the risk of life-threatening pulmonary complications. (author)

Histology-based classification predicts pattern of recurrence and improves risk stratification in primary retroperitoneal sarcoma

Science.gov (United States)

Tan, Marcus C.B.; Brennan, Murray F.; Kuk, Deborah; Agaram, Narasimhan P.; Antonescu, Cristina; Qin, Li-Xuan; Moraco, Nicole; Crago, Aimee M.; Singer, Samuel

2015-01-01

Objective To determine the prognostic significance of histologic type/subtype in a large series of patients with primary resected retroperitoneal sarcoma. Summary Background Data The histologic diversity and rarity of retroperitoneal sarcoma has hampered the ability to predict patient outcome. Methods From a single-institution, prospective database, 675 patients treated surgically for primary, non-metastatic retroperitoneal sarcoma during 1982–2010 were identified and histologic type/subtype was reviewed. Clinicopathologic variables were analyzed for association with disease-specific death (DSD), local recurrence (LR), and distant recurrence (DR). Results Median follow-up for survivors was 7.5 years. The predominant histologies were well-differentiated liposarcoma, dedifferentiated liposarcoma, and leiomyosarcoma. Five-year cumulative incidence of DSD was 31%, and factors independently associated with DSD were R2 resection, resection of ≥3 contiguous organs, and histologic type. Five-year cumulative incidence for LR was 39% and for DR was 24%. R1 resection, age, tumor size, and histologic type were independently associated with LR; size, resection of ≥3 organs, and histologic type were independently associated with DR. Liposarcoma and leiomyosarcoma were associated with late recurrence and DSD (as long as 15 years from diagnosis). For solitary fibrous tumor, local recurrence was uncommon (sarcoma. Histology predicts the pattern and incidence of LR and DR and will aid in more accurate patient counseling and selection of patients for adjuvant therapy trials. PMID:25915910

Self-expandable metallic stents for patients with recurrent esophageal carcinoma after failure of primary chemoradiotherapy

International Nuclear Information System (INIS)

Muto, Manabu; Ohtsu, Atsushi; Boku, Narikazu; Yoshida, Shigeaki; Miyata, Yoshinori; Shioyama, Yasukazu

2001-01-01

Recent advances in chemoradiotherapy for esophageal carcinoma have resulted in improved survival rates. However, there are few options for recurrent dysphagia due to refractory carcinoma after failure of primary chemoradiotherapy. The aim of this study was to evaluate the safety and efficacy of self-expandable metallic stent placement for patients with recurrent esophageal carcinoma where definitive chemoradiotherapy has failed. Thirteen consecutive patients with recurrent squamous cell carcinoma of the esophagus, in whom self-expandable metallic stents were placed after failure of primary chemoradiotherapy, were studied retrospectively. All patients had esophageal obstruction or malignant fistula. The oral alimentation status of nine of 13 patients (69%) improved after successful placement of the stent. Following placement of the stent, fever (>38 deg C) and severe chest pain occurred in 85% (11/13) of the patients. In all patients examined, C-reactive protein was elevated within 1 week of the operation. Esophageal perforation occurred in three patients. Stent-related mediastinitis and pneumonia developed in six (46%) and three (23%) patients, respectively. Seven of the 13 patients (54%) died of stent-related pulmonary complications. Although the placement of a self-expandable metallic stent for patients with recurrent esophageal carcinoma after failure of chemoradiotherapy improved their oral alimentation status, we found that this treatment increases the risk of life-threatening pulmonary complications. (author)

Outcome and risk factors of recurrence after thoracoscopic bullectomy in young adults with primary spontaneous pneumothorax.

Science.gov (United States)

Nakayama, Takashi; Takahashi, Yusuke; Uehara, Hirofumi; Matsutani, Noriyuki; Kawamura, Masafumi

2017-07-01

To investigate the risk factors of recurrence of pneumothorax following thoracoscopic bullectomy in young adults. Between January, 2005 and September, 2015, 167 patients aged ≤40 years underwent initial thoracoscopic bullectomy for primary spontaneous pneumothorax (PSP) at our hospital. Recurrence-free probability was calculated from the date of surgery to recurrence or last follow-up, using the Kaplan-Meier method. Sixteen (9.6%) of the 167 patients suffered a recurrence (collective total, 16 recurrences). The recurrence-free intervals were 3-107 months (median 25.8 months), and the 5-year recurrence-free probability was 85.9%. Multivariate Cox analysis demonstrated that age ≤23 years (p = 0.029) and a history of ipsilateral pneumothorax before surgery (p = 0.029) were significantly associated with higher risk of recurrence. The 5-year recurrence-free probability was 72.3% for patients aged ≤23 years and a history of ipsilateral pneumothorax before surgery and 94.1% for those with neither of these factors (p = 0.001). Recurrence developed within 3 years after surgery in 14 of the 16 patients. Patients ≤23 years of age with a history of ipsilateral pneumothorax before surgery are at significantly high risk of its recurrence, frequently within 3 years; thus, the risk of postoperative recurrence of a pneumothorax must be kept in mind.

Association of MMP-2 and MMP-9 expression with recurrences in primary spontaneous pneumothorax.

Science.gov (United States)

Huang, Ying-Fong; Chiu, Wen-Chin; Chou, Shah-Hwa; Su, Yu-Han; Chen, Yu-Wen; Chai, Chee-Yin; Huang, Chih-Jen; Huang, Ming-Yii; Yuan, Shyng-Shiou F; Lee, Yi-Chen

2017-01-01

Primary spontaneous pneumothorax (PSP) is a common benign problem. However, PSP recurrence is still a troublesome complication for most patients. This study intended to determine the role of matrix metalloproteinase-2 (MMP-2) and MMP-9 in type II pneumocytes of patients with PSP and its relation with recurrence. Ninety-one patients who had undergone needlescopic video-assisted thoracoscopic surgery wedge resection of lung with identifiable blebs for PSP were included in this study. Immunohistochemical (IHC) staining was used to measure the expression of MMP-2 and MMP-9 in lung tissues of PSP patients. The results were further correlated with clinicopathological parameters and recurrence rates using chi-square or Fisher's exact test. The value of MMP-2 and MMP-9 for overall recurrence was analyzed by univariate and multivariable Cox regression model. IHC data revealed that MMP-2 and MMP-9 staining was predominantly observed in type II pneumocytes of patients with PSP. We found that MMP-2 and MMP-9 expression in PSP, especially male PSP patients, was significantly correlated with recurrence. In the univariate and multivariate analyses, MMP-2 and MMP-9 were statistically significant risk factors for overall recurrence in PSP patients. Therefore, high expression levels of MMP-2 and MMP-9 in type II pneumocytes show a positive correlation with PSP recurrence risk. Further studies are needed to validate whether reduction of MMP-2 and MMP-9 expression may be a promising way for decreasing the risk of PSP recurrence in the future. Copyright © 2016. Published by Elsevier Taiwan.

Pancreatic Cancer Arising From the Remnant Pancreas: Is It a Local Recurrence or New Primary Lesion?

Science.gov (United States)

Hashimoto, Daisuke; Chikamoto, Akira; Masuda, Toshiro; Nakagawa, Shigeki; Imai, Katsunori; Yamashita, Yo-Ichi; Reber, Howard A; Baba, Hideo

2017-10-01

Local recurrence of pancreatic cancer (PC) can occur in the pancreatic remnant. In addition, new primary PC can develop in the remnant. There are limited data available regarding this so-called remnant PC. The aim of this review was to describe the characteristics and therapeutic strategy regarding remnant PC. A literature search was performed using Medline published in English according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The incidence of remnant PC has been reported to be 3% to 5%. It is difficult to distinguish local recurrence from new primary PC. Genetic diagnosis such as Kirsten rat sarcoma viral oncogene homolog mutation may resolve this problem. For patients with remnant PC, repeated pancreatectomy can be performed. Residual total pancreatectomy is the most common procedure. Recent studies have described the safety of the operation because of recent surgical progress and perioperative care. The patients with remnant PC without distant metastasis have shown good long-term outcomes, especially those who underwent repeated pancreatectomy. Adjuvant chemotherapy may contribute to longer survival. In conclusion, this review found that both local recurrence and new primary PC can develop in the pancreatic remnant. Repeated pancreatectomy for the remnant PC is a feasible procedure and can prolong patient survival.

Correlation of matrix metalloproteinase-2 and -9 expression with recurrences in primary spontaneous pneumothorax patients.

Science.gov (United States)

Chiu, Wen-Chin; Lee, Yi-Chen; Su, Yu-Han; Chai, Chee-Yin; Hu, Stephen Chu-Sung; Yuan, Shyng-Shiou F; Chou, Shah-Hwa

2016-12-01

Primary spontaneous pneumothorax (PSP) is a common benign disorder. However, unpredictable recurrence is a major concern for most patients. The aim of the present study was to assess the role of matrix metalloproteinase-2 (MMP-2) and MMP-9 in alveolar macrophages of patients with PSP and its relationship with recurrence. Ninety-two patients who received needlescopic video-assisted thoracoscopic surgery (NVATS) wedge resection of lung with identifiable blebs for PSP were enrolled for the study. Immunohistochemistry was performed to evaluate the expression of MMP-2 and MMP-9 in lung tissues of patients with PSP. The result was correlated with clinicopathological variables and recurrence rates by the chi-square test. The value of MMP-2 and MMP-9 for overall recurrence was evaluated by univariate and multivariable Cox regression analyses. The MMP-2 and MMP-9 staining was predominantly observed in alveolar macrophages of patients with PSP. We found that MMP-2 (recurrence: Pcorrelated with recurrence and smoking status. In the multivariate analyses, MMP-2 [hazard ratio (HR) =2.83; 95% confidence interval (CI): 1.37-5.85, P=0.005) and MMP-9 (HR =2.25; 95% CI: 1.19-4.24, P=0.013) were statistically significant risk factors for overall recurrence in PSP patients. High expression levels of MMP-2 and MMP-9 showed a positive correlation with recurrence in PSP patients. Further studies are required to test whether inhibition of MMP-2 and MMP-9 expression renders a promising approach for reducing the risk of PSP recurrence in the future.

Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor

International Nuclear Information System (INIS)

Park, Lily; De Laney, Thomas F.; Liebsch, Norbert J.; Hornicek, Francis J.; Goldberg, Saveli; Mankin, Henry; Rosenberg, Andrew E.; Rosenthal, Daniel I.; Suit, Herman D.

2006-01-01

Purpose: To assess the efficacy of definitive treatment of sacral chordoma by high-dose proton/photon-beam radiation therapy alone or combined with surgery. Methods and Materials: The records of 16 primary and 11 recurrent sacral chordoma patients treated from November 1982 to November 2002 by proton/photon radiation therapy alone (6 patients) or combined with surgery (21 patients) have been analyzed for local control, survival, and treatment-related morbidity. The outcome analysis is based on follow-up information as of 2005. Results: Outcome results show a large difference in local failure rate between patients treated for primary and recurrent chordomas. Local control results by surgery and radiation were 12/14 vs. 1/7 for primary and recurrent lesions. For margin-positive patients, local control results were 10 of 11 and 0 of 5 in the primary and recurrent groups, respectively; the mean follow-up on these locally controlled patients was 8.8 years (4 at 10.3, 12.8, 17, and 21 years). Radiation alone was used in 6 patients, 4 of whom received ≥73.0 Gy (E); local control was observed in 3 of these 4 patients for 2.9, 4.9, and 7.6 years. Conclusion: These data indicate a high local control rate for surgical and radiation treatment of primary (12 of 14) as distinct from recurrent (1 of 7) sacral chordomas. Three of 4 chordomas treated by ≥73.0 Gy (E) of radiation alone had local control; 1 is at 91 months. This indicates that high-dose proton/photon therapy offers an effective treatment option

Application of empowerment theory for CNS practice.

Science.gov (United States)

Carlson-Catalano, J M

1993-11-01

Power is necessary for the clinical nurse specialist (CNS) to successfully conduct objectives of practice in bureaucratic hospital settings. To obtain power, the CNS could use strategies of an empowerment theory to fully operationalize roles in hospitals. This article will discuss how the CNS may be empowered utilizing strategies in four empowering categories. In addition, the many benefits of empowering the CNS are reviewed.

Recurrence of primary hyperoxaluria: An avoidable catastrophe following kidney transplant

Directory of Open Access Journals (Sweden)

Madiwale C

2008-01-01

Full Text Available Primary hyperoxaluria is a rare autosomal recessive disease due to deficiency of an oxalate-metabolizing liver enzyme, which results in nephrolithiasis and renal failure. Concomitant liver and kidney transplant is recommended as isolated kidney transplant is inevitably complicated by recurrence of the disease. We present a 25-year-old man with end-stage nephrolithiatic renal disease who underwent bilateral nephrectomy, followed by kidney transplantation. There was progressive worsening of kidney function two weeks post transplant. Review of nephrectomy and transplant kidney biopsy showed abundant calcium oxalate crystals and further workup revealed hyperoxaluria, which was previously unsuspected. Later he developed fever, breathlessness, hemiparesis and died 10 weeks after transplant. Autopsy revealed multi-organ deposits of oxalate crystals as well as widespread zygomycosis. This case emphasizes the need for careful pre-transplant evaluation of patients with renal calculus disease in order to exclude primary hyperoxaluria.

Absceso recidivante por Nocardia asteroides en una paciente portadora de poliglobulia primaria Recurrent brain abscess caused by Nocardia asteroides in a patient with primary polycythaemia

Directory of Open Access Journals (Sweden)

Carlos Aboal

2006-06-01

aspiration and the beginning of an antimicrobial therapy are essential to the patient’s good evolution. This paper presents a patient with a primary polycythaemia and a recurrent brain abscess by Nocardia asteroides, probably of dental origin.

Central Nervous System (CNS Disease Triggering Takotsubo Syndrome

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Josef Finsterer

2016-01-01

Full Text Available Takotsubo syndrome (TTS is usually triggered by psychological or physical stress. One of the many physical sources of stress are central nervous system (CNS disorders. CNS disorders most frequently triggering TTS include subarachnoid bleeding, epilepsy, ischemic stroke, migraine, and intracerebral bleeding. More rare CNS-triggers of TTS include posterior reversible encephalopathy syndrome (PRES, amyotrophic lateral sclerosis, encephalitis, or traumatic brain or spinal cord injury. TTS triggered by any of the CNS disorders needs to be recognized since adequate treatment of TTS may improve the general outcome from the CNS disorder as well. Neurologists need to be aware of TTS as a complication of specific CNS disorders but TTS may be triggered also by CNS disorders so far not recognised as causes of TTS.

The predictive value of preoperative {sup 18}F-fluorodeoxyglucose PET for postoperative recurrence in patients with localized primary gastrointestinal stromal tumour

Energy Technology Data Exchange (ETDEWEB)

Miyake, Kanae Kawai; Nakamoto, Yuji; Togashi, Kaori [Kyoto University Hospital, Department of Diagnostic Imaging and Nuclear Medicine, Kyoto (Japan); Mikami, Yoshiki [Kyoto University Hospital, Department of Diagnostic Pathology, Kyoto (Japan); Kumamoto University Hospital, Department of Diagnostic Pathology, Kumamoto (Japan); Tanaka, Shiro [Kyoto University, Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto (Japan); Higashi, Tatsuya [Shiga Medical Center Research Institute, Shiga (Japan); Tadamura, Eiji [Sakazaki Clinic, Department of Radiology, Kyoto (Japan); Saga, Tsuneo [National Institute of Radiological Sciences, Dianostic Imaging Group, Molecular Imaging Center, Chiba (Japan); Minami, Shunsuke [Shiga Medical Center for Adults, Department of Radiology, Shiga (Japan)

2016-12-15

To assess the potential value of preoperative {sup 18}F-FDG PET to predict postoperative recurrence of solitary localized primary gastrointestinal stromal tumour (GIST) after radical resection. A total of 46 patients with primary GIST who received preoperative {sup 18}F-FDG PET and underwent complete resection without neoadjuvant therapy were retrospectively studied. PET findings, including ring-shaped uptake and intense uptake, were compared with Joensuu risk grades using Fisher's exact test. The prognostic value of the preoperative clinico-imaging variables - age ≥60 years, male, ring-shaped uptake, intense uptake, tumour size >5 cm, heterogeneous CT attenuation and lower gastrointestinal origin - and Joensuu high risk for recurrence-free survival was evaluated using log-rank test and multivariate Cox regression analysis. Ring-shaped uptake and intense uptake were significantly associated with Joensuu high risk. Univariate analysis showed that ring-shaped uptake, intense uptake, size >5 cm and Joensuu high risk were significantly associated with inferior recurrence-free survival. Multivariate analysis showed that ring-shaped uptake (P = 0.004) and Joensuu high risk (P = 0.021) were independent adverse prognostic factors of postoperative recurrence. Ring-shaped uptake on preoperative {sup 18}F-FDG PET may be a potential predictor of postoperative tumour recurrence of localized primary GISTs. (orig.)

Effects of various cone-beam computed tomography settings on the detection of recurrent caries under restorations in extracted primary teeth

OpenAIRE

Kamburo?lu, K?van?; S?nmez, G?l; Berkta?, Zeynep Serap; Kurt, Hakan; ?zen, Do?ukan

2017-01-01

Purpose The aim of this study was to assess the ex vivo diagnostic ability of 9 different cone-beam computed tomography (CBCT) settings in the detection of recurrent caries under amalgam restorations in primary teeth. Materials and Methods Fifty-two primary teeth were used. Twenty-six teeth had dentine caries and 26 teeth did not have dentine caries. Black class II cavities were prepared and restored with amalgam. In the 26 carious teeth, recurrent caries were left under restorations. The oth...

Salvage definitive chemo-radiotherapy for locally recurrent oesophageal carcinoma after primary surgery: retrospective review

International Nuclear Information System (INIS)

Baxi, S. H.; Burmeister, B.; Harvey, J. A.; Smithers, M.; Thomas, J.

2008-01-01

Full text: To determine the overall survival and gastrointestinal toxicity for patients treated with salvage definitive chemo-radiotherapy after primary surgery for locoregional relapse of oesophageal carcinoma. A retrospective review of 525 patients who had a resection for oesophageal or oesophagogastric carcinoma at Princess Alexandra Hospital identified 14 patients treated with salvage definitive radiotherapy or chemo-radiotherapy, following localized recurrence of their disease. We analysed the patient and treatment characteristics to determine the median overall survival as the primary end point. Gastrointestinal toxicity was examined to determine if increased toxicity occurred when the stomach was irradiated within the intrathoracic radiotherapy field. The median overall survival for patients treated with curative intent using salvage definitive chemo-radiotherapy was 16 months and the 2-year overall survival is 21%. One patient is in clinical remission more than 5 years after therapy. Age <60 years old and nodal recurrence were favourable prognostic factors. Treatment compliance was 93% with only one patient unable to complete the intended schedule. Fourteen per cent of patients experienced grade 3 or 4 gastrointestinal toxicity. Salvage definitive chemo-radiotherapy should be considered for good performance status patients with oesophageal carcinoma who have a locoregional relapse after primary surgery. The schedule is tolerable with low toxicity and an acceptable median survival

No recurrence of sporadic primary hyperparathyroidism when cure is established 6 months after parathyroidectomy

NARCIS (Netherlands)

Witteveen, Janneke E.; Kievit, Job; Morreau, Hans; Romijn, Johannes A.; Hamdy, Neveen A. T.

2010-01-01

Cure rate for primary hyperparathyroidism (PHPT) is reported to be 94-100% 1 year after surgery, but recent data suggest recurrence in 4% of the patients 1-5 years post-operatively. The aim of our study was to establish the cure rate and its maintenance in the long-term after parathyroidectomy (PTx)

Primary central nervous system lymphoma in immunocompetent patients: spectrum of findings and differential characteristics.

Science.gov (United States)

Gómez Roselló, E; Quiles Granado, A M; Laguillo Sala, G; Pedraza Gutiérrez, S

2018-02-23

Primary central nervous system (CNS) lymphomas are uncommon and their management differs significantly from that of other malignant tumors involving the CNS. This article explains how the imaging findings often suggest the diagnosis early. The typical findings in immunocompetent patients consist of a supratentorial intraaxial mass that enhances homogeneously. Other findings to evaluate include multifocality and incomplete ring enhancement. The differential diagnosis of primary CNS lymphomas should consider mainly other malignant tumors of the CNS such as glioblastomas or metastases. Primary CNS lymphomas tend to have less edema and less mass effect; they also tend to spare the adjacent cortex. Necrosis, hemorrhage, and calcification are uncommon in primary CNS lymphomas. Although the findings in morphologic sequences are characteristic, they are not completely specific and atypical types are sometimes encountered. Advanced imaging techniques such as diffusion or especially perfusion provide qualitative and quantitative data that play an important role in differentiating primary CNS lymphomas from other brain tumors. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR-Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors.

Science.gov (United States)

Felsberg, Jörg; Hentschel, Bettina; Kaulich, Kerstin; Gramatzki, Dorothee; Zacher, Angela; Malzkorn, Bastian; Kamp, Marcel; Sabel, Michael; Simon, Matthias; Westphal, Manfred; Schackert, Gabriele; Tonn, Jörg C; Pietsch, Torsten; von Deimling, Andreas; Loeffler, Markus; Reifenberger, Guido; Weller, Michael

2017-11-15

Purpose: Approximately 40% of all glioblastomas have amplified the EGFR gene, and about half of these tumors express the EGFRvIII variant. The prognostic role of EGFRvIII in EGFR -amplified glioblastoma patients and changes in EGFRvIII expression in recurrent versus primary glioblastomas remain controversial, but such data are highly relevant for EGFRvIII-targeted therapies. Experimental Design: EGFR -amplified glioblastomas from 106 patients were assessed for EGFRvIII positivity. Changes in EGFR amplification and EGFRvIII status from primary to recurrent glioblastomas were evaluated in 40 patients with EGFR -amplified tumors and 33 patients with EGFR -nonamplified tumors. EGFR single-nucleotide variants (SNV) were assessed in 27 patients. Data were correlated with outcome and validated in 150 glioblastoma patients from The Cancer Genome Atlas (TCGA) consortium. Results: Sixty of 106 EGFR -amplified glioblastomas were EGFRvIII-positive (56.6%). EGFRvIII positivity was not associated with different progression-free or overall survival. EGFRvIII status was unchanged at recurrence in 35 of 40 patients with EGFR -amplified primary tumors (87.5%). Four patients lost and one patient gained EGFRvIII positivity at recurrence. None of 33 EGFR- nonamplified glioblastomas acquired EGFR amplification or EGFRvIII at recurrence. EGFR SNVs were frequent in EGFR -amplified tumors, but were not linked to survival. Conclusions: EGFRvIII and EGFR SNVs are not prognostic in EGFR -amplified glioblastoma patients. EGFR amplification is retained in recurrent glioblastomas. Most EGFRvIII-positive glioblastomas maintain EGFRvIII positivity at recurrence. However, EGFRvIII expression may change in a subset of patients at recurrence, thus repeated biopsy with reassessment of EGFRvIII status is recommended for patients with recurrent glioblastoma to receive EGFRvIII-targeting agents. Clin Cancer Res; 23(22); 6846-55. ©2017 AACR . ©2017 American Association for Cancer Research.

Magnetic resonance imaging guided reirradiation of recurrent and second primary head and neck cancer

Directory of Open Access Journals (Sweden)

Allen M. Chen, MD

2017-04-01

Conclusions: Our preliminary findings show that reirradiation with MRI guided radiation therapy results in effective disease control with relatively low morbidity for patients with recurrent and second primary cancers of the head and neck. The superior soft tissue resolution of the MRI scans that were used for planning and delivery has the potential to improve the therapeutic ratio.

microRNAs in CNS disorders

DEFF Research Database (Denmark)

Kocerha, Jannet; Kauppinen, Sakari; Wahlestedt, Claes

2009-01-01

RNAs (miRNAs) have been identified in the mammalian central nervous system (CNS) and are reported to mediate pivotal roles in many aspects of neuronal functions. Disruption of miRNA-based post-transcriptional regulation has been implicated in a range of CNS disorders as one miRNA is predicted to impact...

Supratentorial CNS malformations

International Nuclear Information System (INIS)

Zlatareva, D.

2012-01-01

Full text: Clinical suspicion of a developmental anomaly of the central nervous system (CNS) is a frequent indication for performing and magnetic resonance imaging (MRI) examination of the brain. Classification systems for malformation of the CNS are constantly revised according to newer scientific research. Developmental abnormalities can be classified in two main types. The first category consists of disorders of organogenesis in which genetic defects or any ischemic, metabolic, toxic or infectious insult to the developing brain can cause malformation. These malformations result from abnormal neuronal and glial proliferation and from anomalies of neuronal migration and or cortical organization. They are divided into supra- and infratentorial and may involve grey or white matter or both. The second category of congenital brain abnormalities is disorders of histogenesis which result from abnormal cell differentiation with a relatively normal brain appearance. Supratentorial CNS malformations could be divided into anomalies in telencephalic commissure, holoprosencephalies and malformations in cortical development. There are three main telencephalic commissures: the anterior commissure, the hippocampal commissure and the corpus callosum. Their morphology (hypoplasia, hyperplasia, agenesis, dysgenesis, even atrophy) reflects the development of the brain. Their agenesis, complete or partial, is one of the most commonly observed features in the malformations of the brain and is a part of many syndromes. Malformations of cortical development (MCD) are heterogeneous group of disease which result from disruption of 3 main stages of cortical development. The common clinical presentation is refractory epilepsy and or developmental delay. The most common MCD are heterotopias, focal cortical dysplasia, polymicrogyria, schizencephaly, pachygyria and lizencephaly. The exact knowledge of the brain anatomy and embryology is mandatory to provide a better apprehension of the

Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy

Science.gov (United States)

2014-12-29

Fatigue; Malignant Ovarian Mixed Epithelial Tumor; Neuropathy; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Pain; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Primary anti-phospholipid antibody syndrome causing recurrent venous thrombosis and thrombocytopenia in a patient with Addison's disease.

Science.gov (United States)

Elebrashy, Ibrahim; Yousief, Elham; Saif, Aasem

2014-12-01

We report a case of Addison's disease presenting with recurrent deep venous thrombosis and thrombocytopenia and proved to have primary anti-phospholipid antibody syndrome. The case report highlights the shared autoimmune nature of both diseases.

Targeting PRMT5 as a Novel Radiosensitization Approach for Primary and Recurrent Prostate Cancer Treatment

Science.gov (United States)

2015-08-01

primary and recurrent prostate cancer cells toRT During the third grant period. we generated stable cell liens to indue bly express PRMT5 shRNA using...significant impact on the reporter gene activity (data not shown). Taken together, these results suggest that these SNPs have negligible effect on the 1.8 kb

Treatment Challenges of a Primary Vertebral Artery Aneurysm Causing Recurrent Ischemic Strokes

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Davide Strambo

2017-01-01

Full Text Available Background. Extracranial vertebral artery aneurysms are a rare cause of embolic stroke; surgical and endovascular therapy options are debated and long-term complication may occur. Case Report. A 53-year-old man affected by neurofibromatosis type 1 (NF1 came to our attention for recurrent vertebrobasilar embolic strokes, caused by a primary giant, partially thrombosed, fusiform aneurysm of the left extracranial vertebral artery. The aneurysm was treated by endovascular approach through deposition of Guglielmi Detachable Coils in the proximal segment of the left vertebral artery. Six years later the patient presented stroke recurrence. Cerebral angiography and Color Doppler Ultrasound well characterized the unique hemodynamic condition developed over the years responsible for the new embolic event: the aneurysm had been revascularized from its distal portion by reverse blood flow coming from the patent vertebrobasilar axis. A biphasic Doppler signal in the left vertebral artery revealed a peculiar behavior of the blood flow, alternately directed to the aneurysm and backwards to the basilar artery. Surgical ligation of the distal left vertebral artery and excision of the aneurysm were thus performed. Conclusion. This is the first described case of NF1-associated extracranial vertebral artery aneurysm presenting with recurrent embolic stroke. Complete exclusion of the aneurysm from the blood circulation is advisable to achieve full resolution of the embolic source.

Immobilization in external rotation combined with abduction reduces the risk of recurrence after primary anterior shoulder dislocation.

Science.gov (United States)

Heidari, Kamran; Asadollahi, Shadi; Vafaee, Reza; Barfehei, Abbas; Kamalifar, Hossein; Chaboksavar, Zein Alabedin; Sabbaghi, Mohammad

2014-06-01

We aimed to compare the effectiveness of immobilization in abduction and external rotation vs immobilization in adduction and internal rotation after primary anterior dislocation of the shoulder. The study randomized 102 patients (age range, 15-55 years) with the diagnosis of primary anterior dislocation of the shoulder to receive immobilization in adduction and internal rotation (AdIR, n = 51) using sling and swathe bandage or immobilization in abduction and external rotation (AbER, n = 51) with a stabilizer brace. Patients received a rehabilitation program 3 weeks after the intervention. After a 24-month follow-up, 33.3% in the AdIR group and 3.9% in the AbER group had recurrence (P patients in the AbER group (19.6%) and 3 in the AdIR group (5.8%) discontinued shoulder immobilization before 3 weeks (P = .03). In patients without recurrence, the anterior apprehension test was positive in 6 of 34 in the AdIR group (17.6%) and in 4 of 49 in the AbER group (8.1%, P = .19). Immobilization with the shoulder joint in abduction and external rotation is an effective method to reduce the risk of recurrence after primary anterior shoulder dislocations and should be preferred to the traditional method of immobilization in adduction and internal rotation in clinical practice. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Staging of primary head and neck tumors and detection of recurrences

International Nuclear Information System (INIS)

Adams, S.; Baum, R.P.; Knecht, R.; Hoer, G.

2001-01-01

Squamous cell carcinomas represent the vast majority of all malignant tumors of the head and neck region. Lymph node involvement is the most important prognostic factor affecting survival of patients with head and neck cancer. The effectiveness of surgical treatment depends on the complete excision of all tumor tissue and an accurate preoperative diagnosis. Tumor-node-metastasis (TNM) staging is therefore mandatory. In comparison to positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG PET), morphological imaging modalities (CT, MRI) have been applied for the localization of primary head and neck tumors because of their better anatomical resolution. Metabolic tumor imaging using FDG PET is superior to morphological imaging by CT and MRI in the detection of small cervical lymph node metastases (Class 1a indication). Increased FDG uptake has also been observed in benign inflammatory lesions after radiation therapy, therefore detection of local recurrence with FDG PET can be problematic. To ensure a high diagnostic accuracy it is been suggested to perform FDG PET not earlier than 3 months after radiation therapy (Class 1a indication for the diagnosis of local recurrence). (orig.) [de

SINS/CNS Nonlinear Integrated Navigation Algorithm for Hypersonic Vehicle

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Yong-jun Yu

2015-01-01

Full Text Available Celestial Navigation System (CNS has characteristics of accurate orientation and strong autonomy and has been widely used in Hypersonic Vehicle. Since the CNS location and orientation mainly depend upon the inertial reference that contains errors caused by gyro drifts and other error factors, traditional Strap-down Inertial Navigation System (SINS/CNS positioning algorithm setting the position error between SINS and CNS as measurement is not effective. The model of altitude azimuth, platform error angles, and horizontal position is designed, and the SINS/CNS tightly integrated algorithm is designed, in which CNS altitude azimuth is set as measurement information. GPF (Gaussian particle filter is introduced to solve the problem of nonlinear filtering. The results of simulation show that the precision of SINS/CNS algorithm which reaches 130 m using three stars is improved effectively.

Frequency of chromosome 17 aneuploidy in primary and recurrent pterygium by interphase-fluorescence in situ hybridization.

Science.gov (United States)

Kamis, Umit; Kerimoglu, Hurkan; Ozkagnici, Ahmet; Acar, Hasan

2006-01-01

To investigate chromosome 17 numerical aberrations by using fluorescence in situ hybridization (FISH) in pterygia and to find out whether there is any association between chromosome 17 aneuploidy and recurrent pterygia. Pterygium tissue samples were taken from 21 patients by surgical excision. Eighteen of them had primary and 3 had recurrent pterygium. Peripheral whole blood interphase cells obtained from 11 healthy subjects were assigned as control group. The cells from pterygium tissue and peripheral blood were incubated with a hypotonic solution and fixed in order to obtain interphase nuclei. FISH analysis with chromosome-17-specific alpha-satellite DNA probe was performed on both the interphase nuclei of pterygium tissue (of patients) and peripheral whole blood cells of controls. The mean percentage of chromosome 17 aneuploidy was 4.71% for the pterygia group and 4.41% for the controls. No significant difference of chromosome 17 aneuploidy was observed between the patients and the controls. When the group of patients with recurrences was compared with the group without recurrences, there was a significant difference in the frequency of chromosome 17 aneuploidy (U = 17, p = 0.029). Chromosome 17 aneuploidy is probably not an important factor in the formation of pterygium, but it may be related to recurrence.

Correlation of FDG-PET and MRI/CT with histopathology in primary diagnosis, lymph node staging and diagnosis of recurrency of head and neck cancer

International Nuclear Information System (INIS)

Poepperl, G.; Tiling, R.; Hahn, K.; Tatsch, K.; Lang, S.; Dagdelen, O.; Jaeger, L.

2002-01-01

Aim: Correct staging of head and neck cancer is important for the patient's prognosis and further therapeutic strategies. Aim of the present study was to investigate the diagnostic value of FDG-PET regarding the pre-surgical diagnosis of primary tumor and cervical lymph node metastases, the diagnosis of tumour recurrence, and the localisation of unknown primary, further to compare the results to those of morphological imaging modalities (CT/MRI) and to correlate the results of both methods with histopathological findings. Patients/Methods: 115 patients (pts) (72 x primary diagnosis, 37 x recurrence, and 6 x unknown primary) underwent FDG-PET (ECAT EXACT HR+) and CT or MRI. Results were correlated with histopathological findings in terms of detection of primary and recurrent tumors as well as lymph node metastases. Results: Regarding the pre-surgical diagnosis, sensitivity and specificity for identifying primary tumors were 85% and 100% for PET and 88% and 75% for CT/MRI, respectively. Accuracy was 86% for PET and 87% for CT/MRI. Sensitivity and specificity for detecting primary lymph node envolvement were 71%/86% for PET and 68% with morphological imaging. In 23 pts histopathology revealed pT1 stages with tumor diameters [de

Risk of Local Recurrence of Benign and Borderline Phyllodes Tumors

DEFF Research Database (Denmark)

Borhani-Khomani, Kaveh; Talman, Maj-Lis Møller; Kroman, Niels

2016-01-01

women aged 18 years or older, operated from 1999 to 2014, with resected benign or borderline PTs. Information on age, size of primary tumor and recurrence, histological grade, surgical treatment, margin size, and local recurrence were collected from the national Danish Pathology Register. RESULTS.......1-192). We identified 30 local recurrences, i.e., a recurrence rate of 6.3 %. Twenty-three recurrences had similar or lower histological grading than the primary tumor, one primary benign PT recurred as a tumor with unclear diagnosis, and one primary borderline PT recurred as malignant. The number...

Characteristics and dynamics of cognitive impairment in patients with primary and recurrent cerebral ischemic hemispheric stroke

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A. A. Kozyolkin

2014-08-01

Full Text Available Acute cerebrovascular disease is a global medical and social problem of the modern angioneurology, occupying leading positions in the structure of morbidity and mortality among adult population of the world. Ischemic stroke – is one of the most common pathology. Today this disease took out the world pandemic. More than 16 million new cases of cerebral infarction recorded in the world each year and it “kills” about 7 million of people. About 111,953 cases of cerebral stroke were registered in 2013 in Ukraine. Cognitive impairment, t hat significantly disrupt daily activities and life of the patient, is one of the most significant post-stroke complications that have social, medical and biological significance. Aim. The purpose of this investigation was to study features and dynamics of cognitive impairments in patients with primary and recurrent cerebral hemispheric ischemic stroke (CHIS in the acute stage of the disease. Materials and methods. To achieve the aim, and the decision of tasks in the clinic of nervous diseases Zaporozhye State Medical University (supervisor - Doctor of Medicine, Professor Kozelkin A. based on the department of acute cerebrovascular disease were performed comparative, prospective cohort study, which included comprehensive clinical and paraclinical examinations of 41 patients (26 men and 15 women aged 45 to 85 years (mean age 66,4 ± 1,4 years with acute left-hemispheric (2 patients and right - hemispheric (39 patients CHIS . First up was a group of 28 patients (19 men and 9 women, mean age 65,6 ± 1,6 years, who suffered from primary CHIS. The second group consisted of 13 patients (7 men and 6 women, mean age 68,1 ± 2,5 years with recurrent CHIS. The groups were matched by age, sex, localization of the lesion and the initial level of neurological deficit. All patients underwent physical examination, neurological examination. Dynamic clinical neurological examination assessing the severity of stroke was conducted

Primary CNS Nonamyloidogenic Light Chain Deposition Disease: Case Report and Brief Review.

Science.gov (United States)

Mercado, Juan Jose; Markert, James M; Meador, William; Chapman, Philip; Perry, Arie; Hackney, James R

2017-12-01

The true incidence of light chain deposition disease (LCDD) restricted to the central nervous system (CNS) is unknown. To our knowledge only 7 cases of LCDD restricted to the brain have been previously reported. We herein describe an unusual example. A 44-year-old man presented with a history of ischemic retinopathy in 2004 and left lower extremity hypoesthesia in 2007 that progressed gradually to left-sided weakness and numbness in the 2 years prior to his hospitalization in 2015. A stereotactic brain biopsy was performed, displaying nonspecific hyaline deposits of amorphous "amyloid-like" material involving deep brain white matter and vessels. These were Congo red negative and were accompanied by a sparse lymphoplasmacytic infiltrate. Plasma cells demonstrated kappa light chain class restriction by chromogenic in situ hybridization (CISH). There was patchy reactivity with kappa immunohistochemistry in the amorphous deposits. A diagnosis of light chain deposition disease was made. Subsequent systemic myeloma and lymphoma workups were negative. Previously reported cases have included men and women, spanning the ages of 19 and 72 years, often presenting with hemiparesis, hypoesthesia, or seizures. Deposits have been reported in the cerebrum and cerebellum. T2/FLAIR (fluid attenuation inversion recovery) changes are usual, but lesions may or may not produce contrast enhancement. The light chain deposition may be of kappa or lambda class. Most lesions have been accompanied by local lymphoid and/or plasma cell infiltrates exhibiting light chain restriction of the same class as the deposits. In summary, LCDD limited to the CNS is a rare lesion consisting of deposition of amyloid-like, but Congo red-negative monotypic light chain usually produced by local lymphoplasmacytic infiltrates.

Menopausal status dependence of the timing of breast cancer recurrence after surgical removal of the primary tumour

International Nuclear Information System (INIS)

Demicheli, Romano; Bonadonna, Gianni; Hrushesky, William JM; Retsky, Michael W; Valagussa, Pinuccia

2004-01-01

Information on the metastasis process in breast cancer patients undergoing primary tumour removal may be extracted from an analysis of the timing of clinical recurrence. The hazard rate for local-regional and/or distant recurrence as the first event during the first 4 years after surgery was studied in 1173 patients undergoing mastectomy alone as primary treatment for operable breast cancer. Subset analyses were performed according to tumour size, axillary nodal status and menopausal status. A sharp two-peaked hazard function was observed for node-positive pre-menopausal patients, whereas results from node-positive post-menopausal women always displayed a single broad peak. The first narrow peak among pre-menopausal women showed a very steep rise to a maximum about 8–10 months after mastectomy. The second peak was considerably broader, reaching its maximum at 28–30 months. Post-menopausal patients displayed a wide, nearly symmetrical peak with maximum risk at about 18–20 months. Peaks displayed increasing height with increasing axillary lymph node involvement. No multi-peaked pattern was evident for either pre-menopausal or post-menopausal node-negative patients; however, this finding should be considered cautiously because of the limited number of events. Tumour size influenced recurrence risk but not its timing. Findings resulting from the different subsets of patients were remarkably coherent and each observed peak maintained the same position on the time axis in all analysed subsets. The risk of early recurrence for node positive patients is dependent on menopausal status. The amount of axillary nodal involvement and the tumour size modulate the risk value at any given time. For pre-menopausal node-positive patients, the abrupt increase of the first narrow peak of the recurrence risk suggests a triggering event that synchronises early risk. We suggest that this event is the surgical removal of the primary tumour. The later, broader, more symmetrical risk

P-glycoprotein trafficking as a therapeutic target to optimize CNS drug delivery.

Science.gov (United States)

Davis, Thomas P; Sanchez-Covarubias, Lucy; Tome, Margaret E

2014-01-01

The primary function of the blood-brain barrier (BBB)/neurovascular unit is to protect the central nervous system (CNS) from potentially harmful xenobiotic substances and maintain CNS homeostasis. Restricted access to the CNS is maintained via a combination of tight junction proteins as well as a variety of efflux and influx transporters that limits the transcellular and paracellular movement of solutes. Of the transporters identified at the BBB, P-glycoprotein (P-gp) has emerged as the transporter that is the greatest obstacle to effective CNS drug delivery. In this chapter, we provide data to support intracellular protein trafficking of P-gp within cerebral capillary microvessels as a potential target for improved drug delivery. We show that pain-induced changes in P-gp trafficking are associated with changes in P-gp's association with caveolin-1, a key scaffolding/trafficking protein that colocalizes with P-gp at the luminal membrane of brain microvessels. Changes in colocalization with the phosphorylated and nonphosphorylated forms of caveolin-1, by pain, are accompanied by dynamic changes in the distribution, relocalization, and activation of P-gp "pools" between microvascular endothelial cell subcellular compartments. Since redox-sensitive processes may be involved in signaling disassembly of higher-order structures of P-gp, we feel that manipulating redox signaling, via specific protein targeting at the BBB, may protect disulfide bond integrity of P-gp reservoirs and control trafficking to the membrane surface, providing improved CNS drug delivery. The advantage of therapeutic drug "relocalization" of a protein is that the physiological impact can be modified, temporarily or long term, despite pathology-induced changes in gene transcription. © 2014 Elsevier Inc. All rights reserved.

Effects on DHEA levels by estrogen in rat astrocytes and CNS co-cultures via the regulation of CYP7B1-mediated metabolism

DEFF Research Database (Denmark)

Fex Svenningsen, Åsa; Wicher, Grzegorz; Lundqvist, Johan

2011-01-01

The neurosteroid dehydroepiandrosterone (DHEA) is formed locally in the CNS and has been implicated in several processes essential for CNS function, including control of neuronal survival. An important metabolic pathway for DHEA in the CNS involves the steroid hydroxylase CYP7B1. In previous...... studies, CYP7B1 was identified as a target for estrogen regulation in cells of kidney and liver. In the current study, we examined effects of estrogens on CYP7B1-mediated metabolism of DHEA in primary cultures of rat astrocytes and co-cultures of rat CNS cells. Astrocytes, which interact with neurons...... whereby estrogen can exert protective effects in the CNS may involve increase of the levels of DHEA by suppression of its metabolism....

Recurrence of Crystalline Nephropathy after Kidney Transplantation in APRT Deficiency and Primary Hyperoxaluria

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Guillaume Bollée

2015-09-01

Full Text Available Purpose of review: To provide transplant physicians with a summary of the pathogenesis and diagnosis of adenine phosphoribosyl transferase (APRT deficiency and primary hyperoxaluria and, focussed on kidney transplantation, and to discuss interventions aimed at preventing and treating the recurrence of crystalline nephropathy in renal transplant recipients. Source of information: Pubmed literature search. Setting: Primary hyperoxaluria and APRT deficiency are rare inborn errors of human metabolism. The hallmark of these diseases is the overproduction and urinary excretion of compounds (2,8 dihydroxyadenine in APRT deficiency, oxalate in primary hyperoxaluria that form urinary crystals. Although recurrent urolithiasis represents the main clinical feature of these diseases, kidney injury can occur as a result of crystal precipitation within the tubules and interstitium, a condition referred to as crystalline nephropathy. Some patients develop end-stage renal disease (ESRD and may become candidates for kidney transplantation. Since kidney transplantation does not correct the underlying metabolic defect, transplant recipients have a high risk of recurrence of crystalline nephropathy, which can lead to graft loss. In some instances, the disease remains undiagnosed until after the occurrence of ESRD or even after kidney transplantation. Key messages: Patients with APRT deficiency or primary hyperoxaluria may develop ESRD as a result of crystalline nephropathy. In the absence of diagnosis and adequate management, the disease is likely to recur after kidney transplantation, which often leads to rapid loss of renal allograft function. Primary hyperoxaluria, but not APRT deficiency, becomes a systemic disease at low GFR with oxalate deposition leading to malfunction in non-renal organs (systemic oxalosis. We suggest that these diagnoses should be considered in patients with low glomerular filtration rate (GFR and a history of kidney stones. In APRT

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

NARCIS (Netherlands)

Gast, M.C.; van Tinteren, H.; Bontenbal, M.; van Hoesel, R.Q.; Nooij, M.A.; Rodenhuis, S.; Span, P.N.; Tjan-Heijnen, V.C.; de Vries, E.G.; Harris, N.; Twisk, J.W.R.; Schellens, J.H.; Beijnen, J.H.

2008-01-01

Background: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods: Two

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

NARCIS (Netherlands)

M.C.W. Gast; H. van Tinteren (Harm); M. Bontenbal (Marijke); R.Q.G.C.M. van Hoesel (René); M.A. Nooij; S. Rodenhuis (Sjoerd); P.N. Span (Paul); V.C.G. Tjan-Heijnen (Vivianne); E. de Vries (Esther); N. Harris (Nathan); J.W.R. Twisk (Jos); J.H.M. Schellens (Jan); J.H. Beijnen (Jos)

2008-01-01

textabstractBackground: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

NARCIS (Netherlands)

Gast, Marie-Christine W.; van Tinteren, Harm; Bontenbal, Marijke; van Hoesel, Rene Q. G. C. M.; Nooij, Marianne A.; Rodenhuis, Sjoerd; Span, Paul N.; Tjan-Heijnen, Vivianne C. G.; de Vries, Elisabeth G. E.; Harris, Nathan; Twisk, Jos W. R.; Schellens, Jan H. M.; Beijnen, Jos H.

2008-01-01

ABSTRACT: BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients.

NARCIS (Netherlands)

Gast, M.C.; Tinteren, H. van; Bontenbal, M.; Hoesel, R.Q. van; Nooij, M.A.; Rodenhuis, S.; Span, P.N.; Tjan-Heijnen, V.C.; Vries, E.G.F. de; Harris, N.; Twisk, J.W.R.; Schellens, J.H.; Beijnen, J.H.

2008-01-01

BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two

Robotic Image-Guided Stereotactic Radiotherapy, for Isolated Recurrent Primary, Lymph Node or Metastatic Prostate Cancer

International Nuclear Information System (INIS)

Jereczek-Fossa, Barbara Alicja; Beltramo, Giancarlo; Fariselli, Laura; Fodor, Cristiana; Santoro, Luigi; Vavassori, Andrea; Zerini, Dario; Gherardi, Federica; Ascione, Carmen; Bossi-Zanetti, Isa; Mauro, Roberta; Bregantin, Achille; Bianchi, Livia Corinna; De Cobelli, Ottavio; Orecchia, Roberto

2012-01-01

Purpose: To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)–based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. Methods and Materials: Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [ 11 C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). Results: The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. Conclusions: CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor

Recurrent endometrial cancer: patterns of recurrent disease and assessment of prognosis

Energy Technology Data Exchange (ETDEWEB)

Sohaib, S.A. [Department of Radiology, Royal Marsden Hospital, London (United Kingdom); Houghton, S.L. [Department of Radiology, Royal Marsden Hospital, London (United Kingdom); Meroni, R. [Department of Academic Radiology, St Bartholomew' s Hospital, London (United Kingdom); Rockall, A.G. [Department of Academic Radiology, St Bartholomew' s Hospital, London (United Kingdom); Blake, P. [Department of Gynaecological Oncology, Royal Marsden Hospital, London (United Kingdom); Reznek, R.H. [Department of Academic Radiology, St Bartholomew' s Hospital, London (United Kingdom)

2007-01-15

Aim: To evaluate patterns of disease and identify factors predicting outcome in patients presenting with recurrent endometrial adenocarcinoma following primary surgery. Materials and methods: A retrospective review was performed of the imaging and clinical data in 86 patients (median age 66 years, range 42-88 years) presenting with recurrent endometrial adenocarcinoma following primary surgery. Results: Following primary surgery recurrent disease occurred within 2 years in 64% and within 3 years in 87%. Relapse was seen within lymph nodes in 41 (46%), the vagina in 36 (42%) the peritoneum in 24 (28%) and the lung in 21 (24%). Unusual sites of disease included spleen, pancreas, rectum, muscle and brain. Univariate survival analysis showed the factors significant for poor outcome were: multiple sites of disease, liver and splenic disease, haematogenous, peritoneal and nodal spread, poorly differentiated tumour, and early relapse. The presence of disease within the vagina, bladder or lung was not associated with poor prognosis. Multivariate analysis identified multiple sites of disease, liver and splenic metastases to be independent predictors of poor outcome. Conclusion: The most frequently observed sites of relapse are: lymph nodes, vagina, peritoneum and lung. Significant predictors of poor outcome in recurrent disease are multiple sites of disease and liver and splenic metastases.

An invertebrate model for CNS drug discovery

DEFF Research Database (Denmark)

Al-Qadi, Sonia; Schiøtt, Morten; Hansen, Steen Honoré

2015-01-01

BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple,...... barriers. CONCLUSION: Findings suggest a conserved mechanism of brain efflux activity between insects and vertebrates, confirming that this model holds promise for inexpensive and high-throughput screening relative to in vivo models, for CNS drug discovery....

Re-recurrence after operation for recurrent inguinal hernia. A nationwide 8-year follow-up study on the role of type of repair

DEFF Research Database (Denmark)

Bisgaard, Thue; Bay-Nielsen, M.; Kehlet, H.

2008-01-01

the surgical strategy and results after recurrent inguinal hernia repairs. METHODS: Prospective recording of all primary and subsequent recurrent inguinal hernia repairs from January 1, 1998 to December 31, 2005, in the national Danish Hernia Database, using the reoperation rate as a proxy for recurrence...... = 1124) was significantly reduced after laparoscopic operation for recurrence (1.3% (95% CI: 0.4-3.0)) compared with open repairs for recurrence (Lichtenstein 11.3% (8.2-15.2), nonmesh 19.2% (14.0-25.4), mesh (non-Lichtenstein) 7.2% (4.0 - 11.8)). After primary nonmesh (n = 616), non-Lichtenstein mesh (n...... = 277), and laparoscopic repair (n = 100) there was no significant difference in re-reoperation rates between a laparoscopic repair and all open techniques of repair for recurrence. CONCLUSION: Laparoscopic repair is recommended for reoperation of a recurrence after primary open Lichtenstein repair...

Interstitial brachytherapy with 192-IR in treatment of recurrent malignant primary brain tumors

International Nuclear Information System (INIS)

Cardenes, R.; Martinez, R.; Victoria, C.; Nunez, L.; Clavo, B.; Sancedo, G.

1994-01-01

Seven patients with recurrent malignant primary brain tumors after surgery and radiation therapy were treated at the Clinica Puerta de Hierro (Madrid) by interstitial brachytherapy with 192-Ir sources. Implantations were performed using computerized tomography and dose prescription were determined following the Paris system rules for interstitial implants. The means dose deliberated was 50 to 65 Gy to the reference isodoses. At the last follow-up all patients except for one are alive and without evidence of progression of the disease. (Author) 35 refs

Transnasal endoscopic medial maxillectomy in recurrent maxillary sinus inverted papilloma.

Science.gov (United States)

Kamel, Reda H; Abdel Fattah, Ahmed F; Awad, Ayman G

2014-12-01

Maxillary sinus inverted papilloma entails medial maxillectomy and is associated with high incidence of recurrence. To study the impact of prior surgery on recurrence rate after transnasal endoscopic medial maxillectomy. Eighteen patients with primary and 33 with recurrent maxillary sinus inverted papilloma underwent transnasal endoscopic medial maxillectomy. Caldwell-Luc operation was the primary surgery in 12 patients, transnasal endoscopic resection in 20, and midfacial degloving technique in one. The follow-up period ranged between 2 to 19.5 years with an average of 8.8 years. Recurrence was detected in 8/51 maxillary sinus inverted papilloma patients (15.7 %), 1/18 of primary cases (5.5 %), 7/33 of recurrent cases (21.2 %); 3/20 of the transnasal endoscopic resection group (15%) and 4/12 of the Caldwell-Luc group (33.3%). Redo transnasal endoscopic medial maxillectomy was followed by a single recurrence in the Caldwell-Luc group (25%), and no recurrence in the other groups. Recurrence is more common in recurrent maxillary sinus inverted papilloma than primary lesions. Recurrent maxillary sinus inverted papilloma after Caldwell-Luc operation has higher incidence of recurrence than after transnasal endoscopic resection.

Carbon-ion radiotherapy for locally advanced primary or postoperative recurrent epithelial carcinoma of the lacrimal gland

International Nuclear Information System (INIS)

Mizoguchi, Nobutaka; Tsuji, Hiroshi; Toyama, Shingo; Kamada, Tadashi; Tsujii, Hirohiko; Nakayama, Yuko; Mizota, Atsushi; Ohnishi, Yoshitaka

2015-01-01

Purpose: To evaluate the applicability of carbon ion beams for the treatment of carcinoma of the lacrimal gland with regard to normal tissue morbidity and local tumor control. Methods and materials: Between April 2002 and January 2011, 21 patients with locally advanced primary epithelial carcinoma of the lacrimal gland were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy (CIRT) at the National Institute of Radiological Sciences. Acute radiation toxicity was the primary endpoint of this dose-escalation study and the late toxicity, local control, and overall survival were additionally evaluated as secondary endpoints. Of the 21 subjects enrolled, all patients were followed for more than 6 months and analyzed. Results: The radiation dose was increased from the initial dose of 48.0 Gy equivalents (GyE)/12 fractions at 10% increments up to 52.8 GyE. Of the 21 patients, five received a total dose of 48.0 GyE, and 16 received a total dose of 52.8 GyE. No patient developed grade 3 or higher skin toxicity. As late ocular/visual toxicity, three patients had grade 3 retinopathy and seven patients lost their vision. Among the 10 patients treated until May 2005, five patients had local recurrence, three of whom had marginal recurrence. Therefore, the margin for the CTV (clinical target volume) was set to a range according to the orbital exenteration since June 2005. After the application of the extended margin, no local recurrence has been observed. The three-year overall survival and local control rates were 82.2% and 79.0%, respectively. Conclusion: CIRT can be applied for primary epithelial carcinoma of the lacrimal gland, with a borderline acceptable morbidity and sufficient antitumor effect when an extended margin is adopted

CNS infections in immunocompetent patients

International Nuclear Information System (INIS)

Hartmann, K.M.; Zimmer, A.; Reith, W.

2008-01-01

This article gives a review of the most frequent infective agents reasonable for CNS infections in immunocompetent patients as well as their localisation and imaging specifications. MRI scanning is the gold standard to detect inflammatory conditions in the CNS. Imaging can be normal or nonspecifically altered although the infection is culturally or bioptically proven. There are no pathognomonic, pathogen-specific imaging criteria. The localization and dimension of the inflammation depends on the infection pathway. (orig.) [de

Expression and lymphatic microvessel density in primary tumors of node-neagtive colorectal cancer patients predict disease recurrence

NARCIS (Netherlands)

Doekhie, F.S.; Morreau, H.; de Bock, G.H.; Speetjens, F.M.; Dekker-Ensink, N.G.; Putter, H.; vand e Velde, C.J.H.; Tollenaar, R.A.E.M.; Kuppen, P.J.K.; Sialyl lewis, X.

2008-01-01

Up to 30% of curatively resected colorectal cancer patients with tumor-negative lymph nodes, show disease recurrence. We assessed whether these high-risk patients can be identified by examining primary tumors for the following blood and lymphatic vasculature markers: A) sialyl Lewis X (sLeX),

Bovine-associated CNS species resist phagocytosis differently

Science.gov (United States)

2013-01-01

Background Coagulase-negative staphylococci (CNS) cause usually subclinical or mild clinical bovine mastitis, which often remains persistent. Symptoms are usually mild, mostly only comprising slight changes in the appearance of milk and possibly slight swelling. However, clinical mastitis with severe signs has also been reported. The reasons for the differences in clinical expression are largely unknown. Macrophages play an important role in the innate immunity of the udder. This study examined phagocytosis and killing by mouse macrophage cells of three CNS species: Staphylococcus chromogenes (15 isolates), Staphylococcus agnetis (6 isolates) and Staphylococcus simulans (15 isolates). Staphylococcus aureus (7 isolates) was also included as a control. Results All the studied CNS species were phagocytosed by macrophages, but S. simulans resisted phagocytosis more effectively than the other CNS species. Only S. chromogenes was substantially killed by macrophages. Significant variations between isolates were seen in both phagocytosis and killing by macrophages and were more common in the killing assays. Significant differences between single CNS species and S. aureus were observed in both assays. Conclusion This study demonstrated that differences in the phagocytosis and killing of mastitis-causing staphylococci by macrophages exist at both the species and isolate level. PMID:24207012

Effectiveness of leukocyte immunotherapy in primary recurrent spontaneous abortion (RSA).

Science.gov (United States)

Gharesi-Fard, Behrouz; Zolghadri, Jaleh; Foroughinia, Leila; Tavazoo, Fahimeh; Samsami Dehaghani, Alamtaj

2007-09-01

Recurrent spontaneous abortion (RSA) is defined as three or more sequential abortions before the twentieth week of gestation. There are evidences to support an allo-immunologic mechanism for RSA. One of the methods for treatment of RSA is leukocyte therapy; however there is still controversy about effectiveness of this method. To evaluate the effectiveness of leukocyte therapy for treatment of RSA. Ninety two non-pregnant women with at least three sequential abortions (60 primary & 32 secondary aborters) recognized as RSA were referred to our Laboratory for immunotherapy. All the cases were immunized by isolated lymphocytes from their husbands. Fifty to 100 million washed and resuspended mononuclear cells were injected by I.V., S.C., and I.D. route. The result of each injection was checked by WBC cross matching between couples after four weeks of injections. Immunization was repeated in fifth week to a maximum of 3 times if needed. Eighty one age-matched non-pregnant RSA women (52 primary and 29 secondary aborters) with at least three sequential abortions were also included in this study as controls. The control group was not immunized. 67 out of 92 (72.8%) immunized cases and 44 out of 81 controls (54.3%) showed a successful outcome of pregnancy (pRSA patients. Despite the current controversy and limitation of leukocyte therapy in RSA, the results of our investigation provide evidence supporting the use of allo-immunization in improving the outcome of pregnancy in primary RSA patients.

Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas.

Science.gov (United States)

Felsberg, Jörg; Thon, Niklas; Eigenbrod, Sabina; Hentschel, Bettina; Sabel, Michael C; Westphal, Manfred; Schackert, Gabriele; Kreth, Friedrich Wilhelm; Pietsch, Torsten; Löffler, Markus; Weller, Michael; Reifenberger, Guido; Tonn, Jörg C

2011-08-01

Epigenetic silencing of the O(6) -methylguanine-DNA methyltransferase (MGMT) gene promoter is associated with prolonged survival in glioblastoma patients treated with temozolomide (TMZ). We investigated whether glioblastoma recurrence is associated with changes in the promoter methylation status and the expression of MGMT and the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 in pairs of primary and recurrent glioblastomas of 80 patients, including 64 patients treated with radiotherapy and TMZ after the first operation. Among the primary tumors, the MGMT promoter was methylated in 31 patients and unmethylated in 49 patients. In 71 patients (89%), the MGMT promoter methylation status of the primary tumor was retained at recurrence. MGMT promoter methylation, but not MGMT protein expression, was associated with longer progression-free survival, overall survival and postrecurrence survival (PRS). Moreover, PRS was increased under salvage chemotherapy. Investigation of primary and recurrent glioblastomas of 43 patients did not identify promoter methylation in any of the four MMR genes. However, recurrent glioblastomas demonstrated significantly lower MSH2, MSH6 and PMS2 protein expression as detected by immunohistochemistry. In conclusion, reduced expression of MMR proteins, but not changes in MGMT promoter methylation, is characteristic of glioblastomas recurring after the current standards of care. Copyright © 2011 UICC.

Effects on functional outcome after IORT-containing multimodality treatment for locally advanced primary and locally recurrent rectal cancer

NARCIS (Netherlands)

Mannaerts, GHH; Rutten, HJT; Martijn, H; Hanssens, PEJ; Wiggers, T

2002-01-01

Purpose: In the treatment of patients with locally advanced primary or locally recurrent rectal cancer, much attention is focused on. the oncologic outcome. Little is known about the functional outcome. In this study, the functional outcome after a multimodality treatment for locally advanced

CNS embryonal tumours: WHO 2016 and beyond.

Science.gov (United States)

Pickles, J C; Hawkins, C; Pietsch, T; Jacques, T S

2018-02-01

Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours. This integration of histological features with genetic information has significantly changed the diagnostic work-up and reporting of tumours of the CNS. However, this remains challenging in embryonal tumours due to their previously unaccounted tumour heterogeneity. We describe the recent revisions made to the 4th edition of the WHO classification of CNS tumours and review the main changes, while highlighting some of the more common diagnostic testing strategies. © 2017 British Neuropathological Society.

Malignant lymphoma in central nervous system (CNS)

International Nuclear Information System (INIS)

Fujiyoshi, Kenji; Fukuyama, Hidenao; Akiguchi, Ichiro; Kameyama, Masakuni; Nishimura, Toshio.

1984-01-01

A 71-year-old male was admitted to Kohka Public Hospital on January 4, 1980, because of frequent vomiting and recent memory loss. Two weeks before admission upper G-I series showed no abnormalities. Physical and neurological examinations revealed no abnormalities except for slightly apathetic appearance and recent memory loss. Mild pleocytosis and marked increase of protein in CSF were observed. CT scan on January 17 showed high density areas in both medial sides of temporal lobes with remarkable contrast enhancement. His memory and, consciousness disturbances gradually aggravated, accompanied by abnormal density spreading around the ventricle walls like ventriculitis. He was transfered to Kyoto University Hospital on March 17, and malignant lymphoma was diagnosed on the basis of CSF cytology. Radiation and chemotherapy alleviated the CNS involvement and he regained normal mental function. On June 16, he developed pneumonia followed by status epilepticus. Autopsy findings revealed no lymphoid cell infiltration, but fibrous tissues in both hippocampal gyri and lymphomatous cells in the liver, which could not be suspected on clinical examinations. Apparent malignant lymphoma cells were not found in lymph nodes. This case indicated peculiar evolution of malignant lymphoma from liver to CNS or vice versa. We could not decide which organ was primary. CT findings of this case was very interesting; they resembled ventriculitis, which simulate tumors such as medulloblastoma or ependymoma spreading under ependymal lining. (author)

Evaluation of several FDG PET parameters for prediction of soft tissue tumour grade at primary diagnosis and recurrence

Energy Technology Data Exchange (ETDEWEB)

Fendler, Wolfgang P. [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Department of Nuclear Medicine, Munich (Germany); Chalkidis, Rebecca P.; Ilhan, Harun [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Knoesel, Thomas [Ludwig-Maximilians-University of Munich, Institute of Pathology, Munich (Germany); Herrmann, Ken [Julius-Maximilians-University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Issels, Rolf D.; Lindner, Lars H. [Ludwig-Maximilians-University of Munich, Department of Internal Medicine III, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Bartenstein, Peter [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Cyran, Clemens C. [Ludwig-Maximilians-University of Munich, Department of Clinical Radiology, Munich (Germany); Hacker, Marcus [Vienna General Hospital, Department of Nuclear Medicine, Vienna (Austria)

2015-08-15

This study evaluates the diagnostic accuracy of SUV-based parameters derived from [{sup 18} F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in order to optimize non-invasive prediction of soft tissue tumour (STT) grade. One hundred and twenty-nine lesions from 123 patients who underwent FDG-PET for primary staging (n = 79) or assessment of recurrence (n = 44) of STT were analyzed retrospectively. Histopathology was the reference standard for tumour grading. Absolute values and tumour-to-liver ratios of several standardized uptake value (SUV) parameters were correlated with tumour grading. At primary diagnosis SUV{sub max}, SUV{sub peak}, SUV{sub max}/SUV{sub liver} and SUV{sub peak}/SUV{sub liver} showed good correlation with tumour grade. SUV{sub peak} (area under the receiver-operating-characteristic, AUC-ROC: 0.82) and SUV{sub peak}/SUV{sub liver} (AUC-ROC: 0.82) separated best between low grade (WHO intermediate, grade 1 sarcoma, and low risk gastrointestinal stromal tumours, GISTs) and high grade (grade 2/3 sarcoma and intermediate/high risk GISTs) lesions: optimal threshold for SUV{sub peak}/SUV{sub liver} was 2.4, which resulted in a sensitivity of 79 % and a specificity of 81 %. At disease recurrence, the AUC-ROC was <0.75 for each parameter. A tumour SUV{sub peak} of at least 2.4 fold mean liver uptake predicts high grade histopathology with good diagnostic accuracy at primary staging. At disease recurrence, FDG-PET does not reliably separate high and low grade lesions. (orig.)

Maintenance pharmacotherapy for recurrent major depressive disorder in primary care: A 5-year follow-up study.

Science.gov (United States)

Riihimäki, K; Vuorilehto, M; Isometsä, E

2017-03-01

Most practice guidelines recommend maintenance antidepressant treatment for recurrent major depressive disorder. However, the degree to which such guidance is actually followed in primary health care has remained obscure. We investigated the provision of maintenance antidepressant treatment within a representative primary care five-year cohort study. In the Vantaa Primary Care Depression Study, a stratified random sample of 1119 adult patients was screened for depression using the Prime-MD. Depressive and comorbid psychiatric disorders were diagnosed using SCID-I/P and SCID-II interviews. Of the 137 patients with depressive disorders, 82% completed the prospective five-year follow-up. A graphic life chart enabling evaluation of the longitudinal course of episodes plus duration of pharmacotherapies was used. In accordance with national guidelines, an indication for maintenance treatment was defined to exist after three or more lifetime major depressive episodes (MDEs); maintenance treatment was to commence four months after onset of full remission. Of the cohort patients, 34% (46/137) had three or more lifetime MDEs, thus indicating the requirement for maintenance pharmacotherapy. Of these, half (54%, 25/46) received maintenance treatment, for only 29% (489/1670) of the months indicated. In this cohort of depressed primary care patients, half of patients with indications for maintenance treatment actually received it, and only for a fraction of the time indicated. Antidepressant maintenance treatment for the prevention of recurrences is unlikely to be subject to large-scale actualization as recommended, which may significantly undermine the potential public health benefits of treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Recurrent Anion Gap Acidosis: An Unusual Presentation of X-Linked Adrenoleukodystrophy in a Five-year-old Male.

Science.gov (United States)

Schwab, Joel; Pena, Loren; Sigman, Laura; Waggoner, Darrel

2010-01-01

We are presenting a five-year-old male with recurrent anion gap acidosis. During his last admission, it was detected that he had elevated VLCFA and the evaluation discovered that he had X-linked Adrenooleukodystrophy. He had the Addisonian only phenotype without any clinical or radiographic CNS findings. We were unable to find any other reports of this presentation of ALD. If the work-up of recurrent anion gap acidosis does not uncover an etiology, X-linked ALD should be considered in the differential diagnosis.

Immunostimulatory sutures that treat local disease recurrence following primary tumor resection

Energy Technology Data Exchange (ETDEWEB)

Intra, Janjira; Zhang Xueqing; Salem, Aliasger K [Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242 (United States); Williams, Robin L; Zhu Xiaoyan [Department of Surgery, Roy J and Lucille Carver College of Medicine, University of Iowa, Iowa City, IA 52242 (United States); Sandler, Anthony D, E-mail: aliasger-salem@uiowa.edu [Department of Surgery and Center for Cancer and Immunology Research, Children' s National Medical Center, Washington DC 20010 (United States)

2011-02-15

Neuroblastoma is a common childhood cancer that often results in progressive minimal residual disease after primary tumor resection. Cytosine-phosphorothioate-guanine oligonucleotides (CpG ODN) have been reported to induce potent anti-tumor immune responses. In this communication, we report on the development of a CpG ODN-loaded suture that can close up the wound following tumor excision and provide sustained localized delivery of CpG ODN to treat local disease recurrence. The suture was prepared by melt extruding a mixture of polylactic acid-co-glycolic acid (PLGA 75:25 0.47 dL g{sup -1}) pellets and CpG ODN 1826. Scanning electron microscopy images showed that the sutures were free of defects and cracks. UV spectrophotometry measurements at 260 nm showed that sutures provide sustained release of CpG ODN over 35 days. Syngeneic female A/J mice were inoculated subcutaneously with 1 x 10{sup 6} Neuro-2a murine neuroblastoma wild-type cells and tumors were grown between 5 to 10 mm before the tumors were excised. Wounds from the tumor resection were closed using CpG ODN-loaded sutures and/or polyglycolic acid Vicryl suture. Suppression of neuroblastoma recurrence and mouse survival were significantly higher in mice where wounds were closed using the CpG ODN-loaded sutures relative to all other groups. (communication)

Innate Interferons Regulate CNS Inflammation

DEFF Research Database (Denmark)

Dieu, Ruthe; Khorooshi, Reza M. H.; Mariboe, Anne

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) whose pathology is characterised by demyelination and axonal damage. This results from interplay between CNS-resident glia, infiltrating leukocytes and a plethora of cytokines and chemokines. Currently...... potential IFN-inducing receptor that signals through NF-kB. Receptor activator of NF-kB (RANK) belongs to the TNF-receptor superfamily and has been shown to induce IFN-beta in medullary thymic epithelial cells affecting autoimmune regulatory processes and osteoclast precursor cells in association to bone...

Air pollution: mechanisms of neuroinflammation and CNS disease.

Science.gov (United States)

Block, Michelle L; Calderón-Garcidueñas, Lilian

2009-09-01

Air pollution has been implicated as a chronic source of neuroinflammation and reactive oxygen species (ROS) that produce neuropathology and central nervous system (CNS) disease. Stroke incidence and Alzheimer's and Parkinson's disease pathology are linked to air pollution. Recent reports reveal that air pollution components reach the brain; systemic effects that impact lung and cardiovascular disease also impinge upon CNS health. While mechanisms driving air pollution-induced CNS pathology are poorly understood, new evidence suggests that microglial activation and changes in the blood-brain barrier are key components. Here we summarize recent findings detailing the mechanisms through which air pollution reaches the brain and activates the resident innate immune response to become a chronic source of pro-inflammatory factors and ROS, culminating in CNS disease.

[18F]fluoroethylcholine-PET/CT imaging for radiation treatment planning of recurrent and primary prostate cancer with dose escalation to PET/CT-positive lymph nodes

Directory of Open Access Journals (Sweden)

Wahl Andreas

2011-05-01

Full Text Available Abstract Background At present there is no consensus on irradiation treatment volumes for intermediate to high-risk primary cancers or recurrent disease. Conventional imaging modalities, such as CT, MRI and transrectal ultrasound, are considered suboptimal for treatment decisions. Choline-PET/CT might be considered as the imaging modality in radiooncology to select and delineate clinical target volumes extending the prostate gland or prostate fossa. In conjunction with intensity modulated radiotherapy (IMRT and imaged guided radiotherapy (IGRT, it might offer the opportunity of dose escalation to selected sites while avoiding unnecessary irradiation of healthy tissues. Methods Twenty-six patients with primary (n = 7 or recurrent (n = 19 prostate cancer received Choline-PET/CT planned 3D conformal or intensity modulated radiotherapy. The median age of the patients was 65 yrs (range 45 to 78 yrs. PET/CT-scans with F18-fluoroethylcholine (FEC were performed on a combined PET/CT-scanner equipped for radiation therapy planning. The majority of patients had intermediate to high risk prostate cancer. All patients received 3D conformal or intensity modulated and imaged guided radiotherapy with megavoltage cone beam CT. The median dose to primary tumours was 75.6 Gy and to FEC-positive recurrent lymph nodal sites 66,6 Gy. The median follow-up time was 28.8 months. Results The mean SUVmax in primary cancer was 5,97 in the prostate gland and 3,2 in pelvic lymph nodes. Patients with recurrent cancer had a mean SUVmax of 4,38. Two patients had negative PET/CT scans. At 28 months the overall survival rate is 94%. Biochemical relapse free survival is 83% for primary cancer and 49% for recurrent tumours. Distant disease free survival is 100% and 75% for primary and recurrent cancer, respectively. Acute normal tissue toxicity was mild in 85% and moderate (grade 2 in 15%. No or mild late side effects were observed in the majority of patients (84%. One patient had

Infection or Glioma? The False Dilemma of Primary Central Nervous System Histiocytic Sarcoma.

Science.gov (United States)

Clifton, William; Akinduro, Oluwaseun Oluwadara; Lopez-Chiriboga, Sebastian; Whitaker, Dale Alan; Reimer, Ronald

2017-10-01

Primary central nervous system (CNS) histiocytic sarcoma is an extremely rare lymphoproliferative disorder that affects the CNS and behaves aggressively. Only 27 cases of primary CNS histiocytic sarcoma have been reported. The paucity of literature on this entity has made diagnosis and treatment difficult both for the surgeon and the pathologist. In this case of primary CNS histiocytic sarcoma, a middle-aged woman presented from an outside institution with a supposed cerebellar abscess. Intraoperative frozen pathology was initially interpreted as high-grade glioma; however, final pathology demonstrated histiocytic sarcoma. This report makes a significant contribution to the literature on this rare malignant disease by outlining a similar presentation among several cases and providing a thorough overview of existing criteria for diagnosis and management. Copyright © 2017 Elsevier Inc. All rights reserved.

Phase I/IIa study of intratumoral/intracerebral or intravenous/intracerebral administration of Parvovirus H-1 (ParvOryx) in patients with progressive primary or recurrent glioblastoma multiforme: ParvOryx01 protocol

International Nuclear Information System (INIS)

Geletneky, Karsten; Hajda, Jacek; Huesing, Johannes; Rommelaere, Jean; Schlehofer, Joerg R; Leuchs, Barbara; Dahm, Michael; Krebs, Ottheinz; Knebel Doeberitz, Magnus von; Huber, Bernard

2012-01-01

The treatment of patients with malignant brain tumors remains a major oncological problem. The median survival of patients with glioblastoma multiforme (GBM), the most malignant type, is only 15 months after initial diagnosis and even less after tumor recurrence. Improvements of standard treatment including surgery and radio-chemotherapy have not lead to major improvements. Therefore, alternative therapeutics such as oncolytic viruses that specifically target and destroy cancer cells are under investigation. Preclinical data of oncolytic parvovirus H-1 (H-1PV) infection of glioma cells demonstrated strong cytotoxic and oncosuppressing effects, leading to a phase I/IIa trial of H-1PV in patients with recurrent GBM (ParvOryx01). ParvOryx01 is the first trial with a replication competent oncolytic virus in Germany. ParvOryx01 is an open, non-controlled, two groups, intra-group dose escalation, single center, phase I/IIa trial. 18 patients with recurrent GBM will be treated in 2 groups of 9 patients each. Treatment group 1 will first receive H-1PV by intratumoral injection and second by administration into the walls of the tumor cavity during tumor resection. In treatment group 2 the virus will initially be injected intravenously and afterwards, identical to group 1, into the surrounding brain tissue during tumor removal. Main eligibility criteria are: age of 18 years, unifocal recurrent GBM, amenable to complete or subtotal resection. Dose escalation will be based on the Continual Reassessment Method. The primary objective of the trial is local and systemic safety and tolerability and to determine the maximum tolerated dose (MTD). Secondary objectives are proof of concept (PoC) and Progression-free Survival (PFS) up to 6 months. This is the first trial with H-1PV in patients with recurrent GBM. The risks for the participants appear well predictable and justified. Furthermore, ParvOryx01 will be the first assessment of combined intratumoral and intravenous application

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

Directory of Open Access Journals (Sweden)

Harris Nathan

2008-12-01

Full Text Available Abstract Background Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63 were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS for biomarker finding. Initial results were validated by analysis of sample set II (n = 371, using one-dimensional gel-electrophoresis. Results In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity ≤ 20 or > 20, identified as haptoglobin (Hp alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014. Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2, of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 – 1.34, p = 0.5221 and 1.03 (95% CI: 0.65 – 1.64, p = 0.8966 for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. Conclusion In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive

Recurrent hepatoblastoma with localization by PET-CT

Energy Technology Data Exchange (ETDEWEB)

Figarola, Maria S.; McQuiston, Samuel A. [University of South Alabama, Department of Radiology, Mobile, AL (United States); Wilson, Felicia [University of South Alabama, Pediatric Hematology-Oncology, Mobile, AL (United States); Powell, Randall [University of South Alabama, Surgery Department, Mobile, AL (United States)

2005-12-01

Hepatoblastoma is the most common primary liver tumor in children, accounting for 79% of pediatric liver malignancies in children younger than 15 years, with most cases reported before the age of 5 years. Localization of primary and recurrent disease is necessary for appropriate clinical decision-making and treatment. We present a case of recurrent hepatoblastoma heralded by rising alpha-fetoprotein levels. After unsuccessful localization by conventional CT and MRI, positron emission tomography CT imaging localized the sites of recurrence. (orig.)

High Nrf2 expression in alveolar type I pneumocytes is associated with low recurrences in primary spontaneous pneumothorax.

Science.gov (United States)

Chen, Yu-Wen; Chiu, Wen-Chin; Chou, Shah-Hwa; Su, Yu-Han; Huang, Ying-Fong; Lee, Yen-Lung; Yuan, Shyng-Shiou F; Lee, Yi-Chen

2017-10-01

Recurrent primary spontaneous pneumothorax (PSP) is a troublesome problem and a major concern for the patients. This study examined whether nuclear factor erythroid 2-related factor 2 (Nrf2) expression in alveolar type I pneumocytes was associated with the clinical manifestations of PSP patients including disease recurrence. Eighty-eight PSP patients who were managed with needlescopic video-assisted thoracoscopic surgery (NVATS) were included in this study. Immunohistochemistry (IHC) was assessed to determine Nrf2 expression in resected lung tissues and the results were correlated with clinicopathological characteristics by the chi-square or the Fisher's exact test. The prognostic value of Nrf2 for overall recurrence was evaluated by univariate and multivariable Cox regression model. The expression of Nrf2 was observed in type I pneumocytes of lung tissues from PSP patients by IHC. We found that low Nrf2 expression in PSP patients, especially in young (age ≤ 20, p = 0.033) and body mass index (BMI) ≥18 kg/m 2 (p = 0.019) groups, was significantly correlated with PSP recurrence. In the univariate and multivariate analyses, high Nrf2 expression was a significant protective factor for overall recurrence in PSP patients (univariate: p = 0.026; multivariate: p = 0.004). The expression level of Nrf2 in alveolar type I pneumocytes was a potential factor involved in PSP recurrence. Our findings suggest that elevated Nrf2 expression in PSP patients may be a promising way for reducing PSP recurrence. Copyright © 2017. Published by Elsevier Taiwan.

Biomarkers for CNS involvement in pediatric lupus

Science.gov (United States)

Rubinstein, Tamar B; Putterman, Chaim; Goilav, Beatrice

2015-01-01

CNS disease, or central neuropsychiatric lupus erythematosus (cNPSLE), occurs frequently in pediatric lupus, leading to significant morbidity and poor long-term outcomes. Diagnosing cNPSLE is especially difficult in pediatrics; many current diagnostic tools are invasive and/or costly, and there are no current accepted screening mechanisms. The most complicated aspect of diagnosis is differentiating primary disease from other etiologies; research to discover new biomarkers is attempting to address this dilemma. With many mechanisms involved in the pathogenesis of cNPSLE, biomarker profiles across several modalities (molecular, psychometric and neuroimaging) will need to be used. For the care of children with lupus, the challenge will be to develop biomarkers that are accessible by noninvasive measures and reliable in a pediatric population. PMID:26079959

CNS adverse events associated with antimalarial agents. Fact or fiction?

NARCIS (Netherlands)

Phillips-Howard, P. A.; ter Kuile, F. O.

1995-01-01

CNS adverse drug events are dramatic, and case reports have influenced clinical opinion on the use of antimalarials. Malaria also causes CNS symptoms, thus establishing causality is difficult. CNS events are associated with the quinoline and artemisinin derivatives. Chloroquine, once considered too

3rd ENRI International Workshop on ATM/CNS

CERN Document Server

2014-01-01

The Electronic Navigation Research Institute (ENRI) held its third　International Workshop on ATM / CNS in 2013 with the theme of "Drafting　the future sky". There is worldwide activity taking place in the research and development　of modern air traffic management (ATM) and its enabling technologies in　Communication, Navigation and Surveillance (CNS). Pioneering work is necessary to contribute to the global harmonization　of air traffic management and control. At this workshop, leading experts　in  research, industry and academia from around the world met to share　their ideas and approaches on ATM/CNS related topics.

CNS penetration of ART in HIV-infected children

NARCIS (Netherlands)

van den Hof, Malon; Blokhuis, Charlotte; Cohen, Sophie; Scherpbier, Henriette J.; Wit, Ferdinand W. N. M.; Pistorius, M. C. M.; Kootstra, Neeltje A.; Teunissen, Charlotte E.; Mathot, Ron A. A.; Pajkrt, Dasja

2018-01-01

Background: Paediatric data on CNS penetration of antiretroviral drugs are scarce. Objectives: To evaluate CNS penetration of antiretroviral drugs in HIV-infected children and explore associations with neurocognitive function. Patients and methods: Antiretroviral drug levels were measured in paired

RECURRENT CROUP IN CHILDREN

Directory of Open Access Journals (Sweden)

S. L. Piskunova

2014-01-01

Full Text Available The article presents the results of examination of 1849 children, entering children's infectioushospitalofVladivostokwith the clinical picture of croup of viral etiology. The clinical features of primary and recurrent croup are described. Frequency of recurrent croup inVladivostokis 8%. Children with a recurrent croup had the burdened premorbid background, and also persistent herpetic infections (cytomegalic infection in 42,9% cases, cytomegalic infection in combination with the herpes simplex virus -1. Frequency of croups substantially rose in the period of epidemic of influenza.

Growth of breast cancer recurrences assessed by consecutive MRI

International Nuclear Information System (INIS)

Millet, Ingrid; Bouic-Pages, Emmanuelle; Hoa, Denis; Azria, David; Taourel, Patrice

2011-01-01

Women with a personal history of breast cancer have a high risk of developing an ipsi- or contralateral recurrence. We aimed to compare the growth rate of primary breast cancer and recurrences in women who had undergone prior breast magnetic resonance imaging (MRI). Three hundred and sixty-two women were diagnosed with breast cancer and had undergone breast MRI at the time of diagnosis in our institution (2005 - 2009). Among them, 37 had at least one prior breast MRI with the lesion being visible but not diagnosed as cancer. A linear regression of tumour volume measured on MRI scans and time data was performed using a generalized logistic model to calculate growth rates. The primary objective was to compare the tumour growth rate of patients with either primary breast cancer (no history of breast cancer) or ipsi- or contralateral recurrences of breast cancer. Twenty women had no history of breast cancer and 17 patients were diagnosed as recurrences (7 and 10 were ipsi- and contralateral, respectively). The tumour growth rate was higher in contralateral recurrences than in ipsilateral recurrences (growth rate [10 -3 days -1 ] 3.56 vs 1.38, p < .001) or primary cancer (3.56 vs 2.09, p = 0.01). Differences in tumour growth were not significant for other patient-, tumour- or treatment-related characteristics. These findings suggest that contralateral breast cancer presents accelerated growth compared to ipsilateral recurrences or primary breast events

Complex treatment of primary brain neuroblastoma with four local recurrences for period of 5 years -clinical case from our practice

International Nuclear Information System (INIS)

Marinova, L.; Georgiev, R.; Mihaylova, I.; Belcheva, M.

2017-01-01

We present a clinical case of 17 years old girl with primary brain neuroblastoma (supratentorial primitive neuro-ectodermal tumor - PNET in right temporo-parietal brain region). Complex treatment has been applied, including subtotal operation, standard fractioned cranio-spinal external beam radiotherapy with boost up to 56 Gy in the locus of the tumor remnant and 6 courses of adjuvant chemotherapy with Carboplatin and Etoposide. Despite the applied local treatment methods (radical surgery, standard fractioned cranio-spinal external beam radiotherapy and radio-surgery with single total dose of 14 Gy), four recurrences have appeared for period of 5 years in the locus of the primary tumor. The risk of appearance of local recurrences, necessitating re-operations, chemotherapy, bone marrow transplantation of stem cells and radio-surgery was discussed. We are also discussing the radio sensitivity of the PNET and the possibilities for overcoming it with implementation of hyper fractioned cranio-spinal external beam radiotherapy in combination with chemotherapy, followed by bone marrow transplantation of stem cells. Key words: Primary Brain Neuroblastoma. Radio Sensitivity. Cranio-Spinal External Beam Radiotherapy. Adjuvant Chemotherapy [bg

Recurrence in affective disorder

DEFF Research Database (Denmark)

Kessing, L V; Olsen, E W; Andersen, P K

1999-01-01

The risk of recurrence in affective disorder is influenced by the number of prior episodes and by a person's tendency toward recurrence. Newly developed frailty models were used to estimate the effect of the number of episodes on the rate of recurrence, taking into account individual frailty toward...... recurrence. The study base was the Danish psychiatric case register of all hospital admissions for primary affective disorder in Denmark during 1971-1993. A total of 20,350 first-admission patients were discharged with a diagnosis of major affective disorder. For women with unipolar disorder and for all...... kinds of patients with bipolar disorder, the rate of recurrence was affected by the number of prior episodes even when the effect was adjusted for individual frailty toward recurrence. No effect of episodes but a large effect of the frailty parameter was found for unipolar men. The authors concluded...

Does Full Wound Rupture following Median Pilonidal Closure Alter Long-Term Recurrence Rate?

Science.gov (United States)

Doll, Dietrich; Matevossian, Edouard; Luedi, Markus M; Schneider, Ralf; van Zypen, Dominic; Novotny, Alexander

2015-01-01

The purpose of this study was to examine the recurrence rate of wound rupture in primary pilonidal sinus disease (PSD) after median closure. A total of 583 patients from the German military cohort were interviewed. We compared the choice of surgical therapy, wound dehiscence (if present) and long-term recurrence-free survival for patients with primary open treatment, marsupialization and primary median treatment (closed vs. secondary open, respectively). Actuarial recurrence rate was determined using the Kaplan-Meier calculation with a follow-up of up to 20 years after primary PSD surgery. Patients with excision followed by primary open wound treatment showed a significantly lower 5- than 10-year recurrence rate (8.3 vs. 11.2%) compared to the patients with primary midline closure (17.4 vs. 20.5%, p = 0.03). The 20-year recurrence rate was 28% in primary open wound treatment versus 44% in primary midline closure without wound rupture. In contrast to these findings, long-term recurrence rates following secondary open wound treatment (12.2% at 5 years vs. 17.1% at 10 years) tended to be higher (although not significantly, p = 0.57) compared to primary open treatment (8.3% at 5 years vs. 11.2% at 10 years). There was no statistical difference in long-term recurrence rates between secondary open and primary midline closure (p = 0.7). Hence, despite only a short wound closure time experienced before wound rupture, the patient does not fully benefit from an open wound treatment in terms of recurrence rate. The postoperative pilonidal sinus wound rupture of primary midline closures did not significantly increase the 5- and 10-year long-term recurrence rates compared to uneventfully healing primary midline closures. © 2015 S. Karger AG, Basel.

An evaluation of factors predicting breast recurrence and prognosis after recurrence, on distinguishing intramammary and extramammary recurrence, in breast-conserving surgery

Energy Technology Data Exchange (ETDEWEB)

Nishimura, Reiki; Nagao, Kazuharu; Miyayama, Haruhiko [Kumamoto City Hospital (Japan)] (and others)

2001-06-01

Recurrence of cancer in the breast is an important problem in breast-conserving therapy. We evaluated risk factors for recurrence from the viewpoint of recurrence type and outcome after recurrence. Of 533 cases of breast cancer treated with breast-conserving surgery from April 1989 through July 2000, disease in 66 recurred (12.4%) and were classified as 23 cases of breast recurrence only, 16 cases of both breast recurrence and distant metastasis, and 27 cases of distant metastasis only. The clinical factors examined included age, lymphatic invasion, nodal status, extensive intraductal component (EIC), proliferative activity, and estrogen receptor (ER) status. Of the 39 cases of breast recurrence, 19 had intramammary tumors and 20 had extramammary tumors of the skin, subcutaneous tissue, or muscle, including 8 cases with inflammatory breast recurrence. Multivariate analysis showed that factors correlated with breast recurrence were age, ER status, proliferative activity, and surgical margin. EIC-comedo was related to intramammary recurrence, whereas lymphatic invasion and nodal status were related to extramammary recurrence. Postoperative irradiation was an effective treatment for tumors in young women and tumors with positive margins or a comedo component. Outcome after breast recurrence depended on nodal status at primary operation, and survival rates were worst in patients with inflammatory breast recurrence. In conclusion, age, EIC-comedo status, the surgical margin, and negative ER status were correlated with breast recurrence. Countermeasures against these factors should be investigated. (author)

An evaluation of factors predicting breast recurrence and prognosis after recurrence, on distinguishing intramammary and extramammary recurrence, in breast-conserving surgery

International Nuclear Information System (INIS)

Nishimura, Reiki; Nagao, Kazuharu; Miyayama, Haruhiko

2001-01-01

Recurrence of cancer in the breast is an important problem in breast-conserving therapy. We evaluated risk factors for recurrence from the viewpoint of recurrence type and outcome after recurrence. Of 533 cases of breast cancer treated with breast-conserving surgery from April 1989 through July 2000, disease in 66 recurred (12.4%) and were classified as 23 cases of breast recurrence only, 16 cases of both breast recurrence and distant metastasis, and 27 cases of distant metastasis only. The clinical factors examined included age, lymphatic invasion, nodal status, extensive intraductal component (EIC), proliferative activity, and estrogen receptor (ER) status. Of the 39 cases of breast recurrence, 19 had intramammary tumors and 20 had extramammary tumors of the skin, subcutaneous tissue, or muscle, including 8 cases with inflammatory breast recurrence. Multivariate analysis showed that factors correlated with breast recurrence were age, ER status, proliferative activity, and surgical margin. EIC-comedo was related to intramammary recurrence, whereas lymphatic invasion and nodal status were related to extramammary recurrence. Postoperative irradiation was an effective treatment for tumors in young women and tumors with positive margins or a comedo component. Outcome after breast recurrence depended on nodal status at primary operation, and survival rates were worst in patients with inflammatory breast recurrence. In conclusion, age, EIC-comedo status, the surgical margin, and negative ER status were correlated with breast recurrence. Countermeasures against these factors should be investigated. (author)

Advising potential recipients on the use of organs from donors with primary central nervous system tumors.

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Warrens, Anthony N; Birch, Rhiannon; Collett, David; Daraktchiev, Maren; Dark, John H; Galea, George; Gronow, Katie; Neuberger, James; Hilton, David; Whittle, Ian R; Watson, Christopher J E

2012-02-27

Deciding to use an organ from a donor with a primary central nervous system (CNS) tumor necessitates offsetting the risk of tumor transmission with the chances of survival if the patient waits for another offer of a transplant. Published data vary in the quoted risk of tumor transmission. We used data obtained by reviewing 246 UK recipients of organs taken from donors with CNS tumors and found no evidence of a difference in overall patient mortality for recipients of a kidney, liver, or cardiothoracic organ, compared with recipients of organs from donors without a CNS tumor. Recent publication of the UK experience of transplanting organs from CNS tumor donors found no transmission in 448 recipients of organs from 177 donors with a primary CNS tumor (Watson et al., Am J Transplant 2010; 10: 1437). This 0% transmission rate is associated with an upper 95% confidence interval limit of 1.5%. Using a series of assumptions of risk, we compared the risks of dying as a result of the transmission of a primary brain tumor with the risks of dying if not transplanted. On this basis, the use of kidneys from a donor with a primary CNS tumor provides a further 8 years of life over someone who waited for a donor who did not have a primary CNS tumor, in addition to the life years gained by the transplant itself. The benefits for the recipients of livers and cardiothoracic organs were less, but there was no disadvantage in the impact on life expectancy.

A comparative study of propranolol versus silver nitrate cautery in the treatment of recurrent primary epistaxis in children

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Ahmed, Ahmed E; Abo El-Magd, Essam A; Hasan, Gamal M; El-Asheer, Osama M

2015-01-01

Background Epistaxis is a common medical problem in pediatric population. Although in most cases it is mild and self-limiting, a proportion of childhood epistaxis is massive, recurrent, or resistant to conventional management. Objective To compare effectiveness of propranolol as a treatment option for childhood epistaxis versus conventional silver nitrate cautery. Study design and methodology This is a prospective interventional comparative study that was carried out during a period of 1 year (January 1, 2013 to December 31, 2013) at Qena University Hospital and Assiut University Children’s Hospital. One hundred children aged 6–12 years who presented with epistaxis to Qena University Hospital and Assiut University Children’s Hospital during the study period and fulfilling the inclusion criteria were included in the study. They were randomly assigned into one of two interventional groups, where 50 children were treated with oral propranolol (propranolol treatment group) and another 50 children were treated with conventional silver nitrate cautery (cauterization treatment group) for their epistaxis. Propranolol was given at a dose of 1.5–2 mg/kg/day (divided into three doses). Patients were followed for 6 months after their discharge for recurrence of epistaxis. Results Both groups of patients showed minimal recurrent epistaxis with rates of 14% for propranolol treated group and 12% for cauterization group, with no statistically significant difference between both groups. Local pain was found to be more in patients treated with silver nitrate cauterization. Conclusion Treatment of primary epistaxis with propranolol or silver nitrate cautery showed equal rates of recurrence, and local nasal pain was slightly more among silver nitrate cauterization treated group. Propranolol could be a favorable treatment option for patients with primary epistaxis. Further studies that include multiple centers and larger number of patients are recommended for more clarification

Effects on functional outcome after IORT-containing multimodality treatment for locally advanced primary and locally recurrent rectal cancer

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Mannaerts, Guido H.H.; Rutten, Harm J.T.; Martijn, Hendrik; Hanssens, Patrick E.J.; Wiggers, Theo

2002-01-01

Purpose: In the treatment of patients with locally advanced primary or locally recurrent rectal cancer, much attention is focused on the oncologic outcome. Little is known about the functional outcome. In this study, the functional outcome after a multimodality treatment for locally advanced primary and locally recurrent rectal cancer is analyzed. Methods and Materials: Between 1994 and 1999, 55 patients with locally advanced primary and 66 patients with locally recurrent rectal cancer were treated with high-dose preoperative external beam irradiation, followed by extended surgery and intraoperative radiotherapy. To assess long-term functional outcome, all patients still alive (n = 97) were asked to complete a questionnaire regarding ongoing morbidity, as well as functional and social impairment. Seventy-six of the 79 patients (96%) returned the questionnaire. The median follow-up was 14 months (range: 4-60 months). Results: The questionnaire revealed fatigue in 44%, perineal pain in 42%, radiating pain in the leg(s) in 21%, walking difficulties in 36%, and voiding dysfunction in 42% of the patients as symptoms of ongoing morbidity. Functional impairment consisted of requiring help with basic activities in 15% and sexual inactivity in 56% of the respondents. Social handicap was demonstrated by loss of former lifestyle in 44% and loss of professional occupation in 40% of patients. Conclusions: As a result of multimodality treatment, the majority of these patients have to deal with long-term physical morbidity, the need for help with daily care, and considerable social impairment. These consequences must be weighed against the chance of cure if the patient is treated and the disability eventually caused by uncontrolled tumor progression if the patient is not treated. These potential drawbacks should be discussed with the patient preoperatively and taken into account when designing a treatment strategy

Mer tyrosine kinase promotes the survival of t(1;19)-positive acute lymphoblastic leukemia (ALL) in the central nervous system (CNS).

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Krause, Sarah; Pfeiffer, Christian; Strube, Susanne; Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Loges, Sonja; Waizenegger, Jonas; Ben-Batalla, Isabel; Cario, Gunnar; Möricke, Anja; Stanulla, Martin; Schrappe, Martin; Schewe, Denis M

2015-01-29

Patients with t(1;19)-positive acute lymphoblastic leukemia (ALL) are prone to central nervous system (CNS) relapses, and expression of the TAM (Tyro3, Axl, and Mer) receptor Mer is upregulated in these leukemias. We examined the functional role of Mer in the CNS in preclinical models and performed correlative studies in 64 t(1;19)-positive and 93 control pediatric ALL patients. ALL cells were analyzed in coculture with human glioma cells and normal rat astrocytes: CNS coculture caused quiescence and protection from methotrexate toxicity in Mer(high) ALL cell lines, which was antagonized by short hairpin RNA-mediated knockdown of Mer. Mer expression was upregulated, prosurvival Akt and mitogen-activated protein kinase signaling were activated, and secretion of the Mer ligand Galectin-3 was stimulated. Mer(high) t(1;19) primary cells caused CNS involvement to a larger extent in murine xenografts than in their Mer(low) counterparts. Leukemic cells from Mer(high) xenografts showed enhanced survival in coculture. Treatment of Mer(high) patient cells with the Mer-specific inhibitor UNC-569 in vivo delayed leukemia onset, reduced CNS infiltration, and prolonged survival of mice. Finally, a correlation between high Mer expression and CNS positivity upon initial diagnosis was observed in t(1;19) patients. Our data provide evidence that Mer is associated with survival in the CNS in t(1;19)-positive ALL, suggesting a role as a diagnostic marker and therapeutic target. © 2015 by The American Society of Hematology.

PEG minocycline-liposomes ameliorate CNS autoimmune disease.

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Wei Hu

Full Text Available Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE.Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number.Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.

The farnesoid-X-receptor in myeloid cells controls CNS autoimmunity in an IL-10-dependent fashion.

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Hucke, Stephanie; Herold, Martin; Liebmann, Marie; Freise, Nicole; Lindner, Maren; Fleck, Ann-Katrin; Zenker, Stefanie; Thiebes, Stephanie; Fernandez-Orth, Juncal; Buck, Dorothea; Luessi, Felix; Meuth, Sven G; Zipp, Frauke; Hemmer, Bernhard; Engel, Daniel Robert; Roth, Johannes; Kuhlmann, Tanja; Wiendl, Heinz; Klotz, Luisa

2016-09-01

Innate immune responses by myeloid cells decisively contribute to perpetuation of central nervous system (CNS) autoimmunity and their pharmacologic modulation represents a promising strategy to prevent disease progression in Multiple Sclerosis (MS). Based on our observation that peripheral immune cells from relapsing-remitting and primary progressive MS patients exhibited strongly decreased levels of the bile acid receptor FXR (farnesoid-X-receptor, NR1H4), we evaluated its potential relevance as therapeutic target for control of established CNS autoimmunity. Pharmacological FXR activation promoted generation of anti-inflammatory macrophages characterized by arginase-1, increased IL-10 production, and suppression of T cell responses. In mice, FXR activation ameliorated CNS autoimmunity in an IL-10-dependent fashion and even suppressed advanced clinical disease upon therapeutic administration. In analogy to rodents, pharmacological FXR activation in human monocytes from healthy controls and MS patients induced an anti-inflammatory phenotype with suppressive properties including control of effector T cell proliferation. We therefore, propose an important role of FXR in control of T cell-mediated autoimmunity by promoting anti-inflammatory macrophage responses.

Differentiating Primary CNS Lymphoma from Malignant Glioma using 123I-IMP SPECT and Arterial Spin labeling

International Nuclear Information System (INIS)

Ito, Tamio; Sato, Kenichi; Ozaki, Yoshimaru; Asanome, Taku; Nakamura, Hirohiko; Ono, Hidetoshi

2016-01-01

Using conventional CT or MRI methods, the differentiation of primary central nervous system lymphoma (PCNSL) and malignant glioma (MG) is difficult because of overlapping imaging characteristics. Pretreatment differentiation between PCNSL and MG is essential for therapeutic decision making because post operative adjuvant therapy is extremely different. We examined the utility of N-isopropyl-p-[ 123 I]iodoamphetamine SPECT (IMP SPECT) and arterial spin labeling (ASL) in differentiating PCNSL from MG. Twenty PCNSL and ten MG patients underwent IMP SPECT and ASL. Early SPECT image (E) was initiated 20 min after intravenous injection of 222 MBq 123 I-IMP, and delayed image (D) and ultrade-layed image (UD) were initiated 3 h and 24 h, respectively, after the injection. SPECT images were visually analyzed with a color-grading scale (low, iso, and high), and the tumor-to-normal activity ratio (T/N) was calculated for all three images. The pulsed ASL was performed using a 3-T system. We set regions of interest in the tumor and symmetrically in the contralateral white matter on the cerebral blood flow (CBF) map and estimated tumor blood flow (TBF)/CBF ratio (TBF/CBF). 1) IMP SPECT: (1) Visual image analysis of PCNSL cases showed high accumulation of 123 I-IMP up-take on D and UD, whereas most MG cases showed low accumulation. (2) T/Ns of PCNSL were significantly higher than those of MG on D and UD (E: 1.13 vs. 0.95, p>0.05; D: 1.23 vs. 0.86, p<0.01; UD: 1.40 vs. 0.86, p<0.01). 2) ASL: TBF/CBFs of MG were higher than those of PCNSL, particularly in glioblastoma patients [1.84 vs. 6.22 (III; 1.51, IV; 8.58)]. IMP SPECT and ASL are helpful tools for differentiating primary CNS lymphoma from MG. Using these examinations, we could perform adjuvant therapy without biopsy in deep-seated tumors. (author)

Prophylactic CNS therapy in childhood leukemia

International Nuclear Information System (INIS)

Yokoyama, Takashi; Hiyoshi, Yasuhiko; Fujimoto, Takeo

1982-01-01

This study was designed to evaluate the efficacy of CNS-prophylaxis with high-dose methotrexate (MTX). Seventy children with previously untreated acute lymphoblastic leukemia (ALL) entered to this study between July 1978 and December 1980. According to initial white blood count (WBC), they were stratified to induce remission with; vincristine and prednine in low initial WBC ( lt 25,000/mm 3 ) group and these two agents plus adriamycin in high initial WBC ( gt 25,000/mm 3 ) group. After inducing remission, 62 children who achieved CR, received different CNS-prophlaxis; using a regimen of three doses of weekly high-dose MTX (1,000 mg/m 2 ) 6-hour infusion, which was repeated every 12 weeks-Group A (n = 14); high-dose MTX followed by 2400 rad cranial irradiation plus three doses of i.t. MT X-Group B (n = 15), 2400 rad cranial irradiation plus three doses of i.t. MTX-Group C (n = 16), and in 17 patients with high initial WBC, same as in Group A-Group D (n = 17). During an intravenous 6-h infusion of MTX at a dose of 1,000 mg/m 2 , the CSF concentration of MTX rose to 2.3 +- 2.4 x 10 -6 M after initiation of infusion and remained in 10 -7 M level for 48 hours. CNS-leukemia terminated complete remission in one of 14 children in Group A, two of 15 in Group B, two of 16 in Group C and two of 17 in Group D. The cumulative incidence of CNS-leukemia at 20 months calculated by the technique of Kaplan and Meier was 0% i n Group A, 18.1% in Group B, 7.1% in Group C and 50.8% in Group D. There was no statistical difference among Groups A, B and C. These data suggested that CNS-prophylaxis with high-dose intravenous MTX was effective as well as 2400 rad cranial irradiation plus three doses of i.t. MTX in childhood ALL with low initial WBC. (author)

Clinically Significant Prostate Cancer Local Recurrence After Radiation Therapy Occurs at the Site of Primary Tumor: Magnetic Resonance Imaging and Step-Section Pathology Evidence

International Nuclear Information System (INIS)

Pucar, Darko; Hricak, Hedvig; Shukla-Dave, Amita; Kuroiwa, Kentaro; Drobnjak, Marija; Eastham, James; Scardino, Peter T.; Zelefsky, Michael J.

2007-01-01

Purpose: To determine whether prostate cancer local recurrence after radiation therapy (RT) occurs at the site of primary tumor by retrospectively comparing the tumor location on pre-RT and post-RT magnetic resonance imaging (MRI) and using step-section pathology after salvage radical prostatectomy (SRP) as the reference standard. Methods and Materials: Nine patients with localized prostate cancer were treated with intensity modulated RT (69-86.4 Gy), and had pre-RT and post-RT prostate MRI, biopsy-proven local recurrence, and SRP. The location and volume of lesions on pre-RT and post-RT MRI were correlated with step-section pathology findings. Tumor foci >0.2 cm 3 and/or resulting in extraprostatic disease on pathology were considered clinically significant. Results: All nine significant tumor foci (one in each patient; volume range, 0.22-8.63 cm 3 ) were detected both on pre-RT and post-RT MRI and displayed strikingly similar appearances on pre-RT and post-RT MRI and step-section pathology. Two clinically insignificant tumor foci (≤0.06 cm 3 ) were not detected on imaging. The ratios between tumor volumes on pathology and on post-RT MRI ranged from 0.52 to 2.80. Conclusions: Our study provides a direct visual confirmation that clinically significant post-RT local recurrence occurs at the site of primary tumor. Our results are in agreement with reported clinical and pathologic results and support the current practice of boosting the radiation dose within the primary tumor using imaging guidance. They also suggest that monitoring of primary tumor with pre-RT and post-RT MRI could lead to early detection of local recurrence amenable to salvage treatment

Recurrent myelinoclastic diffuse sclerosis: a case report of a child with Schilder's variant of multiple sclerosis

International Nuclear Information System (INIS)

Fitzgerald, M.J.; Coleman, L.T.

2000-01-01

Myelinoclastic diffuse sclerosis (MDS, Schilder's disease) is a rare CNS demyelinating disorder affecting mainly children and usually presenting as an intracranial mass lesion. We report the first case of recurrent intracranial MDS where the third episode of demyelination involved the cervical spinal cord. This may represent a subset of the disease, which should be considered as Schilder's variant (childhood form) of multiple sclerosis. (orig.)

Autoimmune process in CNS under Cs-137 inner irradiation

International Nuclear Information System (INIS)

Lisyany, N.I.; Liubich, L.D.

1996-01-01

Autoimmune hypothesis as to the development of radiation-induced brain injuries stands high among the concepts of the CNS post-radiation damage pathogenesis. To study the changes occurring in a living organism affected by a small-dose radiation due to incorporated radionuclides as well as to create adequate models are of critical importance in the post-Chernobyl period. The effects of chronic small-dose inner radiation on the development of autoimmune responses were evaluated by determining the level of the CNS proteins and protein-induced antibodies to the CNS components. (author)

High dose rate intraoperative radiation therapy (HDR-IORT) as part of the management strategy for locally advanced primary and recurrent rectal cancer

International Nuclear Information System (INIS)

Harrison, Louis B.; Minsky, Bruce D.; Enker, Warren E.; Mychalczak, Borys; Guillem, Jose; Paty, Philip B.; Anderson, Lowell; White, Carol; Cohen, Alfred M.

1998-01-01

Purpose: Primary unresectable and locally advanced recurrent rectal cancer presents a significant clinical challenge. Local failure rates are high in both situations. Under such circumstances, there is a significant need to safely deliver tumoricidal doses of radiation in an attempt to improve local control. For this reason, we have incorporated a new approach utilizing high dose rate intraoperative radiation therapy (HDR-IORT). Methods and Materials: Between 11/92-12/96, a total of 112 patients were explored, of which 68 patients were treated with HDR-IORT, and 66 are evaluable. The majority of the 44 patients were excluded for unresectable disease or for distant metastases which eluded preoperative imaging. There were 22 patients with primary unresectable disease, and 46 patients who presented with recurrent disease. The histology was adenocarcinoma in 64 patients, and squamous cell carcinoma in four patients. In general, the patients with primary unresectable disease received preoperative chemotherapy with 5-fluorouracil (5-FU) and leucovorin, and external beam irradiation to 4500-5040 cGy, followed by surgical resection and HDR-IORT (1000-2000 cGy). In general , the patients with recurrent disease were treated with surgical resection and HDR-IORT (1000-2000 cGy) alone. All surgical procedures were done in a dedicated operating room in the brachytherapy suite, so that HDR-IORT could be delivered using the Harrison-Anderson-Mick (HAM) applicator. The median follow-up is 17.5 months (1-48 mo). Results: In primary cases, the actuarial 2-year local control is 81%. For patients with negative margins, the local control was 92% vs. 38% for those with positive margins (p = 0.002). The 2-year actuarial disease-free survival was 69%; 77% for patients with negative margins vs. 38% for patients with positive margins (p = 0.03). For patients with recurrent disease, the 2-year actuarial local control rate was 63%. For patients with negative margins, it was 82%, while it was

The Nord-Trøndelag Health Study shows increased prevalence of primary recurrent headaches among adolescents over a four-year period.

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Jacobsena, Brit A; Dyb, Grete; Hagen, Knut; Stovner, Lars J; Holmen, Turid L; Zwart, John-Anker

2017-12-29

Objective Earlier epidemiological studies have shown that headaches are frequent among adolescents, especially girls. In particular, recurrent primary headache disorders such as migraine and tension-type headaches are common complaints in this age group. Headaches are increasingly being recognized as a significant health problem in adolescents and can lead to significant disabilities by affecting their lives, their school performance and their social lives. The aim of this study was to compare the prevalence of primary headaches among adolescents aged 16-20 years in Norway in two periods. Very few replicate studies have re-evaluated the prevalence of primary headaches in this age range and it is uncertain whether the prevalence is increasing. Methods Two cross-sectional, population-based studies were conducted in Norway from 1995 to 1997 (Young-HUNT 1) and from 1999 to 2001 (Young-HUNT 2). In Young-HUNT 1, 2594 adolescents in 2nd and 3rd grade in upper secondary school (aged 16-20 years) completed a comprehensive questionnaire including one question regarding headache during the last 12 months. In addition, 1730 of the students were interviewed about their headache complaints. In Young-HUNT 2, 2373 adolescents aged 16-20 years completed the same questionnaire and 1655 were interviewed in the same way as the earlier survey. The interviews were performed by trained nurses, and respondents were asked if they had experienced recurrent headache during the last year. If so, the headache was classified as migraine (MI), tensiontype headache (TTH) or non-classifiable headache (NCH). Headache frequency during the past year was recorded according to the following categories: Less than 1 day per month (less than monthly), 1-3 days per month (monthly), 1-5 days per week (weekly), or more than 5 days per week (daily). Results The participation rate was 88% in Young-HUNT 1 and 81% in Young-HUNT 2. The overall prevalence of having had headaches during the last 12 months did not

A Phase I Study of the Combination of Sorafenib With Temozolomide and Radiation Therapy for the Treatment of Primary and Recurrent High-Grade Gliomas

International Nuclear Information System (INIS)

Den, Robert B.; Kamrava, Mitchell; Sheng, Zhi; Werner-Wasik, Maria; Dougherty, Erin; Marinucchi, Michelle; Lawrence, Yaacov R.; Hegarty, Sarah; Hyslop, Terry; Andrews, David W.; Glass, Jon; Friedman, David P.; Green, Michael R.; Camphausen, Kevin; Dicker, Adam P.

2013-01-01

Purpose: Despite recent advances in the management of high-grade and recurrent gliomas, survival remains poor. Antiangiogenic therapy has been shown to be efficacious in the treatment of high-grade gliomas both in preclinical models and in clinical trials. We sought to determine the safety and maximum tolerated dose of sorafenib when combined with both radiation and temozolomide in the primary setting or radiation alone in the recurrent setting. Methods and Materials: This was a preclinical study and an open-label phase I dose escalation trial. Multiple glioma cell lines were analyzed for viability after treatment with radiation, temozolomide, or sorafenib or combinations of them. For patients with primary disease, sorafenib was given concurrently with temozolomide (75 mg/m 2 ) and 60 Gy radiation, for 30 days after completion of radiation. For patients with recurrent disease, sorafenib was combined with a hypofractionated course of radiation (35 Gy in 10 fractions). Results: Cell viability was significantly reduced with the combination of radiation, temozolomide, and sorafenib or radiation and sorafenib. Eighteen patients (11 in the primary cohort, 7 in the recurrent cohort) were enrolled onto this trial approved by the institutional review board. All patients completed the planned course of radiation therapy. The most common toxicities were hematologic, fatigue, and rash. There were 18 grade 3 or higher toxicities. The median overall survival was 18 months for the entire population. Conclusions: Sorafenib can be safely combined with radiation and temozolomide in patients with high-grade glioma and with radiation alone in patients with recurrent glioma. The recommended phase II dose of sorafenib is 200 mg twice daily when combined with temozolomide and radiation and 400 mg with radiation alone. To our knowledge, this is the first publication of concurrent sorafenib with radiation monotherapy or combined with radiation and temozolomide.

Correlation among academic performance, recurrent abdominal pain and other factors in Year-6 urban primary-school children in Malaysia.

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Boey, C C M; Omar, A; Arul Phillips, J

2003-07-01

The present study aimed to investigate the extent to which recurrent abdominal pain and other factors were associated with academic achievement among Year-6 (12 years of age) schoolchildren. The present study was a cross-sectional survey conducted from September to November 2001. Schoolchildren were recruited from primary schools that were selected randomly from a list of all primary schools in Petaling Jaya, Malaysia, using random sampling numbers. Information concerning recurrent abdominal pain, socio-economic status, life events, demographic and other details was obtained using a combination of questionnaires and interviews. Academic achievement was assessed using a score based on the Malaysian Primary School Achievement Examination. An overall score at or above the mean was taken to indicate high academic achievement while a score below the mean indicated poor academic achievement. A total of 1971 children were studied (958 boys and 1013 girls: 1047 Malays, 513 Chinese and 411 Indians). Of these children, 456 (23.1%) fulfilled the criteria for recurrent abdominal pain. Using the method of binary logistic regression analysis, the following factors were found to be independently associated with poor academic performance: a low socio-economic status (odds ratio (OR) 1.30; 95% confidence interval (CI) 1.25-1.35); male sex (OR 1.61; 95% CI 1.26-2.05); the death of a close relative (OR 2.22; 95% CI 1.73-2.85); the divorce or separation of parents (OR 3.05; 95% CI 1.73-5.40); the commencement of work by the mother (OR 1.34; 95% CI 1.02-1.76); hospitalization of the child in the 12 months prior to the study (OR 1.83; 95% CI 1.12-3.01); lack of health-care consultation (OR 1.80; 95% CI 1.36-2.36); missing breakfast (OR 1.47; 95% CI 1.07-2.02); and lack of kindergarten education (OR 1.35; 95% CI 1.04-1.75). Many factors, such as socio-economic status and recent life events, were associated with poor academic performance. Recurrent abdominal pain did not correlate

Histogram analysis of apparent diffusion coefficient maps for differentiating primary CNS lymphomas from tumefactive demyelinating lesions.

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Lu, Shan Shan; Kim, Sang Joon; Kim, Namkug; Kim, Ho Sung; Choi, Choong Gon; Lim, Young Min

2015-04-01

This study intended to investigate the usefulness of histogram analysis of apparent diffusion coefficient (ADC) maps for discriminating primary CNS lymphomas (PCNSLs), especially atypical PCNSLs, from tumefactive demyelinating lesions (TDLs). Forty-seven patients with PCNSLs and 18 with TDLs were enrolled in our study. Hyperintense lesions seen on T2-weighted images were defined as ROIs after ADC maps were registered to the corresponding T2-weighted image. ADC histograms were calculated from the ROIs containing the entire lesion on every section and on a voxel-by-voxel basis. The ADC histogram parameters were compared among all PCNSLs and TDLs as well as between the subgroup of atypical PCNSLs and TDLs. ROC curves were constructed to evaluate the diagnostic performance of the histogram parameters and to determine the optimum thresholds. The differences between the PCNSLs and TDLs were found in the minimum ADC values (ADCmin) and in the 5th and 10th percentiles (ADC5% and ADC10%) of the cumulative ADC histograms. However, no statistical significance was found in the mean ADC value or in the ADC value concerning the mode, kurtosis, and skewness. The ADCmin, ADC5%, and ADC10% were also lower in atypical PCNSLs than in TDLs. ADCmin was the best indicator for discriminating atypical PCNSLs from TDLs, with a threshold of 556×10(-6) mm2/s (sensitivity, 81.3 %; specificity, 88.9%). Histogram analysis of ADC maps may help to discriminate PCNSLs from TDLs and may be particularly useful in differentiating atypical PCNSLs from TDLs.

Radiotherapy in Locoregional Recurrent Breast Carcinoma

International Nuclear Information System (INIS)

Ha, Sung Whan; Yang, Mi Gyoung; Chung, Woong Ki; Park, Charn Il; Bang, Yung Jue; Kim, Noe Kyung; Choe, Kuk Jin

1988-01-01

Thirty eight women with recurrent breast carcinoma involving chest wall and/or regional lymph nodes after surgery with or without systemic therapy were treated with radiation between 1979 and 1986. Among them, 5 patients were excluded from analysis because of incomplete treatment. The median follow up of survivors was 30 months (ranged 1-79 months). Fifteen (45%) patients had their disease confined to the chest wall and eighteen patients had lymph node involvement as some of their locoregional recurrent disease. Within 36 months after the initial treatment, 87% of recurrences manifested themselves. All patients had radiotherapy to at least the site of involvement. In 8 patients, recurrent tumors were treated with complete excision followed by radiation. Of the remaining 25 patients, 18(72%) had complete response (CR) following radiotherapy. The actuarial 3-year survival of all patients following locoregional recurrence was 50%. Three year survival was 24% in those 25 patients who had recurrences within 24 months of the initial treatment. For those 8 patients whose recurrences occurred after more than 24 month disease free interval, the 3-year survival was 100%. For those patients with recurrences confined to chest wall alone, 3-year survival was 57%. The patients who had lymph node involvement as part of their locoregional recurrences had a 43% 3-year survival. The majority of them developed distant metastases. Those patients who had a CR showed 63% 3-year survival. On the other hand, 1 year survival was only 33% for those patients who had a less than CR. Three patients developed carcinoma of the contralateral breast following radiotherapy. Three year survival following locoregional recurrence was 40% for patients whose initial treatment for their primary breast carcinoma was surgery and adjuvant systemic therapy. For those patients whose primary breast carcinoma was treated by surgery alone, the 3-year survival following locoregional recurrence was 71%. In

Engineering progress of CNS concept in Hanaro

International Nuclear Information System (INIS)

Choi, C.O.; Park, K.N.; Park, S.H.

1997-01-01

The Korea Atomic Energy research Institute (KAERI) strives to provide utilizing facilities on and around the Hanaro reactor in order to activate advanced researches by neutron application. As one of the facilities to be installed, the conceptual design work of CNS was started in 1996 with a project schedule of 5 years so that its installation work can be finished by the year 2000. And the major engineering targets of this CNS facility are established for a minimum physical interference with the present facilities of the Hanaro, a reach-out of very-high-gain factors in the cold neutron flux, a simplicity of the maintenance of the facility, and a safety in the operation of the facility as well as the reactor. For the conceptual design of Hanaro CNS, the experience of utilization and production of cold neutron at WWR-M reactor Gatchina, Russia has been used with that of elaborations for PIK reactor in design for neutron guide systems and instruments. (author)

Results of salvage surgery for mammary recurrence following breast-conserving therapy

International Nuclear Information System (INIS)

Kurtz, J.M.; Amalric, R.; Brandone, H.; Ayme, Y.; Spitalier, J.M.

1988-01-01

A retrospective analysis was performed of 118 surgically treated mammary recurrences, occurring following primary conservative excision and radiation therapy for clinical Stages I and II breast cancer. Actuarial cancer-specific survival following salvage surgery was 72% at 5 years and 58% at 10 years. With a median followup of 7 years, further local-regional recurrences were observed in 20 of the 118 patients, many of whom could be treated by further surgery. Actuarial survival after recurrence was significantly influenced by initial clinical stage, as well as by the disease-free interval following primary therapy, but was similar for both premenopausal and postmenopausal patients and for patients treated by radical or breast-conserving salvage operations. For recurrences after the fifth year, actuarial survival following salvage surgery was 83% and 68% at 5 and 10 years, respectively. Survival for Stage I patients was favorable regardless of disease-free interval. It is concluded that recurrences in the breast following primary treatment with limited surgery and irradiation have a considerably more favorable prognosis than that of local failures after primary radical surgery. Suggestions for the management of these recurrences are presented

Sleep disorders in children after treatment for a CNS tumour.

Science.gov (United States)

Verberne, Lisa M; Maurice-Stam, Heleen; Grootenhuis, Martha A; Van Santen, Hanneke M; Schouten-Van Meeteren, Antoinette Y N

2012-08-01

The long-term survival of children with a central nervous system (CNS) tumour is improving. However, they experience late effects, including altered habits and patterns of sleep. We evaluated the presence and type of sleep disorders and daytime sleepiness in these children, and its associations with clinical characteristics and daily performance (fatigue and psychosocial functioning). In a cross-sectional study at the outpatient clinic of the Emma Children's Hospital AMC (February-June 2010), sleep, fatigue and psychosocial functioning were analysed in 31 CNS tumour patients (mean age: 11.8years; 20 boys) and compared with 78 patients treated for a non-CNS malignancy (mean age: 9.7years; 41 boys) and norm data. Questionnaires applied were the Sleep Disorder Scale for Children, the Epworth Sleepiness Scale, the Pediatric Quality of Life Inventory, and the Strengths and Difficulties Questionnaire. Sleeping habits and endocrine deficiencies were assessed with a self-developed questionnaire. Increased somnolence was found in CNS tumour patients compared with those with a non-CNS malignancy (8.8±2.8 versus 7.5±2.7; Psleep. No specific risk factors were identified for a sleep disorder in CNS tumour patients, but their excessive somnolence was correlated with lower fatigue related quality of life (QoL) (r=-0.78, Psleep quality and diminish fatigue. © 2011 European Sleep Research Society.

Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach

NARCIS (Netherlands)

Yamamoto, Yumi; Valitalo, Pyry A.; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Beukers, Margot W.; Kokki, Hannu; Kokki, Merja; Danhof, Meindert; van Hasselt, Johan G. C.; de Lange, Elizabeth C. M.

2018-01-01

Knowledge of drug concentration-time profiles at the central nervous system (CNS) target-site is critically important for rational development of CNS targeted drugs. Our aim was to translate a recently published comprehensive CNS physiologically-based pharmacokinetic (PBPK) model from rat to human,

Applications of Genomic Sequencing in Pediatric CNS Tumors.

Science.gov (United States)

Bavle, Abhishek A; Lin, Frank Y; Parsons, D Williams

2016-05-01

Recent advances in genome-scale sequencing methods have resulted in a significant increase in our understanding of the biology of human cancers. When applied to pediatric central nervous system (CNS) tumors, these remarkable technological breakthroughs have facilitated the molecular characterization of multiple tumor types, provided new insights into the genetic basis of these cancers, and prompted innovative strategies that are changing the management paradigm in pediatric neuro-oncology. Genomic tests have begun to affect medical decision making in a number of ways, from delineating histopathologically similar tumor types into distinct molecular subgroups that correlate with clinical characteristics, to guiding the addition of novel therapeutic agents for patients with high-risk or poor-prognosis tumors, or alternatively, reducing treatment intensity for those with a favorable prognosis. Genomic sequencing has also had a significant impact on translational research strategies in pediatric CNS tumors, resulting in wide-ranging applications that have the potential to direct the rational preclinical screening of novel therapeutic agents, shed light on tumor heterogeneity and evolution, and highlight differences (or similarities) between pediatric and adult CNS tumors. Finally, in addition to allowing the identification of somatic (tumor-specific) mutations, the analysis of patient-matched constitutional (germline) DNA has facilitated the detection of pathogenic germline alterations in cancer genes in patients with CNS tumors, with critical implications for genetic counseling and tumor surveillance strategies for children with familial predisposition syndromes. As our understanding of the molecular landscape of pediatric CNS tumors continues to advance, innovative applications of genomic sequencing hold significant promise for further improving the care of children with these cancers.

Local recurrence risk after previous salvage mastectomy.

Science.gov (United States)

Tanabe, M; Iwase, T; Okumura, Y; Yoshida, A; Masuda, N; Nakatsukasa, K; Shien, T; Tanaka, S; Komoike, Y; Taguchi, T; Arima, N; Nishimura, R; Inaji, H; Ishitobi, M

2016-07-01

Breast-conserving surgery is a standard treatment for early breast cancer. For ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery, salvage mastectomy is the current standard surgical procedure. However, it is not rare for patients with IBTR who have received salvage mastectomy to develop local recurrence. In this study, we examined the risk factors of local recurrence after salvage mastectomy for IBTR. A total of 118 consecutive patients who had histologically confirmed IBTR without distant metastases and underwent salvage mastectomy without irradiation for IBTR between 1989 and 2008 were included from eight institutions in Japan. The risk factors of local recurrence were assessed. The median follow-up period from salvage mastectomy for IBTR was 4.6 years. Patients with pN2 or higher on diagnosis of the primary tumor showed significantly poorer local recurrence-free survival than those with pN0 or pN1 at primary tumor (p mastectomy for IBTR. Further research and validation studies are needed. (UMIN-CTR number UMIN000008136). Copyright © 2016 Elsevier Ltd. All rights reserved.

Essentials and Perspectives of Computational Modelling Assistance for CNS-oriented Nanoparticle-based Drug Delivery Systems.

Science.gov (United States)

Kisała, Joanna; Heclik, Kinga I; Pogocki, Krzysztof; Pogocki, Dariusz

2018-05-16

The blood-brain barrier (BBB) is a complex system controlling two-way substances traffic between circulatory (cardiovascular) system and central nervous system (CNS). It is almost perfectly crafted to regulate brain homeostasis and to permit selective transport of molecules that are essential for brain function. For potential drug candidates, the CNS-oriented neuropharmaceuticals as well as for those of primary targets in the periphery, the extent to which a substance in the circulation gains access to the CNS seems crucial. With the advent of nanopharmacology the problem of the BBB permeability for drug nano-carriers gains new significance. Compare to some other fields of medicinal chemistry, the computational science of nanodelivery is still prematured to offer the black-box type solutions, especially for the BBB-case. However, even its enormous complexity can be spell out the physical principles, and as such subjected to computation. Basic understanding of various physico-chemical parameters describing the brain uptake is required to take advantage of their usage for the BBB-nanodelivery. This mini-review provides a sketchy introduction into essential concepts allowing application of computational simulation to the BBB-nanodelivery design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Primary CNS lymphoma in a patient treated with azathioprine

DEFF Research Database (Denmark)

Glesner, Matilde Kanstrup; Ocias, Lukas Frans; Larsen, Thomas Stauffer

2014-01-01

with surrounding oedema. There was cerebrospinal fluid pleocytosis, and Epstein-Barr virus (EBV) DNA was detected in the spinal fluid by PCR. A brain biopsy confirmed the suspicion of primary brain lymphoma. EBV-associated primary brain lymphoma is a relevant differential diagnosis in patients with long......A 33-year-old man treated with azathioprine for 12 years for Crohn's disease presented with headache, nausea and vomiting accompanied by difficulty in putting words together and slight mental confusion. Prednisolone and antibiotics were without effect. MRI of the brain showed multiple focal lesions...

Mycobacterium tuberculosis-infected human monocytes down-regulate microglial MMP-2 secretion in CNS tuberculosis via TNFα, NFκB, p38 and caspase 8 dependent pathways

Directory of Open Access Journals (Sweden)

Elkington Paul T

2011-05-01

Full Text Available Abstract Tuberculosis (TB of the central nervous system (CNS is a deadly disease characterized by extensive tissue destruction, driven by molecules such as Matrix Metalloproteinase-2 (MMP-2 which targets CNS-specific substrates. In a simplified cellular model of CNS TB, we demonstrated that conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb, but not direct infection, unexpectedly down-regulates constitutive microglial MMP-2 gene expression and secretion by 72.8% at 24 hours, sustained up to 96 hours (P M.tb-infected monocyte-dependent networks paradoxically involves the pro-inflammatory mediators TNF-α, p38 MAP kinase and NFκB in addition to a novel caspase 8-dependent pathway.

Ectopic recurrence of craniopharyngioma: Reporting three new cases.

Science.gov (United States)

Yang, Yang; Shrestha, David; Shi, Xiang-En; Zhou, Zhongqing; Qi, Xueling; Qian, Hai

2015-04-01

Ectopic recurrence of craniopharyngioma is extremely rare following transcranial procedures of primary tumour. Here we describe 3 new cases of ectopic recurrence along the surgical route after transcranial gross total resection of primary tumour. All 3 cases are male adults--2 of them had papillary-type tumour with the other being adamantinomatous. All ectopic tumours were safely resected via repeated craniotomy. Long-term surveillance of patients with resected craniopharyngioma is essential.

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients.

Science.gov (United States)

Roth, Patrick; Keller, Andreas; Hoheisel, Jörg D; Codo, Paula; Bauer, Andrea S; Backes, Christina; Leidinger, Petra; Meese, Eckart; Thiel, Eckhard; Korfel, Agnieszka; Weller, Michael

2015-02-01

Despite improved therapeutic regimens, primary CNS lymphoma (PCNSL) remains a therapeutic challenge. A prognostic classification of PCNSL patients may represent an important step towards optimised patient-adapted therapy. However, only higher age and low Karnofsky Performance Status (KPS) have repeatedly been reported to be associated with shorter overall survival (OS). Here we characterised microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analysed by next generation sequencing. The STS group comprised 20 patients with a median OS of 3 months and was compared to 20 LTS patients with a median OS of 55 months. The cohorts were balanced for age and KPS. Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short- and long-term survivors with maximal Area Under Curve (AUC) above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time polymerase chain reaction (PCR) in a validation cohort consisting of 20 STS and LTS patients. In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Permanent I-125 interstitial implant in the management of high grade CNS malignancies in children

International Nuclear Information System (INIS)

Vaishampayan, N.; Zamorano, L.; Aronin, P.; Gaspar, L.; Canady, A.; Lattin, P.; Ezzell, G.; Yakar, D.; Chungbin, S.; Fontanesi, J.

1996-01-01

Purpose/Objective: To evaluate the efficacy and complications associated with the use of permanent I-125 interstitial implants in children with high grade CNS malignancies. Materials and Methods: Between May of 1990 and September of 1994, fourteen children received permanent I-125 interstitial implant brachytherapy as initial therapy (n=8) or at time of recurrence (n=6). Histologies included Glioblastoma Multiforme (n=2), Anaplastic Astrocytoma (n=9) and others (n=3). Pre-implant surgical procedures included: Gross Total Resection (n=2), Subtotal Resection (n=8) or Biopsy alone (n=4). Six patients received pre-implant external beam irradiation (dose range 3,500-6500 cGy) and three patients received post-implant external beam irradiation (dose range 5,040-5,060 cGy). Implant dose range was 8,294-10,368 cGy over the lifetime of the implant (median 10,368 cGy). Results: At last follow-up (median 17.5 months; range 4-56 months), eight children were alive. Six out of the eight had no evidence of disease progression while the remaining had radiologic evidence of progression. Implant complications (n=2) included skin necrosis and bone flap infection. Conclusions: Based on this initial review, we continue to investigate the use of permanent I-125 interstitial brachytherapy in the treatment of high grade CNS malignancies in children and will discuss and compare these results with those of other 'Boost' series

Opioids and breast cancer recurrence

DEFF Research Database (Denmark)

Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

2015-01-01

BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

Effects of various cone-beam computed tomography settings on the detection of recurrent caries under restorations in extracted primary teeth.

Science.gov (United States)

Kamburoğlu, Kıvanç; Sönmez, Gül; Berktaş, Zeynep Serap; Kurt, Hakan; Özen, Doĝukan

2017-06-01

The aim of this study was to assess the ex vivo diagnostic ability of 9 different cone-beam computed tomography (CBCT) settings in the detection of recurrent caries under amalgam restorations in primary teeth. Fifty-two primary teeth were used. Twenty-six teeth had dentine caries and 26 teeth did not have dentine caries. Black class II cavities were prepared and restored with amalgam. In the 26 carious teeth, recurrent caries were left under restorations. The other 26 intact teeth that did not have caries served as controls. Teeth were imaged using a 100×90-mm field of view and a 0.2-mm voxel size with 9 different CBCT settings. Four observers assessed the images using a 5-point scale. Kappa values were calculated to assess observer agreement. CBCT settings were compared with the gold standard using a receiver operating characteristic analysis. The area under the curve (AUC) values for each setting were compared using the chi-square test, with a significance level of α=.05. Intraobserver kappa values ranged from 0.366 to 0.664 for observer 1, from 0.311 to 0.447 for observer 2, from 0.597 to 1.000 for observer 3, and from 0.869 to 1 for observer 4. Furthermore, interobserver kappa values among the observers ranged from 0.133 to 0.814 for the first reading and from 0.197 to 0.805 for the second reading. The highest AUC values were found for setting 5 (0.5916) and setting 3 (0.5886), and were not found to be statistically significant ( P >.05). Variations in tube voltage and tube current did not affect the detection of recurrent caries under amalgam restorations in primary teeth.

Effects of various cone-beam computed tomography settings on the detection of recurrent caries under restorations in extracted primary teeth

Energy Technology Data Exchange (ETDEWEB)

Kamburoglu, Kivanc; Sonmez, Gul; Kurt, Hakan; Berktas, Zeynep Serap [Dept. of Dentomaxillofacial Radiology, Faculty of Dentistry, Ankara University, Ankara (Turkmenistan); Ozen, Dogukan [Dept. of Biostatistics, Faculty of Veterinary Medicine, Ankara University, Ankara (Turkmenistan)

2017-06-15

The aim of this study was to assess the ex vivo diagnostic ability of 9 different cone-beam computed tomography (CBCT) settings in the detection of recurrent caries under amalgam restorations in primary teeth. Fifty-two primary teeth were used. Twenty-six teeth had dentine caries and 26 teeth did not have dentine caries. Black class II cavities were prepared and restored with amalgam. In the 26 carious teeth, recurrent caries were left under restorations. The other 26 intact teeth that did not have caries served as controls. Teeth were imaged using a 100×90-mm field of view and a 0.2-mm voxel size with 9 different CBCT settings. Four observers assessed the images using a 5-point scale. Kappa values were calculated to assess observer agreement. CBCT settings were compared with the gold standard using a receiver operating characteristic analysis. The area under the curve (AUC) values for each setting were compared using the chi-square test, with a significance level of α=.05. Intraobserver kappa values ranged from 0.366 to 0.664 for observer 1, from 0.311 to 0.447 for observer 2, from 0.597 to 1.000 for observer 3, and from 0.869 to 1 for observer 4. Furthermore, interobserver kappa values among the observers ranged from 0.133 to 0.814 for the first reading and from 0.197 to 0.805 for the second reading. The highest AUC values were found for setting 5 (0.5916) and setting 3 (0.5886), and were not found to be statistically significant (P>.05). Variations in tube voltage and tube current did not affect the detection of recurrent caries under amalgam restorations in primary teeth.

Effects of various cone-beam computed tomography settings on the detection of recurrent caries under restorations in extracted primary teeth

International Nuclear Information System (INIS)

Kamburoglu, Kivanc; Sonmez, Gul; Kurt, Hakan; Berktas, Zeynep Serap; Ozen, Dogukan

2017-01-01

The aim of this study was to assess the ex vivo diagnostic ability of 9 different cone-beam computed tomography (CBCT) settings in the detection of recurrent caries under amalgam restorations in primary teeth. Fifty-two primary teeth were used. Twenty-six teeth had dentine caries and 26 teeth did not have dentine caries. Black class II cavities were prepared and restored with amalgam. In the 26 carious teeth, recurrent caries were left under restorations. The other 26 intact teeth that did not have caries served as controls. Teeth were imaged using a 100×90-mm field of view and a 0.2-mm voxel size with 9 different CBCT settings. Four observers assessed the images using a 5-point scale. Kappa values were calculated to assess observer agreement. CBCT settings were compared with the gold standard using a receiver operating characteristic analysis. The area under the curve (AUC) values for each setting were compared using the chi-square test, with a significance level of α=.05. Intraobserver kappa values ranged from 0.366 to 0.664 for observer 1, from 0.311 to 0.447 for observer 2, from 0.597 to 1.000 for observer 3, and from 0.869 to 1 for observer 4. Furthermore, interobserver kappa values among the observers ranged from 0.133 to 0.814 for the first reading and from 0.197 to 0.805 for the second reading. The highest AUC values were found for setting 5 (0.5916) and setting 3 (0.5886), and were not found to be statistically significant (P>.05). Variations in tube voltage and tube current did not affect the detection of recurrent caries under amalgam restorations in primary teeth

Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

Directory of Open Access Journals (Sweden)

Jacinta Nwamaka Nwogu

2016-01-01

Full Text Available Neurological complications associated with the human immunodeficiency virus (HIV are a matter of great concern. While antiretroviral (ARV drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.

Species distribution and in vitro antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis.

NARCIS (Netherlands)

Hamza, O.J.M.; Matee, M.I.N.; Moshi, M.J.; Simon, E.N.; Mugusi, F.; Mikx, F.H.M.; Palenstein Helderman, W.H. van; Rijs, A.J.M.M.; Ven, A.J.A.M. van der; Verweij, P.E.

2008-01-01

BACKGROUND: In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis. METHODS: A total of 296 clinical oral yeasts were isolated from 292 HIV-infected patients

Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs

Science.gov (United States)

Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A.; Thörn, Karolina; Cairns, Tina M.; Wegmann, Frank; Sattentau, Quentin J.; Eisenberg, Roselyn J.; Cohen, Gary H.; Harandi, Ali M.

2016-01-01

Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes. PMID:28082979

Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.

Science.gov (United States)

Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A; Thörn, Karolina; Cairns, Tina M; Wegmann, Frank; Sattentau, Quentin J; Eisenberg, Roselyn J; Cohen, Gary H; Harandi, Ali M

2016-01-01

Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.

CNS-directed gene therapy for lysosomal storage diseases

OpenAIRE

Sands, Mark S; Haskins, Mark E

2008-01-01

Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders usually caused by deficient activity of a single lysosomal enzyme. As most lysosomal enzymes are ubiquitously expressed, a deficiency in a single enzyme can affect multiple organ systems, including the central nervous system (CNS). At least 75% of all LSDs have a significant CNS component. Approaches such as bone marrow transplantation (BMT) or enzyme replacement therapy (ERT) can effectively treat the systemic dis...

Enteric neurons show a primary cilium.

Science.gov (United States)

Luesma, Ma José; Cantarero, Irene; Castiella, Tomás; Soriano, Mario; Garcia-Verdugo, José Manuel; Junquera, Concepción

2013-01-01

The primary cilium is a non-motile cilium whose structure is 9+0. It is involved in co-ordinating cellular signal transduction pathways, developmental processes and tissue homeostasis. Defects in the structure or function of the primary cilium underlie numerous human diseases, collectively termed ciliopathies. The presence of single cilia in the central nervous system (CNS) is well documented, including some choroid plexus cells, neural stem cells, neurons and astrocytes, but the presence of primary cilia in differentiated neurons of the enteric nervous system (ENS) has not yet been described in mammals to the best of our knowledge. The enteric nervous system closely resembles the central nervous system. In fact, the ultrastructure of the ENS is more similar to the CNS ultrastructure than to the rest of the peripheral nervous system. This research work describes for the first time the ultrastructural characteristics of the single cilium in neurons of rat duodenum myenteric plexus, and reviews the cilium function in the CNS to propose the possible role of cilia in the ENS cells. © 2012 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

A New Option for the Reconstruction of Primary or Recurrent Ischial Pressure Sores: Hamstring-Adductor Magnus Muscle Advancement Flap and Direct Closure.

Science.gov (United States)

Burm, Jin Sik; Hwang, Jungil; Lee, Yung Ki

2018-04-01

Owing to the high recurrence rates of ischial pressure sores, surgeons should consider the possibility of future secondary flap surgery during flap selection. The purpose of this article is to present a new surgical option for the reconstruction of primary or recurrent ischial pressure sores using a simple hamstring-adductor magnus advancement flap and direct closure. After horizontal fusiform skin excision, complete bursa excision and ischiectomy were performed. The tenomuscular origin of the adductor magnus and the conjoined tenomuscular origin of the biceps femoris long head and semitendinosus were isolated and completely detached from the inferior border of the ischial tuberosity. They were then advanced in a cephalad direction without detachment of the distal tendon or muscle and securely affixed to the sacrotuberous ligament. The wound was directly closed without further incision or dissection. Twelve ischial pressure sores (6 primary and 6 recurrent; 12 patients) were surgically corrected. The follow-up period was 12 to 65 months. All patients healed successfully without early postoperative complications, such as hematoma, seroma, infection, wound dehiscence, or partial necrosis. Late complications included wound disruption 5 weeks after surgery that spontaneously healed in 1 case and recurrence 3 years later in another case. The new surgical option presented herein, which involves hamstring-adductor magnus advancement flap and direct closure, is a simple and reliable method for providing sufficient muscle bulk to fill the dead space and proper padding to the bone stump while preserving the main vascular perforators and pedicles as well as future surgical options.

Salvage liver transplantation for patients with recurrent hepatocellular carcinoma after curative resection.

Directory of Open Access Journals (Sweden)

LinWei Wu

Full Text Available OBJECTIVE: To summarize the experience with salvage liver transplantation (SLT for patients with recurrent hepatocellular carcinoma (HCC after primary hepatic resection in a single center. METHODS: A total of 376 adult patients with HCC underwent orthotopic liver transplantation (OLT at Organ Transplantation Center, the First Affiliated Hospital of Sun Yat-sen University, between 2004 and 2008. Among these patients, 36 underwent SLT after primary liver curative resection due to intrahepatic recurrence. During the same period, one hundred and forty-seven patients with HCC within Milan criteria underwent primary OLT (PLTW group, the intra-operative and post-operative parameters were compared between these two groups. Furthermore, we compared tumor recurrence and patient survival of patients with SLT to 156 patients with HCC beyond Milan criteria (PLTB group. Cox Hazard regression was made to identify the risk factors for tumor recurrence. RESULTS: The median interval between initial liver resection and SLT was 35 months (1-63 months. The intraoperative blood loss (P0.05. When compared to those patients with HCC beyond Milan criteria undergoing primary OLT, patients undergoing SLT achieved a better survival and a lower tumor recurrence. Cox Proportional Hazards model showed that vascular invasion, including macrovascular and microvascular invasion, as well as AFP level >400 IU/L were risk factors for tumor recurrence after LT. CONCLUSIONS: In comparison with primary OLT, although SLT is associated with increased operation difficulties, it provides a good option for patients with HCC recurrence after curative resection.

Genetic models for CNS inflammation

DEFF Research Database (Denmark)

Owens, T; Wekerle, H; Antel, J

2001-01-01

The use of transgenic technology to over-express or prevent expression of genes encoding molecules related to inflammation has allowed direct examination of their role in experimental disease. This article reviews transgenic and knockout models of CNS demyelinating disease, focusing primarily on ...

Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence.

Science.gov (United States)

Abid, Muhammad Bilal; De Mel, Sanjay; Abid, Muhammad Abbas; Tan, Kong Bing; Chng, Wee Joo

2016-07-02

Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.

Endoluminal high dose rate brachytherapy in the treatment of primary and recurrent bronchogenic tree malignancies

Directory of Open Access Journals (Sweden)

Maria Fortunato

2009-03-01

Full Text Available Introduction: Locally advanced tumours as the initial form of presentation of tumours in the bronchial tree are not a rare event. Bronchogenic recurrence is frequent in the natural history of some tumours. The choice of therapeutic options from the raft available depends on such variables as initial therapy, place of recurrence, symptoms and patient's physical status. Aim: To demonstrate the advantages of endoluminal brachytherapy (EBT with high dose rate (HDR in primary and recurrent tumour of the bronchial tree. Material and methods: A retrospective study of seven patients (pts with primary tumours of the colon, trachea and lung. Tracheobronchial recurrence (trachea, two pts, bronchus, five pts occurred betweenMarch 2003 and September 2004. Patients under-went EBT with HDR for primary or recurrent therapy in association with external radiotherapy, laser therapy and chemotherapy with palliative or curative intention. EBT with HDR doses of 5 to 7 Gy in 2 to 4 fractions at 1 cm from the source axis were given. Treatment included endoluminal application of Ir192 with a French 6 catheter. Results: There was symptomatic relief related to reduction of tumour in six of the seven patients treated. In one of the six patients studied, there was progression of the local disease between the second and third fractions of the treatment (obstruction of the trachea. In a mean follow up of 17 (2-40 months between EBT and this study, three patients are alive, one has no evidence of disease while two have had bronchial recurrence, four patients have died, one after massive haemoptysis and three due to disease progression. Discussion and conclusions: Patients undergoing brachytherapy for symptomatic primary tumours or endobronchial recurrence show good tolerance, important symptom relief and improved quality of life. Despite the small size of our sample, it is clear that EBT with HDR plays an important role in the palliative/curative treatment of these patients

A signature of epithelial-mesenchymal plasticity and stromal activation in primary tumor modulates late recurrence in breast cancer independent of disease subtype.

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Cheng, Qing; Chang, Jeffrey T; Gwin, William R; Zhu, Jun; Ambs, Stefan; Geradts, Joseph; Lyerly, H Kim

2014-07-25

Despite improvements in adjuvant therapy, late systemic recurrences remain a lethal consequence of both early- and late-stage breast cancer. A delayed recurrence is thought to arise from a state of tumor dormancy, but the mechanisms that govern tumor dormancy remain poorly understood. To address the features of breast tumors associated with late recurrence, but not confounded by variations in systemic treatment, we compiled breast tumor gene expression data from 4,767 patients and established a discovery cohort consisting of 743 lymph node-negative patients who did not receive systemic neoadjuvant or adjuvant therapy. We interrogated the gene expression profiles of the 743 tumors and identified gene expression patterns that were associated with early and late disease recurrence among these patients. We applied this classification to a subset of 46 patients for whom expression data from microdissected tumor epithelium and stroma was available, and identified a distinct gene signature in the stroma and also a corresponding tumor epithelium signature that predicted disease recurrence in the discovery cohort. This tumor epithelium signature was then validated as a predictor for late disease recurrence in the entire cohort of 4,767 patients. We identified a novel 51-gene signature from microdissected tumor epithelium associated with late disease recurrence in breast cancer independent of the molecular disease subtype. This signature correlated with gene expression alterations in the adjacent tumor stroma and describes a process of epithelial to mesenchymal transition (EMT) and tumor-stroma interactions. Our findings suggest that an EMT-related gene signature in the tumor epithelium is related to both stromal activation and escape from disease dormancy in breast cancer. The presence of a late recurrence gene signature in the primary tumor also suggests that intrinsic features of this tumor regulate the transition of disseminated tumor cells into a dormant phenotype with

Persistent and recurrent hyperparathyroidism.

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Guerin, Carole; Paladino, Nunzia Cinzia; Lowery, Aoife; Castinetti, Fréderic; Taieb, David; Sebag, Fréderic

2017-06-01

Despite remarkable progress in imaging modalities and surgical management, persistence or recurrence of primary hyperparathyroidism (PHPT) still occurs in 2.5-5% of cases of PHPT. The aim of this review is to expose the management of persistent and recurrent hyperparathyroidism. A literature search was performed on MEDLINE using the search terms "recurrent" or "persistent" and "hyperparathyroidism" within the past 10 years. We also searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Before considering reoperation, the surgeon must confirm the diagnosis of PHPT. Then, the patient must be evaluated with new imaging modalities. A single adenoma is found in 68% of cases, multiglandular disease in 28%, and parathyroid carcinoma in 3%. Others causes (<1%) include parathyromatosis and graft recurrence. The surgeon must balance the benefits against the risks of a reoperation (permanent hypocalcemia and recurrent laryngeal nerve palsy). If surgery is necessary, a focused approach can be considered in cases of significant imaging foci, but in the case of multiglandular disease, a bilateral neck exploration could be necessary. Patients with multiple endocrine neoplasia syndromes are at high risk of recurrence and should be managed regarding their hereditary pathology. The cure rate of persistent-PHPT or recurrent-PHPT in expert centers is estimated from 93 to 97%. After confirming the diagnosis of PHPT, patients with persistent-PHPT and recurrent-PHPT should be managed in an expert center with all dedicated competencies.

Can injured adult CNS axons regenerate by recapitulating development?

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Hilton, Brett J; Bradke, Frank

2017-10-01

In the adult mammalian central nervous system (CNS), neurons typically fail to regenerate their axons after injury. During development, by contrast, neurons extend axons effectively. A variety of intracellular mechanisms mediate this difference, including changes in gene expression, the ability to form a growth cone, differences in mitochondrial function/axonal transport and the efficacy of synaptic transmission. In turn, these intracellular processes are linked to extracellular differences between the developing and adult CNS. During development, the extracellular environment directs axon growth and circuit formation. In adulthood, by contrast, extracellular factors, such as myelin and the extracellular matrix, restrict axon growth. Here, we discuss whether the reactivation of developmental processes can elicit axon regeneration in the injured CNS. © 2017. Published by The Company of Biologists Ltd.

Netrin-1 Confines Rhombic Lip-Derived Neurons to the CNS

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Andrea R. Yung

2018-02-01

Full Text Available During brainstem development, newborn neurons originating from the rhombic lip embark on exceptionally long migrations to generate nuclei important for audition, movement, and respiration. Along the way, this highly motile population passes several cranial nerves yet remains confined to the CNS. We found that Ntn1 accumulates beneath the pial surface separating the CNS from the PNS, with gaps at nerve entry sites. In mice null for Ntn1 or its receptor DCC, hindbrain neurons enter cranial nerves and migrate into the periphery. CNS neurons also escape when Ntn1 is selectively lost from the sub-pial region (SPR, and conversely, expression of Ntn1 throughout the mutant hindbrain can prevent their departure. These findings identify a permissive role for Ntn1 in maintaining the CNS-PNS boundary. We propose that Ntn1 confines rhombic lip-derived neurons by providing a preferred substrate for tangentially migrating neurons in the SPR, preventing their entry into nerve roots.

CNS complications of rotavirus gastroenteritis

International Nuclear Information System (INIS)

Volosinova, D.

2010-01-01

Rotavirus infection may be accompanied by serious complications, e.g. disabilities central nervous system (CNS). Theory rotavirus penetration across the blood-brain barrier and subsequent rota-associated convulsions by the 2-year case-history of the patient. Rotavirosis minor gastrointestinal symptoms may lead to erroneous diagnosis. (author)

Primary lymphoma of the testis

International Nuclear Information System (INIS)

Buskirk, S.J.; Evans, R.G.; Banks, P.M.; O'Connell, M.J.; Earle, J.D.

1982-01-01

Seventeen patients with initial presentation of lymphoma of the testis were evaluated at the Mayo Clinic between 1969 and 1979. The mean age of the patients was 69 years with 15 of the 17 patients age 60 and older at the time of diagnosis. All histologies were diffuse according to the Rappaport classification with 12 of 17 patients being histiocytic. Eleven of the 15 State I/sub E/A and II/sub E/A patients were treated with radiation therapy alone with doses ranging from 2,600 to 4,000 rad. Eight of these 11 Stage I/sub E/A patients experienced recurrence; in five of these eight, the first site of recurrence was Waldeyer's ring and adjacent structures. Four patients were treated initially with chemotherapy. In all four patients the lymphoma recurred, in two patients in the central nervous system (CNS). The survival rate at two years was 73% in Stage I/sub E/A patients and 25% in Stage II/sub E/A patients. There were no survivors at two years in those patients presenting with Stage IV disease. As patients with testicular lymphoma have a relatively high incidence of secondary involvement of Waldeyer's ring and the CNS, careful evaluation of these areas should be performed as part of the routine staging procedures. In view of the high incidence of secondary involvement of distant sites, systemic treatment should be given full consideration in addition to local irradiation as part of the initial treatment of patients with localized disease

Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors

NARCIS (Netherlands)

Vermeulen, Jeroen F; van Hecke, Wim; Spliet, Wim G M; Villacorta Hidalgo, José; Fisch, Paul; Broekhuizen, Roel; Bovenschen, Niels

2016-01-01

BACKGROUND: Central nervous system (CNS) primitive neuroectodermal tumors (PNETs) are malignant primary brain tumors that occur in young infants. Using current standard therapy, up to 80% of the children still dies from recurrent disease. Cellular immunotherapy might be key to improve overall

CNS Involvement in AML Patient Treated with 5-Azacytidine

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Diamantina Vasilatou

2014-01-01

Full Text Available Central nervous system (CNS involvement in acute myeloid leukemia (AML is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.

Safety, Efficacy and Recurrence rate following tenosynovectomy and ...

African Journals Online (AJOL)

Objective: This study was conducted to compare the safety, efficacy and recurrence rate of primary tenosynovectomy versus intralesional steroid injection in the treatment of sclerosing tenosynovitis of deQuervain. Method: A prospective, comparative study of the safety, efficacy and recurrence rate following intralesional ...

Treatment of locally recurrent rectal cancer

International Nuclear Information System (INIS)

Kococik, Z.; Kococik, M.

2007-01-01

The suggested classifications of locally recurrent rectal cancer are based on the presence of symptoms and the degree of tumour fixation to the pelvic wall, or, otherwise, account for factor T in the TMN system. Although the results of rectal cancer treatment have improved, which may be attributed to total meso rectal excision and application of perioperative radiotherapy and radiochemotherapy, the ratio of cases of locally recurrent rectal cancer still amount from several to over a dozen percent. Among the available diagnostic methods for detecting locally recurrent rectal cancer after anterior rectal resection, endorectal sonography is of special importance. In the estimation of prognostic factors the lack of vascular invasion in recurrent cancer and the long period between the treatment of primary rectal cancer and the development of recurrence are a sign of good prognosis, while pain prior to recurrence treatment and male sex diminish the chances for cure. Locally recurrent rectal cancer impairs the patient's quality of life in all measurable aspects, but even after complete recovery we observe severe disturbances of sexual activity in most patients, and a number of patients require hygiene pads or suffer from chronic pain. Local recurrence of rectal cancer is more commonly qualified for excision after surgical treatment only, than after preoperative radiotherapy. The probability of total recurrent rectal cancer excision increases when the patient is younger, the primary tumours was less advanced and the first operation was sphincter-sparing surgery. Progress in the surgical treatment of recurrent rectal cancer was brought on by the introduction of the composite musculocutaneous flap to compensate the loss of perineal tissue. The application of intraoperative radiotherapy improves treatment results of recurrent rectal cancer, however at the cost of more frequent, serious postoperative complications and intense pain. In inoperable cases high dose regional

Adverse CNS-effects of beta-adrenoceptor blockers.

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Gleiter, C H; Deckert, J

1996-11-01

In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis

DEFF Research Database (Denmark)

Espejo, C; Carrasco, J; Hidalgo, J

2001-01-01

Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Metallothioneins-I+II are antioxidant proteins induced in the CNS by immobilisation stress, trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS isoform metallothionein......-III has been related to Alzheimer's disease. We have analysed metallothioneins-I-III expression in the CNS of mice with experimental autoimmune encephalomyelitis. Moreover, we have examined the putative role of interferon-gamma, a pro-inflammatory cytokine, in the control of metallothioneins expression...

Primary postural instability: a cause of recurrent sudden falls in the elderly.

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Djaldetti, R; Lorberboym, M; Melamed, E

2006-12-01

Elderly patients with recurrent falls are frequently diagnosed with an extrapyramidal syndrome. This study aims to characterise a distinct group of patients with recurrent falls and postural instability as a hallmark of the clinical examination. The study took place in the Movement Disorders Unit, Rabin Medical Center, Petah Tiqva, Israel among 26 patients with recurrent falls who had no clinical evidence of a neurodegenerative disease. Medical records, neurological examination and brain imaging studies were assessed. Falls in these patients were sudden, unprovoked, with no vertigo or loss of consciousness. All had postural instability with minimal or no abnormality on the neurological examination. Brain imaging showed diffuse ischaemic changes in 65%. [(123)I]-FPCIT SPECT with the dopamine transporter ligand, performed in five patients, was normal in all. Recurrent falls might be caused by a neurological syndrome that primarily affects balance control. The importance of identifying this disorder is its distinction from other parkinsonian syndromes causing falls.

Species distribution and in vitro antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis

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Rijs Antonius JMM

2008-08-01

Full Text Available Abstract Background In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis. Methods A total of 296 clinical oral yeasts were isolated from 292 HIV-infected patients with oropharyngeal candidiasis at the Muhimbili National Hospital, Dar es Salaam, Tanzania. Identification of the yeasts was performed using standard phenotypic methods. Antifungal susceptibility to fluconazole, itraconazole, miconazole, clotrimazole, amphotericin B and nystatin was assessed using a broth microdilution format according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI; M27-A2. Results Candida albicans was the most frequently isolated species from 250 (84.5% patients followed by C. glabrata from 20 (6.8% patients, and C. krusei from 10 (3.4% patients. There was no observed significant difference in species distribution between patients with primary and recurrent oropharyngeal candidiasis, but isolates cultured from patients previously treated were significantly less susceptible to the azole compounds compared to those cultured from antifungal naïve patients. Conclusion C. albicans was the most frequently isolated species from patients with oropharyngeal candidiasis. Oral yeast isolates from Tanzania had high level susceptibility to the antifungal agents tested. Recurrent oropharyngeal candidiasis and previous antifungal therapy significantly correlated with reduced susceptibility to azoles antifungal agents.

Stress Reduction in Improving Quality of Life in Patients With Recurrent Gynecologic or Breast Cancer

Science.gov (United States)

2015-10-08

Anxiety Disorder; Depression; Fatigue; Leydig Cell Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Pain; Peritoneal Carcinomatosis; Pseudomyxoma Peritonei; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Endometrial Carcinoma; Recurrent Fallopian Tube Cancer; Recurrent Gestational Trophoblastic Tumor; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Recurrent Uterine Sarcoma; Recurrent Vaginal Cancer; Recurrent Vulvar Cancer

CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

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Rezai-Zadeh, Kavon; Gate, David; Town, Terrence

2009-12-01

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies.

Science.gov (United States)

Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

2016-01-01

The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.

Causes of CNS inflammation and potential targets for anticonvulsants.

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Falip, Mercé; Salas-Puig, Xavier; Cara, Carlos

2013-08-01

Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

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Alerie Guzman De La Fuente

2017-08-01

Full Text Available The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.

[Sucessful dietetic-therapy in primary intestinal lymphangiectasia and recurrent chylous ascites: a case report].

Science.gov (United States)

Martín, C Campos; García, A Fernández-Argüelles; Restrepo, J M Rabat; Pérez, A Sendón

2007-01-01

Primary intestinal lymphangiectasia is a lymphatic system's disorder, where lymphatic drainage is blockaged. Clinically it produces malabsorption, protein-losing enteropathy, hypogammaglobulin in blood, and several degrees of malnutrition. Its treatment is not easy and includes dietetic-therapy and drugs. A 35-year-old-woman case report is exposed. She has recurrent chylosa ascites, requiring several admissions and evacuatory paracentesis. After food-fat was replaced by medium-chain triacyl-glicerol-enriched diet, a clinical, analytical and anthropometric improvement was demonstrated. The major way of treatment in intestinal lymphangiectasia in this case is the employement of specific-diet and adaptaded-basic-food. It's difficult and high collaboration of the patient is required, being necessary medical revisions during the whole life, due to the not well known evolution of this long-standing disease.

Cerebral blood flow variations in CNS lupus

International Nuclear Information System (INIS)

Kushner, M.J.; Tobin, M.; Fazekas, F.; Chawluk, J.; Jamieson, D.; Freundlich, B.; Grenell, S.; Freemen, L.; Reivich, M.

1990-01-01

We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery

Brain parenchyma involvement as isolated central nervous system relapse of systemic non-Hodgkin lymphoma: An International Primary CNS Lymphoma Collaborative Group report

NARCIS (Netherlands)

N.D. Doolittle (Nancy); L.E. Abrey (Lauren); T.N. Shenkier (Tamara); T. Siegal (Tali); J.E.C. Bromberg (Jacolien); E.A. Neuwelt (Edward); C. Soussain (Carole); K. Jahnke (Kristoph); P. Johnston (Patrick); G. Illerhaus (Gerald); D. Schiff (David); T.T. Batchelor (Tracy); S. Montoto (Silvia); D.F. Kraemer (Dale); E. Zucca (Emanuele)

2008-01-01

textabstractIsolated central nervous system (CNS) relapse involving the brain parenchyma is a rare complication of systemic non-Hodgkin lymphoma. We retrospectively analyzed patient characteristics, management, and outcomes of this complication. After complete response to initial non-Hodgkin

Observations at the CNS-PNS border of ventral roots connected to a neuroma

Directory of Open Access Journals (Sweden)

Sten Remahl

2010-10-01

Full Text Available Previous studies have shown that numerous sprouts originating from a neuroma, after nerve injury in neonatal animals, can invade spinal nerve roots. In this study the border between the central and peripheral nervous system (CNS-PNS border of ventral roots in kittens was examined with both light and electron microscopy after early postnatal sciatic nerve resection. A transient ingrowth of substance P positive axons was observed into the CNS, but no spouts remained 6 weeks after the injury. Using serial sections and electron microscopy it was possible to identify small bundles of unmyelinated axons that penetrated from the root fascicles for a short distance into the CNS. These axons ended blindly, sometimes with a growth cone-like terminal swelling filled with vesicles. The axon bundles were accompanied by p75 positive cells in both the root fascicles and the pia mater, but not in the CNS. It may thus be suggested that neurotrophin presenting p75 positive cells could facilitate axonal growth into the pia mater and that the lack of such cells in the CNS compartment might contribute to the failure of growth into the CNS. A maldevelopment of myelin sheaths at the CNS-PNS border of motor axons was observed and it seems possible that this could have consequences for the propagation of action potential across this region after neonatal nerve injury.

Basic Concepts of CNS Development.

Science.gov (United States)

Nowakowski, R. S.

1987-01-01

The goals of this review are to: (1) provide a set of concepts to aid in the understanding of complex processes which occur during central nervous system (CNS) development; (2) illustrate how they contribute to our knowlege of adult brain anatomy; and (3) delineate how modifications of normal developmental processes may affect the structure and…

The retina as a window to the brain-from eye research to CNS disorders.

Science.gov (United States)

London, Anat; Benhar, Inbal; Schwartz, Michal

2013-01-01

Philosophers defined the eye as a window to the soul long before scientists addressed this cliché to determine its scientific basis and clinical relevance. Anatomically and developmentally, the retina is known as an extension of the CNS; it consists of retinal ganglion cells, the axons of which form the optic nerve, whose fibres are, in effect, CNS axons. The eye has unique physical structures and a local array of surface molecules and cytokines, and is host to specialized immune responses similar to those in the brain and spinal cord. Several well-defined neurodegenerative conditions that affect the brain and spinal cord have manifestations in the eye, and ocular symptoms often precede conventional diagnosis of such CNS disorders. Furthermore, various eye-specific pathologies share characteristics of other CNS pathologies. In this Review, we summarize data that support examination of the eye as a noninvasive approach to the diagnosis of select CNS diseases, and the use of the eye as a valuable model to study the CNS. Translation of eye research to CNS disease, and deciphering the role of immune cells in these two systems, could improve our understanding and, potentially, the treatment of neurodegenerative disorders.

Does Local Recurrence of Prostate Cancer After Radiation Therapy Occur at the Site of Primary Tumor? Results of a Longitudinal MRI and MRSI Study

International Nuclear Information System (INIS)

Arrayeh, Elnasif; Westphalen, Antonio C.; Kurhanewicz, John; Roach, Mack; Jung, Adam J.; Carroll, Peter R.; Coakley, Fergus V.

2012-01-01

Purpose: To determine if local recurrence of prostate cancer after radiation therapy occurs at the same site as the primary tumor before treatment, using longitudinal magnetic resonance (MR) imaging and MR spectroscopic imaging to assess dominant tumor location. Methods and Materials: This retrospective study was HIPAA compliant and approved by our Committee on Human Research. We identified all patients in our institutional prostate cancer database (1996 onward) who underwent endorectal MR imaging and MR spectroscopic imaging before radiotherapy for biopsy-proven prostate cancer and again at least 2 years after radiotherapy (n = 124). Two radiologists recorded the presence, location, and size of unequivocal dominant tumor on pre- and postradiotherapy scans. Recurrent tumor was considered to be at the same location as the baseline tumor if at least 50% of the tumor location overlapped. Clinical and biopsy data were collected from all patients. Results: Nine patients had unequivocal dominant tumor on both pre- and postradiotherapy imaging, with mean pre- and postradiotherapy dominant tumor diameters of 1.8 cm (range, 1–2.2) and 1.9 cm (range, 1.4–2.6), respectively. The median follow-up interval was 7.3 years (range, 2.7–10.8). Dominant recurrent tumor was at the same location as dominant baseline tumor in 8 of 9 patients (89%). Conclusions: Local recurrence of prostate cancer after radiation usually occurs at the same site as the dominant primary tumor at baseline, suggesting supplementary focal therapy aimed at enhancing local tumor control would be a rational addition to management.

HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix

Science.gov (United States)

Paveliev, Mikhail; Fenrich, Keith K.; Kislin, Mikhail; Kuja-Panula, Juha; Kulesskiy, Evgeny; Varjosalo, Markku; Kajander, Tommi; Mugantseva, Ekaterina; Ahonen-Bishopp, Anni; Khiroug, Leonard; Kulesskaya, Natalia; Rougon, Geneviève; Rauvala, Heikki

2016-01-01

Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPσ (protein tyrosine phosphatase sigma). Our in vivo studies using two-photon imaging of CNS injuries support the in vitro studies and show that HB-GAM increases dendrite regeneration in the adult cerebral cortex and axonal regeneration in the adult spinal cord. Our findings may enable the development of novel therapies for CNS injuries. PMID:27671118

The influence of psycho-emotional stress in children of primary school age on the incidence of recurrent upper respiratory tract infections and the functional state of the myocardium

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L.S. Ovcharenko

2017-10-01

Full Text Available Background. Scientific and technical progress, intensification of educational process and information overload have a negative effect on unformed central nervous system of primary schoolchildren, causing stress, which affects the increase in the incidence of recurrent upper respiratory tract infections (URTI and the functional state of the myocardium. In view of this, we analyzed a functional state of myocardium in children with recurrent URTI. The critical duration of the work of primary school child with electronic means of communication, which affects the quality of nighttime sleep and the nature of awakening in the morning, was established. We have studied the relationship of the above mentioned with the incidence of URTI, the level of school anxiety and functional reserve of the myocardium. The purpose of the study was to evaluate the functional reserve of the myocardium in children of primary school age, depending on the incidence of URTI and the level of psycho-emotional activity. Materials and me­thods. 239 children aged 6 to 9 years were examined. The analysis of the functional reserve of the myocardium was carried out in pupils with different incidence of the URTI, depending on the age. The influence of electronic communications on the quality of nighttime sleep and morning awakening was stu­died, and the level of school anxiety was evaluated. During the study, children were divided into two groups. Group 1 — children with recurrent acute respiratory diseases (n = 143. Group 2 — children who occasionally have URTI (n = 96. Results. Out of 239 children with recurrent acute respiratory infections, we have identified 173 children with reduced functional reserve of the myocardium (72.4 %. Among children with recurrent URTI, the incidence of reduced functional reserve of the myocardium was 76.2 %, and in occasionally ill children — 66.7 %. Children with recurrent URTI use electronic means of communication more often than

VIIP: Central Nervous System (CNS) Modeling

Science.gov (United States)

Vera, Jerry; Mulugeta, Lealem; Nelson, Emily; Raykin, Julia; Feola, Andrew; Gleason, Rudy; Samuels, Brian; Ethier, C. Ross; Myers, Jerry

2015-01-01

Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.

CNS metastasis from malignant uveal melanoma: a clinical and histopathological characterisation

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Holfort, S K; Lindegaard, J; Isager, P

2008-01-01

was observed in two cases (14%). The amount of tumour infiltrating lymphocytes was pronounced in three cases (23%). CONCLUSION: The proportion of uveal melanoma patients having CNS metastasis was 0.7%. Eleven patients had multiple organ metastases, and the average time from the initial CNS symptoms to death...

Early Ectopic Recurrence of Craniopharyngioma in the Cerebellopontine Angle.

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Mahdi, Mohamad-Motaz Al; Krauss, Joachim K; Nakamura, Makoto; Brandis, Almuth; Hong, Bujung

2018-01-01

Ectopic recurrence of craniopharyngioma in the cerebellopontine angle after surgical resection of a suprasellar craniopharyngioma is rare. Thus, only 5 cases were reported with a delay ranging between 4 and 26 years after removal of the primary tumor. We report a unique case of ectopic recurrence of craniopharyngioma in the cerebellopontine angle, which occurred at only 4 months after surgical resection of the primary tumor. A 24-year-old man underwent resection of a suprasellar craniopharyngioma via a right pterional approach four months earlier. During follow-up, cerebral magnetic resonance imaging (MRI) showed a round homogeneous contrast-enhancing tumor in the right cerebellopontine angle with neither relation to the internal auditory canal nor to the dura mater. After microsurgical resection, histopathological findings revealed ectopic recurrence of craniopharyngioma with similar tumors like the primary tumor. Although infrequent, craniopharyngioma may disseminate via the cerebrospinal fluid during surgical resection and grow in an ectopic place. Early follow-up and MRI scan following resection of a craniopharyngioma is recommended.

Interneuron progenitor transplantation to treat CNS dysfunction

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Muhammad O Chohan

2016-08-01

Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

[A review of the effects of lithium on cognitive functions: Effects on the neuropsychiatrically challenged CNS].

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Tsaltas, E; Kontis, D

2009-04-01

Recent data attribute neuroprotective and neurotrophic actions to lithium, leading to expectations of cognitive enhancement action. This hypothesis is at odds with the predominant view of clinical psychiatr y which, on the basis of older clinical data as well as on subjective reports of lithiumtreated patients, associates lithium with cognitive blurring and specific memory deficits. Review of the older data and their integration with more recent clinical and experimental work on the primary effects of lithium on cognitive functioning led us to two central conclusions: (a) Data on the primary cognitive effects of lithium, considered in their entirety, do not support a picture of serious or long-lasting cognitive decline. On the contrary, recent evidence suggests cognitive enhancement under certain conditions. (b) The conditions which appear to promote the emergence of cognitive enhancement under lithium are conditions of challenge to the cognitive systems, such as increased task difficulty resulting in deterioration in the performance of untreated controls. We are suggesting that alternative challenges to cognitive functioning, which therefore would facilitate the emergence of lithium's cognitive enhancement action, include biological insults to the central nervous system (CNS). This second part of our review of the cognitive effects of lithium therefore focuses on studies of its action on cognitive dysfunction associated with functional or biological challenge to the CNS, such as stress, trauma, neurodegenerative and psychiatric disorders.

Health-related quality of life after surgery for primary advanced rectal cancer and recurrent rectal cancer a review

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Thaysen, Henriette Vind

2012-01-01

, physical, social, role and sexual function seemed to be impaired for a varying time after surgery. All the studies had methodical problems due to small sample size (12-44 patients) and different points of time for the assessment of HRQoL (12.3-47 months) which made it difficult to determine the period...... studies concerning surgery for primary advanced or recurrent rectal cancer and describing methods used for measuring HRQoL were considered. Results Seven studies were identified including two prospective longitudinal, three cross-sectional and two based on qualitative data. Global quality of life...

Neuroprotective effects of estrogen in CNS injuries: insights from animal models

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Raghava N

2017-07-01

Full Text Available Narayan Raghava,1 Bhaskar C Das,2 Swapan K Ray1 1Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA; 2Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA Abstract: Among the estrogens that are biosynthesized in the human body, 17β-estradiol (estradiol or E2 is the most common and the best estrogen for neuroprotection in animal models of the central nervous system (CNS injuries such as spinal cord injury (SCI, traumatic brain injury (TBI, and ischemic brain injury (IBI. These CNS injuries are not only serious health problems, but also enormous economic burden on the patients, their families, and the society at large. Studies from animal models of these CNS injuries provide insights into the multiple neuroprotective mechanisms of E2 and also suggest the possibility of translating the therapeutic efficacy of E2 in the treatment SCI, TBI, and IBI in humans in the near future. The pathophysiology of these injuries includes loss of motor function in the limbs, arms and their extremities, cognitive deficit, and many other serious consequences including life-threatening paralysis, infection, and even death. The potential application of E2 therapy to treat the CNS injuries may become a trend as the results are showing significant therapeutic benefits of E2 for neuroprotection when administered into the animal models of SCI, TBI, and IBI. This article describes the plausible mechanisms how E2 works with or without the involvement of estrogen receptors and provides an overview of the known neuroprotective effects of E2 in these three CNS injuries in different animal models. Because activation of estrogen receptors has profound implications in maintaining and also affecting normal physiology, there are notable impediments in translating E2 therapy to the clinics for neuroprotection in CNS injuries in humans. While E2 may not yet be the sole molecule for

Foxp3+ regulatory T cells control persistence of viral CNS infection.

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Dajana Reuter

Full Text Available We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified mice and recombinant measles virus (MV. Using this model infection we investigated the role of regulatory T cells (Tregs as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+ CD25(+ Foxp3(+ Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+ T cells predominantly recognising the H-2D(b-presented viral hemagglutinin epitope MV-H(22-30 (RIVINREHL were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p. application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT in DEREG (depletion of regulatory T cells-mice induced an increase of virus-specific CD8(+ effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.

MRI features and pathologic types of benign meningiomas and their correlation with tumor recurrence

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Du Tieqiao; Zhu Mingwang; Zhao Dianjiang; Qi Xueling; Wang Lining; Zhang Xufei

2014-01-01

Objective: To determine MR manifestations and pathologic types of benign meningiomas and their relationship with tumor recurrence. Methods: There were 218 patients (160 females,58 males; age range 4-79 years) with benign meningiomas in the study, including 31 recurrent meningiomas (recurrence group)and 187 primary meningiomas (primary group). All patients were proved by postoperative pathology. Differences of pathological types and MRI manifestations between the recurrence group and the primary group were evaluated by using χ 2 test and rank sum test. Logistic regression analysis was performed by taking tumor recurrence as the dependent variable, and age, gender, vital structures involvement and pathologic types as independent variables. The recurrent time intervals were compared by rank sum test. Results: There were 30 patients with intracranial vital structures involvement or extreintracranial communication tumors in the recurrent group, which was obviously higher than that of the primary group (61 patients). The difference was statistically significant (χ 2 =57.672, P=0.001). The tumors located in the skull-base and juxtasinus in the recurrent group were obviously more than those in the primary group, and difference was statistically significant (χ 2 =10.990, P=0.001). Multi-logistic regression analysis showed that the recurrent risk of benign meningiomas was elevated significantly only with vital structure involvement or extreintracranial communication tumors (wald χ 2 =31.863, OR=3.820, P=0.001). The recurrent risk of dural sinus involvement was 3.820 times of cerebral artery trunk and cranial nerves involvement, and the risk of the latter was 3.820 times of the non-involved. There was no statistical difference between the two groups in pathology type, location, peritumoral edema, tumor morphology and tumor size. The relapse time of dural sinus involvement and cerebral artery trunk involvement in the recurrent group was 24(13 to 180) and 126(12 to 187

Novel agents in CNS myeloma treatment.

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Gozzetti, Alessandro; Cerase, Alfonso

2014-01-01

Central nervous system localization of multiple myeloma (CNS-MM) accounts for about 1% of all MM.Treatment is still unsatisfactory. Many treatments have been described in the literature: chemotherapy (CHT), intrathecal therapy (IT), and radiotherapy (RT), with survivals reported between one month and six months. Recent drugs such as the immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib) have changed the treatment of patients with MM, both younger and older, with a significant improvement in response and survival. The activity of new drugs in CNSMM has been reported but is still not well known. Bortezomib does not cross the blood brain barrier (BBB), and IMID’s seem to have only a minimal crossover. The role of novel agents in CNS MM management will be discussed as well as the potential role of other new immunomodulatory drugs (pomalidomide) and proteasome inhibitors that seem to cross the BBB and hold promise into the treatment of this rare and still incurable localization of the disease.

Algorithms for Zero-Dimensional Ideals Using Linear Recurrent Sequences

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Neiger, Vincent; Rahkooy, Hamid; Schost, Éric

2017-01-01

Inspired by Faugére and Mou´s sparse FGLM algorithm, we show how using linear recurrent multi-dimensional sequences can allow one to perform operations such as the primary decomposition of an ideal, by computing of the annihilator of one or several such sequences.......Inspired by Faugére and Mou´s sparse FGLM algorithm, we show how using linear recurrent multi-dimensional sequences can allow one to perform operations such as the primary decomposition of an ideal, by computing of the annihilator of one or several such sequences....

AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders.

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Ivachtchenko, Alexandre V; Lavrovsky, Yan; Okun, Ilya

2016-05-25

Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2-2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41-3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer's disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis.

Recurrent meningitis in a child with IgG3 subclass deficiency.

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Vehapoglu, Aysel; Ozgurhan, Gamze; Demir, Aysegul Dogan; Uzuner, Selcuk; Nursoy, Mustafa Atilla; Turkmen, Serdar

2014-08-01

Recurrent meningitis is an uncommon life-threatening condition. Here, the case of a 6-year-old boy is reported who had two episodes of meningitis with an IgG3 subclass deficiency. The boy had aseptic meningitis at the age of 3 years, followed by bacterial meningitis at the age of 4 years. Primary immunoglobulin deficiencies are a group of disorders associated with an increased incidence and/or severity of infection. Recurrent infections, sinusitis, bronchitis, and pneumonia are the most frequently observed illnesses in patients with IgG subclass deficiencies, of which an IgG3 subclass deficiency is the most common, especially in adults. Although cases of recurrent viral or bacterial meningitis have been reported, herein a patient is presented with recurrence of aseptic and bacterial meningitis 1 year after the initial episode. Some researchers recommend that all children with episodes of recurrent meningitis should be screened for primary immunoglobulin or complement deficiencies.

Management of glioblastoma after recurrence: A changing paradigm

International Nuclear Information System (INIS)

Mallick, S.; Benson, R.; Hakim, A.; Rath, G.K.

2016-01-01

Glioblastoma remains the most common primary brain tumor after the age of 40 years. Maximal safe surgery followed by adjuvant chemoradiotherapy has remained the standard treatment for glioblastoma (GBM). But recurrence is an inevitable event in the natural history of GBM with most patients experiencing it after 6–9 months of primary treatment. Recurrent GBM poses great challenge to manage with no well-defined management protocols. The challenge starts from differentiating radiation necrosis from true local progression. A fine balance needs to be maintained on improving survival and assuring a better quality of life. Treatment options are limited and ranges from re-excision, re-irradiation, systemic chemotherapy or a combination of these. Re-excision and re-irradiation must be attempted in selected patients and has been shown to improve survival outcomes. To facilitate the management of GBM recurrences, a treatment algorithm is proposed

True recurrence vs. new primary ipsilateral breast tumor relapse: An analysis of clinical and pathologic differences and their implications in natural history, prognoses, and therapeutic management

International Nuclear Information System (INIS)

Smith, Tanya E.; Lee, Daesung; Turner, Bruce C.; Carter, Darryl; Haffty, Bruce G.

2000-01-01

Purpose: The purpose of this study was to classify all ipsilateral breast tumor relapses (IBTR) in patients treated with conservative surgery and radiation therapy (CS+RT) as either new primary tumors (NP) or true local recurrences (TR) and to assess the prognostic and therapeutic implications of this classification. Methods and Materials: Of the 1152 patients who have been treated at Yale-New Haven Hospital before 1990, 136 patients have experienced IBTR as their primary site of failure. These relapses were classified as either NP or TR. Specifically, patients were classified as NP if the recurrence was distinctly different from the primary tumor with respect to the histologic subtype, the recurrence location was in a different location, or if the flow cytometry changed from aneuploid to diploid. This information was determined by a detailed review of each patient's hospital and/or radiotherapy record, mammograms, and pathologic reports. Results: As of 2/99, with a mean follow-up of 14.2 years, the overall ipsilateral breast relapse-free rate for all 1152 patients was 86% at 10 years. Using the classification scheme outlined above, 60 patient relapses were classified as TR, 70 were classified as NP and 6 were unable to be classified. NP patients had a longer mean time to breast relapse than TR patients (7.3 years vs. 3.7 years, p < 0.0001) and were significantly younger than TR patients (48.9 years vs. 54.5 years, p < 0.01). Patients developed both TR and NP at similar rates until approximately 8 years, when TR rates stabilized but NP rates continued to rise. By 15 years following original diagnosis, the TR rate was 6.8% compared to 13.1% for NP. Of the patients who had been previously tested for BRCA1/2 mutations, 17% (8/52) had deleterious mutations. It is noteworthy that all patients with deleterious mutations had new primary IBTR, while patients without deleterious mutations had both TR and NP (p = 0.06). Ploidy was evenly distributed between TR and NP but NP

Modeling the recurrent failure to thrive in less than two-year children: recurrent events survival analysis.

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Saki Malehi, Amal; Hajizadeh, Ebrahim; Ahmadi, Kambiz; Kholdi, Nahid

2014-01-01

This study aimes to evaluate the failure to thrive (FTT) recurrent event over time. This longitudinal study was conducted during February 2007 to July 2009. The primary outcome was growth failure. The analysis was done using 1283 children who had experienced FTT several times, based on recurrent events analysis. Fifty-nine percent of the children had experienced the FTT at least one time and 5.3% of them had experienced it up to four times. The Prentice-Williams-Peterson (PWP) model revealed significant relationship between diarrhea (HR=1.26), respiratory infections (HR=1.25), urinary tract infections (HR=1.51), discontinuation of breast-feeding (HR=1.96), teething (HR=1.18), initiation age of complementary feeding (HR=1.11) and hazard rate of the first FTT event. Recurrence nature of the FTT is a main problem, which taking it into account increases the accuracy in analysis of FTT event process and can lead to identify different risk factors for each FTT recurrences.

Feasibility and safety of GliaSite brachytherapy in treatment of CNS tumors following neurosurgical resection

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Wernicke A

2010-01-01

Full Text Available Purpose: To investigate feasibility and safety of GliaSite brachytherapy for treatment of central nervous system (CNS tumors following neurosurgical resection. We report mature results of long-term follow-up, outcomes and toxicity. Materials and Methods: In the period from 2004 to 2007, 10 consecutive adult patients with recurrent, newly diagnosed, and metastatic brain malignancies underwent GliaSite brachytherapy following maximally safe neurosurgical resection. While 6/10 (60% patients were treated for recurrence, having previously been treated with external beam radiotherapy (EBRT, 4/10 (40% received radiotherapy (RT for the first time. A median dose of 52.0 Gy (range, 45.0 - 60.0 Gy was prescribed to 0.5 cm - 1.0 cm from the balloon surface. Radiation Therapy Oncology Group (RTOG criteria were used to assess toxicities associated with this technique. Follow-up was assessed with MRI scans and was available on all enrolled patients. Results: Median follow-up was 38 months (range, 18 - 57 months. Mean size of GliaSite balloon was 3.4 cm (range, 2.0 - 4.0 cm. Median survival was 14.0 months for the entire cohort after the treatment. The 17.6 and 16.0 months average survival for newly diagnosed and recurrent high grade gliomas (HGG, respectively, translated into a three-month improvement in survival in patients with newly diagnosed HGG compared to historical controls (P = 0.033. There were no RTOG grades 3 or 4 acute or late toxicities. Follow-up magnetic resonance imaging (MRI imaging did not identify radiation necrosis. Conclusions: Our data indicate that treatment with GliaSite brachytherapy is feasible, safe and renders acceptable local control, acute and long-term toxicities. We are embarking on testing larger numbers of patients with this treatment modality.

Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

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Hur, Eun-Mi; Lee, Byoung Dae

2014-12-01

Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

Microtubule-Targeting Agents Enter the Central Nervous System (CNS: Double-edged Swords for Treating CNS Injury and Disease

Directory of Open Access Journals (Sweden)

Eun-Mi Hur

2014-12-01

Full Text Available Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

EMMPRIN, an upstream regulator of MMPs, in CNS biology.

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Kaushik, Deepak Kumar; Hahn, Jennifer Nancy; Yong, V Wee

2015-01-01

Matrix metalloproteinases (MMPs) are engaged in pathologies associated with infections, tumors, autoimmune disorders and neurological dysfunctions. With the identification of an upstream regulator of MMPs, EMMPRIN (Extracellular matrix metalloproteinase inducer, CD147), it is relevant to address if EMMPRIN plays a role in the pathology of central nervous system (CNS) diseases. This would enable the possibility of a more upstream and effective therapeutic target. Indeed, conditions including gliomas, Alzheimer's disease (AD), multiple sclerosis (MS), and other insults such as hypoxia/ischemia show elevated levels of EMMPRIN which correlate with MMP production. In contrast, given EMMPRIN's role in CNS homeostasis with respect to regulation of monocarboxylate transporters (MCTs) and interactions with adhesion molecules including integrins, we need to consider that EMMPRIN may also serve important regulatory or protective functions. This review summarizes the current understanding of EMMPRIN's involvement in CNS homeostasis, its possible roles in escalating or reducing neural injury, and the mechanisms of EMMPRIN including and apart from MMP induction. Copyright © 2015 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

A unique case of primary effusion lymphoma-like lymphoma showing disappearance and recurrence of the body cavity effusion.

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Koeda, Chikahiko; Sato, Takashi; Matsumoto, Yuki; Usui, Yuta; Kunugida, Fusanori; Ogawa, Muneyoshi

2017-03-01

Primary effusion lymphoma-like lymphoma (PEL-LL) is a rare B-cell lymphoma that the etiology remains unclear. We describe a case of PEL-LL with a pleuropericardial effusion. Diagnosis required long period of time as it followed a unique progress of disappearance and recurrence of the body cavity effusion. We finally had a diagnosis of B-cell lymphoma by the immunocytochemistry of effusion using the cell block procedure. Authors consider that it is valuable to actively try the cell block procedure at the time of the first drainage for early diagnosis, if the body cavity effusion due to the malignancy is suspected.

Sentinel lymph node biopsy in local recurrence of cutaneous melanoma

International Nuclear Information System (INIS)

Junqueira, G. Jr.; Bodanese, B.; Boff, M.F.; Espindola, M.B.; Haack, R.L.; Frigeri, C.D.L.

2004-01-01

Full text: Locally recurrent disease in patients with melanoma is usually defined as cutaneous or subcutaneous arising within 5 cm of the primary site after complete excision of the primary lesion. It may represent residual disease not excised with the primary tumor or the outgrowth of the satellite lesions, which are common with melanoma. Lymphatic mapping and sentinel lymph node (SLN) biopsy is highly accurate in staging nodal basins at risk of regional metastases in primary melanoma patients and identifies those who may benefit from earlier lymphadenectomy. Our purpose was to evaluate the efficacy of sentinel lymph node mapping and biopsy in local recurrence of cutaneous melanoma when the primary lesion was less than 1.0mm thick. Three patients with local recurrence of cutaneous melanoma underwent sentinel lymph node mapping and biopsy. All patients underwent preoperative lymphoscintigraphy to identify the lymphatic basin and the site of the sentinel node. All patients subsequently underwent intra-operative lymphatic mapping and selective lymph node biopsy with vital blue dye and hand-held gamma probe. Excised SLN were analysed by conventional histological staining (H and E) and immunohistochemical staining. In all patients the lymphatic mapping and sentinel lymph node biopsy was successful. The SLN biopsy was negative in two patients and positive in one who underwent therapeutic lymph node dissection. Our results indicate that the SLN mapping and biopsy is also possible in patients having local recurrence of cutaneous melanoma. Although long-term results are not available, early results are promising. (author)

Therapeutic potential of agmatine for CNS disorders.

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Neis, Vivian B; Rosa, Priscila B; Olescowicz, Gislaine; Rodrigues, Ana Lúcia S

2017-09-01

Agmatine is a neuromodulator that regulates multiple neurotransmitters and signaling pathways. Several studies have focused on elucidating the mechanisms underlying the neuroprotective effects of this molecule, which seems to be mediated by a reduction in oxidative damage, neuroinflammation, and proapoptotic signaling. Since these events are implicated in acute and chronic excitotoxicity-related disorders (ischemia, epilepsy, traumatic brain injury, spinal cord injury, neurodegenerative, and psychiatric disorders) as well as in nociception, agmatine has been proposed as a therapeutic strategy for the treatment of central nervous system (CNS) disorders. Agmatine also stimulates the expression of trophic factors and adult neurogenesis, contributing to its ability to induce endogenous repair mechanisms. Therefore, considering its wide range of biological effects, this review summarizes the current knowledge about its protective and regenerative properties in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical impact of PSMA-based 18F-DCFBC PET/CT imaging in patients with biochemically recurrent prostate cancer after primary local therapy

International Nuclear Information System (INIS)

Mena, Esther; Lindenberg, Maria L.; Bergvall, Ethan; Ton, Anita T.; McKinney, Yolanda; Eclarinal, Philip; Choyke, Peter L.; Turkbey, Baris; Shih, Joanna H.; Adler, Stephen; Harmon, Stephanie; Weaver, Juanita; Forest, Alicia; Citrin, Deborah; Dahut, William; Afari, George; Bhattacharyya, Sibaprasad; Mease, Ronnie C.; Pomper, Martin G.; Merino, Maria J.; Pinto, Peter; Wood, Bradford J.; Jacobs, Paula

2018-01-01

The purpose of our study was to assess 18 F-DCFBC PET/CT, a PSMA targeted PET agent, for lesion detection and clinical management of biochemical relapse in prostate cancer patients after primary treatment. This is a prospective IRB-approved study of 68 patients with documented biochemical recurrence after primary local therapy consisting of radical prostatectomy (n = 50), post radiation therapy (n = 9) or both (n = 9), with negative conventional imaging. All 68 patients underwent whole-body 18 F-DCFBC PET/CT, and 62 also underwent mpMRI within one month. Lesion detection with 18 F-DCFBC was correlated with mpMRI findings and pre-scan PSA levels. The impact of 18 F-DCFBC PET/CT on clinical management and treatment decisions was established after 6 months' patient clinical follow-up. Forty-one patients (60.3%) showed at least one positive 18 F-DCFBC lesion, for a total of 79 lesions, 30 in the prostate bed, 39 in lymph nodes, and ten in distant sites. Tumor recurrence was confirmed by either biopsy (13/41 pts), serial CT/MRI (8/41) or clinical follow-up (15/41); there was no confirmation in five patients, who continue to be observed. The 18 F-DCFBC and mpMRI findings were concordant in 39 lesions (49.4%), and discordant in 40 lesions (50.6%); the majority (n = 32/40) of the latter occurring because the recurrence was located outside the mpMRI field of view. 18 F-DCFBC PET positivity rates correlated with PSA values and 15%, 46%, 83%, and 77% were seen in patients with PSA values <0.5, 0.5 to <1.0, 1.0 to <2.0, and ≥2.0 ng/mL, respectively. The optimal cut-off PSA value to predict a positive 18 F-DCFBC scan was 0.78 ng/mL (AUC = 0.764). A change in clinical management occurred in 51.2% (21/41) of patients with a positive 18 F-DCFBC result, generally characterized by starting a new treatment in 19 patients or changing the treatment plan in two patients. 18 F-DCFBC detects recurrences in 60.3% of a population of patients with biochemical recurrence, but results

Clinical impact of PSMA-based 18F-DCFBC PET/CT imaging in patients with biochemically recurrent prostate cancer after primary local therapy.

Science.gov (United States)

Mena, Esther; Lindenberg, Maria L; Shih, Joanna H; Adler, Stephen; Harmon, Stephanie; Bergvall, Ethan; Citrin, Deborah; Dahut, William; Ton, Anita T; McKinney, Yolanda; Weaver, Juanita; Eclarinal, Philip; Forest, Alicia; Afari, George; Bhattacharyya, Sibaprasad; Mease, Ronnie C; Merino, Maria J; Pinto, Peter; Wood, Bradford J; Jacobs, Paula; Pomper, Martin G; Choyke, Peter L; Turkbey, Baris

2018-01-01

The purpose of our study was to assess 18 F-DCFBC PET/CT, a PSMA targeted PET agent, for lesion detection and clinical management of biochemical relapse in prostate cancer patients after primary treatment. This is a prospective IRB-approved study of 68 patients with documented biochemical recurrence after primary local therapy consisting of radical prostatectomy (n = 50), post radiation therapy (n = 9) or both (n = 9), with negative conventional imaging. All 68 patients underwent whole-body 18 F-DCFBC PET/CT, and 62 also underwent mpMRI within one month. Lesion detection with 18 F-DCFBC was correlated with mpMRI findings and pre-scan PSA levels. The impact of 18 F-DCFBC PET/CT on clinical management and treatment decisions was established after 6 months' patient clinical follow-up. Forty-one patients (60.3%) showed at least one positive 18 F-DCFBC lesion, for a total of 79 lesions, 30 in the prostate bed, 39 in lymph nodes, and ten in distant sites. Tumor recurrence was confirmed by either biopsy (13/41 pts), serial CT/MRI (8/41) or clinical follow-up (15/41); there was no confirmation in five patients, who continue to be observed. The 18 F-DCFBC and mpMRI findings were concordant in 39 lesions (49.4%), and discordant in 40 lesions (50.6%); the majority (n = 32/40) of the latter occurring because the recurrence was located outside the mpMRI field of view. 18 F-DCFBC PET positivity rates correlated with PSA values and 15%, 46%, 83%, and 77% were seen in patients with PSA values <0.5, 0.5 to <1.0, 1.0 to <2.0, and ≥2.0 ng/mL, respectively. The optimal cut-off PSA value to predict a positive 18 F-DCFBC scan was 0.78 ng/mL (AUC = 0.764). A change in clinical management occurred in 51.2% (21/41) of patients with a positive 18 F-DCFBC result, generally characterized by starting a new treatment in 19 patients or changing the treatment plan in two patients. 18 F-DCFBC detects recurrences in 60.3% of a population of patients with biochemical recurrence, but

Mechanisms of CNS invasion and damage by parasites.

Science.gov (United States)

Kristensson, Krister; Masocha, Willias; Bentivoglio, Marina

2013-01-01

Invasion of the central nervous system (CNS) is a most devastating complication of a parasitic infection. Several physical and immunological barriers provide obstacles to such an invasion. In this broad overview focus is given to the physical barriers to neuroinvasion of parasites provided at the portal of entry of the parasites, i.e., the skin and epithelial cells of the gastrointestinal tract, and between the blood and the brain parenchyma, i.e., the blood-brain barrier (BBB). A description is given on how human pathogenic parasites can reach the CNS via the bloodstream either as free-living or extracellular parasites, by embolization of eggs, or within red or white blood cells when adapted to intracellular life. Molecular mechanisms are discussed by which parasites can interact with or pass across the BBB. The possible targeting of the circumventricular organs by parasites, as well as the parasites' direct entry to the brain from the nasal cavity through the olfactory nerve pathway, is also highlighted. Finally, examples are given which illustrate different mechanisms by which parasites can cause dysfunction or damage in the CNS related to toxic effects of parasite-derived molecules or to immune responses to the infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Multi-institutional Outcomes of Endoscopic Management of Stricture Recurrence after Bulbar Urethroplasty.

Science.gov (United States)

Sukumar, Shyam; Elliott, Sean P; Myers, Jeremy B; Voelzke, Bryan B; Smith, Thomas G; Carolan, Alexandra Mc; Maidaa, Michael; Vanni, Alex J; Breyer, Benjamin N; Erickson, Bradley A

2018-05-03

Approximately 10-20% of patients will have a recurrence after urethroplasty. Initial management of these recurrences is often with urethral dilation (UD) or direct vision internal urethrotomy (DVIU). In the current study, we describe outcomes of endoscopic management of stricture recurrence after bulbar urethroplasty. We retrospectively reviewed bulbar urethroplasty data from 5 surgeons from the Trauma and Urologic Reconstruction Network of Surgeons. Men who underwent UD or DVIU for urethroplasty recurrence were identified. Recurrence was defined as inability to pass a 17Fr cystoscope through the area of reconstruction. The primary outcome was the success rate of recurrence management. Comparisons were made between UD and DVIU and then between endoscopic management of recurrences after excision and primary anastomosis urethroplasty (EPA) versus substitutional repairs using time-to-event statistics. There were 53 men with recurrence that were initially managed endoscopically. Median time to urethral stricture recurrence after urethroplasty was noted to be 5 months. At a median follow-up of 5 months, overall success was 42%. Success after UD (n=1/10, 10%) was significantly lower than after DVIU (n=21/43, 49%; p urethroplasty. DVIU is more successful for patients with a recurrence after a substitution urethroplasty compared to after EPA, perhaps indicating a different mechanism of recurrence for EPA (ischemic) versus substitution urethroplasty (non-ischemic). Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Effectiveness of Prescription-Based CNS Stimulants on Hospitalization in Patients With Schizophrenia

DEFF Research Database (Denmark)

Rohde, Christopher; Polcwiartek, Christoffer; Asztalos, Marton

2018-01-01

were used to investigate the effectiveness of CNS stimulants in patients with schizophrenia between 1995 and 2014; a mirror-image model with 605 individuals, using paired t tests and Wilcoxon signed rank tests, and a follow-up study with 789 individuals, using a conditional risk-set model. RESULTS: CNS...

Infratentorial brain tumors in children and adolescents - the significance of MRI in the diagnosis of primary and recurrent tumors

International Nuclear Information System (INIS)

Engelbrecht, V.; Kahn, T.; Moedder, U.

1994-01-01

MRI is the current method of choice for the diagnosis of infratentorial tumors in children and adolescents. The present article discusses the individual tumor entities on the basis of their magnetic resonance imaging characteristics in the patient pool of 1991/1992. New magnetic resonance imaging procedures are considered for infratentorial vascular anomalies. In addition to its use in the primary diagnosis, the significance of MRI for the detection of recurrences is discussed. Problems arising after prior surgery and irradiation as well as metastasization through CSF pathways are also mentioned. (orig.) [de

Recurrence and mortality according to Estrogen Receptor status for breast cancer patients undergoing conservative surgery. Ipsilateral breast tumour recurrence dynamics provides clues for tumour biology within the residual breast

International Nuclear Information System (INIS)

Demicheli, Romano; Ardoino, Ilaria; Boracchi, Patrizia; Coradini, Danila; Agresti, Roberto; Ferraris, Cristina; Gennaro, Massimiliano; Hrushesky, William JM; Biganzoli, Elia

2010-01-01

the study was designed to determine how tumour hormone receptor status affects the subsequent pattern over time (dynamics) of breast cancer recurrence and death following conservative primary breast cancer resection. Time span from primary resection until both first recurrence and death were considered among 2825 patients undergoing conservative surgery with or without breast radiotherapy. The hazard rates for ipsilateral breast tumour recurrence (IBTR), distant metastasis (DM) and mortality throughout 10 years of follow-up were assessed. DM dynamics displays the same bimodal pattern (first early peak at about 24 months, second late peak at the sixth-seventh year) for both estrogen receptor (ER) positive (P) and negative (N) tumours and for all local treatments and metastatic sites. The hazard rates for IBTR maintain the bimodal pattern for ERP and ERN tumours; however, each IBTR recurrence peak for ERP tumours is delayed in comparison to the corresponding timing of recurrence peaks for ERN tumours. Mortality dynamics is markedly different for ERP and ERN tumours with more early deaths among patients with ERN than among patients with ERP primary tumours. DM dynamics is not influenced by the extent of conservative primary tumour resection and is similar for both ER phenotypes across different metastatic sites, suggesting similar mechanisms for tumour development at distant sites despite apparently different microenvironments. The IBTR risk peak delay observed in ERP tumours is an exception to the common recurrence risk rhythm. This suggests that the microenvironment within the residual breast tissue may enforce more stringent constraints upon ERP breast tumour cell growth than other tissues, prolonging the latency of IBTR. This local environment is, however, apparently less constraining to ERN cells, as IBTR dynamics is similar to the corresponding recurrence dynamics among other distant tissues

Hypofractionated stereotactic radiation therapy for recurrent glioblastoma: single institutional experience

International Nuclear Information System (INIS)

Ciammella, Patrizia; Podgornii, Ala; Galeandro, Maria; D’Abbiero, Nunziata; Pisanello, Anna; Botti, Andrea; Cagni, Elisabetta; Iori, Mauro; Iotti, Cinzia

2013-01-01

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Tumor control and survival have improved with the use of radiotherapy (RT) plus concomitant and adjuvant chemotherapy, but the prognosis remain poor. In most cases the recurrence occurs within 7–9 months after primary treatment. Currently, many approaches are available for the salvage treatment of patients with recurrent GBM, including resection, re-irradiation or systemic agents, but no standard of care exists. We analysed a cohort of patients with recurrent GBM treated with frame-less hypofractionated stereotactic radiation therapy with a total dose of 25 Gy in 5 fractions. Of 91 consecutive patients with newly diagnosed GBM treated between 2007 and 2012 with conventional adjuvant chemo-radiation therapy, 15 underwent salvage RT at recurrence. The median time interval between primary RT and salvage RT was 10.8 months (range, 6–54 months). Overall, patients undergoing salvage RT showed a longer survival, with a median survival of 33 vs. 9.9 months (p= 0.00149). Median overall survival (OS) from salvage RT was 9.5 months. No patients demonstrated clinically significant acute morbidity, and all patients were able to complete the prescribed radiation therapy without interruption. Our results suggest that hypofractionated stereotactic radiation therapy is effective and safe in recurrent GBM. However, until prospective randomized trials will confirm these results, the decision for salvage treatment should remain individual and based on a multidisciplinary evaluation of each patient

Objective and subjective image quality of primary and recurrent squamous cell carcinoma on head and neck low-tube-voltage 80-kVp computed tomography

Energy Technology Data Exchange (ETDEWEB)

Scholtz, Jan-Erik; Kaup, Moritz; Kraft, Johannes; Noeske, Eva-Maria; Schulz, Boris; Burck, Iris; Kerl, J.M.; Bauer, Ralf W.; Lehnert, Thomas; Vogl, Thomas J.; Wichmann, Julian L. [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology, Frankfurt (Germany); Scheerer, Friedrich [University Hospital Frankfurt, Department of Cranio-Maxillofacial and Plastic Facial Surgery, Frankfurt (Germany); Wagenblast, Jens [University Hospital Frankfurt, Department of Otolaryngology, Head and Neck Surgery, Frankfurt (Germany)

2015-03-26

To investigate low-tube-voltage 80-kVp computed tomography (CT) of head and neck primary and recurrent squamous cell carcinoma (SCC) regarding objective and subjective image quality. We retrospectively evaluated 65 patients (47 male, 18 female; mean age: 62.1 years) who underwent head and neck dual-energy CT (DECT) due to biopsy-proven primary (n = 50) or recurrent (n = 15) SCC. Eighty peak kilovoltage and standard blended 120-kVp images were compared. Attenuation and noise of malignancy and various soft tissue structures were measured. Tumor signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Subjective image quality was rated by three reviewers using 5-point grading scales regarding overall image quality, lesion delineation, image sharpness, and image noise. Radiation dose was assessed as CT dose index volume (CTDI{sub vol}). Interobserver agreement was calculated using intraclass correlation coefficient (ICC). Mean tumor attenuation (153.8 Hounsfield unit (HU) vs. 97.1 HU), SNR (10.7 vs. 8.3), CNR (8.1 vs. 4.8), and subjective tumor delineation (score, 4.46 vs. 4.13) were significantly increased (all P < 0.001) with 80-kVp acquisition compared to standard blended 120-kVp images. Noise of all measured structures was increased in 80-kVp acquisition (P < 0.001). Overall interobserver agreement was good (ICC, 0.86; 95 % confidence intervals: 0.82-0.89). CTDI{sub vol} was reduced by 48.7 % with 80-kVp acquisition compared to standard DECT (4.85 ± 0.51 vs. 9.94 ± 0.81 mGy cm, P < 0.001). Head and neck CT with low-tube-voltage 80-kVp acquisition provides increased tumor delineation, SNR, and CNR for CT imaging of primary and recurrent SCC compared to standard 120-kVp acquisition with an accompanying significant reduction of radiation exposure. (orig.)

Current approaches to enhance CNS delivery of drugs across the brain barriers

Directory of Open Access Journals (Sweden)

Lu CT

2014-05-01

Full Text Available Cui-Tao Lu,1 Ying-Zheng Zhao,2,3 Ho Lun Wong,4 Jun Cai,5 Lei Peng,2 Xin-Qiao Tian1 1The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 2Hainan Medical College, Haikou City, Hainan Province, People’s Republic of China; 3College of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang Province, People’s Republic of China; 4School of Pharmacy, Temple University, Philadelphia, PA, USA; 5Departments of Pediatrics and Anatomical Sciences and Neurobiology, University of Louisville School of Medicine Louisville, KY, USA Abstract: Although many agents have therapeutic potentials for central nervous system (CNS diseases, few of these agents have been clinically used because of the brain barriers. As the protective barrier of the CNS, the blood–brain barrier and the blood–cerebrospinal fluid barrier maintain the brain microenvironment, neuronal activity, and proper functioning of the CNS. Different strategies for efficient CNS delivery have been studied. This article reviews the current approaches to open or facilitate penetration across these barriers for enhanced drug delivery to the CNS. These approaches are summarized into three broad categories: noninvasive, invasive, and miscellaneous techniques. The progresses made using these approaches are reviewed, and the associated mechanisms and problems are discussed. Keywords: drug delivery system, blood–brain barrier (BBB, central nervous system, brain-targeted therapy, cerebrospinal fluid (CSF

Intra-abdominal recurrence of colorectal cancer detected by radioimmunoguided surgery (RIGS system)

International Nuclear Information System (INIS)

Sardi, A.; Workman, M.; Mojzisik, C.; Hinkle, G.; Nieroda, C.; Martin, E.W. Jr.

1989-01-01

Since 1986, 32 patients with metastatic colorectal cancer have undergone second-look radioimmunoguided surgery (RIGS system). The primary tumor was located in the right and transverse colon in 11 patients, left and sigmoid colon in 16, and rectum in five. The carcinoembryonic antigen level was elevated in 30 patients (94%); all patients underwent a computed tomographic scan of the abdomen and pelvis. The overall sensitivity of the computed tomographic scan was 41% (abdomen other than liver, 27%; liver, 58%; and pelvis, 22%). The RIGS system identified recurrent tumor in 81% of the patients. The most common site of metastasis was the liver (41%), independent of the primary location. Local/regional recurrences alone accounted for 40% of all recurrences. In six patients (18%), recurrent tumor was found only with the RIGS system. The RIGS system is more dependable in localizing clinically obscure metastases than other methods, and carcinoembryonic antigen testing remains the most accurate preoperative method to indicate suspected recurrences

Recurrent spine surgery patients in hospital administrative database

Directory of Open Access Journals (Sweden)

M. Sami Walid

2012-02-01

Full Text Available Introduction: Hospital patient databases are typically used by administrative staff to estimate loss-profit ratios and to help with the allocation of hospital resources. These databases can also be very useful in following rehospitalization. This paper studies the recurrence of spine surgery patients in our hospital population based on administrative data analysis. Methods: Hospital data on 4,958 spine surgery patients operated between 2002 and 2009 were retrospectively reviewed. After sorting the cohort per ascending discharge date, the patient official name, consisting of first, middle and last names, was used as the variable determining duplicate cases in the SPSS statistical program, designating the first case in each group as primary. Yearly recurrence rate and change in procedure distribution were studied. In addition, hospital charges and length of stay were compared using the Wilcoxon-Mann-Whitney test. Results: Of 4,958 spine surgery patients 364 (7.3% were categorized as duplicate cases by SPSS. The number of primary cases from which duplicate cases emerged was 327 meaning that some patients had more than two spine surgeries. Among primary patients (N=327 the percentage of excision of intervertebral disk procedures was 33.3% and decreased to 15.1% in recurrent admissions of the same patients (N=364. This decrease was compensated by an increase in lumbar fusion procedures. On the other hand, the rate of cervical fusion remained the same. The difference in hospital charges between primary and duplicate patients was $2,234 for diskectomy, $6,319 for anterior cervical fusion, $8,942 for lumbar fusion – lateral technique, and $12,525 for lumbar fusion – posterior technique. Recurrent patients also stayed longer in hospital, up to 0.9 day in lumbar fusion – posterior technique patients. Conclusion: Spine surgery is associated with an increasing possibility of additional spine surgery with rising invasiveness and cost.

When the Tail Can't Wag the Dog: The Implications of CNS-Intrinsic Initiation of Neuroinflammation

Directory of Open Access Journals (Sweden)

Deirdre S Davis

2009-04-01

Full Text Available The CNS (central nervous system is unquestionably the central organ that regulates directly or indirectly all physiological systems in the mammalian body. Yet, when considering the defence of the CNS from pathogens, the CNS has often been considered passive and subservient to the pro-inflammatory responses of the immune system. In this view, neuroinflammatory disorders are examples of when the tail (the immune system wags the dog (the CNS to the detriment of an individual's function and survival.

Primary Cutaneous Aspergillosis in an Immunocompetent Patient

African Journals Online (AJOL)

are the lungs, central nervous system (CNS), and sinuses, however, the rare cutaneous infection is usually associated with immunodeficiency. Primary cutaneous infection, especially in immunocompetent patients, is extremely rare, but an increase in prevalence has been noted in the last. 20 years. The predisposing factors ...

Comparison of serum YKL-40 bio marker levels in primary prostate cancer and recurrent cases after radiotherapy

International Nuclear Information System (INIS)

Ziada, M.M.S.

2012-01-01

YKL-40, also called human cartilage glycoprotein-39 is homologs of family 18 glycosyl hydrolases secreted by human macrophages.Although high levels of YKL-40 is associated with several diseases. YKL-40, a growth factor for connective tissue cells, a migration factor for endothelial and vascular smooth muscle cells, is expressed by several types of solid human carcinoma, including prostate carcinoma. The aim of this study was to evaluate diagnostic role of serum YKL-40 levels in primary prostate cancer and detection of recurrences after radiotherapy. Methods: YKL-40 determined in serum samples from 50 patients with primary prostate cancer and 25 patients with benign prostatic hyperplasia as control. Serum YKL-40 levels were measured by ELISA. PSA levels were also measured by using IMMULIT system. Results: Serum YKL-40 levels were significantly higher (P= 0.000) in patients with prostate cancer compared with control group whereas no significant elevation in BPH. Conclusion: High serum YKL-40 levels in patients with primary prostate cancer indicate that YKL-40 may have a function in the Progression of malignant diseases, whereas no significant elevation was observed in benign prostatic hyperplasia. Further studies are needed to elucidate the biologic role of YKL-40 in cancer aggressiveness and in progression of malignant diseases.

Recurrences of Bell's palsy.

Science.gov (United States)

Cirpaciu, D; Goanta, C M; Cirpaciu, M D

2014-01-01

Bell's palsy in known as the most common cause of facial paralysis, determined by the acute onset of lower motor neuron weakness of the facial nerve with no detectable cause. With a lifetime risk of 1 in 60 and an annual incidence of 11-40/100,000 population, the condition resolves completely in around 71% of the untreated cases. Clinical trials performed for Bell's palsy have reported some recurrences, ipsilateral or contralateral to the side affected in the primary episode of facial palsy. Only few data are found in the literature. Melkersson-Rosenthal is a rare neuromucocutaneous syndrome characterized by recurrent facial paralysis, fissured tongue (lingua plicata), orofacial edema. We attempted to analyze some clinical and epidemiologic aspects of recurrent idiopathic palsy, and to develop relevant correlations between the existing data in literature and those obtained in this study. This is a retrospective study carried out on a 10-years period for adults and a five-year period for children. A number of 185 patients aged between 4 and 70 years old were analyzed. 136 of them were adults and 49 were children. 22 of 185 patients with Bell's palsy (12%) had a recurrent partial or complete facial paralysis with one to six episodes of palsy. From this group of 22 cases, 5 patients were diagnosed with Melkersson-Rosenthal syndrome. The patients' age was between 4 and 70 years old, with a medium age of 27,6 years. In the group studied, fifteen patients, meaning 68%, were women and seven were men. The majority of patients in our group with more than two facial palsy episodes had at least one episode on the contralateral side. Our study found a significant incidence of recurrences of idiopathic facial palsy. Recurrent idiopathic facial palsy and Melkersson-Rosenthal syndrome is diagnosed more often in young females. Recurrence is more likely to occur in the first two years from the onset, which leads to the conclusion that we should have a follow up of patients

Nootropic, anxiolytic and CNS-depressant studies on different plant sources of shankhpushpi.

Science.gov (United States)

Malik, Jai; Karan, Maninder; Vasisht, Karan

2011-12-01

Shankhpushpi, a well-known drug in Ayurveda, is extensively used for different central nervous system (CNS) effects especially memory enhancement. Different plants are used under the name shankhpushpi in different regions of India, leading to an uncertainty regarding its true source. Plants commonly used under the name shankhpushpi are: Convolvulus pluricaulis Chois., Evolvulus alsinoides Linn., both from Convolvulaceae, and Clitoria ternatea Linn. (Leguminosae). To find out the true source of shankhpushpi by evaluating and comparing memory-enhancing activity of the three above mentioned plants. Anxiolytic, antidepressant and CNS-depressant activities of these three plants were also compared and evaluated. The nootropic activity of the aqueous methanol extract of each plant was tested using elevated plus-maze (EPM) and step-down models. Anxiolytic, antidepressant and CNS-depressant studies were evaluated using EPM, Porsolt?s swim despair and actophotometer models, respectively. C. pluricaulis extract (CPE) at a dose of 100 mg/kg, p.o. showed maximum nootropic and anxiolytic activity (p nootropic, anxiolytic and CNS-depressant activity. The results of memory-enhancing activity suggest C. pluricaulis to be used as true source of shankhpushpi.

Drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection.

Science.gov (United States)

Xu, Chuan; Huang, Xin-En; Wang, Shu-Xiang; Lv, Peng-Hua; Sun, Ling; Wang, Fu-An; Wang, Li-Fu

2014-01-01

To compare drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection. We collect 42 patients with obstructive jaundice caused by recurrence and metastasis after tumor resection from January 2008 - August 2012, for which percutaneous transhepatic catheter drainage (pTCD)/ percutaneous transhepatic biliary stenting (pTBS) were performed. In 25 patients drainage was combined with anti-tumor treatment, antineoplastic therapy including intra/postprodure local treatment and postoperative systemic chemotherapy, the other 17 undergoing drainage only. We assessed the two kinds of treatment with regard to patient prognosis. Both treatments demonstrated good effects in reducing bilirubin levels in the short term and promoting liver function. The time to reobstruction was 125 days in the combined group and 89 days in the drainage only group; the mean survival times were 185 and 128 days, the differences being significant. Interventional drainage in the treatment of the obstructive jaundice caused by recurrence and metastasis after tumor resection can decrease bilirubin level quickly in a short term and promote the liver function recovery. Combined treatment prolongs the survival time and period before reobstruction as compared to drainage only.

Rate of recurrence and malignant transformation in 88 cases with inverted papilloma between 1998-2008

DEFF Research Database (Denmark)

Nygren, Alexander; Kiss, Katalin; von Buchwald, Christian

2016-01-01

Conclusions The recurrence rate of IP in the current study is comparable to international and national studies. When the primary tumour was located in the frontal or the sphenoid sinus, the tumour seemed more likely to recur. Some recurrences were more than 2 years after primary surgery, suggesti...

Value of computerized tomography in the diagnosis of primary and recurrent pituitary gland tumors

International Nuclear Information System (INIS)

Imhof, H.; Kuester, W.; Eslami-Nejad, S.

1979-01-01

The results of cranial computerized tomography (CCT) of 33 patients with questionable space-occupying lesions in the sella-region are compared with clinical, radiological and surgical reports. Five pituitary gland tumors could be detected for the first time. Four of them are verified by surgery. In eight cases recurrent pituitary glant tumors are suspected. Surprisingly these tumors could be found by surgery only in three cases, while in the remaining five cases only scar-tissue was demonstrable. The high accuracy of CCT in the detection of pituitary gland tumors and the possibility to save the patient expensive and high invasive examinations as well, makes CCT in the presence of corresponding clinical signs to a diagnostic 'must'. It is undecided whether in the cases with possible recurrent tumors, there are real recurrent tumors, which could not be detected by surgery, or only scar tissue. In the latter case scar tissue and recurrent pituitary gland tumors are very similar with CCT. (orig.) 891 MG/orig. 892 CKA [de

Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development.

Directory of Open Access Journals (Sweden)

Kate Kosmac

2013-03-01

Full Text Available Infection of the developing fetus with human cytomegalovirus (HCMV is a major cause of central nervous system disease in infants and children; however, mechanism(s of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV.

CT urography in women with primary or recurrent pelvic tumors. Background and initial experiences; CT-Urographie bei Frauen mit primaeren oder rezidivierenden Beckentumoren. Hintergrund und erste Erfahrungen

Energy Technology Data Exchange (ETDEWEB)

Seifert, S.; Mueller-Lisse, U.G.; Degenhart, C.; Mourched, F.; Reiser, M.F. [Klinikum der Ludwig-Maximilians-Universitaet, Campus Innenstadt, Institut fuer Klinische Radiologie, Muenchen (Germany); Jundt, K. [Klinikum der Ludwig-Maximilians-Universitaet, Campus Innenstadt, Klinik und Poliklinik fuer Gynaekologie und Geburtshilfe, Muenchen (Germany); Stief, C.G.; Mueller-Lisse, U.L. [Klinikum der Ludwig-Maximilians-Universitaet, Campus Innenstadt, Klinik und Poliklinik fuer Urologie, Muenchen (Germany)

2011-07-15

Malignant tumors of the female pelvis account for 12-13% of newly diagnosed solid neoplasms among women in the USA and Germany. German guidelines advocate diagnostic imaging for local recurrence and metastasis while there are no recommendations for primary tumors. As excretory urography has been replaced by the excretory phase of computed tomography urography (CTU) in many institutions, two independent observers retrospectively evaluated CTUs of primary or recurrent female pelvic tumors to rule out associations between CTU findings and subsequent urologic measures. Among 31 CTUs of 27 women (age 29-84 years, mean 57 years) with 15 primary and 13 recurrent tumors, 83-100% of unremarkable proximal, middle and distal ureter segments were completely delineated in the excretory phase (delay 6-29 min, mean 16 min). The most common pathological findings included distal ureter obstruction (n=19, 61%), bladder compression (n=13, 42%) and bladder invasion (n=8, 26%). Out of 20 pathologically altered urinary tracts 8 were subsequently subjected to urologic measures (2-tailed Fisher exact test, p=0.0215) but none of the 10 unremarkable urinary tracts were treated. It appears that CTU is a sensible pre-therapeutic test for the urinary tract for primary and recurrent female pelvic tumors. (orig.) [German] Maligne Beckentumoren stellen 12-13% aller neu diagnostizierten soliden Neoplasien bei Frauen in den USA und in Deutschland dar. Deutsche Leitlinien befuerworten bildgebende Untersuchungen bei Lokalrezidiven und Metastasen; fuer Primaertumoren gibt es keine einschlaegigen Empfehlungen. Da das Ausscheidungsurogramm durch die Ausscheidungsaufnahme der CT-Urographie (CTU) weitgehend abgeloest ist, wurde bei weiblichen Beckentumoren oder deren Rezidive der Zusammenhang zwischen CTU-Befunden und nachfolgenden operativen urologischen Massnahmen retrospektiv von 2 unabhaengigen Auswertern geprueft. Bei 31 CTUs von 27 Frauen (Alter 29-84, Median 57 Jahre) mit 15 Primaertumoren und 13

The shifting landscape of metastatic breast cancer to the CNS.

Science.gov (United States)

Quigley, Matthew R; Fukui, Olivia; Chew, Brandon; Bhatia, Sanjay; Karlovits, Steven

2013-07-01

The improved survival following the diagnosis of breast cancer has potentially altered the characteristics and course of patients presenting with CNS involvement. We therefore sought to define our current cohort of breast cancer patients with metastatic disease to the CNS in regard to modern biomarkers and clinical outcome. Review of clinical and radiographic records of women presenting to a tertiary medical center with the new diagnosis of CNS metastatic disease from breast cancer. This was a retrospective review from patients identities obtained from two prospective databases. There were 88 women analyzed who were treated over the period of January 2003 to February 2010, average age 56.9 years. At the time of initial presentation of CNS disease, 68 % of patients had multiple brain metastases, 17 % had a solitary metastasis, and 15 % had only leptomeningeal disease (LMD). The median survival for all patients from the time of diagnosis of breast disease was 50.0 months, and 9.7 months from diagnosis of CNS involvement. The only factor related to overall survival was estrogen receptor-positive pathology (57.6 v. 38.2 months, p = .02 log-rank); those related to survival post CNS diagnosis were presentation with LMD (p = .004, HR = 3.1, Cox regression) and triple-negative hormonal/HER2 status (p = .02, HR = 2.3, Cox regression). Patients with either had a median survival of 3.1 months (no patients in common). Of the 75 patients who initially presented with metastatic brain lesions, 20 (26 %) subsequently developed LMD in the course of their disease (median 10.4 months), following which survival was grim (1.8 months median). Symptoms of LMD were most commonly lower extremity weakness (14/33), followed by cranial nerve deficits (11/33). The recently described Graded Prognostic Assessment (GPA) tumor index stratified median survival at 2.5, 5.9, 13.1, and 21.7 months, respectively, for indices of 1-4 (p = .004, log-rank), which

Value of (18F)-FDG positron emission tomography, computed tomography, and magnetic resonance imaging in diagnosing primary and recurrent ovarian carcinoma

International Nuclear Information System (INIS)

Kubik-Huch, R.A.; Doerffler, W.; Marincek, B.; Schulthess, G.K.; Steinert, H.C.; Koechli, O.R.; Haller, U.; Seifert, B.

2000-01-01

The aim of this study was to compare prospectively the accuracy of whole-body positron emission tomography (PET), CT and MRI in diagnosing primary and recurrent ovarian cancer. Nineteen patients (age range 23-76 years) were recruited with suspicious ovarian lesions at presentation (n = 8) or follow-up for recurrence (n = 11). All patients were scheduled for laparotomy and histological confirmation. Whole-body PET with FDG, contrast-enhanced spiral CT of the abdomen, including the pelvis, and MRI of the entire abdomen were performed. Each imaging study was evaluated separately. Imaging findings were correlated with histopathological diagnosis. The sensitivity, specificity and accuracy for lesion characterization in patients with suspicious ovarian lesions (n = 7) were, respectively: 100, 67 and 86 % for PET; 100, 67 and 86 % for CT; and 100, 100 and 100 % for MRI. For the diagnosis of recurrent disease (n = 10), PET had a sensitivity of 100 %, specificity of 50 % and accuracy of 90 %. The PET technique was the only technique which correctly identified a single transverse colon metastasis. Results for CT were 40, 50 and 43 %, and for MRI 86, 100 and 89 %, respectively. No statistically significant difference was seen. Neither FDG PET nor CT nor MRI can replace surgery in the detection of microscopic peritoneal disease. No statistically significant difference was observed for the investigated imaging modalities with regard to lesion characterization or detection of recurrent disease; thus, the methods are permissible alternatives. The PET technique, however, has the drawback of less accurate spatial assignment of small lesions compared with CT and MRI. (orig.)

Clinical impact of PSMA-based {sup 18}F-DCFBC PET/CT imaging in patients with biochemically recurrent prostate cancer after primary local therapy

Energy Technology Data Exchange (ETDEWEB)

Mena, Esther [Molecular Imaging Program, National Cancer Institute, NIH, Bethesda, MD (United States); Lindenberg, Maria L.; Bergvall, Ethan; Ton, Anita T.; McKinney, Yolanda; Eclarinal, Philip; Choyke, Peter L.; Turkbey, Baris [Molecular Imaging Program, National Cancer Institute, NIH, Bethesda, MD (United States); Shih, Joanna H. [National Cancer Institute, NIH, Division of Cancer treatment and Diagnosis: Biometric Research Program, Bethesda, MD (United States); Adler, Stephen; Harmon, Stephanie; Weaver, Juanita; Forest, Alicia [National Cancer Institute, Campus at Frederick, Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick, MD (United States); Citrin, Deborah [Radiation Oncology Branch, Center for Cancer Research. National Cancer Institute, NIH, Bethesda, MD (United States); Dahut, William [National Cancer Institute, NIH, Genitourinary Malignancies Branch, Bethesda, MD (United States); Afari, George; Bhattacharyya, Sibaprasad [Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (United States); Mease, Ronnie C.; Pomper, Martin G. [Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Merino, Maria J. [Laboratory of Pathology, NCI, NIH, Bethesda, MD (United States); Pinto, Peter [National Cancer Institute, NIH, Urologic Oncology Branch, Bethesda, MD (United States); Wood, Bradford J. [National Cancer Institute, NIH, Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, Bethesda, MD (United States); Jacobs, Paula [National Cancer Institute, NIH, Cancer Imaging Program, Rockville, MD (United States)

2018-01-15

The purpose of our study was to assess {sup 18}F-DCFBC PET/CT, a PSMA targeted PET agent, for lesion detection and clinical management of biochemical relapse in prostate cancer patients after primary treatment. This is a prospective IRB-approved study of 68 patients with documented biochemical recurrence after primary local therapy consisting of radical prostatectomy (n = 50), post radiation therapy (n = 9) or both (n = 9), with negative conventional imaging. All 68 patients underwent whole-body {sup 18}F-DCFBC PET/CT, and 62 also underwent mpMRI within one month. Lesion detection with {sup 18}F-DCFBC was correlated with mpMRI findings and pre-scan PSA levels. The impact of {sup 18}F-DCFBC PET/CT on clinical management and treatment decisions was established after 6 months' patient clinical follow-up. Forty-one patients (60.3%) showed at least one positive {sup 18}F-DCFBC lesion, for a total of 79 lesions, 30 in the prostate bed, 39 in lymph nodes, and ten in distant sites. Tumor recurrence was confirmed by either biopsy (13/41 pts), serial CT/MRI (8/41) or clinical follow-up (15/41); there was no confirmation in five patients, who continue to be observed. The {sup 18}F-DCFBC and mpMRI findings were concordant in 39 lesions (49.4%), and discordant in 40 lesions (50.6%); the majority (n = 32/40) of the latter occurring because the recurrence was located outside the mpMRI field of view. {sup 18}F-DCFBC PET positivity rates correlated with PSA values and 15%, 46%, 83%, and 77% were seen in patients with PSA values <0.5, 0.5 to <1.0, 1.0 to <2.0, and ≥2.0 ng/mL, respectively. The optimal cut-off PSA value to predict a positive {sup 18}F-DCFBC scan was 0.78 ng/mL (AUC = 0.764). A change in clinical management occurred in 51.2% (21/41) of patients with a positive {sup 18}F-DCFBC result, generally characterized by starting a new treatment in 19 patients or changing the treatment plan in two patients. {sup 18}F-DCFBC detects recurrences in 60.3% of a population of

Primary malignant melanoma of the vagina with repeated local recurrences and brain metastasis

Directory of Open Access Journals (Sweden)

Li-Te Lin

2011-08-01

Full Text Available Malignant melanoma of the vagina, a very rare malignancy, has a notoriously aggressive behavior associated with a high risk of local recurrence and distant metastasis. At present, there are various treatment options for this disease but no standard guideline. We describe a case of a 54-year-old woman with a locally advanced melanoma of the vagina, who underwent radical surgery, biochemotherapy with interferon-α-2b, chemotherapy, radiotherapy, and repeat excision of local recurrent lesions and brain metastasis. In conclusion, malignant melanoma of the vagina has a high risk for local recurrence. Repeated local excision followed by biochemotherapy is a tolerable treatment.

Rectal bacteriotherapy for recurrent Clostridium difficile-associated diarrhoea

DEFF Research Database (Denmark)

Tvede, M; Tinggaard, M; Helms, M

2015-01-01

Clostridium difficile infection is one of the most common nosocomial infections. Among other alternatives to standard treatment with vancomycin for recurrent infection are faecal microbiota transplantation and rectal bacteriotherapy with a fixed mixture of intestinal bacterial strains isolated from...... for relapsing C. difficile in Denmark, 2000-2012. The primary end point was recurrent diarrhoea within 30 days after treatment. A total of 55 patients were included in this case series. Thirty-five patients (64%) had no recurrence within 30 days of bacteriotherapy. Patients with recurrence tended to be older....... difficile episode less than 6 months before bacteriotherapy. The most common adverse events were abdominal pain (10.9%) and worsening diarrhoea (4.3%). One patient was hospitalized 10 days after treatment with appendicitis, fever, and Escherichia coli bacteremia. The results from this study indicate...

[Selective neck dissection for treating recurrent branchial anomalies].

Science.gov (United States)

Chen, Liangsi; Song, Xinhan; Zhang, Siyi; Han, Zhijuan; Luo, Xiaoning; Chen, Shaohua; Zhan, Jiandong

2011-01-01

To evaluate the role of selective neck dissection in the treatment of recurrent branchial anomalies. The clinical data of 18 patients with recurrent branchial anomalies were retrospectively analyzed. In accordance with the embryologic and anatomic features of branchial anomalies, different types of selective neck dissection were applied. With dissection and protection of important vessels, nerves and other structures, enbloc resection principles were applied to extirpate branchial lesions, scarrings and inflammatory granuloma during the operation. Of all 18 patients, 16 cases were healed with primary healing, 2 cases with local incision infection were healed after dressing changes. A temporary facial nerve paralysis occurred in 1 case with recurrent first branchial cleft fistula postoperatively, and completely recovered 2 months after operation. A postoperative temporary vocal cord paralysis occurred in 1 case with recurrent fourth branchial cleft fistula, and totally recuperated 1 month after operation. No recurrences were found in all 18 cases with a follow-up period of 12-78 months (average 35 months). Selective neck dissection is a safe and effective surgical procedure for the radical treatment of recurrent branchial anomalies.

Ketamine displaces the novel NMDA receptor SPET probe [123I]CNS-1261 in humans in vivo

International Nuclear Information System (INIS)

Stone, James M.; Erlandsson, Kjell; Arstad, Erik; Bressan, Rodrigo A.; Squassante, Lisa; Teneggi, Vincenza; Ell, Peter J.; Pilowsky, Lyn S.

2006-01-01

[ 123 I]CNS-1261 [N-(1-naphthyl)-N'-(3-iodophenyl)-N-methylguanidine] is a high-affinity SPET ligand with selectivity for the intrachannel PCP/ketamine/MK-801 site of the N-methyl-D-aspartate (NMDA) receptor. This study evaluated the effects of ketamine (a specific competitor for the intrachannel PCP/ketamine/MK-801 site) on [ 123 I]CNS-1261 binding to NMDA receptors in vivo. Ten healthy volunteers underwent 2 bolus-plus-infusion [ 123 I]CNS-1261 scans, one during placebo and the other during a ketamine challenge. Ketamine administration led to a significant decrease in [ 123 I]CNS-1261 V T in most of the brain regions examined (P 123 I]CNS-1261 appears to be a specific ligand in vivo for the intrachannel PCP/ketamine/MK-801 NMDA binding site

Hepatic angiosarcoma manifested as recurrent hemoperitoneum

Science.gov (United States)

Lee, Seung-Woo; Song, Chun-Young; Gi, Young-Hwa; Kang, Sang-Beom; Kim, Yon-Soo; Nam, Soon-Woo; Lee, Dong-Soo; Kim, Jong-Ok

2008-01-01

Angiosarcoma is a rare tumor that account for less than 1% of all sarcomas. Although hepatic angiosarcoma usually presents with unspecific symptoms, it rapidly progresses and has a high mortality. We report a rare case of primary hepatic angiosarcoma manifested as recurrent hemoperitoneum. PMID:18473427

[11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter

DEFF Research Database (Denmark)

Vase, Karina Højrup; Peters, Dan; Nielsen, Elsebeth Ø

2014-01-01

-azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. METHODS: Labeling of NS8880 with [11C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [11C]methanolate...... yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [11C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [11C]NS8880. CONCLUSION: Based...... on the pre-clinical results obtained so far [11C]NS8880 displays promising properties for PET imaging of NET....

Morphological evaluation of fetus CNS and its related anomalies

International Nuclear Information System (INIS)

Oi, Shizuo; Tamaki, Norihiko; Matsumoto, Satoshi; Katayama, Kazuaki; Mochizuki, Matsuto

1989-01-01

The fetus central nervous system was evaluated morphologically by ultrasonography (US), magnetic resonance imaging (MRI), and CT scan to analyze the prenatal diagnostic value for CNS anomalies. A total of 31 patients with 42 lesions had been diagnosed during the preceding 7 years. The patients included 24 with hydrocephalus, three with anencephaly, three with myeloschisis, three with holoprosencephaly, three with an encephalocele, two with a Dandy-Walker cyst, one with hydroencephalodysplasia, one with an intracranial neoplasm, one with sacrococcygeal teratoma, and one with sacral agenesis. Compared with US and MRI, CT proved to be more accurate in the detection of spine and cranium-bone morphology. This finding seems to be valuable in the diagnosis of spina bifida, cranium bifidum and some cases of hypertensive hydrocephalus, especially in the axial view. MRI was definitely superior in the anatomico-pathological diagnosis of cerebral dysgenesis, ventriculomegaly, intracranial tumors, and other brain parenchymal changes in view of multi-dimensional analysis. The most considerable disadvantage of MRI in the diagnosis of a fetus CNS anomaly is the poor information about spine and cranium morphology. A super-conducting MRI system is still insufficient to demonstrate the spinal cord of a fetus. US was routinely used, and the multidimensional slices were useful for screening the CNS abnormalies. Some of the fetus brain lesions, such as intracranial hematomas, had a specific echogenecity on US. However, US sometimes failed to demarcate the cerebral parenchymal or subdural morphological changes because its artifacts had hyperchoic shadows. While US, MRI, and CT were valuable diagnostic tools in the morphological evaluation of fetus CNS and its related anomalies, each modality has different diagnostic advantages and disadvantages. Improvement can be expected when these diagnostic imaging modalities are complementary, depending upon the nature of the anatomy. (J.P.N.)

Analysis of neurocognitive function and CNS endpoints in the PROTEA trial

DEFF Research Database (Denmark)

Clarke, Amanda; Johanssen, Veronika; Gerstoft, Jan

2014-01-01

INTRODUCTION: During treatment with protease inhibitor monotherapy, the number of antiretrovirals with therapeutic concentrations in the cerebrospinal fluid (CSF) is lower, compared to standard triple therapy. However, the clinical consequences are unclear. METHODS: A total of 273 patients with HIV...... and the Grooved Pegboard Test at screening, baseline and at Week 48. A global neurocognitive score (NPZ-5) was derived by averaging the standardized results of the five domains. In a central nervous system (CNS) sub-study (n=70), HIV RNA levels in the CNS were evaluated at baseline and Week 48. Clinical adverse...... events related to the CNS were collected at each visit. RESULTS: Patients were 83% male and 88% White, with median age 43 years. There were more patients with nadir CD4 count below 200 cells/µL in the DRV/r monotherapy arm (41/137, 30%) than the triple therapy arm (30/136, 22%). At Week 48...

Management of Biochemical Recurrence after Primary Localized Therapy for Prostate Cancer

International Nuclear Information System (INIS)

Darwish, Oussama M.; Raj, Ganesh V.

2012-01-01

Clinically localized prostate cancer is typically managed by well established therapies like radical prostatectomy, brachytherapy, and external beam radiation therapy. While many patients can be cured with definitive local therapy, some will have biochemical recurrence (BCR) of disease detected by a rising serum prostate-specific antigen (PSA). Management of these patients is nuanced and controversial. The natural history indicates that a majority of patients with BCR will not die from prostate cancer but from other causes. Despite this, a vast majority of patients with BCR are empirically treated with non-curable systemic androgen deprivation therapy (ADT), with its myriad of real and potential side effects. In this review article, we examined the very definition of BCR after definitive local therapy, the current status of imaging studies in its evaluation, the need for additional therapies, and the factors involved in the decision making in the choice of additional therapies. This review aims to help clinicians with the management of patients with BCR. The assessment of prognostic factors including absolute PSA level, time to recurrence, PSA kinetics, multivariable nomograms, imaging, and biopsy of the prostatic bed may help stratify the patients into localized or systemic recurrence. Patients with low-risk of systemic disease may be cured by a salvage local therapy, while those with higher risk of systemic disease may be offered the option of ADT or a clinical trial. An algorithm incorporating these factors is presented.

A comprehensive profile of recurrent glioblastoma

DEFF Research Database (Denmark)

Campos, B.; Olsen, Lars Rønn; Urup, T.

2016-01-01

In spite of relentless efforts to devise new treatment strategies, primary glioblastomas invariably recur as aggressive, therapy-resistant relapses and patients rapidly succumb to these tumors. Many therapeutic agents are first tested in clinical trials involving recurrent glioblastomas. Remarkab...... 2016; doi:10.1038/onc.2016.85....

Primary Central Nervous System Tumours in Children and ...

African Journals Online (AJOL)

Primary CNS tumours are the commonest childhood solid tumours in most developed countries, accounting for 25-30% of cases. In our environment they occur less frequently. These tumours are nonetheless the cause of significant morbidity and mortality in the paediatric age group worldwide. However paediatric CNS ...

Nuclear innovation through collaboration. 35th Annual CNS conference and 39th CNS/CNA student conference

International Nuclear Information System (INIS)

2015-01-01

The Canadian Nuclear Society (CNS) held its 35th Annual Conference in Saint John, New Brunswick, Canada on May 31 to June 3, 2015, combined with the 39th Annual CNS/CNA Student Conference. With the theme of the conference, 'Nuclear Innovation through Collaboration', more than 425 delegates, exhibitors and students were in attendance. The conference commenced with two strong plenary sessions on Utility Collaborations to Improve Lifetime Performance; and, Performance Improvement Programs: Goals and Experience. The second day consisted of the panel discussions on International Developments in Used Nuclear Fuel Repository Programs, and two plenary sessions on: Enterprise Risk Management; and, Vendor Role in a Continuously Improving Industry. The third day contained a number of interesting features, including plenary sessions on Waste Management and Decommissioning; Developing Technologies and Resources, and a panel discussion on the Transportation of Used Nuclear Fuel. All three days of the conference also contained parallel sessions with over 100 technical papers presented at the main and student sessions. The technical session titles were: Refurbishment and Life Extension; Thermalhydraulics; Nuclear Materials; WMD - Radiation Monitoring; Safety and Licensing; Communication; Safety and Licensing; Instrumentation and Control; Advanced Reactor Designs; WMD - Deep Geological Repository Packaging; Reactor Physics; Chemistry and Materials; Advanced Fuel Cycles; Waste Management and Decommissioning; and, Medical Physics and Radiation Biology.

Metallothionein expression and roles in the CNS

DEFF Research Database (Denmark)

Penkowa, Milena

2002-01-01

  Metallothioneins (MTs) are low-molecular-weight (6-7 kDa) nonenzymatic proteins (60-68 amino acid residues, 25-30% being cysteine) expressed ubiquitous in the animal kingdom. In the central nervous system (CNS), three MT isoforms are known, namely MT-I to MT-III. MT-I and MT-II (MT...

CNS Involvement in Hemophagocytic Lymphohistiocytosis: CT and MR Findings

International Nuclear Information System (INIS)

Chung, Tae Woong

2007-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by proliferation of benign histiocytes, and this commonly involves the liver, spleen, lymph nodes, bone marrow and central nervous system (CNS). We report here on the CT and MR imaging findings in a case of CNS HLH that showed multiple ring enhancing masses mimicking abscess or another mass on the CT and MR imaging. emophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by nonmalignant diffuse infiltration of multiple organs, including the central nervous system (CNS), by lymphocytes and histiocytes (1). Many radiologic reports describing diffuse white matter infiltrations, parenchymal atrophy and calcification have been published, but the characteristics of these findings remain non-specific, especially in immunocompromised patients. We present here a case of HLH in a 3-year-old boy who presented with multiple ring enhancing lesions involving the brain. In conclusion, although the CT and MRI findings of HLH with ring enhancing parenchymal lesions are nonspecific and mimic abscess, and especially in the immunosuppressed patients, increased diffusion at the center on DWI may be a finding of HLH to differentiate it from abscess, which has restricted diffusion at the center. However, the pathologic correlation with DWI according to the lesion stage certainly needs further study with a larger number of patients

Is risk of central nervous system (CNS) relapse related to adjuvant taxane treatment in node-positive breast cancer? Results of the CNS substudy in the intergroup Phase III BIG 02-98 Trial

DEFF Research Database (Denmark)

Pestalozzi, B.C.; Francis, P.; Quinaux, E.

2008-01-01

BACKGROUND: Breast cancer central nervous system (CNS) metastases are an increasingly important problem because of high CNS relapse rates in patients treated with trastuzumab and/or taxanes. PATIENTS AND METHODS: We evaluated data from 2887 node-positive breast cancer patients randomised in the BIG...

Randomized phase III trial (GORTEC 98-03) comparing re-irradiation plus chemotherapy versus methotrexate in patients with recurrent or a second primary head and neck squamous cell carcinoma, treated with a palliative intent

International Nuclear Information System (INIS)

Tortochaux, Jacques; Tao Yungan; Tournay, Elodie; Lapeyre, Michel; Lesaunier, Francois; Bardet, Etienne; Janot, Francois; Lusinchi, Antoine; Benhamou, Ellen; Bontemps, Patrick; Maingon, Philippe; Calais, Gilles; Daly-Schveitzer, Nicolas; Verrelle, Pierre; Bourhis, Jean

2011-01-01

Purpose: This randomized phase III trial investigated the potential benefit of concurrent re-irradiation, fluorouracil and hydroxyurea versus methotrexate for patients treated with palliative intent for recurrent or second primary head and neck squamous cell carcinoma (HNSCC) in previously irradiated area. Patients and methods: Patients with recurrent HNSCC or a second primary not amenable to curative-intent treatment were randomized to the R-RT arm (concurrent re-irradiation, fluorouracil and hydroxyurea) or to the Ch-T arm (methotrexate). The primary endpoint was overall survival (OS). Due to a very slow accrual, the trial was closed after inclusion of 57 patients. Results: Fifty-seven patients were included. All patients died in the two arms with a maximal follow-up of 5 years. Although four complete responses were achieved in R-RT arm, (none in Ch-T arm) re-irradiation did not improve OS compared with methotrexate (23% versus 22% at 1 year, NS). Sixteen patients experienced clinical grade ≥3 late toxicities (>6 months), 11 in R-RT arm and five in Ch-T arm. Conclusions: Premature discontinuation of the trial did not allow us to draw firm conclusions. However, there was no suggestion that concurrent re-irradiation, fluorouracil and hydroxyurea improved OS compared to methotrexate alone in patients treated with palliative intent for a recurrent or second primary HNSCC.

Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine Model of CNS Neuroinflammation.

Directory of Open Access Journals (Sweden)

Kristel Kegler

Full Text Available Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas

Assessment of sleep quality in benign paroxysmal positional vertigo recurrence.

Science.gov (United States)

Wang, Yun; Fei Xia, Fei; Wang, Wei; Hu, Wenli

2018-06-08

Despite the availability of highly effective treatments, there is a significant recurrence rate of benign paroxysmal positional vertigo (BPPV). This study is aimed to quantitatively measure sleep quality in BPPV patients and correlate it with the recurrence of BPPV. In this longitudinal cohort study, the clinical records of 67 elderly or middle-aged adult patients who were diagnosed with BPPV at Neurology Clinic, Beijing Chaoyang Hospital affiliated to Capital Medical University between 2013 and 2014. The "Recurrent" and "Non-recurrent" BPPV were respectively defined. Primary data collection included the medical history, blood test and Pittsburgh sleep quality index measurement. Among the total 67 patients after successful treatment, recurrent BPPV is observed in 37.31% patients (n = 25) within 2 years. Among all 11 variables analyzed between recurrent and non-recurrent groups, only the Pittsburgh Sleep Quality Index (PSQI) scores showed significant difference (P quality, sleep latency, sleep duration, the use of sleep-aid medication and daytime dysfunctions (all P quality) had higher risk of BPPV recurrence (OR = 1.17, 95% CI: 1.04-1.32, P= 0.0082). The sleep quality in patients with BPPV recurrence is significantly poorer compared to non-recurrent patients. Our result suggested sleep quality as measured by PSQI is an independent risk factor of BPPV recurrence.

The effect of comorbid alcoholism on recurrence in affective disorder

DEFF Research Database (Denmark)

Kessing, L V

1999-01-01

BACKGROUND: Studies of the effect of comorbid alcoholism on the risk of recurrence in affective disorder have given contradictory results. METHOD: Using survival analysis, the rate of recurrence was calculated in a case register study including all hospital admissions with primary affective...... an auxiliary diagnosis of alcoholism. Patients with a current auxiliary diagnosis of alcoholism had increased rate of recurrence following the first three affective episodes but not following subsequent episodes compared with patients without auxiliary diagnoses. The effect of alcoholism declined...... with the number of episodes. In contrast, no effect was found of other auxiliary diagnoses on the rate of recurrence. CONCLUSION: Rehospitalisation data suggest that concurrent alcoholism increases the risk of recurrence of affective episodes during the initial course of unipolar and bipolar disorder but has...

Mindfulness-based cognitive therapy is effective as relapse prevention for patients with recurrent depression in Scandinavian primary health care.

Science.gov (United States)

Lilja, Josefine L; Zelleroth, Clara; Axberg, Ulf; Norlander, Torsten

2016-10-01

This study examined the effectiveness of mindfulness-based cognitive therapy (MBCT) in primary care for patients with recurrent depression (major depressive disorder: MDD). According to the World Health Organization (WHO), MDD is now the leading cause of disease burden in middle- and high-income countries. Patients (N = 45) with three or more previous depressive episodes were recruited to participate in MBCT as a preventative intervention. Using a benchmarking approach, outcome data was compared with data from a recent efficacy study. The methodology is a rigorous approach to assessing effectiveness when evidence-based UK protocols are transferred into the existing Scandinavian service delivery. Additionally, a person-centred methodological approach was used to assess clinical significance on the Reliable Change Index (RCI). The analysis revealed comparable or larger effects from pre-test to post-test in reduced psychiatric symptoms, increased quality of life and level of mindfulness, and the effects were maintained over 14 months. Analysis of the relapse rate in the current study (16%) compared to the TAU in the efficacy study (68%) yielded an h value of 0.78, a moderate effect size. Only 13% dropped out of the treatment. According to the RCI findings, 65% to 67% of participants in the clinical group improved, no individual worsened, and women showed a significantly greater improvement of depression and anxiety than men. Therapeutic alliance and motivation had no impact on the outcome. The overall result suggests that MBCT can be implemented successfully in Scandinavian primary health care as a preventive intervention for patients with recurrent depression. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Intraoperative squash smear cytology in CNS lesions: A study of 150 pediatric cases

Directory of Open Access Journals (Sweden)

Arpita Jindal

2017-01-01

Full Text Available Background: Tumors of the central nervous system in the pediatric age group occur relatively frequently during the early years of life. Brain tumors are the most common solid malignancies of childhood and only second to acute childhood leukemia. Squash cytology is an indispensable diagnostic aid to central nervous system (CNS lesions. The definitive diagnosis of brain lesions is confirmed by histological examination. Aim: To study the cytology of CNS lesions in pediatric population and correlate it with histopathology. Materials and Methods: One hundred and fifty cases of CNS lesions in pediatric patients were studied over a period of 2 years. Intraoperative squash smears were prepared, stained with hematoxylin and eosin, and examined. Remaining sample was subjected to histopathological examination. Results: Medulloblastoma (24.0% was the most frequently encountered tumor followed by pilocyctic astrocytoma (21.33% and ependymoma (13.33%. Diagnostic accuracy of squash smear technique was 94.67% when compared with histological diagnosis. Conclusion: Smear cytology is a fairly accurate tool for intraoperative CNS consultations.

Does endoscopic ultrasound improve detection of locally recurrent anal squamous-cell cancer?

Science.gov (United States)

Peterson, Carrie Y; Weiser, Martin R; Paty, Philip B; Guillem, Jose G; Nash, Garrett M; Garcia-Aguilar, Julio; Patil, Sujata; Temple, Larissa K

2015-02-01

Evaluating patients for recurrent anal cancer after primary treatment can be difficult owing to distorted anatomy and scarring. Many institutions incorporate endoscopic ultrasound to improve detection, but the effectiveness is unknown. The aim of this study is to compare the effectiveness of digital rectal examination and endoscopic ultrasound in detecting locally recurrent disease during routine follow-up of patients with anal cancer. This study is a retrospective, single-institution review. This study was conducted at an oncologic tertiary referral center. Included were 175 patients with nonmetastatic anal squamous-cell cancer, without persistent disease after primary chemoradiotherapy, who had at least 1 posttreatment ultrasound and examination by a colorectal surgeon. The primary outcomes measured were the first modality to detect local recurrence, concordance, crude cancer detection rate, sensitivity, specificity, and predictive value. Eight hundred fifty-five endoscopic ultrasounds and 873 digital rectal examinations were performed during 35 months median follow-up. Overall, ultrasound detected 7 (0.8%) mesorectal and 32 (3.7%) anal canal abnormalities; digital examination detected 69 (7.9%) anal canal abnormalities. Locally recurrent disease was found on biopsy in 8 patients, all detected first or only with digital examination. Four patients did not have an ultrasound at the time of diagnosis of recurrence. The concordance of ultrasound and digital examination in detecting recurrent disease was fair at 0.37 (SE, 0.08; 95% CI, 0.21-0.54), and there was no difference in crude cancer detection rate, sensitivity, specificity, and negative or positive predictive values. The heterogeneity of follow-up timing and examinations is not standardized in this study but is reflective of general practice. Endoscopic ultrasound did not provide any advantage over digital rectal examination in identifying locally recurrent anal cancer, and should not be recommended for

Intellectual abilities among survivors of childhood leukaemia as a function of CNS irradiation

International Nuclear Information System (INIS)

Eiser, C.

1978-01-01

Twenty-eight children in remission at least 2 years after completing chemotherapy for acute lymphoblastic leukaemia were assessed on standardised psychological tests. It was found that 7 who never had central nervous system (CNS) irradiation and 9 having prophylactic CNS irradiation at least 6 months after diagnosis tended to perform at average or above levels, while those 10 each having prophylactic CNS irradiation (within 2 months of diagnosis) were generally at lower ability. Within the latter group 3 children showed serious intellectual impairments, while the group as a whole functioned especially poorly on quantitative tasks and those involving speeded performance with abstract material. General language ability was not affected. Practical and theoretical implications are discussed. (author)

Results of radiotherapy in recurrent endometrial carcinoma: A retrospective analysis of 51 patients

International Nuclear Information System (INIS)

Kuten, A.; Grigsby, P.W.; Perez, C.A.; Fineberg, B.; Garcia, D.M.; Simpson, J.R.

1989-01-01

A retrospective analysis was performed of 51 patients with locoregional recurrence of endometrial carcinoma, treated by radiotherapy between 1959 and 1986. There were 17 patients (33%) with isolated vaginal recurrence, 12 patients (24%) with vaginal recurrence with pelvic extension, 7 patients (14%) with pelvic recurrence only, and 15 patients (29%) with simultaneous locoregional and distant failure. Eighty percent of the recurrences occurred within 3.5 years from primary treatment; time to relapse was shorter in patients with advanced-stage, high-grade malignancy at original diagnosis. Locoregional control was achieved in 18 patients (35%). Complete tumor regression in the vagina, irrespective of extravaginal pelvic disease status or distant metastasis, occurred in 28 of 34 patients with vaginal involvement (82%). The 5- and 10-year overall actuarial survivals for all patients were 18 and 12.5%, respectively. The 5- and 10-year progression-free survivals of patients with isolated vaginal recurrences were 40% and 29%, respectively; the 5-year progression-free survival of patients with vaginal recurrence with pelvic extension was 20%. There were no survivors beyond 1.5 years among patients with pelvic recurrence (p = 0.02). All patients with simultaneous locoregional and distant failure were dead by 3.5 years. Stage at original diagnosis, time to relapse from primary treatment, histologic pattern, and grade of malignancy were prognosticators of survival. Five patients (10%) developed a total of ten radiation-related sequelae

Laparoscopic Surgery for Recurrent Crohn's Disease

Directory of Open Access Journals (Sweden)

Antonino Spinelli

2012-01-01

Full Text Available In spite of the recent improvements in drug therapy, surgery still represents the most frequent treatment for Crohn's disease (CD complications. Laparoscopy has been widely applied over the last twenty years in colorectal surgery and was associated with lower postoperative pain, shorter hospitalization, faster return to daily activities, and better cosmetic results. Laparoscopy experienced a slower diffusion in inflammatory bowel disease surgery than in oncologic colorectal surgery, but proved to be safe and effective, and is currently considered the gold standard for the treatment of primary uncomplicated ileocolic CD. Indications for laparoscopy in CD have recently been widened to embrace more complicated or recurrent CD. This paper reviews the available data on the subset of recurrent CD patients. The reported results indicate that laparoscopy may be safely applied even in selected recurrent CD cases in hands of IBD surgeons with broad laparoscopic experience.

Correlation of standardized uptake value and apparent diffusion coefficient in integrated whole-body PET/MRI of primary and recurrent cervical cancer.

Science.gov (United States)

Grueneisen, Johannes; Beiderwellen, Karsten; Heusch, Philipp; Buderath, Paul; Aktas, Bahriye; Gratz, Marcel; Forsting, Michael; Lauenstein, Thomas; Ruhlmann, Verena; Umutlu, Lale

2014-01-01

To evaluate a potential correlation of the maximum standard uptake value (SUVmax) and the minimum apparent diffusion coefficient (ADCmin) in primary and recurrent cervical cancer based on integrated PET/MRI examinations. 19 consecutive patients (mean age 51.6 years; range 30-72 years) with histopathologically confirmed primary cervical cancer (n = 9) or suspected tumor recurrence (n = 10) were prospectively enrolled for an integrated PET/MRI examination. Two radiologists performed a consensus reading in random order, using a dedicated post-processing software. Polygonal regions of interest (ROI) covering the entire tumor lesions were drawn into PET/MR images to assess SUVmax and into ADC parameter maps to determine ADCmin values. Pearson's correlation coefficients were calculated to assess a potential correlation between the mean values of ADCmin and SUVmax. In 15 out of 19 patients cervical cancer lesions (n = 12) or lymph node metastases (n = 42) were detected. Mean SUVmax (12.5 ± 6.5) and ADCmin (644.5 ± 179.7 × 10(-5) mm2/s) values for all assessed tumor lesions showed a significant but weak inverse correlation (R = -0.342, p correlation between SUVmax and ADCmin (R = -0.692, p correlation. These initial results of this emerging hybrid imaging technique demonstrate the high diagnostic potential of simultaneous PET/MR imaging for the assessment of functional biomarkers, revealing a significant and strong correlation of tumor metabolism and higher cellularity in cervical cancer lesions.

Recurrent Syncope due to Esophageal Squamous Cell Carcinoma

OpenAIRE

Casini, Alessandro; Tschanz, Elisabeth; Dietrich, Pierre-Yves; Nendaz, Mathieu

2011-01-01

Syncope is caused by a wide variety of disorders. Recurrent syncope as a complication of malignancy is uncommon and may be difficult to diagnose and to treat. Primary neck carcinoma or metastases spreading in parapharyngeal and carotid spaces can involve the internal carotid artery and cause neurally mediated syncope with a clinical presentation like carotid sinus syndrome. We report the case of a 76-year-old man who suffered from recurrent syncope due to invasion of the right carotid sinus b...

Factors associated with recurrent bacterial empyema thoracis

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Apichat Tantraworasin

2018-07-01

Full Text Available Summary: Background: Empyema thoracis (ET is one of the common thoracic diseases frequently found in developing countries. In the past, only a few studies have analyzed recurrent ET, and none had clearly identified the prognostic factors for recurrence. The aim of this study is to identify the prognostic factors of recurrent ET in Northern Thailand. Methods: A retrospective cohort study was conducted. All patients diagnosed with Stage II and III ET at Maharaj Nakorn Chiang Mai Hospital (a tertiary-care hospital in northern Thailand between January 1, 2007 and November 31, 2012 were enrolled in this study. All clinical data were extracted from the medical recording system. The primary outcome was recurrent disease. Multivariable Cox’s proportion hazard model was used to identify the independent prognostic factors for recurrence. Results: There were 382 patients enrolled in this study, and 34 patients (8.9% had recurrent disease. The most common gram-positive and gram-negative pathogens found were Staphylococcus aureus and Acinetobacter baumannii, respectively. Three independent prognostic factors for recurrent disease were nonsepsis status prior to the surgery [hazard ratio (HR = 12.3; 95% confidence interval (CI, 4.25–35.43], nonperforming decortication (HR = 5.4; 95% CI, 1.82–15.92, and persistent pleural spaces (HR = 4.1; 95% CI, 1.93–8.68. Conclusions: Clinical characteristics, surgical procedure, and persistent pleural spaces were independent prognostic factors for ET recurrence in this study. Decortication and early thoracoplasty in patients who had persistent pleural space should be considered. Large cohort studies are warranted to support these findings. Keywords: empyema thoracis, incidence, prognostic factor, pyothorax, recurrence

Radiotherapy for Locoregional Recurrent Cervix Cancer after Surgery

International Nuclear Information System (INIS)

Yang, Mi Gyoung

1994-01-01

Purpose: The role of radiotherapy in the management of patients with locoregional recurrent cervix cancer after radical surgery were retrospectively analyzed. Methods and materials: Twenty-eight patients treated with radiotherapy for locoregional recurrence after primary surgery for carcinoma of the cervix between 1989 and 1993 were analyzed. The median follow-up of survivors was 15 months (ranged 7-43 months). Eight patients had their disease confined to the vagina and 19 patients(68%) had pelvic mass as part of their locoregional recurrent disease. Within 24 months after the initial surgery, 82% of recurrences manifested themselves. All patients had whole pelvic irradiation with or without intracavitary radiotherapy(ICR). Results: Complete response(CR) was achieved in 18 patients(64%). Five of eighteen patients(28%) with initial CR developed second locoregional recurrence. Response to radiotherapy correlated strongly with tumor volume, site of recurrence and total radiation dose. The overall 2 year survival rate was 43% and the disease free survival was 31%. Survival rate was significantly influenced by the factors of interval from operation to recurrence, size and site of recurrent tumor, radiation dose, response of radiotherapy, lymph node status as initial presentation. The principal cause of death was lung metastasis(36%). Conclusion: Radiotherapy is an excellent modality for control of locoregional recurrent cervix cancer. To improve local control and survival rate, whole pelvic external radiotherapy in addition to ICR with more than 75.0Gy at the depth of 1.0cm from vaginal mucosa is needed and frequent follow up and early detection of recurrence is suggested as well

Recurrent glioblastomas exhibit higher expression of biomarkers with stem-like properties

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B N Nandeesh

2018-01-01

Full Text Available Background: Despite advances in the treatment of glioblastoma (GBM, the prognosis of patients continues to remain dismal. This unfavorable prognosis is mainly attributed to the tumor's propensity for progression and recurrence, which in turn is due to the highly aggressive nature of the persisting GBM cells that actively egress from the main tumor mass into the surrounding normal brain tissue. Such a recurrent tumor described to have a more malignant potential is highly invasive and resistant to current therapies, probably due to increased stemness and preferential selection of therapy-resistant clones of tumor cells. However, there is a paucity of literature on the expression of biomarkers in the recurrent GBM tumors that could have a role in conferring this aggressiveness. Aim: To identify the differences in the expression pattern of selected biomarkers in paired tissue samples of GBM. Material and Methods: A retrospective study on 30 paired samples of GBM (newly diagnosed/primary and recurrent archived in the Department of Neuropathology, NIMHANS (2006–2009, was carried out. After obtaining clinical and demographic details, tumors were characterized histomorphologically and immunohistochemically on formalin-fixed paraffin-embedded tissues with reference to expression of biomarkers such as p53, epidermal growth factor receptor (EGFR, insulin-like growth factor binding protein 3 (IGFBP-3, sex determining region Y-box 2 (SOX2, and topoisomerase 2 A (Top2A. The results were statistically analyzed. Results: It was observed that while p53 and IGFBP-3 expression remained unaltered in paired samples, a significant increase in the expression of EGFR (P < 0.01 was noted in the recurrent tumors. Among the other biomarkers, SOX2 expression was higher in the recurrent tumors when compared to the primary tumors (P < 0.01. Conversely, the expression of Top2A was reduced in recurrent tumors (P = 0.05. Mild elevation in the expression of IGFBP-3 was

Glypicans and FGFs in CNS Development and Function

NARCIS (Netherlands)

Galli, Antonella

2003-01-01

One of the most important events during central nervous system (CNS) development is the communication between cells. Cell-to-cell signaling implicates the interaction between a signaling molecules (or ligands) and their receptors. Ligand-receptor interaction is a tightly regulated process and is

Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

Energy Technology Data Exchange (ETDEWEB)

Vuillemenot, Brian R., E-mail: bvuillemenot@bmrn.com [BioMarin Pharmaceutical Inc., Novato, CA (United States); Kennedy, Derek [BioMarin Pharmaceutical Inc., Novato, CA (United States); Reed, Randall P.; Boyd, Robert B. [Northern Biomedical Research, Inc., Muskegon, MI (United States); Butt, Mark T. [Tox Path Specialists, LLC, Hagerstown, MD (United States); Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O' Neill, Charles A. [BioMarin Pharmaceutical Inc., Novato, CA (United States)

2014-05-15

CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

International Nuclear Information System (INIS)

Vuillemenot, Brian R.; Kennedy, Derek; Reed, Randall P.; Boyd, Robert B.; Butt, Mark T.; Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O'Neill, Charles A.

2014-01-01

CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

Disruption of the blood-brain barrier as the primary effect of CNS irradiation.

Science.gov (United States)

Rubin, P; Gash, D M; Hansen, J T; Nelson, D F; Williams, J P

1994-04-01

The blood-brain barrier (BBB) is believed to be unique in organ microcirculation due to the 'tight junctions' which exist between endothelial cells and, some argue, the additional functional components represented by the perivascular boundary of neuroglial cells; these selectively exclude proteins and drugs from the brain parenchyma. This study was designed to examine the effects of irradiation on the BBB and determine the impact of the altered pathophysiology on the production of central nervous system (CNS) late effects such as demyelination, gliosis and necrosis. Rats, irradiated at 60 Gy, were serially sacrificed at 2, 6, 12 and 24 weeks. Magnetic resonance image analysis (MRI) was obtained prior to sacrifice with selected animals from each group. The remaining animals underwent horse-radish peroxidase (HRP) perfusion at the time of sacrifice. The serial studies showed a detectable disruption of the BBB at 2 weeks post-irradiation and this was manifested as discrete leakage; late injury seen at 24 weeks indicated diffuse vasculature leakage, severe loss of the capillary network, cortical atrophy and white matter necrosis. Reversal or repair of radiation injury was seen between 6 and 12 weeks, indicating a bimodal peak in events. Blood-brain barrier disruption is an early, readily recognizable pathophysiological event occurring after radiation injury, is detectable in vivo/in vitro by MRI and HRP studies, and appears to precede white matter necrosis. Dose response studies over a wide range of doses, utilizing both external and interstitial irradiation, are in progress along with correlative histopathologic and ultrastructural studies.

[Therapy and course of recurrent odontogenic keratocyst. A case report].

Science.gov (United States)

Schultz, Christoph B; Pajarola, Gion F; Grätz, Klaus W

2005-01-01

Recurrence following the surgical treatment of keratocysts of the jaws may present a major problem to the oral surgeon. The surgical treatment of patients with odontogenic keratocysts is concerning the high recurrence rate demanding and difficult. It has been suggested that recurrence is a consequence of technical of microcysts in the mucosa overlying the recurrent lesions. Attemps have been made to reduce this high recurrence rate by improved surgical techniques, such as removal of superadjacent mucosa, smoothing of the osseous wall of the cystic cavity, resection of neighboring parts of the mandible, tanning of the epithelial lining of the cyst with Carnoy's solution and marsupialisation. On the basis of a case report it was the aim of the authors to present the surgical treatment of odontogenic, recurrent keratocysts at the Clinic for Maxillo-Facial Surgery, University Hospital Zurich, from the primary operation following the Brosch-procedure in 1971 up to the latest cystectomy in 2004.

Insomnia and its associations in patients with recurrent glial neoplasms

OpenAIRE

Robertson, Matthew E.; McSherry, Frances; Herndon, James E.; Peters, Katherine B.

2016-01-01

Background Patient with neurological disorders and cancer can develop sleep disturbance, in particular insomnia. Etiology of insomnia is multi-factorial in primary brain tumour patients with possible causes including corticosteroids, psychoactive medications, co-morbid psychiatric/medical conditions, and damage to neuronal tissue. Findings To understand better insomnia in recurrent glioma patients, a single-center retrospective analysis was performed looking at recurrent glioma patients from ...

Recurrent varicocele

Directory of Open Access Journals (Sweden)

Katherine Rotker

2016-01-01

Full Text Available Varicocele recurrence is one of the most common complications associated with varicocele repair. A systematic review was performed to evaluate varicocele recurrence rates, anatomic causes of recurrence, and methods of management of recurrent varicoceles. The PubMed database was evaluated using keywords "recurrent" and "varicocele" as well as MESH criteria "recurrent" and "varicocele." Articles were not included that were not in English, represented single case reports, focused solely on subclinical varicocele, or focused solely on a pediatric population (age <18. Rates of recurrence vary with the technique of varicocele repair from 0% to 35%. Anatomy of recurrence can be defined by venography. Management of varicocele recurrence can be surgical or via embolization.

[Current insights about recurrence of glomerular diseases after renal transplantation].

Science.gov (United States)

Kofman, Tomek; Oniszczuk, Julie; Lang, Philippe; Grimbert, Philippe; Audard, Vincent

2018-05-01

Recurrence of glomerular disease after renal transplantation is a frequent cause of graft loss. Incidence, risk factors and outcome of recurrence are widely due to the underlying glomerular disease. Graft biopsy analysis is required to confirm the definitive diagnosis of recurrence and to start an appropriate therapy that, in some cases, remains challenging to prevent graft failure. Increased use of protocol biopsy and recent advances in our understanding of the pathogenesis of some glomerular diseases with the identification of some relevant biomarkers provide a unique opportunity to initiate kidney-protective therapy at early stages of recurrence on the graft. This review summarizes our current knowledge on the management of many recurrent primary and secondary glomerulonephritis after kidney transplantation. Copyright © 2018 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

Ketamine displaces the novel NMDA receptor SPET probe [{sup 123}I]CNS-1261 in humans in vivo

Energy Technology Data Exchange (ETDEWEB)

Stone, James M. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom)]. E-mail: j.stone@iop.kcl.ac.uk; Erlandsson, Kjell [Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom); Arstad, Erik [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Bressan, Rodrigo A. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Squassante, Lisa [GlaxoSmithKline (GSK), Verona 37135 (Italy); Teneggi, Vincenza [GlaxoSmithKline (GSK), Verona 37135 (Italy); Ell, Peter J. [Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom); Pilowsky, Lyn S. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom)

2006-02-15

[{sup 123}I]CNS-1261 [N-(1-naphthyl)-N'-(3-iodophenyl)-N-methylguanidine] is a high-affinity SPET ligand with selectivity for the intrachannel PCP/ketamine/MK-801 site of the N-methyl-D-aspartate (NMDA) receptor. This study evaluated the effects of ketamine (a specific competitor for the intrachannel PCP/ketamine/MK-801 site) on [{sup 123}I]CNS-1261 binding to NMDA receptors in vivo. Ten healthy volunteers underwent 2 bolus-plus-infusion [{sup 123}I]CNS-1261 scans, one during placebo and the other during a ketamine challenge. Ketamine administration led to a significant decrease in [{sup 123}I]CNS-1261 V {sub T} in most of the brain regions examined (P<.05). [{sup 123}I]CNS-1261 appears to be a specific ligand in vivo for the intrachannel PCP/ketamine/MK-801 NMDA binding site.

Nuclear innovation through collaboration. 35th Annual CNS conference and 39th CNS/CNA student conference

Energy Technology Data Exchange (ETDEWEB)

NONE

2015-07-01

The Canadian Nuclear Society (CNS) held its 35th Annual Conference in Saint John, New Brunswick, Canada on May 31 to June 3, 2015, combined with the 39th Annual CNS/CNA Student Conference. With the theme of the conference, 'Nuclear Innovation through Collaboration', more than 425 delegates, exhibitors and students were in attendance. The conference commenced with two strong plenary sessions on Utility Collaborations to Improve Lifetime Performance; and, Performance Improvement Programs: Goals and Experience. The second day consisted of the panel discussions on International Developments in Used Nuclear Fuel Repository Programs, and two plenary sessions on: Enterprise Risk Management; and, Vendor Role in a Continuously Improving Industry. The third day contained a number of interesting features, including plenary sessions on Waste Management and Decommissioning; Developing Technologies and Resources, and a panel discussion on the Transportation of Used Nuclear Fuel. All three days of the conference also contained parallel sessions with over 100 technical papers presented at the main and student sessions. The technical session titles were: Refurbishment and Life Extension; Thermalhydraulics; Nuclear Materials; WMD - Radiation Monitoring; Safety and Licensing; Communication; Safety and Licensing; Instrumentation and Control; Advanced Reactor Designs; WMD - Deep Geological Repository Packaging; Reactor Physics; Chemistry and Materials; Advanced Fuel Cycles; Waste Management and Decommissioning; and, Medical Physics and Radiation Biology.

Angiopoietin-2 polymorphism in women with idiopathic recurrent miscarriage.

Science.gov (United States)

Pietrowski, Detlef; Tempfer, Clemens; Bettendorf, Hertha; Bürkle, Bernd; Nagele, Fritz; Unfried, Gertrud; Keck, Christoph

2003-10-01

To investigate the relationship between idiopathic recurrent miscarriage and a polymorphism of the gene encoding for angiopoietin-2 (ANGPT2), an autochthonous modulator of angiogenesis during pregnancy. Prospective case control study. Academic research institution. One hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation, and 125 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss. Peripheral venous puncture. Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the different ANGPT2 alleles. No association between mutant (mt) allele and the occurrence of idiopathic recurrent miscarriage was found. Between women with primary and secondary idiopathic recurrent miscarriage, no statistically significant differences with respect to allele frequencies were observed. This is the first report on the ANGPT2 gene polymorphism in women with idiopathic recurrent miscarriage, demonstrating that the investigated polymorphism is not associated with idiopathic recurrent miscarriage in a white population.

Origin of Tumor Recurrence After Intensity Modulated Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Raktoe, Sawan A.S. [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Dehnad, Homan, E-mail: h.dehnad@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Raaijmakers, Cornelis P.J. [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Braunius, Weibel [Department of ENT Head and Neck Surgery, University Medical Center Utrecht, Utrecht (Netherlands); Terhaard, Chris H.J. [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands)

2013-01-01

Purpose: To model locoregional recurrences of oropharyngeal squamous cell carcinomas (OSCC) treated with primary intensity modulated radiation therapy (IMRT) in order to find the origins from which recurrences grow and relate their location to original target volume borders. Methods and Materials: This was a retrospective analysis of OSCC treated with primary IMRT between January 2002 and December 2009. Locoregional recurrence volumes were delineated on diagnostic scans and coregistered rigidly with treatment planning computed tomography scans. Each recurrence was analyzed with two methods. First, overlapping volumes of a recurrence and original target were measured ('volumetric approach') and assessed as 'in-field', 'marginal', or 'out-field'. Then, the center of mass (COM) of a recurrence volume was assumed as the origin from where a recurrence expanded, the COM location was compared with original target volume borders and assessed as 'in-field', 'marginal', or 'out-field'. Results: One hundred thirty-one OSCC were assessed. For all patients alive at the end of follow-up, the mean follow-up time was 40 months (range, 12-83 months); 2 patients were lost to follow-up. The locoregional recurrence rate was 27%. Of all recurrences, 51% were local, 23% were regional, and 26% had both local and regional recurrences. Of all recurrences, 74% had imaging available for assessment. Regarding volumetric analysis of local recurrences, 15% were in-field gross tumor volume (GTV), and 65% were in-field clinical tumor volume (CTV). Using the COM approach, we found that 70% of local recurrences were in-field GTV and 90% were in-field CTV. Of the regional recurrences, 25% were volumetrically in-field GTV, and using the COM approach, we found 54% were in-field GTV. The COM of local out-field CTV recurrences were maximally 16 mm outside CTV borders, whereas for regional recurrences, this was 17 mm. Conclusions: The

Altered self-perception in adult survivors treated for a CNS tumor in childhood or adolescence: population-based outcomes compared with the general population

Science.gov (United States)

Hörnquist, Lina; Rickardsson, Jenny; Lannering, Birgitta; Gustafsson, Göran; Boman, Krister K.

2015-01-01

Background Survivors of pediatric CNS tumors are at risk for persistent tumor/treatment-related morbidity, physical disability and social consequences that may alter self-perception, vital for self-identity, mental health and quality of survival. We studied the long-term impact of childhood CNS tumors and their treatment on the self-perception of adult survivors and compared outcomes with those of the general population. Methods The cohort included 697 Swedish survivors diagnosed with a primary CNS tumor during 1982–2001. Comparison data were randomly collected from a stratified general population sample. Survivors and general population individuals were compared as regards self-perception in 5 domains: body image, sports/physical activities, peers, work, and family, and with a global self-esteem index. Within the survivor group, determinants of impact on self-perception were identified. Results The final analyzed sample included 528 survivors, 75.8% of the entire national cohort. The control sample consisted of 995, 41% of 2500 addressed. Survivors had significantly poorer self-perception outcomes in domains of peers, work, body image, and sports/physical activities, and in the global self-perception measure, compared with those of the general population (all P type and a history of cranial radiation therapy were associated with outcomes. Conclusion An altered self-perception is a potential late effect in adult survivors of pediatric CNS tumors. Self-perception and self-esteem are significant elements of identity, mental health and quality of survival. Therefore, care and psychosocial follow-up of survivors should include measures for identifying disturbances and for assessing the need for psychosocial intervention. PMID:25332406

Breast cancer recurrence after reoperation for surgical bleeding

DEFF Research Database (Denmark)

Pedersen, Rikke Nørgaard; Bhaskaran, K; Heide-Jørgensen, U

2017-01-01

BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group...... database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from.......i. 0·89 to 1·26). The estimates did not vary by site of breast cancer recurrence. CONCLUSION: In this large cohort study, there was no evidence of an association between reoperation for bleeding and breast cancer recurrence....

Recurrent left ventricular myxoma presenting as cerebrovascular accidents in a teenage girl.

Science.gov (United States)

Vermeulen, Tom; Conraads, Viviane M; Vrints, Christiaan; Rodrigus, Inez E

2009-12-01

Myxoma cordis is the most frequent primary cardiac tumour in adults. Paediatric primary cardiac tumours are rare, the most common type being rhabdomyoma. Atrial and ventricular myxomas occur infrequently in the paediatric age group. Intracardiac myxomas are seen with an estimated incidence of 0.5 per million population per year. Approximately 70% of the affected patients are of female gender. Recurrences are rare (1.3%). Asymptomatic recurrences are observed in young patients who have a familial history of tumour or multifocal myxomas. Although rare, cardiac aetiology (atrial fibrillation, intracardiac thrombi, patent foramen ovale, myxoma, endocarditis) should be considered. In children presenting with central neurological symptoms, a cardiac aetiology has to be considered. We describe a rare case of an 18-year-old girl presenting with a recurrent left ventricular myxoma, accompanied by neurological deficits.

Neonatal CNS infection and inflammation caused by Ureaplasma species: rare or relevant?

Science.gov (United States)

Glaser, Kirsten; Speer, Christian P

2015-02-01

Colonization with Ureaplasma species has been associated with adverse pregnancy outcome, and perinatal transmission has been implicated in the development of bronchopulmonary dysplasia in preterm neonates. Little is known about Ureaplasma-mediated infection and inflammation of the CNS in neonates. Controversy remains concerning its incidence and implication in the pathogenesis of neonatal brain injury. In vivo and in vitro data are limited. Despite improving care options for extremely immature preterm infants, relevant complications remain. Systematic knowledge of ureaplasmal infection may be of great benefit. This review aims to summarize pathogenic mechanisms, clinical data and diagnostic pitfalls. Studies in preterm and term neonates are critically discussed with regard to their limitations. Clinical questions concerning therapy or prophylaxis are posed. We conclude that ureaplasmas may be true pathogens, especially in preterm neonates, and may cause CNS inflammation in a complex interplay of host susceptibility, serovar pathogenicity and gestational age-dependent CNS vulnerability.

Local Recurrence in Rectal Cancer: Anatomic Localization and Effect on Radiation Target

International Nuclear Information System (INIS)

Syk, Erik; Torkzad, Michael R.; Blomqvist, Lennart; Nilsson, Per J.; Glimelius, Bengt

2008-01-01

Purpose: To determine the sites of local recurrence after total mesorectal excision for rectal cancer in an effort to optimize the radiation target. Methods and Materials: A total of 155 patients with recurrence after abdominal resection for rectal cancer were identified from a population-based consecutive cohort of 2,315 patients who had undergone surgery by surgeons trained in the total mesorectal excision procedure. A total of 99 cross-sectional imaging studies were retrieved and re-examined by one radiologist. The clinical records were examined for the remaining patients. Results: Evidence of residual mesorectal fat was identified in 50 of the 99 patients. In 83 patients, local recurrence was identified on the imaging studies. All recurrences were within the irradiated volume if the patients had undergone preoperative radiotherapy or within the same volume if they had not. The site of recurrence was in the lower 75% of the pelvis, anatomically below the S1-S2 interspace for all patients. Only 5 of the 44 recurrences in patients with primary tumors >5 cm from the anal verge were in the lowest 20% of the pelvis. Six recurrences involved the lateral lymph nodes. Conclusion: These data suggest that a lowering of the upper limit of the clinical target volume could be introduced. The anal sphincter complex with surrounding tissue could also be excluded in patients with primary tumors >5 cm from the anal verge

Alcohol intake alters immune responses and promotes CNS viral persistence in mice.

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Loftis, Jennifer M; Taylor, Jonathan; Raué, Hans-Peter; Slifka, Mark K; Huang, Elaine

2016-10-01

Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. Published by Elsevier B.V.

Focal salvage iodine-125 brachytherapy for prostate cancer recurrences after primary radiotherapy: A retrospective study regarding toxicity, biochemical outcome and quality of life

International Nuclear Information System (INIS)

Peters, Max; Maenhout, Metha; Voort van Zyp, Jochem R.N. van der; Moerland, Marinus A.; Moman, Maaike R.; Steuten, Lotte M.G.; Deursen, Marijke J.H. van; Vulpen, Marco van

2014-01-01

Purpose: Whole-gland salvage for recurrent prostate cancer (PCa) shows high failure and toxicity rates. Early and adequate localization of recurrences enables focal salvage, thereby potentially improving functional outcomes, while maintaining cancer control. Materials and methods: Retrospective analysis yielded 20 focal salvage I125 brachytherapy patients for locally recurrent PCa after primary radiotherapy. Tumor was defined by multiparametric MRI and correspondence with transrectal biopsies. Dose data were obtained intra-operatively. The tumor was prescribed ⩾144 Gy. Toxicity was scored by the Common Terminology Criteria for Adverse Events version 4 (CTCAE-4). Biochemical failure (BF) was defined using the Phoenix criteria (PSA-nadir + 2.0 ng/ml). Quality of life (QoL) was measured by SF-36 Health Survey and European Organization of Research and Treatment of Cancer (EORTC) C30+3 and PR25 questionnaires. Results: With a median follow-up of 36 months (range 10–45), six patients experienced BF, of which three had no initial response. Grade 3 genitourinary (GU) toxicity occurred in one patient (a urethral stricture). The five previously potent patients retained erectile function. QoL remained decreased with regard to urinary symptoms. Conclusion: Focal salvage I125 brachytherapy showed one grade 3 GU toxicity in the 20 treated patients. Biochemical response and QoL were acceptable

Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer.

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Matulonis, Ursula A; Berlin, Suzanne; Ivy, Percy; Tyburski, Karin; Krasner, Carolyn; Zarwan, Corrine; Berkenblit, Anna; Campos, Susana; Horowitz, Neil; Cannistra, Stephen A; Lee, Hang; Lee, Julie; Roche, Maria; Hill, Margaret; Whalen, Christin; Sullivan, Laura; Tran, Chau; Humphreys, Benjamin D; Penson, Richard T

2009-11-20

Angiogenesis is important for epithelial ovarian cancer (EOC) growth, and blocking angiogenesis can lead to EOC regression. Cediranib is an oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR) -1, VEGFR-2, VEGFR-3, and c-kit. We conducted a phase II study of cediranib for recurrent EOC or peritoneal or fallopian tube cancer; cediranib was administered as a daily oral dose, and the original dose was 45 mg daily. Because of toxicities observed in the first 11 patients, the dose was lowered to 30 mg. Eligibility included 16 weeks, or CA-125 nonprogression > 16 weeks), which was the primary end point, was 30%; eight patients (17%; 95% CI, 7.6% to 30.8%) had a PR, six patients (13%; 95% CI, 4.8% to 25.7%) had SD, and there were no CRs. Eleven patients (23%) were removed from study because of toxicities before two cycles. Grade 3 toxicities (> 20% of patients) included hypertension (46%), fatigue (24%), and diarrhea (13%). Grade 2 hypothyroidism occurred in 43% of patients. Grade 4 toxicities included CNS hemorrhage (n = 1), hypertriglyceridemia/hypercholesterolemia/elevated lipase (n = 1), and dehydration/elevated creatinine (n = 1). No bowel perforations or fistulas occurred. Median PFS was 5.2 months, and median OS has not been reached; median follow-up time is 10.7 months. Cediranib has activity in recurrent EOC, tubal cancer, and peritoneal cancer with predictable toxicities observed with other TKIs.

Lower rates of symptom recurrence and surgical revision after primary compared with secondary endoscopic third ventriculostomy for obstructive hydrocephalus secondary to aqueductal stenosis in adults.

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Sankey, Eric W; Goodwin, C Rory; Jusué-Torres, Ignacio; Elder, Benjamin D; Hoffberger, Jamie; Lu, Jennifer; Blitz, Ari M; Rigamonti, Daniele

2016-05-01

OBJECT Endoscopic third ventriculostomy (ETV) is the treatment of choice for obstructive hydrocephalus; however, the success of ETV in patients who have previously undergone shunt placement remains unclear. The present study analyzed 103 adult patients with aqueductal stenosis who underwent ETV for obstructive hydrocephalus and evaluated the effect of previous shunt placement on post-ETV outcomes. METHODS This study was a retrospective review of 151 consecutive patients who were treated between 2007 and 2013 with ETV for hydrocephalus. One hundred three (68.2%) patients with aqueductal stenosis causing obstructive hydrocephalus were included in the analysis. Postoperative ETV patency and aqueductal and cisternal flow were assessed by high-resolution, gradient-echo MRI. Post-ETV Mini-Mental State Examination, Timed Up and Go, and Tinetti scores were compared with preoperative values. Univariate and multivariate analyses were performed comparing the post-ETV outcomes in patients who underwent a primary (no previous shunt) ETV (n = 64) versus secondary (previous shunt) ETV (n = 39). RESULTS The majority of patients showed significant improvement in symptoms after ETV; however, no significant differences were seen in any of the quantitative tests performed during follow-up. Symptom recurrence occurred in 29 (28.2%) patients after ETV, after a median of 3.0 (interquartile range 0.8-8.0) months post-ETV failure. Twenty-seven (26.2%) patients required surgical revision after their initial ETV. Patients who received a secondary ETV had higher rates of symptom recurrence (p = 0.003) and surgical revision (p = 0.003), particularly in regard to additional shunt placement/revision post-ETV (p = 0.005). These differences remained significant after multivariate analysis for both symptom recurrence (p = 0.030) and surgical revision (p = 0.043). CONCLUSIONS Patients with obstructive hydrocephalus due to aqueductal stenosis exhibit symptomatic improvement after ETV, with a

Modeling radiation dosimetry to predict cognitive outcomes in pediatric patients with CNS embryonal tumors including medulloblastoma

International Nuclear Information System (INIS)

Merchant, Thomas E.; Kiehna, Erin N.; Li Chenghong; Shukla, Hemant; Sengupta, Saikat; Xiong Xiaoping; Gajjar, Amar; Mulhern, Raymond K.

2006-01-01

Purpose: Model the effects of radiation dosimetry on IQ among pediatric patients with central nervous system (CNS) tumors. Methods and Materials: Pediatric patients with CNS embryonal tumors (n = 39) were prospectively evaluated with serial cognitive testing, before and after treatment with postoperative, risk-adapted craniospinal irradiation (CSI) and conformal primary-site irradiation, followed by chemotherapy. Differential dose-volume data for 5 brain volumes (total brain, supratentorial brain, infratentorial brain, and left and right temporal lobes) were correlated with IQ after surgery and at follow-up by use of linear regression. Results: When the dose distribution was partitioned into 2 levels, both had a significantly negative effect on longitudinal IQ across all 5 brain volumes. When the dose distribution was partitioned into 3 levels (low, medium, and high), exposure to the supratentorial brain appeared to have the most significant impact. For most models, each Gy of exposure had a similar effect on IQ decline, regardless of dose level. Conclusions: Our results suggest that radiation dosimetry data from 5 brain volumes can be used to predict decline in longitudinal IQ. Despite measures to reduce radiation dose and treatment volume, the volume that receives the highest dose continues to have the greatest effect, which supports current volume-reduction efforts

Recurrence of primary aldosteronism after percutaneous ethanol injection

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Fan-Chi Chang

2012-03-01

Full Text Available Adrenalectomy is the definite treatment for aldosterone-producing adenoma (APA. Percutaneous ethanol or acetic acid injection with computed tomography (CT guidance has been described as a safe, noninvasive, and effective alternative treatment modality in patients with high surgical risk. We report on a man who was 49 years of age and presented with treatment-resistant hypertension and was later diagnosed with APA. CT-guided percutaneous ethanol injection (PEI was performed for this high surgical risk patient. He had aldosteronism recurrence 4 years after the ethanol injection, so a second PEI was performed. The tumor size was reduced and his blood pressure was normalized. Therefore, we suggest that clinicians should closely check aldosterone to renin ration and potassium level if percutaneous chemical ablation is considered in functioning adrenal adenomas.

Cerebral Venous Thrombosis Revealing Primary Sjögren Syndrome: Report of 2 Cases

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A. Mercurio

2013-01-01

Full Text Available Sjögren syndrome (SS is an autoimmune disease of the exocrine glands, characterized by focal lymphocytic infiltration and destruction of these glands. Neurologic complications are quite common, mainly involving the peripheral nervous system (PNS. The most common central nervous system (CNS manifestations are myelopathy and microcirculation vasculitis. However, specific diagnostic criteria for CNS SS are still lacking. We report two cases of primary SS in which the revealing symptom was cerebral venous thrombosis (CVT in the absence of genetic or acquired thrombophilias.

Effectiveness of different treatment modalities for the management of adult-onset granulosa cell tumours of the ovary (primary and recurrent).

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Gurumurthy, Mahalakshmi; Bryant, Andrew; Shanbhag, Smruta

2014-04-21

Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence-based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility-sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non-randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult-onset granulosa cell tumours (GCTs) of the ovary. We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. We searched for randomised controlled trials (RCTs), quasi-RCTs and observational studies that examined women with adult-onset granulosa cell tumours of the ovary (primary and recurrent). For non-randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta-analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non-randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods

Chemokines in the balance: maintenance of homeostasis and protection at CNS barriers

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Jessica L Williams

2014-05-01

Full Text Available In the adult central nervous system (CNS, chemokines and their receptors are involved in developmental, physiological and pathological processes. Although most lines of investigation focus on their ability to induce the migration of cells, recent studies indicate that chemokines also promote cellular interactions and activate signaling pathways that maintain CNS homeostatic functions. Many homeostatic chemokines are expressed on the vasculature of the blood brain barrier including CXCL12, CCL19, CCL20, and CCL21. While endothelial cell expression of these chemokines is known to regulate the entry of leukocytes into the CNS during immunosurveillance, new data indicate that CXCL12 is also involved in diverse cellular activities including adult neurogenesis and neuronal survival, having an opposing role to the homeostatic chemokine, CXCL14, which appears to regulate synaptic inputs to neural precursors. Neuronal expression of CX3CL1, yet another homeostatic chemokine that promotes neuronal survival and communication with microglia, is partly regulated by CXCL12. Regulation of CXCL12 is unique in that it may regulate its own expression levels via binding to its scavenger receptor CXCR7/ACKR3. In this review, we explore the diverse roles of these and other homeostatic chemokines expressed within the CNS, including the possible implications of their dysfunction as a cause of neurologic disease.

Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization-case study.

Science.gov (United States)

de Almeida, Sergio M; Rotta, Indianara; Ribeiro, Clea E; Oliveira, Michelli F; Chaillon, Antoine; de Pereira, Ana Paula; Cunha, Ana Paula; Zonta, Marise; Bents, Joao França; Raboni, Sonia M; Smith, Davey; Letendre, Scott; Ellis, Ronald J

2017-06-01

Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND

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Gaskill, Peter J.; Calderon, Tina M.; Coley, Jacqueline S.; Berman, Joan W.

2013-01-01

Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70% of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers. PMID:23456305

Clearance of an immunosuppressive virus from the CNS coincides with immune reanimation and diversification

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McGavern Dorian B

2007-06-01

Full Text Available Abstract Once a virus infection establishes persistence in the central nervous system (CNS, it is especially difficult to eliminate from this specialized compartment. Therefore, it is of the utmost importance to fully understand scenarios during which a persisting virus is ultimately purged from the CNS by the adaptive immune system. Such a scenario can be found following infection of adult mice with an immunosuppressive variant of lymphocytic choriomeningitis virus (LCMV referred to as clone 13. In this study we demonstrate that following intravenous inoculation, clone 13 rapidly infected peripheral tissues within one week, but more slowly inundated the entire brain parenchyma over the course of a month. During the establishment of persistence, we observed that genetically tagged LCMV-specific cytotoxic T lymphocytes (CTL progressively lost function; however, the severity of this loss in the CNS was never as substantial as that observed in the periphery. One of the most impressive features of this model system is that the peripheral T cell response eventually regains functionality at ~60–80 days post-infection, and this was associated with a rapid decline in virus from the periphery. Coincident with this "reanimation phase" was a massive influx of CD4 T and B cells into the CNS and a dramatic reduction in viral distribution. In fact, olfactory bulb neurons served as the last refuge for the persisting virus, which was ultimately purged from the CNS within 200 days post-infection. These data indicate that a functionally revived immune response can prevail over a virus that establishes widespread presence both in the periphery and brain parenchyma, and that therapeutic enhancement of an existing response could serve as an effective means to thwart long term CNS persistence.

The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

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Forbes, Lindsey H.

2018-01-01

The extracellular environment of the central nervous system (CNS) becomes highly structured and organized as the nervous system matures. The extracellular space of the CNS along with its subdomains plays a crucial role in the function and stability of the CNS. In this review, we have focused on two components of the neuronal extracellular environment, which are important in regulating CNS plasticity including the extracellular matrix (ECM) and myelin. The ECM consists of chondroitin sulfate proteoglycans (CSPGs) and tenascins, which are organized into unique structures called perineuronal nets (PNNs). PNNs associate with the neuronal cell body and proximal dendrites of predominantly parvalbumin-positive interneurons, forming a robust lattice-like structure. These developmentally regulated structures are maintained in the adult CNS and enhance synaptic stability. After injury, however, CSPGs and tenascins contribute to the structure of the inhibitory glial scar, which actively prevents axonal regeneration. Myelin sheaths and mature adult oligodendrocytes, despite their important role in signal conduction in mature CNS axons, contribute to the inhibitory environment existing after injury. As such, unlike the peripheral nervous system, the CNS is unable to revert to a “developmental state” to aid neuronal repair. Modulation of these external factors, however, has been shown to promote growth, regeneration, and functional plasticity after injury. This review will highlight some of the factors that contribute to or prevent plasticity, sprouting, and axonal regeneration after spinal cord injury. PMID:29849554

Recurrence in affective disorder. I. Case register study

DEFF Research Database (Denmark)

Kessing, L V; Andersen, P K; Mortensen, P B

1998-01-01

hospital admissions with primary affective disorder in Denmark during 1971-1993. A total of 20,350 first-admission patients were discharged with a diagnosis of affective disorder, depressive or manic/cyclic type. RESULTS: The rate of recurrence increased with the number of previous episodes in both...... unipolar and bipolar disorder. Initially, the two types of disorders followed markedly different courses, but later in the course of the illness the rate of recurrence was the same for the two disorders. CONCLUSIONS: The course of severe unipolar and bipolar disorder seems to be progressive in nature...

A boy with recurrent swelling of the jaw

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Lien Haverals

2018-01-01

Full Text Available We present a 10-year old boy with recurrent swelling of the right mandibular region. Based on the diagnosis of chronic recurrent parotitis, he received only supportive treatment. Because of frequent relapses, the diagnosis was reconsidered. Magnetic resonance imaging, scintigraphy and biopsy were compatible with chronic osteomyelitis. This lead to a diagnosis of mandibular primary chronic osteomyelitis, an uncommon non-suppurative inflammatory disease of unknown origin. After decortication of the mandible, the patient recovered well. Because there were no further complaints, the follow-up was ended 18 months after the operation.

Metallothionein-1+2 protect the CNS after a focal brain injury

DEFF Research Database (Denmark)

Giralt, Mercedes; Penkowa, Milena; Lago, Natalia

2002-01-01

We have evaluated the physiological relevance of metallothionein-1+2 (MT-1+2) in the CNS following damage caused by a focal cryolesion onto the cortex. In comparison to normal mice, transgenic mice overexpressing the MT-1 isoform (TgMTI* mice) showed a significant decrease of the number...... dramatically reduced the cryolesion-induced oxidative stress and neuronal apoptosis. Remarkably, these effects were also obtained by the intraperitoneal administration of MT-2 to both normal and MT-1+2 knock-out mice. These results fully support the notion that MT-1+2 are essential in the CNS for coping...

The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects

OpenAIRE

de Lange, Elizabeth CM

2013-01-01

Despite enormous advances in CNS research, CNS disorders remain the world?s leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, and indicates a high unmet need for good CNS drugs and drug therapies. Following dosing, not only the chemical properties of the drug and blood?brain barrier (BBB) transport, but also many other processes will ultimately determine brain target site kinetics and consequently the CNS effects. ...

CNS recruitment of CD8+ T lymphocytes specific for a peripheral virus infection triggers neuropathogenesis during polymicrobial challenge.

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Christine M Matullo

2011-12-01

Full Text Available Although viruses have been implicated in central nervous system (CNS diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV and peripherally restricted lymphocytic choriomeningitis virus (LCMV. While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35% of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack.

Quality of Life and Care Needs of Patients With Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Peritoneal Cancer

Science.gov (United States)

2017-05-03

Anxiety; Fatigue; Nausea and Vomiting; Neurotoxicity Syndrome; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Salvage radiation therapy for locally recurrent nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Leung, To-Wai; Tung, Stewart Y.; Sze, Wing-Kin; Sze, Wai-Man; Wong, Victy Y.W.; Wong, Chi-Sing; O, Sai-Ki

2000-01-01

.0008). Better local control for patients who received a TED of 60 Gy or greater was shown. The corresponding 3-year LFFS rates were 29% and 60% (p 0.0004). Subgroup analysis on the ERT and CMT groups showed a 3-year LFFS rate of 33.5% and 57% (p = 0.003). ERT group had an excess of patients with rT3 disease. Further analysis was performed on the rT1-2 patients showing a trend toward improvement in local control in favor of the CMT group (3-year LFFS rates: CMT, 71.7%; ERT, 54%; p = 0.13). Multivariate analyses showed that rT stage (p = 0.002) and TED (p = 0.01; HR, 0.93; 95% confidence interval, 0.88-0.98) remained significant. The 5-year major and central nervous system (CNS) complication-free rates were 26.7% and 47.8%. The following factors were found to be significant on univariate analyses for both complications in the ERT and CMT groups: (1) Modality of treatment: more complications with ERT group; and (2) rT stage. Multivariate analyses showed that the rT stage was significant for predicting the occurrence of major (p 0.004) and CNS complications (p = 0.04). Conclusion: For rT1-2 local recurrences, CMT with at least 60 Gy TED is recommended. The high incidence of major late complications is of serious concern. Ways of improving the local control of Ho's rT3 disease and reducing the risk of late complications should be explored.

Cancers of the Brain and CNS: Global Patterns and Trends in Incidence.

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Mortazavi, S M J; Mortazavi, S A R; Paknahad, M

2018-03-01

Miranda-Filho et al. in their recently published paper entitled "Cancers of the brain and CNS: global patterns and trends in incidence" provided a global status report of the geographic and temporal variations in the incidence of brain and CNS cancers in different countries across continents worldwide. While the authors confirm the role of genetic risk factors and ionizing radiation exposures, they claimed that no firm conclusion could be drawn about the role of exposure to non-ionizing radiation. The paper authored by Miranda-Filho et al. not only addresses a challenging issue, it can be considered as a good contribution in the field of brain and CNS cancers. However, our correspondence addresses a basic shortcoming of this paper about the role of electromagnetic fields and cancers and provides evidence showing that exposure to radiofrequency electromagnetic fields (RF-EMFs), at least at high levels and long durations, can increases the risk of cancer.

Correlation of methylenetetrahydrofolate reductase polymorphism with Hcy metabolism and inflammatory response in patients with recurrent cerebral infarction

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Gai-Zhuang Liu

2017-07-01

Full Text Available Objective: To study the correlation of methylenetetrahydrofolate reductase (MTHFR polymorphism with Hcy metabolism and inflammatory response in patients with recurrent cerebral infarction. Methods: 40 patients with recurrent cerebral infarction who were treated in Yulin Third Hospital between December 2013 and December 2016 were selected as recurrent group, 58 patients with primary cerebral infarction were selected as primary group, and 60 healthy volunteers were selected as control group. Peripheral blood MTHFR gene C677T polymorphism and serum levels of Hcy metabolism indexes and inflammatory response indicators were determined. Results: CC genotype constituent ratio of recurrent group was significantly lower than that of primary group and control group while CT genotype and TT genotype constituent ratio were significantly higher than those of primary group and control group; serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in recurrent group and primary group were significantly higher than those in control group while VitB12 and FA levels were significantly lower than those in control group; serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in recurrent group were significantly higher than those in primary group while VitB12 and FA levels were significantly lower than those in primary group. Serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in patients with CC genotype were significantly lower than those in patients with CT genotype and TT genotype while VitB12 and FA levels were significantly higher than those in patients with CT genotype and TT genotype; serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in patients with CT genotype were significantly lower than those in patients with TT genotype while VitB12 and FA levels were significantly higher than those in patients with TT genotype. Conclusion: MTHFR gene C677T polymorphism is closely related to the recurrence of cerebral infarction, and allele C

Validation of the 12-gene colon cancer recurrence score as a predictor of recurrence risk in stage II and III rectal cancer patients.

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Reimers, Marlies S; Kuppen, Peter J K; Lee, Mark; Lopatin, Margarita; Tezcan, Haluk; Putter, Hein; Clark-Langone, Kim; Liefers, Gerrit Jan; Shak, Steve; van de Velde, Cornelis J H

2014-11-01

The 12-gene Recurrence Score assay is a validated predictor of recurrence risk in stage II and III colon cancer patients. We conducted a prospectively designed study to validate this assay for prediction of recurrence risk in stage II and III rectal cancer patients from the Dutch Total Mesorectal Excision (TME) trial. RNA was extracted from fixed paraffin-embedded primary rectal tumor tissue from stage II and III patients randomized to TME surgery alone, without (neo)adjuvant treatment. Recurrence Score was assessed by quantitative real time-polymerase chain reaction using previously validated colon cancer genes and algorithm. Data were analysed by Cox proportional hazards regression, adjusting for stage and resection margin status. All statistical tests were two-sided. Recurrence Score predicted risk of recurrence (hazard ratio [HR] = 1.57, 95% confidence interval [CI] = 1.11 to 2.21, P = .01), risk of distant recurrence (HR = 1.50, 95% CI = 1.04 to 2.17, P = .03), and rectal cancer-specific survival (HR = 1.64, 95% CI = 1.15 to 2.34, P = .007). The effect of Recurrence Score was most prominent in stage II patients and attenuated with more advanced stage (P(interaction) ≤ .007 for each endpoint). In stage II, five-year cumulative incidence of recurrence ranged from 11.1% in the predefined low Recurrence Score group (48.5% of patients) to 43.3% in the high Recurrence Score group (23.1% of patients). The 12-gene Recurrence Score is a predictor of recurrence risk and cancer-specific survival in rectal cancer patients treated with surgery alone, suggesting a similar underlying biology in colon and rectal cancers. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Recurrent Primary Fibromatosis in the Breast: A Case Report

International Nuclear Information System (INIS)

Lim, Soo Jin; Kang, Young Hae; Lee, Ju Won; Kim, Youn Jeong; Kim, Lucia; Cho, Young Up

2012-01-01

Fibromatosis is a rare benign tumor that presents predominantly as a unilateral, painless, palpable, and firm to hard mass which may be accompanied by skin dimpling and nipple retraction. It is characterized as an infiltrating fibroblastic and myofibroblastic proliferation that can behave in a locally aggressive fashion if incompletely excised. However, it is not known to metastasize. We report a case of a 39-year-old female with recurrent fibromatosis in the breast. Initially, the mass was detected by a screening mammography. It appeared as an oval mass and recurred twice after surgical excision over a 36-month period with a more suspicious appearance.

A safety assessment methodology applied to CNS/ATM-based air traffic control system

Energy Technology Data Exchange (ETDEWEB)

Vismari, Lucio Flavio, E-mail: lucio.vismari@usp.b [Safety Analysis Group (GAS), School of Engineering at University of Sao Paulo (Poli-USP), Av. Prof. Luciano Gualberto, Trav.3, n.158, Predio da Engenharia de Eletricidade, Sala C2-32, CEP 05508-900, Sao Paulo (Brazil); Batista Camargo Junior, Joao, E-mail: joaocamargo@usp.b [Safety Analysis Group (GAS), School of Engineering at University of Sao Paulo (Poli-USP), Av. Prof. Luciano Gualberto, Trav.3, n.158, Predio da Engenharia de Eletricidade, Sala C2-32, CEP 05508-900, Sao Paulo (Brazil)

2011-07-15

In the last decades, the air traffic system has been changing to adapt itself to new social demands, mainly the safe growth of worldwide traffic capacity. Those changes are ruled by the Communication, Navigation, Surveillance/Air Traffic Management (CNS/ATM) paradigm , based on digital communication technologies (mainly satellites) as a way of improving communication, surveillance, navigation and air traffic management services. However, CNS/ATM poses new challenges and needs, mainly related to the safety assessment process. In face of these new challenges, and considering the main characteristics of the CNS/ATM, a methodology is proposed at this work by combining 'absolute' and 'relative' safety assessment methods adopted by the International Civil Aviation Organization (ICAO) in ICAO Doc.9689 , using Fluid Stochastic Petri Nets (FSPN) as the modeling formalism, and compares the safety metrics estimated from the simulation of both the proposed (in analysis) and the legacy system models. To demonstrate its usefulness, the proposed methodology was applied to the 'Automatic Dependent Surveillance-Broadcasting' (ADS-B) based air traffic control system. As conclusions, the proposed methodology assured to assess CNS/ATM system safety properties, in which FSPN formalism provides important modeling capabilities, and discrete event simulation allowing the estimation of the desired safety metric.

A safety assessment methodology applied to CNS/ATM-based air traffic control system

International Nuclear Information System (INIS)

Vismari, Lucio Flavio; Batista Camargo Junior, Joao

2011-01-01

In the last decades, the air traffic system has been changing to adapt itself to new social demands, mainly the safe growth of worldwide traffic capacity. Those changes are ruled by the Communication, Navigation, Surveillance/Air Traffic Management (CNS/ATM) paradigm , based on digital communication technologies (mainly satellites) as a way of improving communication, surveillance, navigation and air traffic management services. However, CNS/ATM poses new challenges and needs, mainly related to the safety assessment process. In face of these new challenges, and considering the main characteristics of the CNS/ATM, a methodology is proposed at this work by combining 'absolute' and 'relative' safety assessment methods adopted by the International Civil Aviation Organization (ICAO) in ICAO Doc.9689 , using Fluid Stochastic Petri Nets (FSPN) as the modeling formalism, and compares the safety metrics estimated from the simulation of both the proposed (in analysis) and the legacy system models. To demonstrate its usefulness, the proposed methodology was applied to the 'Automatic Dependent Surveillance-Broadcasting' (ADS-B) based air traffic control system. As conclusions, the proposed methodology assured to assess CNS/ATM system safety properties, in which FSPN formalism provides important modeling capabilities, and discrete event simulation allowing the estimation of the desired safety metric.

Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

Directory of Open Access Journals (Sweden)

Joseph L Mankowski

Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

Science.gov (United States)

2018-04-10

Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Recurrent urinary tract infections in women.

Science.gov (United States)

Aydin, Abdullatif; Ahmed, Kamran; Zaman, Iftikhar; Khan, Muhammad Shamim; Dasgupta, Prokar

2015-06-01

Recurrent urinary tract infections (UTIs) are more common in women and are frequently defined as ≥2 episodes in the last 6 months or ≥3 episodes in the last 12 months. In a primary care setting, 53 % of women above the age of 55 years and 36 % of younger women report a recurrence within 1 year. Thus, management and prevention of recurrent UTI is of utmost significance. This review aims to highlight the latest research in prevention strategies and suggest a management pathway. A search was conducted on MEDLINE, Embase and the Cochrane Database of Systematic Reviews databases for the latest systematic reviews and high-quality randomized controlled trials. Special emphasis was placed on the remit "recurrent" and strongly adhered to. Furthermore, a Google search was conducted for current guidelines on the management of UTIs. Current prevention strategies include eliminating risk factors that increase the risk of acquiring recurrent UTI and continuous, post-coital and self-initiated antimicrobial prophylaxis. Other prospective preventative strategies, currently under trial, include use of vaccinations, D-mannose and lactobacillus (probiotics). Although risk factors should be identified and addressed accordingly, individualized antibiotic prophylaxis remains the most effective method of management. Non-antibiotic prevention strategies such as cranberry, vitamin C and methenamine salts lack strong evidence to be introduced as routine management options and as alternatives to antibiotics. Based on current evidence and guidelines, a management pathway is recommended. Emerging therapies require further evaluation before they can be recommended.

Genetics Home Reference: primary ciliary dyskinesia

Science.gov (United States)

... primary ciliary dyskinesia also have year-round nasal congestion and a chronic cough. Chronic respiratory tract infections ... likely due to abnormal cilia in the fallopian tubes. Another feature of primary ciliary dyskinesia is recurrent ...

CD11c-expressing cells affect Treg behavior in the meninges during CNS infection1

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O’Brien, Carleigh A.; Overall, Christopher; Konradt, Christoph; O’Hara Hall, Aisling C.; Hayes, Nikolas W.; Wagage, Sagie; John, Beena; Christian, David A.; Hunter, Christopher A.; Harris, Tajie H.

2017-01-01

Treg cells play an important role in the CNS during multiple infections as well as autoimmune inflammation, but the behavior of this cell type in the CNS has not been explored. In mice, infection with Toxoplasma gondii leads to a Th1-polarized parasite-specific effector T cell response in the brain. Similarly, the Treg cells in the CNS during T. gondii infection are Th1-polarized, exemplified by T-bet, CXCR3, and IFN-γ expression. Unlike effector CD4+ T cells, an MHC Class II tetramer reagent specific for T. gondii did not recognize Treg cells isolated from the CNS. Likewise, TCR sequencing revealed minimal overlap in TCR sequence between effector and regulatory T cells in the CNS. Whereas effector T cells are found in the brain parenchyma where parasites are present, Treg cells were restricted to the meninges and perivascular spaces. The use of intravital imaging revealed that activated CD4+ T cells within the meninges were highly migratory, while Treg cells moved more slowly and were found in close association with CD11c+ cells. To test whether the behavior of Tregs in the meninges is influenced by interactions with CD11c+ cells, mice were treated with anti-LFA-1 antibodies to reduce the number of CD11c+ cells in this space. The anti-LFA-1 treatment led to fewer contacts between Tregs and the remaining CD11c+ cells and increased the speed of Treg cell migration. These data suggest that Treg cells are anatomically restricted within the CNS and the interaction with CD11c+ populations regulates their local behavior during T. gondii infection. PMID:28389591

In vivo human apolipoprotein E isoform fractional turnover rates in the CNS.

Directory of Open Access Journals (Sweden)

Kristin R Wildsmith

Full Text Available Apolipoprotein E (ApoE is the strongest genetic risk factor for Alzheimer's disease and has been implicated in the risk for other neurological disorders. The three common ApoE isoforms (ApoE2, E3, and E4 each differ by a single amino acid, with ApoE4 increasing and ApoE2 decreasing the risk of Alzheimer's disease (AD. Both the isoform and amount of ApoE in the brain modulate AD pathology by altering the extent of amyloid beta (Aβ peptide deposition. Therefore, quantifying ApoE isoform production and clearance rates may advance our understanding of the role of ApoE in health and disease. To measure the kinetics of ApoE in the central nervous system (CNS, we applied in vivo stable isotope labeling to quantify the fractional turnover rates of ApoE isoforms in 18 cognitively-normal adults and in ApoE3 and ApoE4 targeted-replacement mice. No isoform-specific differences in CNS ApoE3 and ApoE4 turnover rates were observed when measured in human CSF or mouse brain. However, CNS and peripheral ApoE isoform turnover rates differed substantially, which is consistent with previous reports and suggests that the pathways responsible for ApoE metabolism are different in the CNS and the periphery. We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis.

Elevated interferon-gamma in CNS inflammatory disease: a potential complication for bone marrow reconstitution in MS

DEFF Research Database (Denmark)

Hassan-Zahraee, M; Tran, E H; Bourbonnière, L

2000-01-01

but levels were higher in IFNgamma transgenics. BM transplantation into IFNgamma-deficient recipients also had a high failure rate. Transplants of BM from mice lacking expression of IFNgamma-receptor failed, whereas IFNgamma-deficient grafts survived, suggesting that IFNgamma response status of the graft can......Bone marrow transplantation (BMT) is increasingly used to treat Multiple Sclerosis (MS) a CNS inflammatory disease with elevated CNS and systemic IFNgamma levels. We wished to determine the effect of IFNgamma on BM graft survival in a transgenic mouse model for chronic MS. BM transplantation...... into transgenic mice which express elevated levels of IFNgamma in the CNS was unsuccessful. By contrast, there was 100% survival of even fully allogeneic, T-depleted transplants to transgenics that over express TNFalpha in the CNS, using the same MBP promoter. IFNgamma was detectable in spleen of irradiated mice...

The Impacts of Peptic Ulcer on Stroke Recurrence.

Science.gov (United States)

Xu, Zongliang; Wang, Ling; Lin, Ying; Wang, Zhaojun; Zhang, Yun; Li, Junrong; Li, Shenghua; Ye, Zusen; Yuan, Kunxiong; Shan, Wanying; Liu, Xinfeng; Fan, Xinying; Xu, Gelin

2018-04-10

Peptic ulcer has been associated with an increased risk of stroke. This study aimed to evaluate the impacts of peptic ulcer on stroke recurrence and mortality. Patients with first-ever ischemic stroke were retrospectively confirmed with or without a history of peptic ulcer. The primary end point was defined as fatal and nonfatal stroke recurrence. Risks of 1-year fatal and nonfatal stroke recurrence were analyzed with the Kaplan-Meier method. Predictors of fatal and nonfatal stroke recurrence were evaluated with the Cox proportional hazards model. Among the 2577 enrolled patients with ischemic stroke, 129 (5.0%) had a history of peptic ulcer. The fatal and nonfatal stroke recurrence within 1 year of the index stroke was higher in patients with peptic ulcer than in patients without peptic ulcer (12.4% versus 7.2%, P = .030). Cox proportional hazards model detected that age (hazard ratio [HR] = 1.018, 95% confidence interval [CI] 1.005-1.031, P = .008), hypertension (HR = 1.397, 95% CI 1.017-1.918, P = .039), and history of peptic ulcer (HR = 1.853, 95% CI 1.111-3.091, P = .018) were associated with stroke recurrence. Ischemic stroke patients with peptic ulcer may have an increased risk of stroke recurrence. The results emphasize the importance of appropriate prevention and management of peptic ulcer for secondary stroke prevention. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Staging Primary CNS Lymphoma

Science.gov (United States)

... and organs. This is called metastatic cancer. This animation shows how cancer cells travel from the place ... that can affect thinking, learning, problem solving, speech, reading, writing, and memory. Clinical trials have tested the ...

Altered self-perception in adult survivors treated for a CNS tumor in childhood or adolescence: population-based outcomes compared with the general population.

Science.gov (United States)

Hörnquist, Lina; Rickardsson, Jenny; Lannering, Birgitta; Gustafsson, Göran; Boman, Krister K

2015-05-01

Survivors of pediatric CNS tumors are at risk for persistent tumor/treatment-related morbidity, physical disability and social consequences that may alter self-perception, vital for self-identity, mental health and quality of survival. We studied the long-term impact of childhood CNS tumors and their treatment on the self-perception of adult survivors and compared outcomes with those of the general population. The cohort included 697 Swedish survivors diagnosed with a primary CNS tumor during 1982-2001. Comparison data were randomly collected from a stratified general population sample. Survivors and general population individuals were compared as regards self-perception in 5 domains: body image, sports/physical activities, peers, work, and family, and with a global self-esteem index. Within the survivor group, determinants of impact on self-perception were identified. The final analyzed sample included 528 survivors, 75.8% of the entire national cohort. The control sample consisted of 995, 41% of 2500 addressed. Survivors had significantly poorer self-perception outcomes in domains of peers, work, body image, and sports/physical activities, and in the global self-perception measure, compared with those of the general population (all P self-perception is a potential late effect in adult survivors of pediatric CNS tumors. Self-perception and self-esteem are significant elements of identity, mental health and quality of survival. Therefore, care and psychosocial follow-up of survivors should include measures for identifying disturbances and for assessing the need for psychosocial intervention. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

CNS germinoma: disease control and long-term functional outcome for 12 children treated with craniospinal irradiation

International Nuclear Information System (INIS)

Merchant, Thomas E.; Sherwood, Scot H.; Mulhern, Raymond K.; Rose, Susan R.; Thompson, Stephen J.; Sanford, Robert A.; Kun, Larry E.

2000-01-01

Purpose: To provide evidence that radiation therapy alone in the form of craniospinal irradiation (CSI) and a boost to the primary site of disease provides effective disease control and limited additional morbidity for patients with CNS germinoma. Methods and Materials: Twelve patients with a median age of 12 years (range 9-16 years) with CNS germinoma were treated with CSI (median 25.6 Gy, range 23.4-32 Gy) and a boost to the primary site of disease (50.4 Gy, range 45-54 Gy) between January 1987 and June 1998. All patients were biopsied prior to radiation therapy and none received chemotherapy. No patients were lost to follow-up and the majority had long-term (> 45 month) pre- and postirradiation endocrine and psychology assessment. Results: All 12 patients are alive and no failures have occurred with a median follow-up of 69 months (range 14-143 months). Preirradiation endocrine deficiencies were present in 6 of 6 suprasellar tumors and 1 of 6 pineal tumors; with follow-up there was no substantial difference between age and gender adjusted pre- and postirradiation stature and weight. With long-term follow-up, there were no significant differences between pre- and postirradiation full-scale, verbal, and performance IQ scores. Conclusions: This study confirms the ability of radiation therapy alone to achieve disease control with a high rate of success in pediatric patients and demonstrates that the treatment toxicity faced by these patients may be less than anticipated. Because these patients present with substantial preexisting morbidity at diagnosis and may be of an age where the potential for radiation-related side effects is relatively small, the superiority of treatment alternatives may be difficult to prove

Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis.

Science.gov (United States)

Jordan, Sabine D; Könner, A Christine; Brüning, Jens C

2010-10-01

The central nervous system (CNS) is capable of gathering information on the body's nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus.

Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia

Directory of Open Access Journals (Sweden)

Hammond Robert R

2004-05-01

Full Text Available Abstract HIV-1-associated dementia remains a common subacute to chronic central nervous system degeneration in adult and pediatric HIV-1 infected populations. A number of viral and host factors have been implicated including the HIV-1 120 kDa envelope glycoprotein (gp120. In human post-mortem studies using confocal scanning laser microscopy for microtubule-associated protein 2 and synaptophysin, neuronal dendritic pathology correlated with dementia. In the present study, primary human CNS cultures exposed to HIV-1 gp120 at 4 weeks in vitro suffered gliosis and dendritic damage analogous to that described in association with HIV-1-associated dementia.

Adjunctive Treatment in Juvenile Nasopharyngeal Angiofibroma: How Should We Approach Recurrence?

Science.gov (United States)

Scholfield, Daniel W; Brundler, Marie-Anne; McDermott, Ann-Louise; Mussai, Francis; Kearns, Pamela

2016-04-01

A recent case of advanced, recurrent juvenile nasopharyngeal angiofibroma (JNA) at our institution has highlighted the limited evidence regarding adjunctive treatment. We present the case of a 10-year-old boy who is the first to undergo multiple-staged surgical resections alongside vincristine treatment. We performed a review of the literature analyzing the roles of radiation therapy, cytotoxic drugs, and novel targeted agents in JNA relapse. Small cohort studies suggest radiotherapy and flutamide are the most rational treatment options for residual and recurrent JNA. Our review highlights the need for further research into the management of primary and recurrent JNA.

CNS-targets in control of energy and glucose homeostasis.

Science.gov (United States)

Kleinridders, André; Könner, A Christine; Brüning, Jens C

2009-12-01

The exceeding efforts in understanding the signals initiated by nutrients and hormones in the central nervous system (CNS) to regulate glucose and energy homeostasis have largely revolutionized our understanding of the neurocircuitry in control of peripheral metabolism. The ability of neurons to sense nutrients and hormones and to adopt a coordinated response to these signals is of crucial importance in controlling food intake, energy expenditure, glucose and lipid metabolism. Anatomical lesion experiments, pharmacological inhibition of signaling pathways, and, more recently, the analysis of conditional mouse mutants with modifications of hormone and nutrient signaling in defined neuronal populations have broadened our understanding of these complex neurocircuits. This review summarizes recent findings regarding the role of the CNS in sensing and transmitting nutritional and hormonal signals to control energy and glucose homeostasis and aims to define them as potential novel drug targets for the treatment of obesity and type 2 diabetes mellitus.

Recurrent vaginal discharge in children.

Science.gov (United States)

McGreal, Sharon; Wood, Paul

2013-08-01

Childhood vaginal discharge remains a frequent reason for referral from primary to secondary care. The Pediatric and Adolescent Gynecology (PAG) service at Kettering General Hospital was established in 1993 and provides a specialized service that meets the needs of children with gynaecological conditions. To investigate recurrent vaginal discharge noting symptomatology, defining pathogens, common and rarer causes, exploring management regimes, and any changes in practice over time. Retrospective review spanning 15 years identifying prepubertal children attending the outpatient PAG clinic with recurrent vaginal discharge. We reviewed the medical notes individually. 110 patients were identified; 85% were referred from primary care. The age distribution was bimodal at four and eight years. Thirty-five percent of our patients were discharged after the initial consultation. The commonest cause of discharge was vulvovaginitis (82%). Other important causes included suspected sexual abuse (5%), foreign body (3%), labial adhesions (3%), vaginal agenesis (2%). 35% of patients were admitted for vaginoscopy. Vaginal discharge is the most common gynecological symptom in prepubertal girls and can cause repeated clinical episodes. Vulvovaginitis is the most common cause and often responds to simple hygiene measures. Awareness of the less common causes of vaginal discharge is essential. Copyright © 2013 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Evaluation of the Performance of Feedforward and Recurrent Neural Networks in Active Cancellation of Sound Noise

Directory of Open Access Journals (Sweden)

Mehrshad Salmasi

2012-07-01

Full Text Available Active noise control is based on the destructive interference between the primary noise and generated noise from the secondary source. An antinoise of equal amplitude and opposite phase is generated and combined with the primary noise. In this paper, performance of the neural networks is evaluated in active cancellation of sound noise. For this reason, feedforward and recurrent neural networks are designed and trained. After training, performance of the feedforwrad and recurrent networks in noise attenuation are compared. We use Elman network as a recurrent neural network. For simulations, noise signals from a SPIB database are used. In order to compare the networks appropriately, equal number of layers and neurons are considered for the networks. Moreover, training and test samples are similar. Simulation results show that feedforward and recurrent neural networks present good performance in noise cancellation. As it is seen, the ability of recurrent neural network in noise attenuation is better than feedforward network.

Novel Insights of Oligometastases and Oligo-Recurrence and Review of the Literature

Directory of Open Access Journals (Sweden)

Yuzuru Niibe

2012-01-01

Full Text Available Oligometastases and oligo-recurrence are among the most important notions of metastatic and recurrent cancer. The concept of oligometastases is related to the notion that cancer patients with 1–5 metastatic or recurrent lesions that could be treated by local therapy achieve long-term survival or cure, while the concept of oligo-recurrence is related to the notion that cancer patients with 1–5 metastatic or recurrent lesions that could be treated by local therapy have controlled primary lesions. Achievement of long-term survival or cure in patients with oligometastases and oligo-recurrence is cancer and organ specific. These facts rely on the seed and soil theory and multiple steps of cancer progression. Oligo-recurrence is considered to have a better prognosis than oligometastases. In patients with oligometastases and oligo-recurrence, the oligometastases and oligo-recurrence are sometimes cured with only local therapy, which is an example of the abscopal effect, previously described in relation to cure of lesions outside of the field of radiation therapy without systemic therapy. Oligometastases and oligo-recurrence can now be cured by less invasive local treatment methods combined with systemic therapy. The mechanisms of oligometastases and oligo-recurrence, as well as novel insights into these important concepts, are presented in this paper.

Beta-blocker use and clinical outcomes after primary vascular surgery

DEFF Research Database (Denmark)

Høgh, A.; Lindholt, J.S.; Nielsen, Henrik

2013-01-01

To explore the associations between beta-blocker use and clinical outcomes (death, hospitalisation with myocardial infarction (MI) or stroke, major amputation and recurrent vascular surgery) after primary vascular reconstruction.......To explore the associations between beta-blocker use and clinical outcomes (death, hospitalisation with myocardial infarction (MI) or stroke, major amputation and recurrent vascular surgery) after primary vascular reconstruction....

Predictors of recurrence in affective disorder. A case register study

DEFF Research Database (Denmark)

Kessing, Lars Vedel; Andersen, Per Kragh; Mortensen, P.B.

1998-01-01

BACKGROUND: The risk of recurrence in affective disorder is affected by socio-demographic variables such as gender, age at onset and marital status and by illness related factors as the length of previous episodes and the total duration of the illness. The present study investigated how the effect...... of these variables changed with the progression of the illness. METHOD: Using survival analysis, the risk of recurrence was estimated in a case register study including all hospital admissions with primary affective disorder in Denmark during 1971-1993. RESULTS: Totally, 20350 first admission patients had been...... disorder socio-demographic variables such as gender, age at onset and marital status act as risk factors for further recurrence. Later, however, the illness itself seem to follow its own rhythm regardless of prior predictors. LIMITATION: The data relate to re-admissions rather than recurrence...

Mast Cells and Innate Lymphoid Cells: Underappreciated Players in CNS Autoimmune Demyelinating Disease.

Science.gov (United States)

Brown, Melissa A; Weinberg, Rebecca B

2018-01-01

Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis, are autoimmune CNS inflammatory diseases. As a result of a breakdown in the relatively impermeable blood-brain barrier (BBB) in affected individuals, myelin-specific CD4 + and CD8 + T cells gain entry into the immune privileged CNS and initiate myelin, oligodendrocyte, and nerve axon destruction. However, despite the absolute requirement for T cells, there is increasing evidence that innate immune cells also play critical amplifying roles in disease pathogenesis. By modulating the character and magnitude of the myelin-reactive T cell response and regulating BBB integrity, innate cells affect both disease initiation and progression. Two classes of innate cells, mast cells and innate lymphoid cells (ILCs), have been best studied in models of allergic and gastrointestinal inflammatory diseases. Yet, there is emerging evidence that these cell types also exert a profound influence in CNS inflammatory disease. Both cell types are residents within the meninges and can be activated early in disease to express a wide variety of disease-modifying cytokines and chemokines. In this review, we discuss how mast cells and ILCs can have either disease-promoting or -protecting effects on MS and other CNS inflammatory diseases and how sex hormones may influence this outcome. These observations suggest that targeting these cells and their unique mediators can be exploited therapeutically.

Serial brain MRI findings in CNS involvement of familial erythrophagocytic lymphohistiocytosis: a case report

International Nuclear Information System (INIS)

Cho, Kyung Soo; Yoo, Jeong Hyun; Suh, Jeong Soo; Ryu, Kyung Ha; Hong, Ki Sook; Kim, Hak Jin

2002-01-01

Familial erythrophagocytic lymphohistiocytosis is a fatal early childhood disorder characterized by multiorgan lymphohistiocytic infiltration and active hemophagocytosis. Involvement of the central nervous system (CNS) is not uncommon and is characterized by rapidly progressive tissue damage affecting both the gray and white matter. We encountered a case of familial erythrophagocytic lymphohistiocytosis with CNS involvement. Initial T2-weighted MRI of the brain demonstrated high signal intensity in the right thalamus, though after chemotherapy, which led to the relief of neurologic symptoms, this disappeared. After four months. however, the patient's neurologic symptoms recurred, and follow-up T2-weighted MR images showed high signal intensity in the thalami, basal ganglia, and cerebral and cerebellar white matter. Brain MRI is a useful imaging modality for the evaluation of CNS involvement and monitoring the response to treatment

Locoregional recurrence following maxillectomy: implications for microvascular reconstruction.

Science.gov (United States)

Likhterov, Ilya; Fritz, Michael A; El-Sayed, Ivan H; Rahul Seth; Rayess, Hani M; Knott, P Daniel

2017-11-01

Reconstruction of maxillectomy defects offers potential quality-of-life improvement, although cavity coverage may impact surveillance of recurrent malignancy. We describe the pattern of postmaxillectomy locoregional recurrence. Retrospective review. Patients from 2001 to 2011 at the University of California, San Francisco and the Cleveland Clinic. Among 75 patients with malignancy resulting in partial or total maxillectomy, 57 were treated with obturators and 18 underwent reconstructive surgery. Disease recurrence occurred primarily locally (19 of 22 cases of recurrence, 25% of the cohort) at a mean of 17 months postoperatively. Recurrence was associated with T4 disease, positive margins, and surveillance imaging. Four (5.3%) patients required flap mobilization/obturator removal to obtain biopsy. Salvage surgery was attempted in 13 of the 19 cases with recurrent disease (68%) and was successful in six (46%) patients. Of these, five patients initially had Brown type 1 or type 2 defects. The free flap had to be revised in one (1.3%) patient to achieve successful salvage. Maxillectomy provides good long-term locoregional oncologic control, with cure being correlated to disease stage at presentation and negative margins after initial surgery. Patients with recurrent disease whose initial resection resulted in a Brown class 3 defect or greater were rarely successfully salvaged. Surveillance is best performed with a combination of physical exam and imaging. Obturator removal/flap mobilization rarely impedes the diagnosis of recurrent disease, and either modality should be offered to appropriate patients in the primary setting if significant quality-of-life improvement is likely. 4. Laryngoscope, 127:2534-2538, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Novel CNS drug discovery and development approach: model-based integration to predict neuro-pharmacokinetics and pharmacodynamics.

Science.gov (United States)

de Lange, Elizabeth C M; van den Brink, Willem; Yamamoto, Yumi; de Witte, Wilhelmus E A; Wong, Yin Cheong

2017-12-01

CNS drug development has been hampered by inadequate consideration of CNS pharmacokinetic (PK), pharmacodynamics (PD) and disease complexity (reductionist approach). Improvement is required via integrative model-based approaches. Areas covered: The authors summarize factors that have played a role in the high attrition rate of CNS compounds. Recent advances in CNS research and drug discovery are presented, especially with regard to assessment of relevant neuro-PK parameters. Suggestions for further improvements are also discussed. Expert opinion: Understanding time- and condition dependent interrelationships between neuro-PK and neuro-PD processes is key to predictions in different conditions. As a first screen, it is suggested to use in silico/in vitro derived molecular properties of candidate compounds and predict concentration-time profiles of compounds in multiple compartments of the human CNS, using time-course based physiology-based (PB) PK models. Then, for selected compounds, one can include in vitro drug-target binding kinetics to predict target occupancy (TO)-time profiles in humans. This will improve neuro-PD prediction. Furthermore, a pharmaco-omics approach is suggested, providing multilevel and paralleled data on systems processes from individuals in a systems-wide manner. Thus, clinical trials will be better informed, using fewer animals, while also, needing fewer individuals and samples per individual for proof of concept in humans.

Statin treatment and risk of recurrent venous thromboembolism

DEFF Research Database (Denmark)

Nguyen, Cu Dinh; Andersson, Charlotte; Jensen, Thomas Bo

2013-01-01

Objectives Statins may decrease the risk of primary venous thromboembolism (VTE), that is, deep vein thrombosis (DVT) and pulmonary embolism (PE) but the effect of statins in preventing recurrent VTE is less clear. The aim of this study was therefore to investigate the association between statin ...

Immune regulation and CNS autoimmune disease

DEFF Research Database (Denmark)

Antel, J P; Owens, T

1999-01-01

The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity...... and duration of the tissue directed injury. Convergence of research, involving direct manipulation of specific cells and molecular mediators in animal models and in vitro analysis of human immune and neural cells and tissues, is providing increasing insight into the role of these immune regulatory functions...

Evaluation of the Performance of Feedforward and Recurrent Neural Networks in Active Cancellation of Sound Noise

OpenAIRE

Mehrshad Salmasi; Homayoun Mahdavi-Nasab

2012-01-01

Active noise control is based on the destructive interference between the primary noise and generated noise from the secondary source. An antinoise of equal amplitude and opposite phase is generated and combined with the primary noise. In this paper, performance of the neural networks is evaluated in active cancellation of sound noise. For this reason, feedforward and recurrent neural networks are designed and trained. After training, performance of the feedforwrad and recurrent networks in n...

Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1

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Wilson Pak-Kin Lou

2018-01-01

Full Text Available Adult mammalian central nervous system (CNS neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we studied the transcriptome and translatome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identified a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were down-regulated in the total RNA fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at the transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovered a global evolutionarily conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.

Detail Design of the hydrogen system and the gas blanketing system for the HANARO-CNS

International Nuclear Information System (INIS)

Choi, Jung Woon; Kim, Hark Rho; Kim, Young Ki; Wu, Sang Ik; Kim, Bong Su; Lee, Yong Seop

2007-04-01

The cold neutron source (CNS), which will be installed in the vertical CN hole of the reflector tank at HANARO, makes thermal neutrons to moderate into the cold neutrons with the ranges of 0.1 ∼ 10 meV passing through a moderator at about 22K. A moderator to produce cold neutrons is liquid hydrogen, which liquefies by the heat transfer with cryogenic helium flowing from the helium refrigeration system (HRS). Because of its installed location, the hydrogen system is designed to be surrounded by the gas blanketing system to notify the leakage on the system and to prevent hydrogen leakage out of the CNS. The hydrogen system, consisted of hydrogen charging unit, hydrogen storage unit, hydrogen buffer tank, and hydrogen piping, is designed to smoothly and safely supply hydrogen to and to draw back hydrogen from the IPA of the CNS under the HRS operation mode. Described is that calculation for total required hydrogen amount in the CNS as well as operation schemes of the hydrogen system. The gas blanketing system (GBS) is designed for the supply of the compressed nitrogen gas into the air pressurized valves for the CNS, to isolate the hydrogen system from the air and the water, and to prevent air or water intrusion into the vacuum system as well as the hydrogen system. All detail descriptions are shown inhere as well as the operation scheme for the GBS

Photodynamic therapy for recurrent respiratory papillomatosis.

Science.gov (United States)

Lieder, Anja; Khan, Muhammad K; Lippert, Burkard M

2014-06-05

Recurrent respiratory papillomatosis (RRP) is a benign condition of the mucosa of the upper aerodigestive tract. It is characterised by recurrent papillomatous lesions and is associated with human papillomavirus (HPV). Frequent recurrence and rapid papilloma growth are common and in part responsible for the onset of potentially life-threatening symptoms. Most patients afflicted by the condition will require repeated surgical treatments to maintain their airway, and these may result in scarring and voice problems. Photodynamic therapy introduces a light-sensitising agent, which is administered either orally or by injection. This substance (called a photo-sensitiser) is selectively retained in hyperplastic and neoplastic tissue, including papilloma. It is then activated by light of a specific wavelength and may be used as a sole or adjuvant treatment for RRP. To assess the effects of photodynamic therapy in the management of recurrent respiratory papillomatosis (RRP) in children and adults. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 27 January 2014. Randomised controlled trials utilising photodynamic therapy as sole or adjuvant therapy in participants of any age with proven RRP versus control intervention. Primary outcome measures were symptom improvement (respiratory distress/dyspnoea and voice quality), quality of life improvement and recurrence-free interval. Secondary outcomes included reduction in the frequency of surgical intervention, reduction in disease volume and adverse effects of treatment.   We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible and results are presented descriptively. We included one trial with a total of 23

Flavonoids and the CNS

DEFF Research Database (Denmark)

Jäger, Anna Katharina; Saaby, Lasse

2011-01-01

Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure....... Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic ß-glucocidase. The absorbed aglycone is then conjugated by methylation......, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABA(A)-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine...

A map of taste neuron projections in the Drosophila CNS

Indian Academy of Sciences (India)

2014-07-08

Jul 8, 2014 ... information that they represent. The extensive ... physiology and behaviour in the wild type and in these mutants .... taste information is processed in the CNS. 2. ..... gene affecting the specificity of the chemosensory neurons of.

Chromosomal abnormalities in couples with recurrent abortions in ...

African Journals Online (AJOL)

The study was to investigate the prevalence of chromosomal abnormalities in couples with two or more recurrent miscarriages of unknown cause. The study population included 55 women and 32 male partners with medical history of 2 or more consecutive abortions and primary infertility. The controls were 20 healthy ...

Phantom limb pain: a case of maladaptive CNS plasticity?

DEFF Research Database (Denmark)

Flor, Herta; Nikolajsen, Lone; Jensen, Troels Staehelin

2006-01-01

might be a phenomenon of the CNS that is related to plastic changes at several levels of the neuraxis and especially the cortex. Here, we discuss the evidence for putative pathophysiological mechanisms with an emphasis on central, and in particular cortical, changes. We cite both animal and human...

Recurrent primary lumbar vertebra chondrosarcoma: Marginal resection and Iodine-125 seed therapy

Directory of Open Access Journals (Sweden)

Chunpeng Ren

2014-01-01

Full Text Available Chondrosarcomas are uncommon in the spinal column. En bloc excisions with wide margins are of critical importance but not always feasible in spine. We report the outcome in a case of recurrent lumbar vertebral chondrosarcoma treated with marginal resection and iodine-125 seeds placed in the resected tumor bed.

Literature Review of Saccharomyces boulardii in the Treatment of Refractory Recurrent Clostridium difficile Infection

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Rachel Warila

2017-09-01

Full Text Available Objective: To evaluate the efficacy of S. boulardii for the treatment of recurrent C. difficile infections.Methods: Eligible articles included S. boulardii in patients with recurrent C. difficile infection. The primary endpoint examined was clinical resolution of infection with no further recurrences during follow-up.Results: Six studies met inclusion criteria. A case report showed resolution of recurrences in one patient, and an experimental trial showed a trend towards decreased recurrences in patients receiving S. boulardii (85% no further recurrences. Two randomized controlled trials found a significant decrease in recurrences for S. boulardii versus placebo (34.6% vs 64.7%, P=0.04; 16.7% vs 50%, P=0.05. One meta-analysis determined significant efficacy for S. boulardii in reducing relapses (RR 0.59, 95% CI 0.35-0.98, while another concluded there was insufficient evidence to recommend probiotics for C. difficile infection.Conclusions: S. boulardii may be considered for patients with recurrent C. difficile infection, refractory to antibiotic regimens alone.

Comparison of the association of sac growth and coil compaction with recurrence in coil embolized cerebral aneurysms.

Directory of Open Access Journals (Sweden)

Anna L Hoppe

Full Text Available In recurrent cerebral aneurysms treated by coil embolization, coil compaction is regarded as the presumptive mechanism. We test the hypothesis that aneurysm growth is the primary recurrence mechanism. We also test the hypothesis that the coil mass will translate a measurable extent when recurrence occurs.An objective, quantitative image analysis protocol was developed to determine the volumes of aneurysms and coil masses during initial and follow-up visits from 3D rotational angiograms. The population consisted of 15 recurrence and 12 non-recurrence control aneurysms initially completely coiled at a single center. An investigator sensitivity study was performed to assess the objectivity of the methods. Paired Wilcoxon tests (p<0.05, one-tailed were performed to assess for aneurysm and coil growth. The translation of the coil mass center at follow-up was computed. A Mann Whitney U-Test (p<0.05, one-tailed was used to compare translation of coil mass centers between recurrence and control subjects.Image analysis protocol was found to be insensitive to the investigator. Aneurysm growth was evident in the recurrence cohort (p=0.003 but not the control (p=0.136. There was no evidence of coil compaction in either the recurrence or control cohorts (recurrence: p=0.339; control: p=0.429. The translation of the coil mass centers was found to be significantly larger in the recurrence cohort than the control cohort (p=0.047.Aneurysm sac growth, not coil compaction, was the primary mechanism of recurrence following successful coil embolization. The coil mass likely translates to a measurable extent when recurrence occurs and has the potential to serve as a non-angiographic recurrence marker.

Recurrent Meningitis.

Science.gov (United States)

Rosenberg, Jon; Galen, Benjamin T

2017-07-01

Recurrent meningitis is a rare clinical scenario that can be self-limiting or life threatening depending on the underlying etiology. This review describes the causes, risk factors, treatment, and prognosis for recurrent meningitis. As a general overview of a broad topic, the aim of this review is to provide clinicians with a comprehensive differential diagnosis to aide in the evaluation and management of a patient with recurrent meningitis. New developments related to understanding the pathophysiology of recurrent meningitis are as scarce as studies evaluating the treatment and prevention of this rare disorder. A trial evaluating oral valacyclovir suppression after HSV-2 meningitis did not demonstrate a benefit in preventing recurrences. The data on prophylactic antibiotics after basilar skull fractures do not support their use. Intrathecal trastuzumab has shown promise in treating leptomeningeal carcinomatosis from HER-2 positive breast cancer. Monoclonal antibodies used to treat cancer and autoimmune diseases are new potential causes of drug-induced aseptic meningitis. Despite their potential for causing recurrent meningitis, the clinical entities reviewed herein are not frequently discussed together given that they are a heterogeneous collection of unrelated, rare diseases. Epidemiologic data on recurrent meningitis are lacking. The syndrome of recurrent benign lymphocytic meningitis described by Mollaret in 1944 was later found to be closely related to HSV-2 reactivation, but HSV-2 is by no means the only etiology of recurrent aseptic meningitis. While the mainstay of treatment for recurrent meningitis is supportive care, it is paramount to ensure that reversible and treatable causes have been addressed for further prevention.

CLIPPERS among patients diagnosed with non-specific CNS neuroinflammatory diseases

DEFF Research Database (Denmark)

Kerrn-Jespersen, B M; Lindelof, M; Illes, Zsolt

2014-01-01

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is an inflammatory CNS disorder characterized by 1) subacute onset of cerebellar and brainstem symptoms, 2) peripontine contrast-enhancing perivascular lesions with a "salt-and-pepper" appeara...

Recurrent Syncope due to Esophageal Squamous Cell Carcinoma

Directory of Open Access Journals (Sweden)

A. Casini

2011-09-01

Full Text Available Syncope is caused by a wide variety of disorders. Recurrent syncope as a complication of malignancy is uncommon and may be difficult to diagnose and to treat. Primary neck carcinoma or metastases spreading in parapharyngeal and carotid spaces can involve the internal carotid artery and cause neurally mediated syncope with a clinical presentation like carotid sinus syndrome. We report the case of a 76-year-old man who suffered from recurrent syncope due to invasion of the right carotid sinus by metastases of a carcinoma of the esophagus, successfully treated by radiotherapy. In such cases, surgery, chemotherapy or radiotherapy can be performed. Because syncope may be an early sign of neck or cervical cancer, the diagnostic approach of syncope in patients with a past history of cancer should include the possibility of neck tumor recurrence or metastasis and an oncologic workout should be considered.

[Ear, nose, and throat manifestations in patients with primary immunodeficiencies].

Science.gov (United States)

Galicia, G; Betancourt, M A; Canales, L E; Cristerna, L

1999-01-01

To determine the flowgram for the timely diagnosis of the immunodeficiencies congenital primary, based on the demonstrations otorrinolaringol recurrent chronicles to difficult control, with or without associated systemic diseases. Retrospective study, descriptive and observational that included patient with diagnostic of primary known immunodeficiency. They were checked the clinical files to know their evolution and medical treatment-surgical. They were found 10 patient with diagnostic of some primary immunodeficiency; this was made based on the infectious symptoms otolaryngal chronic recurrent to difficult control; they were six men and four women between the four and 36 years old. They were found the following immunodeficiencies: one of hyper-IgM, three by IgG, variable common three, a deficit with C3 of the complement, two of IgA more atopia. The chronicle sinusitis or recurrent and the otitis mean chronicle or recurrent can be the only demonstrations of a patient with primary immunodeficiency. The immunology evaluation must include, at least: hematic biometric completes with differential, seric levels of immunoglobulins, the same as subclass of IgG, C4 and C3 of the complement, response to immunization with proteins (diphtheria and tetanus), and polysaccharide antigens (pneumovax).

Imaging of chronic recurrent multifocal osteomyelitis of childhood first presenting with isolated primary spinal involvement

International Nuclear Information System (INIS)

Anderson, S.E.; Heini, P.; Kalbermatten, D.; Sauvain, M.J.; Stauffer, E.; Geiger, L.; Johnston, J.O.; Roggo, A.; Steinbach, L.S.

2003-01-01

Initial presentation with primary spinal involvement in chronic recurrent multifocal osteomyelitis of childhood (CRMO) is rare. Our objective was to review the imaging appearances of three patients who had CRMO who initially presented with isolated primary spinal involvement.Design and patients The imaging, clinical, laboratory and histology findings of the three patients were retrospectively reviewed. Imaging included seven spinal MR imaging scans, one computed tomography scan, nine bone scans, two tomograms and 16 radiographs. These were reviewed by two musculoskeletal radiologists and a consensus view is reported. All three patients presented with atraumatic spinal pain and had extensive bone spinal pathology. The patients were aged 11, 13 and 12 years. There were two females and one male.Results and conclusions The initial patient had thoracic T6 and T8 vertebra plana. Bone scan showed additional vertebral body involvement. Follow-up was available over a 3 year period. The second patient had partial collapse of T9 and, 2 years later, of C6. Subsequently extensive multifocal disease ensued and follow-up was available over 8 years. The third patient initially had L3 inferior partial collapse and 1 year later T8 involvement with multifocal disease. Follow-up was available over 3 years. The imaging findings of the three patients include partial and complete vertebra plana with a subchondral line adjacent to endplates associated with bone marrow MR signal alterations. Awareness of the imaging appearances may help the radiologist to include this entity in the differential diagnosis in children who present with spinal pathology and no history of trauma. Histopathological examination excludes tumor and infection but with typical imaging findings may not always be necessary. (orig.)

Which drug or drug delivery system can change clinical practice for brain tumor therapy?

OpenAIRE

Siegal, Tali

2013-01-01

The prognosis and treatment outcome for primary brain tumors have remained unchanged despite advances in anticancer drug discovery and development. In clinical trials, the majority of promising experimental agents for brain tumors have had limited impact on survival or time to recurrence. These disappointing results are partially explained by the inadequacy of effective drug delivery to the CNS. The impediments posed by the various specialized physiological barriers and active efflux mechanis...

Primary amebic meningoencephalitis due to Naegleria fowleri in a South American tapir.

Science.gov (United States)

Lozano-Alarcón, F; Bradley, G A; Houser, B S; Visvesvara, G S

1997-05-01

Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris are known to cause fatal central nervous system (CNS) disease in human beings. N. fowleri causes acute, fulminating primary amebic meningoencephalitis (PAM), which generally leads to death within 10 days. Acanthamoeba spp. and B. mandrillaris cause chronic granulomatous amebic encephalitis, which may last for 8 weeks. Acanthamoeba spp. and B. mandrillaris also cause CNS disease in animals. N. fowleri, however, has been described only in human beings. This report is the first of PAM in an animal, a South American tapir. Dry cough, lethargy, and coma developed in the animal, and its condition progressed to death. At necropsy, lesions were seen in the cerebrum, cerebellum, and lungs. The CNS had severe, suppurative meningoencephalitis with many neutrophils, fibrin, plasma cells, and amebas. Amebas were 6.5 microns to 9 microns in diameter and had a nucleus containing a large nucleolus. Amebas in the sections reacted with a monoclonal antibody specific for N. fowleri in the immunofluorescent assay and appeared bright green.

Skin Cancer of the Head and Neck With Perineural Invasion: Defining the Clinical Target Volumes Based on the Pattern of Failure

International Nuclear Information System (INIS)

Gluck, Iris; Ibrahim, Mohannad; Popovtzer, Aron; Teknos, Theodoros N.; Chepeha, Douglas B.; Prince, Mark E.; Moyer, Jeffrey S.; Bradford, Carol R.; Eisbruch, Avraham

2009-01-01

Purpose: To analyze patterns of failure in patients with head-and-neck cutaneous squamous cell carcinoma (HNCSCC) and clinical/radiologic evidence of perineural invasion (CPNI), in order to define neural clinical target volume (CTV) for treatment planning. Methods and Materials: Patients treated with three-dimensional (3D) conformal or intensity-modulated radiotherapy (IMRT) for HNCSCC with CPNI were included in the study. A retrospective review of the clinical charts, radiotherapy (RT) plans and radiologic studies has been conducted. Results: Eleven consecutive patients with HNCSCCs with CPNI were treated from 2000 through 2007. Most patients underwent multiple surgical procedures and RT courses. The most prevalent failure pattern was along cranial nerves (CNs), and multiple CNs were ultimately involved in the majority of cases. In all cases the involved CNs at recurrence were the main nerves innervating the primary tumor sites, as well as their major communicating nerves. We have found several distinct patterns of disease spread along specific CNs depending on the skin regions harboring the primary tumors, including multiple branches of CN V and VII. These patterns and the pertinent anatomy are detailed in the this article. Conclusions: Predictable disease spread patterns along cranial nerves supplying the primary tumor sites were found in this study. Awareness of these patterns, as well as knowledge of the relevant cranial nerve anatomy, should be the basis for CTV definition and delineation for RT treatment planning.

Changes in the ER, PgR, HER2, p53 and Ki-67 biological markers between primary and recurrent breast cancer: discordance rates and prognosis

Directory of Open Access Journals (Sweden)

Tashima Rumiko

2011-10-01

Full Text Available Abstract Background In breast cancer, ER/PgR, HER2, and Ki-67 are important biological markers for predicting prognosis and making effective treatment decisions. In addition, changes in markers due to relapse are also clinically experienced; however, the frequency and clinical significance are still not fully understood. Thus, changes in markers and their correlations with prognosis were investigated. Patients and Methods Out of the patients with relapse from 1997 to March 2011, there were 97 consecutive patients from whom the lesion was resected and evaluated by immunostaining. The biopsy sites were chest wall, lymph node, ipsilateral breast tumor recurrence, lungs, bones, ovaries and brain. The markers sought were ER, PgR, HER2, p53 and Ki-67. Results The hormone receptor positive rate from the primary tumor to recurrence decreased from 63.9% to 57.7% and from 56.7% to 43.3% for ER and PgR, respectively. Changes in the positive/negative evaluation were seen at the rate of 10.3% and 25.8% for ER and PgR, respectively. The Ki-67 index increased significantly from a mean of 29.1% at primary tumor to 36.3% at relapse. When divided into 2 groups ( Conclusion Estrogen receptor and PgR decreased while Ki-67 increased due to relapse; however, the rate of change was high for PgR and Ki-67. Change in the subtypes was seen in 25%. In addition, PgR at relapse and Ki-67 at primary tumor were significant factors for post-relapse prognosis while PgR becoming negative was a poor prognostic factor. These findings are important for making effective treatment decisions.

Inflammatory cytokines in the brain: does the CNS shape immune responses?

Science.gov (United States)

Owens, T; Renno, T; Taupin, V; Krakowski, M

1994-12-01

Immune responses in the central nervous system (CNS) have traditionally been regarded as representing the intrusion of an unruly, ill-behaved mob of leukocytes into the well-ordered and organized domain of thought and reason. However, results accumulated over the past few years suggest that, far from being an immunologically privileged organ, T lymphocytes may be regular and frequent visitors to the CNS, for purposes of immune surveillance. Here, Trevor Owens and colleagues propose that the brain itself can regulate or shape immune responses therein. Furthermore, given that the immune cells may be subverted to autoimmunity, they suggest that the study of inflammatory autoimmune disease in the brain may shed light on the ability of the local environment to regulate immune responses.

Recurrent meningitis associated with frontal sinus tuber encephalocele in a patient with tuberous sclerosis.

Science.gov (United States)

Elbabaa, Samer K; Riggs, Angela D; Saad, Ali G

2011-07-01

Tuberous sclerosis complex (TSC) is a genetic neurocutaneous disorder that commonly affects the CNS. The most commonly associated brain tumors include cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). The authors report an unusual case of recurrent meningitis due to a tuber-containing encephalocele via the posterior wall of the frontal sinus. An 11-year-old girl presented with a history of TSC and previous SEGA resection via interhemispheric approach. She presented twice within 4 months with classic bacterial meningitis. Cerebrospinal fluid cultures revealed Streptococcus pneumoniae. Computed tomography and MR imaging of the brain showed a right frontal sinus encephalocele via a posterior frontal sinus wall defect. Both episodes of meningitis were treated successfully with standard regimens of intravenous antibiotics. The neurosurgical service was consulted to discuss surgical options. Via a bicoronal incision, a right basal frontal craniotomy was performed. A large frontal encephalocele was encountered in the frontal sinus. The encephalocele was herniating through a bony defect of the posterior sinus wall. The encephalocele was ligated and resected followed by removing frontal sinus mucosa and complete cranialization of frontal sinus. Repair of the sinus floor was conducted with fat and pericranial grafts followed by CSF diversion via lumbar drain. Histopathology of the resected encephalocele showed a TSC tuber covered with respiratory (frontal sinus) mucosa. Tuber cells were diffusely positive for GFAP. The patient underwent follow-up for 2 years without evidence of recurrent meningitis or CSF rhinorrhea. This report demonstrates that frontal tubers of TSC can protrude into the frontal sinus as acquired encephaloceles and present with recurrent meningitis. To the authors' knowledge, recurrent meningitis is not known to coincide with TSC. Careful clinical and radiographic follow-up for frontal tubers in patients with TSC is

A Novel Robust H∞ Filter Based on Krein Space Theory in the SINS/CNS Attitude Reference System

Directory of Open Access Journals (Sweden)

Fei Yu

2016-03-01

Full Text Available Owing to their numerous merits, such as compact, autonomous and independence, the strapdown inertial navigation system (SINS and celestial navigation system (CNS can be used in marine applications. What is more, due to the complementary navigation information obtained from two different kinds of sensors, the accuracy of the SINS/CNS integrated navigation system can be enhanced availably. Thus, the SINS/CNS system is widely used in the marine navigation field. However, the CNS is easily interfered with by the surroundings, which will lead to the output being discontinuous. Thus, the uncertainty problem caused by the lost measurement will reduce the system accuracy. In this paper, a robust H∞ filter based on the Krein space theory is proposed. The Krein space theory is introduced firstly, and then, the linear state and observation models of the SINS/CNS integrated navigation system are established reasonably. By taking the uncertainty problem into account, in this paper, a new robust H∞ filter is proposed to improve the robustness of the integrated system. At last, this new robust filter based on the Krein space theory is estimated by numerical simulations and actual experiments. Additionally, the simulation and experiment results and analysis show that the attitude errors can be reduced by utilizing the proposed robust filter effectively when the measurements are missing discontinuous. Compared to the traditional Kalman filter (KF method, the accuracy of the SINS/CNS integrated system is improved, verifying the robustness and the availability of the proposed robust H∞ filter.

Factors Predictive of Tumor Recurrence and Survival After Initial Complete Response of Esophageal Squamous Cell Carcinoma to Definitive Chemoradiotherapy

International Nuclear Information System (INIS)

Ishihara, Ryu; Yamamoto, Sachiko; Iishi, Hiroyasu; Takeuchi, Yoji; Sugimoto, Naotoshi; Higashino, Koji; Uedo, Noriya; Tatsuta, Masaharu; Yano, Masahiko; Imai, Atsushi; Nishiyama, Kinji

2010-01-01

Purpose: To assess factors predictive of recurrent disease and survival after achieving initial complete response (CR) to chemoradiotherapy (CRT) for esophageal cancer. Methods and Materials: Patients who had clinical Stage I-IVA esophageal cancer and received definitive CRT between 2001 and 2007 were retrospectively analyzed. Results: Of 269 patients with esophageal cancer, 110 who achieved CR after definitive CRT were included in the analyses. Chemoradiotherapy mainly consisted of 2 cycles of cisplatin and fluorouracil with concurrent radiotherapy of 60 Gy in 30 fractions. We identified 28 recurrences and 28 deaths during follow-up. The cumulative 1- and 3-year recurrence rates were 18% and 32%, respectively. By univariate and multivariate analyses, tumor category (hazard ratio [HR] 6.6; 95% confidence interval [CI] 1.4-30.2; p = 0.015) was an independent risk factor for local recurrence, whereas age (HR 3.9; 95% CI 1.1-14.0; p = 0.034) and primary tumor location (HR 4.5; 95% CI 1.6-12.4; p = 0.004) were independent risk factors for regional lymph node or distant recurrences. The cumulative overall 1- and 3-year survival rates were 91% and 66%, respectively. As expected, recurrence was associated with poor survival (p = 0.019). By univariate and multivariate analyses, primary tumor location (HR 3.8; 95% CI 1.2-12.0; p = 0.024) and interval to recurrence (HR 4.3; 95% CI 1.3-14.4; p = 0.018) were independent factors predictive of survival after recurrence. Conclusion: Risk of recurrence after definitive CRT for esophageal cancer was associated with tumor category, age, and primary tumor location; this information may help in improved prognostication for these patients.

MTR-18 Predictive Biomarkers Of Bevacizumab Response In Recurrent Glioblastoma Patients

DEFF Research Database (Denmark)

Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn

2015-01-01

Bevacizumab (BEV) plus chemotherapy has shown activity in recurrent glioblastoma (GBM). However, the prognosis varies and only one third of patients have a durable clinical response to BEV combination therapy. Recent findings from a randomized phase-3 study (AVAglio) indicate that patients...... with the proneural GBM subtype have a survival benefit when treated with BEV in combination with standard treatment. However, no validated biomarkers able to predict BEV response have been identified and the biology reflecting a clinical BEV response is poorly understood. The primary objective of this study...... was to evaluate the predictive and prognostic value of GBM subtypes in recurrent GBM patients treated with BEV therapy. The secondary objective was to identify biomarkers able to predict response to BEV therapy in recurrent GBM patients. METHODS: A total of 90 recurrent GBM patients treated with BEV combination...

Maternal stress, nutrition and physical activity: Impact on immune function, CNS development and psychopathology.

Science.gov (United States)

Marques, Andrea Horvath; Bjørke-Monsen, Anne-Lise; Teixeira, Antônio L; Silverman, Marni N

2015-08-18

Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying

SPARC and GluA1-Containing AMPA Receptors Promote Neuronal Health Following CNS Injury

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Emma V. Jones

2018-02-01

Full Text Available The proper formation and maintenance of functional synapses in the central nervous system (CNS requires communication between neurons and astrocytes and the ability of astrocytes to release neuromodulatory molecules. Previously, we described a novel role for the astrocyte-secreted matricellular protein SPARC (Secreted Protein, Acidic and Rich in Cysteine in regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs and plasticity at developing synapses. SPARC is highly expressed by astrocytes and microglia during CNS development but its level is reduced in adulthood. Interestingly, SPARC has been shown to be upregulated in CNS injury and disease. However, the role of SPARC upregulation in these contexts is not fully understood. In this study, we investigated the effect of chronic SPARC administration on glutamate receptors on mature hippocampal neuron cultures and following CNS injury. We found that SPARC treatment increased the number of GluA1-containing AMPARs at synapses and enhanced synaptic function. Furthermore, we determined that the increase in synaptic strength induced by SPARC could be inhibited by Philanthotoxin-433, a blocker of homomeric GluA1-containing AMPARs. We then investigated the effect of SPARC treatment on neuronal health in an injury context where SPARC expression is upregulated. We found that SPARC levels are increased in astrocytes and microglia following middle cerebral artery occlusion (MCAO in vivo and oxygen-glucose deprivation (OGD in vitro. Remarkably, chronic pre-treatment with SPARC prevented OGD-induced loss of synaptic GluA1. Furthermore, SPARC treatment reduced neuronal death through Philanthotoxin-433 sensitive GluA1 receptors. Taken together, this study suggests a novel role for SPARC and GluA1 in promoting neuronal health and recovery following CNS damage.

Malignant lymphoma in central nervous system (CNS). Report of a case with characteristic CT finding and amnesia

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Fujiyoshi, Kenji; Fukuyama, Hidenao; Akiguchi, Ichiro; Kameyama, Masakuni [Kyoto Univ. (Japan). Faculty of Medicine; Nishimura, Toshio

1984-07-01

A 71-year-old male was admitted to Kohka Public Hospital on January 4, 1980, because of frequent vomiting and recent memory loss. Two weeks before admission upper G-I series showed no abnormalities. Physical and neurological examinations revealed no abnormalities except for slightly apathetic appearance and recent memory loss. Mild pleocytosis and marked increase of protein in CSF were observed. CT scan on January 17 showed high density areas in both medial sides of temporal lobes with remarkable contrast enhancement. His memory and, consciousness disturbances gradually aggravated, accompanied by abnormal density spreading around the ventricle walls like ventriculitis. He was transfered to Kyoto University Hospital on March 17, and malignant lymphoma was diagnosed on the basis of CSF cytology. Radiation and chemotherapy alleviated the CNS involvement and he regained normal mental function. On June 16, he developed pneumonia followed by status epilepticus. Autopsy findings revealed no lymphoid cell infiltration, but fibrous tissues in both hippocampal gyri and lymphomatous cells in the liver, which could not be suspected on clinical examinations. Apparent malignant lymphoma cells were not found in lymph nodes. This case indicated peculiar evolution of malignant lymphoma from liver to CNS or vice versa. We could not decide which organ was primary. CT findings of this case was very interesting; they resembled ventriculitis, which simulate tumors such as medulloblastoma or ependymoma spreading under ependymal lining.

Risk factors for recurrent vulvovaginal candidiasis

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Janković Slobodan

2010-01-01

Full Text Available Background/Aim. Recurrent vulvovaginal candidiasis is relatively frequent condition, and may have serious health consequences, like chronic vulvovaginal pain syndrome. The aim of our study was to determine possible risk factors for recurrent vulvovaginal candidiasis in non-pregnant females within the reproductive age. Methods. The design of our study was of a case-control type. Case and control patients were selected from the gynecological patients at six primary care facilities in Serbia and in Montenegro. The data on the patients' health condition, concomitant therapy and diseases were taken from their records, and the data on habits were obtained by unstructured interview. For potential risk factors crude odds ratios were calculated, and then adjusted by logistic regression. Results. A total of fifty-one patients had four or more episodes of vulvovaginal candidiasis during the last year (cases, and 132 patients with one to three episodes of vulvovaginal candidiasis were sampled as controls, matched by age. The only two significant associations were found between recurrent vulvovaginal candidiasis and continual wearing of panty liners during the last year (Odds ratio - ORadjusted: 3.97; confidence interval - CI: 1.57-10.02; p = 0.004, and between recurrent vulvovaginal candidiasis and predominant use of vaginal tampons during menstruation in the last year (ORadjusted: 4.25; CI: 1.11-16.27; p = 0.035. The synergistic effect was observed for the concurrent continual wearing of panty liners during the last year and selfmedication with antimycotics. Conclusions. Local factors, like wearing of panty liners or use of tampons during menstruation, may promote recurrence of vulvovaginal candidiasis, especially in patients who practice selfmedication with antimycotics.

Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions

DEFF Research Database (Denmark)

Kuhlmann, Tanja; Remington, Leah; Maruschak, Brigitte

2007-01-01

to be strongly expressed in mature oligodendrocytes in vivo. In the present investigation we analyzed the expression patterns of Nogo-A in adult mouse and human CNS as well as in demyelinating animal models and multiple sclerosis lesions. Nogo-A expression was compared with that of other frequently used...... oligodendroglial markers such as CC1, CNP, and in situ hybridization for proteolipid protein mRNA. Nogo-A strongly and reliably labeled oligodendrocytes in the adult CNS as well as in demyelinating lesions and thus represents a valuable tool for the identification of oligodendrocytes in human and mouse CNS tissue...

Comparative analysis of acid sphingomyelinase distribution in the CNS of rats and mice following intracerebroventricular delivery.

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Christopher M Treleaven

Full Text Available Niemann-Pick A (NPA disease is a lysosomal storage disorder (LSD caused by a deficiency in acid sphingomyelinase (ASM activity. Previously, we reported that biochemical and functional abnormalities observed in ASM knockout (ASMKO mice could be partially alleviated by intracerebroventricular (ICV infusion of hASM. We now show that this route of delivery also results in widespread enzyme distribution throughout the rat brain and spinal cord. However, enzyme diffusion into CNS parenchyma did not occur in a linear dose-dependent fashion. Moreover, although the levels of hASM detected in the rat CNS were determined to be within the range shown to be therapeutic in ASMKO mice, the absolute amounts represented less than 1% of the total dose administered. Finally, our results also showed that similar levels of enzyme distribution are achieved across rodent species when the dose is normalized to CNS weight as opposed to whole body weight. Collectively, these data suggest that the efficacy observed following ICV delivery of hASM in ASMKO mice could be scaled to CNS of the rat.

[Choice of surgical approaches for salvage surgery of primary lesion recurrence and residual cases of nasopharyngeal carcinoma].

Science.gov (United States)

Tao, Zhong-Qiang; Si, Yong-Feng; Lan, Sheng-Yong; Zhang, Zheng; Deng, Zhuo-Xia; Huang, Bo; Zhou, Ri-Jing; Lu, Jin-Long

2011-02-01

The choice of surgical approaches for salvage surgery based on the location and invasion of recurrent and residual lesions of nasopharyngeal carcinoma (NPC), surgical results, complications, and survival were assessed. Thirty-seven cases with recurrent and residual lesions of NPC underwent salvage surgery between March 1991 and January 2005 were analysed retrospectively. Of 37 patients, 23 were men and 14 women, with a median age of 46.5 years (26 - 57 years); 4 were at stage I, 10 at stage II, 14 at stage III, and 9 at stage IV; 5 cases were with cervical metastasis, including 3 cases of N1 and 2 cases N2. All recurrent and residual lesions of NPC were determined by biopsy. On the location and invasion of recurrent and residual lesions of NPC, 8 cases underwent endoscopic resection of lesions, 12 cases of the palate nasopharyngectomy, 5 cases of maxillary swing, 4 cases of maxillary swing plus prerenal approach, 2 cases of lateral rhinotomy plus coronal flap approach, and 6 cases transfacial plus nasal pyramid swing approach. Five cases with cervical metastasis received neck dissection in addition to the operations for recurrent and residual lesions of NPC. Postoperatively 31 cases received radiotherapy with dosage of 60 Gy, among them 15 cases with concurrent chemoradiation therapy, and 6 cases with clear surgical margin did not received radiotherapy or chemotherapy. The cases were followed up for 12 - 72 months, with a median of 45 months. Total resection for the recurrent and residual lesions of NPC accounted for 91.8% (34/37) and subtotal resection for 8.2% (3/37). The accident of perioperative complications was 24.3% (9/37). The 3- and 5-year overall disease-free survival rates (DFSR) were 62.1% and 43.3%, respectively. The 3- and 5-year overall survival rates (OSR) were 72.9% and 51.3%, respectively. The 5 year DFSR of cases at stage I-IV were 100%, 40%, 28% and 11% (χ(2) = 10.0, P < 0.01), respectively. The 5 year OSR were 100%, 70%, 35% and 28% (χ(2

Oncological outcome, complications, lower urinary tract symptoms, and health-related quality of life after low-dose-rate salvage brachytherapy for recurrent prostate cancer following primary radiotherapy: a report of 8 cases

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Makito Miyake

2017-07-01

Full Text Available Purpose: We evaluated our experience with low-dose-rate salvage brachytherapy for local recurrence after primary prostate radiotherapy, and described the changes in lower urinary tract symptoms and health-related quality of life. Material and methods: Between 2011 and 2016, eight men with local recurrence after primary prostate radiotherapy underwent iodine-125 salvage brachytherapy with a prescribed dose of 110 or 145 Gy. Recurrence-free survival was evaluated with a post-treatment prostate-specific antigen profile. The toxicity and changes in lower urinary tract symptoms and health-related quality of life during the follow-up were evaluated on the Common Terminology Criteria for Adverse Events version 4.0, International Prostate Symptom Score, Short Form-8, and Expanded Prostate Cancer Index Composite, respectively. Results: The median follow-up was 12.2 months (range, 8.3-71.9 after salvage brachytherapy. Of all eight patients, two (25% experienced treatment failure, one of whom developed left seminal vesicle recurrence 36 months after salvage brachytherapy for the right seminal vesicle recurrence, while the other developed bone metastases after 6 months. The International Prostate Symptom Scores peaked at 3 months, and returned to baseline by 6 months. The scores of all domains of health-related quality of life remained unchanged during the 12-month follow-up after salvage brachytherapy. Early grade ≤ 2 genitourinary toxicity was observed in five patients (63%, and late grade 2 gastrointestinal toxicity in one patient (13% having persistent diarrhea. No patient required intermittent catheterization and no grade 3 or greater toxicity occurred during follow-up. Conclusions: The present study is our experiment of eight patients undergoing salvage brachytherapy, suggesting that this modality is noninvasive, safe, and an effective salvage local treatment in selected patients. To our knowledge, this is the first study to evaluate lower urinary

Recurrent hydatosis at the site of non-union humerus fracture

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Mohsen Nourbakhsh

2012-01-01

Full Text Available Hydatid disease is still endemic in several regions of the world and is caused by two species of tapeworms, Echinococcus granulosus and Echinococcus alveolaris. It primary involves liver and lung, and bone involvement is relatively rare (0.2-4%, where it is most commonly seen in the spine. The skeletal involvement is usually due to secondary extension such as hematogenous spread. The disease has usually a silent manifestation until a complication exists; so, many cases are diagnosed intraoperatively. Treatment of hydatid disease because of its bone involvement and spillage of fluid with subsequent contamination seeding is difficult, so it has a high mortality rate and many cases will recur. Therefore, we can prevent these occurrences if we treat hydatid disease completely and in the primary stage. Adjuvant medical treatment, if the diagnosis is known, prevents systemic spread and recurrence. Here, we present a primary recurrent hydatosis at the site of non-union humerus fracture. We have pointed out osseous hydatosis as one of the important differential diagnoses in destructive bone lesions and the necessity of its radical resection.

Chemoradiotherapy of Anal Carcinoma: Survival and Recurrence in an Unselected National Cohort

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Bentzen, Anne Gry, E-mail: anne.gry.bentzen@unn.no [Department of Oncology, University Hospital of Northern Norway, Tromso (Norway); Institute of Clinical Medicine, University of Tromso, Tromso (Norway); Guren, Marianne G.; Wanderas, Eva H. [Department of Oncology, Oslo University Hospital, Oslo (Norway); Frykholm, Gunilla [Department of Oncology, St. Olav' s University Hospital, Trondheim, Norway and The Norwegian Radiation Protection Authority (NRPA), Osteras (Norway); Tveit, Kjell M. [Department of Oncology, Oslo University Hospital, Oslo (Norway); Faculty of Medicine, University of Oslo, Oslo (Norway); Wilsgaard, Tom [Department of Community Medicine, University of Tromso, Tromso (Norway); Dahl, Olav [Section of Oncology, Institute of Medicine, University of Bergen and Department of Oncology, Haukeland University Hospital, Bergen (Norway); Balteskard, Lise [Department of Oncology, University Hospital of Northern Norway, Tromso (Norway); Centre for Clinical Documentation and Evaluation, Northern Norway Regional Health Authority, Tromso (Norway)

2012-06-01

Purpose: To evaluate treatment results, elucidate whether national guidelines were followed, and identify areas demanding further treatment optimization. Methods and Material: Between July 2000 and June 2007, 328 patients were treated with curatively intended chemoradiotherapy (CRT) for nonmetastatic squamous cell carcinoma of the anal region, according to national treatment guidelines based on tumor stage. Results: Complete response after CRT was obtained in 87% of patients, rising to 93% after salvage surgery. Chemotherapy, elective irradiation of the groin and salvage surgery were performed to a lesser extent in elderly patients, mainly because of frailty and comorbidity. Recurrence occurred in 24% of the patients, resulting in a 3- and 5-year recurrence-free survival (RFS) of 79% and 74%, respectively. Locoregional recurrences dominated, most commonly in the primary tumor site. Recurrence was treated with curative intent in 45% of the cases. The 3- and 5-year overall survival were 79% and 66%, and cancer-specific survival (CSS) were 84% and 75%, respectively. The risk of adverse outcome increased significantly with more locally advanced tumors and for male gender in multivariable analyses for RFS and CSS. Conclusions: The treatment results are in accordance with similar cohorts. The primary treatment control rate was high, but there was a significant risk of locoregional recurrence in advanced tumors. The loyalty to national guidelines was broad, although individual adjustments occurred. However, caution to avoid toxicity must not lead to inadequate treatment. Male gender seems to have inferior outcome.

Chemoradiotherapy of Anal Carcinoma: Survival and Recurrence in an Unselected National Cohort

International Nuclear Information System (INIS)

Bentzen, Anne Gry; Guren, Marianne G.; Wanderås, Eva H.; Frykholm, Gunilla; Tveit, Kjell M.; Wilsgaard, Tom; Dahl, Olav; Balteskard, Lise

2012-01-01

Purpose: To evaluate treatment results, elucidate whether national guidelines were followed, and identify areas demanding further treatment optimization. Methods and Material: Between July 2000 and June 2007, 328 patients were treated with curatively intended chemoradiotherapy (CRT) for nonmetastatic squamous cell carcinoma of the anal region, according to national treatment guidelines based on tumor stage. Results: Complete response after CRT was obtained in 87% of patients, rising to 93% after salvage surgery. Chemotherapy, elective irradiation of the groin and salvage surgery were performed to a lesser extent in elderly patients, mainly because of frailty and comorbidity. Recurrence occurred in 24% of the patients, resulting in a 3- and 5-year recurrence-free survival (RFS) of 79% and 74%, respectively. Locoregional recurrences dominated, most commonly in the primary tumor site. Recurrence was treated with curative intent in 45% of the cases. The 3- and 5-year overall survival were 79% and 66%, and cancer-specific survival (CSS) were 84% and 75%, respectively. The risk of adverse outcome increased significantly with more locally advanced tumors and for male gender in multivariable analyses for RFS and CSS. Conclusions: The treatment results are in accordance with similar cohorts. The primary treatment control rate was high, but there was a significant risk of locoregional recurrence in advanced tumors. The loyalty to national guidelines was broad, although individual adjustments occurred. However, caution to avoid toxicity must not lead to inadequate treatment. Male gender seems to have inferior outcome.

Compliance of patients concerning recommended radiotherapy in breast cancer. Association with recurrence, age, and hormonal therapy

International Nuclear Information System (INIS)

Winzer, K.J.; Gruber, C.; Badakhshi, H.; Charite Universitaetsmedizin Berlin; Hinkelbein, M.; Denkert, C.

2012-01-01

Background and purpose: In this study, we investigated how often guidelines for radiation therapy in patients with breast cancer are not complied with, which patient group is mostly affected, and how this influences local recurrence. Patients and methods: All patients (n = 1,903) diagnosed between November 2003 and December 2008 with primary invasive or intraductal breast cancer in the interdisciplinary breast center of the Charite Hospital Berlin were included and followed for a median 2.18 years. Results: Patients who, in contrast to the recommendation of the interdisciplinary tumor board, did not undergo postoperative radiation experienced a fivefold higher local recurrence rate (p < 0.0005), corresponding to a 5-year locoregional recurrence-free survival of 74.5% in this group. The 5-year locoregional recurrence-free survival of patients following the recommendations was 93.3%. Guideline compliance was dependent on age of patients, acceptance of adjuvant hormonal treatment or chemotherapy, and increased diameter of the primary tumor. Multiple logistic regression analysis showed an association between compliance and age or hormonal therapy. Conclusion: In order to avoid local recurrence patients should be motivated to comply with guideline driven therapy. Since a higher number of local recurrences is observed in health services research compared to clinical research, studies on the value of adjuvant treatment following local recurrence should be performed. (orig.)

Tendencies the treatment of the central nervous system (CNS) tumors

International Nuclear Information System (INIS)

Alert Silva, Jose; Jimenez Medina, Jose

2004-01-01

It is known that the treatment of the central nervous system (CNS) tumors is based on the use of surgery and radiotherapy (RT) and that chemotherapy (QMT) is used even more, as well as the other drugs. A bibliographic review was made to update the knowledge on the current trends and perspectives of RT applied to CNS tumors. The following were found among them: a) combinations of RT and CMT; b) radiosensitizers incorporated to the radiant treatment; c) angiogenesis inhibitors associated with RT; d) the scale-up or increase of the RT doses thanks to the development of new technologies, such as 3 D conformal radiotherapy, intensity- modulated radiotherapy, surgery and others. Another field of research is that of the changes in the rhythm or fractioning of the RT: hyperfractionated, accelerated, combinations of both, etc., which will allow mainly to increase the dosage scale-up

Commercial viability of CNS drugs: balancing the risk/reward profile.

Science.gov (United States)

Johnson, Ginger S

2014-01-01

CNS has historically been a formidable therapeutic area in which to innovate owing to biological (e.g., complex neurobiology, difficulty reaching the target), as well as clinical (e.g., subjective clinical endpoints, high placebo response, lack of biomarkers) challenges. In the current market where many of the larger diseases are dominated by a generic standard of care, commercial challenges now make the triple threat of scientific-clinical-commercial risk too much for many players to tackle. However, opportunities do exist for smaller biotech companies to concentrate on narrowly focused patient populations associated with high unmet need for which risk can be tightly defined. In CNS, there are two major areas to balance the risk/reward profile and create commercially viable opportunities: To realize value, all companies (start-ups and big players) must define, measure and quantify clear and meaningful value to all stakeholders: physicians, patients, caregivers and payers. © 2013.

Metallothionein Expression and Roles During Neuropathology in the CNS

DEFF Research Database (Denmark)

Penkowa, Milena

2006-01-01

, their receptors and neurotrophins (TGFb, TGFb-Receptor, bFGF, bFGF-Receptor, VEGF, NT-3, NT-4/5, NGF); angiogenesis; and growth cone formation. Hence, MT-I+II enhance CNS tissue repair as seen clearly after the cryogenic injury, after which MT-I+II promote substitution of the necrotic lesion cavity with a glial...

Endovascular transplantation of stem cells to the injured rat CNS

Energy Technology Data Exchange (ETDEWEB)

Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan [Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Department of Neuroradiology, Stockholm (Sweden); Le Blanc, Katarina [Karolinska University Hospital, Department of Stem Cell Research, Karolinska Institutet, Department of Clinical Immunology, Stockholm (Sweden)

2009-10-15

Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

Endovascular transplantation of stem cells to the injured rat CNS

International Nuclear Information System (INIS)

Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan; Le Blanc, Katarina

2009-01-01

Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

Lung Radiofrequency Ablation: Potential as a Therapy to Oligometastasis and Oligo-Recurrence

OpenAIRE

Hiraki, Takao; Kanazawa, Susumu

2012-01-01

The early results (e.g., patient survival) of RFA for the treatment of patients with NSCLC and pulmonary metastasis from various primary lesions including colorectal cancer, lung cancer, hepatocellular carcinoma, renal cell carcinoma, and sarcoma appear encouraging and suggest the potential to offer long-term survival for the patients with oligo-recurrence or oligometastasis of lung cancer. The usefulness of RFA for oligo-recurrence or oligometastasis of lung cancer should be clarified by pro...

A clinical assessment of laser surgery for recurrent tongue cancer following radiotherapy

International Nuclear Information System (INIS)

Ishii, Junnosuke; Fujita, Kunio; Komatsubara, Hideki; Umeda, Masahiro; Komori, Takahide

2004-01-01

Laser surgery can control intraoperative hemorrhaging and enable lesions to be accurately removed since, unlike an electrotome, it does not effect electrocontractility. It can also reduce postoperative pain and dysfunction. This study investigated the efficacy of laser surgery in recurrent tongue cancer following radiotherapy. Of the total of 105 patients with squamous cell carcinoma of the tongue (T1, T2N0) who underwent radiotherapy at the Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, at some point between 1980 and 1998, 24 (22.9%) experienced local recurrence. Sixteen of these patients underwent surgical removal of the tumor. Of these 16 patients, 8 (4 early- and 4 late-stage recurrence) had partial glossectomy by laser surgery. Following laser surgery, 2 (1 early- and 1 late-stage recurrence) of the 8 patients died from neck metastasis and another 2 (early-stage recurrence) died from other diseases. The primary and neck tumors are both under control in 3 (late-stage recurrence) of the remaining 4 patients. Laser surgery for late-stage recurrent tongue cancer following radiotherapy appears to be a suitable treatment, although comprehensive glossectomy with/without radical neck dissection is necessary for early-stage recurrent cases after radiotherapy. (author)

The Prognostic Value of {sup 18}F-FDG PET/CT for Early Recurrence in Operable Breast Cancer: Comparison with TNM Stage

Energy Technology Data Exchange (ETDEWEB)

O, Joo Hyun; Choi, Woo Hee; Han, Eun Ji; Choi, Eunkyoung; Chae, Byung Joo; Park, Yonggyu; Kim, Sung Hoon [The Catholic Univ. of Korea, Seoul (Korea, Republic of)

2013-12-15

We evaluated whether the maximum standardized uptake values (SUV{sub max}) of primary tumor from the initial staging by {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) of patients with breast cancer could identify patients at risk for early recurrence within 2 years, particularly in comparison to the American Joint Committee on Cancer (AJCC) stage. We reviewed the staging {sup 18}F-FDG PET/CT images of patients with primary breast cancer and their medical records. The SUV{sub max} of the primary tumor was measured. The presence or absence of FDG uptake in the axillary lymph node (ALN) was also assessed. The patient's pathologic primary tumor stage (pT), pathologic regional lymph node stage (pN), stage grouping, age, estrogen receptor (ER) and progesterone receptor (PR) status, and neoadjuvant chemotherapy history were evaluated with the FDG uptake parameters for recurrence within 2 years following the end of first-line therapy. Recurrence within 2 years was present in 9.1%(n =40) out of the 441 patients assessed. The FDG uptake in ALN, pT, pN, stage grouping and neoadjuvant chemotherapy history were prognostic for early recurrence, while primary tumor SUV{sub max}, age, and ER or PR status were not significant on logistic regression. On multivariate analysis, only the stage grouping (odds ratio 2.79; 95 % CI 1.73, 4.48; p <0.0001) and neoadjuvant chemotherapy history (odds ratio 2.70; 95 % CI 1.22, 5.98; p =0.0141) could identify patients at increased risk for recurrence within 2 years. Primary tumor FDG uptake measured by SUV{sub max}, and visual assessment of FDG uptake in the ALN in the initial staging PET/CT of patients with breast cancer may not have additional prognostic value compared with the AJCC stage grouping for early recurrence.

Health-related Quality of Life after complex rectal surgery for primary advanced rectal cancer and locally recurrent rectal cancer

DEFF Research Database (Denmark)

Thaysen, Henriette Vind

2013-01-01

postoperative morbidity, Health-related Quality of Life (HRQoL) is an important issue. The overall aim of this thesis was therefore to evaluate HRQoL in patients with PARC and LRRC treated with COMP-RCS and curative intent. In study I a review of the literature was undertaken to provide an overview of HRQo......Advances in the treatment of rectal cancer, have made it possible to perform complex rectal cancer surgery (COMP-RCS) with curative intent in patients with primary advanced rectal caner (PARC) and local recurrent rectal cancer (LRRC). Due to the complexity of the treatment and its high...... in the study was 164 (86%) patients treated with standard rectal cancer surgery (STAN-RCS). The Danish version showed satisfactory psychometric properties for the scales concerning body image, sexual functioning, male sexual problems and defecations problems. Reduced psychometric properties were found...

Radiation therapy for pre-sacral recurrence of rectal carcinoma following primary surgery

International Nuclear Information System (INIS)

Yamanashi, Shunji; Yokoyama, Suguru; Kirita, Maruyuki; Katou, Yasuharu; Takeuchi, Kazuo; Kumamoto, Yoshikazu

2006-01-01

Between April 2002 and December 2005, we treated 15 patients who were suffering from pre-sacral recurrence of rectal cancer with or without liver metastases, using multi-portal irradiation and oral intake of tegafur-uracil (UFT) (300 mg/day), to assess pain relief and local control. Radiation therapy was given 2.1 to 2.4 Gy daily fractions, and total tumor dose was set up at a landmark of 66 Gy/30 fractions/6 weeks (time-dose-fractionation (TDF)=115, corresponding to 70 Gy), varying by recurrent tumor volume. The follow-up time was ranged from 3 to 37 months (median=14.7 months), and median survival was 14.8 months. Pain remission time was 3 to 36 months (median=10.4 months). No severe morbidity which induced by radiation therapy was observed in follow-up duration. The median survival has become unfavorite, but the multi-portal irradiation of high dose delivery is useful for improvement of quality of life (QOL) and beneficial as a palliative therapy. To improvement of local control and prognosis, combined modality with more effective regimen of chemotherapy is expected. (author)

CSF Hypocretin-1 Levels and Clinical Profiles in Narcolepsy and Idiopathic CNS Hypersomnia in Norway

Science.gov (United States)

Heier, Mona Skard; Evsiukova, Tatiana; Vilming, Steinar; Gjerstad, Michaela D.; Schrader, Harald; Gautvik, Kaare

2007-01-01

Objective: To evaluate the relationship between CSF hypocretin-1 levels and clinical profiles in narcolepsy and CNS hypersomnia in Norwegian patients. Method: CSF hypocretin-1 was measured by a sensitive radioimmunoassay in 47 patients with narcolepsy with cataplexy, 7 with narcolepsy without cataplexy, 10 with idiopathic CNS hypersomnia, and a control group. Results: Low hypocretin-1 values were found in 72% of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy. Patients with low CSF hypocretin-1 levels reported more extensive muscular involvement during cataplectic attacks than patients with normal levels. Hypnagogic hallucinations and sleep paralysis occurred more frequently in patients with cataplexy than in the other patient groups, but with no correlation to hypocretin-1 levels. Conclusion: About three quarters of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy had low CSF hypocretin-1 values, and appear to form a distinct clinical entity. Narcolepsy without cataplexy could not be distinguished from idiopathic CNS hypersomnia by clinical symptoms or biochemical findings. Citation: Heier MS; Evsiukova T; Vilming S; Gjerstad MD; Schrader H; Gautvik K. CSF hypocretin-1 levels and clinical profiles in narcolepsy and idiopathic CNS hypersomnia in norway. SLEEP 2007;30(8):969-973. PMID:17702265

Sites of recurrent disease and prognostic factors in SCLC patients treated with radiochemotherapy

Directory of Open Access Journals (Sweden)

Rebecca Bütof

2017-12-01

Full Text Available Objectives: Concurrent radiochemotherapy (RCHT is standard treatment in locally advanced small cell lung cancer (SCLC patients. Due to conflicting results on elective nodal irradiation (ENI or selective node irradiation (SNI there is no clear evidence on optimal target volumes. Therefore, the purposes of this study were to assess the sites of recurrent disease in SCLC and to evaluate the feasibility of SNI versus ENI. Methods: A retrospective single-institution study of 43 consecutive patients treated with RCHT was performed. After state-of-the-art staging including FDG-PET/CT, all patients underwent three-dimensional conformal radiotherapy to a total dose of 45 Gy in twice-daily fractions of 1.5 Gy starting concurrently with the first or second chemotherapy cycle. All sites of loco-regional recurrences were correlated to the initial tumor and dose delivered. The impact of potential prognostic variables on outcome was evaluated using the Cox-regression model. Results: 13 patients (30% relapsed locally or regionally: six within the initial primary tumor volume, five within the initially affected lymph nodes, one metachronously within primary tumor and initially affected lymph nodes, and one both inside and outside of the initial nodal disease. All sites of loco-regional recurrence had received 92–106% of the prescribed dose. Conclusion: In our study most recurrences occurred within the primary tumor or initially affected lymph nodes, or distantly. We did not register any case of isolated nodal failure, supporting the use of selective nodal irradiation, possibly with the addition of supraclavicular irradiation in patients with nodal disease in the upper mediastinum. Keywords: Small cell lung cancer, Recurrence, Radiotherapy, Selective node irradiation

Palmitoylethanolamide in CNS health and disease.

Science.gov (United States)

Mattace Raso, Giuseppina; Russo, Roberto; Calignano, Antonio; Meli, Rosaria

2014-08-01

The existence of acylethanolamides (AEs) in the mammalian brain has been known for decades. Among AEs, palmitoylethanolamide (PEA) is abundant in the central nervous system (CNS) and conspicuously produced by neurons and glial cells. Antihyperalgesic and neuroprotective properties of PEA have been mainly related to the reduction of neuronal firing and to control of inflammation. Growing evidence suggest that PEA may be neuroprotective during CNS neurodegenerative diseases. Advances in the understanding of the physiology and pharmacology of PEA have potentiated its interest as useful biological tool for disease management. Several rapid non-genomic and delayed genomic mechanisms of action have been identified for PEA as peroxisome proliferator-activated receptor (PPAR)-α dependent. First, an early molecular control, through Ca(+2)-activated intermediate- and/or big-conductance K(+) channels opening, drives to rapid neuronal hyperpolarization. This is reinforced by the increase of the inward Cl(-) currents due to the modulation of the gamma aminobutyric acid A receptor and by the desensitization of the transient receptor potential channel type V1. Moreover, the gene transcription-mediated mechanism sustains the long-term anti-inflammatory effects, by reducing pro-inflammatory enzyme expression and increasing neurosteroid synthesis. Overall, the integration of these different modes of action allows PEA to exert an immediate and prolonged efficacious control in neuron signaling either on inflammatory process or neuronal excitability, maintaining cellular homeostasis. In this review, we will discuss the effect of PEA on metabolism, behavior, inflammation and pain perception, related to the control of central functions and the emerging evidence demonstrating its therapeutic efficacy in several neurodegenerative diseases. Copyright © 2014. Published by Elsevier Ltd.

Single and multiple gland disease in primary hyperparathyroidism

OpenAIRE

Bonjer, Jaap

1992-01-01

textabstractThe scope of this thesis is: To review diagnostic procedures in primary hyperparathyroidism To review localization studies of parathyroid glands in hyperparathyroidism primary To assess the optima! surgical hyperparathyroidism by studying the recurrent hyperparathyroidism treatment of primary rates of persistent or To attempt to classify primary hyperparathyroidism by histopathology To determine DNA patterns in parathyroid glands in primary hyperparathyroidism

Modelling the endothelial blood-CNS barriers: a method for the production of robust in vitro models of the rat blood-brain barrier and blood-spinal cord barrier.

Science.gov (United States)

Watson, P Marc D; Paterson, Judy C; Thom, George; Ginman, Ulrika; Lundquist, Stefan; Webster, Carl I

2013-06-18

Modelling the blood-CNS barriers of the brain and spinal cord in vitro continues to provide a considerable challenge for research studying the passage of large and small molecules in and out of the central nervous system, both within the context of basic biology and for pharmaceutical drug discovery. Although there has been considerable success over the previous two decades in establishing useful in vitro primary endothelial cell cultures from the blood-CNS barriers, no model fully mimics the high electrical resistance, low paracellular permeability and selective influx/efflux characteristics of the in vivo situation. Furthermore, such primary-derived cultures are typically labour-intensive and generate low yields of cells, limiting scope for experimental work. We thus aimed to establish protocols for the high yield isolation and culture of endothelial cells from both rat brain and spinal cord. Our aim was to optimise in vitro conditions for inducing phenotypic characteristics in these cells that were reminiscent of the in vivo situation, such that they developed into tight endothelial barriers suitable for performing investigative biology and permeability studies. Brain and spinal cord tissue was taken from the same rats and used to specifically isolate endothelial cells to reconstitute as in vitro blood-CNS barrier models. Isolated endothelial cells were cultured to expand the cellular yield and then passaged onto cell culture inserts for further investigation. Cell culture conditions were optimised using commercially available reagents and the resulting barrier-forming endothelial monolayers were characterised by functional permeability experiments and in vitro phenotyping by immunocytochemistry and western blotting. Using a combination of modified handling techniques and cell culture conditions, we have established and optimised a protocol for the in vitro culture of brain and, for the first time in rat, spinal cord endothelial cells. High yields of both CNS

High-dose rate intra-operative radiation therapy for local advanced and recurrent colorectal cancer

International Nuclear Information System (INIS)

Harrison, L.B.; Mychalczak, B.; Enker, W.; Anderson, L.; Cohen, A.E.; Minsky, B.

1996-01-01

In an effort to improve the local control for advanced and recurrent cancers of the rectum, we have integrated high-dose rate intra-operative radiation therapy (HDR-IORT) into the treatment program. Between 11/92 and 10/95, 47 patients (pts) were treated. There were 26 males and 21 females whose ages ranged from 30-80 (median = 62) years. There were 19 pts with primary unresectable rectal cancer, and 28 pts who were treated for recurrent rectal cancer. Histology was adenocarcinoma - 45 pts, squamous cancer - 2 pts. The range of follow-up is 1-34 months (median = 14 months). The majority of primary unresectable pts received pre-operative radiation therapy (4500-5040 cGy) with chemotherapy (5-FU with Leucovorin) 4-6 weeks later, they underwent resection + HDR-IORT (1200 cGy). For the 28 pts with recurrent cancer, the majority received surgery and HDR-IORT alone because they had received prior RT. For the pts with primary unresectable disease, actuarial 2-year local control was 77%, actuarial distant metastasis-free survival was 71%, disease free survival was 66%, and overall survival was 84%. For those pts with recurrent disease, actuarial 2-year local control rate was 65%, distant metastasis-free survival was 65%, disease free survival was 47%, and overall survival was 61%. Complications occurred in 36%. There were no cases where the anatomical distribution of disease, or technical limitations prevented the adequate delivery of HDR-IORT. We conclude that this technique was most versatile, and enabled all appropriate pts to receive IORT. The preliminary data in terms of local control are encouraging, even for the poor prognostic sub-group of pts with recurrent cancer

Suppression of Cancer Stemness p21-regulating mRNA and microRNA Signatures in Recurrent Ovarian Cancer Patient Samples

LENUS (Irish Health Repository)

Gallagher, Michael F

2012-01-19

Abstract Background Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs). However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene microarrays and meta-analysis of our previously published microRNA (miRNA) data to assess the involvement of cancer stemness signatures in recurrent ovarian disease. Methods Microarray analysis was used to characterise early regulation events in an embryonal carcinoma (EC) model of cancer stemness. This was then compared to our previously published microarray data from a study of primary versus recurrent ovarian disease. In parallel, meta-analysis was used to identify cancer stemness miRNA signatures in tumor patient samples. Results Microarray analysis demonstrated a 90% difference between gene expression events involved in early regulation of differentiation in murine EC (mEC) and embryonic stem (mES) cells. This contrasts the known parallels between mEC and mES cells in the undifferentiated and well-differentiated states. Genelist comparisons identified a cancer stemness signature set of genes in primary versus recurrent data, a subset of which are known p53-p21 regulators. This signature is present in primary and recurrent or in primary alone but essentially never in recurrent tumors specifically. Meta-analysis of miRNA expression showed a much stronger cancer stemness signature within tumor samples. This miRNA signature again related to p53-p21 regulation and was expressed prominently in recurrent tumors. Our data indicate that the regulation of p53-p21 in ovarian cancer involves, at least partially, a cancer stemness component. Conclusion We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p53-p21