Zoledronic acid in metastatic chondrosarcoma and advanced sacrum chordoma: two case reports

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Capasso Elena

2009-01-01

Full Text Available Abstract Introduction Chondrosarcomas and chordomas are usually chemoresistant bone tumors and may have a poor prognosis when advanced. They are usually associated with worsening pain difficult to control. Patients and Methods Zoledronic acid was used in a 63-year-old man with metastatic chondrosarcoma and in a 66-year-old woman with a diagnosis of sacrum chordoma both reporting severe pain related to tumor. Results In the first case, zoledronic acid was able to maintain pain control despite disease progression following chemotherapy, in the other case, zoledronic acid only produced significant clinical benefit. Conclusion Control of pain associated with bone tumors such as chondrosarcoma and chondroma may significantly improve from use of zoledronic acid, independently from tumor response to other treatments. Evaluation on larger series are needed to confirm the clinical effect of this bisphosphonate on such tumors.

Bilateral retrobulbar optic neuropathy as the only sign of zoledronic acid toxicity.

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Lavado, Félix Manco; Prieto, Marta Para; Osorio, María Rosalba Ramoa; Gálvez, María Isabel López; Leal, Lucía Manzanas

2017-10-01

Bisphosphonates may rarely cause ocular adverse effects and retrobulbar optic neuropathy (RON) secondary to zoledronic acid is very rare. A 67-year-old man was referred because of progressive and painless decrease vision in the left eye. He had been treated with 7 cycles of zoledronic acid infusions because of metastatic prostate cancer. On examination, VA was 20/20 in the right eye (OD) and 20/50 in the left eye (OS). The optic nerve was unremarkable OU. Pattern visual evoked potentials (pVEP) and electroretinography were performed with the result of VEP responses abolished in OS, and the VEP waveform within the normal range amplitude and delayed peak latencies in OD. Due to the high suspicion of bilateral RON secondary to zoledronic acid, we decided to discontinue the treatment. Two months later, VA was 20/20 OD and hand motions OS, with relative afferent pupillary defect and a pallor of the optic disc in OS. The diagnosis of bilateral RON secondary to zoledronic acid infusions was confirmed, and it was only partially reversible. Zoledronic acid is a potent new generation bisphosphonate increasingly used in oncologic patients and it is usually well tolerated. Optic nerve toxicity is not a side effect recognised by either the Food and Drug Administration or the drug manufacturers, and to our knowledge, this is the first case of zoledronic acid-related bilateral RON with late onset. In conclusion, patients treated with bisphosphonates should be informed about the possibility of ocular side-effects, and ophthalmologists should be consider discontinuing the drug. Copyright © 2017 Elsevier Ltd. All rights reserved.

The bisphosphonate zoledronic acid effectively targets lung cancer cells by inhibition of protein prenylation

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Xie, Fan; Li, Pengcheng; Gong, Jianhua; Zhang, Jiahong; Ma, Jingping

2015-01-01

Aberrant activation of oncoproteins such as members of the Ras family is common in human lung cancers. The proper function of Ras largely depends on a post-translational modification termed prenylation. Bisphosphonates have been shown to inhibit prenylation in cancer cells. In this study, we show that zoledronic acid, a third generation bisphosphonate, is effective in targeting lung cancer cells. This is achieved by the induction of apoptosis and inhibition of proliferation, through suppressing the activation of downstream Ras and EGFR signalling by zoledronic acid. The combination of zoledronic acid and paclitaxel or cisplatin (commonly used chemotherapeutic drugs for lung cancer) augmented the activity of either drug alone in in vitro lung cancer cellular system and in vivo lung xenograft mouse model. Importantly, zoledronic acid inhibits protein prenylation as shown by the increased levels of unprenylated Ras and Rap1A. In addition, the effects of zoledronic acid were reversed in the presence of geranylgeraniol and farnesol, further confirming that mechanism of zoledroinc acid's action in lung cancer cells is through prenylation inhibition. Since zoledronic acid is already available for clinic use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of lung cancer. - Highlights: • Zoledronic acid (ZA) is effectively against lung cancer cells in vitro and in vivo. • ZA acts on lung cancer cells through inhibition of protein prenylation. • ZA suppresses global downstream phosphorylation of Ras signalling. • ZA enhances the effects of chemotherapeutic drugs in lung cancer cells.

The bisphosphonate zoledronic acid effectively targets lung cancer cells by inhibition of protein prenylation

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Xie, Fan [Department of Respiratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China); Li, Pengcheng [Department of Oncology, Wuhan Union Hospital Affiliated to Huazhong University of Science and Technology, Wuhan (China); Gong, Jianhua; Zhang, Jiahong [Department of Respiratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China); Ma, Jingping, E-mail: mjpjzhospital@hotmail.com [Department of Respiratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China)

2015-11-27

Aberrant activation of oncoproteins such as members of the Ras family is common in human lung cancers. The proper function of Ras largely depends on a post-translational modification termed prenylation. Bisphosphonates have been shown to inhibit prenylation in cancer cells. In this study, we show that zoledronic acid, a third generation bisphosphonate, is effective in targeting lung cancer cells. This is achieved by the induction of apoptosis and inhibition of proliferation, through suppressing the activation of downstream Ras and EGFR signalling by zoledronic acid. The combination of zoledronic acid and paclitaxel or cisplatin (commonly used chemotherapeutic drugs for lung cancer) augmented the activity of either drug alone in in vitro lung cancer cellular system and in vivo lung xenograft mouse model. Importantly, zoledronic acid inhibits protein prenylation as shown by the increased levels of unprenylated Ras and Rap1A. In addition, the effects of zoledronic acid were reversed in the presence of geranylgeraniol and farnesol, further confirming that mechanism of zoledroinc acid's action in lung cancer cells is through prenylation inhibition. Since zoledronic acid is already available for clinic use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of lung cancer. - Highlights: • Zoledronic acid (ZA) is effectively against lung cancer cells in vitro and in vivo. • ZA acts on lung cancer cells through inhibition of protein prenylation. • ZA suppresses global downstream phosphorylation of Ras signalling. • ZA enhances the effects of chemotherapeutic drugs in lung cancer cells.

Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma

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Kopecka, Joanna; Gazzano, Elena; Sara, Orecchia; Ghigo, Dario; Riganti, Chiara

2015-01-01

The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells. PMID:25544757

Fracture risk and zoledronic acid therapy in men with osteoporosis

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Boonen, Steven; Reginster, Jean-Yves; Kaufman, Jean-Marc

2012-01-01

Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis.......Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis....

Acute bilateral uveitis and right macular edema induced by a single infusion of zoledronic acid for the treatment of postmenopausal osteoporosis as a substitution for oral alendronate: a case report.

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Tian, Yiming; Wang, Rui; Liu, Lianyuan; Ma, Chunming; Lu, Qiang; Yin, Fuzai

2016-02-11

Zoledronic acid-induced uveitis (ZAIU) is rare but severe, and has been recently considered part of an acute phase reaction. Only 15 cases have been reported since 2005. Here we describe a case with macular edema, which is the first reported case observed after long-term alendronate tolerance. A 63-year-old Asian woman received her first intravenous zoledronic acid treatment for the management of postmenopausal osteoporosis as a more convenient substitute for oral alendronate. Twenty-four hours later, bilateral eye irritations, periorbital swelling, blurred vision, and diplopia presented. The complete blood count and transaminase levels were normal, but the erythrocytic sedimentation, C-reactive protein, and serum C4 levels were elevated. On detailed ophthalmological examination, a diagnosis of bilateral acute uveitis and macular edema in the right eye was made. The ocular symptoms were not improved until administration of topical and oral steroids. Complete resolution was achieved. There was no rechallenge of bisphosphonates, and no recurrence at 6 months follow-up. Based on an extensive review, abnormal fundus is rarely reported, especially in cases of macular edema. Rechallenge with zoledronic acid in five cases induced no additional uveitis, and changing the medication to pamidronate in another patient was also tolerated. Interestingly, our patient suffered from uveitis soon after intravenous zoledronate exposure after a two-year tolerance to oral alendronate. This is the first report of zoledronic acid induced uveitis with macular edema after long-term alendronate tolerance. Prior oral alendronate may not entirely prevent ZAIU. Steroids are usually necessary in the treatment of ZAIU. Bisphosphonate rechallenge is not fully contraindicated, and prior steroid administration may be a more reasonable treatment choice according to the available evidence.

Incidence of osteonecrosis of the jaw in women with postmenopausal osteoporosis in the health outcomes and reduced incidence with zoledronic acid once yearly pivotal fracture trial.

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Grbic, John T; Landesberg, Regina; Lin, Shou-Qing; Mesenbrink, Peter; Reid, Ian R; Leung, Ping-Chung; Casas, Noemi; Recknor, Christopher P; Hua, Ye; Delmas, Pierre D; Eriksen, Erik F

2008-01-01

The authors determined incidence of osteonecrosis of the jaw (ONJ) in a large, prospective three-year clinical trial of zoledronic acid in women with postmenopausal osteoporosis (PMO). A total of 7,714 women with PMO received intravenous zoledronic acid 5 mg or a placebo. No spontaneous reports of ONJ were received. An independent, blinded adjudication committee searched the trial's adverse event database by using 60 terms. On an ongoing basis, the committee reviewed the identified events, and it defined ONJ as exposed bone in the maxillofacial area with delayed healing for more than six weeks despite appropriate care. One participant who received a placebo and one participant who received zoledronic acid experienced delayed healing associated with infection. Both conditions resolved after antibiotic therapy, débridement or both. The occurrence of ONJ is rare in a PMO population, and delayed healing of lesions can occur with and without bisphosphonate use over three years. The low incidence of ONJ must be assessed in the context of the clinical benefit of zoledronic acid therapy in reducing hip, vertebral and nonvertebral fractures in this at-risk population. There is no evidence to suggest that healthy patients with osteoporosis who are receiving bisphosphonates require any special treatment beyond routine dental care or to support altering standard treatment practices.

PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells.

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Anitua, Eduardo; Zalduendo, Mar; Troya, María; Orive, Gorka

2016-04-01

Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is a common problem in patients undergoing long-term administration of highly potent nitrogen-containing bisphosphonates (N-BPs). This pathology occurs via bone and soft tissue mechanism. Zoledronic acid (ZA) is the most potent intravenous N-BP used to prevent bone loss in patients with bone dysfunction. The objective of this in vitro study was to evaluate the role of different ZA concentrations on the cells from human oral cavity, as well as the potential of plasma rich in growth factors (PRGF) to overcome the negative effects of this BP. Primary human gingival fibroblasts and primary human alveolar osteoblasts were used. Cell proliferation was evaluated by means of a fluorescence-based method. A colorimetric assay to detect DNA fragmentation undergoing apoptosis was used to determine cell death, and the expression of both NF-κB and pNF-κB were quantified by Western blot analysis. ZA had a cytotoxic effect on both human gingival fibroblasts and human alveolar osteoblasts. This BP inhibits cell proliferation, stimulates apoptosis, and induces inflammation. However, the addition of PRGF suppresses all these negative effects of the ZA. PRGF shows a cytoprotective role against the negative effects of ZA on primary oral cells. At present, there is no definitive treatment for bisphosphonates-related osteonecrosis of the jaw (BRONJ), being mainly palliatives. Our results revealed that PRGF has a cytoprotective role in cells exposed to zoledronic acid, thus providing a reliable adjunctive therapy for the treatment of BRONJ pathology.

Zoledronic Acid Treatment in Primary Bone Marrow Edema Syndrome.

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Flores-Robles, Bryan Josué; Sanz-Sanz, Jesus; Sanabria-Sanchinel, Adel Abel; Huntley-Pascual, Dixie; Andréu Sánchez, José Luis; Campos Esteban, José; Blanco, Ricardo; Merino-Argumanez, Carolina; Espinosa-Malpartida, Maria; Ramos-Giráldez, Maria Consuleo; Godoy-Tundidor, Hildegarde; Jiménez-Palop, Maria Mercedes; Barbadillo Mateos, Carmen; Villa-Alcázar, Luis Fernando; Isasi, Carlos Maria; Mulero, Juan Bartolome

2017-03-01

Primary bone marrow edema syndrome (BMES) is characterized by the combination of joint pain and distinctive magnetic resonance imaging changes. It has been suggested that the use of bisphosphonate drugs reduce symptom severity. Our objective was to review cases of patients diagnosed with BMES in the last 7 years who had been treated with zoledronic acid. Access to a pharmaceutical database was gained in order to obtain a list of zoledronic acid prescriptions. Based on clinical and MRI criteria for BMES, patients were selected. Baseline pain intensity was evaluated on a scale of 0 to 3 and was also assessed after 3 and 12 months. Functional recovery was evaluated by noting if a patient had returned to carrying out his or her normal daily activities. Out of 633 patients, 17 cases of BMES were identified (8 men), with a median age of 54 ± 14.1 years. The most frequently affected joint was the ankle (9), followed by the hip. Sixteen patients presented with moderate to severe pain initially. Of those patients, 13 had no pain after 12 months. Zoledronic acid is a option in the management of BMES, since 75% of patients treated with it presented with a complete response.

Zoledronic acid and alendronate sodium and the implications in orthodontic movement.

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Franzoni, J S; Soares, F M P; Zaniboni, E; Vedovello Filho, M; Santamaria, M P; Dos Santos, G M T; Esquisatto, M A M; Felonato, M; Mendonca, F A S; Franzini, C M; Santamaria, M

2017-08-01

To evaluate orthodontic tooth movement (OTM) in rats treated with two types of bisphosphonates (BPs), alendronate sodium (A) and zoledronic acid (Z). In all, 15 male Wistar rats were randomly divided into three groups. Group OTM+A: orthodontic tooth movement and subcutaneous administration of alendronate sodium (2.5 mg/kg); Group OTM+Z: orthodontic tooth movement and subcutaneous administration of zoledronic acid (0.02 mg/kg), and Group OTM: orthodontic tooth movement and subcutaneous injection of saline. The BPs were administered once a day during 25 days before OTM started and during 10 days of OTM. The left upper first molar was moved with a stainless-steel closed coil spring which delivered an initial force of 0.4N. OTM was measured with a digital caliper comparing the moved and the contralateral side. The histomorphometric analysis counted the number of osteoclasts, inflammatory cells, blood vessels and fibroblasts (n/10 4  m 2 ) in periodontal ligament (PDL) of the distobuccal root. A reduction of 58.3% of OTM was found in Group OTM+A and 99.6% in Group OTM+Z, when compared with Group OTM. There was a significant decrease of osteoclasts and inflammatory cells in BP-treated groups. Blood vessels and fibroblastic cells decreased mainly in Group OTM+Z. Alendronate sodium and zoledronic acid have similar effects on the periodontal tissue during orthodontic treatment in rats. Especially, zoledronic acid can affect orthodontic tooth movement. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A comparative study of zoledronic acid and once weekly Alendronate in the management of acute Charcot arthropathy of foot in patients with diabetes mellitus

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R Bharath

2013-01-01

Full Text Available Aim: The aim of this study was to assess and compare the response to two forms of treatment-immobilization with zoledronic acid injection and immobilization with oral weekly Alendronate, in patients with diabetes mellitus and acute Charcot arthropathy (CA of foot in terms of clinical and radiological parameters. Material and Methods: Patients attending the endocrinology and podiatry clinic with history of diabetes mellitus and Acute CA were taken for study. The patients were randomized into two treatment groups. Group Z-zoledronic acid injection along with total contact cast (TCC. Group A-Tab. Alendronate 70 mg. once a week till the complete clinical resolution of acute CA along with TCC. Forty-five patients were randomized and 40 of them completed the study. The primary end point was complete clinical resolution of acute CA-defined as temperature difference between normal and affected foot <1oF. Results: Among the 40 patients, 30 (75% had complete clinical resolution. The mean number of days taken for complete clinical resolution since the initiation of treatment (either Zoledronic acid or Alendronate was approximately 122 days. There was no significant difference in a number of days required for complete clinical resolution, between the two forms of therapy. There was more than 50% reduction in the visual score between the baseline and the final scan. The target to non-target ratio in the skeletal phase also showed an average of 40% reduction from the baseline to the final skeletal scintigraphy. Conclusion: Both Intravenous Zoledronic acid and oral alendronate had comparable efficacy with respect to the time taken for attaining complete clinical resolution of acute CA of foot. However, Alendronate therapy was cost effective among the two. 99m Tc MDP bone scan can be used as an adjuvant to the clinical parameters in assessing the response to therapy.

Once-yearly zoledronic acid in hip fracture prevention

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Demontiero, Oddom; Duque, Gustavo

2009-01-01

Osteoporosis is an escalating global problem. Hip fractures, the most catastrophic complication of osteoporosis, continue to cause significant mortality and morbidity despite increasing availability of effective preventative agents. Among these agents, oral bisphosphonates have been the first choice for the treatment and prevention of osteoporotic fractures. However, the use of oral bisphosphonates, especially in the older population, has been limited by their side effects and method of administration thus compromising their persistent use. The resultant low adherence by patients has undermined their full potential and has been associated with an increase in the incidence of fragility fractures. Recently, annual intravenous zoledronic acid (ZOL) has been approved for osteoporosis. Randomized controlled trials have demonstrated ZOL to be safe, have good tolerability and produce significant effect on bone mass and microarchitecture. Adherence has also been shown to be better with ZOL. Furthermore two large trials firmly demonstrated significant anti-osteoporotic effect (∼59% relative risk reduction of hip fractures) and mortality benefit (28% reduction in mortality) of ZOL in older persons with recent hip fractures. In this review, we report the current evidence on the use of ZOL for the prevention of hip fractures in the elderly. We also report the pharmacological characteristics and the advantages and disadvantages of ZOL in this particular group. PMID:19503777

Use of Zoledronic Acid in Paediatric Craniofacial Fibrous Dysplasia

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Chiara Di Pede

2016-01-01

Full Text Available We describe a case of a paediatric patient affected by mandibular fibrous dysplasia (FD with severe and chronic pain who was successfully treated with zoledronic acid (ZOL: a third-generation bisphosphonate. Further research is needed to assess its safety and efficacy as a treatment option for FD in the paediatric population.

Reproductive hormone analyses and effects of adjuvant zoledronic acid in early breast cancer – An AZURE (BIG 01/04 sub-study

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Caroline Wilson

2017-11-01

Full Text Available Purpose: Adjuvant bisphosphonates have been shown to improve disease outcomes in early breast cancer in women who are postmenopausal at the start of treatment. We explored the influence of pretreatment serum levels of reproductive hormones in the hypothalamic-pituitary-gonadal (HPG axis from a subset of patients included in the AZURE trial to investigate their impact on disease recurrence and whether reproductive hormone measurements are of value in selecting patients for treatment with adjuvant zoledronic acid.Patients and methods; The AZURE trial is an academic, multi-centre, international phase III trial that randomised patients to standard adjuvant therapy (chemotherapy and/or endocrine therapy±intravenous zoledronic acid, 4 mg for 5 years. Serum from 865 patients taken at randomisation was stored at −80 °C prior to central batch analysis for inhibin A, oestradiol and follicle stimulating hormone (FSH. We assessed the clinical value of pretreatment hormone levels for predicting invasive disease free survival (IDFS, skeletal recurrence and distant recurrence and response to treatment with zoledronic acid. Results: Oestradiol in the postmenopausal range (26 IU/l was associated with a longer time to bone as first recurrence (HR 0.66 95%CI: 0.41–1.04 p=0.072 compared to an FSH ≤26 IU/l. When all 3 hormone levels were within the assay specified postmenopausal range, a trend to improved IDFS was seen with addition of zoledronic acid in biochemically postmenopausal women only (postmenopausal HR=0.81; 95%CI: 0.54–1.22, non-postmenopausal HR=0.99; 95%CI: 0.69–1.39 with risk reductions that mirrored the results of the main AZURE study, although the interaction between menopausal status and treatment effect was not statistically significant (p=0.47. Conclusion: Oestradiol and FSH may influence the pattern of disease recurrence with postmenopausal levels possibly creating a less conducive environment for the

A Modified method for reducing renal injury in zoledronic acid treatment of hypercalcemia and adverse skeletal events

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Jiang Liu

2013-01-01

Full Text Available Aims: In this paper, we have reported a previously undescribed risk factor of deterioration of renal function in zoledronic acid treatment of skeletal metastasis - high serum calcium level. Based on this consideration, a modified method of treatment of hypercalcemia (HCM with zoledronic acid is suggested in this paper. Material and Methods: Bone scan findings of 1090 cancer patients were analyzed, of which 26 had intense renal parenchymal uptake as a result of HCM or bone metastases. Subsequently, a total of 56 bone metastases patients with zoledronic acid treatment were divided into three groups: HCM group who were pre-treated to normal serum calcium level (13 patients, HCM group (19 patients, and normal serum calcium group (24 patients. Results: More patients with intense renal parenchymal uptake were hyperglycemic, statistically significantly (18/26 versus 19/1064, P = 2.1, E-78. No more patients with intense renal parenchymal uptake were associated with bone metastases (14/26 versus 438/1064, P = 0.20. Subsequently, more HCM patients receiving zoledronic acid treatment showed renal injury compared to patients with normal serum calcium level (5/15 versus 2/24, P < 0.05 and HCM patients with pre-treatment to normal serum calcium level (5/15 versus 1/17, P < 0.05. Conclusions: Intense renal parenchymal uptake of bisphosphonates is closely related to HCM rather than to bone metastases in cancer patients. The serum calcium should be measured and reduced to normal level before zoledronic acid is used in managements of adverse skeletal events in order to decrease the risk of renal injury.

Assessment on zoledronic acid use in patients with bone metastatic breast cancer

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Soriano Garcia, Jorge L; Batista Albuerne, Noyde; Lima Perez, Mayte

2010-01-01

The biphosphonates are the cornerstone in the bone metastases treatment. In present paper the effectiveness and safety of the zoledronic acid (ZA) use in patients with bone metastatic breast cancer (MBC)

Effect of zoledronic acid on reducing femoral bone mineral density loss following total hip arthroplasty: A meta-analysis from randomized controlled trails.

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Gao, Jian; Gao, Chong; Li, Hui; Wang, Guo-Sheng; Xu, Chang; Ran, Jian

2017-11-01

This meta-analysis aimed to assess the efficiency of intravenous administration of zoledronic acid on reducing femoral periprosthetic bone mineral density loss in patients undergoing primary total hip arthroplasty (THA). A systematic search was performed in Medline (1966-2017.07.31), PubMed (1966-2017.07.31), Embase (1980-2017.07.31), ScienceDirect (1985-2017.07.31) and the Cochrane Library (1966-2017.07.31). Fixed/random effect model was used according to the heterogeneity tested by I 2 statistic. Sensitivity analysis was conducted and publication bias was assessed. Meta-analysis was performed using Stata 11.0 software. Four studies including 185 patients met the inclusion criteria. The present meta-analysis indicated that there were significant differences between groups in terms of periprosthetic bone mineral density in Gruen zone 1 (SMD = 0.752, 95% CI: 0.454 to 1.051, P = 0.000), 2 (SMD = 0.524, 95% CI: 0.230 to 0.819, P = 0.000), 4 (SMD = 0.400, 95% CI: 0.107 to 0.693, P = 0.008), 6 (SMD = 0.893, 95% CI: 0.588 to 1.198, P = 0.000) and 7 (SMD = 0.988, 95% CI: 0.677 to 1.300, P = 0.000). Intravenous administration of zoledronic acid could significantly reduce periprosthetic bone mineral density loss (Gruen zone 1, 2, 4, 6 and 7) after THA. In addition, no severe adverse events were identified. High-quality RCTs with large sample size were still required. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: a proof of principle pilot study.

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Clive, Amelia O; Hooper, Clare E; Edey, Anthony J; Morley, Anna J; Zahan-Evans, Natalie; Hall, David; Lyburn, Iain; White, Paul; Braybrooke, Jeremy P; Sequeiros, Iara; Lyen, Stephen M; Milton, Tim; Kahan, Brennan C; Maskell, Nick A

2015-01-01

Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans. We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated. Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI -4.7 to 13.0)) or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates. This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further. UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.

A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: a proof of principle pilot study.

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Amelia O Clive

Full Text Available Animal studies have shown Zoledronic Acid (ZA may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD. We performed a pilot study to evaluate its effects in humans.We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1 to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI from randomisation to week 5. Multiple secondary endpoints were also evaluated.Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline. At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD 4.16 (95%CI -4.7 to 13.0 or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3. Two of nine (22% in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo. There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9, side effects or serious adverse event rates.This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further.UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.

Addition of docetaxel and/or zoledronic acid to standard of care for hormone-naive prostate cancer: a cost-effectiveness analysis.

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Zhang, Pengfei; Wen, Feng; Fu, Ping; Yang, Yu; Li, Qiu

2017-07-31

The effectiveness of the addition of docetaxel and/or zoledronic acid to the standard of care (SOC) for hormone-naive prostate cancer has been evaluated in the STAMPEDE trial. The object of the present analysis was to evaluate the cost-effectiveness of these treatment options in the treatment of advanced hormone-naive prostate cancer in China. A cost-effectiveness analysis using a Markov model was carried out from the Chinese societal perspective. The efficacy data were obtained from the STAMPEDE trial and health utilities were derived from previous studies. Transition probabilities were calculated based on the survival in each group. The primary endpoint in the analysis was the incremental cost-effectiveness ratio (ICER), and model uncertainties were explored by 1-way sensitivity analysis and probabilistic sensitivity analysis. SOC alone generated an effectiveness of 2.65 quality-adjusted life years (QALYs) at a lifetime cost of $20,969.23. At a cost of $25,001.34, SOC plus zoledronic acid was associated with 2.69 QALYs, resulting in an ICER of $100,802.75/QALY compared with SOC alone. SOC plus docetaxel gained an effectiveness of 2.85 QALYs at a cost of $28,764.66, while the effectiveness and cost data in the SOC plus zoledronic acid/docetaxel group were 2.78 QALYs and $32,640.95. Based on the results of the analysis, SOC plus zoledronic acid, SOC plus docetaxel, and SOC plus zoledronic acid/docetaxel are unlikely to be cost-effective options in patients with advanced hormone-naive prostate cancer compared with SOC alone.

Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study.

Science.gov (United States)

Nuzzo, F; Gallo, C; Lastoria, S; Di Maio, M; Piccirillo, M C; Gravina, A; Landi, G; Rossi, E; Pacilio, C; Labonia, V; Di Rella, F; Bartiromo, A; Buonfanti, G; De Feo, G; Esposito, G; D'Aniello, R; Maiolino, P; Signoriello, S; De Maio, E; Tinessa, V; Colantuoni, G; De Laurentiis, M; D'Aiuto, M; Di Bonito, M; Botti, G; Giordano, P; Daniele, G; Morabito, A; Normanno, N; de Matteis, A; Perrone, F

2012-08-01

To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid. A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan. Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively). In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.

The rabbit biodistribution of a therapeutic dose of zoledronic acid labeled with Tc-99m

International Nuclear Information System (INIS)

Asikoglu, Makbule; Gamze Durak, Funda

2009-01-01

The aim of the present study was to label a therapeutic dose of zoledronic acid (ZOL) with Tc-99m, evaluate its in vitro stability and compare its biodistribution to 99m Tc-methylene biphosphonate ( 99m Tc-MDP) in normal rabbits. Preparation of 0.50 mg of 99m Tc-ZOL was carried out by the reduction of 99m Tc-pertechnetate in the presence of stannous chloride. The radiolabeling efficiency was found to be greater than 99%. The labeled complex was stable at least up to 6 h at room temperature determined by paper chromatography. 99m Tc-ZOL and 99m Tc-MDP were administered intravenously to the rabbits for scintigraphic studies. Between 99m Tc-ZOL and 99m Tc-MDP, there were no significant differences in the ratios of femur/BG and lumbar vertebrae/BG, whereas epiphysis/BG and the kidney/BG ratios of 99m Tc-MDP were higher than 99m Tc-ZOL at the static studies.

Zoledronic acid enhances the effect of radiotherapy for bone metastases from renal cell carcinomas. More than a 24-month median follow-up

International Nuclear Information System (INIS)

Takeda, Naoki; Isu, Kazuo; Hiraga, Hiroaki; Shinohara, Nobuo; Minami, Akio; Kamata, Hajime

2012-01-01

Renal cell carcinoma (RCC) is thought to respond unreliably to radiotherapy (RT). Zoledronic acid significantly reduces the risk of skeletal complications. This study investigated whether RT with zoledronic acid prolonged the time to bone-lesion progression in comparison with RT alone. Twenty-seven patients (34 lesions) with bone metastases secondary to RCC undergoing treatment with RT with or without zoledronic acid were retrospectively evaluated at two institutions between 1999 and 2009. Twelve patients were treated with RT alone from 1999 to 2008 (RT group). Fifteen patients were treated with RT and zoledronic acid from 2006 to 2009 (RT+Z group). The time to skeletal-related events and pain progression were assessed from patients' medical records. The median (range) follow-up was 26 (3-75) and 24 (3-55) months in the RT and RT+Z groups, respectively. Three patients (three lesions) in the RT+Z group had skeletal-related events (SREs). In contrast, six patients (eight lesions) in the RT group had SREs. SREs comprised pathological fractures in five, additional surgeries in three, spinal cord or cauda equine compression in two, and repeat RT in one. There was a significant difference in SRE-free survival time and duration of site-specific pain response between groups. RT combined with zoledronic acid significantly prolonged SRE-free survival and duration of pain response compared with RT alone in the treatment of osseous metastases from RCC. (author)

Local effect of zoledronic acid on new bone formation in posterolateral spinal fusion with demineralized bone matrix in a murine model.

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Zwolak, Pawel; Farei-Campagna, Jan; Jentzsch, Thorsten; von Rechenberg, Brigitte; Werner, Clément M

2018-01-01

Posterolateral spinal fusion is a common orthopaedic surgery performed to treat degenerative and traumatic deformities of the spinal column. In posteriolateral spinal fusion, different osteoinductive demineralized bone matrix products have been previously investigated. We evaluated the effect of locally applied zoledronic acid in combination with commercially available demineralized bone matrix putty on new bone formation in posterolateral spinal fusion in a murine in vivo model. A posterolateral sacral spine fusion in murine model was used to evaluate the new bone formation. We used the sacral spine fusion model to model the clinical situation in which a bone graft or demineralized bone matrix is applied after dorsal instrumentation of the spine. In our study, group 1 received decortications only (n = 10), group 2 received decortication, and absorbable collagen sponge carrier, group 3 received decortication and absorbable collagen sponge carrier with zoledronic acid in dose 10 µg, group 4 received demineralized bone matrix putty (DBM putty) plus decortication (n = 10), and group 5 received DBM putty, decortication and locally applied zoledronic acid in dose 10 µg. Imaging was performed using MicroCT for new bone formation assessment. Also, murine spines were harvested for histopathological analysis 10 weeks after surgery. The surgery performed through midline posterior approach was reproducible. In group with decortication alone there was no new bone formation. Application of demineralized bone matrix putty alone produced new bone formation which bridged the S1-S4 laminae. Local application of zoledronic acid to demineralized bone matrix putty resulted in significant increase of new bone formation as compared to demineralized bone matrix putty group alone. A single local application of zoledronic acid with DBM putty during posterolateral fusion in sacral murine spine model increased significantly new bone formation in situ in our model. Therefore, our

A simple RP-HPLC method for related substances of zoledronic acid in pharmaceutical products

Directory of Open Access Journals (Sweden)

L. Maheswara Reddy

2017-02-01

Full Text Available A novel, selective and sensitive reverse phase-high performance liquid chromatography (RP-HPLC method has been developed for the validated estimation of imidazol-1-yl-acetic acid in zoledronic acid formulations. The separation was achieved on a 5 μ C18 column (250 × 4.6 mm using a mobile phase that consists of the buffer (4.5 g of di-potassium hydrogen phosphate anhydrous and 2.0 g of tetra butyl ammonium hydrogen sulphate (TBAHS in 1000 mL of water and methanol in the ratio of 900:100 v/v. The flow rate was maintained at 1.0 mL min−1. The detection of the constituents was done at 215 nm using a UV detector. The retention times of imidazol-1-yl-acetic acid and zoledronic acid were 7.2 and 10.2 min respectively. Recovery studies were satisfactory and the correlation coefficient, 0.999 indicates linearity of the method within the limits. The developed method can be applicable for regular qualitative analysis.

Multicompartment vectors as novel drug delivery systems: selective activation of Tγδ lymphocytes after zoledronic acid delivery.

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Agrati, Chiara; Marianecci, Carlotta; Sennato, Simona; Carafa, Maria; Bordoni, Veronica; Cimini, Eleonora; Tempestilli, Massimo; Pucillo, Leopoldo P; Turchi, Federica; Martini, Federico; Borioni, Giorgio; Bordi, Federico

2011-04-01

Multicompartment nanoscopic carriers can be easily assembled by inducing the aggregation of anionic "hybrid" niosomes by means of cationic biocompatible polyelectrolytes. The resulting vesicle clusters, whose size and overall net charge can be easily controlled by varying the polyelectrolyte-to-particle charge ratio, show an interesting potential for multidrug delivery. In this article we provide strong evidence for their effective use in vitro as multicompartment vectors selectively directed toward monocyte/macrophage cells, showing that the monocyte/macrophage-mediated activation of Tγδ lymphocytes induced by zoledronic acid is enhanced by a factor 10(3) when the zoledronic acid is intracellularly delivered through these carriers. Furthermore, the multicompartment ɛ-polylysine niosome clusters, with their intrinsic selectivity toward macrophages, appear particularly suitable for implementing therapeutic strategies against chronically infected macrophages. ɛ-polylysine niosome clusters, with their intrinsic selectivity toward macrophages, offer the potential for multidrug delivery. The effectiveness of aminobisphosphonate zoledronate is demonstrated to enhance the recruitment of Tγδ lymphocytes by macrophages by 2 orders of magnitude, suggesting a new therapeutic strategy for addressing pathologies featuring chronically infected macrophages. Copyright © 2011 Elsevier Inc. All rights reserved.

Zoledronic acid as compared with observation in multiple myeloma patients at biochemical relapse: results of the randomized AZABACHE Spanish trial

Science.gov (United States)

García-Sanz, Ramón; Oriol, Albert; Moreno, María J.; de la Rubia, Javier; Payer, Angel R.; Hernández, Miguel T.; Palomera, Luis; Teruel, Ana I.; Blanchard, María J.; Gironella, Mercedes; Ribas, Paz; Bargay, Joan; Abellá, Eugenia; Granell, Miquel; Ocio, Enrique M.; Ribera, Josep M.; San Miguel, Jesús F.; Mateos, María V.

2015-01-01

This study analyzed the anti-myeloma effect of zoledronic acid monotherapy by investigating patients at the time of asymptomatic biochemical relapse. One hundred patients were randomized to receive either zoledronic acid (4 mg iv/4 weeks, 12 doses) (n=51) or not (n=49). Experimental and control groups were well balanced for disease and prognostic features. Zoledronic acid did not show an antitumor effect according to changes in M-component. However, there were fewer symptomatic progressions in the experimental group than in the control group (34 versus 41, respectively; P=0.05) resulting in a median time to symptoms of 16 versus 10 months (P=0.161). The median time to next therapy was also slightly longer for the treated group than the untreated, control group (13.4 versus 10.1 months), although the difference was not statistically significant (P=0.360). The pattern of relapses was different for treated versus control patients: progressive bone disease (8 versus 20), anemia (24 versus 18), renal dysfunction (1 versus 2), and plasmacytomas (1 versus 1, respectively). This concurred with fewer skeletal-related events in the treated group than in the control group (2 versus 14), with a projected 4-year event proportion of 6% versus 40% (P<0.001). In summary, zoledronic acid monotherapy does not show an antitumor effect on biochemical relapses in multiple myeloma, but does reduce the risk of progression with symptomatic bone disease and skeletal complications. This trial was registered in the ClinicalTrials.gov database with code NCT01087008 PMID:26069291

Diminished Progression of Periapical Lesions with Zoledronic Acid in Ovariectomized Rats.

Science.gov (United States)

Wayama, Marcelo Tadahiro; Yoshimura, Hitoshi; Ohba, Seigo; Yoshida, Hisato; Matsuda, Shinpei; Kobayashi, Junichi; Kobayashi, Motohiro; Gomes Filho, João Eduardo; Sano, Kazuo

2015-12-01

The aim of this study was to investigate the effects of systemically administered zoledronic acid (ZOL) on the progression of periapical lesions in estrogen-deficient rats. Female Wistar rats were divided into the following groups: SHAM-veh, sham surgery treated with vehicle (physiological saline); OVX-veh, ovariectomy treated with vehicle; SHAM-ZOL, sham surgery treated with ZOL; and OVX-ZOL, ovariectomy treated with ZOL. Vehicle or ZOL was administered intravenously once a week for 4 weeks. The pulp of the mandibular first molar of all rats was exposed to the oral environment to induce a periapical lesion, and the lesions were analyzed after 7 and 30 days. The mandibles were examined by micro-computed tomographic imaging and histopathologic, histometric, and immunohistochemical analyses. Histopathologically, the OVX-veh group had more severe inflammation and bone loss and a larger number of cells that were positive for tartrate-resistant acid phosphatase compared with the SHAM-veh and OVX-ZOL groups; the SHAM-veh and OVX-ZOL groups were similar to each other. The SHAM-ZOL group had the lowest magnitude of these conditions. Tomographically, the OVX-veh group had greater bone loss than the other groups at both time points. The SHAM-veh, SHAM-ZOL, and OVX-ZOL groups had similar bone loss at both time points. In the sagittal section on day 30, the SHAM-ZOL group had lower bone loss compared with the SHAM-veh and OVX-ZOL groups. The hypoestrogenic condition aggravates the progression of periapical lesions. ZOL therapy may help contain bone destruction of periapical lesions. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Long-term leukopenia in a lung transplanted patient with cystic fibrosis treated with zoledronic acid

DEFF Research Database (Denmark)

Karahasanovic, A; Thorsteinsson, A-L; Bjarnason, N H

2016-01-01

report a case of a young woman with CF, lung transplantation and low bone mass developing long-term leukopenia after treatment with zoledronic acid. The leukopenia, with a strong affection of the neutrocytes, lasted for 4 months and the condition only went into remission after granulocyte-colony...

A pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma

Directory of Open Access Journals (Sweden)

Jamil MO

2017-06-01

Full Text Available Muhammad Omer Jamil, Mary S Jerome, Deborah Miley, Katri S Selander, Francisco Robert Division of Hematology and Oncology, Department of Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA Purpose: Malignant pleural mesothelioma (MPM is a rare malignancy with a dismal median survival of <12 months with current therapy. Single and combination chemotherapy regimens have shown only modest clinical benefit. In preclinical studies, nitrogen-containing bisphosphonates (zoledronic acid inhibit growth of mesothelioma cells by different mechanisms: inhibition of mevalonate pathway, inhibition of angiogenesis, activation of apoptosis through caspase activation, and alteration in activity of matrix metalloproteinases, thereby affecting invasiveness of cancer cells.Patients and methods: We investigated the role of zoledronic acid in a pilot, single-arm trial of MPM patients with Eastern Cooperative Oncology Group (ECOG performance status (PS 0–2 who had progressed on prior treatments or had not received systemic therapy due to poor PS. Primary end point was composite response rate by modified response evaluation criteria in solid tumors and/or metabolic response by 2-deoxy-2-[fluorine-18]fluoro-d-glucose (18F-FDG positron emission tomography criteria. Secondary end points were progression-free survival (PFS and overall survival (OS. Exploratory end points include the effect of zoledronic acid therapy on vascular endothelial growth factor (VEGF, basic fibroblast growth factor, interleukin 8, transforming growth factor beta, mesothelin, and osteopontin levels.Results: Eight male patients (median age of 62 years with the following clinical characteristics were treated; ECOG PS was 0–2, 75% with epithelioid type, and 62% had prior chemotherapy. Overall composite response rate was 12.5% and the clinical benefit rate (response + stable disease was 37.5%. Median PFS was 2 months (0.5–21 months and median OS was

Pregnancy and Lactation-Associated Osteoporosis: Bone Histomorphometric Analysis and Response to Treatment with Zoledronic Acid.

Science.gov (United States)

Grizzo, Felipe Merchan Ferraz; da Silva Martins, Janaina; Pinheiro, Marcelo M; Jorgetti, Vanda; Carvalho, Maria Dalva Barros; Pelloso, Sandra Marisa

2015-10-01

Pregnancy and lactation-associated osteoporosis (PAO) is a rare condition with little known pathophysiology. Most cases are diagnosed in the third trimester of pregnancy or in the first weeks postpartum, particularly in first pregnancies. Vertebral fractures are most commonly observed and characterised by prolonged severe pain, functional limitations and a loss of height. Measurements of bone mineral density and biochemical markers of bone remodelling are the clinical methods most commonly used for the management of these patients. However, a bone biopsy with histomorphometric analysis has been considered to be the gold-standard. Few studies have evaluated the histomorphometry in patients with this clinical condition and none of them performed the procedure at the beginning of the clinical assessment. In this study, we report a case of PAO in a 31-year-old postpartum patient who had undergone a twin pregnancy. We describe the clinical, laboratory tests and imaging features. Bone histomorphometry showed a high resorption rate and excellent evolution after 1 year of treatment with intravenous zoledronic acid. Our data suggest that osteoclastogenesis plays a central role in the pathophysiological processes of this disease.

The effect of a single infusion of zoledronic acid on early implant migration in total hip arthroplasty. A randomized, double-blind, controlled trial.

Science.gov (United States)

Friedl, Gerald; Radl, Roman; Stihsen, Christoph; Rehak, Peter; Aigner, Reingard; Windhager, Reinhard

2009-02-01

Aseptic loosening is the most frequent cause of implant failure in total hip arthroplasty. While a direct link between aseptic loosening and periprosthetic bone loss remains elusive, there is plentiful evidence for a close association with early implant migration. The present trial was primarily designed to evaluate whether a single infusion of 4 mg of zoledronic acid prevented early implant migration in patients with osteonecrosis of the femoral head. Fifty patients were consecutively enrolled to receive either zoledronic acid or saline solution after cementless total hip arthroplasty. Radiographs, biochemical parameters of bone turnover, and the Harris hip-rating score were determined preoperatively and at each follow-up examination at seven weeks, six months, one year, and yearly thereafter. The median follow-up period was 2.8 years. We found a significant subsidence of the stem of up to a mean (and standard deviation) of -1.2 +/- 0.6 mm at two years within the control group, and the cups had a mean medialization of 0.6 +/- 1.0 mm and a mean cranialization of 0.6 +/- 0.8 mm (p < 0.001). Treatment with zoledronic acid effectively minimized the migration of the cups in both the transverse and the vertical direction (mean, 0.15 +/- 0.6 mm and 0.06 +/- 0.6 mm, respectively; p < 0.05), while only a trend to decreased subsidence of the stem was detected. Finally, the Harris hip score rapidly increased over time in both treatment groups, although this increase was significantly more pronounced in the zoledronate-treated group than in the control group (analysis of variance, p = 0.008). A single infusion of zoledronic acid shows promise in improving initial fixation of a cementless implant, which may improve the clinical outcome of total hip arthroplasty in patients with osteonecrosis of the femoral head.

A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone

DEFF Research Database (Denmark)

Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner

2016-01-01

-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay...

Zoledronic acid in children with osteogenesis imperfecta and Bruck syndrome: a 2-year prospective observational study.

Science.gov (United States)

Otaify, G A; Aglan, M S; Ibrahim, M M; Elnashar, M; El Banna, R A S; Temtamy, S A

2016-01-01

Treatment with zoledronic acid (ZA) over 2 years, among 33 children with osteogenesis imperfecta (OI) and five Bruck syndrome cases, showed reduction in fracture rates, pain, and improvement in bone mineral density (BMD) and motor milestones of development. This is the first study reporting the use of bisphosphonates in patients with Bruck syndrome (BS). OI and BS are genetic disorders that result in bone fragility and reduced BMD. There is little literature describing the efficacy and safety of ZA in this population. In this study, we assess the response to treatment with ZA at six monthly intervals in Egyptian children with OI and BS for a period of 2 years. Thirty-three patients with OI and five patients with BS were treated with 0.1 mg/kg ZA intravenously every 6 months for 2 years during which they were followed up using different parameters. A clinical severity score (CSS) was applied to the patients before and 2 years after the start of therapy. Comparison of disease severity and response to ZA treatment between autosomal-dominant (AD) and autosomal-recessive (AR) OI patients was also done. After 6 months of treatment, OI and BS patients showed a significant increase in BMD Z-scores (P < 0.003 in the spine and P < 0.004 in the hip), together with a significant drop in fracture rate (P < 0.001), relief of pain (P < 0.001), and improvement in ambulation (P < 0.001). CSS was significantly reduced after 2 years of treatment in both OI and BS patients. AR-OI patients were more severely affected than AD-OI patients and showed more significant improvement. Zoledronic acid proved to be safe and effective in the treatment of OI and BS. The biannual infusion protocol was convenient to patients. There was a positive correlation between disease severity and benefits of the treatment. The use of the CSS proved to be of value in the assessment of the degree of severity in OI, and with some modifications, it was a valuable tool for the assessment of

Determination of rat vertebral bone compressive fatigue properties in untreated intact rats and zoledronic-acid-treated, ovariectomized rats

NARCIS (Netherlands)

Brouwers, J.E.M.; Ruchselman, M.; Rietbergen, van B.; Bouxsein, M.L.

2009-01-01

Summary Compressive fatigue properties of whole vertebrae, which may be clinically relevant for osteoporotic vertebral fractures, were determined in untreated, intact rats and zoledronic-acid-treated, ovariectomized rats. Typical fatigue behavior was found and was similar to that seen in other

Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture

DEFF Research Database (Denmark)

Eriksen, Erik Fink; Lyles, Kenneth W; Colón-Emeric, Cathleen S

2009-01-01

undergone surgical repair of hip fracture. In this analysis, we examined whether timing of the first infusion of zoledronic acid study drug after hip fracture repair influenced the antifracture efficacy and mortality benefit observed in the study. A total of 2127 patients (1065 on active treatment and 1062...... was approximately 6 wk. Posthoc analyses were performed by dividing the study population into 2-wk intervals (calculated from time of first infusion in relation to surgical repair) to examine effects on BMD, fracture, and mortality. Analysis by 2-wk intervals showed a significant total hip BMD response......Annual infusions of zoledronic acid (5 mg) significantly reduced the risk of vertebral, hip, and nonvertebral fractures in a study of postmenopausal women with osteoporosis and significantly reduced clinical fractures and all-cause mortality in another study of women and men who had recently...

[Efficacy of zoledronic acid combined with chemotherapy in treatment of skeletal metastases of non-small cell lung cancer and the bone metabolic markers].

Science.gov (United States)

Hu, Xiao-ye; Zou, Qing-feng; Jin, Chuan; Li, Wei-dong; Chen, Wen-sheng; Ma, Lei

2010-06-01

To evaluate the clinical efficacy of zoledronic acid combined with chemotherapy in the management of skeletal metastasis of non-small cell lung cancer (NSCLC) and investigate the value in urine amino-terminal telopeptide of type I collagen (uNTX) and serum bone specific alkaline phosphatase (sBALP) in monitoring skeletal metastasis of NSCLC. From February, 2007 to January, 2009, 32 NSCLC patients with bone metastases received treatment with zoledronic acid at the dose of 4 mg given every 3 weeks and platinum-based chemotherapy (each cycle lasting for 3 weeks). Before and during the treatments, uNTX and sBALP were measured in these patients using ELISA and precipitation with wheat germ lectin, respectively. The patients were followed up for skeletal-related events (SREs) and status of survival. A significant decrease occurred in the pain scores and analgesic use in the patients after the therapy. SREs were not observed during the treatment. Serum creatinine and calcium levels underwent no significant variation during the treatment. Eleven patients reported 14 possible zoledronic acid-related adverse events. The concentration of uNTX and sBALP in patients with bone metastases was above the upper limit of the normal range. A positive correlation was observed between the levels of the markers and the extent of bone metastases. At the third month, uNTX and sBALP were significantly lowered, but radionuclide whole-body bone imaging showed no obvious changes. Of the 32 patients, 24 had elevated uNTX values, which became normal after the treatment in 15 patients and remained elevated in the other 9 patients. SREs occurred in these two subgroups at the rates of 53% and 89% (P=0.039), respectively. Twenty-six patients had elevated sBALP level, and 16 of them exhibited normal sBALP level after the treatment. The incidences of SREs in the patients with elevated and normal sBALP level were 50% and 90% (P=0.038), respectively. The levels of uNTX/Cr and sBALP were not correlated

Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management

Directory of Open Access Journals (Sweden)

Luca Dalle Carbonare

2010-08-01

Full Text Available Luca Dalle Carbonare, Mirko Zanatta, Adriano Gasparetto, Maria Teresa ValentiClinic of Internal Medicine D, Department of Medicine, University of Verona, ItalyAbstract: Bisphosphonates (BPs are widely used in the treatment of postmenopausal ­osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively. The former inhibit farnesyl diphosphate synthase while the latter induce the production of toxic analogs of adenosine triphosphate. These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action. Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation. Several randomized control trials have demonstrated that NBPs significantly improve bone mineral density, suppress bone turnover, and reduce the incidence of both vertebral and nonvertebral fragility fractures. Although they are generally considered safe, some side effects are reported (esophagitis, acute phase reaction, hypocalcemia, uveitis, and compliance with therapy is often inadequate. In particular, gastrointestinal discomfort is frequent with the older daily oral administrations and is responsible for a high proportion of discontinuation. The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.Keywords: bisphosphonates, osteoporosis, safety, tolerability, zoledronic acid

Early inhibitory effects of zoledronic acid in tooth extraction sockets in dogs are negated by recombinant human bone morphogenetic protein.

Science.gov (United States)

Gerard, David A; Carlson, Eric R; Gotcher, Jack E; Pickett, David O

2014-01-01

This study was conducted with 2 purposes. The first was to determine the effect of a single dose of zoledronic acid (ZA) on the healing of a tooth extraction socket in dogs. The second was to determine if placement of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) - INFUSE, (Medtronic, Memphis, TN) into these extraction sockets would inhibit the inhibition on bone healing and remodeling by ZA. Nine adult female beagle dogs (2 to 3 yr old) were placed into 3 groups of 3 dogs each. Group I received 15 mL of sterile saline intravenously; group II received 2.5 mg of ZA intravenously; and group III received 5 mg of ZA intravenously. Forty-five days after treatment, all dogs underwent extraction of noncontiguous right and left mandibular first molars and second premolars. In group I, the right mandibular extraction sockets had nothing placed in them, whereas the left mandibular sockets had only ACS placed in them. In groups II and III, the right mandibular sockets had rhBMP-2/ACS placed in them, whereas the left mandibular sockets had only ACS placed. All extraction sockets were surgically closed. Tetracycline was given intravenously 5 and 12 days later, and all animals were euthanized 15 days after tooth extraction. The extraction sockets and rib and femur samples were harvested immediately after euthanasia, processed, and studied microscopically. A single dose of ZA significantly inhibited healing and bone remodeling in the area of the tooth extractions. The combination of rhBMP-2/ACS appeared to over-ride some of the bone remodeling inhibition of the ZA and increased bone fill in the extraction sites, and remodeling activity in the area was noted. The effects of rhBMP-2/ACS were confined to the area of the extraction sockets because bone activity at distant sites was not influenced. A single dose of ZA administered intravenously inhibits early healing of tooth extraction sockets and bone remodeling in this animal model. The

Percutaneous kyphoplasty combined with zoledronic acid infusion in the treatment of osteoporotic thoracolumbar fractures in the elderly

OpenAIRE

Shi,Chen; Zhang,Mi; Cheng,An-Yuan; Huang,Zi-Feng

2018-01-01

Chen Shi,1,* Mi Zhang,2,* An-Yuan Cheng,1 Zi-Feng Huang1 1Department of Trauma Surgery, Wuhan No 1 Hospital, Wuhan, China; 2Department of Orthopedics, Wuhan No 5 Hospital, Wuhan, China *These authors contributed equally to this work Objective: We studied the efficacy of zoledronic acid (ZOL) infusion on radiographic and clinical outcomes after percutaneous kyphoplasty (PKP) for elderly patients with osteoporotic thoracolumbar fractures (osteoporotic vertebral compression fractures...

Percutaneous kyphoplasty combined with zoledronic acid infusion in the treatment of osteoporotic thoracolumbar fractures in the elderly

OpenAIRE

Shi C; Zhang M; Cheng AY; Huang ZF

2018-01-01

Chen Shi,1,* Mi Zhang,2,* An-Yuan Cheng,1 Zi-Feng Huang1 1Department of Trauma Surgery, Wuhan No 1 Hospital, Wuhan, China; 2Department of Orthopedics, Wuhan No 5 Hospital, Wuhan, China *These authors contributed equally to this work Objective: We studied the efficacy of zoledronic acid (ZOL) infusion on radiographic and clinical outcomes after percutaneous kyphoplasty (PKP) for elderly patients with osteoporotic thoracolumbar fractures (osteoporotic vertebral compression fractures [OV...

Short-term effect of zoledronic acid upon fracture resistance of the mandibular condyle and femoral head in an animal model.

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Camacho-Alonso, Fabio; López-Jornet, Pía; Vicente-Hernández, Ascensión

2013-05-01

The aim of this study was to compare the effects in terms of resistance to fracture of the mandibular condyle and femoral head following different doses of zoledronic acid in an animal model. A total of 80 adult male Sprague-Dawley rats were included in a prospective randomized study. The animals were randomly divided into four groups of 20 rats each. Group 1 (control) received sterile saline solution, while groups 2, 3 and 4 received a accumulated dose of 0.2 mg, 0.4 mg and 0.6 mg of zoledronic acid, respectively. The animals were sacrificed 28 days after the last dose, and the right hemimandible and the right femur were removed. The fracture strength was measured (in Newtons) with a universal test machine using a 1 kN load connected to a metal rod with one end angled at 30 degrees. The cross-head speed was 1 mm/min. Later, the specimens were observed under a scanning electron microscope with backscattered electron imaging (SEM-BSE). At last, chemical analysis and elemental mapping of the mineral bone composition were generated using a microanalytical system based on energy-dispersive and X-ray spectrometry (EDX). A total of 160 fracture tests were performed. The fracture resistance increased in mandible and femur with a higher accumulated dose of zoledronic acid. Statistically significant differences were recorded versus the controls with all the studies groups. The chemical analysis in mandible showed a significantly increased of calcium and phosphorous to compare the control with all of the study groups; however, in femur no statistically significant differences between the four study groups were observed. The administration of bisphosphonates increases the fracture resistance in mandible and femur.

Novel therapeutic intervention for osteoporosis prepared with strontium hydroxyapatite and zoledronic acid: In vitro and pharmacodynamic evaluation

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Khajuria, Deepak Kumar, E-mail: deepak_kumarkhajuria@yahoo.co.in [The Musculoskeletal Genetics Laboratory, Faculty of Medicine in the Galilee, Bar-Ilan University, Safed (Israel); Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore (India); Vasireddi, Ramakrishna; Trebbin, Martin [Hamburg Center for Ultrafast Imaging, University of Hamburg, Hamburg (Germany); Karasik, David [The Musculoskeletal Genetics Laboratory, Faculty of Medicine in the Galilee, Bar-Ilan University, Safed (Israel); Razdan, Rema [Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore (India)

2017-02-01

Osteoporosis therapeutics has been monopolized mainly by bisphosphonates, which are potent anti-osteoporotic drugs, while they do not promote bone formation or replenish the already resorbed bone. Although strontium substituted hydroxyapatite (SrHA) has been proclaimed to improve bone properties in an osteoporotic animal model, there is no published data on direct delivery of SrHA nanoparticles by bisphosphonate-like zoledronic acid (ZOL) to the bone. Therefore, this study was designed to investigate the potential of using SrHA/ZOL nanoparticle-based drug formulation in an ovariectomized rat model of postmenopausal osteoporosis. SrHA and SrHA/ZOL nanoparticles were prepared and characterized by field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Twelve weeks after ovariectomy, rats were treated with either single intravenous dose of SrHA/ZOL (100, 50 or 25 μg/kg); ZOL (100 μg/kg); or SrHA (100 μg/kg). Saline-treated OVX and SHAM-OVX groups served as controls. The energy-dispersive X-ray (EDX) microanalysis of bone specimen obtained from SrHA/ZOL groups yielded range between 64.3 ± 6.7 to 66.9 ± 6.8 of calcium weight (wt) % and 1.64 ± 0.6 to 1.74 ± 0.8 of calcium/phosphorus (Ca/P) ratio which was significantly higher when compared with 39.7 ± 9.3 calcium and 1.30 ± 0.2 Ca/P ratio for OVX group. Moreover, the strontium wt% in SrHA/ZOL group (between 3.1 ± 0.5 and 6.8 ± 0.4) was significantly higher than SrHA group (1.8 ± 0.9). These results confirmed targeted delivery of SrHA nanoparticles by ZOL to the bone. Therapy with SrHA/ZOL showed significant improvements in trabecular bone microarchitecture and mechanical strength as compared to ZOL or SrHA (p < 0.05). Moreover, treatment with SrHA/ZOL significantly precluded an increase in serum bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase than either ZOL or SrHA (p < 0.05). These results strongly implicate

Zoledronic acid enhances antitumor efficacy of liposomal doxorubicin.

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Hattori, Yoshiyuki; Shibuya, Kazuhiko; Kojima, Kaori; Miatmoko, Andang; Kawano, Kumi; Ozaki, Kei-Ichi; Yonemochi, Etsuo

2015-07-01

Previously, we found that the injection of zoledronic acid (ZOL) into mice bearing tumor induced changes of the vascular structure in the tumor. In this study, we examined whether ZOL treatment could decrease interstitial fluid pressure (IFP) via change of tumor vasculature, and enhance the antitumor efficacy of liposomal doxorubicin (Doxil®). When ZOL solution was injected at 40 µg/mouse per day for three consecutive days into mice bearing murine Lewis lung carcinoma LLC tumor, depletion of macrophages in tumor tissue and decreased density of tumor vasculature were observed. Furthermore, ZOL treatments induced inflammatory cytokines such as interleukin (IL)-10 and -12, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-α in serum of LLC tumor-bearing mice, but not in normal mice, indicating that ZOL treatments might induce an inflammatory response in tumor tissue. Furthermore, ZOL treatments increased antitumor activity by Doxil in mice bearing a subcutaneous LLC tumor, although they did not significantly increase the tumor accumulation of doxorubicin (DXR). These results suggest that ZOL treatments might increase the therapeutic efficacy of Doxil via improvement of DXR distribution in a tumor by changing the tumor vasculature. ZOL treatment can be an alternative approach to increase the antitumor effect of liposomal drugs.

Zoledronic acid improves bone mineral density, reduces bone turnover and improves skeletal architecture over 2 years of treatment in children with secondary osteoporosis

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Simm, Peter J; Johannesen, Jesper; Briody, Julie

2011-01-01

There are limited data on the use of bisphosphonate therapy for secondary osteoporoses in childhood, and no previous reports of the use of zoledronic acid in this group. We report 20 children with a variety of underlying primary diagnoses with associated secondary osteoporosis, who were treated w...

Monitoring changes in quality of life in patients with lung cancer under treatment with chemotherapy and co administration of zoledronic acid by using specialized questionnaires.

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Tremmas, Ioannis; Petsatodis, George; Potoupnis, Michael; Laskou, Stella; Giannakidis, Dimitrios; Mantalovas, Stylianos; Koulouris, Charilaos; Katsaounis, Athanasios; Pavlidis, Efstathios; Amaniti, Aikaterini; Huang, Haidong; Bai, Chong; Shi, Dongchen; Dardas, Athanasios; Zarogoulidis, Paul; Sardeli, Chrisanthi; Konstantinou, Fotis; Katsikogiannis, Nikolaos; Zarogoulidis, Konstantinos; Karapantzos, Ilias; Karapantzou, Chrysanthi; Shen, Xiaping; Kesisoglou, Isaak; Sapalidis, Konstantinos

2018-01-01

Background: Due to the severity of the primary disease in patients with lung cancer, quality of life (QoL) is often overlooked. Factors that form QoL should be taken in consideration when planning the appropriate treatment and determining therapy targets, because of the increasing frequency of bone metastasis leading to high levels of pain. Purpose of this study is to assess quality of life in patients with lung cancer, before and after treatment combined with zoledronic acid. Methods and materials: QoL was assessed in 80 patients (49 males-31 females), of which 45 developed bone metastasis. Prior and post treatment (with co administration of zoledronic acid) seven reliable scales: Pittsburgh Sleep Quality index (PSQI), Epworth Sleeping Scale (ess), Dyspnea Scale (ds), Fatigue Severity Scale (FSS), Brief Pain Inventory (BPI), Fact-G scale for sleep quality and EQ-5D for general health condition. Results: Statistically positive correlations were verified between PSQI-DS, PSQI-FSS, BPI-ESS, DS-FSS, DS-BPI and BPI-FSS (pbetterment in quality of life was marked (p<0,001). Although significant decrease in fatigue levels was observed (p<0,001) there has been an increase in dyspnea symptoms (p<0,001). Conclusions: Significant improvement was apparent when zoledronic acid was co administered in any treatment in patients with lung cancer. Sleep quality, fatigue and pain parameters also improved, with no positive impact on the symptoms of dyspnea.

Farnesyl diphosphate synthase is involved in the resistance to zoledronic acid of osteosarcoma cells. : resistance of osteosarcoma to nitrogen bisphosphonates

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Ory , Benjamin; Moriceau , Gatien; Trichet , Valérie; Blanchard , Frédéric; Berreur , Martine; Rédini , Françoise; Rogers , Michael; Heymann , Dominique

2008-01-01

International audience; We recently demonstrated original anti-tumor effects of zoledronic acid (Zol) on osteosarcoma cell lines independently of their p53 and Rb status. The present study investigated the potential Zol-resistance acquired by osteosarcoma cells after prolonged treatment. After 12 weeks of culture in the presence of 1 microm Zol, the effects of high doses of Zol (10-100 microm) were compared between the untreated rat (OSRGA, ROS) and human (MG63, SAOS2) osteosarcoma cells and ...

Self-assembling nanoparticles encapsulating zoledronic acid inhibit mesenchymal stromal cells differentiation, migration and secretion of proangiogenic factors and their interactions with prostate cancer cells

Czech Academy of Sciences Publication Activity Database

Borghese, C.; Casagrande, N.; Pivetta, E.; Colombatti, A.; Boccellino, M.; Amler, Evžen; Normanno, N.; Caraglia, M.; de Rosa, G.; Aldinucci, D.

2017-01-01

Roč. 8, č. 26 (2017), s. 42926-42938 ISSN 1949-2553 Institutional support: RVO:68378041 Keywords : zoledronic acid * self-assembling nanoparticles * mesenchymal stromal cells * prostate cancer * tumor microenvironment Subject RIV: FP - Other Medical Disciplines OBOR OECD: Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction) Impact factor: 5.168, year: 2016

Enhancing cytotoxic and apoptotic effect in OVCAR-3 and MDAH-2774 cells with all-trans retinoic acid and zoledronic acid: a paradigm of synergistic molecular targeting treatment for ovarian cancer

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Kısım Aslı

2010-07-01

Full Text Available Abstract Background Ovarian cancer is the most fatal gynecologic malignancies in the world. Although, platinum based treatments are widely used, the disease becomes treatment refractory within two years, and novel treatment options should be searched. All- trans retinoic acid (ATRA induces growth arrest, differentiation and cell death in some types of cancer cells and its combination with various anticancer agents results in enhanced cytotoxicity. Zoledronic acid is a common bisphosphonate known for its anticancer effects beyond its current use in the treatment of cancer-induced bone disease. We aimed to investigate the possible additive/synergistic effect of both agents in OVCAR-3 and MDAH-2774 ovarian cancer cell lines, since both agents show superiority to conventional cytotoxics in terms of adverse events. Methods XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. OligoGeArray® which consists of 112 apoptosis related genes was used to elucidate the genetic changes within cancer cells. To validate our oligoarray results, quantitative real-time PCR was performed on four selected genes that were maximally effected by the combination treatment: lymphotoxin beta receptor (LTBR, myeloid cell leukemia-1 (MCL-1, tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A, TNFRSF1A-associated death domain protein (TRADD. Results We demonstrated that a novel combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in both ovarian cancer cells. While the combination therapy significantly induced proapoptotic genes such as tumor necrosis factor receptor superfamily (TNFRSF, TRADD and caspase 4, some of the antiapoptotic genes such as members of MCL-1, LTBR, BAG3 and Bcl-2 family members were inhibited. Conclusions These are the preliminary molecular results of a novel combination treatment of

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

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

2015-08-01

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

Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage

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Sprigg, Nikola; Robson, Katie; Bath, Philip

2016-01-01

RATIONALE: Outcome after intracerebral hemorrhage remains poor. Tranexamic acid is easy to administer, readily available, inexpensive, and effective in other hemorrhagic conditions. AIM: This randomized trial aims to test the hypothesis that intravenous tranexamic acid given within 8 h...... of spontaneous intracerebral hemorrhage reduces death or dependency. DESIGN: Phase III prospective double-blind randomized placebo-controlled trial. Participants within 8 h of spontaneous intracerebral hemorrhage are randomized to receive either intravenous tranexamic acid 1 g 10 min bolus followed by 1 g 8 h......, and institutionalization. DISCUSSION: This pragmatic trial is assessing efficacy of tranexamic acid after spontaneous intracerebral hemorrhage. Recruitment started in 2013; as of 15th January 2016 1355 participants have been enrolled, from 95 centers in seven countries. Recruitment is due to end in 2017. TICH-2 Trial...

Combined Use of Zoledronic Acid Augments Ursolic Acid-Induced Apoptosis in Human Osteosarcoma Cells through Enhanced Oxidative Stress and Autophagy

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Chia-Chieh Wu

2016-11-01

Full Text Available Ursolic acid (UA, a naturally occurring pentacyclic triterpene acid found in many medicinal herbs and edible plants, triggers apoptosis in several tumor cell lines but not in human bone cancer cells. Most recently, we have demonstrated that UA exposure reduces the viability of human osteosarcoma MG-63 cells through enhanced oxidative stress and apoptosis. Interestingly, an inhibitor of osteoclast-mediated bone resorption, zoledronic acid (ZOL, also a third-generation nitrogen-containing bisphosphonate, is effective in the treatment of bone metastases in patients with various solid tumors. In this present study, we found that UA combined with ZOL to significantly suppress cell viability, colony formation, and induce apoptosis in two lines of human osteosarcoma cells. The pre-treatment of the antioxidant had reversed the oxidative stress and cell viability inhibition in the combined treatment, indicating that oxidative stress is important in the combined anti-tumor effects. Moreover, we demonstrated that ZOL combined with UA significantly induced autophagy and co-administration of autophagy inhibitor reduces the growth inhibitory effect of combined treatment. Collectively, these data shed light on the pathways involved in the combined effects of ZOL and UA that might serve as a potential therapy against osteosarcoma.

Intravenous Tranexamic Acid Decreases Allogeneic Transfusion Requirements in Periacetabular Osteotomy.

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Bryan, Andrew J; Sanders, Thomas L; Trousdale, Robert T; Sierra, Rafael J

2016-01-01

Bernese (Ganz) periacetabular osteotomy is associated with significant blood loss and the need for perioperative transfusion. Tranexamic acid decreases blood loss and minimizes transfusion rates in total joint arthroplasty. However, no reports have described its use in patients undergoing Bernese periacetabular osteotomy. This study reports the use of intravenous tranexamic acid in these patients. The study included 137 patients (150 hips) who underwent isolated periacetabular osteotomy at a single institution between 2003 and 2014. Of these, 68 patients (75 hips) received intravenous tranexamic acid 1 g at the time of incision and 1 g at the time of closure. A group of 69 patients (75 hips) served as control subjects who underwent periacetabular osteotomy without administration of intravenous tranexamic acid. Thromboembolic disease was defined as deep venous thrombosis or pulmonary embolism occurring within 6 weeks of surgery. Outcomes measured included transfusion requirements, pre- and postoperative hemoglobin values, operative times, and thromboembolic disease rates. Aspirin was used as the thromboembolic prophylactic regimen in 95% of patients. The rate of allogeneic transfusion was 0 in the tranexamic acid group compared with 21% in the control group (P=.0001). No significant difference was found in the autologous cell salvage requirement (.96 vs 1.01; P=.43) or the thromboembolic disease rate between the tranexamic acid group and the control group (2.67% vs 1.33%; P=.31). The use of intravenous tranexamic acid led to a decreased transfusion requirement with no increased risk of thromboembolic disease in this contemporary cohort of patients undergoing periacetabular osteotomy. Copyright 2016, SLACK Incorporated.

Zoledronic acid inhibits vasculogenic mimicry in murine osteosarcoma cell line in vitro.

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Fu, Dehao; He, Xianfeng; Yang, Shuhua; Xu, Weihua; Lin, Tao; Feng, Xiaobo

2011-06-30

To study the effects of zoledronic acid (ZA) on the vasculogenic mimicry of osteosarcoma cells in vitro. A Three-dimensional culture of LM8 osteosarcoma cells on a type I collagen matrix was used to investigate whether osteosarcoma cells can develop vasculogenic mimicry, and to determine the effects of ZA on this process. In addition, the cellular ultrastructural changes were observed using scanning electron microscopy and laser confocal microscopy. The effects of ZA on the translocation of RhoA protein from the cytosol to the membrane in LM8 cells were measured via immunoblotting. ZA inhibited the development of vasculogenic mimicry by the LM8 osteosarcoma cells, decreased microvilli formation on the cell surface, and disrupted the F-actin cytoskeleton. ZA prevented translocation of RhoA protein from the cytosol to the membrane in LM8 cells. ZA can impair RhoA membrane localization in LM8 cells, causing obvious changes in the ultrastructure of osteosarcoma cells and induce cell apoptosis, which may be one of the underlying mechanisms by which the agent inhibits the development of vasculogenic mimicry by the LM8 cells.

Zoledronic acid inhibits vasculogenic mimicry in murine osteosarcoma cell line in vitro

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Lin Tao

2011-06-01

Full Text Available Abstract Background To study the effects of zoledronic acid (ZA on the vasculogenic mimicry of osteosarcoma cells in vitro. Methods A Three-dimensional culture of LM8 osteosarcoma cells on a type I collagen matrix was used to investigate whether osteosarcoma cells can develop vasculogenic mimicry, and to determine the effects of ZA on this process. In addition, the cellular ultrastructural changes were observed using scanning electron microscopy and laser confocal microscopy. The effects of ZA on the translocation of RhoA protein from the cytosol to the membrane in LM8 cells were measured via immunoblotting. Results ZA inhibited the development of vasculogenic mimicry by the LM8 osteosarcoma cells, decreased microvilli formation on the cell surface, and disrupted the F-actin cytoskeleton. ZA prevented translocation of RhoA protein from the cytosol to the membrane in LM8 cells. Conclusions ZA can impair RhoA membrane localization in LM8 cells, causing obvious changes in the ultrastructure of osteosarcoma cells and induce cell apoptosis, which may be one of the underlying mechanisms by which the agent inhibits the development of vasculogenic mimicry by the LM8 cells.

Evaluation of the efficacy of zoledronic acid and amifostine on radiation induced bone loss in mice

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Kim, Jin Wook; Lee, Sueum; Kang, Sohi; Moon, Cahng Jong; Kim, Jong Choon; Kim, Sung Ho [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of); Jung, Uhee; Jo, Sung Kee [Advanced Radiation Technology Institute, Jeungeup (Korea, Republic of); Jang, Jong Sik [College of Ecology and Environmental Science, Kyungpook National University, Sangju (Korea, Republic of)

2016-09-15

This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Treatment of ZA (100 μg·kg{sup -1}·week{sup -1}) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. The results indicate that ZA can prevent radiation-induced bone loss in mice.

Influence of zoledronic acid on disseminated tumor cells in bone marrow and survival: results of a prospective clinical trial

International Nuclear Information System (INIS)

Banys, Malgorzata; Wackwitz, Birgit; Hirnle, Peter; Wallwiener, Diethelm; Fehm, Tanja; Solomayer, Erich-Franz; Gebauer, Gerhard; Janni, Wolfgang; Krawczyk, Natalia; Lueck, Hans-Joachim; Becker, Sven; Huober, Jens; Kraemer, Bernhard

2013-01-01

The presence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with reduced clinical outcome. Bisphosphonate treatment was shown to eradicate DTC from BM in several studies. This controlled randomized open-label multi-center study aimed to investigate the influence of zoledronic acid (ZOL) on DTC and survival of breast cancer patients (Clinical Trial Registration Number: NCT00172068). Patients with primary breast cancer and DTC-positive bone marrow were randomized to treatment with ZOL plus adjuvant systemic therapy (n = 40) or adjuvant systemic therapy alone (n = 46) between 03/2002 and 12/2004. DTC were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3 and by cytomorphology. The change in DTC numbers at 12 months and 24 months versus baseline, as well as patient outcomes were evaluated. 86 patients could be included into survival analysis (median follow-up: 88 months, range: 8–108 mths). Patients in the control group were more likely to die during follow-up than those in the ZOL-group (11% vs. 2%, p = 0.106). 15% of patients in the control group presented with relapse whereas only 8% of ZOL group patients developed metastatic or recurrent disease during follow-up (p = 0.205). At 24 months, 16% of patients from the control group were still DTC positive, whereas all patients treated with ZOL became DTC negative (p = 0.032). Patients presenting with persistent DTC 12 months after diagnosis had significantly shorter overall survival (p = 0.011). Bisphosphonate therapy contributes to eradication of disseminated tumor cells. The positive influence of bisphosphonates on survival in the adjuvant setting may be due to their effects on DTC. ClinicalTrials.gov Identifier: http://clinicaltrials.gov/show/NCT00172068 [Zoledronic Acid in the Treatment of Breast Cancer With Minimal Residual Disease in the Bone Marrow (MRD-1)

Amino Acid Metabolism in Acute Renal Failure: Influence of Intravenous Essential L-Amino Acid Hyperalimentation Therapy

Science.gov (United States)

Abel, Ronald M.; Shih, Vivian E.; Abbott, William M.; Beck, Clyde H.; Fischer, Josef E.

1974-01-01

A solution of 8 essential I-amino acids and hypertonic dextrose was administered to 5 patients in acute postoperative renal failure in a program of hyperalimentation designed to decrease the patient's catabolic state and to accrue certain metabolic benefits. A sixth patient receiving intravenous glucose alone served as a control. The pretreatment plasma concentrations of amino acids in all 6 patients did not differ significantly from normal; following intravenous essential amino acids at a dose of approximately 12.6 gm/24 hours, no significant elevations out of the normal range of these substances occurred. Since urinary excretion rates did not dramatically increase, urinary loss was excluded as a possible cause for the failure of increase of plasma concentrations. The results suggest that the administration of an intravenous solution of 1-amino acids and hypertonic dextrose is associated with rapid clearance from the blood of these substances and, with a failure of increased urinary excretion, indirect evidence of amino acid utilization for protein synthesis has been obtained. Histidine supplementation in patients with acute renal failure is probably unnecessary based on the lack of significant decreases in histidine concentrations in these patients. PMID:4850497

Inhibition of Zoledronic Acid on Cell Proliferation and Invasion of Lung Cancer Cell Line 95D

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Mingming LI

2009-03-01

Full Text Available Background and objective Abnormal proliferation and metastasis is the basic characteristic of malignant tumors. The aim of this work is to explore the effects of zoledronic acid on cell proliferation and invasion in lung cancer cell line 95D. Methods The effect of zoledrnic acid (ZOL on proliferation of lung cancer cell line 95D was detected by MTT. The expression of proliferation and invasion-relation genes and proteins were detected by Western blot, RT-PCR and immunofluorescence. Changes of invasion of lung cancer cell numbers were measured by polycarbonates coated with Matrigel. Results ZOL could inhibit the proliferation of lung cancer cell line 95D in vitro in a time-dependant and a dose-dependant manner. With time extending after ZOL treated, the mRNA expresion of VEGF, MMP9, MMP2 and protein expression of VEGF, MMP9, ERK1/ ERK2 were decreased. The results of Tanswell invasion showed the numbers of invasive cells were significantly reduced in 95D cells treated with ZOL 4 d and 6 d later. Conclusion ZOL could inhibit cell proliferation and invasion of lung cancer cell line 95D.

Zoledronate inhibits ischemia-induced neovascularization by impairing the mobilization and function of endothelial progenitor cells.

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Shih-Hung Tsai

Full Text Available BACKGROUND: Bisphosphonates are a class of pharmacologic compounds that are commonly used to treat postmenopausal osteoporosis and malignant osteolytic processes. Studies have shown that bone marrow-derived endothelial progenitor cells (EPCs play a significant role in postnatal neovascularization. Whether the nitrogen-containing bisphosphonate zoledronate inhibits ischemia-induced neovascularization by modulating EPC functions remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Unilateral hindlimb ischemia was surgically induced in wild-type mice after 2 weeks of treatment with vehicle or zoledronate (low-dose: 30 μg/kg; high-dose: 100 μg/kg. Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio was significantly lower in wild-type mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in controls 4 weeks after ischemic surgery (control vs. low-dose vs. high-dose: 87±7% vs. *61±18% vs. **49±17%, *p<0.01, **p<0.005 compared to control. Capillary densities were also significantly lower in mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in control mice. Flow cytometry analysis showed impaired mobilization of EPC-like cells (Sca-1(+/Flk-1(+ after surgical induction of ischemia in mice treated with zoledronate but normal levels of mobilization in mice treated with vehicle. In addition, ischemic tissue from mice that received zoledronate treatment exhibited significantly lower levels of the active form of MMP-9, lower levels of VEGF, and lower levels of phosphorylated eNOS and phosphorylated Akt than ischemic tissue from mice that received vehicle. Results of the in vitro studies showed that incubation with zoledronate inhibited the viability, migration, and tube-forming capacities of EPC. CONCLUSIONS/SIGNIFICANCE: Zoledronate inhibited ischemia-induced neovascularization by impairing EPC mobilization and angiogenic functions

Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

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Søe, Kent; Plesner, Torben; Jakobsen, Erik H

2013-01-01

Zoledronic acid (Zol) is used to treat bone disease in both multiple myeloma (MM) and breast cancer patients with bone metastasis (BC). However, bones of MM and BC patients show a difference in retention of the bisphosphonate used for bone scintigraphy. Therefore, we hypothesized that disease...... of Zol correlated with bone-specific alkaline phosphatase (bALP) levels in BC (p = 0.001), and with CTX/bALP in Zol naive MM patients (p = 0.012). Especially in BC patients, WBrt correlated with age (p = 0.014) independently of kidney function. In MM patients WBrt was found to primarily correlate...... with the extent of bone disease (p = 0.028). Multivariate linear regression analyses of the entire cohort pointed out that WBrt of Zol was best predicted by age (p ...

Antitumor activity of zoledronic acid in primary breast cancer cells determined by the ATP tumor chemosensitivity assay

International Nuclear Information System (INIS)

Fehm, Tanja; Zwirner, Manfred; Wallwiener, Diethelm; Seeger, Harald; Neubauer, Hans

2012-01-01

The NeoAzure study has demonstrated that the use of the bisphosphonate zoledronic acid (Zol) in the neoadjuvant setting increases the rate of complete response in primary breast cancer and therefore indicates direct antitumor activity. The purpose of this study was to compare the antitumor effect of Zol with standard chemotherapy in primary breast cancer cells using ATP-tumor chemosensitivity assay (ATP-TCA). Breast cancer specimens were obtained from patients with breast cancer who underwent primary breast cancer surgery at the Department of Obstetrics and Gynecology, Tübingen, Germany, between 2006 through 2009. Antitumor effects of Zol, TAC (Docetaxel, Adriamycin, Cyclophosphamide) and FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide) were tested in 116 fresh human primary breast cancer specimens using ATP-TCA. ATP-TCA results were analyzed with different cut-off levels for the half maximal inhibitory concentration (IC50), for IC90 and for the sensitivity index (IndexSUM). Each single agent or combination was tested at six doubling dilutions from 6.25, 12.5, 25, 50, 100, and 200% of test drug concentrations (TDC) derived from the plasma peak concentrations determined by pharmacokinetic data. The assay was carried out in duplicate wells with positive and negative controls. The median IndexSUM value was lower for Zol than for the combined regimen FEC (36.8%) and TAC (12.9%), respectively, indicating increased antitumor activity of Zol in primary breast cancer cells. The difference regarding Zol and FEC was significant (p < 0.05). The median IC50 value for Zol (8.03% TDC) was significantly lower than the IC50 values for FEC (33.5% TDC) and TAC (19.3% TDC) treatment (p < 0.05). However, the median IC90 value for Zol (152.5% TDC) was significantly higher than the IC90 value obtained with TAC (49.5% TDC; p < 0.05), but similar to the IC90 value for FEC (180.9% TDC). In addition a significant positive correlation was observed for the IndexSum of Zol and the ER status

Comparative pharmacoeconomic analysis of the use of Bonviva® (ibandronat to prevent fractures in postmenopausal osteoporosis

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E A Pyadushkina

2012-01-01

Full Text Available Objective: to make a pharmacoeconomic analysis of the use of oral (a 150-mg tablet once a month and injectable (a solution for intravenous bolus injection of 3 mg in 3 ml once every 3 months ibandronate in patients with postmenopausal osteoporosis (OP. Material and methods. The cost minimization method was used to calculate differences in the cost of using oral ibandronate, alendronate, and strontium ranelate in patients with postmenopausal OP for a year. The budgetary impact of administration of intravenous bisphosphonates (ibandronate and zoledronic acid was analyzed in patients with OP in a hospital context. A model calculator based on the Microsoft Excel software was applied to estimate how the expenditures of a health care facility were changing when different shares of drugs (ibandronate and zoledronic acid were used in purchase patterns. The cost of therapy with bisphosphonates (ibandronate and zoledronic acid, concomitant therapy (calcium and vitamin D, expendable materials, and therapy for adverse reactions (ARs due to the use of bisphophonates was considered in terms of the incidence of these ARs. Results. Among the oral drugs, ibandronate is more economically sound than alendronate: the difference in annual treatment costs was 7090.02 and 7334.31 rubles per patient, respectively, in favor of ibandronate. The inpatient use of only intravenous ibandronate versus the real administration practice determined on the basis of the data of the Farmekspert Marketing Researches Center on purchases in the hospital segment (30% for ibandronate and 70% for zoledronic acid considerably reduces the expenditures of a hospital, the saving will be 185416.06 rubles per year (if injections will be made in 20 patients. With 100% use of ibandronate, one can additionally provide 39 inpatients with bisphosphonate injections without additional expenditures.

Zoledronic acid use in patients with bone metastases from renal cell carcinoma or bladder cancer.

Science.gov (United States)

Saad, Fred; Eastham, James A

2010-06-01

Approximately 30% of patients with renal cell carcinoma (RCC) and 40% of patients with bladder cancer develop bone metastases that can disrupt normal bone homeostasis and place patients at risk for potentially life-limiting skeletal-related events (SREs). In the absence of bone-directed therapies, patients with RCC may experience up to four SREs per year. In patients with bone metastases from RCC or bladder cancer, zoledronic acid (ZOL) significantly reduced the risk of SREs compared with placebo. In addition to its bone-protective effects, preclinical and early clinical evidence indicates that ZOL prevents tumor progression. For example, retrospective subset analysis in patients with RCC indicated that ZOL extended time to disease progression and demonstrated a trend toward improved overall survival compared with placebo. Additionally, a study in patients with bone metastases from bladder cancer demonstrated that ZOL improved 1-year overall survival compared with placebo. Bone metastases place a heavy burden on patients with RCC or bladder cancer, and early, continuous treatment with ZOL may provide anticancer benefits in addition to important patient quality of life. 2010. Published by Elsevier Inc.

Modulation of Tumor Cell Metabolism by Laser Photochemotherapy with Cisplatin or Zoledronic Acid In Vitro.

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Heymann, Paul Günther Baptist; Henkenius, Katharina Sabine Elisabeth; Ziebart, Thomas; Braun, Andreas; Hirthammer, Klara; Halling, Frank; Neff, Andreas; Mandic, Robert

2018-03-01

Laser photochemotherapy is a new approach in cancer treatment using low-level laser therapy (LLLT) to enhance the effect of chemotherapy. In order to evaluate the effect of LLLT on tumor cells, HeLa cells were treated with cisplatin or zoledronic acid (ZA) followed by LLLT. Cell viability was evaluated with 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Oxidative phosphorylation and glycolysis were measured using extracellular flux analysis. Immunocytochemistry of heat-shock protein 70 (HSP70) and western blot analysis were performed. LLLT alone increased viability and was associated with lower oxidative phosphorylation but higher glycolysis rates. Cisplatin and ZA alone lowered cell viability, glycolysis and oxidative phosphorylation. This effect was significantly enhanced in conjunction with LLLT and was accompanied by reduced oxidative phosphorylation and collapse of glycolysis. Our observations indicate that LLLT may raise the cytotoxicity of cisplatin and ZA by modulating cellular metabolism, pointing to a possible application in cancer treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta.

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Biggin, Andrew; Zheng, Linda; Briody, Julie N; Coorey, Craig P; Munns, Craig F

2015-01-01

Intravenous bisphosphonate therapy is the first-line treatment in moderate-to-severe osteogenesis imperfecta (OI), but there are varied treatment protocols with little data on long-term efficacy. This study evaluates the clinical outcomes when transitioning from active bisphosphonate treatment to maintenance therapy. A retrospective review was conducted on 17 patients before treatment, following active treatment (zoledronate 0.05 mg/kg 6-monthly or pamidronate 6-9 mg/kg/year) and after establishment on maintenance treatment for more than 2 years (zoledronate 0.025 mg/kg 6-monthly or pamidronate lean tissue mass increased during active treatment. These improvements were maintained during the period of maintenance treatment. Vertebral height improved in fractured thoracic vertebrae from pre-treatment to active therapy and improved further during maintenance treatment. Metacarpal cortical thickness and relative cortical area also increased over the treatment periods. Maintenance intravenous bisphosphonate therapy preserved the beneficial effects of active treatment at the doses stated above. Further studies are required to determine the optimal bisphosphonate treatment regimen in the management of children with OI. © 2015 S. Karger AG, Basel.

Effect of Nd:YAG laser light on post-extractive socket healing in rats treated with zoledronic acid and dexamethasone

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Mergoni, Giovanni; Merigo, Elisabetta; Passerini, Pietro; Corradi, Domenico; Maestri, Roberta; Bussolati, Ovidio; Bianchi, Massimiliano; Sala, Roberto; Govoni, Paolo; Namour, Samir; Vescovi, Paolo

2016-03-01

Introduction The effect of low level laser therapy (LLLT) on the healing process could be useful for the prevention of post-extractive Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ). The aim of the study was to investigate the effect of LLLT on the post-extractive socket healing in rats treated with zoledronic acid and dexamethasone. Material and Methods Thirty male Sprague-Dawley rats were divided in 4 groups: control group (C, n = 5), laser group (L, n = 5), treatment group (T, n = 10) and treatment plus laser group (T+L, n = 10). Rats of group T and T+L received zoledronate 0,1 mg/Kg and dexamethasone 1 mg/Kg every 2 days for 10 weeks. Rats of group C and L were infused with vehicle. After 9 weeks the first maxillary molars were extracted in all rats. Rats of groups L and T+L received laser therapy (Nd:YAG, 1064 nm, 1.25W, 15Hz, 5 min, 14.37 J/cm2) in the socket area at days 0, 2, 4 and 6 after surgery. At 8 days from extraction, the sockets were clinically assessed with a grading score and the wound area was measured with a dedicate software. Histomorphometric evaluation and western blot analysis of osteopontin and osteocalcin expression were performed. Results Group T+L showed a trend toward a better clinical grading score compared to group T (grade I 22% Vs 28 % - grade II 56% Vs 28% - grade III 22% Vs 44%, respectively). The average wound area was similar among the groups. Inhibition of osteoclastic alveolar bone resorption was found in groups T and T+L (Phealing in conditions at risk for MRONJ development.

Intravenous amino acids in third trimester isolated oligohydramnios

International Nuclear Information System (INIS)

Qureshi, F.U.

2011-01-01

To determine the efficacy of maternal administration of intravenous amino acid solution in improving amniotic fluid volume in cases of isolated oligohydramnios and to observe its impact on mode of delivery and neonatal outcome. Study Design: A prospective case series. Methodology: Forty two women with singleton pregnancy, well established gestational age and clinically and sonographically proven isolated oligohydramnios in the third trimester before 36 weeks were administered amino acid solution intravenously after excluding cases of premature rupture of membranes, congenital anomaly of fetus, maternal pulmonary, cardiovascular and hypertensive disorders, and severe placental insufficiency (raised S/D ratio). Pre-infusion and postinfusion Amniotic fluid Index (AFI) was measured and repeated weekly. Women were followed till delivery. Results: According to repeated measurement analysis of variance, mean pre-infusion AFI was 4.7 cm, mean one week postinfusion AFI was 5.8 cm, mean two week post-infusion AFI was 6.2 cm and mean three week AFI was 6.3 cm (p-value 0.029, significant). Cesarean section became a predominant mode of delivery in this group without a firm evidence of associated fetal compromise. Conclusion: Amino acid infusion is an effective therapy for raising AFI in isolated oligohydramnios in this case series. Liberal use of cesarean section in this selected group should be carefully re-evaluated. (author)

Development of superior bone scintigraphic agent from a series of {sup 99m}Tc-labeled zoledronic acid derivatives

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Lin Jianguo [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Qiu Ling, E-mail: qiulingwx@gmail.com [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Cheng Wen [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Luo Shineng, E-mail: shineng914@yahoo.com.cn [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Xue Li; Zhang Shu [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China)

2012-05-15

Two novel zoledronic acid (ZL) derivatives, 1-hydroxy-4-(1H-imidazol-1-yl)butane-1,1-diyldiphosphonic acid (IBDP) and 1-hydroxy-5-(1H-imidazol-1-yl)pentane-1,1-diyldiphosphonic acid (IPeDP), were prepared and labeled with the radionuclide technetium-99m in a high labeling yield. In vitro stabilities of these radiolabeled complexes were measured by the radio-HPLC analysis as a function of time, which showed excellent stability with the radiochemical purity of over 95% at 6 h post preparation. Their in vivo biological performances were evaluated and compared with those of {sup 99m}Tc-ZL and {sup 99m}Tc-MDP (methylenediphosphonic acid). The biodistribution in mice and scintigraphic images of the rabbit showed that the tracer agent {sup 99m}Tc-IPeDP had highly selective uptake in the skeletal system and rapid clearance from the blood and soft tissues and an excellent scintigraphic image can be obtained in a shorter time post injection with clear visualization of the skeleton and low soft tissue activity. These preclinical studies suggest that {sup 99m}Tc-IPeDP would be a novel superior bone scintigraphic agent. - Highlights: Black-Right-Pointing-Pointer Two novel diphosphonic acids were labeled with the {sup 99m}Tc in high labeling yield. Black-Right-Pointing-Pointer {sup 99m}Tc-IPeDP had high uptake in skeletal system and rapid clearance from blood. Black-Right-Pointing-Pointer {sup 99m}Tc-IPeDP reveals attractive biological features as superior bone scanning agent.

Downregulation of CXCR4 Expression and Functionality After Zoledronate Exposure in Canine Osteosarcoma.

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Byrum, M L; Pondenis, H C; Fredrickson, R L; Wycislo, K L; Fan, T M

2016-07-01

The establishment and progression of metastases remains the life-limiting factor for dogs diagnosed with osteosarcoma (OS). The pattern of metastases is likely regulated through interactions between chemokine receptors and chemokines, and perturbations in these signaling cascades responsible for cytoskeletal organization and directional migration have the potential to alter metastatic cell trafficking behaviors. Zoledronate will impair directional migration of OS cells through downregulation of chemokine (C-X-C motif) receptor 4 (CXCR4) expression and functionality. Nineteen archived tumor specimens and plasma from 20 dogs with OS. Prospectively, the expressions of CXCR4 were studied in OS cell lines and spontaneous tumor samples. The effect of zoledronate on CXCR4 expression and functionality was investigated by characterizing responses in 3 OS cell lines. In 19 OS specimens and 20 dogs with OS, changes in CXCR4 expression and circulating CXCR4 concentrations were characterized in response to zoledronate therapy respectively. All canine OS cells express CXCR4, and zoledronate reduces CXCR4 expression and functionality by 27.7% (P < .0001), through augmented proteasome degradation and reduced prenylation of heterotrimeric G-proteins in 33% of tumor cell lines evaluated. In OS-bearing dogs, zoledronate reduces CXCR4 expressions by 40% within the primary tumor compared to untreated controls (P = .03) and also decreases the circulating concentrations of CXCR4 in 18 of 20 dogs with OS. Zoledronate can alter CXCR4 expression and functionality in OS cells, and consequent perturbations in CXCR4 intracellular signaling cascades might influence patterns of metastases. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Efeito do ácido zoledrônico em tíbias de ratas ooforectomizadas: estudo prospectivo e randomizado Effects of zoledronic acid on ooforectomized rats' tibiae: a prospective and randomized study

Directory of Open Access Journals (Sweden)

Fernando Roberto Alves Pereira

2009-02-01

Full Text Available OBJETIVO: Investigar as repercussões clínicas, biomecânicas e histomorfométricas do ácido zoledrônico em tíbias de ratas osteoporóticas, após ooforectomia bilateral. MÉTODOS: Foram estudadas, prospectivamente, 40 ratas da linhagem Wistar (Rattus novergicus albinus. Com 60 dias de vida, os animais foram aleatorizados em dois grupos de acordo com o procedimento cirúrgico: ooforectomia bilateral (O (n=20 e pseudo-cirurgia ("sham" (P (n=20. Após 30 dias, os animais foram divididos em quatro subgrupos, de acordo com a administração de 0,1mg/kg de ácido zoledrônico (AZ ou água destilada (AD: OAZ (n=10, OAD (n=10, PAZ (n=10 e PAD (n=10. Após 12 meses, os animais foram eutanasiados e suas tíbias analisadas. No estudo clínico foi considerado o peso dos animais; no estudo biomecânico foram realizados ensaios compressivos e na análise histomorfométrica foi determinada a área trabecular óssea. RESULTADOS: Os grupos "O" tiveram aumento de peso significativamente maior que os grupos "P" (p=0,005. Os grupos OAZ e PAZ tiveram aumento, não significativo, de peso quando comparados aos grupos OAD (p=0,47 e PAD (p=0,68. Os grupos com ácido zoledrônico e com água destilada suportaram carga máxima, semelhante (p=0,2, no momento em que ocorreu fratura. Nos grupos com ácido zoledrônico verificou-se o aumento não significante da área trabecular óssea quando comparados aos grupos com água destilada (p=0,21. Houve correlação positiva entre a área trabecular e a carga máxima (p=0,04; r=0,95. CONCLUSÃO: O ácido zoledrônico não influiu significativamente no peso dos animais. Os resultados mostraram aumento, não significante, tanto da resistência óssea diafisária tibial, como da área trabecular óssea.OBJECTIVE: To investigate clinical, biomechanic and histomorphometric effects of zoledronic acid on osteoporotic rats'tibiae after bilateral ooforectomy. METHODS: 40 female Wistar (Rattus novergicus albinus rats were prospectively

[gammadelta T cells stimulated by zoledronate kill osteosarcoma cells].

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Jiang, Hui; Xu, Qiang; Yang, Chao; Cao, Zhen-Guo; Li, Zhao-Xu; Ye, Zhao-Ming

2010-12-01

To investigate the cytotoxicity of human γδT cells from PBMCs stimulated by zoledronate against osteosarcoma cell line HOS in vitro and in vivo and evaluate the relavent pathways. The peripheral blood mononuclear cells (PBMCs)of healthy donors were stimulated by single dose zoledronate and cultured in the present of IL-2 for two weeks, analysising the percentage of γδT cells on a FACSCalibur cytometer.Study the cytotoxicity of γδT cells against the osteosarcoma line HOS using LDH release assay kit. Pre-treatment of γδT cells with anti-human γδTCR antibody, anti-human NKG2D antibody and concanamycin A to bolck the relavent pathways for evaluating the mechenisms of its cytotoxicity. In vivo, BALB/c mice were inoculated subcutaneously osteosarcoma cell HOS for developing hypodermal tumors. And they were randomized into two groups: unteated group, γδT cell therapy group. Tumor volume and weight of the two groups were compared. After two weeks of culture, γδT cells from zoledronate-stimulated PBMCs could reach (95±3)%. When the E:T as 6:1, 12:1, 25:1, 50:1, the percentage of osteosarcoma cell HOS killed by γδT cells was 26.8%, 31.5%, 37.8%, 40.9%, respectively.When anti-huma γδTCR antibody, anti-human NKG2D antibody and concanamycin A blocked the relavent pathways, the percentage was 32.3%, 4.7%, 16.7% ( E:T as 25:1), respectively. In vivo, the tumor inhibition rate of the group of γδT cell therapy was 42.78%. γδT cells derived from PBMCs stimulated by zoledronate can acquired pure γδT cells. And they show strong cytoxicity against osteosarcoma cell line HOS in vitro and in vivo.

The impact of zoledronic acid on regenerate and native bone after consolidation and removal of the external fixator: an animal model study.

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Saghieh, Said; Khoury, Nabil J; Tawil, Ayman; Masrouha, Karim Z; Musallam, Khaled M; Khalaf, Kinda; Dosh, Laura; Jaouhari, Rosemarie Reich; Birjawi, Ghina; El-Hajj-Fuleihan, Ghada

2010-02-01

We investigated the role of zoledronic acid on the regenerate and native bone after consolidation and removal of the external fixator in a rabbit model of distraction osteogenesis using 28 New Zealand white rabbits. The rabbits were randomly distributed into two groups. The first group received three doses of zoledronic acid (ZA) 0.1 mg/kg subcutaneously at weekly intervals while the second group received injections of sterile saline. Distraction started on day 7 at a rate of 0.8 mm/day for 12 days. At week 3 the average lengthening, regenerate density, and regenerate continuity were comparable between the two groups. At week 11 the regenerate in the treated group had a significant increase in Bone Mineral Density (BMD) and Bone Mineral Content (BMC) compared to the placebo group. On axial compression, the regenerate showed an increase in the peak load and a higher modulus of elasticity in the treated group. At 6 months, radiographs demonstrated signs of osteopenia of the proximal metaphysis in the control group, and failure of new bone formation around the pin sites in the treated group. BMC and BMD value differences between the two groups were not statistically significant. Histologically, there was persistence of more bone trabeculae in the medullary canal of the regenerate with the persistence of the pin-holes in the treated group. Mechanically, the regenerates in the treated group remain stronger in resisting the axial compression. The proximal fragment in the treated group exhibited a statistically significant decrease in the peak load, toughness and efail %. In conclusion, bisphosphonate-treated rabbits have a stronger regenerate during distraction, and directly after removal of the fixator. They do not develop disuse osteopenia in their lengthened tibia. This treatment may shorten the time in the external fixator and prevent fragility fractures in the treated extremity. However, its long-term safety has not yet been established. (c) 2009 Elsevier Inc. All

Toxicity of a dental adhesive compared with ionizing radiation and zoledronic acid.

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Alcaraz, Miguel; Olivares, Amparo; Achel, Daniel-Giyngiri; García-Cruz, Emilio; Fondevilla-Soler, Adriana; Canteras-Jordana, Manuel

2015-07-01

To determine the toxicity of aqueous dilutions of a universal self-priming dental adhesive (DA) and comparing these with those elicited by exposure to ionizing radiation (IR), Zoledronic acid (Z) treatment and the synergic effects of the combined treatment with IR+Z. The genotoxic effect of DA was determined by the increase in the frequency of micronuclei in cytokinesis-blocked in cultured human lymphocytes before and after exposure to 2Gy of X-rays. The cytotoxic effect was studied by using the MTT cell viability test in normal prostate cell lines (PNT2) after exposure to different X-ray doses (0Gy-20Gy). The cell lines divided into different groups and treated with different test substances: DA in presence of O2, DA in absence of O2, Z-treated and control. An in vitro dose-dependent and time-dependent cytotoxic effect of DA, Z and IR on PNT2 cells (p>0.001) was demonstrated. DA without-O2, following the recommendations of manufacturers, had a more pronounced effect of increasing cell death than DA with-O2 (p<0.001). In the genotoxicity assay, DA at 25% of its original concentration significantly increased chromosome damage (p<0.001). The samples studied were found to be toxic, and the samples photo-polymerized in absence of O2 showed a bigger cytotoxic effect comparable to the additive toxic effect showed by the combined treatment of IR+Z. Additional effort should be carried out to develop adhesives, which would reduce the release of hazardous substances; since toxic effects are similar to that reported by other agents whose clinical use is controlled by the health authorities.

Safety profile of the intravenous administration of brain-targeted stable nucleic acid lipid particles

Directory of Open Access Journals (Sweden)

Mariana Conceição

2016-03-01

Full Text Available In a clinical setting, where multiple administrations of the therapeutic agent are usually required to improve the therapeutic outcome, it is crucial to assess the immunogenicity of the administered nanoparticles. In this data work, we investigated the safety profile of the repeated intravenous administration of brain-targeted stable nucleic acid lipid particles (RVG-9r-targeted SNALPs. To evaluate local activation of the immune system, we performed analysis of mouse tissue homogenates and sections from cerebellum. To investigate peripheral activation of the immune system, we used serum of mice that were intravenously injected with RVG-9r-targeted SNALPs. These data are related and were discussed in the accompanying research article entitled “Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado–Joseph disease neurological phenotype” (Conceição et al., in press [1].

Zoledronate induces apoptosis in cells from fibro-cellular membrane of unicameral bone cyst (UBC).

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Yu, John; Chang, Seong-Sil; Suratwala, Sanjeev; Chung, Woo-Sik; Abdelmessieh, Peter; Lee, Hahn-Jun; Yang, Jay; Lee, Francis Young-In

2005-09-01

Unicameral bone cyst (UBC) is a benign cystic lesion in children which is prone to fracture. Various treatments are available, but recurrence after different types of percutaneous injection therapy can cause bone destruction and pathologic fracture. The potential therapeutic effects of anti-resorptive agents, such as bisphosphonates, have not been investigated for UBC. The objective of this study was to characterize the cells from the fibro-cellular membrane of unicameral bone cyst (UBC cells) and to determine whether zoledronate, a nitrogen-containing bisphosphonate, could induce apoptosis in UBC cells. Flow cytometry and immunoblotting were performed in order to determine whether zoledronate induced apoptosis. Cells derived from normal human trabecular bones were used as controls against UBC cells to compare the effect of zoledronate in inducing apoptosis. Immunohisto/cytochemistry (IHC/ICC) and mini-array analyses were performed on tissues and cultured cells. Isolated peripheral blood mononuclear cells were incubated with conditioned media from the UBC cells to determine whether they are capable of inducing osteoclastogenesis. UBC membrane is composed of cells staining positively with CD68, SDF-1, STRO-1 and RANKL, but in vitro cells showed no staining with antibodies to CD68 and STRO-1, suggesting that there was a clonal selection of stromal cells during cell culture. UBC cells also express RUNX2 (runt-related transcription factor-2, core binding factor-1), a key transcription factor for osteoblastic differentiation. In addition, media collected from UBC cells induced a generation of multi-nucleated osteoclast-like cells of peripheral blood mononuclear cells. Zoledronate induced apoptosis of UBC cells in a dose-dependent manner. Apoptosis was evidenced by induction of the active cleaved form of caspase-3. The baseline apoptotic fractions were similar in UBC cells and trabecular bone cells. However, in the overall apoptotic fractions in this study, trabecular

Effect of intravenous amino acids on interdigestive antroduodenal motility and small bowel transit time.

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Gielkens, H A; van den Biggelaar, A; Vecht, J; Onkenhout, W; Lamers, C B; Masclee, A A

1999-02-01

Patients on total parenteral nutrition have an increased risk of developing gallstones because of gall bladder hypomotility. High dose amino acids may prevent biliary stasis by stimulating gall bladder emptying. To investigate whether intravenous amino acids also influence antroduodenal motility. Eight healthy volunteers received, on three separate occasions, intravenous saline (control), low dose amino acids (LDA), or high dose amino acids (HDA). Antroduodenal motility was recorded by perfusion manometry and duodenocaecal transit time (DCTT) using the lactulose breath hydrogen test. DCTT was significantly prolonged during LDA and HDA treatment compared with control. The interdigestive motor pattern was maintained and migrating motor complex (MMC) cycle length was significantly reduced during HDA compared with control and LDA due to a significant reduction in phase II duration. Significantly fewer phase IIIs originated in the gastric antrum during LDA and HDA compared with control. Duodenal phase II motility index was significantly reduced during HDA, but not during LDA, compared with control. Separate intravenous infusion of high doses of amino acids in healthy volunteers: (1) modulates interdigestive antroduodenal motility; (2) shortens MMC cycle length due to a reduced duration of phase II with a lower contractile incidence both in the antrum and duodenum (phase I remains unchanged whereas the effect on phase III is diverse: in the antrum phase III is suppressed and in the duodenum the frequency is increased); and (3) prolongs interdigestive DCTT.

Sclerostin Blockade and Zoledronic Acid Improve Bone Mass and Strength in Male Mice With Exogenous Hyperthyroidism.

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Tsourdi, Elena; Lademann, Franziska; Ominsky, Michael S; Rijntjes, Eddy; Köhrle, Josef; Misof, Barbara M; Roschger, Paul; Klaushofer, Klaus; Hofbauer, Lorenz C; Rauner, Martina

2017-11-01

Hyperthyroidism in mice is associated with low bone mass, high bone turnover, and high concentrations of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either increasing bone formation with sclerostin antibodies (Scl-Ab) or reducing bone turnover with bisphosphonates on bone mass and strength in hyperthyroid mice. Twelve-week-old C57BL/6 male mice were rendered hyperthyroid using l-thyroxine (T4; 1.2 µg/mL added to the drinking water) and treated with 20 mg/kg Scl-Ab twice weekly or 100 µg/kg zoledronic acid (ZOL) once weekly or phosphate-buffered saline for 4 weeks. Hyperthyroid mice displayed a lower trabecular bone volume at the spine (-42%, P hyperthyroid mice increased trabecular bone volume at the spine by threefold and twofold, respectively. Serum bone formation and resorption markers were increased in hyperthyroid mice and suppressed by treatment with ZOL but not Scl-Ab. Trabecular bone stiffness at the lumbar vertebra was 63% lower in hyperthyroid mice (P hyperthyroidism, was increased by Scl-Ab by 71% and ZOL by 22% (both P hyperthyroid mice was restored by treatment with Scl-Ab and ZOL. Thus, bone-forming and antiresorptive drugs prevent bone loss in hyperthyroid mice via different mechanisms. Copyright © 2017 Endocrine Society.

Synergistic effects of intravenous and intra-articular tranexamic acid on reducing hemoglobin loss in revision total knee arthroplasty: a prospective, randomized, controlled study.

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Yuan, Xiangwei; Wang, Jiaxing; Wang, Qiaojie; Zhang, Xianlong

2018-04-01

Tranexamic acid decreases blood loss in primary total knee arthroplasty, and no related prospective randomized clinical trials have been conducted to evaluate the effectiveness and safety of tranexamic acid in revision total knee arthroplasty. Thus, we conducted this work to evaluate the synergistic effects of intravenous plus intra-articular tranexamic acid on reducing hemoglobin loss compared with intra-articular tranexamic acid alone in revision total knee arthroplasty. This prospective, controlled study randomized 96 patients undergoing revision total knee arthroplasty into two groups: an intravenous plus intra-articular tranexamic acid group (48 patients who received 20 mg/kg intravenous tranexamic acid and 3.0 g intra-articular tranexamic acid); and an intra-articular tranexamic acid alone group (48 patients who received the same intravenous volume of normal saline and 3.0 g intra-articular tranexamic acid). The primary outcome was hemoglobin loss. Secondary outcomes included the volume of drain output, the percentage of patients who received transfusions, the number of units transfused, and thromboembolic events. The baseline data, preoperative hemoglobin, and tourniquet time were similar in both groups. There was significantly less hemoglobin loss in the intravenous plus intra-articular tranexamic acid group compared with the intra-articular tranexamic acid alone group (2.7 ± 0.6 g/dL and 3.7 ± 0.7 g/dL; p tranexamic acid alone group, the intravenous plus intra-articular tranexamic acid group also had significantly less drain output, fewer patients who received transfusions, and fewer units transfused (all p tranexamic acid alone, combined intravenous plus intra-articular tranexamic acid significantly reduced hemoglobin loss and the need for transfusion without an apparent increase in thromboembolic events in patients who underwent revision total knee arthroplasty. © 2018 AABB.

[Single intravenous tranexamic acid dose to reduce blood loss in primary total knee replacement].

Science.gov (United States)

Sanz-Reig, J; Parra Ruiz, B; Ferrández Martínez, J; Martínez López, J F

2016-01-01

To evaluate the effectiveness and safety of a single intravenous dose of tranexamic acid in order to reduce blood loss in total knee replacement. Prospective observational study of the administration of tranexamic acid in patients undergoing primary total knee arthroplasty from November 2013 to February 2015, in which an autologous blood recovery system was used. The study included 98 patients, distributed into two groups of 49 patients according to whether or not they received intravenous tranexamic acid. The primary endpoint was the number of patients requiring autologous transfusion from the recovery system autologous blood recovery system. No drop-outs were recorded during follow-up. There were no significant differences between groups as regards the preoperative and hospital variables. The mean preoperative haemoglobin and haematocrit at 24 and 48 hours postoperatively were similar in both groups. The average volume of bleeding in the autologous blood recovery system and estimated average blood loss was lower in patients who had been administered tranexamic acid, with significant differences. No patients in the group that was administered tranexamic acid required blood autotransfusion. The transfusion rate was zero in the two groups. No adverse events related to the administration of tranexamic acid were recorded. Intravenous administration of tranexamic acid, according to the described protocol, has presented a non-autotransfusion or allo-transfusion rate of 100%, with no increased incidence of thrombotic events. Thus, its use in this group of patients is recommended. The indication should be individualized, its use justified in the patient medical records, and informed consent is mandatory. Copyright © 2015 SECOT. Published by Elsevier Espana. All rights reserved.

Dgroup: DG00787 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available DG00787 Chemical ... DGroup Zoledronic acid ... D08689 ... Zoledronic acid (INN) D01968 ... Zoledron...ic acid (USAN); Zoledronic acid hydrate (JAN) ... D06378 ... Zoledronate disodium (USAN) D06379 ... Zoledron...ate trisodium (USAN) D10515 ... Zoledronic acid hemipentahydrate (JAN) Other ... DG01600 ... Bisphosphonate ATC code: M05BA08 Bisphosphonates FDPS [HSA:2224] [KO:K00787] ...

Osteogenesis imperfecta type V: Genetic and clinical findings in eleven Chinese patients.

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Liu, Yi; Wang, Jiawei; Ma, Doudou; Lv, Fang; Xu, Xiaojie; Xia, Weibo; Jiang, Yan; Wang, Ou; Xing, Xiaoping; Zhou, Peiran; Wang, Jianyi; Yu, Wei; Li, Mei

2016-11-01

Osteogenesis imperfecta (OI) type V is a rare inherited disease characterized by multiple fractures, intraosseous membrane calcification, and hypercallus formation. We investigate the causative gene, phenotype and also observe the effects of zoledronic acid in Chinese OI type V patients. The clinical phenotype and causative gene mutation was investigated in eleven patients with type V OI. Patients were given a dose of zoledronic acid 5mg intravenously. Fracture incidence and Z-score of bone mineral density (BMD) were evaluated. Serum levels of biomarkers such as cross linked C-telopeptide of type I collagen (β-CTX) and safety parameters were assessed. The c.-14C>T mutation in the 5' untranslated region of IFITM5 was detected in all patients. The phenotype was largely variable, and no significant correlation of genotype and phenotype was found. After one dose of zoledronic acid infusion, fracture incidence significantly dropped from 2fractures/year before treatment to 0fracture/year after treatment (P=0.01). Z score of lumbar spine BMD elevated from -2.6 to -1.3 (P<0.001). Serum β-CTX level decreased by 50% (P<0.05). No serious adverse event was found. No obvious correlation was found between the genotype and phenotype. Zoledronic acid had significantly skeletal protective effects in OI of type V. Copyright © 2016 Elsevier B.V. All rights reserved.

Randomized Controlled Trial of Zoledronic Acid plus Chemotherapy versus Chemotherapy Alone as Neoadjuvant Treatment of HER2-Negative Primary Breast Cancer (JONIE Study.

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Yoshie Hasegawa

Full Text Available Zoledronic acid (ZOL is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. Its benefit for the prevention of skeletal complications due to bone metastases has been established. However, the antitumor efficacy of ZOL, although suggested by multiple preclinical and clinical studies, has not yet been clinically proven. We performed the present randomized Phase 2 trial to investigate the antitumor effect of ZOL with chemotherapy (CT.Asian patients with HER2-negative invasive breast cancer were randomly assigned to either the CT or CT+ZOL (CTZ group. One hundred and eighty-eight patients were randomized to either the CT group (n = 95 or the CTZ group (n = 93 from March 2010 to April 2012, and 180 patients were assessed. All patients received four cycles of FEC100 (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2, followed by 12 cycles of paclitaxel at 80 mg/m2 weekly. ZOL (4 mg was administered three to four times weekly for 7 weeks to the patients in the CTZ group. The primary endpoint was the pathological complete response (pCR rate, which was defined as no invasive cancer in the breast tissue specimen. Safety was assessed in all patients who received at least one dose of the study drug.This randomized controlled trial indicated that the rates of pCR in CTZ group (14.8% was doubled to CT group (7.7%, respectively (one-sided chi-square test, p = 0.068, though the additional efficacy of zoledronic acid was not demonstrated statistically. The pCR rate in postmenopausal patients was 18.4% and 5.1% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.071, and that in patients with triple-negative breast cancer was 35.3% and 11.8% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.112. Thus the addition of ZOL to neoadjuvant CT has potential anticancer benefits in postmenopausal patients and

Zoledronic acid at subtoxic dose extends osteoblastic stage span of primary human osteoblasts.

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Zara, Susi; De Colli, Marianna; di Giacomo, Viviana; Zizzari, Vincenzo Luca; Di Nisio, Chiara; Di Tore, Umberto; Salini, Vincenzo; Gallorini, Marialucia; Tetè, Stefano; Cataldi, Amelia

2015-04-01

This study aimed to check the effect of zoledronic acid (ZA) at subtoxic dose on human osteoblasts (HOs) in terms of cell viability, apoptosis occurrence, and differentiation induction. ZA belongs to the family of bisphosphonates (BPs), largely used in the clinical practice for the treatment of bone diseases, often associated with jaw osteonecrosis onset. Their pharmacological action consists in the direct block of the osteoclast-mediated bone resorption along with indirect action on osteoblasts. HOs were treated choosing the highest limit concentration (10(-5) M) which does not induce toxic effects. Live/dead staining, flow cytometry, mitochondrial membrane potential assay, osteocalcin western blotting, gp38 RT-PCR, collagen type I, PGE2, and IL-6 ELISA assays were performed. Similar viability level between control and ZA-treated samples is found along with no significant increase of apoptotic and necrotic cells in ZA-treated sample. To establish if an early apoptotic pathway was triggered, Bax expression and mitochondrial membrane potential were evaluated finding a higher protein expression in control sample and a good integrity of mitochondrial membrane in both experimental points. Type I collagen secretion and alkaline phosphatase (ALP) activity appear increased in ZA-treated sample, osteocalcin expression level is reduced in ZA-treated cells, whereas no modifications of gp38 mRNA level are evidenced. No statistical differences are identified in PGE2 secretion level whereas IL-6 secretion is lower in ZA-treated HOs with respect to control ones. These results highlight that ZA, delaying the osteoblastic differentiation process versus the osteocytic lineage, strengthens its pharmacological activity enhancing bone density. The knowledge of ZA effects on osteoblasts at subtoxic dose allows to improve therapeutic protocols in order to strengthen drug pharmacological activity through a combined action on both osteoclastic and osteoblastic cells.

Uric acid therapy improves the outcomes of stroke patients treated with intravenous tissue plasminogen activator and mechanical thrombectomy.

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Chamorro, Ángel; Amaro, Sergio; Castellanos, Mar; Gomis, Meritxell; Urra, Xabier; Blasco, Jordi; Arenillas, Juan F; Román, Luis S; Muñoz, Roberto; Macho, Juan; Cánovas, David; Marti-Fabregas, Joan; Leira, Enrique C; Planas, Anna M

2017-06-01

Background Numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischemic stroke, making the search for new treatments imperative. Uric acid is an endogenous antioxidant making it a drug candidate to improve stroke outcomes. Aim To report the effects of uric acid therapy in stroke patients receiving intravenous thrombolysis and mechanical thrombectomy. Methods Forty-five patients with proximal vessel occlusions enrolled in the URICO-ICTUS trial received intravenous recombinant tissue plasminogen activator within 4.5 h after stroke onset and randomized to intravenous 1000 mg uric acid or placebo (NCT00860366). These patients also received mechanical thrombectomy because a brain computed tomogaphy angiography confirmed the lack of proximal recanalization at the end of systemic thrombolysis. The primary outcome was good functional outcome at 90 days (modified Rankin Score 0-2). Safety outcomes included mortality, symptomatic intracerebral bleeding, and gout attacks. Results The rate of successful revascularization was >80% in the uric acid and the placebo groups but good functional outcome was observed in 16 out of 24 (67%) patients treated with uric acid and 10 out of 21 (48%) treated with placebo (adjusted Odds Ratio, 6.12 (95% CI 1.08-34.56)). Mortality was observed in two out of 24 (8.3%) patients treated with uric acid and one out of 21 (4.8%) treated with placebo (adjusted Odds Ratio, 3.74 (95% CI 0.06-226.29)). Symptomatic cerebral bleeding and gout attacks were similar in both groups. Conclusions Uric acid therapy was safe and improved stroke outcomes in stroke patients receiving intravenous thrombolysis followed by thrombectomy. Validation of this simple strategy in a larger trial is urgent.

Safety of intravenous tranexamic acid in patients undergoing majororthopaedic surgery: a meta-analysis of randomised controlled trials

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Franchini, Massimo; Mengoli, Carlo; Marietta, Marco; Marano, Giuseppe; Vaglio, Stefania; Pupella, Simonetta; Mannucci, Pier Mannuccio; Liumbruno, Giancarlo M.

2018-01-01

Among the various pharmacological options to decrease peri-operative bleeding, tranexamic acid appears to be one of the most interesting. Several trials have consistently documented the efficacy of this synthetic drug in reducing the risk of blood loss and the need for allogeneic blood transfusion in patients undergoing total hip and knee arthroplasty. The safety of intravenous tranexamic acid in major orthopaedic surgery, particularly regarding the risk of venous thromboembolism, was systematically analysed in this review. A systematic search of the literature identified 73 randomised controlled trials involving 4,174 patients and 2,779 controls. The raw overall incidence of venous thromboembolism was 2.1% in patients who received intravenous tranexamic acid and 2.0% in controls. A meta-analytic pooling showed that the risk of venous thromboembolism in tranexamic acid-treated patients was not significantly different from that of controls (risk difference: 0.01%, 95% confidence interval [CI]: −0.05%, 0.07%; risk ratio: 1.067, 95% CI: 0.760–1.496). Other severe drug-related adverse events occurred very rarely (0.1%). In conclusion, the results of this systematic review and meta-analysis show that intravenous tranexamic acid is a safe pharmacological treatment to reduce blood loss and transfusion requirements in patients undergoing major orthopaedic surgery. PMID:29337665

Early, middle, or late administration of zoledronate alleviates spontaneous nociceptive behavior and restores functional outcomes in a mouse model of CFA-induced arthritis.

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Morado-Urbina, Carlos Eduardo; Alvarado-Vázquez, Perla Abigail; Montiel-Ruiz, Rosa Mariana; Acosta-González, Rosa Issel; Castañeda-Corral, Gabriela; Jiménez-Andrade, Juan Miguel

2014-11-01

This study was performed to evaluate whether early, middle, or late treatment of zoledronate, an approved bisphosphonate that blocks bone resorption, can reduce nociceptive behaviors in a mouse arthritis model. Arthritis was produced by repeated intra-articular knee injections of complete Freund's adjuvant (CFA). A dose-response curve with zoledronate (3, 30, 100, and 300 μg/kg, i.p., day 4 to day 25, twice weekly for 3 weeks) was performed, and the most effective dose of zoledronate (100 μg/kg, i.p.) was initially administered at different times of disease progression: day 4 (early), day 15 (middle), or day 21 (late) and continued until day 25 after the first CFA injection. Flinching of the injected extremity (spontaneous nociceptive behavior), vertical rearings and horizontal activity (functional outcomes), and knee edema were assessed. Zoledronate improved both functional outcomes and reduced flinching behavior. At day 25, the effect of zoledronate on flinching behavior and vertical rearings was greater in magnitude when it was given early or middle rather than late in the treatment regimen. Chronic zoledronate did not reduce knee edema in CFA-injected mice nor functional outcomes in naïve mice by itself. These results suggest that zoledronate may have a positive effect on arthritis-induced nociception and functional disabilities. © 2014 Wiley Periodicals, Inc.

Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment

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Vessella Robert L

2006-01-01

Full Text Available Abstract Background After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL, a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment. Methods Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis. Results ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone. Conclusion In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option.

Zoledronic acid produces combinatory anti-tumor effects with cisplatin on mesothelioma by increasing p53 expression levels.

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Shinya Okamoto

Full Text Available We examined anti-tumor effects of zoledronic acid (ZOL, one of the bisphosphonates agents clinically used for preventing loss of bone mass, on human mesothelioma cells bearing the wild-type p53 gene. ZOL-treated cells showed activation of caspase-3/7, -8 and -9, and increased sub-G1 phase fractions. A combinatory use of ZOL and cisplatin (CDDP, one of the first-line anti-cancer agents for mesothelioma, synergistically or additively produced the cytotoxicity on mesothelioma cells. Moreover, the combination achieved greater anti-tumor effects on mesothelioma developed in the pleural cavity than administration of either ZOL or CDDP alone. ZOL-treated cells as well as CDDP-treated cells induced p53 phosphorylation at Ser 15, a marker of p53 activation, and up-regulated p53 protein expression levels. Down-regulation of p53 levels with siRNA however did not influence the ZOL-mediated cytotoxicity but negated the combinatory effects by ZOL and CDDP. In addition, ZOL treatments augmented cytotoxicity of adenoviruses expressing the p53 gene on mesothelioma. These data demonstrated that ZOL-mediated augmentation of p53, which was not linked with ZOL-induced cytotoxicity, played a role in the combinatory effects with a p53 up-regulating agent, and suggests a possible clinical use of ZOL to mesothelioma with anti-cancer agents.

Comparison of topical versus intravenous tranexamic acid in primary total knee arthroplasty: a meta-analysis of randomized controlled and prospective cohort trials.

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Wang, Hao; Shen, Bin; Zeng, Yi

2014-12-01

There has been much debate and controversy about the optimal regimen of tranexamic acid in primary total knee arthroplasty. The purpose of this study was to undertake a meta-analysis to compare the efficacy of topical and intravenous regimen of tranexamic acid in primary total knee arthroplasty. A systematic review of the electronic databases PubMed, CENTRAL, Web of Science, and Embase was undertaken. All randomized controlled trials and prospective cohort studies evaluating the effectiveness of topical and intravenous tranexamic acid during primary total knee arthroplasty were included. The focus of the analysis was on the outcomes of blood loss, transfusion rate, and thromboembolic complications. Subgroup analysis was performed when possible. Of 328 papers identified, six trials were eligible for data extraction and meta-analysis comprising 679 patients (739 knees). We found no statistically significant difference between topical and intravenous administration of tranexamic acid in terms of blood loss, transfusion requirements and thromboembolic complications. Topical tranexamic acid has a similar efficacy to intravenous tranexamic acid in reducing both blood loss and transfusion rate without sacrificing safety in primary total knee arthroplasty. II. Copyright © 2014 Elsevier B.V. All rights reserved.

Local application of zoledronate for maximum anchorage during space closure.

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Ortega, Adam J A J; Campbell, Phillip M; Hinton, Robert; Naidu, Aparna; Buschang, Peter H

2012-12-01

Orthodontists have used various compliance-dependent physical means such as headgears and intraoral appliances to prevent anchorage loss. The aim of this study was to determine whether 1 local application of the bisphosphonate zoledronate could be used to prevent anchorage loss during extraction space closure in rats. Thirty rats had their maxillary left first molars extracted and their maxillary left second molars protracted into the extraction space with a 10-g nickel-titanium closing coil for 21 days. Fifteen control rats received a local injection of phosphate-buffered saline solution, and 15 experimental rats received 16 μg of the bisphosphonate zoledronate. Bisphosphonate was also delivered directly into the extraction site and left undisturbed for 5 minutes. Cephalograms and incremental thickness gauges were used to measure tooth movements. Tissues were analyzed by microcomputed tomography and histology. The control group demonstrated significant (P <0.05) tooth movements throughout the 21-day period. They showed significantly greater tooth movements than the experimental group beginning in the second week. The experimental group showed no significant tooth movement after the first week. The microcomputed tomography and histologic observations showed significant bone loss in the extraction sites and around the second molars of the controls. In contrast, the experimental group had bone preservation and bone fill. There was no evidence of bisphosphonate-associated osteonecrosis in any sample. A single small, locally applied dose of zoledronate provided maximum anchorage and prevented significant bone loss. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Effects of intravenous solutions on acid-base equilibrium: from crystalloids to colloids and blood components.

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Langer, Thomas; Ferrari, Michele; Zazzeron, Luca; Gattinoni, Luciano; Caironi, Pietro

2014-01-01

Intravenous fluid administration is a medical intervention performed worldwide on a daily basis. Nevertheless, only a few physicians are aware of the characteristics of intravenous fluids and their possible effects on plasma acid-base equilibrium. According to Stewart's theory, pH is independently regulated by three variables: partial pressure of carbon dioxide, strong ion difference (SID), and total amount of weak acids (ATOT). When fluids are infused, plasma SID and ATOT tend toward the SID and ATOT of the administered fluid. Depending on their composition, fluids can therefore lower, increase, or leave pH unchanged. As a general rule, crystalloids having a SID greater than plasma bicarbonate concentration (HCO₃-) cause an increase in plasma pH (alkalosis), those having a SID lower than HCO₃- cause a decrease in plasma pH (acidosis), while crystalloids with a SID equal to HCO₃- leave pH unchanged, regardless of the extent of the dilution. Colloids and blood components are composed of a crystalloid solution as solvent, and the abovementioned rules partially hold true also for these fluids. The scenario is however complicated by the possible presence of weak anions (albumin, phosphates and gelatins) and their effect on plasma pH. The present manuscript summarises the characteristics of crystalloids, colloids, buffer solutions and blood components and reviews their effect on acid-base equilibrium. Understanding the composition of intravenous fluids, along with the application of simple physicochemical rules best described by Stewart's approach, are pivotal steps to fully elucidate and predict alterations of plasma acid-base equilibrium induced by fluid therapy.

Combined Intra-Articular and Intravenous Tranexamic Acid Reduces Blood Loss in Total Knee Arthroplasty

DEFF Research Database (Denmark)

Nielsen, Christian Skovgaard; Jans, Øivind; Ørsnes, Thue

2016-01-01

BACKGROUND: In total knee arthroplasty, both intravenous (IV) and intra-articular (IA) administration of tranexamic acid (TXA) have been shown to reduce blood loss in several randomized controlled trials, although routine use of systemic TXA is considerably more common. However, to our knowledge...

Fracture during intravenous bisphosphonate treatment in a child with osteogenesis imperfecta: an argument for a more frequent, low-dose treatment regimen.

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Biggin, Andrew; Briody, Julie N; Ormshaw, Elizabeth; Wong, Karen K Y; Bennetts, Bruce H; Munns, Craig F

2014-01-01

Intravenous bisphosphonate therapy is the mainstay of medical treatment in osteogenesis imperfecta (OI) and has been shown to increase bone mass, decrease bone pain, improve mobility, and reduce the incidence of fractures. Sclerotic metaphyseal lines parallel to the growth plate are seen on long bone radiographs following cyclical intravenous therapy. These areas create stress risers within the bone that may act as foci for subsequent fractures as exemplified in this clinical case. An 8-year-old girl with OI sustained a distal radial fracture following 3 years of treatment with 6-monthly intravenous zoledronate. Her diagnosis, response to treatment, and subsequent fracture at a sclerotic metaphyseal line is described. Peripheral quantitative computer tomography was used to characterise the presence of multiple stress risers at the distal forearm. Trabecular bone mineral density fluctuated from 34 to 126% compared to neighbouring 2-mm regions. There remain many unanswered questions about optimal bisphosphonate treatment regimens in children with OI. The formation of stress risers following intravenous bisphosphonate treatment raises the hypothesis that a more frequent and low-dose bisphosphonate regimen would provide more uniform dosing of bone in the growing child and reduce the likelihood of fractures compared to current treatment practices.

Effect of intravenous omega-3 fatty acid infusion and hemodialysis on fatty acid composition of free fatty acids and phospholipids in patients with end-stage renal disease.

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Madsen, Trine; Christensen, Jeppe Hagstrup; Toft, Egon; Aardestrup, Inge; Lundbye-Christensen, Søren; Schmidt, Erik B

2011-01-01

Patients treated with hemodialysis (HD) have been reported to have decreased levels of ω-3 polyunsaturated fatty acids (PUFAs) in plasma and cells. The aim of this study was to investigate the effect of ω-3 PUFAs administered intravenously during HD, as well as the effect of HD treatment, on the fatty acid composition of plasma free fatty acids (FFAs), plasma phospholipids, and platelet phospholipids. Forty-four HD patients were randomized to groups receiving either a single dose of a lipid emulsion containing 4.1 g of ω-3 PUFAs or placebo (saline) administered intravenously during HD. Blood was drawn immediately before (baseline) and after (4 hours) HD and before the next HD session (48 hours). Fatty acid composition was measured using gas chromatography. The increase in ω-3 FFAs was greater in the ω-3 PUFA group compared with the placebo group, whereas the increase in total FFAs was similar between the 2 groups. In the ω-3 PUFA group, ω-3 PUFAs in plasma phospholipids were higher after 48 hours than at baseline, and in platelet phospholipids, ω-3 PUFAs increased after 4 hours. In the placebo group, no changes were observed in ω-3 PUFAs in plasma and platelet phospholipids. Intravenous ω-3 PUFAs administered during HD caused a transient selective increase in ω-3 FFA concentration. Furthermore, ω-3 PUFAs were rapidly incorporated into platelets, and the content of ω-3 PUFAs in plasma phospholipids increased after 48 hours.

The Effect of 3 Versus 6 Years of Zoledronic Acid Treatment of Osteoporosis: A Randomized Extension to the HORIZON-Pivotal Fracture Trial (PFT)

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Black, Dennis M; Reid, Ian R; Boonen, Steven; Bucci-Rechtweg, Christina; Cauley, Jane A; Cosman, Felicia; Cummings, Steven R; Hue, Trisha F; Lippuner, Kurt; Lakatos, Peter; Leung, Ping Chung; Man, Zulema; Martinez, Ruvie Lou Maria; Tan, Monique; Ruzycky, Mary Ellen; Su, Guoqin; Eastell, Richard

2012-01-01

Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly–Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue

Combination Intravenous and Intra-Articular Tranexamic acid compared with Intravenous Only Administration and No Therapy in Total Knee Arthroplasty: A Case Series Study

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Chris Buntting

2016-07-01

This study supports the existing literature and suggests that the use of IV Tranexamic acid alone or in combination with intra-articular dose in TKA may reduce the requirement for transfusion (Level IV evidence. Furthermore, this study suggests that the use of tranexamic acid as a combination of Intravenous and intra-articular administration has no effect on range of motion, or medical complications during hospital stay. Although it was not a statistically significant finding, our study suggested a trend towards a greater reduction in haemoglobin and haematocrit fall in the combination therapy group when compared to IV Tranexamic acid alone

Effect of low-level laser therapy on tissue repair after dental extraction in rats administered zoledronic acid and dexamethasone

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Weber, João Batista Blessmann; Camilotti, Renata Stifelman; Jasper, Juliana; Casagrande, Liliane Cristina Onofre; Maito, Fábio Luiz Dal Moro

2017-05-01

Bisphosphonates (BPs) are being increasingly used for the treatment of metabolic and oncological pathologies involving the skeletal system. Because of the severity of the BP associated osteonecrosis of the jaws, the difficulties of treatment, and patient discomfort, additional support methods for their management are needed. Laser therapy has an easy handling, photobiostimulator effect on tissues healing, so it can be considered a preferred therapy. The aim of this study was to evaluate the influence of low-level laser therapy in the 685- and 830-nm wavelength in the healing process of the bone and soft tissues in rats under BP therapy [zoledronic acid (ZA)] and dexamethasone concomitantly that underwent a surgery for the extraction of upper molars. There were statistically significant differences in the clinical evaluation of the wound and the weight of the animals. Regarding the histological evaluation, it was possible to observe the different maturations of the healing stage between groups. The effect of drug therapy with ZA and dexamethasone in the bone tissue repair process induces osteonecrosis of the jaw in rats and slows down the healing process. In the laser groups, at the stipulated dosimetry, a positive influence on the bone and soft tissue repair process was observed.

USE OF ZOLEDRONIC ACID AND A RАNK LIGAND INHIBITOR IN THE PALLIATIVE TREATMENT OF CANCERS OF THE PROSTATE WITH BONE METASTASES

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S. V. Mushigin

2013-01-01

Full Text Available In the metastatic patterns of the cancer, the tumor foci are located more frequently in the tubular bones and vertebral column, just less frequently in the bones of the pelvis, and even more rarely in those of the shoulder and skull. Bone pain is usually related to the involvement of the periosteum that has an extensive network of nociceptors. Auxiliary exposures that directly affect the intensity of pain syndrome and the strength of bone structures are used in addition to basic therapy options for cancer of the prostate. Among these agents there are bisphosphonates. Once ingested, bisphosphonates are transported by blood to the areas of active bone tissue rearrangement where they are tightly bound to the mineral matrix. Their administration causes a considerable reduction in pain syndrome, a decrease in the frequency of complications of bone metastases, and an increase in time before a first bone complication. Antiresorptive therapy including particularly zoledronic acid (resorba or denosumab is a necessary treatment option in the above category of patients with bone metastases.

USE OF ZOLEDRONIC ACID AND A RАNK LIGAND INHIBITOR IN THE PALLIATIVE TREATMENT OF CANCERS OF THE PROSTATE WITH BONE METASTASES

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S. V. Mushigin

2014-07-01

Full Text Available In the metastatic patterns of the cancer, the tumor foci are located more frequently in the tubular bones and vertebral column, just less frequently in the bones of the pelvis, and even more rarely in those of the shoulder and skull. Bone pain is usually related to the involvement of the periosteum that has an extensive network of nociceptors. Auxiliary exposures that directly affect the intensity of pain syndrome and the strength of bone structures are used in addition to basic therapy options for cancer of the prostate. Among these agents there are bisphosphonates. Once ingested, bisphosphonates are transported by blood to the areas of active bone tissue rearrangement where they are tightly bound to the mineral matrix. Their administration causes a considerable reduction in pain syndrome, a decrease in the frequency of complications of bone metastases, and an increase in time before a first bone complication. Antiresorptive therapy including particularly zoledronic acid (resorba or denosumab is a necessary treatment option in the above category of patients with bone metastases.

Osteoclasts but not osteoblasts are affected by a calcified surface treated with zoledronic acid in vitro

International Nuclear Information System (INIS)

Schindeler, Aaron; Little, David G.

2005-01-01

Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. Recent interest has centered on the effects of bisphosphonates on osteoblasts. Chronic dosing of osteoblasts with solubilized bisphosphonates has been reported to enhance osteogenesis and mineralization in vitro. However, this methodology poorly reflects the in vivo situation, where free bisphosphonate becomes rapidly bound to mineralized bone surfaces. To establish a more clinically relevant cell culture model, we cultured bone cells on calcium phosphate coated quartz discs pre-treated with the potent nitrogen-containing bisphosphonate, zoledronic acid (ZA). Binding studies utilizing [ 14 C]-labeled ZA confirmed that the bisphosphonate bound in a concentration-dependent manner over the 1-50 μM dose range. When grown on ZA-treated discs, the viability of bone-marrow derived osteoclasts was greatly reduced, while the viability and mineralization of the osteoblastic MC3T3-E1 cell line were largely unaffected. This suggests that only bone resorbing cells are affected by bound bisphosphonate. However, this system does not account for transient exposure to unbound bisphosphonate in the hours following a clinical dosing. To model this event, we transiently treated osteoblasts with ZA in the absence of a calcified surface. Osteoblasts proved highly resistant to all transitory treatment regimes, even when utilizing ZA concentrations that prevented mineralization and/or induced cell death when dosed chronically. This study represents a pharmacologically more relevant approach to modeling bisphosphonate treatment on cultured bone cells and implies that bisphosphonate therapies may not directly affect osteoblasts at bone surfaces

Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid

International Nuclear Information System (INIS)

Basso, F G; Pansani, T N; Turrioni, A P S; Hebling, J; De Souza Costa, C A; Kurachi, C; Bagnato, V S

2013-01-01

Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm −2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal–Wallis and Mann–Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions. (paper)

Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid

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Basso, F. G.; Pansani, T. N.; Turrioni, A. P. S.; Kurachi, C.; Bagnato, V. S.; Hebling, J.; de Souza Costa, C. A.

2013-05-01

Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm-2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal-Wallis and Mann-Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions.

Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism.

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Otto, Sven; Pautke, Christoph; Opelz, Christine; Westphal, Ines; Drosse, Inga; Schwager, Joanna; Bauss, Frieder; Ehrenfeld, Michael; Schieker, Matthias

2010-11-01

Osteonecrosis of the jaw has been reported in patients receiving high doses of intravenous nitrogen-containing bisphosphonates (N-BPs) because of malignant disease. The exact pathomechanisms have been elusive and questions of paramount importance remain unanswered. Recent studies have indicated toxic effects of bisphosphonates on different cell types, apart from osteoclast inhibition. Multipotent stem cells play an important role in the processes of wound healing and bone regeneration, which seem to be especially impaired in the jaws of patients receiving high doses of N-BPs. Therefore, the aim of the present study was to investigate the effects of different bisphosphonate derivatives and dose levels combined with varying pH levels on the mesenchymal stem cells in vitro. The effect of 2 N-BPs (zoledronate and ibandronate) and 1 non-N-BP (clodronate) on immortalized mesenchymal stem cells was tested at different concentrations, reflecting 1, 3, and 6 months and 1, 3, 5, and 10 years of exposure to standard oncology doses of the 2 N-BPs and equimolar concentrations of clodronate at different pH values (7.4, 7.0, 6.7, and 6.3). Cell viability and activity were analyzed using a WST assay. Cell motility was investigated using scratch wound assays and visualized using time-lapse microscopy. Both types of bisphosphonates revealed remarkable differences. Zoledronate and ibandronate showed a dose- and pH-dependent cellular toxicity. Increasing concentrations of both N-BPs and an acidic milieu led to a significant decrease in cell viability and activity (P key role in the pathogenesis of osteonecrosis of the jaw in patients receiving high doses of N-BPs for malignant diseases. Also the potency of N-BPs might be different, suggesting a greater risk of osteonecrosis of the jaw with zoledronate. Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Preparation and in vivo biological investigations on a novel radioligand for bone scanning: technetium-99m-labeled zoledronic acid derivative

International Nuclear Information System (INIS)

Lin Jianguo; Qiu Ling; Cheng Wen; Luo Shineng; Ye Wanzhong

2011-01-01

Introduction: To enable imaging at an earlier time after injection, a radiopharmaceutical with higher affinity for bone, larger ratio of bone-to-soft tissue uptake and more rapid clearance from blood is required. The nature of diphosphonic acid is a key factor to determine the advantages of the radiopharmaceuticals. The purpose of this study is to optimize the linker chain between the imidazolyl and geminal diphosphonate group in the zoledronic acid (ZL) to develop novel single photon emission computed tomography (SPECT) bone imaging agent. Methods: A novel ZL derivative, 1-hydroxy-3-(1H-imidazol-1-yl)propane-1,1-diyldiphosphonic acid (IPrDP), was successfully prepared and labeled with 99m Tc in a high labeling yield. Biodistribution of 99m Tc-IPrDP and 99m Tc-ZL in normal mice were studied and compared. SPECT bone scanning was performed on the rabbit and a series of dynamic and static images were recorded by Philips SKY Light emission computed tomography. Results: In the biodistribution studies, 99m Tc-IPrDP exhibits significant advantages on the bone resorption and the clearance from soft tissues compared with 99m Tc-ZL. Kinetics of blood clearance in mice showed that T 1/2α and T 1/2β of 99m Tc-IPrDP were 1.47 min and 46.47 min, while those of 99m Tc-ZL were 2.28 and 52.63 min respectively. Excellent images of the rabbit skeleton can be quickly obtained for 99m Tc-IPrDP, which was faster than 99m Tc-ZL and the clinically widely used bone imaging agent 99m Tc-MDP (technetium-99m labeled with methylenediphosphonate). Conclusions: 99m Tc-IPrDP possesses excellent characteristics for the potential application as a novel bone scanning agent.

The IL-6 receptor super-antagonist Sant7 enhances antiproliferative and apoptotic effects induced by dexamethasone and zoledronic acid on multiple myeloma cells.

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Tassone, Pierfrancesco; Galea, Eulalia; Forciniti, Samantha; Tagliaferri, Pierosandro; Venuta, Salvatore

2002-10-01

Interleukin-6 (IL-6) is the major growth and survival factor for multiple myeloma (MM), and has been shown to protect MM cells from apoptosis induced by a variety of agents. IL-6 receptor antagonists, which prevent the assembly of functional IL-6 receptor complexes, inhibit cell proliferation and induce apoptosis in MM cells. We have investigated whether the IL-6 receptor super-antagonist Sant7 might enhance the antiproliferative and apoptotic effects induced by the combination of dexamethasone (Dex) and zoledronic acid (Zln) on human MM cell lines and primary cells from MM patients. Here we show that each of these compounds individually induced detectable antiproliferative effects on MM cells. Sant7 significantly enhanced growth inhibition and apoptosis induced by Dex and Zln on both MM cell lines and primary MM cells. These results indicate that overcoming IL-6 mediated cell resistance by Sant7 potentiates the effect of glucocorticoides and bisphosphonates on MM cell growth and survival, providing a rationale for therapies including IL-6 antagonists in MM.

Stimulation of gluconeogenesis by intravenous lipids in preterm infants: response depends on fatty acid profile

NARCIS (Netherlands)

van Kempen, Anne A. M. W.; van der Crabben, Saskia N.; Ackermans, Mariëtte T.; Endert, Erik; Kok, Joke H.; Sauerwein, Hans P.

2006-01-01

In preterm infants, both hypo- and hyperglycemia are a frequent problem. Intravenous lipids can affect glucose metabolism by stimulation of gluconeogenesis by providing glycerol, which is a gluconeogenic precursor, and/or free fatty acids (FFA), which are stimulants of the rate of gluconeogenesis.

Extracellular Ca(2+)-dependent enhancement of cytocidal potency of zoledronic acid in human oral cancer cells.

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Inoue, Sayaka; Arai, Naoya; Tomihara, Kei; Takashina, Michinori; Hattori, Yuichi; Noguchi, Makoto

2015-08-15

Direct antitumor effects of bisphosphonates (BPs) have been demonstrated in various cancer cells in vitro. However, the effective concentrations of BPs are typically much higher than their clinically relevant concentrations. Oral cancers frequently invade jawbone and may lead to the release of Ca(2+) in primary lesions. We investigated the effects of the combined application of zoledronic acid (ZA) and Ca(2+) on proliferation and apoptosis of oral cancer cells. Human oral cancer cells, breast cancer cells, and colon cancer cells were treated with ZA at a wide range of concentrations in different Ca(2+) concentration environments. Under a standard Ca(2+) concentration (0.6mM), micromolar concentrations of ZA were required to inhibit oral cancer cell proliferation. Increasing extracellular Ca(2+) concentrations greatly enhanced the potency of the ZA cytocidal effect. The ability of Ca(2+) to enhance the cytocidal effects of ZA was negated by the Ca(2+)-selective chelator EGTA. In contrast, the cytocidal effect of ZA was less pronounced in breast and colon cancer cells regardless of whether extracellular Ca(2+) was elevated. In oral cancer cells incubated with 1.6mM Ca(2+), ZA up-regulated mitochondrial Bax expression and increased mitochondrial Ca(2+) uptake. This was associated with decreased mitochondrial membrane potential and increased release of cytochrome c. We suggest that ZA can specifically produce potent cytocidal activity in oral cancer cells in an extracellular Ca(2+)-dependent manner, implying that BPs may be useful for treatment of oral squamous cell carcinoma with jawbone invasion leading to the hypercalcemic state. Copyright © 2015 Elsevier B.V. All rights reserved.

The effects of intra-articular tranexamic acid given intraoperatively and intravenous tranexamic acid given preoperatively on post surgical bleeding and transfusion rate post total knee arthroplasty

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Aryo N. Triyudanto

2017-01-01

Full Text Available Background: Despite the advances in the design and fixation of implants in total knee replacement (TKR. the amount of postoperative bleeding is still an important issue that has not been resolved. This study aimed to measure the effectiveness of various tranexamic acid administration.Methods: This was a randomized controlled trial study, held from August 2014 to February 2016 at Cipto Mangunkusumo Hospital, Jakarta. Twenty two patients having TKR were divided into three groups: the control group, the tranexamic acid intra-articular-intraoperative group, and the intravenous preoperative group. Intraoperative bleeding, haemoglobin (Hb level on preoperative to five-day-post-surgery, total drain production, total blood tranfusion needed and the drain removal timing were recorded and compared. Numerical data were analyzed by using parametric and non-parametric test, depended on the normality of the data.Results: The amount of blood transfusion needed in both the intra-articular group (200±SD 100 mL and the intravenous group (238±SD 53 mL were significantly different compared to those in the control group (1,016±SD 308.2 mL (p=0.001. Meanwhile, there was no significant difference between the amount of blood transfusion needed in the intra-articular group and the intravenous group. Total drain production in the intra-articular group (328±SD 193 mL and intravenous group (391±SD 185 mL was significantly different compared to the control group (652±SD 150 mL (p=0.003. No significant difference between the levels of both preoperative and postoperative haemoglobin, the amount of intraoperative bleeding, and the duration of drain usage.Conclusion: Intravenous and intra-articular tranexamic acid effectively decreased transfusion volume and drain production in patients undergoing TKR.

Home-based zoledronic acid infusion therapy in patients with solid tumours: compliance and patient-nurse satisfaction.

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Lebret, Thierry; Mouysset, Jean-Loup; Lortholary, Alain; El Kouri, Claude; Bastit, Laurent; Ktiouet, Meryem; Slimane, Khemaies; Murraciole, Xavier; Guérif, Stéphane

2013-06-01

This study aimed to explore patient and nurse satisfaction, compliance with best practice, technical feasibility and safety of home infusion of the bisphosphonate zoledronic acid (ZOL). This was a prospective 1-year survey of home ZOL therapy (4 mg Zometa, 15-min i.v., every 3-4 weeks) in patients with bone metastases secondary to a solid malignancy. A physician questionnaire, nurse satisfaction/feasibility questionnaire and patient satisfaction questionnaire were administered at several time-points. Physician participation rate was 56.5% (87/154). Physicians enrolled 818 patients visited by 381 predominantly community nurses. Of the 788 case report forms received, 763 met inclusion criteria. Patient characteristics were as follows: median age, 68 years (30-95); M/F, 40/60; ECOG-PS 0 or 1, 78.6%; and primary tumour site, breast (55.2%), prostate (28.4%), lung (7.2%) or other (9.4%). Nurse satisfaction rates were high: organisation of home ZOL therapy, 90.9%; ease of infusion, 96.7%; patient-nurse relationship, 97.5%; and relationship with hospital staff, 73%. Patient satisfaction was also very high (95.3%). The main reasons were quality of the nurse-patient relationship (57.6%), less travel/waiting (68.8%), home environment (52.9%) and less disruption to daily routine (36.6%). ZOL therapy was well tolerated, the discontinuation rate due to adverse events (including deaths whether related to diseases progression or not) was 33.6%. The incidence of osteonecrosis of the jaw was 0.6% and of fractures, 0.2%. Practitioner compliance with best practice was 76.7-83.7% for recommended and/or tolerated dosage, 73% for dental hygiene checks at inclusion and 48-56% thereafter, 66% for pre-infusion hydration, and often undocumented for calcium/vitamin D supplementation. Home ZOL therapy was well tolerated. Both patient and nurse satisfaction were very high. However, better compliance with best practice should be encouraged.

In vitro comparison of new bisphosphonic acids and zoledronate effects on human gingival fibroblasts viability, inflammation and matrix turnover.

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De Colli, Marianna; Tortorella, Paolo; Marconi, Guya Diletta; Agamennone, Mariangela; Campestre, Cristina; Tauro, Marilena; Cataldi, Amelia; Zara, Susi

2016-11-01

Bisphosphonates (BPs) are drugs clinically used in resorptive diseases. It was already proved that some clinically relevant BPs can inhibit a class of enzymes called matrix metalloproteinases (MMPs), required during tissue remodelling. Combining the arylsulfonamide function with the bisphosphonic group, several compounds were synthesized to obtain selective inhibitors of MMPs. The aim of the present study was to compare the effect of zoledronic acid (ZA), the most potent bisphosphonate available as therapy, with new sulfonamide containing BPs in an in vitro model of human gingival fibroblasts (HGFs). Western blot was used to measure procollagen I, β1 integrin MMP-8 and MMP-9, phase contrast and MTT for cell viability; L-lactate-dehydrogenase (LDH) measurement was performed for toxicity evaluation and ELISA for prostaglandin E 2 (PGE 2 ) secretion assessment. When compared with ZA, the treatment with the newly synthesized compounds shows increasing viability, procollagen I expression and decreased expression of β1 integrin in HGFs. Higher levels of released LDH, PGE 2 and MMP-9 expression are recorded in ZA-treated HGFs. Increased levels of MMP-8 are recorded in newly synthesized compounds-treated samples. These findings allowed to conclude that new tested BPs did not affect HGFs viability and adhesion, did not induce cellular toxicity, were not responsible for inflammatory event induction and could preserve the physiological matrix turnover. It could be hypothesized that the new molecules were better tolerated by soft tissues, resulting in lesser side effects.

Zoledronic Acid improves clinical outcomes when administered before onset of bone pain in patients with prostate cancer.

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Saad, Fred; Eastham, James

2010-11-01

To evaluate, in an exploratory analysis, the effect of zoledronic acid (ZOL) on skeletal-related event (SRE) incidence as determined by the bone pain levels at study entry. Bone metastases can undermine skeletal integrity long before the onset of symptoms. Treating patients before symptom onset might be more effective in preventing SREs and improving patients' quality of life. ZOL has shown significant reductions in SREs and pain compared with placebo in patients with bone metastases from advanced prostate cancer in a randomized placebo-controlled trial. Patients from a placebo-controlled, Phase III trial of men with castration-resistant prostate cancer, randomized to receive ZOL 4 mg (n = 214) or placebo (n = 208) for ≤ 24 months, were stratified by pain or no pain at baseline. Bone pain was assessed at baseline, week 3, and week 6 and at 6-week intervals thereafter. The primary endpoint was the proportion of patients with ≥ 1 SRE. ZOL significantly reduced the mean pain scores compared with placebo at 3, 9, 21, and 24 months (P ≤ .03 for each point) and reduced the annual incidence of SREs. Among patients without baseline pain, ZOL decreased the percentage of patients with ≥ 1 SRE by 39% and reduced the annual incidence of SREs by 49% compared with placebo. ZOL delayed the onset of bone pain in those patients without pain at baseline compared with placebo. ZOL reduced bone pain and SREs compared with placebo in patients with bone metastases from castration-resistant prostate cancer, irrespective of the baseline pain status, and appeared more efficacious when initiated before the onset of pain. Copyright © 2010 Elsevier Inc. All rights reserved.

Combination sclerostin antibody and zoledronic acid treatment outperforms either treatment alone in a mouse model of osteogenesis imperfecta.

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Little, David G; Peacock, Lauren; Mikulec, Kathy; Kneissel, Michaela; Kramer, Ina; Cheng, Tegan L; Schindeler, Aaron; Munns, Craig

2017-08-01

In this study, we examined the therapeutic potential of anti-Sclerostin Antibody (Scl-Ab) and bisphosphonate treatments for the bone fragility disorder Osteogenesis Imperfecta (OI). Mice with the Amish OI mutation (Col1a2 G610C mice) and control wild type littermates (WT) were treated from week 5 to week 9 of life with (1) saline (control), (2) zoledronic acid given 0.025mg/kg s.c. weekly (ZA), (3) Scl-Ab given 50mg/kg IV weekly (Scl-Ab), or (4) a combination of both (Scl-Ab/ZA). Functional outcomes were prioritized and included bone mineral density (BMD), bone microarchitecture, long bone bending strength, and vertebral compression strength. By dual-energy absorptiometry, Scl-Ab treatment alone had no effect on tibial BMD, while ZA and Scl-Ab/ZA significantly enhanced BMD by week 4 (+16% and +27% respectively, P<0.05). Scl-Ab/ZA treatment also led to increases in cortical thickness and tissue mineral density, and restored the tibial 4-point bending strength to that of control WT mice. In the spine, all treatments increased compression strength over controls, but only the combined group reached the strength of WT controls. Scl-Ab showed greater anabolic effects in the trabecular bone than in cortical bone. In summary, the Scl-Ab/ZA intervention was superior to either treatment alone in this OI mouse model, however further studies are required to establish its efficacy in other preclinical and clinical scenarios. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Early effects of zoledronic acid and teriparatide on bone microarchitecture, remodeling and collagen crosslinks: comparison between iliac crest and lumbar vertebra in ewes.

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Portero-Muzy, N R; Chavassieux, P M; Bouxsein, M L; Gineyts, E; Garnero, P; Chapurlat, R D

2012-10-01

Iliac crest bone biopsies are used to assess the mechanism of action of drug treatments, yet there are little data comparing this site to sites prone to fracture. The purpose of this study was to compare the delay and the amplitude of responses to treatment in two different bone sites. The short-term effects of zoledronic acid and teriparatide on microarchitecture, collagen crosslinks and bone remodeling were evaluated in iliac crest and lumbar vertebrae. Aged ewes (n=8/gr) received either vehicle (CTRL) or a single injection of zoledronic acid (ZOL, 10mg) or daily injections of teriparatide (TPTD, 20 μg/d) for 3 months. Blood samples were collected monthly for assessing bone turnover markers. At the end of the study, a transiliac bone biopsy (IC) and L1 lumbar vertebrae (LV1) were collected to assess bone microarchitecture; pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) content, static and dynamic parameters of bone remodeling. In CTRL, Tb-BV/TV was significantly higher in LV1 than IC (psALP (p<0.001) and sCTX (p<0.001) were observed in the ZOL-group whereas in TPTD-group, after transient increases, they returned to baseline values. When compared to their respective CTRL, ZOL induced significant increases in Tb.BV/TV, Conn.D, Tb.N and Tb.Sp, in IC but not in LV1. Regardless of the site, ZOL markedly depressed the bone turnover: The static parameters of bone formation significantly decreased and the diminution of MS/BS, BFR/BS and Ac.f varied from -94 to -98% vs CTRL (p<0.01 to 0.001). It was associated with a diminution of the DPD content and the PYD/DPD ratio mainly in IC cortices. In contrast, after 3 months, TPTD did not modify the 3D structure and microarchitecture in IC and LV1, except a trend of higher Conn.D in IC, compared to IC-CTRL. TPTD treatment induced a significant increase in cortical porosity in LV1 (p<0.05) when compared to LV1-CTRL. Static parameters of bone formation and resorption were augmented in both sites, significantly

High-Dose Hypofractionated Radiation Therapy for Noncompressive Vertebral Metastases in Combination With Zoledronate: A Phase 1 Study

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Pichon, Baptiste [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Campion, Loïc [Department of Biostatistics, ICO Cancer Center, Saint-Herblain (France); Delpon, Grégory [Department of Medical Physics, ICO Cancer Center, Saint-Herblain (France); CRCNA, Inserm U892, CNRS UMR 6299, Nantes (France); Thillays, François [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Carrie, Christian [Department of Radiation Oncology, Léon Bérard Center, Lyon (France); Cellier, Patrice [Department of Radiation Oncology, ICO Cancer Center, Angers (France); Pommier, Pascal; Laude, Cécile [Department of Radiation Oncology, Léon Bérard Center, Lyon (France); Mervoyer, Augustin [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Hamidou, Hadji [Department of Radiation Oncology, ICO Cancer Center, Angers (France); Mahé, Marc-André [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Supiot, Stéphane, E-mail: stephane.supiot@ico.unicancer.fr [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); CRCNA, Inserm U892, CNRS UMR 6299, Nantes (France)

2016-11-15

Introduction: Hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases gives good results in terms of local control but increases the risk of fracture in the treated volume. Preclinical and clinical studies have shown that zoledronate not only reduces the risk of fracture and stimulates osteoclastic remodeling but also increases the immune response and radiosensitivity. This study aimed to evaluate the tolerability and effectiveness of zoledronate in association with radiation therapy. Patients and Methods: We conducted a multicenter phase 1 study that combined HSRT (3 × 9 Gy) and zoledronate in patients with vertebral metastasis ( (NCT01219790)). The principal objective was the absence of spinal cord adverse reactions at 1 year. The secondary objectives were acute tolerability, the presentation of a bone event, local tumor control, pain control, progression-free survival, and overall survival. Results: Thirty patients (25 male, 5 female), median age 66 years, who were followed up for a median period of 19.2 months, received treatment for 49 vertebral metastases. A grade 3 acute mucosal adverse event occurred in 1 patient during the treatment and in 2 more at 1 month. No late neurologic adverse events were reported at 1 year. The mean pain scores diminished significantly at 1 month (1.35; P=.0125) and 3 months (0.77; P<.0001) compared with pain scores at study entry (2.49). Vertebral collapse in the irradiated zone occurred in 1 (2%) treated vertebra. Control of local disease was achieved in 94% of irradiated patients (3 local recurrences). Conclusion: The combination of zoledronate and HSRT in the treatment of vertebral metastasis is well tolerated and seems to reduce the rate of vertebral collapse, effectively relieve pain, and achieve good local tumor control with no late neurologic adverse effects.

Activity of mevalonate pathway inhibitors against breast and ovarian cancers in the ATP-based tumour chemosensitivity assay

International Nuclear Information System (INIS)

Knight, Louise A; Kurbacher, Christian M; Glaysher, Sharon; Fernando, Augusta; Reichelt, Ralf; Dexel, Susanne; Reinhold, Uwe; Cree, Ian A

2009-01-01

Previous data suggest that lipophilic statins such as fluvastatin and N-bisphosphonates such as zoledronic acid, both inhibitors of the mevalonate metabolic pathway, have anti-cancer effects in vitro and in patients. We have examined the effect of fluvastatin alone and in combination with zoledronic acid in the ATP-based tumour chemosensitivity assay (ATP-TCA) for effects on breast and ovarian cancer tumour-derived cells. Both zoledronic acid and fluvastatin showed activity in the ATP-TCA against breast and ovarian cancer, though fluvastatin alone was less active, particularly against breast cancer. The combination of zoledronic acid and fluvastatin was more active than either single agent in the ATP-TCA with some synergy against breast and ovarian cancer tumour-derived cells. Sequential drug experiments showed that pre-treatment of ovarian tumour cells with fluvastatin resulted in decreased sensitivity to zoledronic acid. Addition of mevalonate pathway components with zoledronic acid with or without fluvastatin showed little effect, while mevalonate did reduced inhibition due to fluvastatin. These data suggest that the combination of zoledronic acid and fluvastatin may have activity against breast and ovarian cancer based on direct anti-cancer cell effects. A clinical trial to test this is in preparation

Comparative study of topical vs. intravenous tranexamic acid regarding blood loss in total knee arthroplasty

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Ari Zekcer

Full Text Available ABSTRACT Objective: To compare topical vs. intravenous tranexamic acid (TA in total knee arthroplasty regarding blood loss and transfusion., Methods: Ninety patients were randomized to receive TA intravenously (20 mg/kg in 100 mL of saline; group IV, topically (1.5 g in 50 mL of saline, sprayed over the operated site, before release of the tourniquet; topical group, or intravenous saline (100 mL with anesthesia; control group. The volume of drained blood in 48, h, the amount of transfused blood, and the serum levels of hemoglobin and hematocrit before and after surgery were evaluated., Results: The groups were similar for gender, age, weight, laterality, and preoperative hemoglobin and hematocrit levels (p> 0.2. The hemoglobin level dropped in all groups when comparing the preoperative and the 48-h evaluations: the control group decreased 3.8 mg/dL on average, while the IV, group had a decrease of 3.0, and the topical group, of 3.2 (p= 0.019. The difference between the control and IV, groups was confirmed by Bonferroni test (p= 0.020. The difference between the control group and the topical group was not significant (p= 0.130, although there was less reduction in hemoglobin in the topical group; the comparison between the IV, group and the topical group was also not significant (p= 1.000. Conclusion: Using topic and IV, tranexamic acid decreased blood loss and the need for transfusion in total knee arthroplasty. Topical application showed results similar to IV use regarding the need for blood transfusion, but without the possible side effects of IV, administration.

A systematic review and meta-analysis comparing combined intravenous and topical tranexamic acid with intravenous administration alone in THA.

Directory of Open Access Journals (Sweden)

Yangbai Sun

Full Text Available To compare the effectiveness and safety of combined intravenous and topical tranexamic acid with intravenous use alone in THA.The electronic databases MEDLINE, EMBASE, BIOSIS, Cochrane central, and further adapted for Google and Google Scholar internet, last updated on Dec 30, 2016, were searched. Evaluated outcomes included total blood loss, transfusion rate, maximum postoperative Hb drop, and incidence of thromboembolic complications. The standard mean difference (SMD or the relative risk (RR was calculated for continuous or dichotomous data respectively. The quality of the trial was assessed, and meta-analyses were performed with the Cochrane Collaboration's RevMan 5.0 software.Five RCTs with 457 patients were included. Combined TXA administration reduced blood loss (SMD, 1.39; 95%CI, 0.55 to 2.23; P<0.00001, I2 = 94%, hemoglobin decline (SMD, 0.84; 95%CI, 0.13 to 1.54; P = 0.01, I2 = 83% and the need for transfusion (RR, 2.58; 95%CI, 1.59 to 4.18; P = 0.65, I2 = 0% without increasing the rate of thromboembolic complications significantly (RR, 0.83; 95%CI, 0.27 to 2.54; P = 0.81, I2 = 0%.The present study has emphasized that combined TXA administration can effectively reduce blood loss, hemoglobin decline and the need for transfusion without increasing the rate of thromboembolic complications.

Zoledronate complexes. III. Two zoledronate complexes with alkaline earth metals: [Mg(C(5)H(9)N(2)O(7)P(2))(2)(H(2)O)(2)] and [Ca(C(5)H(8)N(2)O(7)P(2))(H(2)O)](n).

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Freire, Eleonora; Vega, Daniel R; Baggio, Ricardo

2010-06-01

Diaquabis[dihydrogen 1-hydroxy-2-(imidazol-3-ium-1-yl)ethylidene-1,1-diphosphonato-kappa(2)O,O']magnesium(II), [Mg(C(5)H(9)N(2)O(7)P(2))(2)(H(2)O)(2)], consists of isolated dimeric units built up around an inversion centre and tightly interconnected by hydrogen bonding. The Mg(II) cation resides at the symmetry centre, surrounded in a rather regular octahedral geometry by two chelating zwitterionic zoledronate(1-) [or dihydrogen 1-hydroxy-2-(imidazol-3-ium-1-yl)ethylidene-1,1-diphosphonate] anions and two water molecules, in a pattern already found in a few reported isologues where the anion is bound to transition metals (Co, Zn and Ni). catena-Poly[[aquacalcium(II)]-mu(3)-[hydrogen 1-hydroxy-2-(imidazol-3-ium-1-yl)ethylidene-1,1-diphosphonato]-kappa(5)O:O,O':O',O''], [Ca(C(5)H(8)N(2)O(7)P(2))(H(2)O)](n), consists instead of a Ca(II) cation in a general position, a zwitterionic zoledronate(2-) anion and a coordinated water molecule. The geometry around the Ca(II) atom, provided by six bisphosphonate O atoms and one water ligand, is that of a pentagonal bipyramid with the Ca(II) atom displaced by 0.19 A out of the equatorial plane. These Ca(II) coordination polyhedra are ;threaded' by the 2(1) axis so that successive polyhedra share edges of their pentagonal basal planes. This results in a strongly coupled rhomboidal Ca(2)-O(2) chain which runs along [010]. These chains are in turn linked by an apical O atom from a -PO(3) group in a neighbouring chain. This O-atom, shared between chains, generates strong covalently bonded planar arrays parallel to (100). Finally, these sheets are linked by hydrogen bonds into a three-dimensional structure. Owing to the extreme affinity of zoledronic acid for bone tissue, in general, and with calcium as one of the major constituents of bone, it is expected that this structure will be useful in modelling some of the biologically interesting processes in which the drug takes part.

The bisphosphonate zoledronate prevents vertebral bone loss in mature estrogen-deficient rats as assessed by micro-computed tomography

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Glatt M.

2001-01-01

Full Text Available The effect of long-term treatment with the bisphosphonate zoledronate on vertebral bone architecture was investigated in estrogen-deficient mature rats. 4-month-old rats were ovariectomized and development of cancellous osteopenia was assessed after 1 year. The change of bone architectural parameters was determined with a microtomographic instrument of high resolution. After 1 year of estrogen-deficiency, animals lost 55% of vertebral trabecular bone in comparison to sham operated control animals. Trabecular number (Tb.N and trabecular thickness (Tb.Th were significantly reduced in ovariectomized animals, whereas trabecular separation (Tb.Sp, bone surface to volume fraction (BS/BV and trabecular bone pattern factor (TBPf were significantly increased, indicating a loss of architectural integrity throughout the vertebral body. 3 groups of animals were treated subcutaneously with zoledronate for 1 year with 0.3, 1.5 and 7.5 microgram/kg/week to inhibit osteoclastic bone degradation. Administration started immediately after ovariectomy and treatment dose-dependently prevented the architectural bone deterioration and completely suppressed the effects of estrogen deficiency at the higher doses. The results show that microtomographic determination of static morphometric parameters can be used to quantitate the effects of drugs on vertebral bone architecture in small laboratory animals and that zoledronate is highly effective in this rat model.

Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events

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Acquavella, John; Ehrenstein, Vera; Schiødt, Morten

2016-01-01

OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post-authoriza......OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post...... (120 mg subcutaneously) or zoledronic acid (4 mg intravenously, adjusted for renal function). Patients will be identified using routinely collected data combined with medical chart review in Denmark, Sweden, and Norway. Followup will extend from the first administration of antiresorptive treatment...... to the earliest of death, loss-to-follow-up, or 5 years after therapy initiation. Results will be reported for three treatment cohorts: denosumab-naïve patients, zoledronic acid-naïve patients, and patients who switch from bisphosphonate treatment to denosumab. ONJ cases will be identified in three newly...

Comparison of intravenous versus topical tranexamic acid in total knee arthroplasty: a prospective randomized study.

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Patel, Jay N; Spanyer, Jonathon M; Smith, Langan S; Huang, Jiapeng; Yakkanti, Madhusudhan R; Malkani, Arthur L

2014-08-01

The purpose of this study was to compare the efficacy of topical Tranexamic Acid (TXA) versus Intravenous (IV) Tranexamic Acid for reduction of blood loss following primary total knee arthroplasty (TKA). This prospective randomized study involved 89 patients comparing topical administration of 2.0g TXA, versus IV administration of 10mg/kg. There were no differences between the two groups with regard to patient demographics or perioperative function. The primary outcome measure, perioperative change in hemoglobin level, showed a decrease of 3.06 ± 1.02 in the IV group and 3.42 ± 1.07 in the topical group (P = 0.108). There were no statistical differences between the groups in preoperative hemoglobin level, lowest postoperative hemoglobin level, or total drain output. One patient in the topical group required blood transfusion (P = 0.342). Based on our study, topical Tranexamic Acid has similar efficacy to IV Tranexamic Acid for TKA patients. Copyright © 2014 Elsevier Inc. All rights reserved.

The role of vitamin E in the prevention of zoledronic acid-induced nephrotoxicity in rats: a light and electron microscopy study.

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Sert, İbrahim Unal; Kilic, Ozcan; Akand, Murat; Saglik, Lutfi; Avunduk, Mustafa Cihat; Erdemli, Esra

2018-03-01

Bisphosphonates are widely used in metastatic cancer such as prostate and breast cancer, and their nephrotoxic effects have been established previously. In this study we aimed to evaluate both the nephrotoxic effects of zoledronic acid (ZA) and the protective effects of vitamin E (Vit-E) on this process under light and electron microscopy. A total of 30 male Sprague-Dawley rats were divided into 3 groups. The first group constituted the control group. The second group was given i.v. ZA of 3 mg/kg once every 3 weeks for 12 weeks from the tail vein. The third group received the same dosage of ZA with an additional i.m . injection of 15 mg Vit-E every week for 12 weeks. Tissues were taken 4 days after the last dose of ZA for histopathological and ultrastructural evaluation. Paller score, tubular epithelial thickness and basal membrane thickness were calculated for each group. For group 2, the p -values are all < 0.001 for Paller score, epitelial thickness, and basal membrane thickness. For group 3 (ZA + Vit. E), the p -values are < 0.001 for Paller score, 0.996 for epitelial thickness, and < 0.001 basal membrane thickness. Significant differences were also observed in ultrastructural changes for group 2. However, adding Vit-E to ZA administration reversed all the histopathological changes to some degree, with statistical significance. Administration of ZA had nephrotoxic effects on rat kidney observed under both light and electron microscopy. Concomitant administration of Vit-E significantly reduces toxic histopathological effects of ZA.

Combined application versus topical and intravenous application of tranexamic acid following primary total hip arthroplasty: a meta-analysis.

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Zhang, Pei; Liang, Yuan; Chen, Pengtao; Fang, Yongchao; He, Jinshan; Wang, Jingcheng

2017-02-21

The use of intravenous (IV) or topical tranexamic acid (TXA) in total hip arthroplasty has been proven to be effective and safe in total hip arthroplasty. However, which of these two administration routes is better has not been determined. The combined administration of TXA has been used in total knee arthroplasty with satisfactory results. We hypothesized that combined application of TXA may be the most effective way without increased rate of thrombotic events such as deep vein thrombosis (DVT) and pulmonary embolisms (PE) in patients subjected to primary total hip replacement (THA). A meta-analysis was conducted to compare the efficacy and safety of the combined use of tranexamic acid (TXA) relative to topical or intravenous (IV) use alone for treatment of primary THA. The outcomes included total blood loss, postoperative hemoglobin decline, transfusion rates, and the incidence rates of deep vein thrombosis (DVT) and pulmonary embolisms (PE). We searched electronic databases including PubMed, EMBASE, the Cochrane Library, Web of Science, the Chinese Biomedical Literature database, the CNKI database, and Wanfang Data until September 2016. The references of the included articles were also checked for additional potentially relevant studies. There were no language restrictions for the search. The data of the included studies were analyzed using RevMan 5.3 software. Seven studies met the inclusion criteria, encompassing a total of 1762 patients. Our meta-analysis demonstrated that total blood loss, postoperative hemoglobin decline, and transfusion rates were significantly lower for patients that received the combined treatment compared to patients that received either topical or intravenous administration of TXA. No statistical differences were found in the incidence of deep venous thrombosis (DVT) or pulmonary embolism (PE). The group that received the combined treatment had lower total blood loss, postoperative hemoglobin decline, and transfusion rates without an

Zoledronic acid inhibits pulmonary metastasis dissemination in a preclinical model of Ewing’s sarcoma via inhibition of cell migration

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Odri, Guillaume; Kim, Pui-Pui; Lamoureux, François; Charrier, Céline; Battaglia, Séverine; Amiaud, Jérôme; Heymann, Dominique; Gouin, François; Redini, Françoise

2014-01-01

Ewing’s sarcoma (ES) is the second most frequent primitive malignant bone tumor in adolescents with a very poor prognosis for high risk patients, mainly when lung metastases are detected (overall survival <15% at 5 years). Zoledronic acid (ZA) is a potent inhibitor of bone resorption which induces osteoclast apoptosis. Our previous studies showed a strong therapeutic potential of ZA as it inhibits ES cell growth in vitro and ES primary tumor growth in vivo in a mouse model developed in bone site. However, no data are available on lung metastasis. Therefore, the aim of this study was to determine the effect of ZA on ES cell invasion and metastatic properties. Invasion assays were performed in vitro in Boyden’s chambers covered with Matrigel. Matrix Metalloproteinase (MMP) activity was analyzed by zymography in ES cell culture supernatant. In vivo, a relevant model of spontaneous lung metastases which disseminate from primary ES tumor was induced by the orthotopic injection of 10 6 human ES cells in the tibia medullar cavity of nude mice. The effect of ZA (50 μg/kg, 3x/week) was studied over a 4-week period. Lung metastases were observed macroscopically at autopsy and analysed by histology. ZA induced a strong inhibition of ES cell invasion, probably due to down regulation of MMP-2 and −9 activities as analyzed by zymography. In vivo, ZA inhibits the dissemination of spontaneous lung metastases from a primary ES tumor but had no effect on the growth of established lung metastases. These results suggest that ZA could be used early in the treatment of ES to inhibit bone tumor growth but also to prevent the early metastatic events to the lungs

Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model.

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Tzong-Tyng Hung

Full Text Available BACKGROUND: The bisphosphonate, zoledronic acid (ZOL, can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM, to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. METHODS: The model involves intracardiac injection for arterial dissemination of the RM1(BM cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. FINDINGS: Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. CONCLUSIONS: ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a

Expression of Dlx-5 and Msx-1 in Craniofacial Skeletons and Ilia of Rats Treated With Zoledronate.

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Xuan, Bin; Yang, Pan; Wu, Shichao; Li, Lin; Zhang, Jian; Zhang, Wenyi

2017-05-01

Because of the different embryologic origins of the craniofacial skeleton and ilium, differences in gene expression patterns have been observed between the jaw bones and ilium. Distal-less homeobox (Dlx) genes and Msh homeobox genes, particularly Dlx-5 and Msx-1, play major roles in cell differentiation and osteogenesis. The purpose of this study was to investigate the effects of zoledronate (ZOL) on the craniofacial skeleton and ilium by detecting changes in Dlx-5 and Msx-1 expression at both the protein and messenger RNA levels. A total of 24 female Sprague-Dawley rats were randomly divided into 2 groups: ZOL group (n = 12), in which the rats were injected intraperitoneally with zoledronic acid for 12 weeks, and control group (n = 12), in which the rats were injected with saline solution for 12 weeks. By use of immunohistochemistry, Western blotting, and real-time reverse transcription polymerase chain reaction, the expression levels of Dlx-5 and Msx-1 in the craniofacial skeleton (including the maxilla, mandible, and parietal bone) and ilium were examined. Dlx-5 expression in the maxilla and mandible was increased at the protein and messenger RNA levels in the ZOL group compared with the control group (P Msx-1 expression in the maxilla and mandible was decreased in the ZOL group (P Msx-1 expression in the ilium was decreased in the ZOL group (P Msx-1 expression in the parietal bone was observed between the 2 groups (P > .05). Site-specific differences in the effects of ZOL on the craniofacial skeleton and ilium could be explained by differently altered tendencies in Dlx-5 and Msx-1 expression. The jaw bones were more susceptible to the effects of ZOL than the parietal bone and ilium. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Effect of Zoledronic Acid and Denosumab in Patients With Low Back Pain and Modic Change: A Proof-of-Principle Trial.

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Cai, Guoqi; Laslett, Laura L; Aitken, Dawn; Halliday, Andrew; Pan, Feng; Otahal, Petr; Speden, Deborah; Winzenberg, Tania M; Jones, Graeme

2018-05-01

The aim of this study was to evaluate the effect of zoledronic acid (ZA) and denosumab on low back pain (LBP) and Modic change (MC) over 6 months. Adults aged ≥40 years with significant LBP for at least 6 months duration and MC (type 1, 2, or mixed) were randomized to receive ZA (5 mg/100 mL), denosumab (60 mg), or placebo. LBP was measured monthly by visual analogue scale (VAS) and the LBP Rating Scale (RS). MC was measured from MRIs of T 12 -S 1 vertebrae at screening and 6 months. A total of 103 participants with moderate/severe LBP (mean VAS = 57 mm; mean RS = 18) and median total MC area 538 mm 2 were enrolled. Compared to placebo, LBP reduced significantly at 6 months in the ZA group for RS (-3.3; 95% CI, -5.9 to -0.7) but not VAS (-8.2; 95% CI, -18.8 to +2.4) with similar findings for denosumab (RS, -3.0; 95% CI, -5.7 to -0.3; VAS, -10.7; 95% CI, -21.7 to +0.2). There was little change in areal MC size overall and no difference between groups with the exception of denosumab in those with type 1 Modic change (-22.1 mm 2 ; 95% CI, -41.5 to -2.7). In post hoc analyses, both medications significantly reduced VAS LBP in participants with milder disc degeneration and non-neuropathic pain, and denosumab reduced VAS LBP in those with type 1 MC over 6 months, compared to placebo. Adverse events were more frequent in the ZA group. These results suggests a potential therapeutic role for ZA and denosumab in MC-associated LBP. © 2018 American Society for Bone and Mineral Research. © 2018 American Society for Bone and Mineral Research.

Dental extraction following zoledronate, induces osteonecrosis in rat's jaw.

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Vidal-Gutiérrez, X; Gómez-Clavel, J-F; Gaitán-Cepeda, L-A

2017-03-01

Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is clinically characterized by the presence of exposed bone in the oral cavity that persists for more than eight weeks. Previous attempts to establish an animal model have not sufficiently considered disease features. Our aim was to establish an inexpensive and replicable animal model that develops BRONJ in a short time. Thirty-two male Wistar rats were randomly divided into two groups: control and experimental. In the experimental group, we administered 0.06mg/kg intraperitoneal dose of zoledronic acid (ZA) 7 and 14 days prior to maxillary second molar extraction. At two, four and six weeks after tooth extraction, the animals were euthanized, and we dissected the maxilla following histological procedures. We stained serial slides with hematoxylin and eosin and Masson's trichrome. The samples were harvested for macroscopic, radiologic and histological evaluation of bone changes. At two weeks postextraction, we observed exposed necrotic bone in dental socket areas in experimental groups. Radiological analysis revealed osteolytic lesions accompanied by extensive destruction and sequestrum formation in the same group. Histological examination confirmed the absence of necrotic bone in control groups in contrast with the experimental groups. The percentage of empty lacunae and the number of osteoclasts and the necrotic bone area were significantly increased (p<0.05) in the experimental groups. The animal model using ZA administration to prior dental extraction successfully mimicked human BRONJ lesions. Also, the model was easily replicated, inexpensive and showed different features than other previous BRONJ models.

Cost-Effectiveness of Intravenous Proton Pump Inhibitors in High-Risk Bleeders

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Sander Veldhuyzen van Zanten

2004-01-01

Full Text Available There is unequivocal evidence that proton pump inhibitors (PPIs are currently the most effective acid suppressive agents available. Intravenous (IV formulations have been developed, although only IV pantoprazole is available in Canada. In patients presenting with serious upper gastrointestinal (GI bleeding due to duodenal or gastric ulcers, it has always been believed that IV administration of acid-lowering agents would improve clinical outcomes. The reason behind this thinking is twofold. First, there is in vitro evidence that formed clots are more stable at or near neutral pH (1. Second, by administering the agent intravenously, suppression of acid production is achieved much more quickly, thereby promoting more rapid healing of the ulcer and reducing the risk of persistent or recurrent bleeding. Interestingly and surprisingly, however, the data for intravenous H2-blockers have been disappointing (2. This failure to demonstrate clinical benefit has never been fully explained.

Effect of local injection of Zolena, zoledronic acid made in Iran, on orthodontic tooth movement and root and bone resorption in rats.

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Seifi, Massoud; Asefi, Sohrab; Hatamifard, Ghazal; Lotfi, Ali

2017-01-01

Background. Anchorage control is an essential part of orthodontic treatment planning, especially in adult patients who demand a more convenient treatment. Zoledronic acid (ZA) is an effective choice to address this problem. It is the most potent member of the bisphosphonates family that has an inhibitory effect on bone resorption by suppressing osteoclast function. Therefore, ZA might be a good option for orthodontic anchorage control. The current study evaluated the effect of local administration of Zolena (ZA made in Iran) on orthodontic tooth movement (OTM) and root and bone resorption. Methods. The experimental group consisted of 30 rats in 3 subgroups (n=10). Anesthesia was induced, and one closed NiTi coil spring was installed between the first molar and central incisor unilaterally, except for the negative control group. The positive control group received vestibular injection of 0.01 mL of saline next to the maxillary first molar, and 0.01 mL of the solution was injected at the same site in the ZA group. After 21 days, the rats were sacrificed and the distance between the first and second molars was measured with a leaf gauge. Histological analysis was conducted by a blind pathologist for the number of Howship's lacunae, blood vessels, osteoclast-like cells and root resorption lacunae. Data were analyzed with ANOVA, Tukey test and t-test. Results. There were no significant differences in OTM between the force-applied groups. ZA significantly inhibited bone/root resorption and angiogenesis compared to the positive control group. Conclusion. Zolena did not decrease OTM but significantly inhibited bone and root resorption. Zolena might be less potent than its foreign counterparts.

Topical vs. intravenous administration of tranexamic acid in knee arthroplasty and prevalence of deep venous thrombosis: a randomized clinical trial

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Ari Zekcer

Full Text Available Abstract Background Tranexamic acid (TXA is widely used in orthopedic surgery to reduce perioperative bleeding. Since TXA inhibits fibrinolysis, there is concern that it may increase the risk of thromboembolic events. Objectives To verify the prevalence of deep venous thrombosis (DVT in patients receiving TXA during total knee arthroplasty and to compare topical with intravenous administration of the drug. Methods All patients admitted for total knee arthroplasty due to primary arthrosis between June and November of 2014 were recruited consecutively. Thirty patients were randomized to a “topical group” (1.5 g TXA diluted in 50ml saline sprayed over the area operated, before tourniquet release, 30 to an “intravenous group” (20mg/kg TXA in 100 ml of saline, given at the same time as anesthesia, and 30 to a control group (100 ml of saline, given at the same time as anesthesia. All patients had duplex ultrasound scans of the legs on the 15th postoperative day. Results Deep venous thrombosis events occurred in five of the 90 patients operated (one out of 30 in the topical group [3.3%], four out of 30 in the control group [13.3%], and zero in the intravenous group. All were confirmed by duplex ultrasound scans and all were asymptomatic. Prevalence rates of DVT were similar between groups (p = 0.112 for control vs. intravenous; p = 0.353 for control vs. topical; and p =1.000 for intravenous vs. topical, according to two-sided exact tests. Conclusions Both topical and intravenous administration of TXA are safe with regard to occurrence of DVT, since the number of DVT cases in patients given TXA was not different to the number in those given placebo.

Methodological study on determining endogenous amino acid excretion of broiler chickens by single intravenous injection of 3H-leucine

International Nuclear Information System (INIS)

Yao Junhu; Wang Kangning; Yang Feng; Zhou Anguo; Cai Xuelin; Duanmu Dao

1999-01-01

Forty broiler chickens (1.5 kg of body weight, BW) were randomly divided into 20 groups. Every fifth group was force-fed a nitrogen-free diet (NFD) or a NFd + 3.20% enzyme hydrolysed casein (EHC) diet or diets with 5% and 20% crude protein (CP) in which soybean meal (sol.) was the sole nitrogen source. 30μCi 3 H-leucine/kg BW was intravenously injected into all birds just after the force-feeding. Venous blood samples were taken at 5 min, 4h, 24h, 36h and 48h after the injection, and the amount of excreta for the whole period of 48h was collected. The amino acids excreted after force-feeding NFD + 3.20% EHC of CP5% diet were theoretically endogenous. The ratios of specific radioactivity (SR) in excreta and the value of definite integral in free plasma from 0 to 48 h after injection of labelled leucine were not different (P > 0.05) when NFD, NFD + 3.20% EHC or CP5% diet was fed. From these results and theoretical analysis, it was suggested that for the birds with CP20% diet, the ratio of SR in endogenous leucine and value of definite integral in free plasma from 0 to 48 h after injection of labelled leucine would be the same as that of the birds with NFD diet, and thus endogenous losses of leucine and other amino acids, by the endogenous amino acid pattern measured with NFD diet, could be estimated for CP20% diet. The endogenous amino acid losses measured by this new technique was 120.50% of those measured by NFD method. It was suggested that single intravenous injection of 3 H-leucine first proposed would be more valuable for determining endogenous amino acid losses, especially when practical nitrogen-containing diet was fed

Inhibitory effects of intravenous lansoprazole 30 mg and pantoprazole 40 mg twice daily on intragastric acidity in healthy Chinese volunteers: a randomized, open-labeled, two-way crossover study.

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Zhan, Xian-Bao; Guo, Xiao-Rong; Li, Zhao-Shen; Gong, Yan-Fang; Gao, Jun; Liao, Zhuan; Li, Zhen; Gao, Shen; Liu, Pei

2012-02-01

Until now there has been no study that directly compares the effect of lansoprazole and pantoprazole administered intravenously on intragastric acidity. The aim of this study is to compare the effect of lansoprazole (30 mg) and pantoprazole (40 mg) administered intravenously on gastric acidity. Helicobacter pylori-negative healthy volunteers were recruited in this open-label, randomized, two-way crossover, single centre study. Lansoprazole at 30 mg or pantoprazole at 40 mg was intravenously administered twice daily for 5 consecutive days with at least a 14-day washout interval. Twenty-four-hour intragastric pH was continuously monitored on days 1 and 5 of each dosing period. Twenty-five volunteers completed the 2 dosing periods. The mean intragastric pH values were higher in subjects treated with lansoprazole than those with pantoprazole on both day 1 (6.41 ± 0.14 vs. 5.49 ± 0.13, P=0.0003) and day 5 (7.09 ± 0.07 vs. 6.64 ± 0.07, P=0.0002). Significantly higher percentages of time with intragastric pH >4 and pH >6 were found in the subjects treated with lansoprazole than those with pantoprazole on day 1 (pH >4, 87.12 ± 4.55% vs. 62.28 ± 4.15%, P=0.0012; pH >6, 62.12 ± 4.12% vs. 47.25 ± 3.76%, P=0.0216) and pH >6 on day 5 (76.79 ± 3.77% vs. 58.20 ± 3.77%, P=0.0025). Intravenous lansoprazole produces a longer and more potent inhibitory effect on intragastric acidity than does intravenous pantoprazole.

A randomized controlled trial to compare the efficacy of bisphosphonates in the management of painful bone metastasis

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Krishnangshu Bhanja Choudhury

2011-01-01

Conclusion: The use of bisphosphonates for 6 months or more results in a statistical significant improvement in bone pain, more so with zoledronic acid. Hypercalcemia, an SRE, was significantly less in the zoledronic acid arm.

Bone targeting compounds for radiotherapy and imaging: *Me(III)-DOTA conjugates of bisphosphonic acid, pamidronic acid and zoledronic acid.

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Meckel, M; Bergmann, R; Miederer, M; Roesch, F

2017-01-01

Bisphosphonates have a high adsorption on calcified tissues and are commonly used in the treatment of bone disorder diseases. Conjugates of bisphosphonates with macrocyclic chelators open new possibilities in bone targeted radionuclide imaging and therapy. Subsequent to positron emission tomography (PET) examinations utilizing 68 Ga-labelled analogues, endoradiotheraphy with 177 Lu-labelled macrocyclic bisphosphonates may have a great potential in the treatment of painful skeletal metastases. Based on the established pharmaceuticals pamidronate and zoledronate two new DOTA-α-OH-bisphosphonates, DOTA PAM and DOTA ZOL (MM1.MZ) were successfully synthesized. The ligands were labelled with the positron emitting nuclide 68 Ga and the β - emitting nuclide 177 Lu and compared in in vitro studies and in ex vivo biodistribution studies together with small animal PET and single photon emission computed tomography (SPECT) studies against [ 18 F]NaF and a known DOTA-α-H-bisphosphonate conjugate (BPAPD) in healthy Wistar rats. The new DOTA-bisphosphonates can be labelled in high yield of 80 to 95 % in 15 min with post-processed 68 Ga and >98 % with 177 Lu. The tracers showed very low uptake in soft tissue, a fast renal clearance and a high accumulation on bone. The best compound was [ 68 Ga]DOTA ZOL (SUV Femur  = 5.4 ± 0.6) followed by [ 18 F]NaF (SUV Femur  = 4.8 ± 0.2), [ 68 Ga]DOTA PAM (SUV Femur  = 4.5 ± 0.2) and [ 68 Ga]BPAPD (SUV Femur  = 3.2 ± 0.3). [ 177 Lu]DOTA ZOL showed a similar distribution as the diagnostic 68 Ga complex. The 68 Ga labelled compounds showed a promising pharmacokinetics, with similar uptake profile and distribution kinetics. Bone accumulation was highest for [ 68 Ga]DOTA ZOL , which makes this compound probably an interesting bone targeting agent for a therapeutic approach with 177 Lu. The therapeutic compound [ 177 Lu]DOTA ZOL showed a high target-to-background ratio. SPECT experiments showed concordance

Is Administration of Trastuzumab an Independent Risk Factor for Developing Osteonecrosis of the Jaw Among Metastatic Breast Cancer Patients Under Zoledronic Acid Treatment?

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Pilanci, Kezban Nur; Alco, Gul; Ordu, Cetin; Sarsenov, Dauren; Celebi, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Tecimer, Coskun; Demir, Gokhan; Eralp, Yesim; Okkan, Sait; Ozmen, Vahit

2015-01-01

Abstract One of the most important adverse effects of zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have been identified in the development of ONJ. In this study, we aimed to determine the role of trastuzumab, an antiangiogenic agent, as an independent risk factor for the development of this serious side effect. Our study included 97 patients (mean age: 54 ± 10 years) with breast cancer, recorded in the archives of the Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to bone metastases between March 2006 and December 2013. We recorded the patients’ ages, weights, duration of treatment with ZA, number of ZA infusions, dental procedures, anticancer treatments (chemotherapy, aromatase inhibitor, trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking habits. Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ, the mean time of exposure to ZA was 41 months (range: 13–82) and the mean number of ZA infusions was 38 (range: 15–56). The duration of treatment with ZA and the use of trastuzumab were observed to be 2 factors that influenced the development of ONJ (P = 0.049 and P = 0.028, respectively). The development of ONJ under ZA treatment may be associated solely with the duration of ZA treatment and the concurrent administration of trastuzumab. These findings show that patients who are administered trastuzumab for metastatic breast cancer while undergoing ZA treatment are prone to developing ONJ. Therefore, we recommend intense clinical observation to avoid this particular condition in patients receiving ZA and trastuzumab. PMID:25950681

Prostate-specific antigen kinetics and outcomes in patients with bone metastases from castration-resistant prostate cancer treated with or without zoledronic acid.

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Saad, Fred; Segal, Scott; Eastham, James

2014-01-01

Zoledronic acid (ZOL) is a standard therapy for the prevention of skeletal-related events (SREs) in patients with castration-resistant prostate cancer (CRPC). Although prostate-specific antigen (PSA) is an established marker for monitoring prostate cancer patients, correlations between PSA and disease outcomes during ZOL therapy are unclear. To evaluate the relationships among PSA kinetics, bone-directed therapy with ZOL, and clinical outcomes in men with bone metastases from CRPC using a ZOL phase 3 trial database. Exploratory analyses from a phase 3 trial in men with bone metastases from CRPC (n=643) randomized to ZOL or placebo every 3 wk. PSA levels during the first 3 mo of the study were evaluated in linear and logarithmic (log) models stratified using prognostic factors established in a ZOL phase 3 trial and a CRPC nomogram. Relative risks of SREs, bone disease progression (BDP), and death were calculated per 1 log (nanograms per milliliter) PSA increase. Baseline PSA models used the study median (PSA: 77.3 ng/ml) as the high/low cut-off point. A total of 202 placebo- and 434 ZOL-treated patients were assessable. In both groups, PSA increases correlated with significantly increased risks of death, BDP, and first SRE. In the placebo and ZOL groups, associated increases in risk per 1 log (nanograms per milliliter) PSA increase were 29% (p<0.0001) and 10% (p<0.0074), respectively, for BDP, and 24% (p=0.0010) and 13% (p=0.0079), respectively, for first SRE. Limitations include the retrospective nature of these analyses and the potential confounding effects of concurrent antineoplastic therapies. PSA is an important prognostic tool for survival in patients with bone metastases from CRPC, and these analyses show that PSA is also prognostic for BDP and SREs regardless of bone-targeted therapy. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Comparison between intravenous boluses versus infusion of tranexamic acid (TXA) to reduce bleeding in paediatric cyanotic congenital heart disease (CHD) surgeries

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Junejo, F.; Irfan, M.; Akhtar, M.I.; Hamid, M.; Ahmed, S.S.

2018-01-01

To compare the intravenous boluses and intravenous continuous infusion of tranexamic acid (TXA) to reduce postoperative bleeding in cyanotic congenital heart disease surgeries. Study Design:Single-blinded randomised clinical trial. Place and Duration of Study:Anaesthesia Department, The Aga Khan University Hospital, Karachi, from July 2016 to April 2017. Methodology:Sixty patients of cyanotic congenital heart disease, undergoing either palliative or corrective surgery involving cardiopulmonary bypass (CPB), were recruited. These 60 patients were divided randomly into two groups. The infusion group received intravenous infusion of TXA at 5 mg/kg/hour while the bolus group received three intravenous boluses of 10 mg/kg after induction, after going to bypass and after protamine reversal. Data was collected through predesigned proforma. There were two primary outcomes: postoperative bleeding in the first 24 hours, and chest closure time. Results:Postoperative bleeding was 13.94 (10.27-20.18) ml/kg in the first 24 hours in infusion group and 15.05 (9.04-23.50) ml/kg in the bolus group. Chest closure time was 38.5 (25-45) in infusion group and 30 (20-46.25) minutes in the bolus group. There was no statistically significant and clinical difference between both groups regarding postoperative bleeding in the first 24 hours and chest closure time. Conclusion:These infusion and bolus groups had comparable postoperative bleeding and chest closure time. (author)

Vγ9Vδ2 T cells and zoledronate mediate antitumor activity in an orthotopic mouse model of human chondrosarcoma.

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Sun, L; Li, Y; Jiang, Z; Zhang, J; Li, H; Li, B; Ye, Z

2016-06-01

Chondrosarcoma (CS) is a cartilaginous malignant neoplasm characterized by resistance to conventional adjuvant therapy. The prognosis of unresectable or metastatic CS is poor. Therefore, it is imperative to explore novel therapeutic approaches to improve the treatment efficacy for those CS patients. Emerging data has implicated the synergistic antitumor activity of zoledronate (ZOL) and Vγ9Vδ2 T cells. However, whether ZOL-stimulated Vγ9Vδ2 T cells could infiltrate bone sarcoma and inhibit tumor growth has not been thoroughly answered yet. In this study, Vγ9Vδ2 T cells from healthy donors and CS patients were expanded in the presence of ZOL (1 μM) and IL-2 (400 IU/ml). The antitumor activity of Vγ9Vδ2 T cells to ZOL-pretreated human CS was examined both in vitro and in vivo. ZOL pretreatment substantially enhanced the cytotoxicity of Vγ9Vδ2 T cells to SW1353 and primary CS cells. ZOL potentiated the migration and cytotoxicity of Vγ9Vδ2 T cells to SW1353 in dose- and time-dependent manner. Moreover, weekly intravenous ZOL followed by Vγ9Vδ2 T cells inhibited subcutaneous xenograft growth. Thus, Vγ9Vδ2 T cells were able to infiltrate bone tumor and significantly suppressed the development of orthotopic SW1353 xenografts. Altogether, the study raises the possibility of combining ZOL with Vγ9Vδ2 T cells for CS treatment.

DOES INTRAVENOUS TRANEXAMIC ACID REDUCE BLOOD LOSS DURING SURGICALLY ASSISTED RAPID PALATAL EXPANSION?

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Emine AKBAŞ

2017-10-01

Full Text Available Purpose: The purpose of this study was to evaluate the efficacy of tranexamic acid (TXA in reducing blood loss during surgically assisted rapid palatal expansion (SARPE procedure. Subjects and Methods: A total of 34 patients (12 male, 22 female who had been treated surgically under general anesthesia with SARPE including pterygoid disjunction for transverse maxillary deficiency (TMD were included in this study. The study group (n=17 received intravenous (IV TXA 10 mg/kg as a preoperative bolus; the control group (n=17 received normal saline solution. Preoperative and postoperative haemoglobin and haematocrit values, intraoperative blood loss, and any blood product transfusion were recorded. Results: Blood loss during SARPE was statistically significantly less in the study group than the control group (p=0.0001. Conclusion: Preoperative IV administration of TXA can effectively control blood loss during when SARPE with pterygoid disjunction is performed.

Oral squamous cell carcinoma arising in a patient after hematopoietic stem cell transplantation with bisphosphonate-related osteonecrosis of the jaws.

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Arduino, Paolo G; Scully, Crispian; Chiusa, Luigi; Broccoletti, Roberto

2015-01-01

A 55-year-old man with a history of acute myeloid leukaemia treated with hematopoietic stem cell transplantation and with a 5-year history of bisphosphonate-related osteonecrosis of the jaws, following 12 cycles of intravenous zoledronic acid therapy, presented in December 2009 with a history of increasingly severe unilateral lower jaw pain. Oral examination revealed, as previously, exposed bone in the left mandible, but also a new exophytic mass on the lower-left buccal mucosa. Biopsy confirmed a diagnosis of oral squamous cell carcinoma. To the best of our knowledge, this is the first report of an oral squamous cell carcinoma that appeared adjacent to an area of osteochemonecrosis.

Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.

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Daniel A Monti

Full Text Available Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week, using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier. There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of disease or treatment with gemcitabine or erlotinib. Applying RECIST 1.0 criteria, seven of the nine subjects had stable disease while the other two had progressive disease.These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients. This, combined with the observed response to treatment, suggests the need for a phase II study of longer duration.Clinicaltrials.gov NCT00954525.

Plasma and erythrocyte uptake of omega-3 fatty acids from an intravenous fish oil based lipid emulsion in patients with advanced oesophagogastric cancer.

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Eltweri, A M; Thomas, A L; Fisk, H L; Arshad, A; Calder, P C; Dennison, A R; Bowrey, D J

2017-06-01

It has been demonstrated that short term intravenous (IV) administration of omega-3 polyunsaturated fatty acids (PUFAs) is more effective than oral supplementation at promoting incorporation of the bioactive omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma, blood cells and tissues. The effect of repeated short term IV infusion of omega-3 PUFAs was investigated in patients with advanced oesophagogastric cancer during palliative chemotherapy. Patients with advanced oesophagogastric cancer (n = 21) were recruited into a phase II pilot clinical trial. All patients were scheduled for an intravenous infusion of Omegaven ® (fish oil supplement containing EPA and DHA) at a rate of 2 ml/kg body weight for 4 h once a week for up to six months. Blood samples were collected to assess omega-3 PUFA uptake into plasma non-esterified fatty acids (NEFAs) and phosphatidylcholine (PC) and into red blood cell (RBC) membranes. Fatty acid profiles were analysed by gas chromatography. Twenty patients received at least one Omegaven ® treatment and were included in the analysis. Each infusion of omega-3 PUFAs resulted in increased EPA and DHA in plasma NEFAs, but there was little effect on PUFAs within plasma PC during the infusions. However, with repeated weekly infusion of omega-3 PUFAs, the EPA content of plasma PC and of RBC membranes increased. Repeated weekly omega-3 PUFA infusion is effective in enriching plasma PC and RBC membranes in EPA in patients with advanced oesophagogastric cancer receiving palliative chemotherapy. Clinical Trials.Gov NCT01870791. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Comparison of Intravenous Ranitidine with Pantoprazole in Decreasing Gastric Fluid Acidity in Emergency Cesarean Section

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Alipour M

2013-10-01

Full Text Available Objectives: Peri-operative aspiration of gastric contents is a problem that causes certain respiratory problems including ARDS. Prophylaxis against aspiration of gastric contents is performed routinely in elective surgeries, but there is rare evidence on the efficacy of this method in emergency cesarean section. Materials and Methods: This is a randomized, controlled, double-blinded clinical trial. 60 parturients undergoing emergency cesarean section were randomly assigned into three groups of 20 each. They were allocated into two study and one placebo groups. The study group one and two received intravenous ranitidine (IV 50 mg or IV pantoprazole 40 mg, half an hour before induction of GA, respectively. The placebo group was administered just 5 ml of isotonic saline half an hour before GA induction. After intubation and confirmation of endotracheal tube insertion, the gastric contents were aspirated through a nasogastric tube for evaluation of acidity and volume. Results: A statistical difference between group one and two with the control group was observed in the acidity of gastric contents, but there was no difference in volume. Also, the PH level of gastric contents in patients receiving pantoprazole was significantly higher than the isotonic saline (p

Optimizing dosing frequencies for bisphosphonates in the management of postmenopausal osteoporosis: patient considerations

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John Sunyecz

2008-12-01

Full Text Available John SunyeczMenopauseRx, Inc., Hopwood, PA, USAAbstract: Postmenopausal osteoporosis is common and underrecognized among elderly women. Osteoporotic fractures cause disability and disfigurement and threaten patients’ mobility, independence, and survival. Care for incident fractures in this age group must go beyond orthopedic repair, to assessment and treatment of the underlying bone fragility. Fracture risk can be reduced by vitamin D and calcium supplementation along with antiresorptive drug treatment. First-line osteoporosis pharmacotherapy employs nitrogen-containing bisphosphonates. The inconvenience of daily oral treatment has motivated development of weekly, monthly, and intermittent oral regimens, as well as quarterly and yearly intravenous (iv regimens. Ibandronate is the first bisphosphonate to have shown direct anti-fracture efficacy with a non-daily regimen; it was approved for once-monthly oral dosing in 2005 and for quarterly iv dosing in 2006. Intermittent oral risedronate and yearly iv zoledronic acid were approved in 2007. Newly available regimens with extended dosing intervals reduce the inconvenience of bisphosphonate therapy and provide patients with a range of options from which to select a maximally sustainable course of treatment. This review discusses the development, efficacy, safety, and tolerability of extended-interval bisphosphonate regimens and examines their potential to improve patient acceptance and long-term success of osteoporosis treatment.Keywords: ibandronate, alendronate, risedronate, zoledronic acid, adherence, persistence

Systematic review and meta-analysis of the efficacy and safety of alendronate and zoledronate for the treatment of postmenopausal osteoporosis.

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Serrano, Ana Julissa; Begoña, Leire; Anitua, Eduardo; Cobos, Raquel; Orive, Gorka

2013-12-01

The aim of this meta-analysis was to evaluate the efficacy and safety of two bisphosphonates (alendronate and zoledronate) in the treatment of postmenopausal osteoporosis. The incidence of fractures was considered as primary endpoint. Only randomized trials with a follow-up period of 1 year or more were included in this systematic review and meta-analysis. We excluded studies that included patients with secondary osteoporosis especially in relation to therapy with corticosteroids or other drugs or diseases known to affect bone mineral density. Studies published as subgroup analysis, extension studies, economic evaluations, and comparisons with active control were excluded. The methodological quality of controlled clinical trials that met these inclusion criteria was evaluated. No studies were excluded from analysis due to lack of quality. The risk ratio of hip, vertebral and wrist fractures for alendronate were 0.61 [95% confidence interval (CI) 0.40-0.93], 0.54 (95% CI 0.44-0.66) and 0.65 (95% CI 0.33-1.25), respectively. Zoledronate risk ratio was 0.62 (95% CI 0.46-0.82) and 0.38 (95% CI 0.22-0.67) for hip and vertebral fractures, respectively.

Effects of Zoledronate and Mechanical Loading during Simulated Weightlessness on Bone Structure and Mechanical Properties

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Scott, R. T.; Nalavadi, M. O.; Shirazi-Fard, Y.; Castillo, A. B.; Alwood, J. S.

2016-01-01

Space flight modulates bone remodeling to favor bone resorption. Current countermeasures include an anti-resorptive drug class, bisphosphonates (BP), and high-force loading regimens. Does the combination of anti-resorptives and high-force exercise during weightlessness have negative effects on the mechanical and structural properties of bone? In this study, we implemented an integrated model to mimic mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hindlimb unloading (HU). Our working hypothesis is that CL combined with ZOL in the HU model induces additive structural and mechanical changes. Thirty-two C57BL6 mice (male,16 weeks old, n8group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45gkg), or saline vehicle, prior to experiment. The right tibia was axially loaded in vivo, 60xday to 9N in compression, repeated 3xweek during HU. During the application of compression, secant stiffness (SEC), a linear estimate of slope of the force displacement curve from rest (0.5N) to max load (9.0N), was calculated for each cycle once per week. Ex vivo CT was conducted on all subjects. For ex vivo mechanical properties, non-CL left femurs underwent 3-point bending. In the proximal tibial metaphysis, HU decreased, CL increased, and ZOL increased the cancellous bone volume to total volume ratio by -26, +21, and +33, respectively. Similar trends held for trabecular thickness and number. Ex vivo left femur mechanical properties revealed HU decreased stiffness (-37),and ZOL mitigated the HU stiffness losses (+78). Data on the ex vivo Ultimate Force followed similar trends. After 3 weeks, HU decreased in vivo SEC (-16). The combination of CL+HU appeared additive in bone structure and mechanical properties. However, when HU + CL + ZOL were combined, ZOL had no additional effect (p0.05) on in vivo SEC. Structural data followed this trend with

Effect of short-term intravenous ascorbic acid on reducing ferritin in hemodialysis patients.

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Jalalzadeh, M; Shekari, E; Mirzamohammadi, F; Ghadiani, M H

2012-05-01

Resistance to recombinant erythropoietin (rEPO) in hemodialysis patients may be due to inadequate iron recruitment and defect in iron use. In this cross over randomized clinical trial, 30 hemodialysis patients with serum ferritin levels of ≥500 ng/ml, hemoglobin ≤11.0 g/dl, and transferrin saturation (TSAT) of 20% or less were administrated intravenous iron (50-100 mg/wk) and rEPO (120-360 U/kg/wk) for 6 months. Patients were excluded if there was a clear explanation for rEPO hyporesponsiveness. Patients were divided into two groups. Group1 received standard care and 500 mg of intravenous ascorbic acid (IVAA) with each dialysis session in the first week of each month for a total of 3 months. Group 2 received standard care only. After 2 month washout period, groups were crossed over. Each month hemoglobin (Hb) was assessed. Iron, TIBC (transferrin iron binding capacity), TSAT, iPTH (intact parathyroid hormone), liver enzymes, albumin and cholesterol levels were measured every 3 months. After 3 months of intervention, Hb significantly increased from 10.11 to 12.19 g/dl (P <0 0.001; 95% confidence interval [CI] 2.7-1.4) and TSAT increased from 18.9 to 28.1% (P = 0.008; 95% CI 0.09-3), while ferritin and serum iron declined significantly from 1391 to 938 ng/ml (P = 0.001; 95% CI 216-689), 97.2 to 64.6 (P = 0.001; 95% CI 14.8-50.4) in the study group. Change of Hb over time in IVAA group was significant (P < 0.0005). There were significant differences between two groups in change of Hb level over time (P < 0.0005) and treatment effect (P = 0.002). Baseline laboratory tests were similar in the two groups and there was no carry over effect at phase 2. We showed that low amount of IVAA could reduce ferritin level and enhance Hb and TSAT, suggesting improved iron utilization.

Topical versus intravenous administration of tranexamic acid in primary total hip arthroplasty: a systematic review and meta-analysis of randomized controlled trials

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Sammy A. Hanna

2016-09-01

Full Text Available Tranexamic acid (TA is widely used by orthopedic surgeons to decrease blood loss and the need for transfusion following total hip arthroplasty (THA. Although both intravenous and topical applications are described in the literature, there remains no consensus regarding the optimal regimen, dosage and method of delivery of TA during THA. In addition, concerns still exist regarding the risk of thromboembolic events with intravenous administration. The purpose of this meta-analysis was to compare the efficacy and safety of topical versus intravenous administration of TA in THA. A systemic review of the electronic databases PubMed, CENTRAL, EMBASE and Google Scholar was undertaken to identify all randomized controlled trials (RCTs comparing the topical and intravenous administration of TA during THA, in terms of total blood loss, rate of blood transfusion and incidence of deep venous thrombosis (DVT and pulmonary embolism (PE post-operatively. A meta-analysis was performed to evaluate and compare the efficacy and safety of both methods of administration. Of 248 potentially relevant papers, three RCTs comprising (482 were eligible for data extraction and metaanalysis. The results showed a slightly higher amount of blood loss [Mean Difference (MD – 46.37, P=0.12, 95% confidence interval (CI – 12.54 to 105.29] and rate of transfusion (Risk Ratio 1.30, P=0.39, 95%CI 0.71 to 2.37 postoperatively in the topical TA group, but both did not reach statistical significance. There were 3 cases (1.2% of DVT/PE in the intravenous group and one case (0.4% in the topical group. Topical TA is an effective and safe method to reduce blood loss and the rate of transfusion following primary THA. It has comparative effectiveness to IV administration with slightly less post-operative thromboembolic complications. Larger and better-designed RCTs are required to establish the optimum dosage and regimen for topical use.

In vitro and in vivo investigation of bisphosphonate-loaded hydroxyapatite particles for peri-implant bone augmentation.

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Kettenberger, Ulrike; Luginbuehl, Vera; Procter, Philip; Pioletti, Dominique P

2017-07-01

Locally applied bisphosphonates, such as zoledronate, have been shown in several studies to inhibit peri-implant bone resorption and recently to enhance peri-implant bone formation. Studies have also demonstrated positive effects of hydroxyapatite (HA) particles on peri-implant bone regeneration and an enhancement of the anti-resorptive effect of bisphosphonates in the presence of calcium. In the present study, both hydroxyapatite nanoparticles (nHA) and zoledronate were combined to achieve a strong reinforcing effect on peri-implant bone. The nHA-zoledronate combination was first investigated in vitro with a pre-osteoclastic cell assay (RAW 264.7) and then in vivo in a rat model of postmenopausal osteoporosis. The in vitro study confirmed that the inhibitory effect of zoledronate on murine osteoclast precursor cells was enhanced by loading the drug on nHA. For the in vivo investigation, either zoledronate-loaded or pure nHA were integrated in hyaluronic acid hydrogel. The gels were injected in screw holes that had been predrilled in rat femoral condyles before the insertion of miniature screws. Micro-CT-based dynamic histomorphometry and histology revealed an unexpected rapid mineralization of the hydrogel in vivo through formation of granules, which served as scaffold for new bone formation. The delivery of zoledronate-loaded nHA further inhibited a degradation of the mineralized hydrogel as well as a resorption of the peri-implant bone as effectively as unbound zoledronate. Hyaluronic acid with zoledronate-loaded nHA, thanks to its dual effect on inducing a rapid mineralization and preventing resorption, is a promising versatile material for bone repair and augmentation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Topical versus intravenous tranexamic acid as a blood conservation intervention for reduction of post-operative bleeding in hemiarthroplasty.

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Emara, Walid Mohamed; Moez, Khaled K; Elkhouly, Abeer H

2014-01-01

This study was performed to test the effectiveness of topical tranexamic acid (TXA) in reducing blood loss in pelvic hemiarthoplasty surgeries compared with intravenous TXA, regarding the incidence of thromboembolic complications (deep vein thrombosis [DVT], pulmonary embolism (PE) and cerebrovascular stroke [CVS]). After obtaining institutional ethical approval 60 patients divided into three groups. Group A: Received intravenous TXA Group B: Received topical TXA Group C: Control group (placebo saline). All patients were received general anesthesia and post-operative bleeding, immediate and 24 h post-operatively, hemoglobin concentration, hematocrit, platelets and coagulation profile (prothrombin time, activated partial thromboplastin time and international normalized ratio) baseline, immediate and 24 h post-operatively. Thromboelastography was recorded baseline, immediate and 24 h post-operatively. Incidence of DVT, PE and CVS was recorded. There was statistical significant elevation hemoglobin concentration and hematocrit in both Groups A and B, significant increase in blood loss in Group C, significant increase in number of patients receiving blood in Group C, there was a significant decrease in "r" and "k" times and a significant increase in maximum amplitude and α-angle in Group A, statistically significant increase in the incidence of thromboembolic events in the form of DVT, PE and CVS in Group A. Topical TXA is effective in decreasing post-operative blood loss with possible side-effects of this route of administration.

Intravenous supplementation of acetate, glucose or essential amino acids to an energy and protein deficient diet in lactating dairy goats

DEFF Research Database (Denmark)

Safayi, S.; Nielsen, M. O.

2013-01-01

amino acid supply is suboptimal. Goats were fed a basal diet deficient in energy (90% of requirements) and protein (80% of requirements), and were randomly allocated to 4 treatments in a balanced 4 x 4 Latin square design. The treatments consisted of 4-d continuous intravenous infusions of isoosmotic...... and close to significantly by ACE, but not by GLU treatment. GLU reduced milk protein percentage compared to all other treatments. High milk protein yields on EM and ACE treatments were associated with higher arterial AVD for acetate and oxygen (not significant for ACE), and higher AVD also for beta......In the present experiment we aimed to study, if milk synthesis is more sensitive toward deficiency in supply of amino acids in early (EL) versus late lactation (LL), and if energy yielding substrates in the form of acetate (but not glucose) can contribute to sustain milk (protein) synthesis, when...

Effect of intravenous administration of D-lysergic acid diethylamide on initiation of protein synthesis in a cell-free system derived from brain.

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Cosgrove, J W; Brown, I R

1984-05-01

An initiating cell-free protein synthesis system derived from brain was utilized to demonstrate that the intravenous injection of D-lysergic acid diethylamide (LSD) to rabbits resulted in a lesion at the initiation stage of brain protein synthesis. Three inhibitors of initiation, edeine, poly(I), and aurintricarboxylic acid were used to demonstrate a reduction in initiation-dependent amino acid incorporation in the brain cell-free system. One hour after LSD injection, there was also a measurable decrease in the formation of 40S and 80S initiation complexes in vitro, using either [35S]methionine or [35S]Met-tRNAf. Analysis of the methionine pool size after LSD administration indicated there was no change in methionine levels. Analysis of the formation of initiation complexes in the brain cell-free protein synthesis system prepared 6 h after LSD administration indicated that there was a return to control levels at this time. The effects of LSD on steps in the initiation process are thus reversible.

Histology of peri-implant bone in a failed implant retrieved from an area of osteonecrosis of the jaw in a patient suffering from multiple myeloma and treated with intravenous bisphosphonates

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Marco Degidi

2012-03-01

Full Text Available Background: Osteonecrosis of the jaw (ONJ has been reported in the past few years in patients undergoing treatment with bisphosphonates (BP. Few published histological studies of ONJ can be found in the literature and no study has been reported on the peri-implant bone around a dental implant retrieved from an area of ONJ. The aim of the present case was to report the histology of the peri-implant bone around an implant retrieved from an area of ONJ. Materials and methods: Multiple myeloma was diagnosed to a 72-year-old male. The patient underwent treatment with intravenous pamidronate for 2 years and with intravenous zoledronate for additional 3 years. Five years after the diagnosis, 7 immediately loaded dental implants were inserted in the mandible. A preoperative panoramic radiography did show no pre-existing bone lesions. No healing of the post-extraction sockets of the right third molar and of the left second molar was observed. Three years after the implant insertion a breakdown of the oral mucosa covering the implants was observed. The most distal implant was retrieved with a trephine bur, due to mobility. Discussion: The histological findings showed some areas with osseointegration in patients undergoing BP treatment for malignant disease. Conclusion: There is certainly a temporal association between BP use and development of ONJ, but a correlation does not necessarily mean causation. Moreover, generalisations about this complex relationship cannot be made on the basis of a single case report. In patients undergoing intravenous treatment, clinicians must be aware of the increased risk of implant failure and, probably, implant insertion should be avoided at all, until more conclusive data are available.

Intravenous/oral ciprofloxacin therapy versus intravenous ceftazidime therapy for selected bacterial infections.

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Gaut, P L; Carron, W C; Ching, W T; Meyer, R D

1989-11-30

The efficacy and toxicity of sequential intravenous and oral ciprofloxacin therapy was compared with intravenously administered ceftazidime in a prospective, randomized, controlled, non-blinded trial. Thirty-two patients (16 patients receiving ciprofloxacin and 16 patients receiving ceftazidime) with 38 infections caused by susceptible Pseudomonas aeruginosa, enteric gram-negative rods, Salmonella group B, Serratia marcescens, Pseudomonas cepacia, and Xanthomonas maltophilia at various sites were evaluable for determination of efficacy. Length of therapy varied from seven to 25 days. Concomitant antimicrobials included intravenously administered beta-lactams for gram-positive organisms, intravenous/oral metronidazole and clindamycin for anaerobes, and intravenous/local amphotericin B for Candida albicans. Intravenous administration of 200 mg ciprofloxacin every 12 hours to 11 patients produced peak serum levels between 1.15 and 3.12 micrograms/ml; trough levels ranged between 0.08 and 0.86 micrograms/ml. Overall response rates were similar for patients receiving ciprofloxacin and ceftazidime. Emergence of resistance was similar in both groups--one Enterobacter cloacae and two P. aeruginosa became resistant after ciprofloxacin therapy and two P. aeruginosa became resistant after ceftazidime therapy. The frequency of superinfection with a variety of organisms was also similar in both groups. Adverse events related to ciprofloxacin included transient pruritus at the infusion site and generalized rash leading to drug discontinuation (one patient each), and with ceftazidime adverse effects included pain at the site of infusion and the development of allergic interstitial nephritis (one patient each). Overall, intravenous/oral ciprofloxin therapy appears to be as safe and effective as intravenous ceftazidime therapy in the treatment of a variety of infections due to susceptible aerobic gram-negative organisms.

Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

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Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

2016-01-01

Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

Directory of Open Access Journals (Sweden)

Ryan C Curtis

Full Text Available Clinical studies using definitive-intent stereotactic radiation therapy (SRT for the local treatment of canine osteosarcoma (OSA have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy. Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA and parathyroid hormone (PTH are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total. Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis 8 weeks after radiation in the combined (ZA/PTH treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

The elimination rate of 123I-heptadecanoic acid after intracoronary and intravenous administration

International Nuclear Information System (INIS)

Visser, F.C.; Eenige, M.J. van; Wall, E.E. van der; Engelen, C.J. van; Cock, C.C. de; Roos, J.P.; Westera, G.; Lingen, A. van; Hollander, W. den; Heidendal, G.A.K.

1985-01-01

When calculating the elimination rate of radioactivity after the administration of radioiodinated heptadecanoic acid ( 123 I-HDA), background correction is necessary due to the high level of background activity. In the present study, the subtraction method of Freundlieb et al. was investigated by comparing the half-time values of the elimination rate after intravenous (i.v.) and intracoronary (i.c.) injection. In the latter case, no background correction was necessary. Six patients undergoing cardiac catheterization were studied. Scintigraphy was performed after the injection of 123 I-HDA into the left coronary artery and after i.v. injection. Half-time values are calculated from regions of interest drawn over myocardium perfused by the left-anterior descending branch (LAD) and the left circumflex artery (LCX). In the LAD region, the mean half-time value in the i.c. study was 22 min, while in the corrected i.v. study, the mean value was 27 min. In the LCX region, the half-time values were 24 and 33 min, respectively. The background-subtraction procedure proposed by Freundlieb et al. for i.v.-injected 123 I-HDA is incomplete, as it resulted in half-time values that were higher than those of the i.c. study. (orig.)

Optimal Timing of Bisphosphonate Administration in Combination with Samarium-153 Oxabifore in the Treatment of Painful Metastatic Bone Disease

International Nuclear Information System (INIS)

Rasulova, Nigora; Lyubshin, Vladimir; Arybzhanov, Dauranbek; Sagdullaev, Sh.; Krylov, Valery; Khodjibekov, Marat

2013-01-01

While bisphosphonates are indicated for prevention of skeletal-related events, radionuclide therapy is widely used for treatment of painful bone metastases. Combined radionuclide therapy with bisphosphonates has demonstrated improved effectiveness in achieving bone pain palliation in comparison to mono therapy with radionuclides or bisphosphonates alone. However, there are conflicting reports as to whether bisphosphonates adversely influence skeletal uptake of the bone-seeking radiotracers used for therapy. Recent studies analyzing influence of Zoledronic acid on total bone uptake of Samarium-153 EDTMP (Sm-153 EDTMP) by measuring cumulative urinary activity of Sm-153 on baseline study, as well as in combination with bisphosphonates (administrated 48 hours prior to Sm-153) did not provide any statistically significant difference in urinary excretion of Sm-153 between the two groups. It may be noted that the exact temporal sequence of bisphosphonate administration vis a vis radionuclide therapy has not yet been studied. One of the side effects of bisphosphonates is transient flare effect on bone pain. Radionuclide therapy may also have similar side effect. Keeping in view the above the current study was designed with the main objective of determining the exact timing of bisphosphonate administration in patients receiving combined therapy so as to achieve optimal efficacy of bone pain palliation. Ninety-three patients suffering from metastatic bone pain who received combination therapy with Sm-153 oxabifore (an analog of Sm-153 EDTMP) and Zoledronic acid were divided into three groups according to the timing of Zoledronic acid administration: Group I: 39 patients who received Zoledronic acid 7 or more days prior to Sm-153 oxabifore treatment; Group II: 32 patients who received Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment and Group III: 22 patients who received Zoledronic acid 7 days after Sm-153 oxabifore treatment. Sm-153 oxabifore was administered

Effective combination treatment of GD2-expressing neuroblastoma and Ewing's sarcoma using anti-GD2 ch14.18/CHO antibody with Vγ9Vδ2+ γδT cells.

Science.gov (United States)

Fisher, Jonathan P H; Flutter, Barry; Wesemann, Florian; Frosch, Jennifer; Rossig, Claudia; Gustafsson, Kenth; Anderson, John

Gamma delta T lymphocytes (γδT cells) have pleiotropic properties including innate cytotoxicity, which make them attractive effectors for cancer immunotherapy. Combination treatment with zoledronic acid and IL-2 can activate and expand the most common subset of blood γδT, which express the Vγ9Vδ2 T cell receptor (TCR) (Vδ2 T cells). Vγ9Vδ2 T cells are equipped for antibody-dependent cell-mediated cytotoxicity (ADCC) through expression of the low-affinity FcγR CD16. GD2 is a highly ranked tumor associated antigen for immunotherapy due to bright expression on the cell surface, absent expression on normal tissues and availability of therapeutic antibodies with known efficacy in neuroblastoma. To explore the hypothesis that zoledronic acid, IL-2 and anti-GD2 antibodies will synergize in a therapeutic combination, we evaluated in vitro cytotoxicity and tumor growth inhibition in the GD2 expressing cancers neuroblastoma and Ewing's sarcoma. Vδ2 T cells exert ADCC against GD2-expressing Ewing's sarcoma and neuroblastoma cell lines, an effect which correlates with the brightness of GD2 expression. In an immunodeficient mouse model of small established GD2-expressing Ewing's sarcoma or neuroblastoma tumors, the combination of adoptively transferred Vδ2+ T cells, expanded in vitro with zoledronic acid and IL-2, with anti-GD2 antibody ch14.18/CHO, and with systemic zoledronic acid, significantly suppressed tumor growth compared to antibody or γδT cell-free controls. Combination treatment using ch14.18/CHO, zoledronic acid and IL-2 is more effective than their use in isolation. The already-established safety profiles of these agents make testing of the combination in GD2 positive cancers such as neuroblastoma or Ewing's sarcoma both rational and feasible.

Fractures and mortality in relation to different osteoporosis treatments.

Science.gov (United States)

Yun, Huifeng; Delzell, Elizabeth; Saag, Kenneth G; Kilgore, Meredith L; Morrisey, Michael A; Muntner, Paul; Matthews, Robert; Guo, Lingli; Wright, Nicole; Smith, Wilson; Colón-Emeric, Cathleen; O'Connor, Christopher M; Lyles, Kenneth W; Curtis, Jeffrey R

2015-01-01

Few studies have assessed the effectiveness of different drugs for osteoporosis (OP). We aimed to determine if fracture and mortality rates vary among patients initiating different OP medications. We used the Medicare 5% sample to identify new users of intravenous (IV) zoledronic acid (n=1.674), oral bisphosphonates (n=32.626), IV ibandronate (n=492), calcitonin (n=2.606), raloxifene (n=1.950), or parathyroid hormone (n=549). We included beneficiaries who were ≥65 years of age, were continuously enrolled in fee-for-service Medicare and initiated therapy during 2007-2009. Outcomes were hip fracture, clinical vertebral fracture, and all-cause mortality, identified using inpatient and physician diagnosis codes for fracture, procedure codes for fracture repair, and vital status information. Cox regression models compared users of each medication to users of IV zoledronic acid, adjusting for multiple confounders. During follow-up (median, 0.8-1.5 years depending on the drug), 787 subjects had hip fractures, 986 had clinical vertebral fractures, and 2.999 died. Positive associations included IV ibandronate with hip fracture (adjusted hazard ratio (HR), 2.37; 95% confidence interval (CI) 1.25-4.51), calcitonin with vertebral fracture (HR=1.59, 95%CI 1.04-2.43), and calcitonin with mortality (HR=1.31; 95%CI 1.02-1.68). Adjusted HRs for other drug-outcome comparisons were not statistically significant. IV ibandronate and calcitonin were associated with higher rates of some types of fracture when compared to IV zolendronic acid. The relatively high mortality associated with use of calcitonin may reflect the poorer health of users of this agent.

Intravenous Lipids for Preterm Infants: A Review

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Ghassan S. A. Salama

2015-01-01

Full Text Available Extremely low birth weight infants (ELBW are born at a time when the fetus is undergoing rapid intrauterine brain and body growth. Continuation of this growth in the first several weeks postnatally during the time these infants are on ventilator support and receiving critical care is often a challenge. These infants are usually highly stressed and at risk for catabolism. Parenteral nutrition is needed in these infants because most cannot meet the majority of their nutritional needs using the enteral route. Despite adoption of a more aggressive approach with amino acid infusions, there still appears to be a reluctance to use early intravenous lipids. This is based on several dogmas that suggest that lipid infusions may be associated with the development or exacerbation of lung disease, displace bilirubin from albumin, exacerbate sepsis, and cause CNS injury and thrombocytopena. Several recent reviews have focused on intravenous nutrition for premature neonate, but very little exists that provides a comprehensive review of intravenous lipid for very low birth and other critically ill neonates. Here, we would like to provide a brief basic overview, of lipid biochemistry and metabolism of lipids, especially as they pertain to the preterm infant, discuss the origin of some of the current clinical practices, and provide a review of the literature, that can be used as a basis for revising clinical care, and provide some clarity in this controversial area, where clinical care is often based more on tradition and dogma than science.

Topical fibrin sealant versus intravenous tranexamic acid for reducing blood loss following total knee arthroplasty: A systematic review and meta-analysis.

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Gao, Fuqiang; Ma, Jinhui; Sun, Wei; Guo, Wanshou; Li, Zirong; Wang, Weiguo

2016-08-01

Efficacy and safety of topical application of a fibrin sealant (FS) compared with intravenous administration of tranexamic acid (TXA) for reducing blood loss after total knee arthroplasty (TKA) is controversial. We undertook a meta-analysis to compare the effects of topical application of FS or intravenous administration of TXA on blood loss after TKA. PubMed, Medline, Embase, Web of Science and the Cochrane Library were searched to identify studies comparing FS with TXA for TKA patients. The mean difference (MD) of blood loss, hemoglobin value, and odds ratios (ORs) of transfusion requirements and adverse events in FS and TXA groups were pooled throughout the study. Relevant data were analyzed using RevMan v5.3. Five studies involving 359 patients were included (181 FS vs. 178 TXA). TXA use had a significantly lower prevalence of blood transfusion (OR = 3.14; 95% confidence interval (CI), 1.67 to 5.90, P = 0.0004) and higher hemoglobin level (MD = -1.23; 95% CI, -2.19 to -0.27, P = 0.01) than FS in the early postoperative period. No significant difference was seen in total blood loss between the two groups (MD = 198.06; 95% CI, -267.45 to 663.57; P = 0.40). There were no significant differences in adverse events, superficial infections, or deep-vein thrombosis among study groups. Our meta-analysis suggests that intravenous administration of TXA for patients undergoing TKA may reduce blood-transfusion requirements and maintain higher hemoglobin levels compared with topical application of FS in the early postoperative period. There were no significant differences in total calculated blood loss and prevalence of complications between the two groups. However, owing to the variation of included studies, no firm conclusions can be drawn. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events

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Acquavella J

2016-07-01

Full Text Available John Acquavella,1 Vera Ehrenstein,1 Morten Schiødt,2 Uffe Heide-Jørgensen,1 Anders Kjellman,3,4 Svein Hansen,5 Cecilia Larsson Wexell,6,7 Bente Brokstad Herlofson,8 Sven Erik Noerholt,9 Haijun Ma,10 Katarina Öhrling,11 Rohini K Hernandez,12 Henrik Toft Sørensen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Oral and Maxillofacial Surgery, Rigshospitalet, Copenhagen, Denmark; 3Department of Urology, Karolinska University Hospital, 4Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden; 5Cancer Registry of Norway, Oslo University Hospital, Oslo, Norway; 6Department of Oral and Maxillofacial Surgery, Södra Älvsborg Hospital, Borås, Sweden; 7Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 8Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway; 9Department of Oral and Maxillofacial Surgery, Aarhus University Hospital, Aarhus, Denmark; 10Global Biostatistical Science, Amgen Inc., Thousand Oaks, CA, USA; 11Clinical Development, Amgen Inc., Thousand Oaks, CA, USA; 12Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA Objective: Osteonecrosis of the jaw (ONJ is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post-authorization safety study of cancer patients treated with antiresorptive therapies. Methods: As part of a comprehensive pharmacovigilance plan, developed with regulators’ input, the study will estimate incidence of ONJ and of serious infections among adult cancer patients with bone metastases treated with denosumab (120 mg subcutaneously or zoledronic acid (4 mg intravenously, adjusted for renal function

Advantages and Disadvantages of Bone Protective Agents in Metastatic Prostate Cancer: Lessons Learned

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Christian Thomas

2016-08-01

Full Text Available Nine out of ten metastatic prostate cancer (PCa patients will develop osseous metastases. Of these, every second will suffer from skeletal-related events (SRE. SRE are associated with an increased risk for death, which is markedly increased in the presence of pathological fracture. Moreover, health insurance costs nearly double in the presence of SRE. Zoledronic acid and denosumab are both approved drugs for the prevention or delay of SRE in castration-resistant prostate cancer (CRPC patients with osseous metastases. However, long-term treatment with one of these two drugs is associated with the development of medication-related osteonecrosis of the jaw (MRONJ. Routine inspections of the oral cavity before and during treatment are mandatory in these patients. Regarding imaging techniques, bone scintigraphy seems to be a promising tool to detect early stage MRONJ. Zoledronic acid does not reduce the incidence of SRE in hormone-sensitive PCa. First data shows 3-monthly application of zoledronic acid to be equi-effective to monthly application.

Intentional intravenous mercury injection

African Journals Online (AJOL)

In this case report, intravenous complications, treatment strategies and possible ... Mercury toxicity is commonly associated with vapour inhalation or oral ingestion, for which there exist definite treatment options. Intravenous mercury ... personality, anxiousness, irritability, insomnia, depression and drowsi- ness.[1] However ...

Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Products

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Patrycja Miszczyk

2017-02-01

Full Text Available The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylenebisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction—namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1 as a major product, along with N-ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E macrophages were determined. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid.

Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Products.

Science.gov (United States)

Miszczyk, Patrycja; Wieczorek, Dorota; Gałęzowska, Joanna; Dziuk, Błażej; Wietrzyk, Joanna; Chmielewska, Ewa

2017-02-08

The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction-namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1 ) as a major product, along with N -ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E macrophages were determined. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid.

Intravenous Tranexamic Acid Bolus plus Infusion Is Not More Effective than a Single Bolus in Primary Hip Arthroplasty: A Randomized Controlled Trial.

Science.gov (United States)

Zufferey, Paul J; Lanoiselée, Julien; Chapelle, Céline; Borisov, Dmitry B; Bien, Jean-Yves; Lambert, Pierre; Philippot, Rémi; Molliex, Serge; Delavenne, Xavier

2017-09-01

Preoperative administration of the antifibrinolytic agent tranexamic acid reduces bleeding in patients undergoing hip arthroplasty. Increased fibrinolytic activity is maintained throughout the first day postoperation. The objective of the study was to determine whether additional perioperative administration of tranexamic acid would further reduce blood loss. This prospective, double-blind, parallel-arm, randomized, superiority study was conducted in 168 patients undergoing unilateral primary hip arthroplasty. Patients received a preoperative intravenous bolus of 1 g of tranexamic acid followed by a continuous infusion of either tranexamic acid 1 g (bolus-plus-infusion group) or placebo (bolus group) for 8 h. The primary outcome was calculated perioperative blood loss up to day 5. Erythrocyte transfusion was implemented according to a restrictive transfusion trigger strategy. The mean perioperative blood loss was 919 ± 338 ml in the bolus-plus-infusion group (84 patients analyzed) and 888 ± 366 ml in the bolus group (83 patients analyzed); mean difference, 30 ml (95% CI, -77 to 137; P = 0.58). Within 6 weeks postsurgery, three patients in each group (3.6%) underwent erythrocyte transfusion and two patients in the bolus group experienced distal deep-vein thrombosis. A meta-analysis combining data from this study with those of five other trials showed no incremental efficacy of additional perioperative administration of tranexamic acid. A preoperative bolus of tranexamic acid, associated with a restrictive transfusion trigger strategy, resulted in low erythrocyte transfusion rates in patients undergoing hip arthroplasty. Supplementary perioperative administration of tranexamic acid did not achieve any further reduction in blood loss.

Increased Incretin But Not Insulin Response after Oral versus Intravenous Branched Chain Amino Acids.

Science.gov (United States)

Gojda, Jan; Straková, Radka; Plíhalová, Andrea; Tůma, Petr; Potočková, Jana; Polák, Jan; Anděl, Michal

2017-01-01

Branched chain amino acids (BCAAs) are known to exert an insulinotropic effect. Whether this effect is mediated by incretins (glucagon like peptide 1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) is not known. The aim of this study was to show whether an equivalent dose of BCAA elicits a greater insulin and incretin response when administered orally than intravenously (IV). Eighteen healthy, male subjects participated in 3 tests: IV application of BCAA solution, oral ingestion of BCAA and placebo in an equivalent dose (30.7 ± 1.1 g). Glucose, insulin, C-peptide, glucagon, GLP-1, GIP, valine, leucine and isoleucine concentrations were measured. Rise in serum BCAA was achieved in both BCAA tests, with incremental areas under the curve (iAUC) being 2.1 times greater for IV BCAA compared with those of the oral BCAA test (p BCAA induced comparable insulin response greater than placebo (240 min insulin iAUC: oral 3,411 ± 577 vs. IV 2,361 ± 384 vs. placebo 961.2 ± 175 pmol/L, p = 0.0006). Oral BCAA induced higher GLP-1 (p BCAA tests with no change in the placebo group. An equivalent dose of BCAA elicited a comparable insulin and greater incretin response when administered orally and not when administered through IV. We conclude that insulinotropic effects of BCAA are partially incretin dependent. © 2017 S. Karger AG, Basel.

Established role of bisphosphonate therapy for prevention of skeletal complications from myeloma bone disease.

Science.gov (United States)

Terpos, Evangelos; Dimopoulos, Meletios A; Berenson, James

2011-02-01

Patients with advanced multiple myeloma (MM) often have increased osteolytic activity of osteoclasts and impaired osteogenesis by osteoblasts, resulting in osteolytic bone lesions that increase the risk of skeletal-related events (SREs) including pathologic fracture, the need for radiotherapy or surgery to bone, and spinal cord compression. Such SREs are potentially life-limiting, and can reduce patients' functional independence and quality of life. Bisphosphonates (e.g., oral clodronate and intravenous pamidronate and zoledronic acid) can inhibit osteoclast-mediated osteolysis, thereby reducing the risk of SREs, ameliorating bone pain, and potentially prolonging survival in patients with MM. Extensive clinical experience demonstrates that bisphosphonates are generally well tolerated, and common adverse events are typically mild and manageable. Studies are ongoing to optimize the timing and duration of bisphosphonate therapy in patients with bone lesions from MM. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Unexplained abdominal pain as a driver for inappropriate therapeutics: an audit on the use of intravenous proton pump inhibitors

OpenAIRE

Pauline Siew Mei Lai; Yin Yen Wong; Yong Chia Low; Hui Ling Lau; Kin-Fah Chin; Sanjiv Mahadeva

2014-01-01

Background. Proton pump inhibitors (PPIs) are currently the most effective agents for acid-related disorders. However, studies show that 25–75% of patients receiving intravenous PPIs had no appropriate justification, indicating high rates of inappropriate prescribing. Objective. To examine the appropriate use of intravenous PPIs in accordance with guidelines and the efficacy of a prescribing awareness intervention at an Asian teaching institution. Setting. Prospective audit in a tertiary hosp...

Effect of prolonged intravenous glucose and essential amino acid infusion on nitrogen balance, muscle protein degradation and ubiquitin-conjugating enzyme gene expression in calves

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Scaife Jes R

2008-02-01

Full Text Available Abstract Background Intravenous infusions of glucose and amino acids increase both nitrogen balance and muscle accretion. We hypothesised that co-infusion of glucose (to stimulate insulin and essential amino acids (EAA would act additively to improve nitrogen balance by decreasing muscle protein degradation in association with alterations in muscle expression of components of the ubiquitin-proteasome proteolytic pathway. Methods We examined the effect of a 5 day intravenous infusions of saline, glucose, EAA and glucose + EAA, on urinary nitrogen excretion and muscle protein degradation. We carried out the study in 6 restrained calves since ruminants offer the advantage that muscle protein degradation can be assessed by excretion of 3 methyl-histidine and multiple muscle biopsies can be taken from the same animal. On the final day of infusion blood samples were taken for hormone and metabolite measurement and muscle biopsies for expression of ubiquitin, the 14-kDa E2 ubiquitin conjugating enzyme, and proteasome sub-units C2 and C8. Results On day 5 of glucose infusion, plasma glucose, insulin and IGF-1 concentrations were increased while urea nitrogen excretion and myofibrillar protein degradation was decreased. Co-infusion of glucose + EAA prevented the loss of urinary nitrogen observed with EAA infusions alone and enhanced the increase in plasma IGF-1 concentration but there was no synergistic effect of glucose + EAA on the decrease in myofibrillar protein degradation. Muscle mRNA expression of the ubiquitin conjugating enzyme, 14-kDa E2 and proteasome sub-unit C2 were significantly decreased, after glucose but not amino acid infusions, and there was no further response to the combined infusions of glucose + EAA. Conclusion Prolonged glucose infusion decreases myofibrillar protein degradation, prevents the excretion of infused EAA, and acts additively with EAA to increase plasma IGF-1 and improve net nitrogen balance. There was no evidence of

Comparison of oral versus intravenous application of tranexamic acid in total knee and hip arthroplasty: A systematic review and meta-analysis.

Science.gov (United States)

Zhang, Lu-Kai; Ma, Jian-Xiong; Kuang, Ming-Jie; Zhao, Jie; Wang, Ying; Lu, Bin; Sun, Lei; Ma, Xin-Long

2017-09-01

Tranexamic acid (TXA) is regarded as one of the most important drugs in reducing blood loss and hemoglobin (Hb) drop after total knee arthroplasty (TKA) or total hip arthroplasty (THA). Treatment with tranexamic acid (TXA) by intravenous application has been discussed extensively. Recently, several studies have reported that oral administration has an effect on blood sparing. Therefore, we performed a meta-analysis to investigate the efficacy and safety between oral TXA and intravenous TXA (IV-TXA) for blood sparing in total knee and hip arthroplasty. Randomized controlled trials (RCTs) or retrospective cohort studies (RCSs) about relevant research were searched for by using PubMed (1996-April 2017), Embase (1980-April 2017), and the Cochrane Library (CENTRAL, April 2017). Five studies that compared oral with IV administration of TXA were included in our meta-analysis. Meta-analysis results were collected and analyzed by the software Review Manager 5.3 (Copenhagen: The Nordic Cochrane Center, The Collaboration, 2014). Five studies containing 3474 patients met the inclusion criteria. Our pooled data analysis indicated that oral TXA was as effective as the IV-TXA in terms of the average Hb drop (P = 0.88), total Hb loss (P = 0.57), total blood loss (P = 0.42), transfusion rate (P = 0.16), complications (P = 0.61), and length of hospital stay (P = 1.00). Compared with the IV-TXA method, oral TXA shows similar blood-sparing efficacy for preventing hemoglobin drop, total hemoglobin loss, and total blood loss following TKA or THA. In addition, no significant differences of transfusion rate, complications, or length of hospital stay were found between the 2 groups. However, because of the limited number of included studies, more studies of high quality are needed to further identify the optimal administration time for oral TXA. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Administration of gentamicin and ampicillin by continuous intravenous infusion to newborn infants during parenteral nutrition

DEFF Research Database (Denmark)

Colding, H; Andersen, G E

1982-01-01

Gentamicin and ampicillin were dissolved in an L-amino acid solution especially prepared for newborn infants and infused intravenously over 24 h in 7 babies with serious neonatal surgical problems. Serum concentrations of the antibiotics were maintained rather constant and well above the minimal ...

Ultrasonography-guided peripheral intravenous access versus traditional approaches in patients with difficult intravenous access.

Science.gov (United States)

Costantino, Thomas G; Parikh, Aman K; Satz, Wayne A; Fojtik, John P

2005-11-01

We assess the success rate of emergency physicians in placing peripheral intravenous catheters in difficult-access patients who were unsuccessfully cannulated by emergency nurses. A technique using real-time ultrasonographic guidance by 2 physicians was compared with traditional approaches using palpation and landmark guidance. This was a prospective, systematically allocated study of all patients requiring intravenous access who presented to 2 university hospitals between October 2003 and March 2004. Inclusion criterion was the inability of any available nurse to obtain intravenous access after at least 3 attempts on a subgroup of patients who had a history of difficult intravenous access because of obesity, history of intravenous drug abuse, or chronic medical problems. Exclusion criterion was the need for central venous access. Patients presenting on odd days were allocated to the ultrasonographic-guided group, and those presenting on even days were allocated to the traditional-approach group. Endpoints were successful cannulation, number of sticks, time, and patient satisfaction. Sixty patients were enrolled, 39 on odd days and 21 on even days. Success rate was greater for the ultrasonographic group (97%) versus control (33%), difference in proportions of 64% (95% confidence interval [CI] 39% to 71%). The ultrasonographic group required less overall time (13 minutes versus 30 minutes, for a difference of 17 [95% CI 0.8 to 25.6]), less time to successful cannulation from first percutaneous puncture (4 minutes versus 15 minutes, for a difference of 11 [95% CI 8.2 to 19.4]), and fewer percutaneous punctures (1.7 versus 3.7, for a difference of 2.0 [95% CI 1.27 to 2.82]) and had greater patient satisfaction (8.7 versus 5.7, for a difference of 3.0 [95% CI 1.82 to 4.29]) than the traditional landmark approach. Ultrasonographic-guided peripheral intravenous access is more successful than traditional "blind" techniques, requires less time, decreases the number of

The human experience with intravenous levodopa

Directory of Open Access Journals (Sweden)

Shan H Siddiqi

2016-01-01

Full Text Available Objective: To compile a comprehensive summary of published human experience with levodopa given intravenously, with a focus on information required by regulatory agencies.Background: While safe intravenous (IV use of levodopa has been documented for over 50 years, regulatory supervision for pharmaceuticals given by a route other than that approved by the U.S. Food and Drug Administration (FDA has become increasingly cautious. If delivering a drug by an alternate route raises the risk of adverse events, an investigational new drug (IND application is required, including a comprehensive review of toxicity data.Methods: Over 200 articles referring to IV levodopa were examined for details of administration, pharmacokinetics, benefit and side effects.Results: We identified 142 original reports describing IVLD use in humans, beginning with psychiatric research in 1959-1960 before the development of peripheral decarboxylase inhibitors. Over 2750 subjects have received IV levodopa, and reported outcomes include parkinsonian signs, sleep variables, hormone levels, hemodynamics, CSF amino acid composition, regional cerebral blood flow, cognition, perception and complex behavior. Mean pharmacokinetic variables were summarized for 49 healthy subjects and 190 with Parkinson’s disease. Side effects were those expected from clinical experience with oral levodopa and dopamine agonists. No articles reported deaths or induction of psychosis.Conclusion: Over 2750 patients have received IV levodopa with a safety profile comparable to that seen with oral administration.

Intravenous Therapy: Hazards, Complications and Their Prevention ...

African Journals Online (AJOL)

Breaks in aseptic techniques, faulty handling of parenteral fluid containers, failure to discard out-dated intravenous solutions and tubings contribute to occurrence of intravenous-associated sepsis. Improper technique and lack of pharmaceutical knowledge when adding drugs into intravenous fluids contribute to ...

Highest Plasma Phenylalanine Levels in (Very Premature Infants on Intravenous Feeding; A Need for Concern.

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Ernesto Cortés-Castell

Full Text Available To analyse the association in newborns between blood levels of phenylalanine and feeding method and gestational age.This observational, cross-sectional study included a sample of 11,829 infants between 2008 and 2013 in a Spanish region. Data were recorded on phenylalanine values, feeding method [breast, formula, mixed (breast plus formula, or partial or fully intravenous feeding], gestational age in weeks (<32, 32-37, ≥37, gender and days since birth at the moment of blood collection. Outcomes were [phenylalanine] and [phenylalanine] ≥95th percentile. Associations were analysed using multivariate models [linear (means difference and logistic regression (adjusted odds ratios].Higher phenylalanine values were associated with lower gestational age (p<0.001 and with intravenous feeding (p<0.001.The degree of prematurity and intravenous feeding influenced the plasma concentration of phenylalanine in the newborn. Caution should be taken in [phenylalanine] for newborns with intravenous feeding, monitoring them carefully. Very preterm infants given the recommended amount of amino acids should also be strictly monitored. These findings should be taken into consideration and call for adapting the amounts to the needs of the infant.

Comparison of topical and intravenous administration of tranexamic acid for blood loss control during total joint replacement: Review of literature

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Georgi P. Georgiev

2018-04-01

Full Text Available Purpose: Many randomised controlled trials and meta-analysis studies have presented the efficacy of tranexamic acid (TXA without an increase of complications. However, questions still remain about the type of administration, optimal dose and secondary outcomes of TXA in total hip arthroplasty and total knee arthroplasty. The aim of this review is to summarise the existing information in literature concerning the pharmacological characteristics of TXA, forms, doses, types of application and contraindications for its use. Methods: A literature review containing 63 articles from the PubMed data starting from the first description of tranexamic acid until now was made in trying to present the existing information in a simple and effective way. Results: TXA leads to statistically significant reduction of peri and postoperative bleeding and in that way decreases blood transfusion rates and the infection risk. Topical and intravenous (IV use of TXA revealed similar results, with no increase of deep venous thrombosis. Therefore, topical TXA could be a reasonable alternative in patients with contraindications for IV application of TXA. Conclusions: Blood loss control with TXA, a synthetic analogue of the amino acid lysine, may be an excellent and safe alternative to allogeneic blood transfusion after total hip arthroplasty and total knee arthroplasty. Further studies are needed to establish the efficacy of combined IV and topical administration of TXA with regard to diminishing blood loss and reducing hospital stay. The Translational Potential of this Article: This review briefly presents the pharmacological characteristics of TXA, forms, doses, types of application and contraindications for its use with regard to diminishing blood loss and reducing hospital stay for better therapeutic strategies in orthopaedics. Keywords: Arthroplasty, Review, Tranexamic acid

Use of intravenous tranexamic acid in total knee arthroplasty: a meta-analysis of randomized controlled trials

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FU De-jie

2013-04-01

Full Text Available 【Abstract】 Objective: The effect of tranexamic acid (TA on patients receiving total knee arthroplasty (TKA has been reported in many small clinical trials. But single trials are not sufficient enough to clarify the effectiveness and safety of TA. So, we carried out a meta-analysis of randomized controlled trials to investigate the efficacy and safety of the intravenous use of TA in TKA. Methods: Literatures were retrieved in Cochrane Library, OVID, PubMed, EMBASE, CNKI and Wanfang Data. All the related literatures were checked by two independent investigators and only the high quality randomized con-trolled trials were enrolled. Relevant data were analyzed using RevMan 5.1 to compare the difference of blood loss, transfusion and complications between TA group and con-trol group. Results: There were 353 related literatures and only 22 randomized controlled trials met the inclusion criteria. The use of TA in TKA significantly reduced total blood loss by a mean of 435.41 ml (95% CI 300.62-570.21, P<0.01, post-operative blood loss by a mean of 406.69 ml (95% CI 333.16-480.22, P<0.01. TA also significantly lowered the transfu-sion rate (risk difference 0.30, 95% CI 0.21-0.39, P<0.01 and transfusion volume (mean difference 0.95 unit, 95% CI 0.53-1.37, P<0.01. The risks between TA group and control group in developing deep vein thrombosis and pulmonary embo-lism were not statistically significant. Conclusion: TA is beneficial for patients undergoing TKA, which can significantly reduce total blood loss, post-operative blood loss, transfusion rate, and transfusion volume. Meanwhile TA is recommended to reduce deep vein thrombosis and pulmonary embolism following TKA. Key words: Tranexamic acid; Arthroplasty; Knee; Blood loss, surgical; Meta-analysis

INTRAVENOUS IMMUNOGLOBULIN IN PEDIATRIC RHEUMATOLOGY PRACTICE

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E. I. Alexeeva

2015-01-01

Full Text Available Modern successful treatment of rheumatic diseases is impossible without the use of intravenous immunoglobulin. The use of intravenous immunoglobulin is based on strict indications developed as a result of long-term multicenter controlled studies. The article highlights the issues of using immunoglobulin in pediatric rheumatology practice, and provides the review of literature with the results from the evaluation of the efficiency of intravenous immunoglobulin confirming the efficiency of the drug only for certain rheumatic diseases. 

Unexplained abdominal pain as a driver for inappropriate therapeutics: an audit on the use of intravenous proton pump inhibitors.

Science.gov (United States)

Lai, Pauline Siew Mei; Wong, Yin Yen; Low, Yong Chia; Lau, Hui Ling; Chin, Kin-Fah; Mahadeva, Sanjiv

2014-01-01

Background. Proton pump inhibitors (PPIs) are currently the most effective agents for acid-related disorders. However, studies show that 25-75% of patients receiving intravenous PPIs had no appropriate justification, indicating high rates of inappropriate prescribing. Objective. To examine the appropriate use of intravenous PPIs in accordance with guidelines and the efficacy of a prescribing awareness intervention at an Asian teaching institution. Setting. Prospective audit in a tertiary hospital in Malaysia. Method. Every 4th intravenous PPI prescription received in the pharmacy was screened against hospital guidelines. Interventions for incorrect indication/dose/duration were performed. Patients' demographic data, medical history and the use of intravenous PPI were collected. Included were all adult inpatients prescribed intravenous PPI. Main Outcome Measure. Proportion of appropriate IV PPI prescriptions. Results. Data for 106 patients were collected. Most patients were male [65(61.3%)], Chinese [50(47.2%)], with mean age ± SD = 60.3 ± 18.0 years. Most intravenous PPI prescriptions were initiated by junior doctors from the surgical [47(44.3%)] and medical [42(39.6%)] departments. Only 50/106(47.2%) patients had upper gastrointestinal endoscopy/surgery performed to verify the source of bleeding. Unexplained abdominal pain [81(76.4%)] was the main driver for prescribing intravenous PPIs empirically, out of which 73(68.9%) were for suspected upper gastrointestinal bleed. Overall, intravenous PPI was found to be inappropriately prescribed in 56(52.8%) patients for indication, dose or duration. Interventions on the use of intravenous PPI were most effective when performed by senior doctors (100%), followed by clinical pharmacists (50%), and inpatient pharmacists (37.5%, p = 0.027). Conclusion. Inappropriate intravenous PPI usage is still prevalent despite the enforcement of hospital guidelines. The promotion of prescribing awareness and evidence-based prescribing

H9N2 influenza virus acquires intravenous pathogenicity on the introduction of a pair of di-basic amino acid residues at the cleavage site of the hemagglutinin and consecutive passages in chickens

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Sakoda Yoshihiro

2011-02-01

Full Text Available Abstract Background Outbreaks of avian influenza (AI caused by infection with low pathogenic H9N2 viruses have occurred in poultry, resulting in serious economic losses in Asia and the Middle East. It has been difficult to eradicate the H9N2 virus because of its low pathogenicity, frequently causing in apparent infection. It is important for the control of AI to assess whether the H9N2 virus acquires pathogenicity as H5 and H7 viruses. In the present study, we investigated whether a non-pathogenic H9N2 virus, A/chicken/Yokohama/aq-55/2001 (Y55 (H9N2, acquires pathogenicity in chickens when a pair of di-basic amino acid residues is introduced at the cleavage site of its HA molecule. Results rgY55sub (H9N2, which had four basic amino acid residues at the HA cleavage site, replicated in MDCK cells in the absence of trypsin after six consecutive passages in the air sacs of chicks, and acquired intravenous pathogenicity to chicken after four additional passages. More than 75% of chickens inoculated intravenously with the passaged virus, rgY55sub-P10 (H9N2, died, indicating that it is pathogenic comparable to that of highly pathogenic avian influenza viruses (HPAIVs defined by World Organization for Animal Health (OIE. The chickens inoculated with the virus via the intranasal route, however, survived without showing any clinical signs. On the other hand, an avirulent H5N1 strain, A/duck/Hokkaido/Vac-1/2004 (Vac1 (H5N1, acquired intranasal pathogenicity after a pair of di-basic amino acid residues was introduced into the cleavage site of the HA, followed by two passages by air sac inoculation in chicks. Conclusion The present results demonstrate that an H9N2 virus has the potential to acquire intravenous pathogenicity in chickens although the morbidity via the nasal route of infection is lower than that of H5N1 HPAIV.

Ascorbic acid in bronchial asthma

African Journals Online (AJOL)

1983-04-23

Apr 23, 1983 ... by comparing the pre-ascorbic acid results with those obtained 21/2 hours after the intravenous ... (ASO), C-reactive protein and antibodies to certain respiratory viruses. These investigations were ..... vitamin.6 However, other investigators were unable to detect any protective effects of ascorbic acid on the ...

Pyrogenicity of polyadenylic.polyuridylic acid in rabbits.

Science.gov (United States)

Won, S J; Lin, M T

1991-05-01

Polyadenylic.polyuridylic acid injected intravenously into rabbits produced a rapid-onset, monophasic fever. Pyrogenic tolerance occurred in rabbits following daily injections of polyadenylic.polyuridylic acid. However, direct injection of the agent into the preoptic anterior hypothalamic region of rabbit's brain produced a markedly different fever. After an intrahypothalamic injection of polyadenylic.polyuridylic acid, fever was delayed in onset and persisted for a longer period. At room temperature, the fever was due to both increased metabolism and cutaneous vasoconstriction. In a colder atmosphere the fever was due solely to increased metabolism, whereas in the heat the fever was due to reduction in cutaneous blood flow and respiratory evaporative heat loss. In addition, the fever induced by intravenous polyadenylic.polyuridylic acid injection was reversed by a cyclooxygenase inhibitor, but not by a protein synthesis inhibitor. Polyadenylic.polyuridylic acid was shown to stimulate PGE2 production from rabbit's hypothalamus in vitro. The results reveal that this agent is a prostaglandin-dependent pyrogen.

Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects.

Science.gov (United States)

Raffa, Robert B; Pawasauskas, Jayne; Pergolizzi, Joseph V; Lu, Luke; Chen, Yin; Wu, Sutan; Jarrett, Brant; Fain, Randi; Hill, Lawrence; Devarakonda, Krishna

2018-03-01

Several features favor paracetamol (acetaminophen) administration by the intravenous rather than the oral route in the postoperative setting. This study compared the pharmacokinetics and bioavailability of oral and intravenous paracetamol when given with or without an opioid, morphine. In this randomized, single-blind, parallel, repeat-dose study in healthy adults, subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at 6-h intervals, and morphine infusions (0.125 mg/kg) at the 2nd and 3rd intervals. Comparisons of plasma pharmacokinetic profiles were conducted before, during, and after opioid co-administrations. Twenty-two subjects were included in the pharmacokinetic analysis. Observed paracetamol peak concentration (C max ) and area under the plasma concentration-time curve over the dosing interval (AUC 0-6 ) were reduced when oral paracetamol was co-administered with morphine (reduced from 11.6 to 7.25 µg/mL and from 31.00 to 25.51 µg·h/mL, respectively), followed by an abruptly increased C max and AUC 0-6 upon discontinuation of morphine (to 13.5 µg/mL and 52.38 µg·h/mL, respectively). There was also a significantly prolonged mean time to peak plasma concentration (T max ) after the 4th dose of oral paracetamol (2.84 h) compared to the 1st dose (1.48 h). However, pharmacokinetic parameters of paracetamol were not impacted when intravenous paracetamol was co-administered with morphine. Morphine co-administration significantly impacted the pharmacokinetics of oral but not intravenous paracetamol. The abrupt release of accumulated paracetamol at the end of morphine-mediated gastrointestinal inhibition following oral but not intravenous administration of paracetamol suggests that intravenous paracetamol provides a better option for the management of postoperative pain. CLINICALTRIALS. NCT02848729.

Mycotic aneurysms in intravenous drug abusers: the utility of intravenous digital subtraction angiography

International Nuclear Information System (INIS)

Shetty, P.C.; Krasicky, G.A.; Sharma, R.P.; Vemuri, B.R.; Burke, M.M.

1985-01-01

Two-hundred thirteen intravenous digital subtraction angiographic (DSA) examinations were performed on 195 intravenous drug abusers to rule out the possibility of a mycotic aneurysm in a groin, neck, or upper extremity infection. Twenty-three surgically proved cases of mycotic aneurysm were correctly identified with no false positive results. In addition, six cases of major venous occlusion were documented. The authors present the results of their experience and conclude that DSA is an effective and cost-efficient method of examining this high risk patient population

[Renal response to intravenous administration of sodium bicarbonate in newborn infants of different gestational ages].

Science.gov (United States)

Jasso-Gutiérrez, L; Araujo, B; Fuse-Moteji, R; del Castillo, E D

1976-01-01

The study comprised a series of 16 neonates made up of 5 patients of 33 weeks of gestation, 5 infants of 35 weeks and 6 more of 40 weeks of gestation. Blood pH, PaCO2 and HCO3- were measured together with bicarbonate, ammonium, titrable acidity and hydrogen ions in urine before and after intravenous infusion of sodium bicarbonate. Before infusion of bicarbonate, titrable acidity, ammonium and net acidity in urine were higher in accordance with a greater gestational age. As the administration of bicarbonate elapsed, titrable acidity, ammonium and net acidity dropped with increase in concentration of bicarbonate. A hypothesis is set forth that the differences found in the factors evaluated in urine before administration of bicarbonate depend on the physiologic characteristics set in the newborn by gestational age.

Clofibric Acid Increases the Formation of Oleic Acid in Endoplasmic Reticulum of the Liver of Rats

OpenAIRE

広瀬, 明彦; 山崎, 研; 坂本, 武史; 須永, 克佳; 津田, 整; 光本, 篤史; 工藤, なをみ; 川嶋, 洋一

2011-01-01

The effects of 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid) on the formation of oleic acid (18:1) from stearic acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [14C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) clofibric acid for 7 days; and the distribution of radiolabeled fatty acids among subcellul...

Orthostatic stability with intravenous levodopa

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Shan H. Siddiqi

2015-08-01

Full Text Available Intravenous levodopa has been used in a multitude of research studies due to its more predictable pharmacokinetics compared to the oral form, which is used frequently as a treatment for Parkinson’s disease (PD. Levodopa is the precursor for dopamine, and intravenous dopamine would strongly affect vascular tone, but peripheral decarboxylase inhibitors are intended to block such effects. Pulse and blood pressure, with orthostatic changes, were recorded before and after intravenous levodopa or placebo—after oral carbidopa—in 13 adults with a chronic tic disorder and 16 tic-free adult control subjects. Levodopa caused no statistically or clinically significant changes in blood pressure or pulse. These data add to previous data that support the safety of i.v. levodopa when given with adequate peripheral inhibition of DOPA decarboxylase.

Unexplained abdominal pain as a driver for inappropriate therapeutics: an audit on the use of intravenous proton pump inhibitors

Directory of Open Access Journals (Sweden)

Pauline Siew Mei Lai

2014-06-01

Full Text Available Background. Proton pump inhibitors (PPIs are currently the most effective agents for acid-related disorders. However, studies show that 25–75% of patients receiving intravenous PPIs had no appropriate justification, indicating high rates of inappropriate prescribing.Objective. To examine the appropriate use of intravenous PPIs in accordance with guidelines and the efficacy of a prescribing awareness intervention at an Asian teaching institution.Setting. Prospective audit in a tertiary hospital in Malaysia.Method. Every 4th intravenous PPI prescription received in the pharmacy was screened against hospital guidelines. Interventions for incorrect indication/dose/duration were performed. Patients’ demographic data, medical history and the use of intravenous PPI were collected. Included were all adult inpatients prescribed intravenous PPI.Main Outcome Measure. Proportion of appropriate IV PPI prescriptions.Results. Data for 106 patients were collected. Most patients were male [65(61.3%], Chinese [50(47.2%], with mean age ± SD = 60.3 ± 18.0 years. Most intravenous PPI prescriptions were initiated by junior doctors from the surgical [47(44.3%] and medical [42(39.6%] departments. Only 50/106(47.2% patients had upper gastrointestinal endoscopy/surgery performed to verify the source of bleeding. Unexplained abdominal pain [81(76.4%] was the main driver for prescribing intravenous PPIs empirically, out of which 73(68.9% were for suspected upper gastrointestinal bleed. Overall, intravenous PPI was found to be inappropriately prescribed in 56(52.8% patients for indication, dose or duration. Interventions on the use of intravenous PPI were most effective when performed by senior doctors (100%, followed by clinical pharmacists (50%, and inpatient pharmacists (37.5%, p = 0.027.Conclusion. Inappropriate intravenous PPI usage is still prevalent despite the enforcement of hospital guidelines. The promotion of prescribing awareness and evidence

Comparison of postinfusion phlebitis in intravenous push versus intravenous piggyback cefazolin.

Science.gov (United States)

Biggar, Constance; Nichols, Cynthia

2012-01-01

Reducing health care costs without adversely affecting patient safety is a constant challenge for health care institutions. Cefazolin prophylaxis via intravenous push (IVP) is more cost-effective than via intravenous piggyback (IVPB). The purpose of this study was to determine whether patient safety would be compromised (ie, an increased rate of phlebitis) with a change to the IVP method. Rates of phlebitis in orthopedic surgical patients receiving cefazolin prophylaxis via IVP versus IVPB were evaluated in a prospective quasi-experimental design of 240 patients. The first 120 subjects received cefazolin via IVPB, and the second 120 subjects received it via IVP. Results indicated no statistically significant difference in phlebitis rates in the IVPB (3.4%) versus the IVP groups (3.3%).

[Peripheral intravenous catheter-related phlebitis].

Science.gov (United States)

van der Sar-van der Brugge, Simone; Posthuma, E F M Ward

2011-01-01

Phlebitis is a very common complication of the use of intravenous catheters. Two patients with an i.v. catheter complicated by thrombophlebitis are described. Patient A was immunocompromised due to chronic lymphatic leukaemia and developed septic thrombophlebitis with positive blood cultures for S. Aureus. Patient B was being treated with flucloxacillin because of an S. Aureus infection and developed chemical phlebitis. Septic phlebitis is rare, but potentially serious. Chemical or mechanical types of thrombophlebitis are usually less severe, but happen very frequently. Risk factors include: female sex, previous episode of phlebitis, insertion at (ventral) forearm, emergency placement and administration of antibiotics. Until recently, routine replacement of peripheral intravenous catheters after 72-96 h was recommended, but randomised controlled trials have not shown any benefit of this routine. A recent Cochrane Review recommends replacement of peripheral intravenous catheters when clinically indicated only.

Gorham-Stout syndrome of the pelvic girdle treated by radiation therapy. A case report

International Nuclear Information System (INIS)

Heyd, Reinhard; Tselis, Nikolaos; Zamboglou, Nikolaos; Rabeneck, Daniela; Universitaetsklinikum Frankfurt, Frankfurt am Main; Doernenburg, Oliver

2011-01-01

The Gorham-Stout syndrome (GSS) is a rare, benign idiopathic and progressive disorder causing massive osteolysis due to a vascular hyperproliferation replacing the bony structure. Clinical experience concerning the efficacy of radiation therapy (RT) is limited to about 50 of an overall 200 cases reported worldwide. Case Report: A 24-year-old bedridden woman had histologically proven GSS with destruction of the anterior pelvic girdle and received RT for a total dose of 45.0 Gy applied in 5 weekly fractions of 1.8 Gy. In addition, the patient received intravenously 4 mg zoledronic acid once a month. One year after the combined treatment, complete pain relief occurred, and the patient was able to walk without the use of appliances. Imaging studies revealed no progression of the osteolysis but only minimal signs of remineralization. Conclusion: Combined treatment with RT and bisphosphonate administration can prevent the progression of osteolysis in GSS. Total doses of 40-45 Gy are recommended. (orig.)

Gorham-Stout syndrome of the pelvic girdle treated by radiation therapy. A case report

Energy Technology Data Exchange (ETDEWEB)

Heyd, Reinhard; Tselis, Nikolaos; Zamboglou, Nikolaos [Klinikum Offenbach, Offenbach am Main (Germany). Strahlenklinik; Rabeneck, Daniela [Klinikum Offenbach, Offenbach am Main (Germany). Strahlenklinik; Universitaetsklinikum Frankfurt, Frankfurt am Main (Germany). Klinik fuer Strahlentherapie und Onkologie; Doernenburg, Oliver [Klinikum Offenbach, Offenbach am Main (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie

2011-02-15

The Gorham-Stout syndrome (GSS) is a rare, benign idiopathic and progressive disorder causing massive osteolysis due to a vascular hyperproliferation replacing the bony structure. Clinical experience concerning the efficacy of radiation therapy (RT) is limited to about 50 of an overall 200 cases reported worldwide. Case Report: A 24-year-old bedridden woman had histologically proven GSS with destruction of the anterior pelvic girdle and received RT for a total dose of 45.0 Gy applied in 5 weekly fractions of 1.8 Gy. In addition, the patient received intravenously 4 mg zoledronic acid once a month. One year after the combined treatment, complete pain relief occurred, and the patient was able to walk without the use of appliances. Imaging studies revealed no progression of the osteolysis but only minimal signs of remineralization. Conclusion: Combined treatment with RT and bisphosphonate administration can prevent the progression of osteolysis in GSS. Total doses of 40-45 Gy are recommended. (orig.)

Optimizing the use of intravenous therapy in internal medicine.

Science.gov (United States)

Champion, Karine; Mouly, Stéphane; Lloret-Linares, Celia; Lopes, Amanda; Vicaut, Eric; Bergmann, Jean-François

2013-10-01

We aimed to evaluate the impact of physicians' educational programs in the reduction of inappropriate intravenous lines in internal medicine. Fifty-six French internal medicine units were enrolled in a nationwide, prospective, blinded, randomized controlled trial. Forms describing the patients with an intravenous line and internal medicine department characteristics were filled out on 2 separate days in January and April 2007. Following the first visit, all units were randomly assigned to either a specific education program on the appropriate indications of an intravenous line, during February and March 2007, or no training (control group). The Investigators' Committee then blindly evaluated the clinical relevance of the intravenous line according to pre-established criteria. The primary outcome was the percentage of inappropriate intravenous lines. During January 2007, intravenous lines were used in 475 (24.9%) of the 1910 hospitalized patients. Of these, 80 (16.8%) were considered inappropriate. In April 2007, 416 (22.8%) of the 1823 hospitalized patients received an intravenous line, which was considered in 10.2% (21/205) of patients managed by trained physicians, versus 16.6% (35/211) of patients in the control group (relative difference 39%; 95% confidence interval, -0.6-13.3; P = .05). Reduced intravenous administration of fluids, antibiotics, and analgesics accounted for the observed decrease. The use of a simple education program reduced the rate of inappropriate intravenous lines by almost 40% in an internal medicine setting (NCT01633307). Copyright © 2013 Elsevier Inc. All rights reserved.

Complex intravenous anesthesia in interventional procedures

International Nuclear Information System (INIS)

Xie Zonggui; Hu Yuanming; Huang Yunlong; You Yong; Wu Juan; Huang Zengping; Li Jian

2006-01-01

Objective: To evaluate the value and safety of Diprivan and Fentany intravenous administration of analgesia in interventional procedures. Methods: Diprivan with Fentany intravenous administration for analgesia was used in eighty interventional procedures of sixty-five patients, without tracheal tube insertion. Vital signs including HR, BP, arterial oxygen saturation (SpO 2 ) and patients' reaction to operating were recorded. Results: Intravenous anesthesia was cared out successfully in eighty interventional procedures, with patients under sleeping condition during the operation, together with no pain and no agony memory of the procedure. The amount of Diprivan was 500±100 mg and Fentany was 0.2±0.025 mg. Mean arterial pressure and SpO 2 were 11.4±2.2 kPa, 10.6±2.1 kPa and 98±1.0, 96±1.5 respectively before and after ten minutes of the operation, with no significant difference. Conclusions: Diprivan with Fentany intravenous administration for interventional procedure analgesia possess good safety, painless and no agony memory of the procedure; therefor ought to be recommended. (authors)

LOCAL APPLICATION OF TRANEXAMIC ACID IN KNEE REPLACEMENT

Directory of Open Access Journals (Sweden)

E. V. Pshenitsyna

2016-01-01

Full Text Available The purpose of the study – assessment of the efficacy of local application of tranexamic acid in TKA and the choice of the optimal dosage. Materials and methods. 48 patients were included in open-prospective study and were randomized to one of four groups. In the first group tranexamic acid was used as intravenous bolus at the beginning of the operation at a dose of 15 mg/kg. Additionally, after the installation of the prosthetic components, the surgeon performed periarticular infiltration of soft tissue by tranexamic acid solution at a dose of 15 mg/kg. In the second group of patients tranexamic acid was used as 500 mg intravenous bolus before surgery, and 500 mg locally after installation of the prosthesis components. In the third group of patients received tranexamic acid once at the beginning of the operation at a dose of 15 mg/kg iv bolus. In the fourth group tranexam was used after surgery once at a dose of 10 mg/kg. Results. In the first group of patients were achieved statistically significant, 5-6 times, reduction of blood loss on drainage in comparison with other groups, where the volume of postoperative blood loss was not significantly different between groups. Also in the first group recorded the smallest decrease in hemoglobin at the 5th postoperative day compared to the third and fourth groups. Complications associated with the use of tranexamic acid were not revealed. Conclusion. The method of periarticular infiltration by tranexamic acid in combination with its intravenous use in knee joint replacement is an effective and safe method for reduction of post-operative blood loss.

Intra-articular versus intravenous tranexamic acid application in total knee arthroplasty: a meta-analysis of randomized controlled trials.

Science.gov (United States)

Mi, Bobin; Liu, Guohui; Zhou, Wu; Lv, Huijuan; Liu, Yi; Zha, Kun; Wu, Qipeng; Liu, Jing

2017-07-01

The purpose of this meta-analysis was to compare the blood loss and complications of intra-articular (IA) with intravenous (IV) tranexamic acid (TXA) for total knee arthroplasty (TKA). A comprehensive search of studies was conducted to identify related articles in Pubmed, Embase, Cochrane central Register of Controlled Trials, springerLink, OVID and the Research published from January 1980 to September 2016. All studies that compared IA TXA with IV TXA application on TKA were included. Main outcomes of the two methods were collected and analyzed by using Review Manager 5.3. There were 16 randomized controlled trials with 1308 cases met the criteria. Compared with IV TXA, IA TXA had similar blood volume of drainage, hidden blood loss, transfusion rate and complications (P > 0.05). IA TXA had lower total blood loss than IV TXA, and there was significant difference (P  0.05) when compared with IA TXA. Both IA TXA and single dose of IV TXA are effective in reducing total blood loss and postoperative hemoglobin drop without increasing complications of DVT or PE. The current meta-analysis suggests that 1.5 g TXA by IA administration or 1 g TXA by IV administration 10 min before tourniquet deflation is effective and safe in patients undergoing TKA.

Stability studies of lincomycin hydrochloride in aqueous solution and intravenous infusion fluids

Directory of Open Access Journals (Sweden)

Czarniak P

2016-03-01

Full Text Available Petra Czarniak, Michael Boddy, Bruce Sunderland, Jeff D Hughes School of Pharmacy, Curtin University, Perth, WA, Australia Purpose: The purpose of this study was to evaluate the chemical stability of Lincocin® (lincomycin hydrochloride in commonly used intravenous fluids at room temperature (25°C, at accelerated-degradation temperatures and in selected buffer solutions.Materials and methods: The stability of Lincocin® injection (containing lincomycin 600 mg/2 mL as the hydrochloride stored at 25°C±0.1°C in sodium lactate (Hartmann’s, 0.9% sodium chloride, 5% glucose, and 10% glucose solutions was investigated over 31 days. Forced degradation of Lincocin® in hydrochloric acid, sodium hydroxide, and hydrogen peroxide was performed at 60°C. The effect of pH on the degradation rate of lincomycin hydrochloride stored at 80°C was determined.Results: Lincomycin hydrochloride was found to maintain its shelf life at 25°C in sodium lactate (Hartmann’s solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution, with less than 5% lincomycin degradation occurring in all intravenous solutions over a 31-day period. Lincomycin hydrochloride showed less rapid degradation at 60°C in acid than in basic solution, but degraded rapidly in hydrogen peroxide. At all pH values tested, lincomycin followed first-order kinetics. It had the greatest stability near pH 4 when stored at 80°C (calculated shelf life of 4.59 days, and was least stable at pH 2 (calculated shelf life of 0.38 days.Conclusion: Lincocin® injection was chemically found to have a shelf life of at least 31 days at 25°C when added to sodium lactate (Hartmann’s solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution. Solutions prepared at approximately pH 4 are likely to have optimum stability. Keywords: lincomycin, stability, pH, intravenous fluids, IV additives

Computed tomography intravenous cholangiography

International Nuclear Information System (INIS)

Nascimento, S.; Murray, W.; Wilson, P.

1997-01-01

Indications for direct visualization of the bile ducts include bile duct dilatation demonstrated by ultrasound or computed tomography (CT) scanning, where the cause of the bile duct dilatation is uncertain or where the anatomy of bile duct obstruction needs further clarification. Another indication is right upper quadrant pain, particularly in a post-cholecystectomy patient, where choledocholithiasis is suspected. A possible new indication is pre-operative evaluation prior to laparoscopic cholecystectomy. The bile ducts are usually studied by endoscopic retrograde cholangiopancreatography (ERCP), or, less commonly, trans-hepatic cholangiography. The old technique of intravenous cholangiography has fallen into disrepute because of inconsistent bile-duct opacification. The advent of spiral CT scanning has renewed interest in intravenous cholangiography. The CT technique is very sensitive to the contrast agent in the bile ducts, and angiographic and three-dimensional reconstructions of the biliary tree can readily be obtained using the CT intravenous cholangiogram technique (CT IVC). Seven patients have been studied using this CT IVC technique, between February 1995 and June 1996, and are the subject of the present report. Eight further studies have since been performed. The results suggest that CT IVC could replace ERCP as the primary means of direct cholangiography, where pancreatic duct visualization is not required. (authors)

Accumulation of radioactivity in rat brain and peripheral tissues including salivary gland after intravenous administration of 14C-D-aspartic acid

International Nuclear Information System (INIS)

Imai, Kazuhiro; Fukushima, Takeshi; Santa, Tomofumi; Homma, Hiroshi; Sugihara, Juko; Kodama, Hirohiko; Yoshikawa, Masayoshi.

1997-01-01

After the intravenous administration of 14 C-D-aspartic acid (Asp) into Sprague-Dawley rats (male, 7-week-old), the distribution and elimination of radioactivity was investigated by the whole body autoradiography. High radioactivities were detected in pineal gland, pituitary gland and salivary gland at 30 min after administration. The other tissues detected were liver, lung, adrenal gland, pancreas and spleen where D-Asp was reported to occur naturally. After 24 hr, the radioactivities were still detected at high levels in the pineal, pituitary and salivary glands. The data suggested the natural occurrence of D-Asp in salivary gland. After careful examination utilizing fluorescent derivatization and chiral separation by high-performance liquid chromatography, the presence of D-Asp was, for the first time, demonstrated in salivary gland in situ, the concentration of which was 7.85 ± 1.0 nmol/g. The administration of 14 C-L-Asp was also carried out. The data suggested that D-Asp in the circulating blood is one of the sources of the tissue D-Asp. (author)

Intentional intravenous mercury injection | Yudelowitz | South African ...

African Journals Online (AJOL)

Intravenous mercury injection is rarely seen, with few documented cases. Treatment strategies are not clearly defined for such cases, although a few options do show benefit. This case report describes a 29-year-old man suffering from bipolar disorder, who presented following self-inflicted intravenous injection of mercury.

Intravenous iron-containing products: EMA procrastination.

Science.gov (United States)

2014-07-01

A European reassessment has led to identical changes in the summaries of product characteristics (SPCs) for all intravenous iron-containing products: the risk of serious adverse effects is now highlighted, underlining the fact that intravenous iron-containing products should only be used when the benefits clearly outweigh the harms. Unfortunately, iron dextran still remains on the market despite a higher risk of hypersensitivity reactions than with iron sucrose.

Evaluation of Prescriptions and Use of Intravenous Pantoprazole in General Wards and Intensive Care Unit of Shahid Sadoughi Hospital in Yazd

Directory of Open Access Journals (Sweden)

Seyed-Mojtaba Sohrevardi

2016-05-01

Full Text Available Background: Proton pump inhibitors (PPIs are currently the most effective agents for acid related disorders. However, studies show that 25-75% of patients receiving intravenous Pantoprazole had no appropriate justification, indicating high rate of inappropriate prescribing in hospitals. The aim of this study is to examine the appropriate use of intravenous Pantoprazole in accordance with guidelines at Shahid Sadoughi hospital.Methods: From January to April 2015, sample of 100 prescriptions who received Intravenous (IV Pantoprazole were collected with observational and sectional model in Intensive care unit (ICU and general wards of “Shahid Sadoughi” Hospital of Yazd, Iran. Clinical data from patient records are obtained and these data were mapped to establish clinical criteria and appropriate use of Intravenous Pantoprazole.Results: The majority (63% of Intravenous Pantoprazole prescriptions were deemed inappropriate in terms of either indication for use, dose or duration of therapy. 51.5% of the patients were above 55 years old. Endoscopy did not performed in most of the Non UGIB (Non upper gastrointestinal bleeding cases. Most Intravenous Pantoprazole prescriptions were ordered by junior doctors (Intern, and again this group were significantly less likely to prescribe the drug for appropriate reasons when compared with more experienced clinicians.Conclusion: This study suggests that the majority of IV PPI prescriptions in our hospital are inappropriate. Awareness of the result of this article through medical staff could result in more judicious use of intravenous pantoprazole and dose optimization. Physicians and pharmacists can work together to create solutions to inappropriate drug use.

1-3-7 minute intravenous urography

International Nuclear Information System (INIS)

Bahk, Yong Whee; Yoon, Sei Chul; Lee, Myung Hee

1980-01-01

Intravenous urography (IVU) as it is used widely today was probably started in early 1950's after the introduction of triiodobenzoic acid compounds as contrast media. This long cherished traditional method consists of taking radiograms at 5, 15 and 25 minutes after the injection of contrast medium. There are a few modifications of this standard urographic examination such as five minute IVU (Woodruff, 1959), minute-sequence pyelogram (Maxwell et al., 1964), drip infusion pyelography (Schencker, 1964) and nephrotomography (Evans et al., 1955). The present study has been undertaken to test if the conventional standard IVU can be more rapidly performed without losing essential informational contents of urograms. In this new clinical trial, urograms were taken at the end of 1, 3 and 7 minutes instead of 5, 15 and 25 minutes after the intravenous injection of contrast medium. We injected 40 ml of meglumine diatrizoate solution within 30 seconds using an 18G iv needle. (The amount of injected contrast medium has been reduced recently to ordinary single dose of 20 ml for subjects weighing less than 8 kg). Upon viewing the 7 minute film in front of an automatic processor, the examination was terminated after obtaining an upright view unless any further radiogram was indicated. As shown in Tables and Figures, our new 1-3-7 minute method has been proven to provide us with as much essential and useful information as conventional 5-15-25 minute urography. Thus, we were able to finish one examination within 10 minutes without losing any necessary diagnostic information. In some of patients with obstructive uropathy such as stone the examination was extended as long as it was desired. Side reactions were occasional nausea, flushing and rare mild vomiting which never prevented the examination

Microbiological quality of some brands of intravenous fluids ...

African Journals Online (AJOL)

Microbiological quality of some brands of intravenous fluids produced by some pharmaceutical companies in Nigeria was investigated. Membrane filtration method was used for concentration of contaminating organisms in the intravenous fluids. Thioglycollate medium, Tryptone Soya broth, Brilliant Green Agar ...

Administration costs of intravenous biologic drugs for rheumatoid arthritis

OpenAIRE

Soini, Erkki J; Leussu, Miina; Hallinen, Taru

2013-01-01

Background Cost-effectiveness studies explicitly reporting infusion times, drug-specific administration costs for infusions or real-payer intravenous drug cost are few in number. Yet, administration costs for infusions are needed in the health economic evaluations assessing intravenously-administered drugs. Objectives To estimate the drug-specific administration and total cost of biologic intravenous rheumatoid arthritis (RA) drugs in the adult population and to compare the obtained costs wit...

Low-dose intravenous lidocaine as treatment for proctalgia fugax.

Science.gov (United States)

Peleg, Roni; Shvartzman, Pesach

2002-01-01

Proctalgia fugax is characterized by a sudden internal anal sphincter and anorectic ring attack of pain of a short duration. Description of the influence of intravenous lidocaine treatment for proctalgia fugax. A 28-year-old patient suffering of proctalgia fugax for 8 months. Conventional treatment efforts did not improve his condition. A single dose of an intravenous lidocaine infusion completely stopped his pain attacks. Based on the experience reported in this case and the potential benefit of this treatment for proctalgia fugax, controlled studies comparing intravenous lidocaine with placebo should be conducted to confirm the observation and to provide a more concrete basis for the use of intravenous lidocaine for this indication.

Systematic review and meta-analysis of perioperative intravenous tranexamic acid use in spinal surgery.

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Baohui Yang

Full Text Available BACKGROUND: Tranexamic acid (TXA is well-established as a versatile oral, intramuscular, and intravenous (IV antifibrinolytic agent. However, the efficacy of IV TXA in reducing perioperative blood transfusion in spinal surgery is poorly documented. METHODOLOGY: We conducted a meta-analysis of randomized controlled trials (RCTs and quasi-randomized (qi-RCTs trials that included patients for various spinal surgeries, such as adolescent scoliosis surgery administered with perioperative IV TXA according to Cochrane Collaboration guidelines using electronic PubMed, Cochrane Central Register of Controlled Trials, and Embase databases. Additional journal articles and conference proceedings were manually located by two independent researchers. RESULTS: Totally, nine studies were included, with a total sample size of 581 patients. Mean blood loss was decreased in patients treated with perioperative IV TXA by 128.28 ml intraoperatively (ranging from 33.84 to 222.73 ml, 98.49 ml postoperatively (ranging from 83.22 to 113.77 ml, and 389.21 ml combined (ranging from 177.83 to 600.60 ml. The mean volume of transfused packed cells were reduced by 134.55 ml (ranging 51.64 to 217.46 (95% CI; P = 0.0001. Overall, the number of patients treated with TXA who required blood transfusions was lower by 35% than that of patients treated with the comparator and who required blood transfusions (RR 0.65; 95% CI; 0.53 to 0.85; P<0.0001, I(2 = 0%. A dose-independent beneficial effect of TXA was observed, and confirmed in subgroup and sensitivity analyses. A total of seven studies reported DVT data. The study containing only a single DVT case was not combined. CONCLUSIONS: The blood loss was reduced in spinal surgery patients with perioperative IV TXA treatment. Also the percentage of spinal surgery patients who required blood transfusion was significantly decreased. Further evaluation is required to confirm our findings before TXA can be safely used in patients

Methods of preparing and using intravenous nutrient compositions

International Nuclear Information System (INIS)

Beigler, M.A.; Koury, A.J.

1983-01-01

A method for preparing a stable, dry-packaged, sterile, nutrient composition which upon addition of sterile, pyrogen-free water is suitable for intravenous administration to a mammal, including a human, is described. The method comprises providing the nutrients in a specific dry form and state of physical purity acceptable for intravenous administration, sealing the nutrients in a particular type of container adapted to receive and dispense sterile fluids and subjecting the container and its sealed contents to a sterilizing, nondestructive dose of ionizing radiation. The method results in a packaged, sterile nutrient composition which may be dissolved by the addition of sterile pyrogen-free water. The resulting aqueous intravenous solution may be safely administered to a mammal in need of nutrient therapy. The packaged nutrient compositions of the invention exhibit greatly extended storage life and provide an economical method of providing intravenous solutions which are safe and efficacious for use. (author)

Cost-minimization of mabthera intravenous versus subcutaneous administration

NARCIS (Netherlands)

Bax, P.; Postma, M.J.

2013-01-01

Objectives: To identify and compare all costs related to preparing and administrating MabThera for the intravenous and subcutaneous formulations in Dutch hematological patients. The a priori notion is that the costs of subcutaneous MabThera injections are lower compared to intravenous infusion due

Ascorbic acid concentrations in aqueous humor after systemic vitamin C supplementation in patients with cataract: pilot study.

Science.gov (United States)

Hah, Young-Sool; Chung, Hye Jin; Sontakke, Sneha B; Chung, In-Young; Ju, Sunmi; Seo, Seong-Wook; Yoo, Ji-Myong; Kim, Seong-Jae

2017-07-11

To measure ascorbic acid concentration in aqueous humor of patients with cataract after oral or intravenous vitamin C supplementation. Forty-two eyes of 42 patients with senile cataract who underwent uncomplicated cataract surgery were enrolled. Patients (n = 14 each) were administered oral vitamin C (2 g), intravenous vitamin C (20 g) or no treatment (control group) on the day before surgery. Samples of aqueous humor (0.1 cm 3 ) were obtained by anterior chamber aspiration at the beginning of surgery and stored at -80 °C. Ascorbic acid concentration in aqueous humor was measured by high-pressure liquid chromatography. The mean age at surgery was 62.5 years, with no difference among the three groups. The mean ± standard deviation concentrations of ascorbic acid in aqueous humor in the control and oral and intravenous vitamin C groups were 1347 ± 331 μmol/L, 1859 ± 408 μmol/L and 2387 ± 445 μmol/L, respectively. Ascorbic acid concentration was significantly lower in the control than in the oral (P humor is increased by systemic vitamin C supplementation, with intravenous administration being more effective than oral administration.

Pharmacokinetics of oxiracetam and its degraded substance (HOPAA after oral and intravenous administration in rats

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Xinhuan Wan

2014-12-01

Full Text Available The pharmacokinetics of oxiracetam and its degraded substance (4-hydroxy-2-oxo-1-pyrrolidine acetic acid, HOPAA after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method. Three groups of rats after an overnight fasted received 10 g/kg (n = 6 oxiracetam suspensions orally, and 2 g/kg (n = 6 normal or degraded oxiracetam injections intravenously via a caudal tail vein, respectively. Before the pharmacokinetic experiment, a simple safety evaluation test was conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice. There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within two weeks, demonstrating that HOPAA was non-toxic in mice. Following intravenous administration of the normal injections, the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase. The values of t1/2 were 3.1 ± 1.5 h for oxiracetam and 0.8 ± 0.2 h for HOPAA, and the mean residence times (MRT were 1.2 ± 0.1 h and 0.8 ± 0.1 h, respectively. Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections. Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes, and both had a longer t1/2 and MRT than those of intravenous administration. Contents of HOPAA in three groups were calculated based on AUC0–t values of the two analytes. The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetam at the same time for every group. Additionally, the values of absolute bioavailability of oxiracetam were about 8.0% and 7.4% calculated by the normal or degraded oxiracetam injections, which were far less than the value of 75% reported in literature, indicating the necessity of further study.

Essential fatty acid deficiency in surgical patients.

Science.gov (United States)

O'Neill, J A; Caldwell, M D; Meng, H C

1977-01-01

Parenteral nutrition may protect patients unable to eat from malnutrition almost indefinitely. If fat is not also given EFAD will occur. This outlines a prospective study of 28 surgical patients on total intravenous fat-free nutrition to determine the developmental course of EFAD and the response to therapy. Twenty-eight patients ranging from newborn to 66 years receiving parenteral nutrition without fat had regular determinations of the composition of total plasma fatty acids and the triene/tetraene ratio using gas liquid chromatography. Physical signs of EFAD were looked for also. Patients found to have evidence of EFAD were treated with 10% Intralipid. Topical safflower oil was used in three infants. Total plasma fatty acid composition was restudied following therapy. In general, infants on fat-free intravenous nutrition developed biochemical EFAD within two weeks, but dermatitis took longer to become evident. Older individuals took over four weeks to develop a diagnostic triene/tetraene ratio (greater than 0.4; range 0.4 to 3.75). Therapeutic correction of biochemical EFAD took 7 to 10 days but dermatitis took longer to correct. Cutaneous application of safflower oil alleviated the cutaneous manifestations but did not correct the triene/tetraene ratio of total plasma fatty acids. These studies indicate that surgical patients who are unable to eat for two to four weeks, depending upon age and expected fat stores, should receive fat as a part of their intravenous regimen. Images Fig. 7. PMID:404973

Advances in the use of intravenous techniques in ambulatory anesthesia

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Eng MR

2015-07-01

Full Text Available Matthew R Eng,1 Paul F White1,2 1Department of Anesthesiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2White Mountain Institute, The Sea Ranch, CA, USA Summary statement: Advances in the use of intravenous techniques in ambulatory anesthesia has become important for the anesthesiologist as the key perioperative physician in outpatient surgery. Key techniques and choices of anesthetics are important in accomplishing fast track goals of ambulatory surgery. Purpose of review: The anesthesiologist in the outpatient environment must focus on improving perioperative efficiency and reducing recovery times while accounting for patients' well-being and safety. This review article focuses on recent intravenous anesthetic techniques to accomplish these goals. Recent findings: This review is an overview of techniques in intravenous anesthesia for ambulatory anesthesia. Intravenous techniques may be tailored to accomplish outpatient surgery goals for the type of surgical procedure and individual patient needs. Careful anesthetic planning and the application of the plans are critical to an anesthesiologist's success with fast-track ambulatory surgery. Conclusion: Careful planning and application of intravenous techniques are critical to an anesthesiologist's success with fast-track ambulatory surgery. Keywords: intravenous anesthesia, outpatient anesthesia, fast-track surgery

Intravenous versus topical tranexamic acid in primary total hip replacement: A systemic review and meta-analysis.

Science.gov (United States)

Sun, Xiang; Dong, Qiang; Zhang, Yin-Guang

2016-08-01

Total hip arthroplasty (THA) is associated with substantial blood loss. Tranexamic acid (TXA) could reduce perioperative blood loss. The optimal administration routine of TXA remains controversial. The objective of the present systemic review and meta-analysis was to compare the effectiveness and safety of various application methods of tranexamic acid in primary THA. Potential relevant literature was identified from electronic databases including Medline, PubMed, Embase, ScienceDirect, web of science and Cochrane Library. Grey academic studies were also identified from the references of the included literature. There was no language restriction. The pooling of data was carried out by using RevMan 5.1. Three randomized controlled trials (RCTs) and two non-RCTs involving 1614 patients met the inclusion criteria. Current meta-analysis indicated that there were no significant differences in terms of total blood loss (MD = -30.04, 95% CI: -114.67 to 54.59, P = 0.49), postoperative hemoglobin level (MD = -0.29, 95% CI: -0.68 to 0.10, P = 0.14), transfusion rate (RD = -0.02, 95% CI: -0.5 to -0.00, P = 0.09), length of stay ((MD = -0.14, 95% CI: -0.30 to 0.01, P = 0.07) or operation time ((MD = 1.00, 95% CI: -0.31 to 2.31, P = 0.14) between treatment groups. No significant differences were found regarding the incidence of adverse effects such as wound infection (RD = -0.01, 95% CI: -0.06 to 0.04, P = 0.66), myocardial infarction (MI) (RD = -0.01, 95% CI: -0.04 to 0.02, P = 0.61), deep venous thrombosis (DVT) (RD = 0.00, 95% CI: -0.01 to 0.01, P = 0.51) or pulmonary embolism (PE) (RD = RD = 0.00, 95% CI: -0.01 to 0.01, P = 0.63) between groups. The topical administration of TXA in THA carried similar hemostasis effects compared with intravenous use without an increased risk of thrombotic complications. No other adverse effect was identified. Topical TXA application was a simple, safe, effective and cost-effective adjunct for

The intravenous injection of illicit drugs and needle sharing: an historical perspective.

Science.gov (United States)

Zule, W A; Vogtsberger, K N; Desmond, D P

1997-01-01

This study reviewed the literature on the history of needle sharing and intravenous drug abuse. Reports suggest that needle sharing was practiced by drug abusers as early as 1902 in China and 1914 in the United States. Intravenous drug abuse was first mentioned in the literature in 1925. However other references suggest that some opioid users were injecting intravenously prior to 1920. Outbreaks of malaria in Egypt, the United States, and China between 1929 and 1937 were attributed to needle sharing and intravenous injection of opioids. These reports suggest that both needle sharing and intravenous drug use were common by 1937. Factors such as medical use of intravenous injections, enactment and zealous enforcement of antinarcotic laws, and interactions among drug users in institutional settings such as regional hospitals and prisons may have contributed to the spread of both needle sharing and the intravenous technique among drug abusers.

Udredning af børn med urinvejsinfektion. Spiller intravenøs urografi stadig en rolle?

DEFF Research Database (Denmark)

Hansen, A; Wagner, A; Lavard, L D

1996-01-01

Ninety children referred to hospital with urinary tract infections (UTI) were investigated by intravenous urography (IVU), ultrasonography (US) and 99m-Tc dimercaptosuccinic acid scan (DMSA). Fifty-eight children also had a micturition cystourethrography performed. In 36 (40%) of the children...... for treatment or prognosis. In conclusion, IVU is an important supplement to US and DMSA in investigation programs for children with UTI. IVU should be performed in cases of renal scarring or dilatation and in children with recurrent infections....

Hepatic glycogen in humans. II. Gluconeogenetic formation after oral and intravenous glucose

International Nuclear Information System (INIS)

Radziuk, J.

1989-01-01

The amount of glycogen that is formed by gluconeogenetic pathways during glucose loading was quantitated in human subjects. Oral glucose loading was compared with its intravenous administration. Overnight-fasted subjects received a constant infusion or [3- 3 H]glucose and a marker for gluconeogenesis, [U- 14 C]lactate or sodium [ 14 C]bicarbonate [ 14 C]bicarbonate. An unlabeled glucose load was then administered. Postabsorptively, or after glucose infusion was terminated, a third tracer ([6- 3 H]glucose) infusion was initiated along with a three-step glucagon infusion. Without correcting for background stimulation of [ 14 C]glucose production or for dilution of 14 C with citric acid cycle carbon in the oxaloacetate pool, the amount of glycogen mobilized by the glucagon infusion that was produced by gluconeogenesis during oral glucose loading was 2.9 +/- 0.7 g calculated from [U- 14 C]-lactate incorporation and 7.4 +/- 1.3 g calculated using [ 14 C]bicarbonate as a gluconeogenetic marker. During intravenous glucose administration the latter measurement also yielded 7.2 +/- 1.1 g. When the two corrections above are applied, the respective quantities became 5.3 +/- 1.7 g for [U- 14 C]lactate as tracer and 14.7 +/- 4.3 and 13.9 +/- 3.6 g for oral and intravenous glucose with [ 14 C]bicarbonate as tracer (P less than 0.05, vs. [ 14 C]-lactate as tracer). When [2- 14 C]acetate was infused, the same amount of label was incorporated into mobilized glycogen regardless of which route of glucose administration was used. Comparison with previous data also suggests that 14 CO 2 is a potentially useful marker for the gluconeogenetic process in vivo

[Amplification of γδ T cells in PBMCs of healthy donors and osteosarcoma patients stimulated by zoledronate].

Science.gov (United States)

Li, Zhao-xu; Sun, Ling-ling; Cheng, Rui-lin; Sun, Zheng-wang; Ye, Zhao-ming

2012-08-01

To investigate the amplification and cytotoxicity of γδ T cells in peripheral blood mononuclear cells (PBMCs) of healthy donors and osteosarcoma patients stimulated by zoledronate (Zol) and IL-2. PBMCs from healthy donors and osteosarcoma patients were stimulated with IL-2 and Zol+IL-2, respectively. After 14-day culture, the purity of γδ T cells was assessed by flow cytometry. The cytotoxicity of γδ T cells against target cells was analyzed using a standard lactate dehydrogenase release assay with γδ T lymphocyte-sensitive Daudi cells, γδ T lymphocyte-resistant Raji cells and human osteoblast cell line, hFOB, as the target cells. After 2-week culture ex vivo of PBMCs from healthy donors and osteosarcoma patients, compared with stimulation of IL-2, Zol+IL-2 significantly promoted the amplification of γδ T cells. In addition, γδ T cells showed the higher cytotoxicity against Daudi cells, but no cytotoxic effect on normal cells like hFOB. γδ T cells of high purity and high cytotoxicity can be obtained by the stimulation of Zol combined with IL-2 on PBMCs from healthy donors and osteosarcoma patients.

Cost-effectiveness of zoledronic acid in the prevention of skeletal-related events in patients with bone metastases secondary to advanced renal cell carcinoma: application to France, Germany, and the United Kingdom.

Science.gov (United States)

Botteman, M F; Meijboom, M; Foley, I; Stephens, J M; Chen, Y M; Kaura, S

2011-12-01

The use of zoledronic acid (ZOL) has recently been shown to significantly reduce the risk of new skeletal-related events (SREs) in renal cell carcinoma (RCC) patients with bone metastases. The present exploratory study assessed the cost-effectiveness of ZOL in this population, adopting a French, German, and United Kingdom (UK) government payer perspective. This cost-effectiveness model was based on a post hoc retrospective analysis of a subset of patients with RCC who were included in a larger randomized clinical trial of patients with bone metastases secondary to a variety of cancers. In the trial, patients were randomized to receive ZOL (n = 27) or placebo (n = 19) with concomitant antineoplastic therapy every 3 weeks for 9 months (core study) plus 12 months during a study extension. Since the trial did not collect costs or data on the quality-adjusted life years (QALYs) of the patients, these outcomes had to be assumed via modeling exercises. The costs of SREs were estimated using hospital DRG tariffs. These estimates were supplemented with literature-based costs where possible. Drug, administration, and supply costs were obtained from published and internet sources. Consistent with similar economic analyses, patients were assumed to experience quality of life decrements lasting 1 month for each SRE. Uncertainty surrounding outcomes was addressed via multivariate sensitivity analyses. Patients receiving ZOL experienced 1.07 fewer SREs than patients on placebo. Patients on ZOL experienced a gain in discounted QALYs of approximately 0.1563 in France and Germany and 0.1575 in the UK. Discounted SRE-related costs were substantially lower among ZOL than placebo patients (-€ 4,196 in France, - € 3,880 in Germany, and -€ 3,355 in the UK). After taking into consideration the drug therapy costs, ZOL saved € 1,358, € 1,223, and € 719 in France, Germany, and the UK, respectively. In the multivariate sensitivity analyses, therapy with ZOL saved costs in 67

A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures.

OpenAIRE

Davis, S.; Martyn-St James, M.; Sanderson, J.; Stevens, J.; Goka, E.; Rawdin, A.; Sadler, S.; Wong, R.; Campbell, F.; Stevenson, M.; Strong, M.; Selby, P.; Gittoes, N.

2016-01-01

BACKGROUND: Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. OBJECTIVES: To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax(®) and Fosamax(®) Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel(®) and Actonel Once a Week(®), Warner Chilcott UK Ltd), ibandronic acid (Bonviva(®), Roche Products Ltd) and zoledronic acid (Aclasta(®), Novartis Pharmaceuticals UK Ltd)] for the p...

Imaging of chest disease due to intravenous heroin abuse

International Nuclear Information System (INIS)

Lian Xuhui; Chen Zhong; Ye Wenqin

2002-01-01

Objective: To study the imaging findings of the chest disease due to intravenous heroin abuse. Methods: Twenty-five cases of clinically confirmed chest disease due to intravenous heroin abuse were retrospectively analyzed. 25 cases had conventional X-ray film, 6 cases had CT scanning, and 6 cases had echocardiography scanning. Results: On X-ray and CT, the following signs were found: lung making manifold (n = 5), small patchy shadow (n = 15), pneumatocele (n = 16), small cavity (n = 16), small node (n = 7), pleural effusion (n = 8 ), pneumothorax (n = 2), hydropneumothorax (n = 6), pulmonary edema (n = 2), megacardia (n = 11), multiple-shaped lesion (n = 20). On echocardiography, tricuspid vegetation (n = 4) and tricuspid insufficiency (n = 4) were found. Conclusion: The X-ray and CT manifestations of chest inflammation due to intravenous heroin abuse are multiple. The multiple small cavities and pneumatoceles sign are of some value in the diagnosis of lung inflammation due to intravenous heroin abuse among young patients

Catheter indwell time and phlebitis development during peripheral intravenous catheter administration.

Science.gov (United States)

Pasalioglu, Kadriye Burcu; Kaya, Hatice

2014-07-01

Intravenous catheters have been indispensable tools of modern medicine. Although intravenous applications can be used for a multitude of purposes, these applications may cause complications, some of which have serious effects. Of these complications, the most commonly observed is phlebitis. This study was conducted to determine the effect of catheter indwell time on phlebitis development during peripheral intravenous catheter administration. This study determined the effect of catheter indwell time on phlebitis development during peripheral intravenous catheter administration. The study included a total of 103 individuals who were administered 439 catheters and satisfied the study enrollment criteria at one infectious diseases clinic in Istanbul/Turkey. Data were compiled from Patient Information Forms, Peripheral Intravenous Catheter and Therapy Information Forms, reported grades based on the Visual Infusion Phlebitis Assessment Scale, and Peripheral Intravenous Catheter Nurse Observation Forms. The data were analyzed using SPSS. Results : The mean patient age was 53.75±15.54 (standard deviation) years, and 59.2% of the study participants were men. Phlebitis was detected in 41.2% of peripheral intravenous catheters, and the rate decreased with increased catheter indwell time. Analyses showed that catheter indwell time, antibiotic usage, sex, and catheterization sites were significantly associated with development of phlebitis. The results of this study show that catheters can be used for longer periods of time when administered under optimal conditions and with appropriate surveillance.

Phlebitis as a consequence of peripheral intravenous administration of cisatracurium besylate in critically ill patients.

Science.gov (United States)

Meeder, Annelijn M; van der Steen, Marijke S; Rozendaal, Annemieke; van Zanten, Arthur R H

2016-10-03

This case report series describes 3 cases of cisatracurium besylate associated phlebitis after an infusion period of 14-20 hours. No similar cases have been reported in the literature. Association of phlebitis with another neuromuscular blocking agent, atracurium, has been described in the literature. The acidity of atracurium is thought to be the main cause. It is recommended that atracurium is administered only via central venous catheters when indicated to infuse over prolonged periods of time due to the acidity. Cisatracurium is a stereoisomer of atracurium and as such has the same molecular weight. Although cisatracurium also has a similar acidity as atracurium, a recommendation concerning infusion via a central venous catheter is lacking. We suggest prolonged administration of cisatracurium besylate only via centrally placed venous catheters or if not possible to careful monitor relevant peripheral intravenous sites to diminish the risks of phlebitis and associated complications or other cutaneous reactions. 2016 BMJ Publishing Group Ltd.

Is intraarticular administration of tranexamic acid better than its intravenous administration in reducing blood loss after total knee arthroplasty?

Directory of Open Access Journals (Sweden)

Ameet Pispati

2013-01-01

Full Text Available Context: It has been well-established now that intravenous (IV tranexamic acid (TXA is a potent agent to control postoperative blood loss following total knee arthroplasty (TKA. Recently, intraarticular administration of this agent has also shown good efficacy for the same. Aims: Comparison of postoperative blood loss between IV and topical administration of TXA in TKAs. Materials and Design: Eighty-six TKAs on knees were included in this study. Randomization was done so that 40 TKA received 1 g of IV TXA, while 46 had intraarticular administration of 1 g TXA. Subjets and Methods: We compared the postoperative blood loss by calculating the difference in pre- and postop hemoglobin and need for blood transfusion. Functional assessment was done on basis of Western Ontario McMaster Osteo-Arthritis Index (WOMAC scores and complications like postoperative infection, oozing from the wound site and thromboembolic manifestations. Results: Blood loss was significantly less in the intraarticular administration group as compared to the IV injection group. Total blood loss, blood transfusion group, and drain output was also less but the difference was not significant. The functional assessment (WOMAC scores were equivocal and so were the complications including thromboembolic manifestations (two cases each of deep vein thrombosis (DVT and no cases of pulmonary embolism (PE. Conclusion: Intraarticular administration of TXA to prevent postoperative blood loss in TKA is a safe and effective alternative/adjunct to its IV administration.

Osseointegration of biochemically modified implants in an osteoporosis rodent model

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B Stadlinger

2013-07-01

Full Text Available The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX osteoporotic rats (n = 32/group. In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout. Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC, peri-implant bone area (BA, bone volume/tissue volume (BV/TV and bone-mineral density (BMD in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

Intravenous to oral conversion of fluoroquinolones: knowledge versus clinical practice patterns.

Science.gov (United States)

Conort, Ornella; Gabardi, Steven; Didier, Marie-Pauline; Hazebroucq, Georges; Cariou, Alain

2002-04-01

To assess the knowledge of prescribers regarding intravenous to oral conversions of fluoroquinolones, the frequency and time until conversion, and to compare prescriber knowledge with the data collected concerning the reasons stated for continuation of intravenous fluoroquinolones. Prospective chart review and questionnaire. Large teaching hospital in Paris, France. Fifty-one males and females. Data were collected on in-patients receiving intravenous fluoroquinolone for at least three days and hospitalized in one of six in-patient units. Patients receiving intravenous fluoroquinolone for less than three days were excluded. A questionnaire to assess the awareness of a potential conversion was distributed to those practitioners who had patients reviewed during the data-collection phase. The questionnaire revealed the ten most common reasons for continuing intravenous administration for more than three days. However, the physicians agreed that most patients should be converted as soon as possible. Practice patterns differed, with only 17 of 51 patients actually converted to oral therapy. In theory, the clinicians were aware of when to perform the conversion. However, in practice, the frequency of conversion was lower than optimum. Changes in clinical practice are needed to decrease the costs of intravenous therapy, without jeopardizing quality of care.

Subchronic toxicity and immunotoxicity of MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer nanoparticles delivered intravenously into rats

International Nuclear Information System (INIS)

Liao, Longfei; Zhang, Mengtian; Liu, Huan; Zhang, Xuanmiao; Xie, Zhaolu; Zhang, Zhirong; Gong, Tao; Sun, Xun

2014-01-01

Although monomethoxy(polyethyleneglycol)-poly (D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) nanoparticles have been widely studied as a drug delivery system, little is known about their toxicity in vivo. Here we examined the subchronic toxicity and immunotoxicity of different doses of PELGE nanoparticles with diameters of 50 and 200 nm (PELGE50 and PELGE200) in rats. Neither size of PELGE nanoparticles showed obvious subchronic toxic effects during 28 d of continuous intravenous administration based on clinical observation, body weight, hematology parameters and histopathology analysis. PELGE200 nanoparticles showed no overt signs of immunotoxicity based on organ coefficients, histopathology analysis, immunoglobulin levels, blood lymphocyte subpopulations and splenocyte cytokines. Conversely, PELGE50 nanoparticles were associated with an increased organ coefficient and histopathological changes in the spleen, increased serum IgM and IgG levels, alterations in blood lymphocyte subpopulations and enhanced expression of spleen interferon-γ. Taken together, these results suggest that PELGE nanoparticles show low subchronic toxicity but substantial immunotoxicity, which depends strongly on particle size. These findings will be useful for safe application of PELGE nanoparticles in drug delivery systems. (papers)

Subchronic toxicity and immunotoxicity of MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer nanoparticles delivered intravenously into rats

Science.gov (United States)

Liao, Longfei; Zhang, Mengtian; Liu, Huan; Zhang, Xuanmiao; Xie, Zhaolu; Zhang, Zhirong; Gong, Tao; Sun, Xun

2014-06-01

Although monomethoxy(polyethyleneglycol)-poly (D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) nanoparticles have been widely studied as a drug delivery system, little is known about their toxicity in vivo. Here we examined the subchronic toxicity and immunotoxicity of different doses of PELGE nanoparticles with diameters of 50 and 200 nm (PELGE50 and PELGE200) in rats. Neither size of PELGE nanoparticles showed obvious subchronic toxic effects during 28 d of continuous intravenous administration based on clinical observation, body weight, hematology parameters and histopathology analysis. PELGE200 nanoparticles showed no overt signs of immunotoxicity based on organ coefficients, histopathology analysis, immunoglobulin levels, blood lymphocyte subpopulations and splenocyte cytokines. Conversely, PELGE50 nanoparticles were associated with an increased organ coefficient and histopathological changes in the spleen, increased serum IgM and IgG levels, alterations in blood lymphocyte subpopulations and enhanced expression of spleen interferon-γ. Taken together, these results suggest that PELGE nanoparticles show low subchronic toxicity but substantial immunotoxicity, which depends strongly on particle size. These findings will be useful for safe application of PELGE nanoparticles in drug delivery systems.

Optimal timing for intravenous administration set replacement.

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Gillies, D; O'Riordan, L; Wallen, M; Morrison, A; Rankin, K; Nagy, S

2005-10-19

Administration of intravenous therapy is a common occurrence within the hospital setting. Routine replacement of administration sets has been advocated to reduce intravenous infusion contamination. If decreasing the frequency of changing intravenous administration sets does not increase infection rates, a change in practice could result in considerable cost savings. The objective of this review was to identify the optimal interval for the routine replacement of intravenous administration sets when infusate or parenteral nutrition (lipid and non-lipid) solutions are administered to people in hospital via central or peripheral venous catheters. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL, EMBASE: all from inception to February 2004; reference lists of identified trials, and bibliographies of published reviews. We also contacted researchers in the field. We did not have a language restriction. We included all randomized or quasi-randomized controlled trials addressing the frequency of replacing intravenous administration sets when parenteral nutrition (lipid and non-lipid containing solutions) or infusions (excluding blood) were administered to people in hospital via a central or peripheral catheter. Two authors assessed all potentially relevant studies. We resolved disagreements between the two authors by discussion with a third author. We collected data for the outcomes; infusate contamination; infusate-related bloodstream infection; catheter contamination; catheter-related bloodstream infection; all-cause bloodstream infection and all-cause mortality. We identified 23 references for review. We excluded eight of these studies; five because they did not fit the inclusion criteria and three because of inadequate data. We extracted data from the remaining 15 references (13 studies) with 4783 participants. We conclude that there is no evidence that changing intravenous administration sets more often than every 96 hours

Stability studies of lincomycin hydrochloride in aqueous solution and intravenous infusion fluids.

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Czarniak, Petra; Boddy, Michael; Sunderland, Bruce; Hughes, Jeff D

2016-01-01

The purpose of this study was to evaluate the chemical stability of Lincocin(®) (lincomycin hydrochloride) in commonly used intravenous fluids at room temperature (25°C), at accelerated-degradation temperatures and in selected buffer solutions. The stability of Lincocin(®) injection (containing lincomycin 600 mg/2 mL as the hydrochloride) stored at 25°C±0.1°C in sodium lactate (Hartmann's), 0.9% sodium chloride, 5% glucose, and 10% glucose solutions was investigated over 31 days. Forced degradation of Lincocin(®) in hydrochloric acid, sodium hydroxide, and hydrogen peroxide was performed at 60°C. The effect of pH on the degradation rate of lincomycin hydrochloride stored at 80°C was determined. Lincomycin hydrochloride w as found to maintain its shelf life at 25°C in sodium lactate (Hartmann's) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution, with less than 5% lincomycin degradation occurring in all intravenous solutions over a 31-day period. Lincomycin hydrochloride showed less rapid degradation at 60°C in acid than in basic solution, but degraded rapidly in hydrogen peroxide. At all pH values tested, lincomycin followed first-order kinetics. It had the greatest stability near pH 4 when stored at 80°C (calculated shelf life of 4.59 days), and was least stable at pH 2 (calculated shelf life of 0.38 days). Lincocin(®) injection was chemically found to have a shelf life of at least 31 days at 25°C when added to sodium lactate (Hartmann's) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution. Solutions prepared at approximately pH 4 are likely to have optimum stability.

Intravenous Iron Carboxymaltose as a Potential Therapeutic in Anemia of Inflammation.

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Niklas Lofruthe

Full Text Available Intravenous iron supplementation is an effective therapy in iron deficiency anemia (IDA, but controversial in anemia of inflammation (AI. Unbound iron can be used by bacteria and viruses for their replication and enhance the inflammatory response. Nowadays available high molecular weight iron complexes for intravenous iron substitution, such as ferric carboxymaltose, might be useful in AI, as these pharmaceuticals deliver low doses of free iron over a prolonged period of time. We tested the effects of intravenous iron carboxymaltose in murine AI: Wild-type mice were exposed to the heat-killed Brucella abortus (BA model and treated with or without high molecular weight intravenous iron. 4h after BA injection followed by 2h after intravenous iron treatment, inflammatory cytokines were upregulated by BA, but not enhanced by iron treatment. In long term experiments, mice were fed a regular or an iron deficient diet and then treated with intravenous iron or saline 14 days after BA injection. Iron treatment in mice with BA-induced AI was effective 24h after iron administration. In contrast, mice with IDA (on iron deficiency diet prior to BA-IA required 7d to recover from AI. In these experiments, inflammatory markers were not further induced in iron-treated compared to vehicle-treated BA-injected mice. These results demonstrate that intravenous iron supplementation effectively treated the murine BA-induced AI without further enhancement of the inflammatory response. Studies in humans have to reveal treatment options for AI in patients.

Effects of a transmitted light device for pediatric peripheral venipuncture and intravenous cannulation

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Yamazaki S

2011-10-01

Full Text Available Shinya Yamazaki1, Shu Tomita1, Masahiro Watanabe1, Hiroyoshi Kawaai1, Kazuhiro Shimamura2 1Department of Dental Anesthesiology; 2Department of Pediatric Dentistry, Ohu University Dental Hospital, Koriyama City, Fukushima Prefecture, Japan Abstract: Pediatric peripheral venipuncture and intravenous cannulation are difficult. However, successful venipuncture and intravenous cannulation are absolutely required for pediatric clinical risk management. This study assessed the success rate of venipuncture and intravenous cannulation when transmitted light was applied to the pediatric dorsum manus. The subjects included 100 young children who were scheduled for dental treatment or oral surgery under general anesthesia. Anesthesia was induced, and insertion of an intravenous catheter into the dorsum manus was attempted with or without using transmitted light. The patients were evaluated to determine whether the venipuncture was successful, and whether the intravenous cannulation of the external catheter was successful. The success rate of venipuncture was 100% when transmitted light was used, and 83% when the transmitted light was not used (P = 0.000016. In addition, the success rate of intravenous cannulation was 88% when transmitted light was used, and 55% when the transmitted light was not used (P = 0.0000002. The shape of the vein in the dorsum manus can be clearly recognized when transmitted light is used. The use of light significantly increased the success rate of intravenous cannulation, because it allowed direct confirmation of the direction to push the intravenous catheter forward. The use of transmitted light allows for more successful venipuncture and intravenous cannulation in young children. Keywords: transmitted light, pediatric peripheral venipuncture, pediatric peripheral intravenous cannulation

Efficacy and safety of intravenous fentanyl administered by ambulance personnel

DEFF Research Database (Denmark)

Friesgaard, Kristian Dahl; Nikolajsen, Lone; Giebner, Matthias

2016-01-01

BACKGROUND: Management of pain in the pre-hospital setting is often inadequate. In 2011, ambulance personnel were authorized to administer intravenous fentanyl in the Central Denmark Region. The aim of this study was to evaluate the efficacy and safety of intravenous fentanyl administered...... by ambulance personnel. METHODS: Pre-hospital medical charts from 2348 adults treated with intravenous fentanyl by ambulance personnel during a 6-month period were reviewed. The primary outcome was the change in pain intensity on a numeric rating scale (NRS) from before fentanyl treatment to hospital arrival...... patients (1.3%) and hypotension observed in 71 patients (3.0%). CONCLUSION: Intravenous fentanyl caused clinically meaningful pain reduction in most patients and was safe in the hands of ambulance personnel. Many patients had moderate to severe pain at hospital arrival. As the protocol allowed higher doses...

Catheter fracture of intravenous ports and its management.

Science.gov (United States)

Wu, Ching-Yang; Fu, Jui-Ying; Feng, Po-Hao; Kao, Tsung-Chi; Yu, Sheng-Yueh; Li, Hao-Jui; Ko, Po-Jen; Hsieh, Hung-Chang

2011-11-01

Intravenous ports are widely used for oncology patients. However, catheter fractures may lead to the need for re-intervention. We aimed to identify the risk factors associated with catheter fractures. Between January 1 and December 31, 2006, we retrospectively reviewed the clinical data and plain chest films of 1,505 patients implanted with an intravenous port at Chang Gung Memorial Hospital. Different vascular sites were compared using the chi-square or Fisher's exact test for categorical variables, and the t test was used for continuous variables with normal distribution; P port type Arrow French (Fr.) 8.1 (P port and catheter removal is recommended. Female gender, intravenous port implantation via the subclavian route, and the Arrow Fr. 8.1 port were found to be risk factors. Patients with these risk factors should be monitored closely to avoid catheter fractures.

Successful outcome after intravenous gasoline injection.

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Domej, Wolfgang; Mitterhammer, Heike; Stauber, Rudolf; Kaufmann, Peter; Smolle, Karl Heinz

2007-12-01

Gasoline, ingested intentionally or accidentally, is toxic. The majority of reported cases of gasoline intoxication involve oral ingestion or inhalation. Data are scarce on complications and outcomes following hydrocarbon poisoning by intravenous injection. Following a suicide attempt by intravenous self-injection of 10 ml of gasoline, a 26-year-old medical student was admitted to the intensive care unit (ICU) with hemoptysis, symptoms of acute respiratory failure, chest pain, and severe abdominal cramps. Gas exchange was severely impaired and a chest x-ray indicated chemical pneumonitis. Initial treatment consisted of mechanical ventilation, supportive hyperventilation, administration of nitrogen oxide (NO), and prednisone. Unfortunately, the patient developed multi-organ dysfunction syndrome (MODS) complicated by life-threatening severe vasoplegia within 24 hours after gasoline injection. High doses of vasopressors along with massive amounts of parenteral fluids were necessary. Despite fluid replacement, renal function worsened and required hemofiltration on 5 sequential days. After 12 days of intensive care management, the patient recovered completely and was discharged to a psychiatric care facility. Intravenous gasoline injection causes major injury to the lungs, the organ bearing the first capillary bed encountered. Treatment of gasoline poisoning is symptomatic because no specific antidote is available. Early and aggressive supportive care may be conducive to a favorable outcome with minimal residual pulmonary sequelae.

Intravenous Transplantation of Mesenchymal Stromal Cells to Enhance Peripheral Nerve Regeneration

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Stella M. Matthes

2013-01-01

Full Text Available Peripheral nerve injury is a common and devastating complication after trauma and can cause irreversible impairment or even complete functional loss of the affected limb. While peripheral nerve repair results in some axonal regeneration and functional recovery, the clinical outcome is not optimal and research continues to optimize functional recovery after nerve repair. Cell transplantation approaches are being used experimentally to enhance regeneration. Intravenous infusion of mesenchymal stromal cells (MSCs into spinal cord injury and stroke was shown to improve functional outcome. However, the repair potential of intravenously transplanted MSCs in peripheral nerve injury has not been addressed yet. Here we describe the impact of intravenously infused MSCs on functional outcome in a peripheral nerve injury model. Rat sciatic nerves were transected followed, by intravenous MSCs transplantation. Footprint analysis was carried out and 21 days after transplantation, the nerves were removed for histology. Labelled MSCs were found in the sciatic nerve lesion site after intravenous injection and regeneration was improved. Intravenously infused MSCs after acute peripheral nerve target the lesion site and survive within the nerve and the MSC treated group showed greater functional improvement. The results of study suggest that nerve repair with cell transplantation could lead to greater functional outcome.

Preparation of N, N, N-trimethyl chitosan-functionalized retinoic acid ...

African Journals Online (AJOL)

nanocarrier (TR-SLNs) with enhanced anti-cancer activity. ... Retinoic acid (RA), a derivative of vitamin A, is a potential ... intravenous (i.v.) administration; therefore, RA ... °C. Preparation of TMC. TMC was synthesized by reductive methylation.

Osteoporosebehandling kan pauseres efter individuel vurdering

DEFF Research Database (Denmark)

Eiken, Pia Agnete; Abrahamsen, Bo

2017-01-01

In most patients, treatment of osteoporosis is a long-term challenge. Because alendronate and zoledronic acid accumulate in bone with some persistent antifracture efficacy after therapy, it is reasonable to consider a "drug holiday" for low-risk patients. It is recommended that the duration...

Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia

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Marković-Sovtić Gordana

2013-01-01

Full Text Available Background/Aim. Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. Methods. We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. Results. There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. Conclusion. The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

Use of intravenous immunoglobulins in clinical practice

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E.K. Donyush

2011-01-01

Full Text Available Immunoglobulins are main component of immune defense; they take part in anti-infectious resistance of organism and regulate processes of different immune reactions. Intravenous immunoglobulins are the most frequently used products made from donor blood plasma. The need in these drugs is steadily increasing during last 15–20 years, and indications are widening due to modern hightechnology methods of production and cleaning. The article presents modern data on formula, mechanisms of action and indications for different groups of intravenous immunoglobulins (standard, hyperimmune, fortified and description of possible adverse events.Key words: immuglobulines, prophylaxis, treatment, unfavorable reaction, children.

Intravenous microemulsion of docetaxel containing an anti-tumor synergistic ingredient (Brucea javanica oil): formulation and pharmacokinetics.

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Ma, Shilin; Chen, Fen; Ye, Xiaohui; Dong, Yingjie; Xue, Yingna; Xu, Heming; Zhang, Wenji; Song, Shuangshuang; Ai, Li; Zhang, Naixian; Pan, Weisan

2013-01-01

The purpose of this study was to develop a docetaxel microemulsion containing an anti-tumor synergistic ingredient (Brucea javanica oil) and to investigate the characteristics of the microemulsion. Brucea javanica oil contains oleic acid and linoleic acids that have been shown by animal and human studies to inhibit tumor formation. The microemulsion containing Brucea javanica oil, medium-chain triglyceride, soybean lecithin, Solutol®HS 15, PEG 400, and water was developed for docetaxel intravenous administration. A formulation with higher drug content, lower viscosity, and smaller particle size was developed. The droplet size distribution of the dispersed phase of the optimized microemulsion was 13.5 nm, determined using a dynamic light scattering technique. The small droplet size enabled the microemulsion droplets to escape from uptake and phagocytosis by the reticuloendothelial system and increased the circulation time of the drug. The zeta potential was -41.3 mV. The optimized microemulsion was pale yellow, transparent, and non-opalescent in appearance. The value of the combination index was 0.58, showing that there was a synergistic effect when docetaxel was combined with Brucea javanica oil. After a single intravenous infusion dose (10 mg/kg) in male Sprague Dawley rats, the area under the curve of the microemulsion was higher and the half-time was longer compared with that of docetaxel solution alone, and showed superior pharmacokinetic characteristics. These results indicate that this preparation of docetaxel in emulsion is likely to provide an excellent prospect for clinical tumor treatment.

Usefulness of modified intravenous analgesia: initial experience in uterine artery embolization for leiomyomata

International Nuclear Information System (INIS)

Yang, Seung Boo; Jung, Young Jin; Goo, Dong Erk; Jang, Yun Woo

2006-01-01

We wanted to evaluate the usefulness of modified intravenous analgesia for the management of pain during uterine artery embolization for leiomyomata. Between April 2004 and July 2004, 15 patients with symptomatic fibroids underwent uterine artery embolization and pain management. Except the three patients for whom the Visual Analogue Scale (VAS) score was not obtained, twelve patients were included in this study. For pain management, epidural PCA (Patient Controlled Analgesia) was used in two patients, intravenous PCA was used in two patients and modified intravenous analgesia injection was used in eight patients. For all the patients, we used the 2.8 Fr coaxial microcatheter and 500-710 μ m PVA particles for the embolic materials. The protocol of the modified intravenous analgesia injection was as follow, 1) prior to femoral artery puncture, 30 mg of ketorolac tromethamine (Tarasyn)was injected via an intravenous route. 2) At the time that the one side uterine artery embolization was finished, normal saline mixed 150 mg meperidine (Demerol) was administered through the side port of the intravenous line that was used for hydration. 3) Additional ketorolac tromethamine 30 mg was injected after 6 hour. The VAS score and side effects were then checked. After 12 hours, the VAS score was rechecked. If the VAS score was above 4, this was considered as failure of pain management. The VAS scores, complications and side effects for the modified intravenous analgesia injection were compared with that of IV PCA and epidural PCA. The average VAS score of the modified intravenous analgesia injection, intravenous PCA and epidural PCA was 1.4, 1 and 0, respectively; the number of additional intramuscular injections of analgesia was 0.5, 0.5 and 0, respectively. All the patients who underwent epidural PCA had back pain at the puncture site and 1 patient who underwent modified intravenous analgesia injection experienced mild dyspnea, but they easily recovered with such

Usefulness of modified intravenous analgesia: initial experience in uterine artery embolization for leiomyomata

Energy Technology Data Exchange (ETDEWEB)

Yang, Seung Boo; Jung, Young Jin [Soonchunhyang University, Gumi Hospital, Gumi (Korea, Republic of); Goo, Dong Erk; Jang, Yun Woo [Soonchunhyang University Hospital, Seoul (Korea, Republic of)

2006-04-15

We wanted to evaluate the usefulness of modified intravenous analgesia for the management of pain during uterine artery embolization for leiomyomata. Between April 2004 and July 2004, 15 patients with symptomatic fibroids underwent uterine artery embolization and pain management. Except the three patients for whom the Visual Analogue Scale (VAS) score was not obtained, twelve patients were included in this study. For pain management, epidural PCA (Patient Controlled Analgesia) was used in two patients, intravenous PCA was used in two patients and modified intravenous analgesia injection was used in eight patients. For all the patients, we used the 2.8 Fr coaxial microcatheter and 500-710 {mu} m PVA particles for the embolic materials. The protocol of the modified intravenous analgesia injection was as follow, 1) prior to femoral artery puncture, 30 mg of ketorolac tromethamine (Tarasyn)was injected via an intravenous route. 2) At the time that the one side uterine artery embolization was finished, normal saline mixed 150 mg meperidine (Demerol) was administered through the side port of the intravenous line that was used for hydration. 3) Additional ketorolac tromethamine 30 mg was injected after 6 hour. The VAS score and side effects were then checked. After 12 hours, the VAS score was rechecked. If the VAS score was above 4, this was considered as failure of pain management. The VAS scores, complications and side effects for the modified intravenous analgesia injection were compared with that of IV PCA and epidural PCA. The average VAS score of the modified intravenous analgesia injection, intravenous PCA and epidural PCA was 1.4, 1 and 0, respectively; the number of additional intramuscular injections of analgesia was 0.5, 0.5 and 0, respectively. All the patients who underwent epidural PCA had back pain at the puncture site and 1 patient who underwent modified intravenous analgesia injection experienced mild dyspnea, but they easily recovered with such

Urinary calculi composed of uric acid, cystine, and mineral salts: differentiation with dual-energy CT at a radiation dose comparable to that of intravenous pyelography.

Science.gov (United States)

Thomas, Christoph; Heuschmid, Martin; Schilling, David; Ketelsen, Dominik; Tsiflikas, Ilias; Stenzl, Arnulf; Claussen, Claus D; Schlemmer, Heinz-Peter

2010-11-01

To retrospectively evaluate radiation dose, image quality, and the ability to differentiate urinary calculi of differing compositions by using low-dose dual-energy computed tomography (CT). The institutional review board approved this retrospective study; informed consent was waived. A low-dose dual-energy CT protocol (tube voltage and reference effective tube current-time product, 140 kV and 23 mAs and 80 kV and 105 mAs; collimation, 64 × 0.6 mm; pitch, 0.7) for the detection of urinary calculi was implemented into routine clinical care. All patients (n = 112) who were examined with this protocol from July 2008 to August 2009 were included. The composition of urinary calculi was assessed by using commercially available postprocessing software and was compared with results of the reference standard (ex vivo infrared spectroscopy) in 40 patients for whom the reference standard was available. Effective doses were calculated. Image quality was rated subjectively and objectively and was correlated with patient size expressed as body cross-sectional area at the level of acquisition by using Spearman correlation coefficients. One calcified concrement in the distal ureter of an obese patient was mistakenly interpreted as mixed calcified and uric acid. One struvite calculus was falsely interpreted as cystine. All other uric acid, cystine, and calcium-containing calculi were correctly identified by using dual-energy CT. The mean radiation dose was 2.7 mSv. The average image quality was rated as acceptable, with a decrease in image quality in larger patients. Low-dose unenhanced dual-source dual-energy CT can help differentiate between calcified, uric acid, and cystine calculi at a radiation dose comparable to that of conventional intravenous pyelography. Because of decreased image quality in obese patients, only nonobese patients should be examined with this protocol. © RSNA, 2010.

Breast abscess after intravenous methamphetamine injection into the breast.

Science.gov (United States)

Kistler, Amanda; Ajkay, Nicolas

2018-05-01

Intravenous drug use is a problem plaguing our society. We present a case of a young female who injected methamphetamine into her mammary vein, resulting in the formation of a breast abscess. This case demonstrates a rare but dangerous complication of intravenous drug use and a possible differential diagnosis in a patient presenting with a breast abscess. © 2017 Wiley Periodicals, Inc.

Increases in Intravenous Magnesium Use among Hospitalized Patients: An Institution Cross-Sectional Experience

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Bryce A. Kiberd

2015-06-01

Full Text Available Background: Among hospitalized patients, indications for the measurement of magnesium levels and treatment of hypomagnesemia with intravenous magnesium are not well defined. Recently, there have been reports of worldwide shortages of intravenous magnesium sulphate. Objective: To examine secular trends in the administration of intravenous magnesium on hospital wards at a tertiary care institution. The secondary objective is to identify factors associated with magnesium use among admitted patients. Methods: Retrospective cross-section review of hospitalized patients at a single Canadian tertiary care center. Utilization of non-parental nutrition intravenous magnesium from 2003 to 2013 stratified by hospital ward was examined. In addition, patient level data from select wards (including medical and surgical services was examined at early and more recent time period (4/2006 versus 4/2013. Results: Among the 248,329 hospitalized patients, intravenous magnesium use increased by 2.86 fold from 2003 to 2013. Not all wards had an increase whereas some had nearly a 10 fold increase in use. In the sample ( n = 769, (adjusting for admission magnesium level, presence of an indication for intravenous magnesium, ward location, comorbidity and demographics intravenous magnesium administration was higher (25.8 % versus 5.5 % in 2013 versus 2006 (OR 13.91 (95 % CI, 6.21–31.17, p < 0.001. Despite this increase in intravenous magnesium administration, <3 % of patients were admitted on oral magnesium in 2006 and 2013. For patients receiving intravenous magnesium only a minority were discharged on oral therapy despite low levels. Conclusions: This center has witnessed a considerable increase in the use of in-hospital intravenous magnesium over the last 6 years that cannot be explained for by medical indications. The risks and benefits of this therapy deserve further study. If this change in practice is representative of other North American hospitals, it may be

Tranexamic Acid in Bolus Alone Vs Bolus and Continuous Infusion in Hip Arthroscopy

OpenAIRE

Fatih Karaaslan; Roberto Seijas; Andrea Sallent; Oscar Ares; Wenceslao Espinosa; Pedro Alvarez; Ramón Cugat; Patricia Lopez

2017-01-01

AIM: the present study examines the effects of tranexamic acid (TXA) on reducing blood loss during hip arthroscopy, comparing two different methods of administration (bolus vs infusion). METHODS: a prospective study with 70 patients undergoing hip arthroscopy was carried out. The patients within the TXA infusion group (group A) received TXA an 2-g intravenous bolus 30 min before skin incision intravenously followed by 10 mg/kg/h infusion (continued during the entire surgery)...

Effectiveness of intravenous levetiracetam as an adjunctive treatment in pediatric refractory status epilepticus.

Science.gov (United States)

Kim, Jon Soo; Lee, Jeong Ho; Ryu, Hye Won; Lim, Byung Chan; Hwang, Hee; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Kim, Hunmin

2014-08-01

Intravenous levetiracetam (LEV) has been shown to be effective and safe in treating adults with refractory status epilepticus (SE). We sought to investigate the efficacy and safety of intravenous LEV for pediatric patients with refractory SE. We performed a retrospective medical-record review of pediatric patients who were treated with intravenous LEV for refractory SE. Clinical information regarding age, sex, seizure type, and underlying neurological status was collected. We evaluated other anticonvulsants that were used prior to administration of intravenous LEV and assessed loading dose, response to treatment, and any adverse events from intravenous LEV administration. Fourteen patients (8 boys and 6 girls) received intravenous LEV for the treatment of refractory SE. The mean age of the patients was 4.4 ± 5.5 years (range, 4 days to 14.6 years). Ten of the patients were neurologically healthy prior to the refractory SE, and the other 4 had been previously diagnosed with epilepsy. The mean loading dose of intravenous LEV was 26 ± 4.6 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 6 (43%) of the 14 patients. In particular, 4 (57%) of the 7 patients younger than 2 years showed seizure termination. No immediate adverse events occurred during or after infusions. The current study demonstrated that the adjunctive use of intravenous LEV was effective and well tolerated in pediatric patients with refractory SE, even in patients younger than 2 years. Intravenous LEV should be considered as an effective and safe treatment option for refractory SE in pediatric patients.

Usefulness of MR cholangiopancreatography after intravenous morphine administration

International Nuclear Information System (INIS)

Lee, So Jung; Ko, Ji Ho; Cho, Young Duk; Jung, Mi Hee; Yoon, Byung Chull

2007-01-01

We wanted to assess the usefulness of MRCP after intravenous morphine administration in the evaluation of the hepatopancreatic pancreatico-biliary ductal system. We studied 15 patients who were suspected of having disease of hepatopancreatic ductal system and they did not have any obstructive lesion on ultrasonography and/or CT. MRCP was acquired before and after morphine administration (0.04 mg/kg, intravenously). Three radiologists scored the quality of the images of the anatomic structures in the hepatopancreatic ductal system. We directly compared the quality of the images obtained with using the two methods and the improvement of the artifacts by pulsatile vascular compression. The MRCP images obtained after intravenous morphine administration were better than those obtained before morphine administration for visualizing the hepatopancreatic ductal system. On direct comparison, the MRCP images obtained after morphine administration were better in 12 cases, equivocal in two cases, and the images before morphine administration were better in only one case. In three patients, MRCP before morphine injection showed signal loss at the duct across the pulsatile hepatic artery. In two of three patients, MRCP after morphine injection showed no signal loss in this ductal area. MRCP after intravenous morphine administration enables physicians to see the hepatopancreatic ductal system significantly better and the artifacts caused by pulsation of the hepatic artery can be avoided

[Efficacy of intravenous phenobarbital treatment for status epilepticus].

Science.gov (United States)

Muramoto, Emiko; Mizobuchi, Masahiro; Sumi, Yoshihiro; Sako, Kazuya; Nihira, Atsuko; Takeuchi, Akiko; Nakamura, Hirohiko

2013-08-01

Intravenous phenobarbital (IV-PB) therapy was launched in Japan in October 2008. We retrospectively investigated its efficacy and tolerability in patients with status epilepticus. Forty-three consecutive patients received IV-PB for status epilepticus between June 2009 and April 2011. Among them, 39 patients had underlying diseases, which included acute diseases in 19 patients and chronic conditions in 20 patients. Although 18 patients had been taking antiepileptic drugs (AEDs) before the occurrence of status epilepticus, the blood AED concentrations in 8 patients was below the therapeutic levels. Before the administration of IV-PB, 39 patients were treated with intravenous benzodiazepine, 17 patients were treated with intravenous phenytoin, and 15 patients with intravenous infusion of lidocaine. The initial doses of IV-PB ranged from 125 to 1,250 mg (1.9-20.0 mg/kg). Additional doses of IV-PB were required in 12 patients. Seizures were controlled in 35 patients (81%) after IV-PB administration. Cessation of status epilepticus was attained in 24 patients after the initial dose and in 11 patients after additional doses. There were no serious adverse effects, although respiratory suppression was observed in 3 patients and drug eruption was observed in 1 patient. IV-PB is relatively safe and effective for controlling status epilepticus. If the first dose is not effective, additional doses are required up to the recommended maximum dose.

Hydrothorax, hydromediastinum and pericardial effusion: a complication of intravenous alimentation.

Science.gov (United States)

Damtew, B; Lewandowski, B

1984-01-01

Complications secondary to intravenous alimentation are rare but potentially lethal. Massive bilateral pleural effusions and a pericardial effusion developed in a patient receiving prolonged intravenous alimentation. Severe respiratory distress and renal failure ensued. He recovered with appropriate treatment. Images Fig. 1 Fig. 2 Fig. 3 PMID:6428731

Synchrotron-based intravenous cerebral angiography in a small animal model

International Nuclear Information System (INIS)

Kelly, Michael E; Schueltke, Elisabeth; Fiedler, Stephan; Nemoz, Christian; Guzman, Raphael; Corde, Stephanie; Esteve, Francois; LeDuc, Geraldine; Juurlink, Bernhard H J; Meguro, Kotoo

2007-01-01

K-edge digital subtraction angiography (KEDSA), a recently developed synchrotron-based technique, utilizes monochromatic radiation and allows acquisition of high-quality angiography images after intravenous administration of contrast agent. We tested KEDSA for its suitability for intravenous cerebral angiography in an animal model. Adult male New Zealand rabbits were subjected to either angiography with conventional x-ray equipment or synchrotron-based intravenous KEDSA, using an iodine-based contrast agent. Angiography with conventional x-ray equipment after intra-arterial administration of contrast agent demonstrated the major intracranial vessels but no smaller branches. KEDSA was able to visualize the major intracranial vessels as well as smaller branches in both radiography mode (planar images) and tomography mode. Visualization was achieved with as little as 0.5 ml kg -1 of iodinated contrast material. We were able to obtain excellent visualization of the cerebral vasculature in an animal model using intravenous injection of contrast material, using synchrotron-based KEDSA

Experience in using intravenous thrombolysis in ischemic stroke in Tatarstan

Directory of Open Access Journals (Sweden)

Dina Rustemovna Khasanova

2011-01-01

Full Text Available The paper describes experience with intravenous thrombolysis used in a few vascular centers of the Republic of Tatarstan in the past 5 years. Intravenous thrombolysis with alteplase (actilise was carried in 300 patients (188 men and 112 women aged 21 to 79 years (mean age 59.8±13.7 years who had ischemic stroke (IS. Significant positive changes (a neurological deficit decrease on the NIHSS score by ≥ 4 points were observed in 67.3% of cases; mortality was 6.7%. Hemorrhagic events as asymptomatic hemorrhagic transformations were found in 19.3% of cases with the neurological disorders being progressive in 4.6%. Recanalization of internal carotid artery occlusion was recorded only in 24.0% of the patients and that of occlusion of the proximal segments of the middle cerebral artery was in 50.1%. Examples of effective intravenous thrombolysis in IS in the carotid and vertebrobasilar beds are given. Whether intravenous thrombolysis can be more extensively used in IS is discussed.

Effect of intravenous administration of d-lysergic acid diethylamide on subsequent protein synthesis in a cell-free system derived from brain.

Science.gov (United States)

Cosgrove, J W; Clark, B D; Brown, I R

1981-03-01

An initiating cell-free protein synthesis system derived from brain was utilized to demonstrate that the intravenous injection of d-lysergic acid diethylamide (LSD) to rabbits induced a transient inhibition of translation following a brief stimulatory period. Subfractionation of the brain cell-free system into postribosomal supernatant (PRS) and microsome fractions demonstrated that LSD in vivo induced alterations in both of these fractions. In addition to the overall inhibition of translation in the cell-free system, differential effects were noted, i.e., greater than average relative decreases in in vitro labeling of certain brain proteins and relative increases in others. The brain proteins of molecular weights 75K and 95K, which were increased in relative labeling under conditions of LSD-induced hyperthermia, are similar in molecular weight to two of the major "heat shock" proteins reported in tissue culture systems. Injection of LSD to rabbits at 4 degrees C prevented LSD-induced hyperthermia but behavioral effects of the drug were still apparent. The overall decrease in cell-free translation was still observed but the differential labeling effects were not. LSD appeared to influence cell-free translation in the brain at two dissociable levels: (a) an overall decrease in translation that was observed even in the absence of LSD-induced hyperthermia and (b) differential labeling effects on particular proteins that were dependent on LSD-induced hyperthermia.

Effect of Interferon, Polyacrylic Acid, and Polymethacrylic Acid on Tail Lesions in Mice Infected with Vaccinia Virus

Science.gov (United States)

De Clercq, E.; De Somer, P.

1968-01-01

Intravenous inoculation of mice with vaccinia virus produced characteristic lesions of the tail surface which were suppressed by intraperitoneal administration of interferon and polyacrylic acid (PAA). Polymethacrylic acid (PMAA) stimulated the formation of vaccinia virus lesions. For full activity, both interferon and PAA must be given prior to infection. PAA was still significantly effective at small dose levels (3 mg/kg) and achieved protection for at least 4 weeks. Protection increased with increasing molecular weight of the polymer. The mode of action of PAA is discussed. PMID:5676405

First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial.

Science.gov (United States)

Rigby-Jones, Ann E; Sneyd, J Robert; Vijn, Peter; Boen, Patrick; Cross, Maurice

2010-06-29

Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics.

Vascular permeabilization by intravenous arachidonate in the rat peritoneal cavity: antagonism by ethamsylate.

Science.gov (United States)

Hannaert, Patrick; Alvarez-Guerra, Miriam; Hider, Hamida; Chiavaroli, Carlo; Garay, Ricardo P

2003-04-11

The hemostatic agent, ethamsylate, inhibits arachidonic acid metabolism by a mechanism independent of cyclooxygenase activity and blocks carrageenan-induced rat paw edema. Here, ethamsylate was investigated for (i) in vivo actions on the free radical-dependent, permeabilizing responses to arachidonic acid and (ii) its antioxidant potential in vitro. Vascular permeability was equated to the extravasation rate of Evans blue from plasma into the rat peritoneal cavity. Antioxidant potential was investigated by classical in vitro tests for superoxide radicals, hydroxyl radicals (OH(.)), and nitric oxide. Intravenous ethamsylate induced a very important and significant reduction of permeability responses to arachidonate, both when given preventively and cumulatively. Thus, (i) ethamsylate significantly reversed arachidonate-induced permeabilization, even at the lowest dose tested (44+/-5% at 10 mg/kg) and (ii) a maximal reversal (about 70%) was reached between 50 and 200 mg/kg ethamsylate. In contrast, ethamsylate (100 mg/kg) was unable to antagonize the vascular permeabilization induced by serotonin (5-HT). In antioxidant assays, ethamsylate showed scavenging properties against hydroxyl radicals generated by the Fenton reaction (H(2)O(2)/Fe(2+)) even at 0.1 microM (-20+/-3%). OH(.) scavenging by ethamsylate reached 42+/-8% at 10 microM and 57+/-7% at 1 mM and was comparable to that of reference compounds (vitamin E, troxerutin, and mannitol). Conversely, ethamsylate was a poor scavenger of superoxide and nitric oxide radicals. In conclusion, intravenous ethamsylate potently antagonized the peritoneal vascular permeabilization induced by arachidonate, an action likely due to its antioxidant properties, particularly against hydroxyl radical. Such a mechanism can explain previous observations that ethamsylate inhibits carrageenan-induced rat paw edema. Whether it also participates in the hemostatic action of ethamsylate deserves further investigation.

Chenodeoxycholic acid reduces intestinal permeability in newly weaned piglets

NARCIS (Netherlands)

Meer, van der Y.; Gerrits, W.J.J.; Bosch, van den M.; Holst, J.J.; Moreto, M.; Buurman, W.A.; Kulik, W.; Kempen, van T.A.T.G.

2012-01-01

Piglets are highly susceptible to gut health-related problems. Intravenously administered chenodeoxycholic acid (CDCA) affects gut health mediated through glucagon-like peptide 2 (GLP-2). To test whether CDCA is a suitable feed additive for improving gut health, a trial was performed with newly

Effect of vitamin C supplementation on lipid profile, serum uric acid, and ascorbic acid in children on hemodialysis.

Science.gov (United States)

El Mashad, Ghada Mohamed; ElSayed, Hanan M; Nosair, Nahla A

2016-01-01

Children with end-stage renal disease (ESRD) suffer from dyslipidemia and hyperuricemia that might play a causal role in the progression of cardiovascular disease (CVD). The aim of the study is to assess the effects of Vitamin C supplementation on uric acid, ascorbic acid, and serum lipid levels among children on hemodialysis (HD). This prospective study was conducted in the pediatric nephrology unit at Menoufia University Hospital. The study included a total of 60 children with ESRD on maintenance HD therapy. They were divided into two groups: Group I (supplemented group, n = 30) received intravenous Vitamin C supplementation and Group II (control, n = 30) received placebo (intravenous saline) for three months. The results are shown as a mean ± standard deviation. Statistical evaluation was performed by SPSS software (version 11.5) using paired t-test. After supplementation with Vitamin C, the serum Vitamin C and high-density lipoprotein levels increased significantly with a significant reduction in the levels of serum uric acid, cholesterol, low-density lipoproteins, and triglyceride at the end of the study period. No significant changes were observed in the control group. Vitamin C can serve as a useful urate lowering medicine in HD patients to avoid complications of hyperuricemia. Furthermore, it had favorable effects on the lipid profile. This improvement can be considered as a preventive strategy in the progression of CVD in HD patients. Vitamin C supplementation improves ascorbic acid deficiency in these patients.

Effect of vitamin C supplementation on lipid profile, serum uric acid, and ascorbic acid in children on hemodialysis

Directory of Open Access Journals (Sweden)

Ghada Mohamed El Mashad

2016-01-01

Full Text Available Children with end-stage renal disease (ESRD suffer from dyslipidemia and hyperuricemia that might play a causal role in the progression of cardiovascular disease (CVD. The aim of the study is to assess the effects of Vitamin C supplementation on uric acid, ascorbic acid, and serum lipid levels among children on hemodialysis (HD. This prospective study was conducted in the pediatric nephrology unit at Menoufia University Hospital. The study included a total of 60 children with ESRD on maintenance HD therapy. They were divided into two groups: Group I (supplemented group, n = 30 received intravenous Vitamin C supplementation and Group II (control, n = 30 received placebo (intravenous saline for three months. The results are shown as a mean ± standard deviation. Statistical evaluation was performed by SPSS software (version 11.5 using paired t-test. After supplementation with Vitamin C, the serum Vitamin C and high-density lipoprotein levels increased significantly with a significant reduction in the levels of serum uric acid, cholesterol, low-density lipoproteins, and triglyceride at the end of the study period. No significant changes were observed in the control group. Vitamin C can serve as a useful urate lowering medicine in HD patients to avoid complications of hyperuricemia. Furthermore, it had favorable effects on the lipid profile. This improvement can be considered as a preventive strategy in the progression of CVD in HD patients. Vitamin C supplementation improves ascorbic acid deficiency in these patients.

Comparative study on the results of consecutive oral cholecystography and intravenous cholangiography

International Nuclear Information System (INIS)

Lee, Sung Hee; Park, Yang Ok; Yoo, Ho Joon

1974-01-01

Since its introduction in 1924, oral cholecystography has been used as a screening method in the diagnosis of the gallbladder disease. Recently, intravenous cholangiography has become a most valuable method in the diagnosis of biliary tract pathology because of its advantage of simultaneous visualization of the gallbladder and bile ducts in a short time. However, opinions vary considerably as to the significance of nonvisualization of the gallbladder with oral cholecystography. In attempt to evaluate how much intravenous cholangiography does contribute to the diagnosis in the cases that the gallbladder cannot be opacified or can only faintly visualized by the oral method, we have made a clinical observation in 168 patients, in whom intravenous cholangiography had been performed within a week following oral cholecystography, at Korea General Hospital during the last three years from January 1969 to December 1971. The results obtained are summarized as follows; 1. The results of oral cholecystography in 168 cases were as follow; well opacification of the gallbladder in 10 cases, faint opacification in 46 cases and nonopacification in 112 cases. 2. In 37.5% (42 cases) of 112 gallbladder not opacified by the oral method, the gallbladder was subsequently opacified by the intravenous method, and 11.6% (14 cases) turned out to be normal when examined by the intravenous method. 3. Further demonstration of abnormalities could be obtained with the aid intravenous cholangiography in 28 cases (16.6%); cholelithiasis in 12 cases and choledocholithiasis in 16 cases. 4. In every cases of 14 patients whose gallbladder were virtually not opacified by both oral and intravenous methods bit the common bile ducts could be opacified by intravenous cholangiography, definite abnormalities were identified in the gallbladder at surgery

intravenous infusion of chlorimipramine (anafranil)

African Journals Online (AJOL)

the already extensive outpatient facilities at Johannesburg. Hospital as well as the Tara Neuro-Psychiatric Hospital for long-term therapy. Technique of Chlorimipramine Infusion. Initially 1 ampoule of chlorimipramine 25 mg in 250 mg of 5°~ dextrose saline was administered intravenously at the rate of 60 drops per minute.

Intravenous digital subtraction angiography of transplanted kidney artery

International Nuclear Information System (INIS)

Tessier, J.P; Teyssou, H.; Verdier, J.P.; Tison, E.; Meyblum, J.; Marchal, M.

1986-01-01

Results of 351 intravenous digital subtraction angiographs (AN) of transplanted kidneys emphasized reliability of this examination for detection of renal artery stenosis. A prospective study of 219 patients (188 interpretable AN) showed significant stenosis of grafted artery in 22% of cases: 17% of the 126 patients with normal blood pressure and 34% of the 62 cases of hypertension. Digital subtraction allows, with a single injection, assessment of renal artery, nephrogram and excretory cavities, but it is not a substitute for conventional intravenous urography 1 to 2 months after grafting [fr

Postarthroscopy analgesia using intraarticular levobupivacaine and intravenous dexketoprofen trometamol.

Science.gov (United States)

Sahin, Sevtap Hekimoglu; Memiş, Dilek; Celik, Erkan; Sut, Necdet

2015-12-01

The aim of this prospective study was to determine the efficacy of intraarticular levobupivacaine with and without intravenous dexketoprofen trometamol for postarthroscopy analgesia. Sixty patients who underwent arthroscopic knee surgery were randomly assigned to three treatment groups. When the surgical procedure was completed, patients received the following treatments: group I (n = 20) patients received 20 mL intraarticular normal saline and 2 mL intravenous dexketoprofen trometamol (50 mg); group II (n = 20) patients received 20 mL intraarticular 0.5 % levobupivacaine (100 mg) and 2 mL intravenous normal saline; and group III (n = 20) patients received 20 mL intraarticular 0.5 % levobupivacaine (100 mg) and 2 mL intravenous dexketoprofen trometamol (50 mg). The visual analogue scale (VAS) was used, and the total analgesic consumption was assessed at 1, 2, 4, 6, 12, and 24 h post-operatively. The VAS scores at 1, 2, 4, 6, 12, and 24 h post-operatively were significantly increased in group I and group II compared with group III (p dexketoprofen trometamol administration provided better pain relief and less analgesic requirement after arthroscopic knee surgery during the first 24 h than that induced by dexketoprofen alone or levobupivacaine intraarticular alone. II.

Organizational and technological correlates of nurses' trust in a smart intravenous pump.

Science.gov (United States)

Montague, Enid; Asan, Onur; Chiou, Erin

2013-03-01

The aim of this study was to understand technology and system characteristics that contribute to nurses' ratings of trust in a smart intravenous pump. Nurses' trust in new technologies can influence how technologies are used. Trust in technology is defined as a person's belief that a technology will not fail them. Potential outcomes of trust in technology are appropriate trust, overtrust, distrust, and mistrust. Trust in technology is also related to several use-specific outcomes, including appropriate use and inappropriate use such as overreliance, disuse or rejection, or misuse. Understanding trust in relation to outcomes can contribute to designs that facilitate appropriate trust in new technologies. A survey was completed by 391 nurses a year after the implementation of a new smart intravenous pump. The survey assessed trust in the intravenous pump and other elements of the sociotechnical system, individual characteristics, technology characteristics, and organizational characteristics. Results show that perceptions of usefulness, safety, ease of use, and usability are related to ratings of trust in smart intravenous pumps. Other work systemfactors such as perception of work environment, age, experience, quality of work, and perception of work performance are also related to ratings of trust. Nurses' trust in smart intravenous pumps is influenced by both characteristics of the technology and the sociotechnical system. Findings from this research have implications for the design of future smart intravenous pumps and health systems. Recommendations for appropriately trustworthy smart intravenous pumps are discussed. Findings also have implications for how trust in health technologies can be measured and conceptualized in complex sociotechnical systems.

Are intravenous injections of contrast media really less nephrotoxic than intra-arterial injections?

Energy Technology Data Exchange (ETDEWEB)

Nyman, Ulf [University of Lund, Department of Diagnostic Radiology, Trelleborg (Sweden); Almen, Torsten [Skaane University Hospital, Department of Clinical Sciences/Medical Radiology, University of Lund, Malmoe (Sweden); Jacobsson, Bo [University of Gothenburg and the Sahlgrenska Academy, Department of Diagnostic Radiology, The Queen Silvia Children' s Hospital, Goeteborg (Sweden); Aspelin, Peter [Karolinska Institute and University Hospital, Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm (Sweden)

2012-06-15

We oppose the opinion that the intra-arterial administration of iodine-based contrast media (CM) appears to pose a greater risk of contrast medium-induced nephropathy (CIN) than intravenous administration since (1) in intra-arterial coronary procedures and most other intra-arterial angiographic examinations, CM injections are also intravenous relative to the kidneys, (2) there is a lack of comparative trials studying the risk of CIN between intra-arterial and intravenous procedures with matched risk factors and CM doses, (3) a bias selection of patients with fewer risk factors may explain the seemingly lower rate of CIN after CT in comparison with coronary interventions, (4) the rate of CIN following intra-arterial coronary procedures may also be exaggerated owing to other causes of acute kidney failure, such as haemodynamic instability and microembolisation, (5) roughly the same gram-iodine/GFR ratio ({approx}1:1) as a limit of relatively safe CM doses has preliminarily been found for both intravenous CT and intra-arterial coronary procedures and (6) the substantially higher injected intravenous CM dose rate during CT relative to an intra-arterial coronary procedure might actually pose a higher risk of CIN following CT. Key Points circle Most intra-arterial injections of contrast media are intravenous relative to the kidneys. circle No evidence that intravenous CM injections should be less nephrotoxic than intra-arterial. circle Considerably higher dose rates of CM are used for CT relative to intra-arterial procedures. circle Higher dose rates may pose higher nephrotoxic risk for intravenous based CT studies. (orig.)

Comparison of analgesic efficacy of intravenous Paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy.

Science.gov (United States)

Unal, Ciğdem; Cakan, Türkay; Baltaci, Bülent; Başar, Hülya

2013-10-01

[corrected] We aimed to evaluate analgesic efficacy, opioid-sparing, and opioid-related adverse effects of intravenous paracetamol and intravenous dexketoprofen trometamol in combination with iv morphine after total abdominal hysterectomy. Sixty American Society of Anesthesiologist Physical Status Classification I-II patients scheduled for total abdominal hysterectomy were enrolled to this double-blinded, randomized, placebo controlled, and prospective study. Patients were divided into three groups as paracetamol, dexketoprofen trometamol, and placebo (0.9% NaCl) due to their post-operative analgesic usage. Intravenous patient controlled analgesia morphine was used as a rescue analgesic in all groups. Pain scores, hemodynamic parameters, morphine consumption, patient satisfaction, and side-effects were evaluated. Visual Analog Scale (VAS) scores were not statistically significantly different among the groups in all evaluation times, but decrease in VAS scores was statistically significant after the evaluation at 12(th) h in all groups. Total morphine consumption (morphine concentration = 0.2 mg/ml) in group paracetamol (72.3 ± 38.0 ml) and dexketoprofen trometamol (69.3 ± 24.1 ml) was significantly lower than group placebo (129.3 ± 22.6 ml) (P dexketoprofen trometamol after surgery and the increase in global satisfaction score was significant only in group placebo. Dexketoprofen trometamol and Paracetamol didn't cause significant change on pain scores, but increased patients' comfort. Although total morphine consumption was significantly decreased by both drugs, the incidence of nausea and vomiting were similar among the groups. According to results of the present study routine addition of dexketoprofen trometamol and paracetamol to patient controlled analgesia morphine after hysterectomies is not recommended.

Predisposing factors for peripheral intravenous puncture failure in children

OpenAIRE

Negri,Daniela Cavalcante de; Avelar,Ariane Ferreira Machado; Andreoni,Solange; Pedreira,Mavilde da Luz Gonçalvez

2012-01-01

OBJECTIVE: To identify predisposing factors for peripheral intravenous puncture failure in children. METHODS: Cross-sectional cohort study conducted with 335 children in a pediatric ward of a university hospital after approval of the ethics committee. The Wald Chi-squared, Prevalence Ratio (PR) and backward procedure (p≤0.05) tests were applied. RESULTS: Success of peripheral intravenous puncture was obtained in 300 (89.5%) children and failure in 35 (10.4%). The failure rates were sign...

Conversion from intravenous to oral medications: assessment of a computerized intervention for hospitalized patients.

Science.gov (United States)

Fischer, Michael A; Solomon, Daniel H; Teich, Jonathan M; Avorn, Jerry

2003-11-24

Many hospitalized patients continue to receive intravenous medications longer than necessary. Earlier conversion from the intravenous to the oral route could increase patient safety and comfort, reduce costs, and facilitate earlier discharge from the hospital without compromising clinical care. We examined the effect of a computer-based intervention to prompt physicians to switch appropriate patients from intravenous to oral medications. This study was performed at Brigham and Women's Hospital, an academic tertiary care hospital at which all medications are ordered online. We targeted 5 medications with equal oral and intravenous bioavailability: fluconazole, levofloxacin, metronidazole, ranitidine, and amiodarone. We used the hospital's computerized order entry system to prompt physicians to convert appropriate intravenous medications to the oral route. We measured the total use of the targeted medications via each route in the 4 months before and after the implementation of the intervention. We also measured the rate at which physicians responded to the intervention when prompted. The average intravenous defined daily dose declined by 11.1% (P =.002) from the preintervention to the postintervention period, while the average oral defined daily dose increased by 3.7% (P =.002). Length of stay, case-mix index, and total drug use at the hospital increased during the study period. The average total monthly use of the intravenous preparation of all of the targeted medications declined in the 4 months after the intervention began, compared with the 4 months before. In 35.6% of 1045 orders for which a prompt was generated, the physician either made a conversion from the intravenous to the oral version or canceled the order altogether. Computer-generated reminders can produce a substantial reduction in excessive use of targeted intravenous medications. As online prescribing becomes more common, this approach can be used to reduce excess use of intravenous medications

Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial.

Science.gov (United States)

Rossi, Emanuela; Morabito, Alessandro; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; De Maio, Ermelinda; Di Maio, Massimo; Piccirillo, Maria Carmela; De Feo, Gianfranco; D'Aiuto, Giuseppe; Botti, Gerardo; Chiodini, Paolo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2009-07-01

PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

Intravenous microemulsion of docetaxel containing an anti-tumor synergistic ingredient (Brucea javanica oil): formulation and pharmacokinetics

Science.gov (United States)

Ma, Shilin; Chen, Fen; Ye, Xiaohui; Dong, Yingjie; Xue, Yingna; Xu, Heming; Zhang, Wenji; Song, Shuangshuang; Ai, Li; Zhang, Naixian; Pan, Weisan

2013-01-01

The purpose of this study was to develop a docetaxel microemulsion containing an anti-tumor synergistic ingredient (Brucea javanica oil) and to investigate the characteristics of the microemulsion. Brucea javanica oil contains oleic acid and linoleic acids that have been shown by animal and human studies to inhibit tumor formation. The microemulsion containing Brucea javanica oil, medium-chain triglyceride, soybean lecithin, Solutol®HS 15, PEG 400, and water was developed for docetaxel intravenous administration. A formulation with higher drug content, lower viscosity, and smaller particle size was developed. The droplet size distribution of the dispersed phase of the optimized microemulsion was 13.5 nm, determined using a dynamic light scattering technique. The small droplet size enabled the microemulsion droplets to escape from uptake and phagocytosis by the reticuloendothelial system and increased the circulation time of the drug. The zeta potential was −41.3 mV. The optimized microemulsion was pale yellow, transparent, and non-opalescent in appearance. The value of the combination index was 0.58, showing that there was a synergistic effect when docetaxel was combined with Brucea javanica oil. After a single intravenous infusion dose (10 mg/kg) in male Sprague Dawley rats, the area under the curve of the microemulsion was higher and the half-time was longer compared with that of docetaxel solution alone, and showed superior pharmacokinetic characteristics. These results indicate that this preparation of docetaxel in emulsion is likely to provide an excellent prospect for clinical tumor treatment. PMID:24179332

Efficacy and Tolerability of Intravenous Levetiracetam in Children

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Jose eAceves

2013-08-01

Full Text Available Intractable epilepsy in children poses a serious medical challenge. Acute repetitive seizures and status epilepticus leads to frequent emergency room visits and hospital admissions. Permanent neurological damage can occur if there is delay in treatment. It has been shown that these children continue to remain intractable even after acute seizure management with approved FDA agents. Intravenous levetiracetam, a second-generation anticonvulsant was approved by the FDA in 2006 in patients 16 years and older as an alternative when oral treatment is not an option. It has been shown that oral levetiracetam can be used in the treatment of status epilepticus and acute repetitive seizures. Data have been published showing that intravenous levetiracetam is safe and efficacious, and can be used in an acute inpatient setting. This current review will discuss the recent data about the safety and tolerability of intravenous levetiracetam in children and neonates, and emphasize the need for a larger prospective multicenter trial to prove the efficacy of this agent in acute seizure management.

Intravenous voriconazole after toxic oral administration

NARCIS (Netherlands)

Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

Tranexamic Acid Failed to Reverse the Anticoagulant Effect and Bleeding by an Oral Direct Factor Xa Inhibitor Edoxaban.

Science.gov (United States)

Honda, Yuko; Furugohri, Taketoshi; Morishima, Yoshiyuki

2018-01-01

Agents to reverse the anticoagulant effect of edoxaban, an oral direct factor Xa inhibitor, would be desirable in emergency situations. The aim of this study is to determine the effect of tranexamic acid, an antifibrinolytic agent, on the anticoagulant activity and bleeding by edoxaban in rats. A supratherapeutic dose of edoxaban (3 mg/kg) was intravenously administered to rats. Three minutes after dosing, tranexamic acid (100 mg/kg) was given intravenously. Bleeding was induced by making an incision with a blade on the planta 8 min after edoxaban injection and bleeding time was measured. Prothrombin time (PT) and clot lysis were examined. A supratherapeutic dose of edoxaban significantly prolonged PT and bleeding time. Tranexamic acid did not affect PT or bleeding time prolonged by edoxaban, although tranexamic acid significantly inhibited clot lysis in rat plasma. An antifibrinolytic agent tranexamic acid failed to reverse the anticoagulant effect and bleeding by edoxaban in rats. © 2017 S. Karger AG, Basel.

An open-label, prospective, observational study of the efficacy of bisphosphonate therapy for painful osteoid osteoma

Energy Technology Data Exchange (ETDEWEB)

Bousson, Valerie; Parlier-Cuau, Caroline; Laredo, Jean-Denis [AP-HP, Hopital Lariboisiere, Service de Radiologie Osteo-Articulaire, Paris (France); Universite Paris Diderot, Sorbonne Paris Cite, Paris (France); Leturcq, Tifenn; Ea, Hang-Korng; Orcel, Philippe [AP-HP, Hopital Lariboisiere, Service de Rhumatologie, Paris (France); Universite Paris Diderot, Sorbonne Paris Cite, Paris (France); Hauger, Olivier [CHU Pellegrin Bordeaux, Service d' Imagerie Diagnostique et Therapeutique de l' Adulte, Bordeaux (France); Mehsen-Cetre, Nadia; Schaeverbeke, Thierry [CHU Pellegrin Bordeaux, Service de Rhumatologie, Bordeaux (France); Hamze, Bassam [AP-HP, Hopital Lariboisiere, Service de Radiologie Osteo-Articulaire, Paris (France)

2018-02-15

To assess the efficacy of bisphosphonate therapy on bone pain in patients with osteoid osteoma (OO) (main objective), and to describe bisphosphonate-induced changes in nidus mineralisation and regional bone-marrow oedema (BMO). A prospective, observational study was conducted from 2011 to 2014. Patients with risk factors for complications of percutaneous or surgical ablation or recurrence after ablation, were offered once monthly intravenous bisphosphonate treatment until significant pain alleviation was achieved. We included 23 patients. The first two patients received pamidronate and the next 21 zoledronic acid (mean, 2.95 infusions per patient). Bisphosphonate therapy was successful in 19 patients (83%), whose mean pain visual analogue scale score decreased by 76.7%; this pain-relieving effect persisted in 17 patients (74%) with a mean follow-up time of 36 months. Computed tomography (CT) demonstrated a mean nidus density increase of 177.7% (p = 0.001). By magnetic resonance imaging (MRI), mean decreases were 38.4% for BMO surface area and 30.3% for signal intensity (p = 0.001 and p = 0.000, respectively). In 17/23 patients with painful OO managed conservatively with bisphosphonates, long-term final success was achieved. Bisphosphonates may accelerate the spontaneous healing of OO. (orig.)

Adherence of radiopharmaceuticals and labeled cells to intravenous tubing

International Nuclear Information System (INIS)

Segall, G.M.; Gurevich, N.; McDougall, I.R.

1986-01-01

A survey of 67 nuclear medicine departments revealed no agreement on which radiolabeled agents could be injected through intravenous lines (IVs) and which required direct venipuncture. Labeled cells and several common radiopharmaceuticals were tested for adherence to intravenous tubing. Residual activity remaining in the tubing after an adequate flush was less than 1% of the injected dose in each case. Administration of radiolabeled agents through existing IVs is an acceptable alternative to direct venipuncture in many cases

Modes of Action of Intravenous Immunoglobulin in Bullous Pemphigoid.

Science.gov (United States)

Li, Ning; Culton, Donna; Diaz, Luis A; Liu, Zhi

2018-06-01

Bullous pemphigoid is an autoantibody-mediated skin blistering disease. Previous studies revealed that intravenous Ig is therapeutic in animal models of bullous pemphigoid by saturating the IgG-protective receptor FcRn, thereby accelerating degradation of pathogenic IgG. Sasaoka et al. demonstrate that the inhibitory effects of intravenous Ig on bullous pemphigoid are also associated with negative modulation of cytokine production by keratinocytes. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Intravenous Laser Therapy in Young Children with Thermal Injuries

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R. V. Bocharov

2014-01-01

Full Text Available Objective: to evaluate the laboratory and clinical effects of combined intravenous laser therapy in young children with thermalinjuries in the acute period of burn disease.Subjects and methods. Forty children whose mean age was 2.67±0.35 years were examined; thermal injuries accounted for 25.05±1.01% of the total body surface area; of them degrees IIIaIIIb was 19.04±0.85%. A comparison group (n=15 received conventional therapy without taking into account and correcting baseline and current hemostasiological disorders. On day 1, a study group (n=25 had programmed anticoagulant therapy and intravenous laser therapy at different radiation frequencies with a Mustang 20002+ laser therapy apparatus (patent for invention No. 2482894 in addition to the conventional therapy. The laser therapy cycle was 6 to 16 sessions. The investigators estimated and compared the following examined parameters: white blood cell count; leukocytic index of intoxication; plasma average mass molecules at a wavelength of 254 nm; toxogenic granularity of neutrophils; wound exudate discharge time; surgical plasty area; and hospitalization time.Results. The positive laboratory and clinical effects of the performed combined intravenous laser therapy in the combined therapy of burn disease in young children were comparatively shown in the study group patients. The significant decrease in the level of an inflammatory response and endogenous intoxication led to a rapider burn wound cleansing, active epithelization, and reduced surgical plasty volumes.Conclusion. Combined intravenous laser therapy signif icantly exerts antiinflammatory and detoxifying effects in young children with 40% thermal injuries in the acute period of burn disease. Abolishing a systemic inflammatory response by combined intravenous laser therapy initiated early regenerative processes in the burn wound and caused reductions in surgical plasty volumes and hospitalization time, which optimizes ther

Use of general practice by intravenous heroin users on a methadone programme.

OpenAIRE

Leaver, E J; Elford, J; Morris, J K; Cohen, J

1992-01-01

Users of intravenous heroin represent a major challenge for general practice. A study was undertaken in a general practice in central London in 1990 to investigate the use of general practice made by intravenous heroin users who were on a methadone programme. Using information recorded in the patients' notes, 29 intravenous heroin users on a methadone programme were identified; 58 non-drug users (two controls per case) were matched for age, sex and general practitioner. A study of the number ...

Why intravenous moderate sedation should be taught in graduate endodontic programs.

Science.gov (United States)

Montagnese, Thomas Anthony

2012-03-01

The purpose of this opinion article is to present reasons why intravenous moderate sedation should be taught in graduate endodontic programs. Access to oral health care is an area of much interest and concern, but some patients are unable to get endodontic care because they have special needs. Special needs can refer to patients who fear dentistry itself and other aspects of dental treatment. A variety of phobias and medical, developmental, and physical conditions can make it difficult for some patients to tolerate the endodontic care they need and want. Moderate sedation can help many of these patients. Endodontists in general are not trained to provide intravenous moderate sedation. By incorporating intravenous moderate sedation into endodontic practice, many of these patients can be treated. The first step in achieving this goal is to add intravenous moderate sedation training to graduate endodontic programs. The long-term effect will be to make specialty endodontic care available to more people.

Microemulsion formulation of clonixic acid: solubility enhancement and pain reduction.

Science.gov (United States)

Lee, Jung-Mi; Park, Kyung-Mi; Lim, Soo-Jeong; Lee, Mi-Kyung; Kim, Chong-Kook

2002-01-01

Clonixic acid is currently marketed as a salt form because of its poor water-solubility. However, the commercial dosage form causes severe pain after intramuscular or intravenous injection. To improve the solubility of clonixic acid and to reduce pain on injection, clonixic acid was incorporated into oil-in-water microemulsions prepared from pre-microemulsion concentrate composed of varying ratios of oil and surfactant mixture. As an oil phase for drug incorporation, up to 14% castor oil could be included in the pre-microemulsion concentrate without a significant increase in droplet size. Both drug contents and droplet size increased as the weight ratio of Tween 20 to Tween 85 decreased. Taken together, when microemulsions were prepared from pre-microemulsion concentrate composed of 5:12:18 weight ratio of castor oil:Tween 20:Tween 85, clonixic acid could be incorporated at 3.2 mg mL(-1) in the microemulsion with a droplet size of less than 120 nm. The osmotic pressure of this microemulsion was remarkably lower than the commercial formulation, irrespective of the dilution ratios. The rat paw-lick test was used to compare pain responses among formulations. The microemulsion formulation significantly reduced the number of rats licking their paws as well as the total licking time, suggesting less pain induction by the microemulsion formulation. The pharmacokinetic parameters of clonixic acid after intravenous administration of the clonixic acid microemulsion to rats were not significantly different from those of the commercial formulation, lysine clonixinate. The present study suggests that microemulsion is an alternative formulation for clonixic acid with improved characteristics.

Ultrastructural Changes in the Liver of Intravenous Heroin Addicts

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Goran Ilić

2010-02-01

Full Text Available The ultrastructural research has a decisive role in gathering the knowledge on the liver’s response to the influence of some drugs. The aim of the study was to perform an ultrastructurai analysis of the liver in chronic intravenous heroin addicts.The study involved the autopsy conducted on 40 bodies of intravenous heroin addicts and 10 control autopsies. The liver tissue was fixed in glutaraldehyde and moulded with epon for investigation purposes of ultrastructural changes. The analysis was performed using the method of transmission electron microscopy.In the group of intravenous heroin addicts, the liver autopsy samples showed degenerative vesicular and fat changes, chronic active and persistent hepatitis, cirrhosis, reduction in the amount of glycogen in hepatocytes, as well as the Kupffer cell’s dominant hypertrophy. Various changes occur in organelles, plasma membrane of hepatocytes and biliary channels as well as in the nucleus.The most important ultrastructural findings include: hyperplasia and hypertrophy of the smooth endoplasmic reticulum, which is histologically proven vesicular degeneration of hepatocyte occurring as a result of the increased synthesis of enzymes of smooth endoplasmic reticulum due to chronic intravenous heroin intake, and the presence of continuous basal membrane followed by transformation of the sinusoids into capillaries (in the cases of chronic active hepatitis and cirrhosis which leads to a disorder of microcirculation and further progress of cirrhosis.

Intravenous infusion of H2-saline suppresses oxidative stress and elevates antioxidant potential in Thoroughbred horses after racing exercise.

Science.gov (United States)

Yamazaki, Masahiko; Kusano, Kanichi; Ishibashi, Toru; Kiuchi, Masataka; Koyama, Katsuhiro

2015-10-23

Upon intensive, exhaustive exercise, exercise-induced reactive oxygen species may exceed the antioxidant defence threshold, consequently resulting in muscular damage or late-onset chronic inflammation. Recently, the therapeutic antioxidant and anti-inflammatory effects of molecular hydrogen (H2) for human rheumatoid arthritis have been demonstrated. However, it is also important to clarify the effects of administrating H2 in large animals other than humans, as H2 is thought to reach the target organ by passive diffusion upon delivery from the blood flow, indicating that the distance from the administration point to the target is critical. However, data on the effects of H2 on oxidative stress in real-life exhaustive exercise in large animals are currently lacking. We here investigated 13 Thoroughbred horses administered intravenous 2-L saline with or without 0.6-ppm H2 (placebo, N = 6; H2, N = 7) before participating in a high-intensity simulation race. Intravenous H2-saline significantly suppressed oxidative stress immediately, 3 h, and 24 h after the race, although the antioxidant capability was not affected throughout the study. The serum creatine kinase, lactate, and uric acid levels were increased in both groups. Taken together, these results indicate that intravenous H2-saline can significantly and specifically suppress oxidative stress induced after exhaustive racing in Thoroughbred horses.

Acute Chloroform Ingestion Successfully Treated with Intravenously Administered N-acetylcysteine

OpenAIRE

Dell’Aglio, Damon M.; Sutter, Mark E.; Schwartz, Michael D.; Koch, David D.; Algren, D. A.; Morgan, Brent W.

2010-01-01

Chloroform, a halogenated hydrocarbon, causes central nervous system depression, cardiac arrhythmias, and hepatotoxicity. We describe a case of chloroform ingestion with a confirmatory serum level and resultant hepatotoxicity successfully treated with intravenously administered N-acetylcysteine (NAC). A 19-year-old man attempting suicide ingested approximately 75 mL of chloroform. He was unresponsive and intubated upon arrival. Intravenously administered NAC was started after initial stabiliz...

INFECTIVE ENDOCARDITIS IN INTRAVENOUS DRUGS ABUSED PATIENT

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E. Y. Ponomareva

2014-07-01

Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

INFECTIVE ENDOCARDITIS IN INTRAVENOUS DRUGS ABUSED PATIENT

Directory of Open Access Journals (Sweden)

E. Y. Ponomareva

2011-01-01

Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

Intravenous Poison Hemlock Injection Resulting in Prolonged Respiratory Failure and Encephalopathy.

Science.gov (United States)

Brtalik, Douglas; Stopyra, Jason; Hannum, Jennifer

2017-06-01

Poison hemlock (Conium maculatum) is a common plant with a significant toxicity. Data on this toxicity is sparse as there have been few case reports and never a documented poisoning after intravenous injection. We present a case of intravenous poison hemlock injection encountered in the emergency department. We describe a 30-year-old male who presented to the emergency department after a brief cardiac arrest after injecting poison hemlock. The patient had return of spontaneous circulation in the emergency department but had prolonged muscular weakness and encephalopathy later requiring tracheostomy. Intravenous injection of poison hemlock alkaloids can result in significant toxicity, including cardiopulmonary arrest, prolonged weakness, and encephalopathy.

Administration and monitoring of intravenous anesthetics

NARCIS (Netherlands)

Sahinovic, Marko M.; Absalom, Anthony R.; Struys, Michel M. R. F.

2010-01-01

Purpose of review The importance of accuracy in controlling the dose-response relation for intravenous anesthetics is directly related to the importance of optimizing the efficacy and quality of anesthesia while minimizing adverse drug effects. Therefore, it is important to measure and control all

Influences on physicians' choices of intravenous colloids.

Science.gov (United States)

Miletin, Michael S; Stewart, Thomas E; Norton, Peter G

2002-07-01

Controversy over the optimal intravenous fluid for volume resuscitation continues unabated. Our objectives were to characterize the demographics of physicians who prescribe intravenous colloids and determine factors that enter into their decision to choose a colloid. Questionnaire with 61 items. Ten percent ( n = 364) of frequent intravenous fluid prescribers in the province of Ontario, Canada. The response rate was 74%. Colloid use in the past year was reported by 79% of the responding physicians. Important reasons for choosing a colloid included blood loss and manipulation of oncotic pressure. Physicians tended to prefer either albumin or pentastarch, but no important reasons were found for choosing between the two. Albumin with or without crystalloid was preferred in 5/13 scenarios by more than 50% of the respondents, whereas pentastarch was not favored by more than 50% of respondents in any scenario. Physicians practising in critical care areas and teaching hospitals generally preferred pentastarch to albumin. Physicians reporting pentastarch as representing greater than 90% of total colloid use were more likely to have been visited by a drug detailer for pentastarch than those who used less synthetic colloid (54 vs 22%, p distribution. Although albumin appeared to be preferred in more clinical niches, most physicians did not state reasons for choosing between products. Marketing, specialty, location of practice and clinical scenario appear to play significant roles in the utilization of colloid products.

Influence of intravenous opioid dose on postoperative ileus.

Science.gov (United States)

Barletta, Jeffrey F; Asgeirsson, Theodor; Senagore, Anthony J

2011-07-01

Intravenous opioids represent a major component in the pathophysiology of postoperative ileus (POI). However, the most appropriate measure and threshold to quantify the association between opioid dose (eg, average daily, cumulative, maximum daily) and POI remains unknown. To evaluate the relationship between opioid dose, POI, and length of stay (LOS) and identify the opioid measure that was most strongly associated with POI. Consecutive patients admitted to a community teaching hospital who underwent elective colorectal surgery by any technique with an enhanced-recovery protocol postoperatively were retrospectively identified. Patients were excluded if they received epidural analgesia, developed a major intraabdominal complication or medical complication, or had a prolonged workup prior to surgery. Intravenous opioid doses were quantified and converted to hydromorphone equivalents. Classification and regression tree (CART) analysis was used to determine the dosing threshold for the opioid measure most associated with POI and define high versus low use of opioids. Risk factors for POI and prolonged LOS were determined through multivariate analysis. The incidence of POI in 279 patients was 8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of 2 mg or more as the opioid measure most associated with POI. Multivariate analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034), open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p = 0.003) as significant risk factors for POI. Variables associated with increased LOS were POI (p POI and prolonged LOS, particularly when the maximum hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative, nonopioid-based pain management options when this occurs.

Acute transient phlebitis during eptifibatide intravenous injection: case report.

Science.gov (United States)

Hay, Emile; Blaer, Yossef; Shlyakhover, Vladimir; Katz, Amos; Jafari, Jamal

2010-01-01

We present a 56-year-old man who developed acute transient phlebitis of the right cephalic vein during an intravenous injection of eptifibatide (Integrilin, Schering Plough, Kenilworth, NJ). The eptifibatide injections were discontinued, and signs of phlebitis disappeared within minutes. The patient's course was uneventful, and he was discharged home after 8 days. As far as we know, this is the first report of acute transient phlebitis during intravenous eptifibatide injections in the English-language medical literature. Copyright 2010 Elsevier Inc. All rights reserved.

Clinical Evaluation of Ciprofloxacin Intravenous Preparation ...

African Journals Online (AJOL)

The most common site of bacteria infection in humans is the urinary tract. For nosocomial infections it is the catheterized urinary tract. Compromised immune responses in hospitalized patients contribute to the difficulties encountered in treating their infections. In these patients, administration of intravenous antibiotic is ...

Intraosseous Urography Compared with Intravenous Urography: An Experimental Study in the Rabbit Model

OpenAIRE

SAĞLAM, Mutlu; UĞUREL, Şahin

2014-01-01

This study was performed to evaluate the feasibility of bone injection gun assisted intraosseous administration of contrast media as an alternative to the intravenous route for urography. Intravenous urographies were obtained in 6 rabbits. Urographic examinations by the intraosseous route were performed in the same animals 48 h later. After adequate anesthesia, the retroauricular vein was punctured for intravenous injection and a bone injection gun was used for intraosseous injections to the ...

Intravenous infusion of docosahexaenoic acid increases serum concentrations in a dose-dependent manner and increases seizure latency in the maximal PTZ model.

Science.gov (United States)

Trépanier, Marc-Olivier; Kwong, Kei-Man; Domenichiello, Anthony F; Chen, Chuck T; Bazinet, Richard P; Burnham, W M

2015-09-01

Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) that has been shown to raise seizure thresholds in the maximal pentylenetetrazole model following acute subcutaneous (s.c.) administration in rats. Following s.c. administration, however, the dose-response relationship for DHA has shown an inverted U-pattern. The purposes of the present experiment were as follows: (1) to determine the pattern of serum unesterified concentrations resulting from the intravenous (i.v.) infusions of various doses of DHA, (2) to determine the time course of these concentrations following the discontinuation of the infusions, and (3) to determine whether seizure protection in the maximal PTZ model would correlate with serum unesterified DHA levels. Animals received 5-minute i.v. infusions of saline or 25, 50, 100, or 200mg/kg of DHA via a cannula inserted into one of the tail veins. Blood was collected during and after the infusions by means of a second cannula inserted into the other tail vein (Experiment 1). A separate group of animals received saline or 12.5-, 25-, 50-, 100-, or 200 mg/kg DHA i.v. via a cannula inserted into one of the tail veins and were then seizure-tested in the maximal PTZ model either during infusion or after the discontinuation of the infusions. Slow infusions of DHA increased serum unesterified DHA concentrations in a dose-dependent manner, with the 200-mg/kg dose increasing the concentration approximately 260-fold compared with saline-infused animals. Following discontinuation of the infusions, serum concentrations rapidly dropped toward baseline, with half-lives of approximately 40 and 11s for the 25-mg/kg dose and 100-mg/kg dose, respectively. In the seizure-tested animals, DHA significantly increased latency to seizure onset in a dose-dependent manner. Following the discontinuation of infusion, seizure latency rapidly decreased toward baseline. Overall, our study suggests that i.v. infusion of unesterified DHA results in

Intravenous paracetamol and patent ductus arteriosus closure in preterm infants

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Rizky Adriansyah

2017-08-01

Full Text Available Background Indomethacin and ibuprofen are the drugs of choice for closure of patent ductus arteriosus (PDA in preterm infants. However, intravenous preparations are of limited availability in Indonesia. Circumstantial evidence has shown that intravenous paracetamol may be an alternative therapy for PDA closure in premature infants. Objective To evaluate the effect of intravenous paracetamol on PDA closure in preterm infants. Methods A before-and-after study was conducted between May and August 2014 in Cipto Mangunkusumo General Hospital, Jakarta in preterm infants with hemodynamically significant PDAs, as established by echocardiography using the following criteria: duct diameter >1.4 mm/kg, left atrium to aorta ratio >1.4, and mean velocity in the left pulmonary artery >0.42 m/s or mean diastolic velocity in the left pulmonary artery >0.2 m/s. Subjects, aged 2 and 7 days, received intravenous paracetamol (15 mg/kg every six hours for 3 days. Paired T-test was used to compare pre-intervention PDA diameter to those assessed at 24 hours after the intervention and at 14 days of life. Results Twenty-nine subjects had a mean gestational age of 30.8 weeks and mean birth weight of 1,347 grams. Nineteen (65.5% patients had closed PDAs at the day 14 evaluation, 1 experienced PDA reopening, and 9 had failed PDA closure. No liver toxicity was identified. Mean duct diameters before, 24 hours after the intervention, and at 14 days of life were 3.0, 0.9, and 0.6 mm, respectively (P<0.0001. Conclusion Intravenous paracetamol seems to be reasonably effective for PDA closure in preterm infants.

Campaign best practice in intravenous therapy.

Science.gov (United States)

Baldwin, Wayne; Murphy, Jayne; Shakespeare, David; Kelly, Chris; Fox, Louise; Kelly, Matthew

Intravenous therapy is an integral part of nursing care but is associated with a high risk of infection. This article outlines a campaign that aimed to increase awareness of best practice for IV therapy and reduce the risks of healthcare-associated IV infections in hospital and community settings.

Comparison of analgesic efficacy of intravenous Paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy

Directory of Open Access Journals (Sweden)

Çiğdem Ünal

2013-01-01

Full Text Available Backround: We aimed to evaluate analgesic efficacy, opioid-sparing, and opioid-related adverse effects of intravenous paracetamol and intravenous dexketoprofen trometamol in combination with iv morphine after total abdominal hysterectomy. Materials and Methods: Sixty American Society of Anesthesiologist Physical Status Classification I-II patients scheduled for total abdominal hysterectomy were enrolled to this double-blinded, randomized, placebo controlled, and prospective study. Patients were divided into three groups as paracetamol, dexketoprofen trometamol, and placebo (0.9% NaCl due to their post-operative analgesic usage. Intravenous patient controlled analgesia morphine was used as a rescue analgesic in all groups. Pain scores, hemodynamic parameters, morphine consumption, patient satisfaction, and side-effects were evaluated. Results: Visual Analog Scale (VAS scores were not statistically significantly different among the groups in all evaluation times, but decrease in VAS scores was statistically significant after the evaluation at 12 th h in all groups. Total morphine consumption (morphine concentration = 0.2 mg/ml in group paracetamol (72.3 ± 38.0 ml and dexketoprofen trometamol (69.3 ± 24.1 ml was significantly lower than group placebo (129.3 ± 22.6 ml (P < 0.001. Global satisfaction scores of the patients in group placebo was significantly lower than group dexketoprofen trometamol after surgery and the increase in global satisfaction score was significant only in group placebo. Conclusion: Dexketoprofen trometamol and Paracetamol didn′t cause significant change on pain scores, but increased patients′ comfort. Although total morphine consumption was significantly decreased by both drugs, the incidence of nausea and vomiting were similar among the groups. According to results of the present study routine addition of dexketoprofen trometamol and paracetamol to patient controlled analgesia morphine after hysterectomies is not

Intravenous Antiepileptic Drugs in Russia

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P. N. Vlasov

2014-01-01

Full Text Available Launching four intravenous antiepileptic drugs: valproate (Depakene and Convulex, lacosamide (Vimpat, and levetiracetam (Keppra – into the Russian market has significantly broadened the possibilities of rendering care to patients in seizure emergency situations. The chemi- cal structure, mechanisms of action, indications/contraindications, clinical effectiveness and tolerability, advantages/disadvantages, and adverse events of using these drugs in urgent and elective neurology are discussed. 

Rectal dihydroartemisinin versus intravenous quinine in the ...

African Journals Online (AJOL)

Rectal dihydroartemisinin versus intravenous quinine in the treatment of severe malaria: A randomised clinical trial. F Esamai, P Ayuo, W Owino-Ongor, J Rotich, A Ngindu, A Obala, F Ogaro, L Quoqiao, G Xingbo, L Guangqian ...

Effect of intradialytic intravenous administration of omega-3 fatty acids on nutritional status and inflammatory response in hemodialysis patients: a pilot study.

Science.gov (United States)

Szklarek-Kubicka, Magdalena; Fijałkowska-Morawska, Jolanta; Zaremba-Drobnik, Danuta; Uciński, Andrzej; Czekalski, Stanisław; Nowicki, Michał

2009-11-01

Because omega-3 polyunsaturated fatty acids (PUFAs) may have anti-inflammatory properties, we tested the hypothesis that intradialytic, intravenous omega-3 PUFA treatment, combined with dietary supplementation, can modify the inflammatory response to dialysis, and influence the nutritional status of hemodialysis (HD) patients. Twenty HD patients with serum albumin at HD sessions. Body mass index (BMI), serum albumin, transferrin, and lipids were measured before and after treatment. Serum interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) levels were determined before and after the HD session at baseline and after 4 weeks of treatment. No adverse events were evident during the study. There were no significant changes in BMI, serum albumin, transferin, total and low-density lipoprotein cholesterol, and triglycerides. Predialysis hsCRP and IL-6 did not change. There was a significant increase in hsCRP (P=.01) and a tendency of IL-6 concentration to increase during the HD session before treatment (P=.067). In contrast, neither hsCRP (P=.21) nor IL-6 (P=.26) changed during the final HD session. Neither urea reduction ratio nor Kt/V changed significantly during the study, but the normalized protein catabolic ratio increased after treatment (P=.003). Short-term parenteral administration of omega-3 PUFA is safe and well-tolerated by HD patients. The intervention does not significantly influence markers of inflammation or change the nutritional status of chronic HD patients, but it may attenuate the inflammatory response to HD sessions.

Intravenous dex medetomidine or propofol adjuvant to spinal anesthesia in total knee replacement surgery

International Nuclear Information System (INIS)

AlOweidi, A.S.; Al-Mustafa, M.M.; Alghanem, S.M.; Qudaisat, Y.; Halaweh, S.A.; Massad, I.M.; Al Ajlouni, J.M; Mas'ad, D. F.

2011-01-01

The purpose of this study was to compare effect of intravenous dex medetomidine with the intravenous propofol adjuvant to spinal intrathecal anesthesia on the duration of spinal anesthesia and hemodynamic parameters during total knee replacement surgery. Supplementation of spinal anesthesia with intravenous dexemedetomidine or propofol produces good sedation levels without significant clinical hemodynamic changes. Adding dex medetomidine produces significantly longer sensory and motor block than propofol . (authors).

COMPARATIVE STUDY OF EFFECT OF INTRAVENOUS MAGNESIUM SULPHATE AND INTRAVENOUS FENTANYL IN ATTENUATING THE HAEMODYNAMIC RESPONSES TO LARYNGOSCOPY AND INTUBATION

Directory of Open Access Journals (Sweden)

Patta

2016-07-01

Full Text Available AIM To compare the haemodynamic response to laryngoscopy and intubation with intravenous MgSO4 and intravenous fentanyl. METHODS Fifty adult patients were divided into two groups randomly into group M and group F. Patients of group M received 30 mg/kg body weight of IV MgSO4 and group F received IV fentanyl 1.5 µg/kg 5 minutes before intubation. RESULTS IV Fentanyl showed greater degree of haemodynamic stability i.e. rise in heart rate, mean arterial pressure during laryngoscopy and intubation compared to IV MgSO4. IV fentanyl showed side effects like respiratory depression, nausea and vomiting. CONCLUSION IV fentanyl is a better drug in controlling haemodynamic response to laryngoscopy and intubation.

Contrast agent choice for intravenous coronary angiography

International Nuclear Information System (INIS)

Zeman, H.D.; Siddons, D.P.

1989-01-01

The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation x-rays and an iodine containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic x-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the x-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation x-rays is visualizing a coronary artery through the left ventricle or aorta which also contains a contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth

Acute Toxicity of Intravenously Administered Titanium Dioxide Nanoparticles in Mice

OpenAIRE

Xu, Jiaying; Shi, Hongbo; Ruth, Magaye; Yu, Hongsheng; Lazar, Lissy; Zou, Baobo; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

2013-01-01

BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂) nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal mortality, blood biochem...

Use of bis phosphonates in prostate cancer

International Nuclear Information System (INIS)

Della Valle, A.

2004-01-01

Prostate cancer is the second leading cause of cancer death in men in the world, meaning a real public health problem. The prevalence of Bone metastases may reach 100% of those who die from this disease printing a serious decline in the quality of life especially in the occurrence of skeletal-related events. Since three decades we try to find an inhibitor bone resorption which might prevent or treat bone metastases develop bisphosphonates (BF). These can not only inhibit the recruitment and differentiation osteoclast but decrease its half-life leading to early apoptosis. All BF have similar physicochemical properties and pharmacokinetics, but they differ in their anti-resorptive potency, ibandronate and zoledronic acid are BF generation that have been successful in the treatment of pain and decreased bone events in several works, however only one study randomized was conducted to show significant therapeutic advantages bone metastasis of prostate cancer. Although most authors indicate a therapeutic benefit, the evidence is weak and higher costs. Urges the implementation of new studies assessing both ibandronate and zoledronic acid in order to assert its virtues

Intravenous versus topical tranexamic acid administration in primary total knee arthroplasty: a meta-analysis.

Science.gov (United States)

Shin, Young-Soo; Yoon, Jung-Ro; Lee, Hoon-Nyun; Park, Se-Hwan; Lee, Dae-Hee

2017-11-01

This meta-analysis was designed to compare the effectiveness and safety of intravenous (IV) versus topical administration of tranexamic acid (TXA) in patients undergoing primary total knee arthroplasty (TKA) by evaluating the need for allogenic blood transfusion, incidence of postoperative complications, volume of postoperative blood loss, and change in haemoglobin levels. Studies were included in this meta-analysis to check whether they assessed the allogenic blood transfusion rate, postoperative complications including pulmonary thromboembolism (PTE) or deep vein thrombosis (DVT), volume of postoperative blood loss via drainage, estimated blood loss, total blood loss, and change in haemoglobin levels before and after surgery in primary TKA with TXA administered through both the IV and topical routes. Ten studies were included in this meta-analysis. The proportion of patients requiring allogenic blood transfusion (OR 1.34, 95 % CI 0.63-2.81; n.s.) and the proportion of patients who developed postoperative complications including PTE or DVT (OR 0.85, 95 % CI 0.41 to 1.77; n.s.) did not significantly differ between the two groups. There was 52.3 mL less blood loss via drainage (95 % CI -50.74 to 185.66 mL; n.s.), 52.1 mL greater estimated blood loss (95 % CI -155.27 to 51.03 mL; n.s.), and 51.4 mL greater total blood loss (95 % CI -208.16 to 105.31 mL; n.s.) in the topical TXA group as compared to the IV TXA group. The two groups were also similar in terms of the change in haemoglobin levels (0.02 g/dL, 95 % CI -0.36 to 0.39 g/dL; n.s.). In primary TKA, there are no significant differences in the transfusion requirement, postoperative complications, blood loss, and change in haemoglobin levels between the IV and topical administration of TXA. In addition, results from subgroup analysis evaluating the effect of the times of TXA administration through the IV route suggested that double IV dose of TXA is more effective than single dose in terms of the

Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study

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Dorward Heidi

2007-01-01

Full Text Available Abstract Background Hereditary Inclusion Body Myopathy (HIBM is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reactions in the synthesis of sialic acid. Reduced sialylation of muscle glycoproteins, such as α-dystroglycan and neural cell adhesion molecule (NCAM, has been reported in HIBM. Methods We treated 4 HIBM patients with intravenous immune globulin (IVIG, in order to provide sialic acid, because IgG contains 8 μmol of sialic acid/g. IVIG was infused as a loading dose of 1 g/kg on two consecutive days followed by 3 doses of 400 mg/kg at weekly intervals. Results For all four patients, mean quadriceps strength improved from 19.0 kg at baseline to 23.2 kg (+22% directly after IVIG loading to 25.6 kg (+35% at the end of the study. Mean shoulder strength improved from 4.1 kg at baseline to 5.9 kg (+44% directly after IVIG loading to 6.0 kg (+46% at the end of the study. The composite improvement for 8 other muscle groups was 5% after the initial loading and 19% by the end of the study. Esophageal motility and lingual strength improved in the patients with abnormal barium swallows. Objective measures of functional improvement gave variable results, but the patients experienced improvements in daily activities that they considered clinically significant. Immunohistochemical staining and immunoblotting of muscle biopsies for α-dystroglycan and NCAM did not provide consistent evidence for increased sialylation after IVIG treatment. Side effects were limited to transient headaches and vomiting. Conclusion The mild benefits in muscle strength experienced by HIBM patients after IVIG treatment may be related to the provision of sialic acid supplied by IVIG. Other sources of sialic acid are being explored as treatment options for HIBM.

Effects of Rapid Intravenous Rehydration in Children With Mild-to-Moderate Dehydration.

Science.gov (United States)

Janet, Sophie; Molina, Juan Carlos; Marañón, Rafael; García-Ros, Marta

2015-08-01

New guidelines for "rapid or ultrarapid" intravenous rehydration are being developed in different emergency departments. These new guidelines propose a faster administration of fluids and electrolytes than in traditional protocols. However, there is still insufficient evidence to establish a standard protocol. Our objective was to determine the effects of an outpatient rapid intravenous rehydration regimen based on the administration of 0.9% saline + 2.5% dextrose, at a rate of 20 mL/kg per hour for 2 hours, in children with mild-to-moderate isonatremic dehydration resulting from acute gastroenteritis. We performed a 2-institution, prospective, observational, descriptive study. Eighty-three patients were included in the study. All patients underwent a first evaluation, including physical examination, laboratory tests, and assessment of clinical degree of dehydration. After this initial evaluation, all children received our intravenous rehydration regimen. A second evaluation including the same items as in the first one was made after in all the children. Intravenous rehydration was successful in 69 patients (83.1%). It failed in 14 patients (16.8%), who required hospitalization because of persistent vomiting in 9 patients and poor general appearance in 5 patients. After intravenous rehydration, we observed a statistically significant decrease in the levels of ketonemia and uremia and in the Gorelick scale score. However, no significant changes were observed in sodium, chloride, potassium, and osmolarity values. We conclude that, in children with mild-to-moderate dehydration, the administration of 20 mL/kg per hour for 2 hours of 0.9% saline solution + 2.5% glucose improved clinical scores and may be used as an alternative and safe way for intravenous rehydration.

Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration.

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Berkó, Szilvia; Szűcs, Kálmán F; Balázs, Boglárka; Csányi, Erzsébet; Varju, Gábor; Sztojkov-Ivanov, Anita; Budai-Szűcs, Mária; Bóta, Judit; Gáspár, Róbert

2016-01-01

Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Both intravenously and EP-administered neostigmine (0.2-66.7 μg/kg) increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 μg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice.

The prehospital intravenous access assessment: a prospective study on intravenous access failure and access delay in prehospital emergency medicine.

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Prottengeier, Johannes; Albermann, Matthias; Heinrich, Sebastian; Birkholz, Torsten; Gall, Christine; Schmidt, Joachim

2016-12-01

Intravenous access in prehospital emergency care allows for early administration of medication and extended measures such as anaesthesia. Cannulation may, however, be difficult, and failure and resulting delay in treatment and transport may have negative effects on the patient. Therefore, our study aims to perform a concise assessment of the difficulties of prehospital venous cannulation. We analysed 23 candidate predictor variables on peripheral venous cannulations in terms of cannulation failure and exceedance of a 2 min time threshold. Multivariate logistic regression models were fitted for variables of predictive value (P0.6) of their respective receiver operating characteristic curve. A total of 762 intravenous cannulations were enroled. In all, 22% of punctures failed on the first attempt and 13% of punctures exceeded 2 min. Model selection yielded a three-factor model (vein visibility without tourniquet, vein palpability with tourniquet and insufficient ambient lighting) of fair accuracy for the prediction of puncture failure (AUC=0.76) and a structurally congruent model of four factors (failure model factors plus vein visibility with tourniquet) for the exceedance of the 2 min threshold (AUC=0.80). Our study offers a simple assessment to identify cases of difficult intravenous access in prehospital emergency care. Of the numerous factors subjectively perceived as possibly exerting influences on cannulation, only the universal - not exclusive to emergency care - factors of lighting, vein visibility and palpability proved to be valid predictors of cannulation failure and exceedance of a 2 min threshold.

Portable Intravenous Fluid Production Device for Ground Use

Data.gov (United States)

National Aeronautics and Space Administration — There are several medical conditions require the administration of intravenous (IV) fluids, but limitations of mass, volume, shelf-life, transportation, and local...

Anaphylaxis following intravenous paracetamol: the problem is the solution.

Science.gov (United States)

Jain, S S; Green, S; Rose, M

2015-11-01

Paracetamol is a ubiquitous analgesic and antipyretic that is widely administered, including by anaesthetists. Immediate hypersensitivity reactions to intravenous paracetamol are particularly rare. We report two cases involving four separate episodes of anaphylaxis to intravenous paracetamol in different perioperative settings without a past history of intolerance to the oral form. The allergological investigations are described, during which it became evident that both patients were allergic to an excipient (mannitol) present in the formulation and that neither was allergic to the principal agent (paracetamol). The importance of referral and investigation of perioperative drug reactions is underscored by these two cases.

Recurrence of Intravenous Talc Granulomatosis following Single Lung Transplantation

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Richard C Cook

1998-01-01

Full Text Available Advanced pulmonary disease is an unusual consequence of the intravenous injection of oral medications, usually developing over a period of several years. A number of patients with this condition have undergone lung transplantation for respiratory failure. However, a history of drug abuse is often considered to be a contraindication to transplantation in the context of limited donor resources. A patient with pulmonary talc granulomatosis secondary to intravenous methylphenidate injection who underwent successful lung transplantation and subsequently presented with recurrence of the underlying disease in the transplanted lung 18 months after transplantation is reported.

Combined use of intravenous anesthetics and hypothermia in treating refractory status epilepticus

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Guo-ping REN

2015-11-01

Full Text Available The primary choice of treating refractory status epilepticus (RSE is intravenous anesthetics, but the seizures of some patients can not get a good control. Thus, other therapies must be combined. Hypothermia not only can terminate seizures, but also play a part in brain protection. Though combined use of intravenous anesthetics and hypothermia is not a regular clinical scheme, the favorable effect has been proved by a lot of clinical research. This paper mainly focuses on the dose of intravenous anesthetics, the time, temperature and procedure of hypothermia, the indications and contraindications of combined therapy, and so on. DOI: 10.3969/j.issn.1672-6731.2015.11.006

Intravenous dynamic nucleography of the brain

International Nuclear Information System (INIS)

Rosenthall, L.

1972-01-01

The advent of stationary imaging devices has created interest in studying cerebral blood flows and transits with diffusible and nondiffusible radioactive indicators. Much of this has disclosed interesting pathophysiology, but not necessarily of significant diagnostic import to include in routine patient workup. The conventional static brain scan is one of the more useful tests in the nuclear medicine armamentarium for uncovering and localizing intracranial disease. Unfortunately, it does not as a rule clearly distinguish cerebral vascular accidents, neoplasms, arteriovenous malformations, and so forth, which is important from the standpoint of patient management. Aside from clinical impressions a diagnosis is often based on the appearance of the radiocontrast angiogram, which is not always desirable because of the implicit hazards. Thus it is incumbent upon investigators to search for innocuous intravenous methods of identifying the various intracranial afflictions. Intravenous 99 /sup m/Tc-pertechnetate comparisons of brain hemisphere perfusion as a routine complement to static brain imaging are useful. Estimations of disparate radioactive transits are made qualitatively from serial 4 to 5 sec exposure scintiphotographs. (U.S.)

Attenuation of acute plasma cortisol response in calves following intravenous sodium salicylate administration prior to castration.

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Coetzee, J F; Gehring, R; Bettenhausen, A C; Lubbers, B V; Toerber, S E; Thomson, D U; Kukanich, B; Apley, M D

2007-08-01

Pain associated with castration in cattle is an animal welfare concern in beef production. This study examined the effect of oral aspirin and intravenous (i.v.) sodium salicylate on acute plasma cortisol response following surgical castration. Twenty bulls, randomly assigned to the following groups, (i) uncastrated, untreated controls, (ii) castrated, untreated controls, (iii) 50 mg/kg sodium salicylate i.v. precastration and (iv) 50 mg/kg aspirin (acetylsalicylic acid) per os precastration, were blood sampled at 3, 10, 20, 30, 40, 50 min and 1, 1.5, 2, 4, 6, 8, 10 and 12 h postcastration. Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. Data were analyzed using noncompartmental analysis, a simple cosine model, anova and t-tests. Intravenous salicylate V(d(ss)) was 0.18 L/kg, Cl(B) was 3.36 mL/min/kg and t(1/2 lambda) was 0.63 h. Plasma salicylate concentrations above 25 microg/mL coincided with significant attenuation in peak cortisol concentrations (P = 0.029). Peak salicylate concentrations following oral aspirin administration was castrated groups was significantly higher than uncastrated controls (P = 0.018). These findings have implications for designing drug regimens to provide analgesia during routine animal husbandry procedures.

Amorphous, Smart, and Bioinspired Polyphosphate Nano/Microparticles: A Biomaterial for Regeneration and Repair of Osteo-Articular Impairments In-Situ

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Werner E. G. Müller

2018-01-01

Full Text Available Using femur explants from mice as an in vitro model, we investigated the effect of the physiological polymer, inorganic polyphosphate (polyP, on differentiation of the cells of the bone marrow in their natural microenvironment into the osteogenic and chondrogenic lineages. In the form of amorphous Ca-polyP nano/microparticles, polyP retains its function to act as both an intra- and extracellular metabolic fuel and a stimulus eliciting morphogenetic signals. The method for synthesis of the nano/microparticles with the polyanionic polyP also allowed the fabrication of hybrid particles with the bisphosphonate zoledronic acid, a drug used in therapy of bone metastases in cancer patients. The results revealed that the amorphous Ca-polyP particles promote the growth/viability of mesenchymal stem cells, as well as the osteogenic and chondrogenic differentiation of the bone marrow cells in rat femur explants, as revealed by an upregulation of the expression of the transcription factors SOX9 (differentiation towards osteoblasts and RUNX2 (chondrocyte differentiation. In parallel to this bone anabolic effect, incubation of the femur explants with these particles significantly reduced the expression of the gene encoding the osteoclast bone-catabolic enzyme, cathepsin-K, while the expression of the tartrate-resistant acid phosphatase remained unaffected. The gene expression data were supported by the finding of an increased mineralization of the cells in the femur explants in response to the Ca-polyP particles. Finally, we show that the hybrid particles of polyP complexed with zoledronic acid exhibit both the cytotoxic effect of the bisphosphonate and the morphogenetic and mineralization inducing activity of polyP. Our results suggest that the Ca-polyP nano/microparticles are not only a promising scaffold material for repairing long bone osteo-articular damages but can also be applied, as a hybrid with zoledronic acid, as a drug delivery system for

The adverse effects of inadvertent intraoperative intravenous ...

African Journals Online (AJOL)

Inadvertent intravenous injection of 1% phenylephrine (10 mg) induced severe hypertension and tachycardia in a previously healthy female patient undergoing elective gynaecological surgery. This medical error was investigated using the criticalincident technique that is available in our department. This case report ...

[Phlebitis associated to intravenous/infusional therapy].

Science.gov (United States)

Nicotera, Raffaela

2011-01-01

Phlebitis is a common problem associated to intravenous therapies, it may cause pain, sepsis and increased duration of hospitalization. Several factors can increase the risk of phlebitis. The literature review addresses the mechanisms of chemical phlebitis, the characteristics of drugs likely to cause a phlebitis and the main measures to be adopted for prevention and treatment.

High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine.

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Motbey, Craig P; Clemens, Kelly J; Apetz, Nadine; Winstock, Adam R; Ramsey, John; Li, Kong M; Wyatt, Naomi; Callaghan, Paul D; Bowen, Michael T; Cornish, Jennifer L; McGregor, Iain S

2013-09-01

Mephedrone (MMC) is a relatively new recreational drug that has rapidly increased in popularity in recent years. This study explored the characteristics of intravenous MMC self-administration in the rat, with methamphetamine (METH) used as a comparator drug. Male Sprague-Dawley rats were trained to nose poke for intravenous MMC or METH in daily 2 h sessions over a 10 d acquisition period. Dose-response functions were then established under fixed- and progressive-ratio (FR and PR) schedules over three subsequent weeks of testing. Brains were analyzed ex vivo for striatal serotonin (5-HT) and dopamine (DA) levels and metabolites, while autoradiography assessed changes in the regional density of 5-HT and serotonin transporter (SERT) and DA transporter (DAT) and induction of the inflammation marker translocator protein (TSPO). Results showed that MMC was readily and vigorously self-administered via the intravenous route. Under a FR1 schedule, peak responding for MMC was obtained at 0.1 mg/kg/infusion, versus 0.01 mg/kg/infusion for METH. Break points under a PR schedule peaked at 1 mg/kg/infusion MMC versus 0.3 mg/kg/infusion for METH. Final intakes of MMC were 31.3 mg/kg/d compared to 4 mg/kg/d for METH. Rats self-administering MMC, but not METH, gained weight at a slower rate than control rats. METH, but not MMC, self-administration elevated TSPO receptor density in the nucleus accumbens and hippocampus, while MMC, but not METH, self-administration decreased striatal 5-hydroxyindolacetic acid (5-HIAA) concentrations. In summary, MMC supported high levels of self-administration, matching or exceeding those previously reported with other drugs of abuse.

From intravenous to enteral ketogenic diet in PICU: A potential treatment strategy for refractory status epilepticus.

Science.gov (United States)

Chiusolo, F; Diamanti, A; Bianchi, R; Fusco, L; Elia, M; Capriati, T; Vigevano, F; Picardo, S

2016-11-01

Ketogenic diet (KD) has been used to treat refractory status epilepticus (RSE). KD is a high-fat, restricted-carbohydrate regimen that may be administered with different fat to protein and carbohydrate ratios (3:1 and 4:1 fat to protein and carbohydrate ratios). Other ketogenic regimens have a lower fat and higher protein and carbohydrate ratio to improve taste and thus compliance to treatment. We describe a case of RSE treated with intravenous KD in the Pediatric Intensive Care Unit (PICU). An 8-year-old boy was referred to the PICU because of continuous tonic-clonic and myoclonic generalized seizures despite several antiepileptic treatments. After admission he was intubated and treated with intravenous thiopental followed by ketamine. Seizures continued with frequent myoclonic jerks localized on the face and upper arms. EEG showed seizure activity with spikes on rhythmic continuous waves. Thus we decided to begin KD. The concomitant ileus contraindicated KD by the enteral route and we therefore began IV KD. The ketogenic regimen consisted of conventional intravenous fat emulsion, plus dextrose and amino-acid hyperalimentation in a 2:1 then 3:1 fat to protein and carbohydrate ratio. Exclusive IV ketogenic treatment, well tolerated, was maintained for 3 days; peristalsis then reappeared so KD was continued by the enteral route at 3:1 ratio. Finally, after 8 days and no seizure improvement, KD was deemed unsuccessful and was discontinued. Our experience indicates that IV KD may be considered as a temporary "bridge" towards enteral KD in patients with partial or total intestinal failure who need to start KD. It allows a prompt initiation of KD, when indicated for the treatment of severe diseases such as RSE. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Potential effects of omega-3 fatty acids on anemia and inflammatory markers in maintenance hemodialysis patients.

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Gharekhani, Afshin; Khatami, Mohammad-Reza; Dashti-Khavidaki, Simin; Razeghi, Effat; Abdollahi, Alireza; Hashemi-Nazari, Seyed-Saeed; Mansournia, Mohammad-Ali

2014-01-07

Anemia is a common complication among hemodialysis (HD) patients. Although intravenous iron and erythropoiesis-stimulating agents revolutionized anemia treatment, about 10% of HD patients show suboptimal response to these agents. Systemic inflammation and increased serum hepcidin level may contribute to this hyporesponsiveness. Considering the anti-inflammatory properties of omega-3 fatty acids, this study aimed to evaluate potential role of these fatty acids in improving anemia and inflammation of chronic HD patients. In this randomized, placebo-controlled trial, 54 adult patients with HD duration of at least 3 months were randomized to ingest 1800 mg of either omega-3 fatty acids or matching placebo per day for 4 months. Anemia parameters including blood hemoglobin, serum iron, transferrin saturation (TSAT), erythropoietin resistance index, and required dose of intravenous iron and erythropoietin, and serum concentrations of inflammatory/anti-inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, C-reactive protein (CRP), hepcidin, ferritin, intact parathyroid hormone (iPTH), and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and after 4 months of the intervention. 45 subjects (25 in the omega-3 and 20 in the placebo group) completed the study. No significant changes were observed in blood hemoglobin, serum iron, TSAT, and required dose of intravenous iron in either within or between group comparisons. Additionally, erythropoietin resistance index as well as required dose of intravenous erythropoietin showed no significant change in the omega-3 group compared to the placebo group. Although a relative alleviation in inflammatory state appeared in the omega-3 group, the mean differences of inflammatory and anti-inflammatory markers between the two groups did not reach statistically significant level except for IL-10-to-IL-6 ratio and serum ferritin level which showed significant changes in favor of omega-3

Intravenous microemulsion of docetaxel containing an anti-tumor synergistic ingredient (Brucea javanica oil: formulation and pharmacokinetics

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Ma S

2013-10-01

Full Text Available Shilin Ma,1 Fen Chen,1 Xiaohui Ye,2 Yingjie Dong,2 Yingna Xue,1 Heming Xu,1 Wenji Zhang,1 Shuangshuang Song,1 Li Ai,2 Naixian Zhang,2 Weisan Pan1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 2Liaoning Institute of Pharmaceutical Industry, Liaoning, The People's Republic of China Abstract: The purpose of this study was to develop a docetaxel microemulsion containing an anti-tumor synergistic ingredient (Brucea javanica oil and to investigate the characteristics of the microemulsion. Brucea javanica oil contains oleic acid and linoleic acids that have been shown by animal and human studies to inhibit tumor formation. The microemulsion containing Brucea javanica oil, medium-chain triglyceride, soybean lecithin, Solutol®HS 15, PEG 400, and water was developed for docetaxel intravenous administration. A formulation with higher drug content, lower viscosity, and smaller particle size was developed. The droplet size distribution of the dispersed phase of the optimized microemulsion was 13.5 nm, determined using a dynamic light scattering technique. The small droplet size enabled the microemulsion droplets to escape from uptake and phagocytosis by the reticuloendothelial system and increased the circulation time of the drug. The zeta potential was -41.3 mV. The optimized microemulsion was pale yellow, transparent, and non-opalescent in appearance. The value of the combination index was 0.58, showing that there was a synergistic effect when docetaxel was combined with Brucea javanica oil. After a single intravenous infusion dose (10 mg/kg in male Sprague Dawley rats, the area under the curve of the microemulsion was higher and the half-time was longer compared with that of docetaxel solution alone, and showed superior pharmacokinetic characteristics. These results indicate that this preparation of docetaxel in emulsion is likely to provide an excellent prospect for clinical tumor treatment. Keywords: microemulsion, docetaxel

Hemolytic Disease of the Fetus and Newborn due to Intravenous Drug Use.

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Markham, Kara B; Scrape, Scott R; Prasad, Mona; Rossi, Karen Q; O'Shaughnessy, Richard W

2016-03-01

Objectives The objective is to present a pregnancy complication associated with intravenous drug use, namely, that of red blood cell alloimmunization and hemolytic disease of the fetus and newborn. Methods An observational case series is presented including women with red blood cell alloimmunization most likely secondary to intravenous drug abuse Results Five pregnancies were identified that were complicated by red blood cell alloimmunization and significant hemolytic disease of the fetus and newborn, necessitating intrauterine transfusion, an indicated preterm birth, or neonatal therapy. Conclusions As opioid abuse continues to increase in the United States, clinicians should be aware of the potential for alloimmunization to red blood cell antibodies as yet another negative outcome from intravenous drug abuse.

Intravenous paracetamol overdose in a paediatric patient

NARCIS (Netherlands)

Broeks, Ilse J.; Van Roon, Eric N.; Van Pinxteren-Nagler, Evelyn; De Vries, Tjalling W.

2013-01-01

BACKGROUND: Paracetamol is a widely used drug in children. In therapeutic doses, paracetamol has an excellent safety profile. Since the introduction of the intravenous form in 2004, only three reports of accidental overdose in children have been published. The low number probably is due to

Intravenous iron supplementation in children on hemodialysis.

NARCIS (Netherlands)

Leijn, E.; Monnens, L.A.H.; Cornelissen, E.A.M.

2004-01-01

BACKGROUND: Children with end-stage renal disease (ESRD) on hemodialysis (HD) are often absolute or functional iron deficient. There is little experience in treating these children with intravenous (i.v.) iron-sucrose. In this prospective study, different i.v. iron-sucrose doses were tested in

Total intravenous anaesthesia in a goat undergoing craniectomy.

Science.gov (United States)

Vieitez, Verónica; Álvarez Gómez de Segura, Ignacio; López Rámis, Víctor; Santella, Massimo; Ezquerra, Luis Javier

2017-09-15

Cerebral coenurosis is a disease of the central nervous system in sheep and goats, and is usually fatal unless surgical relief is provided. Information regarding neuroanaesthesia in veterinary medicine in goats is scant. We describe anaesthetic management of an intact female goat (2 years; 16 kg) presented for craniectomy. The goat was sedated with xylazine (0.05 mg kg -1 , i.m.) and morphine (0.05 mg kg -1 , i.m.). General anaesthesia was induced 20 min later with propofol and maintained with a constant rate infusion of propofol (0.2 mg kg -1  min -1 ). A cuffed endotracheal tube was placed and connected to a rebreathing (circle) system and mechanical ventilation with 100% oxygen was initiated. A bolus of lidocaine (1 mg kg -1 ), midazolam (0.25 mg kg -1 ) and fentanyl 2.5 μg kg -1 was delivered via the intravenous route followed immediately by a constant rate infusion of lidocaine (50 μg kg -1  min -1 ), midazolam (0.15 mg kg -1  h -1 ) and fentanyl (6 μg kg -1  h -1 ) administered via the intravenous route throughout surgery. Craniectomy was undertaken and the goat recovered uneventfully. Total intravenous anaesthesia with propofol, lidocaine, fentanyl and midazolam could be an acceptable option for anaesthesia during intracranial surgery in goats.

Verification of intravenous catheter placement by auscultation--a simple, noninvasive technique.

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Lehavi, Amit; Rudich, Utay; Schechtman, Moshe; Katz, Yeshayahu Shai

2014-01-01

Verification of proper placement of an intravenous catheter may not always be simple. We evaluated the auscultation technique for this purpose. Twenty healthy volunteers were randomized for 18G catheter inserted intravenously either in the right (12) or left arm (8), and subcutaneously in the opposite arm. A standard stethoscope was placed over an area approximately 3 cm proximal to the tip of the catheter in the presumed direction of the vein to grade on a 0-6 scale the murmur heard by rapidly injecting 2 mL of NaCl 0.9% solution. The auscultation was evaluated by a blinded staff anesthesiologist. All 20 intravenous injection were evaluated as flow murmurs, and were graded an average 5.65 (±0.98), whereas all 20 subcutaneous injections were evaluated as either crackles or no sound, and were graded an average 2.00 (±1.38), without negative results. Sensitivity was calculated as 95%. Specificity and Kappa could not be calculated due to an empty false-positive group. Being simple, handy and noninvasive, we recommend to use the auscultation technique for verification of the proper placement of an intravenous catheter when uncertain of its position. Data obtained in our limited sample of healthy subjects need to be confirmed in the clinical setting.

Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

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Hao Jiqing

2009-03-01

Full Text Available Abstract Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms.

Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

Science.gov (United States)

Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie

2009-01-01

Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934

Effection of percutaneous coronary intenvention compared with intravenous thrombolysis therapy of acute myocardial infarction

International Nuclear Information System (INIS)

Lu Jianhui; Hong Xiaosu; Xu Weiting

2006-01-01

Objective: To evaluate the curative effect of the two successful therapeatic methods on myocardial infarction in the acute and long-term stage: percutaneous coronary intenvention(PCI) and intravenous thrombolysis therapy. Methods: Fifty-six patients of acute myocardial infarction were studied. There was no record of heart failure occurence in the case history for all of them. We randomly assigned them to receive PCI or intravenous thrombolysis therapy, and all of them are treated successfully. Left ventricule ejection fraction (LVEF) and left ventricule end diastole diameter(LVEDD) measured by echocardiography were analyzed. Clinical information about death caused by cardial origin problems were collected and the mean survival days of the patients were 548.7 ± 48.9. Results: The total of 27 patients were assigned to undergo PCI and 29 patients received intravenous thrombolysis therapy. LVEF patients with PCI were 57.6% ± 2.3%, and patients with intravenous thrombolysis therapy were 49.9% ± 1.9%. There were significant difference between the two groups(P 0.5). 548.7 ± 48.9 days survival was accounted for 85.2% in the PCI group, and 79.3% in the intravenous thrombolysis therapy (P>0.5). Multivariate analysis showed that older age, LVEF, were related to 548.7 ± 48.9 days mortality. Conclusion: The results of this study show more acute stage benefit patients treated with PCI using bare stant than those treated with intravenous thrombolysis therapy; But it indicates that there is no more long-term survival for patients treated with PCI by using bare stant compared with those who received intravenous thrombolysis therapy in the patients with light or medium acute myocardial infarction. (authors)

HEADPLAY Personal Cinema System Facilitates Intravenous Cannulation in Children: A Randomized Controlled Trial

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Evangeline Lim

2013-01-01

Full Text Available HEADPLAY personal cinema system (PCS is a portable visual headset/visor through which movie clips may be viewed. We studied the use of HEADPLAY PCS as a distraction tool in facilitating intravenous cannulation in children undergoing anaesthesia. 60 children were enrolled into the study and randomized into 2 groups. EMLA local anaesthetic cream was used to reduce the pain associated with intravenous cannulation. Children in group 1 wore the HEADPLAY visor whereas children in group 2 were subject to conventional distraction therapy. Children were asked to rate their anxiety, pain, and satisfaction scores after intravenous cannulation. Periprocedural anxiety was also determined using the modified Yale Preoperative Anxiety Scale (mYPAS. There were no statistically significant differences in terms of pain and anxiety scores between the 2 groups. Although the satisfaction score of the children in the HEADPLAY PCS group was marginally higher compared to the conventional group, this did not hit statistical significance. 86.6% of children in group 1 reported that they would want to use the visor again for their next intravenous cannulation. We conclude that HEADPLAY PCS is a distraction tool that is acceptable to most children and can contribute towards satisfaction of the intravenous cannulation process in children.

Multi Organ Failure Following Intravenous Gasoline for Suicide: A Case Report

OpenAIRE

Hadi Hamishehkar; Hassan Soleimanpour; Ata Mahmoodpoor

2012-01-01

Hydrocarbons are ubiquitous in daily life and include plant and animal fats, alcohols, solvents, natural gas, petroleum derivates. Majority of intoxication reports of hydrocarbons are due to inhalation or ingestion, but there is few reports about intravenous injection of gasoline. We report a 58 year-old man who injected gasoline intravenously for suicide. He developed soft tissue necrosis of forearm and bilateral pulmonary infiltration. He underwent fasciotomy and extensive debridement of ne...

Microbiological quality of some brands of intravenous fluids ...

African Journals Online (AJOL)

SERVER

2007-10-04

Oct 4, 2007 ... Food, Drug Administration and Control (NAFDAC), have on many occasions ... products from 8 manufacturers were tested for their ... Table 1. Microbial contamination level of brand of intravenous fluids produced by some.

Pharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans

DEFF Research Database (Denmark)

Carl, Peder; Høgskilde, S; Lang-Jensen, T

1994-01-01

Eltanolone, a new intravenous steroid anaesthetic agent was administered intravenously in a dose of 0.6 mg.kg-1 over 45 s to eight healthy male volunteers to evaluate some of its pharmacokinetic and pharmacodynamic effects. Drug concentration-time data were analysed by PCNONLIN, a non...

Oral versus intravenous rehydration therapy in severe gastroenteritis.

Science.gov (United States)

Sharifi, J; Ghavami, F; Nowrouzi, Z; Fouladvand, B; Malek, M; Rezaeian, M; Emami, M

1985-01-01

A controlled, randomised trial comparing the results of oral rehydration therapy with those of intravenous fluid treatment in 470 children with severe gastroenteritis was undertaken. The oral rehydration therapy was divided into two phases--a rehydration phase that used high sodium isotonic fluid at 40 ml/kg per hour and a maintenance phase using low sodium isotonic fluid (sodium 40, potassium 30, bicarbonate 25, chloride 45, and dextrose 130 mmol/l). The results indicate that oral rehydration treatment, used according to this protocol, is successful in treating severe diarrhoea and dehydration, and has considerable advantages over intravenous fluid therapy in reducing complications associated with the treatment of hypernatraemia, in promoting rapid correction of hypokalaemia and acidosis, in decreasing the duration of diarrhoea, and in promoting a greater weight gain at hospital discharge. PMID:3901934

Pharmacokinetics of high-dose intravenous melatonin in humans

DEFF Research Database (Denmark)

Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette Marie

2016-01-01

This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60......, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments...... of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221...

Clinical Experience of Total Intravenous Anesthesia in 77 Renal Transplant Patients

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Pinar Ergenoglu

2013-08-01

Full Text Available Purpose:Renal transplantation significantly improves quality of life compared to hemodialysis in patients with end-stage renal failure. In end-stage renal failure anesthetic technique should be planned carefully, due to changes in volume distribution, drug metabolism, excretion. Results of total intravenous anesthesia, inhalation anesthesia, regional techniques are being investigated. Aim of this study was to present our experience in total intravenous anesthesia in 77 patients, who underwent live and cadaveric donor renal transplantation at Baskent University Faculty of Medicine Adana Teaching and Research Center. Material and Methods:Induction of anesthesia was performed with propofol(2mg/kg and fentanyl(1μg/kg, and rocuronium bromide(0.4-0.5mg/kg was given before intubation. Anesthesia was maintained with total intravenous anesthesia(propofol,50 mcg/kg/min; remifentanil,0.25 mcg/kg/min infusion. Intraoperative fluid, urine volumes were recorded. For preemptive multimodal analgesia, pre-incisional intravenous paracetamol(15mg/kg, intramuscular morphine(0.1mg/kg were given. Postoperative analgesia was maintained with intravenous patient-controlled analgesia(meperidine 10 mg bolus, with a lockout time of 20 minutes. Postoperative pain was recorded using Visual Analogue Scale, level of sedation was assessed by Ramsey Sedation Scale. Results:Study included 64(83.1% live donor transplantations and 13(16.9% cadaveric donor transplantations. Mean total fluid administration was similar between live and cadaveric donor kidney transplantation patients however mean intraoperative urine output was significantly higher in live donor kidney transplantation patients(p<0.001. 57.1% of patients had no pain at 5. minutes postoperatively(Visual Analog Scale Score=0, at 15. minutes postoperatively mean visual analog scale score was 2.6 and the first analgesic requirements were recorded at 39.6 minutes. According to Ramsey Sedation Scale, majority of patients(54

COMPARISON OF THE EFFECTS OF INTERCOSTAL NERVE BLOCK WITH ROPIVACAINE AND INTRAVENOUS PARACETAMOL INFUSION TO INTRAVENOUS PARACETAMOL INFUSION ALONE FOR PAIN CONTROL AFTER OPEN CHOLECYSTECTOMY

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Somnath Dey

2017-11-01

Full Text Available BACKGROUND Postoperative pain after open cholecystectomy is associated with respiratory dysfunction, increased stress response and prolonged hospital stay. We compare intravenous paracetamol (7.5 mg/kg plus intercostal nerve block with local anaesthetic ropivacaine 0.5% to intravenous paracetamol (15 mg/kg on pain control after open cholecystectomy. MATERIALS AND METHODS 140 patients, who underwent for open cholecystectomy, were randomly divided into two groups of 70. The patients were randomly allocated to any of the following two groups depending upon the drug used for analgesia (Group P or Group I Intravenous paracetamol 15 mg/kg was given to patients of group P and paracetamol 7.5 mg/kg with Intercostal nerve block in right side 6-10 intercostal nerves with 2 ml local anaesthetic ropivacaine 0.5% in each space was given to patients of group I just after intubation before incision. When the patients were transferred to postoperative recovery room, intensity of pain was recorded by response from the patients using 100 mm linear visual analogue scale ranging from 0 to 100. The pain scoring was done in the immediate postoperative period (when the patient was able to communicate in the post anaesthesia care unit, at 30 minutes, 1 hr. then hourly up to 24 hrs. till patient complained of pain with VAS score 40 or more. RESULTS The severity of pain in VAS score was lower in immediate postoperative period, at 30 minutes, 1 hour and 2 hours postoperatively in group I than the group P and those were statistically significant (p<0.001. Duration of analgesia also significantly lower in group I. Mean duration of analgesia in group P is 161.9 ± 42.6 min and in group I is 241.3 ± 44.2 min (p<0.001. CONCLUSION Adding Intercostal nerve block to intravenous infusion of Paracetamol infusion (7.5 mg/kg is better than sole intravenous infusion of Paracetamol (15 mg/kg in controlling pain severity even after reducing dose of paracetamol after open

Incarcerated intravenous heroin users: predictors of post-release utilization of methadone maintenance treatment.

Science.gov (United States)

Lin, Huang-Chi; Wang, Peng-Wei; Yang, Yi-Hsin; Tsai, Jih-Jin; Yen, Cheng-Fang

2016-01-01

Incarcerated intravenous heroin users have more problematic patterns of heroin use, but are less likely to access methadone maintenance treatment by their own initiative than heroin users in the community. The present study examined predictors for receiving methadone maintenance treatment post-release among incarcerated intravenous heroin users within a 24-month period. This cohort study recruited 315 incarcerated intravenous heroin users detained in 4 prisons in southern Taiwan and followed up within the 24-month period post-release. Cox proportional hazards regression analysis was applied to determine the predictive effects of sociodemographic and drug-use characteristics, attitude toward methadone maintenance treatment, human immunodeficiency virus serostatus, perceived family support, and depression for access to methadone maintenance treatment after release. There were 295 (93.7%) incarcerated intravenous heroin users released that entered the follow-up phase of the study. During the 24-month follow-up period, 50.8% of them received methadone maintenance treatment. After controlling for the effects of the detainment period before and after recruitment by Cox proportional hazards regression analysis, incarcerated intravenous heroin users who had positive human immunodeficiency virus serostatus (HR = 2.85, 95% CI = 1.80-4.52, p maintenance treatment before committal (HR = 1.94, 95% CI = 1.23-3.05, p maintenance treatment within the 24-month follow-up period. Positive human immunodeficiency virus serostatus with fully subsidized treatment and previous methadone maintenance treatment experiences predicted access of methadone maintenance treatment post-release. Strategies for getting familiar with methadone maintenance treatment during detainment, including providing methadone maintenance treatment prior to release and lowering the economic burden of receiving treatment, may facilitate entry of methadone maintenance treatment for incarcerated intravenous heroin

Intravenous glutathione for skin lightening: Inadequate safety data ...

African Journals Online (AJOL)

protein thiol that protects mammalian cells from oxidative stress. Intravenous (IV) GSH for skin lightening is advertised by clinics in South Africa and internationally online, yet to date no published review on the subject exists. Methods.

Safety of Intravenous Application of Mistletoe (Viscum album L. Preparations in Oncology: An Observational Study

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Megan L. Steele

2014-01-01

Full Text Available Background. Traditional mistletoe therapy in cancer patients involves subcutaneous applications of Viscum album L. preparations, with doses slowly increasing based on patient responses. Intravenous infusion of high doses may improve therapeutic outcomes and is becoming more common. Little is known about the safety of this “off-label” application of mistletoe. Methods. An observational study was performed within the Network Oncology. Treatment with intravenous mistletoe applications is described. The frequency of adverse drug reactions (ADRs to intravenous mistletoe applications was calculated and compared to ADR data from a study on subcutaneous applications. Results. Of 475 cancer patients who received intravenous infusions of Helixor, Abnoba viscum, or Iscador mistletoe preparations, 22 patients (4.6% reported 32 ADRs of mild (59.4% or moderate severity (40.6%. No serious ADRs occurred. ADRs were more frequently reported to i.v. mistletoe administered alone (4.3%, versus prior to chemotherapy (1.6%. ADR frequency differed with respect to preparation type, with Iscador preparations showing a higher relative frequency, compared to Abnoba viscum and Helixor. Overall, patients were almost two times less likely to experience an ADR to intravenous compared to subcutaneous application of mistletoe. Conclusion. Intravenous mistletoe therapy was found to be safe and prospective studies for efficacy are recommended.

Distribution of radiolabelled azelaic acid in eye membranes and fluids of rabbits

International Nuclear Information System (INIS)

Mingrone, G.; Greco, G.; Ciardiello, A.; Passo, S.; Nazzaro-Porro, M.

1984-01-01

A direct cytotoxic effect of 14 C-acelaic on melanocytes of human melanoma has been demonstrated. In view of a possible future therapeutic employment of this drug in the treatment of primary ocular melanoma the route of choice of azelaic acid administration in rabbits was investigated. The results evidenced a sudden and direct blood absorption of topically (by retrobulbar injection) administered azelaic acid. This is in agreement with the high water solubility of azelaic acid sodium salt. These preliminary reports indicate that the elective route of azelaic administration in primitive eye melanoma is intravenously by continuous infusion. (author)

Effects of intravenous diclofenac on postoperative sore throat in ...

African Journals Online (AJOL)

Effects of intravenous diclofenac on postoperative sore throat in patients undergoing laparoscopic surgery at Aga Khan University Hospital, Nairobi: A prospective, randomized, double blind controlled trial.

Early treatment with intravenous lipid emulsion in a potentially lethal hydroxychloroquine intoxication.

Science.gov (United States)

Ten Broeke, R; Mestrom, E; Woo, L; Kreeftenberg, H

2016-06-01

This case report describes the possible benefit of intravenous lipid emulsion in two patients surviving a severe intoxication with hydroxychloroquine in a dose that was previously considered to be lethal. The first case involves a 25-year-old female who ingested 17.5 grams of hydroxychloroquine, approximately one hour before presentation. An ECG showed QRS widening and the lab results showed hypokalaemia. She became unconscious, and developed hypotension and eventually apnoea. After intubation, supportive care consisted of norepinephrine and supplementation of potassium. Moreover, sodium bicarbonate and intravenous lipid emulsion were started to prevent cardiac toxicity. After these interventions, haemodynamic stability was established within a few hours. Although cardiomyopathy was confirmed, the patient recovered after two weeks. The second case concerns a 25-year-old male who took 5 grams of hydroxychloroquine. At presentation, two hours after intake, he showed QTc prolongation and hypokalaemia. The patient was treated with the usual supportive care and, although presentation to hospital was later, with intravenous lipid emulsion. Also this patient recovered. In conclusion, these cases show the benefit of supplemental intravenous lipid emulsion to prevent cardiac toxicity after a severe intoxication with hydroxychloroquine.

Renal function in patients with non-dialysis chronic kidney disease receiving intravenous ferric carboxymaltose

DEFF Research Database (Denmark)

Macdougall, Iain C; Bock, Andreas H; Carrera, Fernando

2017-01-01

BACKGROUND: Preclinical studies demonstrate renal proximal tubular injury after administration of some intravenous iron preparations but clinical data on renal effects of intravenous iron are sparse. METHODS: FIND-CKD was a 56-week, randomized, open-label, multicenter study in which patients...... with non-dialysis dependent chronic kidney disease (ND-CKD), anemia and iron deficiency without erythropoiesis-stimulating agent therapy received intravenous ferric carboxymaltose (FCM), targeting either higher (400-600 μg/L) or lower (100-200 μg/L) ferritin values, or oral iron. RESULTS: Mean (SD) e...... quartiles of FCM dose, change in ferritin or change in TSAT versus change in eGFR. Dialysis initiation was similar between groups. Renal adverse events were rare, with no indication of between-group differences. CONCLUSION: Intravenous FCM at doses that maintained ferritin levels of 100-200 μg/L or 400...

Illicit intravenous drug use in Johannesburg - medical complications ...

African Journals Online (AJOL)

mortality and prevalence of HIV infection. Design. We conducted a ... Table I. Other complications of intravenous drug abuse ... In 2 cases (2%) an initial screen positivity .... patients with Gram-negative, anaerobic or fungal organisms. Our study ...

Intrahepatic Cholestasis of Pregnancy with Severe Elevation of Bile Acids in the Setting of Acute Hepatitis C Infection

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Megan L. Lawlor

2016-01-01

Full Text Available Intrahepatic cholestasis of pregnancy (ICP is a complication of pregnancy resulting in elevation of serum bile acid levels. ICP is often associated with underlying liver disease, including hepatitis C. Bile acids in relationship to the acute infection of hepatitis C virus have not yet been delineated in the literature. A 26-year-old gravida 4 para 2103 with dichorionic, diamniotic twin gestation and history of intravenous drug abuse developed ICP in the setting of acute hepatitis C infection. In addition to clinical symptoms of pruritus and right upper quadrant pain, she developed severe elevation in bile acids, 239 micromol/L, and transaminitis aspartate aminotransferase 1033 U/L, and alanine aminotransferase 448 U/L. She received ursodeoxycholic acid and antenatal testing was performed. Patient delivered vaginally at 33-week gestation following preterm rupture of membranes. Neonates were admitted to NICU and had uncomplicated neonatal courses. In the setting of ICP with significant transaminitis and severe elevation of bile acids, consideration of acute viral hepatitis is important, especially considering the worsening opioid epidemic and concurrent increase in intravenous drug use in the United States. Further study is needed regarding the acute form of HCV infection and its effect on ICP and associated bile acids.

Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

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Kang, Shin-Ae; Tsolmon, Bilegtsaikhan [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Mann, Aman P. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Zheng, Wei; Zhao, Lichao; Zhao, Yan Daniel [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Volk, David E.; Lokesh, Ganesh L.-R. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Morris, Lynsie; Gupta, Vineet; Razaq, Wajeeha [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Rui, Hallgeir [Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107 (United States); Suh, K. Stephen [John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601 (United States); Gorenstein, David G. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Tanaka, Takemi, E-mail: takemi-tanaka@ouhsc.edu [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States)

2015-08-15

The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100 μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500 μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions. - Highlights: • Intravenous administration of ESTA was well tolerated. • ESTA up to 500 μg does not cause hematologic, organs, and immunologic responses. • ESTA-mediated hepatic abnormality was considered minor.

Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

International Nuclear Information System (INIS)

Kang, Shin-Ae; Tsolmon, Bilegtsaikhan; Mann, Aman P.; Zheng, Wei; Zhao, Lichao; Zhao, Yan Daniel; Volk, David E.; Lokesh, Ganesh L.-R.; Morris, Lynsie; Gupta, Vineet; Razaq, Wajeeha; Rui, Hallgeir; Suh, K. Stephen; Gorenstein, David G.; Tanaka, Takemi

2015-01-01

The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100 μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500 μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions. - Highlights: • Intravenous administration of ESTA was well tolerated. • ESTA up to 500 μg does not cause hematologic, organs, and immunologic responses. • ESTA-mediated hepatic abnormality was considered minor

Bisphosphonate-related osteonecrosis of the jaw: historical, ethical, and legal issues associated with prescribing.

Science.gov (United States)

Faiman, Beth; Pillai, Aiswarya Lekshmi Pillai Chandran; Benghiac, Ana Gabriela

2013-01-01

The long-term effects of many drugs are unknown. Established risks are communicated to patients who participate in clinical trials during the informed consent process. However, unknown and unanticipated side effects of medications may occur years after treatment. Patients with metastatic bone cancer experience an imbalance between tumor cells and the bone marrow microenvironment. Increased cytokine release, osteoclastic activity, and uncoupled osteoblastic activity lead to weakened bone structure and osteolytic lesions. The bisphosphonates are a class of drugs available in IV and oral formulations to treat and prevent bone loss and decrease the risk of skeletal-related events. Intravenous bisphosphonates such as zoledronic acid and pamidronate disodium are approved by the US Food and Drug Administration for the treatment of bone pain and hypercalcemia of malignancy and the prevention of painful bone fractures in patients with metastatic bone cancer. Oral bisphosphonates such as alendronate, risedronate, and etidronate are used to reduce the risk of skeletal fractures in patients with osteoporosis and in breast cancer. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but painful complication of treatment characterized by infection, exposed bone, and poor wound healing. In this article, we discuss BRONJ and identify past, present, and future ethical and legal issues surrounding bisphosphonate administration.

Relapse of Neuromyelitis Optica Spectrum Disorder Associated with Intravenous Lidocaine

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Akiyuki Uzawa

2011-01-01

Full Text Available Lidocaine unmasks silent symptoms and eases neuropathic pain in multiple sclerosis patients; however, the effects of lidocaine in neuromyelitis optica have never been reported. We describe the case of a 59-year-old Japanese woman with neuromyelitis optica spectrum disorder who developed optic neuritis 1 day after intravenous lidocaine injection for treating allodynia. Her symptom seemed to result from a relapse of neuromyelitis optica induced by lidocaine administration, and not because of the transient effects of intravenous lidocaine administration. The possibility that lidocaine administration results in relapse of neuromyelitis optica due to its immunomodulating effects cannot be ruled out.

Ab initio design of drug carriers for zoledronate guest molecule using phosphonated and sulfonated calix[4]arene and calix[4]resorcinarene host molecules

Science.gov (United States)

Jang, Yong-Man; Yu, Chol-Jun; Kim, Jin-Song; Kim, Song-Un

2018-04-01

Monomolecular drug carriers based on calix[n]-arenes and -resorcinarenes containing the interior cavity can enhance the affinity and specificity of the osteoporosis inhibitor drug zoledronate (ZOD). In this work we investigate the suitability of nine different calix[4]-arenes and -resorcinarenes based macrocycles as hosts for the ZOD guest molecule by conducting {\\it ab initio} density functional theory calculations for structures and energetics of eighteen different host-guest complexes. For the optimized molecular structures of the free, phosphonated, sulfonated calix[4]-arenes and -resorcinarenes, the geometric sizes of their interior cavities are measured and compared with those of the host-guest complexes in order to check the appropriateness for host-guest complex formation. Our calculations of binding energies indicate that in gaseous states some of the complexes might be unstable but in aqueous states almost all of the complexes can be formed spontaneously. Of the two different docking ways, the insertion of ZOD with the \\ce{P-C-P} branch into the cavity of host is easier than that with the nitrogen containing heterocycle of ZOD. The work will open a way for developing effective drug delivering systems for the ZOD drug and promote experimentalists to synthesize them.

Comparison of palmitic acid kinetics during glucose or ketone body infusions

Energy Technology Data Exchange (ETDEWEB)

Birkhahn, R.H.; Block, D.J.; Birkhahn, G.C.; Thomford, N.R.

1986-03-05

Ketone body interactions can be observed for extended ketosis by infusion by monoacetoacetin (the monoglyceride of acetoacetic acid). Palmitic acid kinetics were compared on the 5th day of glucose or ketone body-glucose infusions. 20 rats were fed complete diets intravenously at the rate of 50 ml/day. All diets contained vitamins, trace minerals, electrolytes, amino acids and 1 kcal/ml of non-protein energy. Rats were divided by energy source: Group A (n = 10) received energy from glucose and Group B (n = 10) from 72% monoacetoacetin plus 28% glucose. Diets were given at 1/2 and 3/4 rats on days 1 and 2, respectively and at full rate for days 3-5. Urinary nitrogen losses, body weight and dietary intake were measured daily. Palmitate kinetics was measured on day 5 using a continuous infusion of (1-/sup 14/C) palmitate and measuring C-14 in breath and plasma and plasma palmitate by GC. The two groups had similar body weight changes and urinary nitrogen losses over the 3 days of full intake Group A had lower plasma palmitate (88 +/- 7 vs 105 +/- 6 micromol/l) but similar turnover (17.1 +/- 2.4 vs 15.0 +/- 1.9 mmol/hr) and oxidation 2.3 +/- 0.3 vs 2.2 +/- 0.05 mmol/hr) compared to Group B. These data show that feeding monoacetoacetin intravenously does not stimulate fatty acid metabolism in the well nourished rat.

Comparison of palmitic acid kinetics during glucose or ketone body infusions

International Nuclear Information System (INIS)

Birkhahn, R.H.; Block, D.J.; Birkhahn, G.C.; Thomford, N.R.

1986-01-01

Ketone body interactions can be observed for extended ketosis by infusion by monoacetoacetin (the monoglyceride of acetoacetic acid). Palmitic acid kinetics were compared on the 5th day of glucose or ketone body-glucose infusions. 20 rats were fed complete diets intravenously at the rate of 50 ml/day. All diets contained vitamins, trace minerals, electrolytes, amino acids and 1 kcal/ml of non-protein energy. Rats were divided by energy source: Group A (n = 10) received energy from glucose and Group B (n = 10) from 72% monoacetoacetin plus 28% glucose. Diets were given at 1/2 and 3/4 rats on days 1 and 2, respectively and at full rate for days 3-5. Urinary nitrogen losses, body weight and dietary intake were measured daily. Palmitate kinetics was measured on day 5 using a continuous infusion of [1- 14 C] palmitate and measuring C-14 in breath and plasma and plasma palmitate by GC. The two groups had similar body weight changes and urinary nitrogen losses over the 3 days of full intake Group A had lower plasma palmitate (88 +/- 7 vs 105 +/- 6 micromol/l) but similar turnover (17.1 +/- 2.4 vs 15.0 +/- 1.9 mmol/hr) and oxidation 2.3 +/- 0.3 vs 2.2 +/- 0.05 mmol/hr) compared to Group B. These data show that feeding monoacetoacetin intravenously does not stimulate fatty acid metabolism in the well nourished rat

Risk factors are different for deep and lobar remote hemorrhages after intravenous thrombolysis.

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Luis Prats-Sanchez

Full Text Available Remote parenchymal haemorrhage (rPH after intravenous thrombolysis is defined as hemorrhages that appear in brain regions without visible ischemic damage, remote from the area of ischemia causing the initial stroke symptom. The pathophysiology of rPH is not clear and may be explained by different underlying mechanisms. We hypothesized that rPH may have different risk factors according to the bleeding location. We report the variables that we found associated with deep and lobar rPH after intravenous thrombolysis.This is a descriptive study of patients with ischemic stroke who were treated with intravenous thrombolysis. These patients were included in a multicenter prospective registry. We collected demographic, clinical and radiological data. We evaluated the number and distribution of cerebral microbleeds (CMB from Magnetic Resonance Imaging. We excluded patients treated endovascularly, patients with parenchymal hemorrhage without concomitant rPH and stroke mimics. We compared the variables from patients with deep or lobar rPH with those with no intracranial hemorrhage.We studied 934 patients (mean age 73.9±12.6 years and 52.8% were men. We observed rPH in 34 patients (3.6%; 9 (0.9% were deep and 25 (2.7% lobar. No hemorrhage was observed in 900 (96.6% patients. Deep rPH were associated with hypertensive episodes within first 24 hours after intravenous thrombolysis (77.7% vs 23.3%, p1 CMB (30.7% vs 4.4%, p = 0.003, lobar CMB (53.8% vs 3.0%, p<0.001 and severe leukoaraiosis (76.9% vs 42%, p = 0.02.A high blood pressure within the first 24 hours after intravenous thrombolysis is associated with deep rPH, whereas lobar rPH are associated with imaging markers of amyloid deposition. Thus, our results suggest that deep and lobar rPH after intravenous thrombolysis may have different mechanisms.

BONE TURNOVER IN OSTEOPOROTIC WOMEN DURING LONG-TERM ORAL BISPHOSPHONATES TREATMENT: IMPLICATIONS FOR TREATMENT FAILURE AND "DRUG HOLIDAY" IN THE REAL WORLD.

Science.gov (United States)

Liel, Yair; Plakht, Ygal; Tailakh, Muhammad Abu

2017-07-01

Little data exist to support concerns over bone turnover suppression during prolonged oral bisphosphonate treatment and on consequences of the recommended "drug holiday." This study was performed to assess bone resorption rates in postmenopausal osteoporotic women on prolonged oral bisphosphonate treatment and in response to switching to "drug holiday" intravenous bisphosphonate, or continuation of oral bisphosphonates. The frequency distribution of the bone resorption marker urinary deoxypyridinoline crosslinks (uDPD), was obtained retrospectively from 211 osteoporotic women attended at an academic hospital endocrine clinic, treated for >2 years with oral bisphosphonates. In some patients, uDPD was re-assessed following modification or continuation of treatment. The mean duration of oral bisphosphonates treatment was 7.2 ± 3.1 years. uDPD was within reference range for premenopausal women in 61.6% of the patients, below in 7.6% of the patients, and above upper limit in 30.8%. uDPD decreased significantly following intravenous zoledronic acid, increased significantly during "drug holiday," and slightly decreased in those continued on oral bisphosphonate treatment. In this real-world study, the majority of women on prolonged oral bisphosphonates maintained bone resorption rates within the normal reference range for premenopausal women. The likelihood for inadequate suppression was considerably greater than that of over-suppression. Implementing a "drug holiday" resulted in a marked increase in bone resorption rates. Additional studies should explore the potential role of bone turnover markers in the evaluation of patients on prolonged oral bisphosphonates and during "drug holiday" in different settings and using additional markers. BMD = bone mineral density; IQR = interquartile range; uDPD = urinary deoxypyridinoline crosslinks.

Analysis and functional consequences of increased Fab-sialylation of intravenous immunoglobulin (IVIG) after lectin fractionation.

Science.gov (United States)

Käsermann, Fabian; Boerema, David J; Rüegsegger, Monika; Hofmann, Andreas; Wymann, Sandra; Zuercher, Adrian W; Miescher, Sylvia

2012-01-01

It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG) might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA) lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1) or acidified lactose (E2) were analyzed for total IgG, F(ab')(2) and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2); again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10%) of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation.

Analysis and functional consequences of increased Fab-sialylation of intravenous immunoglobulin (IVIG after lectin fractionation.

Directory of Open Access Journals (Sweden)

Fabian Käsermann

Full Text Available It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1 or acidified lactose (E2 were analyzed for total IgG, F(ab'(2 and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2; again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10% of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation.

Intravenous glutamine enhances COX-2 activity giving cardioprotection.

LENUS (Irish Health Repository)

McGuinness, Jonathan

2009-03-01

Preconditioning, a highly evolutionary conserved endogenous protective response, provides the most powerful form of anti-infarct protection known. We investigated whether acute intravenous glutamine, through an effect on cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce preconditioning.

Intravenous patient-controlled analgesia for acute postoperative pain

DEFF Research Database (Denmark)

Nikolajsen, Lone; Haroutiunian, Simon

2011-01-01

analgesia in terms of adverse effects and consumption of opioids. Standard orders and nursing procedure protocols are recommended for patients receiving intravenous patient-controlled analgesia to monitor treatment efficacy and development of adverse effects. Some subgroups of patients need special...

Intravenous analgesics for pain management in post- operative ...

African Journals Online (AJOL)

Intravenous analgesics for pain management in post- operative patients: a comparative study of their efficacy and adverse ... patient anxiety, stress, and dissatisfaction. Adequate ... genders who were scheduled to undergo abdominal surgery (hemicolectomy, exploratory ... analysis (n = 48) and separated into three groups.

Treatment of neonatal sepsis with intravenous immune globulin

DEFF Research Database (Denmark)

Brocklehurst, Peter; Farrell, Barbara; King, Andrew

2011-01-01

Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis...

Intravenous immunoglobulin to treat hyperbilirubinemia in neonates with isolated Glucose-6-Phosphate dehydrogenase deficiency

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Wadah Khriesat

2017-04-01

Full Text Available Background Glucose-6-phosphate dehydrogenase deficiency alone or concomitant with ABO isoimmunisation is a widespread indication for neonatal exchange transfusion. Aims To evaluate the effectiveness of Intravenous Immunoglobulin in the treatment of neonatal hyperbilirubinemia due to glucose-6-phosphate dehydrogenase deficiency. Methods A retrospective cohort study was conducted between 2006 and 2014 at the Jordan University of Science and technology. The medical records of 43 infants admitted to the neonatal intensive care unit for isolated glucose-6- phosphate dehydrogenase deficiency hemolytic disease of the newborns were reviewed. Patients were divided into two groups. Group I, a historical cohort, included newborns born between 2006 and 2010, Treatment included phototherapy and exchange transfusion. Group II included newborns born between 2011 and 2014, where, in addition to phototherapy, intravenous immunoglobulin was administered. The duration of phototherapy and number of exchange transfusions were evaluated. Results Of 412 newborns that were admitted with neonatal hyperbilirubinemia, Glucose-6-phosphate dehydrogenase deficiency was present in 43. Of these, 22, did not receive intravenous immunoglobulin and served as a control group. The other 21 newborns received intravenous immunoglobulin. There was no difference in the demographic characteristics between the two groups. Infants in the control group were significantly more likely to receive exchange blood transfusion than infants in the immunoglobulin treatment group, but were significantly less likely to need phototherapy. Conclusion Intravenous immunoglobulin is an effective alternative to exchange transfusion in infants with glucose-6-phosphate dehydrogenase deficiency hemolytic disease of the newborn. It is suggested that intravenous immunoglobulin may be beneficial as a prophylaxis for infants with hyperbilirubinemia.

Acute Respiratory Distress following Intravenous Injection of an Oil-Steroid Solution

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Michael Russell

2011-01-01

Full Text Available A case of acute respiratory distress and hypoxemia following accidental intravenous injection of an oil-steroid solution in a body builder is presented. Chest roentography at the time of presentation showed diffuse bilateral opacities, and computed tomography revealed predominantly peripheral ground-glass opacifications. The patient’s symptoms gradually improved over 48 h and imaging of the chest was unremarkable one week later. The pathophysiology, diagnosis and treatment of this rare but potentially life-threatening complication of intravenous oil injection are discussed.

Contrast agent choice for intravenous coronary angiography

International Nuclear Information System (INIS)

Zeman, H.D.; Siddons, D.P.

1990-01-01

The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation X-rays and an iodine-containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic X-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron radiation source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the X-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation X-rays is visualizing a coronary artery through the left ventricle or aorta which also contain contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth. The X-ray energy spectrum of the X-17 superconduction wiggler beam line at the National Synchrotron Light Source at Brookhaven National Laboratory has been used for these calculations. Both perfect Si crystals and Si crystals with a small mosaic spread are considered as monochromators. Contrast agents containing Gd or Yb seem to have about the optimal calculated signal to noise ratio. (orig./HSI)

Intravenous lignocaine infusion for intractable pain in Ewing's sarcoma

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Nivedita Page

2018-01-01

Full Text Available A 23-year-old female presented to our palliative care center with Ewing's sarcoma of the humerus with lung metastases. Pain in her arm was unrelieved by nonsteroidal anti-inflammatory drugs, neuropathic medication as well as morphine. She could not tolerate any further increase in opioid dose but was so distraught due to the pain that she wanted to die. An intravenous lignocaine infusion in a dose of 2 mg/kg was given over an hour for three successive days. This successfully relieved her pain after which she was settled with her original medication. We feel that in palliative care settings, where intractable pain and tolerance to morphine are so common, intravenous lignocaine infusions could provide a safe and effective tool for pain relief.

A tomographic approach to intravenous coronary arteriography

International Nuclear Information System (INIS)

Ritman, E.L.; Bove, A.A.

1986-01-01

Coronary artery anatomy can be visualized using high speed, volume scanning X-ray CT. A single scan during a bolus injection of contrast medium provides image data for display of all angles of view of the opacified coronary arterial tree. Due to the tomographic nature of volume image data the superposition of contrast filled cardiac chambers, such as would occur in the levophase of an intravenous injection of contrast agent, can be eliminated. Data are presented which support these statements. The Dynamic Spatial Reconstructor (DSR) was used to scan a life-like radiologic phantom of an adult human thorax in which the left atrial and ventricular chambers and the major epicardial coronary arteries were opacified so as to simulate the levophase of an intravenous injection of contrast agent. A catheter filled with diluted contrast agent and with regions of luminal narrowing (i.e. 'stenoses') was advanced along a tract equivalent to a right ventricular catheterization. Ease of visualization of the catheter 'stenoses' and the accuracy with which they can be measured are presented. (Auth.)

Panlobular emphysema in young intravenous Ritalin abusers

International Nuclear Information System (INIS)

Schmidt, R.A.; Glenny, R.W.; Godwin, J.D.; Hampson, N.B.; Cantino, M.E.; Reichenbach, D.D.

1991-01-01

We studied a distinctive group of young intravenous Ritalin abusers with profound obstructive lung disease. Clinically, they seemed to have severe emphysema, but the pathologic basis of their symptoms had not been investigated previously. Seven patients have died and been autopsied: in four, the lungs were fixed, inflated, dried, and examined in detail radiologically, grossly, microscopically, and by electron probe X-ray microanalysis. All seven patients had severe panlobular (panacinar) emphysema that tended to be more severe in the lower lung zones and that was associated with microscopic talc granulomas. Vascular involvement by talc granulomas was variable, but significant interstitial fibrosis was not present. Five patients were tested for alpha-1-antitrypsin deficiency and found to be normal, as were six similar living patients. These findings indicate that some intravenous drug abusers develop emphysema that clinically, radiologically, and pathologically resembles that caused by alpha-1-antitrypsin deficiency but which must have a different pathogenesis. Talc from the Ritalin tablets may be important, but the mechanism remains to be elucidated

Comparison of 2 intravenous insulin protocols: Glycemia variability in critically ill patients.

Science.gov (United States)

Gómez-Garrido, Marta; Rodilla-Fiz, Ana M; Girón-Lacasa, María; Rodríguez-Rubio, Laura; Martínez-Blázquez, Anselmo; Martínez-López, Fernando; Pardo-Ibáñez, María Dolores; Núñez-Marín, Juan M

2017-05-01

Glycemic variability is an independent predictor of mortality in critically ill patients. The objective of this study was to compare two intravenous insulin protocols in critically ill patients regarding the glycemic variability. This was a retrospective observational study performed by reviewing clinical records of patients from a Critical Care Unit for 4 consecutive months. First, a simpler Scale-Based Intravenous Insulin Protocol (SBIIP) was reviewed and later it was compared for the same months of the following year with a Sliding Scale-Based Intravenous Insulin Protocol (SSBIIP). All adult patients admitted to the unit during the referred months were included. Patients in whom the protocol was not adequately followed were excluded. A total of 557 patients were reviewed, of whom they had needed intravenous insulin 73 in the first group and 52 in the second group. Four and two patients were excluded in each group respectively. Glycemic variability for both day 1 (DS1) and total stay (DST) was lower in SSBIIP patients compared to SBIIP patients: SD1 34.88 vs 18.16 and SDT 36.45 vs 23.65 (P<.001). A glycemic management protocol in critically ill patients based on sliding scales decreases glycemic variability. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Hyperammonemic Encephalopathy Resulting From Intravenous Valproate for Status Epilepticus

National Research Council Canada - National Science Library

Richards, Karen

2004-01-01

.... Intravenous vaiproate has been suggested as an alternative to phenytoin and/or phenobarbital in patients with hypersensitivity to or at high risk for the sedative or vasoactive effects of these drugs...

Phase 1A safety assessment of intravenous amitriptyline

NARCIS (Netherlands)

Fridrich, Peter; Colvin, Hans Peter; Zizza, Anthony; Wasan, Ajay D.; Lukanich, Jean; Lirk, Philipp; Saria, Alois; Zernig, Gerald; Hamp, Thomas; Gerner, Peter

2007-01-01

The antidepressant amitriptyline is used as an adjuvant in the treatment of chronic pain. Among its many actions, amitriptyline blocks Na+ channels and nerves in several animal and human models. As perioperative intravenous lidocaine has been suggested to decrease postoperative pain, amitriptyline,

Effect of intravenous transplantation of bone marrow mesenchymal stem cells on neurotransmitters and synapsins in rats with spinal cord injury

Science.gov (United States)

Chen, Shaoqiang; Wu, Bilian; Lin, Jianhua

2012-01-01

Bone marrow mesenchymal stem cells were isolated, purified and cultured in vitro by Percoll density gradient centrifugation combined with the cell adherence method. Passages 3–5 bone marrow mesenchymal stem cells were transplanted into rats with traumatic spinal cord injury via the caudal vein. Basso-Beattie-Bresnahan scores indicate that neurological function of experimental rats was significantly improved over transplantation time (1–5 weeks). Expressions of choline acetyltransferase, glutamic acid decarboxylase and synapsins in the damaged spinal cord of rats was significantly increased after transplantation, determined by immunofluorescence staining and laser confocal scanning microscopy. Bone marrow mesenchymal stem cells that had migrated into the damaged area of rats in the experimental group began to express choline acetyltransferase, glutamic acid decarboxylase and synapsins, 3 weeks after transplantation. The Basso-Beattie- Bresnahan scores positively correlated with expression of choline acetyltransferase and synapsins. Experimental findings indicate that intravenously transplanted bone marrow mesenchymal stem cells traverse into the damaged spinal cord of rats, promote expression of choline acetyltransferase, glutamic acid decarboxylase and synapsins, and improve nerve function in rats with spinal cord injury. PMID:25657678

Errors in the administration of intravenous medication in Brazilian hospitals.

Science.gov (United States)

Anselmi, Maria Luiza; Peduzzi, Marina; Dos Santos, Claudia Benedita

2007-10-01

To verify the frequency of errors in the preparation and administration of intravenous medication in three Brazilian hospitals in the State of Bahia. The administration of intravenous medications constitutes a central activity in Brazilian nursing. Errors in performing this activity may result in irreparable damage to patients and may compromise the quality of care. Cross-sectional study, conducted in three hospitals in the State of Bahia, Brazil. Direct observation of the nursing staff (nurse technicians, auxiliary nurses and nurse attendants), preparing and administering intravenous medication. When preparing medication, wrong patient error did not occur in any of the three hospitals, whereas omission dose was the most frequent error in all study sites. When administering medication, the most frequent errors in the three hospitals were wrong dose and omission dose. The rates of error found are considered low compared with similar studies. The most frequent types of errors were wrong dose and omission dose. The hospitals studied showed different results with the smallest rates of errors occurring in hospital 1 that presented the best working conditions. Relevance to clinical practice. Studies such as this one have the potential to improve the quality of care.

[Intravenous lysine clonixinate for the treatment of migraine: an open pilot study].

Science.gov (United States)

Krymchantowski, A V; Barbosa, J

1999-09-01

Several oral nonsteroidal anti-inflammatory drugs (NSAID) are effective to treat migraine attacks. Despite its efficacy to treat migraine and other pain, there are a few commercial NSAIDs available for intravenous (i.v.) administration. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has been proven effective in various algic syndromes such as renal colic, nerve compression, muscular pain and odontalgias. The aim of this study was to evaluate the efficacy of the i.v. LC in the treatment of severe attacks of migraine. We studied prospectively 19 patients, 17 women and 2 men, ages from 18 to 57 years, with the diagnosis of migraine according to the International Headache Society criteria. The patients were oriented to proceed to the clinic once the headache has started, and were placed under an i.v. infusion of LC and saline in a superficial vein of the forearm, once the intensity reached severe. Evaluating the headache intensity after 30, 60 and 90 minutes, as well as the presence of side effects, we observed that all of the 19 patients were headache free after 90 minutes. Some patients presented mild adverse effects and the vital signs were not significantly affected. We then concluded that the i.v. infusion of the NSAID LC (2-3-chloro-o-toluidin)piridin-3-lysine carboxilate), a derived from the nicotinic acid with a chemical structure that resembles the flufenamic acid, was efficient abolishing a severe migraine attack after 90 minutes in 19 patients. Controlled studies with a double-blind and randomized design, and treating a greater number of patients and attacks are necessary to confirm these initial observations.

Microscopic Evaluation of the Effect of Oral Microbiota on the Development of Bisphosphonate-Related Osteonecrosis of the Jaws in Rats

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Felipe M. Silveira

2017-01-01

Full Text Available Objectives: Osteonecrosis of the jaws is a side effect associated with the use of bisphosphonates. Using histologic analysis, this study aimed to evaluate the influence of microbial colonies in the development of osteonecrosis in the jaws of rats subjected to nitrogenous and non-nitrogenous bisphosphonates, undergoing surgical procedures. Material and Methods: Thirty-four rats (Rattus norvegicus, Wistar strain were allocated randomly into three groups: 12 animals treated with zoledronic acid; 12 animals treated with clodronate; and 10 animals treated with saline. Sixty days after the start of treatment, the animals underwent three extractions of the upper right molars. After 120 days of drug administration, the rats were killed. Histologic analysis was performed on specimens stained with hematoxylin and eosin by the technique of manual counting points using Image-Pro Plus software on images of the right hemimaxilla. Results: Osteonecrosis was induced in the test groups. There was no statistically significant association between the presence of microbial colonies and the presence of non-vital bone (Kruskal-Wallis, P > 0.05. Conclusions: Use of zoledronic acid was associated with non-vital bone and the results suggested that the presence of microbial colonies does not lead to osteonecrosis.

Mercury poisoning through intravenous administration: Two case reports with literature review.

Science.gov (United States)

Lu, Qiuying; Liu, Zilong; Chen, Xiaorui

2017-11-01

Metallic mercury poisoning through intravenous injection is rare, especially for a homicide attempt. Diagnosis and treatment of the disease are challenging. A 34-year-old male presented with pyrexia, chill, fatigue, body aches, and pain of the dorsal aspect of right foot. Another case is that of a 29-year-old male who committed suicide by injecting himself metallic mercury 15 g intravenously and presented with dizzy, dyspnea, fatigue, sweatiness, and waist soreness. The patient's condition in case 1 was deteriorated after initial treatment. Imaging studies revealed multiple high-density spots throughout the body especially in the lungs. On further questioning, the patient's girlfriend acknowledged that she injected him about 40 g mercury intravenously 11 days ago. The diagnosis was then confirmed with a urinary mercury concentration of 4828 mg/L. Surgical excision, continuous blood purification, plasma exchange, alveolar lavage, and chelation were performed successively in case 1. Blood irrigation and chelation therapy were performed in case 2. The laboratory test results and organ function of the patient in case 1 gradually returned to normal. However, in case 2, the patient's dyspnea was getting worse and he finally died due to toxic encephalopathy and respiratory failure. Early diagnosis and appropriate treatment are critical for intravenous mercury poisoning. It should be concerned about the combined use of chelation agents and other treatments, such as surgical excision, hemodialysis and plasma exchange in clinical settings.

The effect of prophylactic intravenous tranexamic acid on blood loss after vaginal delivery in women at low risk of postpartum haemorrhage: a double-blind randomised controlled trial.

Science.gov (United States)

Mirghafourvand, Mojgan; Mohammad-Alizadeh, Sakineh; Abbasalizadeh, Fatemeh; Shirdel, Mina

2015-02-01

To determine the effect of prophylactic tranexamic acid (TA) on calculated and measured blood loss after vaginal delivery in women at low risk of postpartum haemorrhage. In this double-blind randomised controlled trial, 120 women with a singleton pregnancy were randomly allocated to receive either one gram intravenous TA or placebo in addition to 10 IU oxytocin after delivery of the fetus. Calculated blood loss was determined based on haematocrit before delivery and 12-24 h postdelivery. The quantity of blood loss was measured during two time periods: from delivery of the fetus to placental expulsion and from placental expulsion to the end of the second hour after childbirth. The mean (SD) calculated total blood loss (519 (320) vs 659 (402) mL, P = 0.036) and measured blood loss from placental delivery to 2 h postpartum (69 (39) vs 108 (53) mL, P  1000 mL was lower in the TA group (7% vs 18%, P = 0.048). Prophylactic TA reduces blood loss after vaginal delivery in women with a low risk of postpartum haemorrhage. The prophylactic use of TA may reduce blood loss complications and enhance maternal health. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Randomised controlled trial comparing oral and intravenous paracetamol (acetaminophen) plasma levels when given as preoperative analgesia.

Science.gov (United States)

van der Westhuizen, J; Kuo, P Y; Reed, P W; Holder, K

2011-03-01

Gastric absorption of oral paracetamol (acetaminophen) may be unreliable perioperatively in the starved and stressed patient. We compared plasma concentrations of parenteral paracetamol given preoperatively and oral paracetamol when given as premedication. Patients scheduled for elective ear; nose and throat surgery or orthopaedic surgery were randomised to receive either oral or intravenous paracetamol as preoperative medication. The oral dose was given 30 minutes before induction of anaesthesia and the intravenous dose given pre-induction. All patients were given a standardised anaesthetic by the same specialist anaesthetist who took blood for paracetamol concentrations 30 minutes after the first dose and then at 30 minute intervals for 240 minutes. Therapeutic concentrations of paracetamol were reached in 96% of patients who had received the drug parenterally, and 67% of patients who had received it orally. Maximum median plasma concentrations were 19 mg.l(-1) (interquartile range 15 to 23 mg.l(-1)) and 13 mg.l(-1) (interquartile range 0 to 18 mg.l(-1)) for the intravenous and oral group respectively. The difference between intravenous and oral groups was less marked after 150 minutes but the intravenous preparation gave higher plasma concentrations throughout the study period. It can be concluded that paracetamol gives more reliable therapeutic plasma concentrations when given intravenously.

Transient angioedema of small bowel secondary to intravenous iodinated contrast medium

Directory of Open Access Journals (Sweden)

Kirankumar N Kulkarni

2014-01-01

Full Text Available We report the clinical details and imaging findings of a case of transient angioedema of the small bowel following intravenous administration of non-ionic iodinated contrast material in a 17 year old female with no predisposing risk factors. Findings included long segment, symmetric, circumferential, low-density, bowel wall thickening involving the duodenum, jejunum, and most of the ileum on computed tomography scan obtained at 7 min following intravenous contrast material injection. This entity is self-limiting with a favourable clinical outcome and requires no specific treatment but only aggressive clinical monitoring.

Comparison of the image quality of intravenous urograms using low-osmolar contrast media

International Nuclear Information System (INIS)

Kaye, B.; Howard, J.; Foord, K.D.; Cumberland, D.C.

1988-01-01

Almost equivalent, intravenous iodine doses of the three new low-osmolar contrast media, ioxaglate (Hexabrix), iopamidol (Niopam) and iohexol (Omnipaque) have been compared for image quality on the intravenous urogram. Generally good radiographic images were obtained. Iohexol gave better results for the nephrogram and pelvicalyceal distension compared with the other contrast media, but only the nephrogram results were statistically significant. Pyelographic density and ureteric distension and density were similar with all three contrast media. In patients where low-osmolality contrast media need to be used for intravenous urography, we suggest that iohexol gives the best radiographic images. Other factors, such as cost and the relative incidence of side-effects of the low-osmolar contrast media also need to be taken into consideration. (author)

Cost of opioid intravenous patient-controlled analgesia: results from a hospital database analysis and literature assessment

Directory of Open Access Journals (Sweden)

Palmer P

2014-06-01

Full Text Available Pamela Palmer,1 Xiang Ji,2 Jennifer Stephens21AcelRx Pharmaceuticals, Inc., Redwood City, CA, 2Pharmerit International, Bethesda, MD, USABackground: Intravenous patient-controlled analgesia (PCA equipment and opioid cost analyses on specific procedures are lacking. This study estimates the intravenous PCA hospital cost for the first 48 postoperative hours for three inpatient surgeries.Methods: Descriptive analyses using the Premier database (2010–2012 of more than 500 US hospitals were conducted on cost (direct acquisition and indirect cost for the hospital, such as overhead, labor, pharmacy services of intravenous PCA after total knee/hip arthroplasty (TKA/THA or open abdominal surgery. Weighted average cost of equipment and opioid drug and the literature-based cost of adverse events and complications were aggregated for total costs.Results: Of 11,805,513 patients, 272,443 (2.3%, 139,275 (1.2%, and 195,062 (1.7% had TKA, THA, and abdominal surgery, respectively, with approximately 20% of orthopedic and 29% of abdominal patients having specific intravenous PCA database cost entries. Morphine (57% and hydromorphone (44% were the most frequently used PCA drugs, with a mean cost per 30 cc syringe of $16 (30 mg and $21 (6 mg, respectively. The mean number of syringes used for morphine and hydromorphone in the first 48 hours were 1.9 and 3.2 (TKA, 2.0 and 4.2 (THA, and 2.5 and 3.9 (abdominal surgery, respectively. Average costs of PCA pump, intravenous tubing set, and drug ranged from $46 to $48, from $20 to $22, and from $33 to $46, respectively. Pump, tubing, and saline required to maintain patency of the intravenous PCA catheter over 48 hours ranged from $9 to $13, from $8 to $9, and from $20 to $22, respectively. Supplemental non-PCA opioid use ranged from $56 for THA to $87 for abdominal surgery. Aggregated mean intravenous PCA equipment and opioid cost per patient were $196 (THA, $204 (TKA, and $243 (abdominal surgery. Total costs, including

Warming of intravenous and irrigation fluids for preventing inadvertent perioperative hypothermia.

Science.gov (United States)

Campbell, Gillian; Alderson, Phil; Smith, Andrew F; Warttig, Sheryl

2015-04-13

Inadvertent perioperative hypothermia (a drop in core temperature to below 36°C) occurs because of interference with normal temperature regulation by anaesthetic drugs, exposure of skin for prolonged periods and receipt of large volumes of intravenous and irrigation fluids. If the temperature of these fluids is below core body temperature, they can cause significant heat loss. Warming intravenous and irrigation fluids to core body temperature or above might prevent some of this heat loss and subsequent hypothermia. To estimate the effectiveness of preoperative or intraoperative warming, or both, of intravenous and irrigation fluids in preventing perioperative hypothermia and its complications during surgery in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 2), MEDLINE Ovid SP (1956 to 4 February 2014), EMBASE Ovid SP (1982 to 4 February 2014), the Institute for Scientific Information (ISI) Web of Science (1950 to 4 February 2014), Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCOhost (1980 to 4 February 2014) and reference lists of identified articles. We also searched the Current Controlled Trials website and ClinicalTrials.gov. We included randomized controlled trials or quasi-randomized controlled trials comparing fluid warming methods versus standard care or versus other warming methods used to maintain normothermia. Two review authors independently extracted data from eligible trials and settled disputes with a third review author. We contacted study authors to ask for additional details when needed. We collected data on adverse events only if they were reported in the trials. We included in this review 24 studies with a total of 1250 participants. The trials included various numbers and types of participants. Investigators used a range of methods to warm fluids to temperatures between 37°C and 41°C. We found that evidence was of moderate quality because descriptions of trial design were

Floating arterial thrombus related stroke treated by intravenous thrombolysis.

Science.gov (United States)

Vanacker, P; Cordier, M; Janbieh, J; Federau, C; Michel, P

2014-01-01

The effects of intravenous thrombolysis on floating thrombi in cervical and intracranial arteries of acute ischemic stroke patients are unknown. Similarly, the best prevention methods of early recurrences remain controversial. This study aimed to describe the clinical and radiological outcome of thrombolyzed strokes with floating thrombi. We retrospectively analyzed all thrombolyzed stroke patients in our institution between 2003 and 2010 with floating thrombi on acute CT-angiography before the intravenous thrombolysis. The floating thrombus was diagnosed if an elongated thrombus of at least 5 mm length, completely surrounded by contrast on supra-aortic neck or intracerebral arteries, was present on CT-angiography. Demographics, vascular risk factors, and comorbidities were recorded and stroke etiology was determined after a standardized workup. Repeat arterial imaging was performed by CTA at 24 h or before if clinical worsening was noted and then by Doppler and MRA during the first week and at four months. Of 409 thrombolyzed stroke patients undergoing acute CT Angiography, seven (1.7%) had a floating thrombus; of these seven, six had it in the anterior circulation. Demographics, risk factors and stroke severity of these patients were comparable to the other thrombolyzed patients. After intravenous thrombolysis, the floating thrombi resolved completely at 24 h in four of the patients, whereas one had an early recurrent stroke and one developed progressive worsening. One patient developed early occlusion of the carotid artery with floating thrombus and subsequently a TIA. The two patients with a stable floating thrombus had no clinical recurrences. In the literature, only one of four reported cases were found to have a thrombolysis-related early recurrence. Long-term outcome seemed similar in thrombolyzed patients with floating thrombus, despite a possible increase of very early recurrence. It remains to be established whether acute mechanical thrombectomy could be

Pattern of intravenous immunoglobulins (IVIG) use in a pediatric ...

African Journals Online (AJOL)

Pattern of intravenous immunoglobulins (IVIG) use in a pediatric intensive care facility in a resource limited setting. ... Journal Home > Vol 13, No 2 (2013) > ... Results: The clinical diagnoses included neurology (35%), neonatology (16%), ...

Intravenous contrast enhanced computed tomography colonoscopy in children with suspected colonic polyps

International Nuclear Information System (INIS)

Bhatia, Anmol; Saxena, Akshay K.; Kalra, Naveen; Sodhi, Kushaljit S.; Thapa, Babu R.; Rao, Katragadda L.N.; Khandelwal, Niranjan

2013-01-01

Objective: The purpose of this study was to evaluate the diagnostic performance of intravenous contrast enhanced computed tomographic colonoscopy (IVCTC) in the diagnosis of clinically suspected colorectal polyps in children, using conventional colonoscopy (CC) as the gold standard. Methods: This was a prospective study conducted between July 2008 and June 2010. 30 pediatric patients with history of rectal bleeding and clinically suspected to have colorectal polyps were enrolled. All of the patients underwent IVCTC followed by CC. 30 IVCTC and 31 CC were performed in 30 patients. The findings of IVCTC were compared with those of CC. Statistical analysis was performed to obtain diagnostic performance values of IVCTC on per polyp (sensitivity and positive predictive value) and per patient (sensitivity, specificity, positive predictive value and negative predictive value) basis. Results: By IVCTC, 63 polyps were detected in 28 patients of which 53 polyps were eligible for inclusion in the statistical analysis. 60 polyps were detected by CC in 28 patients of which 50 polyps were eligible for inclusion in the statistical analysis. The per polyp sensitivity and positive predictive values were 94% and 88.6% respectively. The per patient sensitivity, specificity, positive predictive value, and negative predictive values were 96.4, 50, 96.4, and 50% respectively. Twenty polyps, in 10 patients, were visualized only after intravenous contrast administration of which 5 polyps, in 5 patients, were likely to have been missed in the absence of the intravenous contrast injection as these polyps were submerged in fluid. Four patients would have had a false negative CTC examination if the intravenous contrast had not been injected; while in another patient, the number of polyps would have been underestimated. Conclusion: CTC is capable of serving as a safe and efficient non-invasive tool for evaluating children with clinically suspected colorectal polyps. Administration of

Detection of the in vivo conversion of 2-pyrrolidinone to gamma-aminobutyric acid in mouse brain.

Science.gov (United States)

Callery, P S; Stogniew, M; Geelhaar, L A

1979-01-01

Labeled gamma-aminobutyric acid was detected in mouse brain following intravenous injections of deuterium labeled 2-pyrrolidinone. [2H6]Pyrrolidinone was prepared by the reduction of [2H4]succinimide with lithium aluminum deuteride. Quantification was accomplished by a gas chromatography mass spectrometry assay method. gamma-Aminobutyric acid and internal standard, 5-aminovaleric acid, were converted to volatile derivatives by treatment with N,N-dimethylformamide dimethyl acetal. Quantitative estimates were derived from peak area measurements obtained from monitoring the parent ions of the gamma-aminobutyric acid and internal standard derivatives by repetitive scanning during the GC run. The conversion of pyrrolidinone to gamma-aminobutyric acid may provide a method for labeling central gamma-aminobutyric acid pools.

Intravenous analgesics for pain management in postoperative patients

African Journals Online (AJOL)

Purpose: To compare the effectiveness of post-operative pain management and associated adverse effects of ketamine and nefopam. Methods: In total, 78 American Society of Anesthesiologists (ASA) grade 1 and 2 patients who had undergone abdominal surgery were given 3 mg of intravenous (IV) morphine as ...

Training requirements for the administration of intravenous contrast ...

African Journals Online (AJOL)

Background. The administration of intravenous contrast media (IVCM) is one of the key areas currently under investigation for inclusion in the South African (SA) radiographers' scope of practice. However, for the radiographers to legally administer IVCM, training guidelines must first be identified, developed and accredited ...

Outcomes of cancer surgery after inhalational and intravenous anesthesia

DEFF Research Database (Denmark)

Soltanizadeh, Sinor; Degett, Thea H; Gögenur, Ismail

2017-01-01

Perioperative factors are probably essential for different oncological outcomes. This systematic review investigates the literature concerning overall mortality and postoperative complications after cancer surgery with inhalational (INHA) and intravenous anesthesia (TIVA). A search was conducted...

Acute chloroform ingestion successfully treated with intravenously administered N-acetylcysteine.

Science.gov (United States)

Dell'Aglio, Damon M; Sutter, Mark E; Schwartz, Michael D; Koch, David D; Algren, D A; Morgan, Brent W

2010-06-01

Chloroform, a halogenated hydrocarbon, causes central nervous system depression, cardiac arrhythmias, and hepatotoxicity. We describe a case of chloroform ingestion with a confirmatory serum level and resultant hepatotoxicity successfully treated with intravenously administered N-acetylcysteine (NAC). A 19-year-old man attempting suicide ingested approximately 75 mL of chloroform. He was unresponsive and intubated upon arrival. Intravenously administered NAC was started after initial stabilization was complete. His vital signs were normal. Admission laboratory values revealed normal serum electrolytes, AST, ALT, PT, BUN, creatinine, and bilirubin. Serum ethanol level was 15 mg/dL, and aspirin and acetaminophen were undetectable. The patient was extubated but developed liver function abnormalities with a peak AST of 224 IU/L, ALT of 583 IU/L, and bilirubin level reaching 16.3 mg/dL. NAC was continued through hospital day 6. Serum chloroform level obtained on admission was 91 μg/mL. The patient was discharged to psychiatry without known sequelae and normal liver function tests. The average serum chloroform level in fatal cases of inhalational chloroform poisoning was 64 μg/mL, significantly lower than our patient. The toxicity is believed to be similar in both inhalation and ingestion routes of exposure, with mortality predominantly resulting from anoxia secondary to central nervous system depression. Hepatocellular toxicity is thought to result from free radical-induced oxidative damage. Previous reports describe survival after treatment with orally administered NAC, we report the first use of intravenously administered NAC for chloroform ingestion. Acute oral ingestion of chloroform is extremely rare. Our case illustrates that with appropriate supportive care, patients can recover from chloroform ingestion, and intravenously administered NAC may be of benefit in such cases.

Persistent renal enhancement after intra-arterial versus intravenous iodixanol administration

International Nuclear Information System (INIS)

Chou, Shinn-Huey; Wang, Zhen J.; Kuo, Jonathan; Cabarrus, Miguel; Fu Yanjun; Aslam, Rizwan; Yee, Judy; Zimmet, Jeffrey M.; Shunk, Kendrick; Elicker, Brett; Yeh, Benjamin M.

2011-01-01

Purpose: To examine the clinical significance of persistent renal enhancement after iodixanol administration. Methods: We retrospectively studied 166 consecutive patients who underwent non-enhanced abdominopelvic CT within 7 days after receiving intra-arterial (n = 99) or intravenous (n = 67) iodixanol. Renal attenuation was measured for each non-enhanced CT scan. Persistent renal enhancement was defined as CT attenuation >55 Hounsfield units (HU). Contrast-induced nephropathy (CIN) was defined as a rise in serum creatinine >0.5 mg/dL within 5 days after contrast administration. Results: While the intensity and frequency of persistent renal enhancement was higher after intra-arterial (mean CT attenuation of 73.7 HU, seen in 54 of 99 patients, or 55%) than intravenous contrast material administration (51.8 HU, seen in 21 of 67, or 31%, p < 0.005), a multivariate regression model showed that the independent predictors of persistent renal enhancement were a shorter time interval until the subsequent non-enhanced CT (p < 0.001); higher contrast dose (p < 0.001); higher baseline serum creatinine (p < 0.01); and older age (p < 0.05). The route of contrast administration was not a predictor of persistent renal enhancement in this model. Contrast-induced nephropathy was noted in 9 patients who received intra-arterial (9%) versus 3 who received intravenous iodixanol (4%), and was more common in patients with persistent renal enhancement (p < 0.01). Conclusion: Persistent renal enhancement at follow-up non-contrast CT suggests a greater risk for contrast-induced nephropathy, but the increased frequency of striking renal enhancement in patients who received intra-arterial rather than intravenous contrast material also reflects the larger doses of contrast and shorter time to subsequent follow-up CT scanning for such patients.

Status epilepticus following intravenous N-acetylcysteine therapy.

Science.gov (United States)

Hershkovitz, E; Shorer, Z; Levitas, A; Tal, A

1996-11-01

A previously healthy 2 1/2-year-old girl developed status epilepticus followed by cortical blindness during intravenous N-acetylcysteine therapy for paracetamol ingestion. The child's vision was almost completely recovered during the 18 months follow-up period. We assume that the cortical blindness was a postictal sequela after prolonged seizure episode, most probably due to respiratory depression induced by N-acetylcysteine.

X-ray diagnostics. Oral and intravenous cholegraphy

International Nuclear Information System (INIS)

1981-04-01

The standard deals with oral and intravenous cholegraphy. It includes information on indications, contraindications, prerequisites and preparations as well as on application and appropriate dosage of contrast media. Parameters on focussing, imaging conditions and on the program of taking radiographies are outlined. The necessity of special examinations according to findings as well as measures concerning radiation protection and hygiene are presented

Real-Time Scintigraphic Assessment of Intravenous Radium-223 Administration for Quality Control

Directory of Open Access Journals (Sweden)

Chadwick L. Wright

2015-01-01

Full Text Available Radium-223 (223Ra dichloride is an approved intravenous radiotherapy for patients with osseous metastases from castration-resistant prostate cancer (CRPC. In addition to the therapeutic alpha radiation, there is additional 223Ra radiation generated which produces photons that can be imaged with conventional gamma cameras. No studies have evaluated real-time and quality imaging during intravenous 223Ra administration to verify systemic circulation and exclude 223Ra extravasation at the injection site. A retrospective review was performed for fifteen 223Ra administrations for CRPC patients which were imaged using a large field of view portable gamma camera (LFOVPGC for the purposes of quality control and patient safety. Dynamic imaging of the chest was performed before, during, and after the 223Ra administration to verify systemic circulation, per institutional clinical protocol. Before and after 223Ra administration, a static image was obtained of the intravenous access site. Dynamic imaging of the chest confirmed systemic administration early during the 1-minute injection period for all patients. There were no cases of focal 223Ra extravasation at the site of intravenous access. These results verify that systemic 223Ra administrations can be quantified with real-time imaging using an LFOVPGC. This simple approach can confirm and quantify systemic circulation of 223Ra early during injection and exclude focal extravasation for the purposes of quality control.

[Effect of intravenous treatment with OK-432 on the bone marrow in patients with lung cancer].

Science.gov (United States)

Fujii, M; Ishikawa, M; Toki, H

1984-03-01

We studied effects of OK-432 on the bone marrow and peripheral blood cells of lung cancer patients. The nuclear cell count of bone marrow increased in 5 to 7 patients upon intravenous treatment with OK-432 compared with 3 of 6 patients who were intramuscularly treated with OK-432. Serial neutrophil counts of bone marrow increased in all 7 patients treated intravenously compared with 3 of 6 patients treated intramuscularly. The mean nuclear cell count or the serial neutrophil count of bone marrow in intravenously treated patients was significantly higher than the pretreatment values (p less than 0.001). In the peripheral blood picture, the difference in white blood cells or neutrophils before and after intravenous treatment was also statistically significant (p less than 0.01). There was no change in the erythrocytic series count of bone marrow and the hemoglobin count. Our results support the superiority of intravenous OK-432 treatment over intramuscular treatment in the growth-accelerating effect on bone marrow cells, especially regarding the neutrophil series.

Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach.

Science.gov (United States)

Rohof, Wout O; Bennink, Roelof J; Boeckxstaens, Guy E

2014-07-01

The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Thirty-six patients with GERD (18 not taking PPIs, 18 taking PPIs; 19 men; age, 55 ± 2.1 y) were analyzed by concurrent high-resolution manometry and pH-impedance monitoring after a standardized meal. The acid pocket was visualized using scintigraphy after intravenous administration of (99m)technetium-pertechnetate. The size of the acid pocket was measured and its position was determined, relative to the diaphragm, using radionuclide markers on a high-resolution manometry catheter. At the end of the study, the acid pocket was aspirated, and its pH level was measured. The number of reflux episodes was comparable between patients on and off PPIs, but the number of acid reflux episodes was reduced significantly in patients on PPIs. In patients on PPIs, the acid pocket was smaller and more frequently located below the diaphragm. The mean pH of the acid pocket was significantly lower in patients not taking PPIs (n = 6) than in those who were (n = 16) (0.9; range, 0.7-1.2 vs 4.0; range, 1.6-5.9; P pH of acid pockets correlated significantly with the lowest pH values measured for refluxate (r = 0.72; P < .01). Based on analyses of acid pockets in patients with GERD, the acid pocket appears to be a reservoir from which reflux occurs when patients are receiving PPIs. PPIs might affect the size, acidity, or position of the acid pocket, which contributes to the efficacy in patients with GERD. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Characterization of an intravenously injected bolus

International Nuclear Information System (INIS)

Samuel, A.M.; Raikar, U.R.; Atmaram, S.H.; Ganatra, R.D.

1976-01-01

A study of some parameters affecting the time activity histogram of an intravenous bolus injection of radioactivity was performed. A scoring system for bolus compactness was attempted. A score of 2 and above was considered to be a satisfactory bolus. Volumes less than 1 ml tended to result in a satisfactory bolus. The nature of radiopharmaceutical injected, different injecters and age of the patient did not affect the score. Thyrotoxic patients gave the best bolus score. (orig.) [de

Deep vein thrombosis of the lower limbs in intravenous drug users

Directory of Open Access Journals (Sweden)

Wiesława Kwiatkowska

2015-04-01

Full Text Available Addiction to intravenously administered drugs has been a serious epidemiological problem for years. Among the related health complications, deep vein thrombosis (DVT is one of the most important. This paper provides an illustrative presentation of DVT in intravenous drug users (IDUs, HIV-positive subjects among them.We searched PubMed, Ovid Journals, Scopus, ScienceDirect, Cochrane Library, Google Scholar and references from articles obtained. The main terms used to identify appropriate studies of DVT in IDUs were ‘intravenous drug users’, ‘substance-related disorders’ and ‘deep vein thrombosis’.No guidelines exist for DVT in intravenous drug users. As many as 47.6% of IDUs report having suffered from DVT. IDUs may constitute approx. 50% of patients under 40 years of age with DVT, this being promoted by multiple vein punctures, groin injections, lack of sterility, insoluble microparticles and other factors. The clinical appearance is more complex than in the general population, which also makes prognosis more difficult. HIV infection can worsen DVT. It often appears as proximal iliofemoral thrombosis, accompanied by local and general complications. Ultrasound with a compression test is an objective method of choice, but must often be complemented with computed tomography. Antithrombotic therapy in IDUs needs to be applied individually. The optimal method is supervised therapy at addiction treatment services.Individual and public preventive measures, among them locally prepared guidelines for DVT in IDUs, may be the most important processes capable of effectively reducing the morbidity of septic and non-septic DVT.

Low Risk of Thromboembolic Events After Routine Administration of Tranexamic Acid in Hip and Knee Arthroplasty

DEFF Research Database (Denmark)

Madsen, Rune V; Nielsen, Christian S.; Kallemose, Thomas

2017-01-01

BACKGROUND: The blood-conserving effect of intravenous (IV) tranexamic acid (TXA) is well-documented for total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, the risk of thromboembolic (TE) events after routine use of TXA is unclear and the safety profile is debated...

Effects of intravenous glucose infusion and nutritional balance on serum concentrations of nonesterified fatty acids, glucose, insulin, and progesterone in nonlactating dairy cows.

Science.gov (United States)

Vieira, F V R; Lopes, C N; Cappellozza, B I; Scarpa, A B; Cooke, R F; Vasconcelos, J L M

2010-07-01

The objective of this study was to evaluate serum concentrations of nonesterified fatty acids, glucose, insulin, and progesterone in nonlactating dairy cows according to nutritional balance and glucose infusion. Ten nonlactating, ovariectomized Gir x Holstein cows were stratified by body weight (BW) and body condition score (BCS) on d -28 of the study, and randomly assigned to 1) negative nutrient balance (NB) or 2) positive nutrient balance (PB). From d -28 to d 0, cows were allocated according to nutritional treatment (5 cows/treatment) into 2 low-quality pastures with reduced forage availability. However, PB cows individually received, on average, 3 kg/cow per day (as-fed) of a concentrate during the study. All cows had an intravaginal progesterone releasing device inserted on d -14, which remained in cows until the end of the study. Cow BW and BCS were assessed again on d 0. On d 0, cows within nutritional treatment were randomly assigned to receive, in a crossover design containing 2 periods of 24h each, 1) intravenous glucose infusion (GLU; 0.5 g of glucose/kg of BW, as a 5% glucose solution administered, on average, at 32 mL/min over a 3-h period), or 2) intravenous saline infusion (SAL; 0.9% solution infused on average at 32 mL/min over a 3-h period). Prior to the beginning of each period, all cows were fasted for 12h. Blood samples were collected, relative to the beginning of the infusion, at -12 and -11.5h (beginning of fasting), and at -0.5, 0, 0.5, 1, 2, 3, 4, 5, and 6h. Following the last blood collection of period 1, cows received (PB) or not (NB) concentrate and were returned to their respective pastures. Changes in BCS and BW were greater in NB cows compared with PB cows (-0.60 and -0.25+/-0.090 for BCS, respectively; -22.4 and 1.2+/-6.58 kg for BW, respectively). Cows receiving GLUC had greater glucose concentrations from 0.5 to 3h relative to infusion compared with SAL cows. Insulin concentrations were greater in PB cows assigned to GLUC compared

Comparison of Caudal Analgesia and Intravenous Diclofenac for ...

African Journals Online (AJOL)

Background: Effective postoperative pain management is a vital determinant to when a child can be safely discharged from the hospital after day case surgery. This study compared the effect of caudal bupivacaine block with intravenous diclofenac for postoperative pain relief in children aged 1-7years undergoing ...

Intravenous Immunoglobulin therapy for anti-E hemolytic disease in the newborn.

Science.gov (United States)

Onesimo, Roberta; Rizzo, Daniela; Ruggiero, Antonio; Valentini, Piero

2010-09-01

Anti-E alloimmunisation is a less common cause of haemolytic disease in the newborn (HDN) and is usually associated with mild to moderate clinical manifestations, that are often less severe than anti-D immunisation. Conventional treatments for HDN are phototherapy and exchange transfusion, the latter still representing a high-risk procedure. Currently, intravenous immunoglobulin has been used as alternative treatment for HDN to reduce the need for exchange transfusion, as well as the length of phototherapy and hospitalisation. We report a case of anti-E HDN treated successfully with intravenous immunoglobulin, as adjuvant treatment to phototherapy.

Postoperative analgesic efficacy of intravenous dexketoprofen in lumbar disc surgery.

Science.gov (United States)

Yazar, Mehmet Akif; Inan, Nurten; Ceyhan, Aysegul; Sut, Esra; Dikmen, Bayazit

2011-07-01

We investigated the postoperative analgesic efficacy and effect on total tramadol consumption of intravenous dexketoprofen trometamol, a new nonsteroidal anti-inflammatory drug, in patients that had undergone lumbar disc surgery. Sixty patients were included in this placebo-controlled, randomized, double-blind study. General anesthesia was applied to both groups. Group D (n=30) received dexketoprofen (50 mg) intravenously 30 minutes before the end of surgery and at the postoperative 12th hour, whereas group C (n=30) received 2 mL of 0.9% NaCL intravenously at the same time points. All patients received a patient controlled analgesia device with a tramadol, 25 mg bolus, 15 minutes lockout protocol, and were followed with visual analog scale, verbal rating scale, modified Aldrete recovery scoring system, and Ramsay sedation scale in the postoperative period. There was no significant difference between the groups for demographic data, duration of surgery, mean arterial pressure, and heart rate. The time to first postoperative analgesic requirement was significantly longer in group D (151.33±81.98 min) than group C (19±5.78 min) (Pdexketoprofen was an effective analgesic for postdiscectomy pain when used alone or in addition to opioids. It is easy to administer and decreases tramadol consumption and opioid-related side effects.

Intravenous ferric carboxymaltose for anaemia in pregnancy.

Science.gov (United States)

Froessler, Bernd; Collingwood, Joshua; Hodyl, Nicolette A; Dekker, Gustaaf

2014-03-25

Iron deficiency is a common nutritional deficiency amongst women of childbearing age. Peri-partum iron deficiency anaemia (IDA) is associated with significant maternal, fetal and infant morbidity. Current options for treatment are limited: these include oral iron supplementation, which can be ineffective and poorly tolerated, and red blood cell transfusions, which carry an inherent risk and should be avoided. Ferric carboxymaltose is a new treatment option that may be better tolerated.The study was designed to assess the safety and efficacy of iron deficiency anaemia (IDA) correction with intravenous ferric carboxymaltose in pregnant women with mild, moderate and severe anaemia in the second and third trimester. Prospective observational study; 65 anaemic pregnant women received ferric carboxymaltose up to 15 mg/kg between 24 and 40 weeks of pregnancy (median 35 weeks gestational age, SD 3.6). Treatment effectiveness was assessed by repeat haemoglobin (Hb) measurements and patient report of well-being in the postpartum period. Safety was assessed by analysis of adverse drug reactions and fetal heart rate monitoring during the infusion. Intravenous ferric carboxymaltose infusion significantly increased Hb values (p anaemia in pregnancy.

Intravenous vs. left ventricular injection of ionic contrast material: hemodynamic implications for digital subtraction angiography

International Nuclear Information System (INIS)

Mancini, G.B.; Ostrander, D.R.; Slutsky, R.A.; Shabetai, R.; Higgins, C.B.

1983-01-01

Because of the increased use of intravenous injection of contrast material for the evaluation of cardiac structure and function by digital subtraction techniques, a study was done to assess the hemodynamic effects of contrast material when used in this fashion in man. In 10 patients, with each serving as his own control, the effects of intravenous and intraventricular injections of sodium meglumine diatrizoate (Renografin 76) in the same dose were compared. There was no difference between these two methods with respect to changes in pulmonary wedge pressures, systemic pressures, and pulmonary vascular resistance. The elevation of mean pulmonary artery and right atrial pressure was greater after the intraventricular injection (p <0.05). The elevated cardiac output and systemic vascular resistance returned to control values somewhat more quickly after the intravenous injection (p<0.001 and p<0.05, respectively); and the increase in cardiac output was greater after the intravenous injection at 1 min (p<0.05), but less than after the intraventricular injection at 2 min (p<0.05). Despite the detection of these statistically significant differences, the magnitude and timing of these differences are too small to justify the notion that imaging by intravenous injections of standard ionic contrast media provides any substantial hemodynamic benefits or decreased risk to the patient

Population pharmacokinetics of buprenorphine following a two-stage intravenous infusion in healthy volunteers

DEFF Research Database (Denmark)

Jensen, Mette Lykke; Foster, David J.R.; Upton, Richard N.

2007-01-01

The aim of this investigation was to characterize the pharmacokinetics of buprenorphine following administration of an intravenous (i.v.) infusion. To date, the population kinetics of buprenorphine has been described for bolus administration only.......The aim of this investigation was to characterize the pharmacokinetics of buprenorphine following administration of an intravenous (i.v.) infusion. To date, the population kinetics of buprenorphine has been described for bolus administration only....

Response of plasma glucose, insulin, and nonesterified fatty acids to intravenous glucose tolerance tests in dairy cows during a 670-day lactation.

Science.gov (United States)

Marett, L C; Auldist, M J; Moate, P J; Wales, W J; Macmillan, K L; Dunshea, F R; Leury, B J

2015-01-01

This experiment investigated the metabolic response of dairy cows undergoing an extended lactation to a frequently sampled intravenous glucose tolerance test. The experiment used 12 multiparous Holstein cows that calved in late winter in a seasonally calving pasture-based system and were managed for a 670-d lactation by delaying rebreeding. In each of four 5-wk experimental periods commencing at approximately 73, 217, 422, and 520 (±9.1) days in milk (DIM), cows were offered a diet of perennial ryegrass (73 and 422 DIM) or pasture hay and silage (217 and 520 DIM) supplemented with 1kg of DM grain (control; CON) or 6kg of DM grain (GRN) as a ration. Daily energy intake was approximately 160 and 215 MJ of metabolizable energy/cow for the CON and GRN treatments, respectively. At all other times, cows were managed as a single herd and grazed pasture supplemented with grain to an estimated minimum daily total intake of 180 MJ of metabolizable energy/cow. Cows were fitted with an indwelling jugular catheter during the final week of each experimental period. The standard intravenous glucose tolerance test using 0.3g of glucose per kilogram of body weight was performed on each cow at approximately 100, 250, 460, and 560 DIM. Plasma concentrations of glucose, insulin, and nonesterified fatty acids (NEFA) responses were measured. Milk yield, milk solids yield, body weight, and basal plasma glucose were greater in the GRN compared with the CON treatment. The area under the plasma response curve relative to baseline (AUC) for glucose, insulin, and NEFA and their apparent fractional clearance rates indicated varied whole body responsiveness to insulin in terms of glucose metabolism throughout the 670-d lactation. The glucose AUC 0 to 20 min postinfusion was increased at 560 DIM, indicating reduced utilization of glucose by the mammary gland at this stage of lactation. The NEFA clearance rate, 6 to 30 min postinfusion, was greater at 460 and 560 DIM. These data indicated an

Pharmacokinetics of oral and intravenous melatonin in healthy volunteers

DEFF Research Database (Denmark)

Andersen, Lars Peter Holst; Werner, Mads Utke; Rosenkilde, Mette Marie

2016-01-01

BACKGROUND: The aim was to investigate the pharmacokinetics of oral and iv melatonin in healthy volunteers. METHODS: The study was performed as a cohort crossover study. The volunteers received either 10 mg oral melatonin or 10 mg intravenous melatonin on two separate study days. Blood samples were...... collected at different time points following oral administration and short iv infusion, respectively. Plasma melatonin concentrations were determined by RIA technique. Pharmacokinetic analyses were performed by "the method of residuals" and compartmental analysis. The pharmacokinetic variables: k a, t 1....../2 absorption, t max, C max, t 1/2 elimination, AUC 0-∞, and bioavailability were determined for oral melatonin. C max, t 1/2 elimination, V d, CL and AUC 0-∞ were determined for intravenous melatonin. RESULTS: Twelve male volunteers completed the study. Baseline melatonin plasma levels did not differ...

Saccharomyces cerevisiae boulardii transient fungemia after intravenous self-inoculation

OpenAIRE

Cohen, Lola; Ranque, Stéphane; Raoult, Didier

2013-01-01

We report the case of a young psychotic intravenous drug user injecting herself with Saccharomyces cervisiae (boulardii). She experienced a 24 h fever, resolving spontaneously confirming, quasi experimentally, the inocuity of this yeast in a non-immunocompromised host.

Effects of albendazole nanoparticles in mice with hepatic echinococosis: Portal vein cannulation versus intravenous administration.

Science.gov (United States)

Zhu, Di-Wen; Zhang, Ming-Xing; Bao, Ying-Jun; Gu, Jun-Peng; Ji, Wei-Zheng; Zhang, Hai-Xiao; Ren, Wei-Xin

2015-07-01

To compare the ABZ and its metabolites concentration in cyst tissue of hepatic alveolar echinococcosis administered by different routes, forty male Wistar rats receiving albendazole nanoparticles from tail vein and portal vein were divided into two groups, the concentration of ABZ and its metabolites ABZSO, ABZSO2, in the cyst tissue, were analyzed by HPLC at 2, 4, 8, 24, 36 h after administration. The parent drug and its metabolites were detected in plasm and the cyst tissue after portal cannulation and intravenous administration. The last results were the concentration of ABZ in the portal cannulation group was higher than in the intravenous group at every time point (p < 0.05). Compared to the intravenous group, the portal cannulation administration of ABZ led to a lower plasm concentration of ABZ. The concentration of ABZ and the active ABZSO were significantly higher in the portal cannulation group than that of the intravenous group. Copyright © 2015 Elsevier Inc. All rights reserved.

Emergency department treatment of viral gastritis using intravenous ondansetron or dexamethasone in children.

Science.gov (United States)

Stork, Christine M; Brown, Kathleen M; Reilly, Tracey H; Secreti, LaLaina; Brown, Lawrence H

2006-10-01

To compare the efficacy of intravenous ondansetron or dexamethasone compared with intravenous fluid therapy alone in children presenting to the emergency department with refractory vomiting from viral gastritis who had failed attempts at oral hydration. This double-blind, randomized, controlled trial was performed in a tertiary care pediatric emergency department. Children aged 6 months to 12 years presenting with more than three episodes of vomiting in the past 24 hours, mild/moderate dehydration, and failed oral hydration were included. Patients with other medical causes were excluded. Subjects were randomized to dexamethasone 1 mg/kg (15 mg maximum), ondansetron 0.15 mg/kg, or placebo (normal saline [NS], 10 mL). All subjects also received intravenous NS at 10-20 mL/kg/hr. Oral fluid tolerance was evaluated at two and four hours. Those not tolerating oral fluids at four hours were admitted. Discharged patients were evaluated at 24 and 72 hours for vomiting and repeat health care visits. The primary study outcome was hospitalization rates between the groups. Data were analyzed using chi-square test, Kruskal-Wallis test, Mantel-Haenszel test, and analysis of variance, with p hydration than NS-treated patients (29 [67.4%]; relative risk, 1.28; 95% confidence interval = 1.02 to 1.68). There were no differences in number of mean episodes of vomiting or repeat visits to health care at 24 and 72 hours in the ondansetron, dexamethasone, or NS groups. In children with dehydration secondary to vomiting from acute viral gastritis, ondansetron with intravenous rehydration improves tolerance of oral fluids after two hours and reduces the hospital admission rate when compared with intravenous rehydration with or without dexamethasone.

Epidural versus intravenous fentanyl for postoperative analgesia following orthopedic surgery: randomized controlled trial

Directory of Open Access Journals (Sweden)

Marcelo Soares Privado

Full Text Available CONTEXT AND OBJECTIVE: Controversy exists regarding the site of action of fentanyl after epidural injection. The objective of this investigation was to compare the efficacy of epidural and intravenous fentanyl for orthopedic surgery. DESIGN AND SETTING: A randomized double-blind study was performed in Hospital São Paulo. METHODS: During the postoperative period, in the presence of pain, 29 patients were divided into two groups: group 1 (n = 14 received 100 µg of fentanyl epidurally and 2 ml of saline intravenously; group 2 (n = 15 received 5 ml of saline epidurally and 100 µg of fentanyl intravenously. The analgesic supplementation consisted of 40 mg of tenoxicam intravenously and, if necessary, 5 ml of 0.25% bupivacaine epidurally. Pain intensity was evaluated on a numerical scale and plasma concentrations of fentanyl were measured simultaneously. RESULTS: The percentage of patients who required supplementary analgesia with tenoxicam was lower in group 1 (71.4% than in group 2 (100%: 95% confidence interval (CI = 0.001-0.4360 (P = 0.001, Fisher's exact test; relative risk, RR = 0.07. Epidural bupivacaine supplementation was also lower in group 1 (14.3% than in group 2 (53.3%: 95% CI = 0.06-1.05 (P = 0.03, Fisher's exact test; RR = 0.26. There was no difference in pain intensity on the numerical scale. Mean fentanyl plasma concentrations were similar in the two groups. CONCLUSION: Intravenous and epidural fentanyl appear to have similar efficacy for reducing pain according to the numerical scale, but supplementary analgesia was needed less frequently when epidural fentanyl was used. CLINICAL TRIAL REGISTRATION NUMBER: NCT00635986

Hypocalcemic action of the several types of salicylic acid analogues.

Science.gov (United States)

Kato, Y; Nishishita, K; Sakai, H; Tatsumi, M; Yamamoto, K

1989-02-01

The present study was performed to see the structure-activity relationships on the aspirin-induced hypocalcemia. Several kinds of salicylic acid (SA) analogues administered orally with a stomach tube. In general, the drugs were suspended in the 2% CMC solution. At the scheduled times after the treatment, 60 microliters of the blood was collected to determine the level of calcium. Aspirin, sodium salt of o-hydroxybenzoic acid (Na-salicylate), sodium salt of m- and p-hydroxybenzoic acid (HBA), 2,5-dihydroxybenzoic acid (DHBA), PAS sodium dihydrate (PAS-Na), salicylamide (SAM) and 2% CMC control were used. Hypocalcemia was induced by aspirin and Na-salicylate but not by m- and p-HBA-Na. In addition, DHBA and PAS caused hypocalcemia when they were administered intravenously but not orally. These results suggest that the carboxyl group must be adjacent to the hydroxyl group on the benzene ring to induce this type of hypocalcemia and that the SA structure would be able to induce hypocalcemia, even in the presence of the additional third substituent on the same ring. On the comparison between aspirin-DL lysine (water soluble aspirin) and SA-DL lysine, SA-DL lysine, which is not an inhibitor of PG synthetase, was more effective on the hypocalcemic action than ASP-DL lysine. The phenomenon was observed at the stage especially immediately after intravenous injection, when the acetyl group may be more responsible to acetylate the PG synthetase in the aspirin-DL lysine group. The present results seems to be consistent with the previous hypothesis that PGs are not involved in the process of aspirin-induced hypocalcemia in the rat.

[Intravenous ethyl alcohol in metabolic resuscitation].

Science.gov (United States)

Agolini, G; Lipartiti, T; Zaffiri, O; Musso, L; Belloni, G P

1980-11-01

Intravenously administered ethyl alcohol may be effective as analgesic and hypotensive peripheric vasoactive drug. In the Intensive Care Departments parenteral ethanol administration is infrequent because no "sure dosage" can be suggested in adults and children. Liver, kidney and C.N.S. diseases can worsen; foetopathy can follow. Drug-ethanol interaction may be particularly important for some patients admitted in Intensive Care Departments. Often the potential caloric support cannot be fully utilized ("empty" calories) and seldom hyperventilation, hyperlactacidemia and impaired protein synthesis can follow.

One Stage Radical Removal of Intravenous Leiomyomatosis Extending to the Right Atrium via the Bilateral Gonadal Veins

Directory of Open Access Journals (Sweden)

X. Gui

Full Text Available : Background: Intravenous leiomyomatosis is a benign and rare smooth muscle cell tumor. Extension to the right heart is exceptional. Among the reported cases, the tumor is usually known to enter through the lumen of the iliac vein and grows into the inferior vena cava; involvement of bilateral gonadal veins is rarely reported. Complete tumor resection is the key to therapy. Case presentation: A 25 year old female Chinese patient suffering from abdominal distention for 1 month, who was diagnosed with intravenous leiomyomatosis extending to the heart, from pre-operative imaging studies, is presented. A one stage procedure with complete excision of the tumor was performed. Histopathological findings confirmed the diagnosis of intravenous leiomyomatosis. The patient's post-operative recovery was uneventful, without recurrence and re-stenosis at 1 year follow up. Conclusion: Intravenous leiomyomatosis may grow within veins along various routes. This case demonstrated intravenous leiomyomatosis with tumor extension through bilateral gonadal veins extending to the heart. It is believed that one stage radical resection can be a practical and effective alternative for the patients in good clinical condition. Long-term follow up is recommended because of the possibility of recurrence and metastases. Keywords: Intravenous leiomyomatosis, Cardiac extending, Extension pathway, Gonadal veins, One-stage operation

The effect of tubing dwell time on insulin adsorption during intravenous insulin infusions.

Science.gov (United States)

Thompson, Cecilia D; Vital-Carona, Jessica; Faustino, E Vincent S

2012-10-01

Insulin adsorbs to plastic tubing, which decreases the concentration of an insulin solution delivered from an intravenous infusion set. Dwelling insulin within tubing before starting the infusion decreases adsorption but delays treatment initiation and wastes time in infusion preparation. The lack of data on dwell time effects results in wide variability in practice. We aim to determine the effect of dwell time on insulin concentration from intravenous infusion tubing. In this in vitro study, we used insulin solutions with concentrations of 0.1 unit/mL, 1 unit/mL, and 10 units/mL. Each solution dwelled in intravenous infusion sets for 0, 15, 30, or 60 min. After the dwell, we measured insulin concentrations from the solution bags and tubing. We repeated each insulin concentration-dwell time combination five times. Comparisons were performed using analyses of variance. For each of the three insulin concentrations, the mean insulin concentrations from the tubing were not significantly different between dwell times. Duration of dwell time did not affect insulin adsorption in polypropylene intravenous infusion sets. We recommend that following a 20-mL flush, insulin infusions can be started without any dwell time. Removal of dwell times may improve clinical practice by minimizing preparation time and will allow faster initiation of insulin infusion therapy.

Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology.

Science.gov (United States)

Xia, Chun-Fang; Zhang, Yufeng; Zhang, Yun; Boado, Ruben J; Pardridge, William M

2007-12-01

The effective delivery of short interfering RNA (siRNA) to brain following intravenous administration requires the development of a delivery system for transport of the siRNA across the brain capillary endothelial wall, which forms the blood-brain barrier in vivo. siRNA was delivered to brain in vivo with the combined use of a receptor-specific monoclonal antibody delivery system, and avidin-biotin technology. The siRNA was mono-biotinylated on either terminus of the sense strand, in parallel with the production of a conjugate of the targeting MAb and streptavidin. Rat glial cells (C6 or RG-2) were permanently transfected with the luciferase gene, and implanted in the brain of adult rats. Following the formation of intra-cranial tumors, the rats were treated with a single intravenous injection of 270 microg/kg of biotinylated siRNA attached to a transferrin receptor antibody via a biotin-streptavidin linker. The intravenous administration of the siRNA caused a 69-81% decrease in luciferase gene expression in the intracranial brain cancer in vivo. Brain delivery of siRNA following intravenous administration is possible with siRNAs that are targeted to brain with the combined use of receptor specific antibody delivery systems and avidin-biotin technology.

Farnesylthiosalicylic acid-loaded lipid-polyethylene glycol-polymer hybrid nanoparticles for treatment of glioblastoma.

Science.gov (United States)

Kaffashi, Abbas; Lüle, Sevda; Bozdağ Pehlivan, Sibel; Sarısözen, Can; Vural, İmran; Koşucu, Hüsnü; Demir, Taner; Buğdaycı, Kadir Emre; Söylemezoğlu, Figen; Karlı Oğuz, Kader; Mut, Melike

2017-08-01

We aimed to develop lipid-polyethylene glycol (PEG)-polymer hybrid nanoparticles, which have high affinity to tumour tissue with active ingredient, a new generation antineoplastic drug, farnesylthiosalicylic acid (FTA) for treatment of glioblastoma. Farnesylthiosalicylic acid-loaded poly(lactic-co-glycolic acid)-1,2 distearoyl-glycerol-3-phospho-ethanolamine-N [methoxy (PEG)-2000] ammonium salt (PLGA-DSPE-PEG) with or without 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) hybrid nanoparticles has been prepared and evaluated for in-vitro characterization. Cytotoxicity of FTA-loaded nanoparticles along with its efficacy on rat glioma-2 (RG2) cells was also evaluated both in vitro (in comparison with non-malignant cell line, L929) and in vivo. Scanning electron microscopy studies showed that all formulations prepared had smooth surface and spherical in shape. FTA and FTA-loaded nanoparticles have cytotoxic activity against RG2 glioma cell lines in cell culture studies, which further increases with addition of DOTAP. Magnetic resonance imaging and histopathologic evaluation on RG2 tumour cells in rat glioma model (49 female Wistar rats, 250-300 g) comparing intravenous and intratumoral injections of the drug have been performed and FTA-loaded nanoparticles reduced tumour size significantly in in-vivo studies, with higher efficiency of intratumoral administration than intravenous route. Farnesylthiosalicylic acid-loaded PLGA-DSPE-PEG-DOTAP hybrid nanoparticles are proven to be effective against glioblastoma in both in-vitro and in-vivo experiments. © 2017 Royal Pharmaceutical Society.

Intravenous versus oral iron supplementation for correction of post-transplant anaemia in renal transplant patients

Directory of Open Access Journals (Sweden)

Mudge David W

2009-06-01

Full Text Available Abstract Background Post-transplant anaemia remains a common problem after kidney transplantation, with an incidence ranging from nearly 80% at day 0 to about 25% at 1 year. It has been associated with poor graft outcome, and recently has also been shown to be associated with increased mortality. Our transplant unit routinely administers oral iron supplements to renal transplant recipients but this is frequently accompanied by side effects, mainly gastrointestinal intolerance. Intravenous iron is frequently administered to dialysis patients and we sought to investigate this mode of administration in transplant recipients after noticing less anaemia in several patients who had received intravenous iron just prior to being called in for transplantation. Methods This study is a single-centre, prospective, open-label, randomised, controlled trial of oral versus intravenous iron supplements in renal transplant recipients and aims to recruit approximately 100 patients over a 12-month period. Patients will be randomised to receive a single dose of 500 mg iron polymaltose (intravenous iron group or 2 ferrous sulphate slow-release tablets daily (oral iron group. The primary outcome is time to normalisation of haemoglobin post-transplant. Prospective power calculations have indicated that a minimum of 48 patients in each group would have to be followed up for 3 months in order to have a 90% probability of detecting a halving of the time to correction of haemoglobin levels to ≥110 g/l in iron-treated patients, assuming an α of 0.05. All eligible adult patients undergoing renal transplantation at the Princess Alexandra Hospital will be offered participation in the trial. Exclusion criteria will include iron overload (transferrin saturation >50% or ferritin >800 μg/l, or previous intolerance of either oral or intravenous iron supplements. Discussion If the trial shows a reduction in the time to correction of anaemia with intravenous iron or less side

ORAL IBOPAMINE SUBSTITUTION IN PATIENTS WITH INTRAVENOUS DOPAMINE DEPENDENCE

NARCIS (Netherlands)

GIRBES, ARJ; MILNER, AR; MCCLOSKEY, BV; ZWAVELING, JH; VANVELDHUISEN, DJ; ZIJLSTRA, JG; LIE, KI

1995-01-01

In a prospective open study we evaluated whether intravenous dopamine infusions can be safely switched to enterally administered ibopamine in dopamine-dependent patients. Six patients defined as being clinically stable, normovolaemic, but dopamine dependent, i.e. with repeated inability to stop

Ultrasound Guidance as a Rescue Technique for Peripheral Intravenous Cannulation

National Research Council Canada - National Science Library

Pappas, Nancy L; Michaud, Terese E; Wolbers, Russell M; Steward, James C; Fevurly, Thomas A; Samolitis, Timothy J; Shoneboom, Bruce A; Watts, Dorraine D

2006-01-01

Peripheral intravenous (W) cannulation can be difficult to perform using the traditional landmark or visual/palpation technique in patients with access difficulties such as deep, sclerotic, small, or fragile veins...

[*C]octanoic acid breath test to measure gastric emptying rate of solids.

Science.gov (United States)

Maes, B D; Ghoos, Y F; Rutgeerts, P J; Hiele, M I; Geypens, B; Vantrappen, G

1994-12-01

We have developed a breath test to measure solid gastric emptying using a standardized scrambled egg test meal (250 kcal) labeled with [14C]octanoic acid or [13C]octanoic acid. In vitro incubation studies showed that octanoic acid is a reliable marker of the solid phase. The breath test was validated in 36 subjects by simultaneous radioscintigraphic and breath test measurements. Nine healthy volunteers were studied after intravenous administration of 200 mg erythromycin and peroral administration of 30 mg propantheline, respectively. Erythromycin significantly enhanced gastric emptying, while propantheline significantly reduced gastric emptying rates. We conclude that the [*C]octanoic breath test is a promising and reliable test for measuring the gastric emptying rate of solids.

Intravenous carbon dioxide as an echocardiographic contrast agent

NARCIS (Netherlands)

R.S. Meltzer (Richard); P.W.J.C. Serruys (Patrick); P.G. Hugenholtz (Paul); J.R.T.C. Roelandt (Jos)

1981-01-01

textabstractIntravenous carbon dioxide (CO2) was employed to cause echocardiographic contrast in 40 patients. One to 3 cc of medically pure CO2 were agitated with 5 to 8 cc of 5% dextrose in water and rapidly injected into an upper extremity vein. Contrast was obtained in all patients. In 33

Tranexamic acid reduces blood loss and blood transfusions in primary total hip arthroplasty: a prospective randomized double-blind study in 40 patients

DEFF Research Database (Denmark)

Husted, Henrik; Blønd, Lars; Sonne-Holm, Stig

2003-01-01

INTRODUCTION: We performed a prospective, randomized, double-blind study on 40 patients scheduled for primary total hip arthroplasty due to arthrosis or osteonecrosis to determine the effect of tranexamic acid on per- and postoperative blood losses and on the number of blood transfusions needed....... PATIENTS AND METHODS: 40 patients were randomized to tranexamic acid (10 mg/kg given as a bolus intravenous injection, followed by a continuous infusion of 1 mg/kg/hour for 10 hours) or placebo (20 mL saline given intravenously) 15 minutes before the incision. We recorded the peroperative and postoperative...... blood losses at removal of the drain 24 hours after the operation and the number of blood transfusions. RESULTS: Patients receiving tranexamic acid had a mean peroperative blood loss of 480 mL versus 622 mL in patients receiving placebo (p = 0.3), a postoperative blood loss of 334 mL versus 609 mL (p...

Multi Organ Failure Following Intravenous Gasoline for Suicide: A Case Report

Directory of Open Access Journals (Sweden)

Hadi Hamishehkar

2012-12-01

Full Text Available Hydrocarbons are ubiquitous in daily life and include plant and animal fats, alcohols, solvents, natural gas, petroleum derivates. Majority of intoxication reports of hydrocarbons are due to inhalation or ingestion, but there is few reports about intravenous injection of gasoline. We report a 58 year-old man who injected gasoline intravenously for suicide. He developed soft tissue necrosis of forearm and bilateral pulmonary infiltration. He underwent fasciotomy and extensive debridement of necrotic tissues, at the operation room. He was intubated and mechanically ventilated because of acute lung injury. He developed acute kidney injury after 2 days. These symptoms seem to be due to extravasation of gasoline from vessels which lead to inflammation, cell damage and organ failure. The patient developed multi organ failure which unfortunately did not respond to our treatment and he died at day 21. Management of gasoline intoxication depends on the rout of exposure. Like other types of toxications, intravenous toxication has pulmonary involvement, however in this case we had multiple organ involvement. It seems that in such cases we should consider early end organ targeted therapy to stop the future organ failure

Multi organ failure following intravenous gasoline for suicide: a case report.

Science.gov (United States)

Mahmoodpoor, Ata; Soleimanpour, Hassan; Hamishehkar, Hadi

2012-01-01

Hydrocarbons are ubiquitous in daily life and include plant and animal fats, alcohols, solvents, natural gas, petroleum derivates. Majority of intoxication reports of hydrocarbons are due to inhalation or ingestion, but there is few reports about intravenous injection of gasoline. We report a 58 year-old man who injected gasoline intravenously for suicide. He developed soft tissue necrosis of forearm and bilateral pulmonary infiltration. He underwent fasciotomy and extensive debridement of necrotic tissues, at the operation room. He was intubated and mechanically ventilated because of acute lung injury. He developed acute kidney injury after 2 days. These symptoms seem to be due to extravasation of gasoline from vessels which lead to inflammation, cell damage and organ failure. The patient developed multi organ failure which unfortunately did not respond to our treatment and he died at day 21. Management of gasoline intoxication depends on the rout of exposure. Like other types of toxications, intravenous toxication has pulmonary involvement, however in this case we had multiple organ involvement. It seems that in such cases we should consider early end organ targeted therapy to stop the future organ failure. © 2012 Tehran University of Medical Sciences. All rights reserved.

Central venous catheter insertion problem solving using intravenous catheter: technical communication

Directory of Open Access Journals (Sweden)

Alemohammad M

2013-02-01

Full Text Available Insertion of central venous catheter is an accepted method for hemodynamic monitor-ring, drug and fluid administration, intravenous access, hemodialysis and applying cardiac pace-maker in hospitalized patients. This procedure can be associated with severe complications. The aim of this article is to provide a practical approach to prevent catheter malposition in states that the guide wire will not pass freely.During central venous insertion in internal jugular vein using modified seldinger technique, when after venous insertion, the passage of the guide wire shows difficulties and don’t pass freely, insertion of an intravenous cannula over the wire and re-insertion of the wire can help to prevent malposition of the wire and the catheter. Use of an intravenous cannula over the guide, in situations that the guide wire cannot pass freely among the needle inserted in internal jugular vein, and re-insertion of the guide can probably prevent or reduce the tissue or vascular trauma and the associated complica-tions. This simple maneuver can be helpful in difficult cases especially in cardiac surgery patients who receive high dose heparin and it is necessary to avoid traumatize-tion of carotid artery.

Efficacy and safety of non-intravenous midazolam for the treatment of status epilepticus in children: a Meta-analysis

Directory of Open Access Journals (Sweden)

Yan LIN

2016-02-01

Full Text Available Objective To evaluate the clinical efficacy and safety of non-intravenous midazolam for treating status epilepticus (SE in children.  Methods Taking midazolam, status epilepticus and children both in Chinese and English as search terms, retrieve in databases such as PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI, VIP and Wanfang Data, assisted by manual searching and Google Scholar, in order to collect randomized controlled trials (RCTs about non-intravenous midazolam for treating SE in children from January 2000 to January 2015. Jadad Scale was used to evaluate the quality of literatures. Meta-analysis was performed by using RevMan 5.3 software. Results There were a total of 258 records after preliminary searching, and 6 RCTs involving 766 episodes were finally included after excluding duplicate ones and those which did not meet the inclusion criteria. The results were as follows: 1 midazolam via intranasal administration was as effective as intravenous diazepam in achieving seizure control in children (RD = -0.070, 95%CI: -0.200—0.060, P = 0.290. However, non-intravenous (intranasal or buccal midazolam showed better effects on seizure control than rectal diazepam (RD = 0.170, 95% CI: 0.030—0.320; P = 0.020. 2 The mean time from arrival at hospital to cessation was not significantly different between intranasal midazolam and intravenous diazepam (SMD = -1.570, 95%CI: -3.280—0.140; P = 0.070. 3 There was no statistical difference between intranasal midazolam and intravenous diazepam for the time from giving drug to cessation (SMD = 0.240, 95%CI: -0.110—0.590; P = 0.170. 4 There was no statistical difference on the occurrence rate of adverse drug reactions between non-intravenous midazolam and intravenous or non-intravenous diazepam (RD = -0.010, 95% CI: -0.030—0.200; P = 0.500.  Conclusions Non-intravenous midazolam is safe and effective in the treatment for status epilepticus in children. However, the

Pattern of intravenous immunoglobulins (IVIG) use in a pediatric ...

African Journals Online (AJOL)

EB

Abstract. Background: Intravenous Immunoglobulin (IVIG) preparations are scarce biological products used for replacement or immunomodulatory effects. Guidelines have been issued by regulatory health authorities to ensure provision of the products for patients who are in severe need. Objectives: The study aimed at ...

Clofibric acid increases the formation of oleic acid in endoplasmic reticulum of the liver of rats.

Science.gov (United States)

Hirose, Akihiko; Yamazaki, Tohru; Sakamoto, Takeshi; Sunaga, Katsuyoshi; Tsuda, Tadashi; Mitsumoto, Atsushi; Kudo, Naomi; Kawashima, Yoichi

2011-01-01

The effects of 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid) on the formation of oleic acid (18:1) from stearic acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [¹⁴C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) clofibric acid for 7 days; and the distribution of radiolabeled fatty acids among subcellular organelles, microsomes, peroxisomes, and mitochondria, was estimated on the basis of correction utilizing the yields from homogenates of marker enzymes for these organelles. The radioactivity was mostly localized in microsomes and the radiolabeled fatty acids present in microsomes were significantly increased by the treatment of rats with clofibric acid. The formation of radiolabeled 18:1 in microsomes markedly increased and incorporations of the formed [¹⁴C]18:1 into PC and phosphatidylethanolamine in microsomes were augmented in response to clofibric acid. The [¹⁴C]18:1 incorporated into PC was mostly located at the C-2 position, but not the C-1 position, of PC, and the radioactivity in 18:1 at the C-2 position of PC was strikingly increased by clofibric acid. These results obtained from the in vivo experiments directly link the findings that clofibric acid treatment induces microsomal stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase in the liver and the findings that the treatment with the drug elevated absolute mass and mass proportion of 18:1 at the C-2 position, but not the C-1 position, of PC in the liver together.

Errors in the administration of intravenous medications in hospital and the role of correct procedures and nurse experience

OpenAIRE

Westbrook, Johanna I; Rob, Marilyn I; Woods, Amanda; Parry, Dave

2011-01-01

Background Intravenous medication administrations have a high incidence of error but there is limited evidence of associated factors or error severity. Objective To measure the frequency, type and severity of intravenous administration errors in hospitals and the associations between errors, procedural failures and nurse experience. Methods Prospective observational study of 107 nurses preparing and administering 568 intravenous medications on six wards across two teaching hospitals. Procedur...

Clinical experience with intravenous radiosensitizers in unresectable sarcomas

International Nuclear Information System (INIS)

Kinsella, T.J.; Glatstein, E.

1987-01-01

Traditionally, adult bone and soft tissue sarcomas have been considered to be ''radioresistant.'' Because of this philosophy, patients who present with locally advanced, unresectable sarcomas often are treated in a palliative fashion, usually with low-dose radiotherapy. Over the last 6 years, 29 patients with unresectable primary or metastatic sarcomas were treated using a combination of intravenous chemical radiosensitizers and high-dose irradiation. Twenty-two of 29 patients achieved clinical local control, with six patients having a complete clinical response. The time to tumor response is often several months or longer, which is in contrast to other tumor histologies (carcinomas, lymphomas), where tumor response usually occurs over several weeks. Several large tumors have shown only a minimal tumor response, yet were found to be sterilized in posttreatment biopsy or autopsy examination. Of 15 patients with primary sarcomas without metastases, 11 patients (73%) remain free of local tumor progression from 12 to 83 months. Adult high-grade sarcomas can be controlled with high-dose radiotherapy and intravenous radiosensitizers, although the precise role of these agents is unclear

The analysis and countermeasures of intravenous infusion operation assessment results analysis in nursing students at different levels

Directory of Open Access Journals (Sweden)

Jiao-rong ZHAO

2013-11-01

Full Text Available Objective:To analyze the problems existed in nursing students at different levels in the process of intravenous infusion, to make judgmental guide towards common problems in clinical teaching, to standardize nursing students’ operations at intravenous infusion, and to avoid errors and disputes. Methods: The authors analyzed the problems in secondary, tertiary, undergraduate nursing students in three levels at a provincial hospital from 2010 to 2012 during intravenous infusion therapy; and the clinical teaching administration means were also discussed. Results: the difference of the problems existed in nursing students at different levels is not significant. P values were greater than 0.05. The top five projects that lost scores are consistent. Conclusion: The key problems that can easily cause errors and disputes are those that mostly occurred in nursing students at intravenous infusion operations. In clinical teaching, judgmental guide on common problems should be emphasized, nursing students’ operations at intravenous infusion should be standardized, the critical awareness towards clinical operations should be developed, errors and disputes should be avoided, and nursing students’ sense of professionalism should be enhanced.

Intravenous versus oral etoposide

DEFF Research Database (Denmark)

Ali, Abir Salwa; Grönberg, Malin; Langer, Seppo W.

2018-01-01

High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently...... administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter- and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS......) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (≤ 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS...

Suicide attempt by intravenous injection of gasoline: a case report.

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Fink, Katrin; Kuehnemund, Alexander; Schwab, Tilmann; Geibel-Zehender, Annette; Bley, Thorsten; Bode, Christoph; Busch, Hans-Joerg

2010-11-01

There is much experience with intoxication by aspiration of volatile hydrocarbon products, whereas intravenous injection of these distillates is rare. There are only few reports that describe a wide variety of associated pathological changes, predominantly in the pulmonary system. We report the case of an intravenous self-injection of gasoline by a young man in a suicide attempt. Immediately after injecting gasoline, the 22-year-old man developed bradycardia, hypotension, and increasing dyspnea. Computed tomography scan of the chest showed signs consistent with diffuse alveolar-toxic damage to the lung. These symptoms and radiological findings are similar to those commonly observed after inhalation of this type of substance. This may have been due to diffusion of gasoline into the alveoli, where its presence leads to this characteristic damage. In this patient, gasoline entered the intramuscular tissue, and the patient developed a soft-tissue phlegmon at the forearm. At operation, gas emanation and superficial necrosis were noted. Nevertheless, the patient's outcome was good, with full recovery within 3 weeks. The major changes in this patient after intravenous injection of gasoline were in the pulmonary system, including hypoxemia and radiological findings that could be related to an exhalation of the volatile substance. In addition, gas in the musculature of the injection area caused a soft-tissue phlegmon. Copyright © 2010 Elsevier Inc. All rights reserved.

Rapid Inpatient Titration of Intravenous Treprostinil for Pulmonary Arterial Hypertension: Safe and Tolerable.

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El-Kersh, Karim; Ruf, Kathryn M; Smith, J Shaun

There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil. Our treprostinil dose escalation protocol included initiation at 2 ng·kg·min with subsequent up-titration by 1 ng·kg·min every 6 to 8 hours as tolerated by side effects. A total of 16 subjects were identified. Thirteen subjects were treprostinil naive (naive group), and 3 subjects were receiving subcutaneous treprostinil but were hospitalized for further intravenous up-titration of treprostinil dose (nonnaive group). In the naive group, the median maximum dose achieved was 20 ng·kg·min with an interquartile range (IQR) of 20-23 ng·kg·min. The median up-titration interval was 6 days (IQR: 4-9). In the nonnaive group, the median maximum dose achieved was 20 ng·kg·min (range: 17-30). The median up-titration interval was 8.5 days (range: 1.5-11). Overall, the median maximum dose achieved was 20 ng·kg·min (IQR: 20-23.5), and the median up-titration interval was 6 days (IQR: 4.6-9.25), with no reported significant adverse hemodynamic events. In patients with pulmonary arterial hypertension, rapid inpatient titration of intravenous treprostinil is safe and tolerable.

Radiotracer studies on the synthesis of prorennin and rennin using 14C-amino acids

International Nuclear Information System (INIS)

Angelo, I.A.; Ganguli, N.C.

1976-01-01

In vivo incorporation of 14 C-amino acids into the prorennin and rennin fractions of the abomasal tissue of the intact animal (i.e. calf) has been investigated by : (1) intravenous injection of the label and subsequent isolation of rennin and prorennin fractions from the excised abomasum and (2) feeding. of milk whey fortified with the label to a fistulated kid and subsequent processing of the abomasal juice for rennet extraction. Prorennin incorporates more radioactivity than rennin. This indicates that abomasal tissue uses blood amino acids for prorennin synthesis, but amino acids fed through dietary channels may not be used for rennin synthesis. (M.G.B.)

Dietary Hyaluronic Acid Migrates into the Skin of Rats

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Mariko Oe

2014-01-01

Full Text Available Hyaluronic acid is a constituent of the skin and helps to maintain hydration. The oral intake of hyaluronic acid increases water in the horny layer as demonstrated by human trials, but in vivo kinetics has not been shown. This study confirmed the absorption, migration, and excretion of 14C-labeled hyaluronic acid (14C-hyaluronic acid. 14C-hyaluronic acid was orally or intravenously administered to male SD rats aged 7 to 8 weeks. Plasma radioactivity after oral administration showed the highest level 8 hours after administration, and orally administered 14C-hyaluronic acid was found in the blood. Approximately 90% of 14C-hyaluronic acid was absorbed from the digestive tract and used as an energy source or a structural constituent of tissues based on tests of the urine, feces, expired air, and cadaver up to 168 hours (one week after administration. The autoradiographic results suggested that radioactivity was distributed systematically and then reduced over time. The radioactivity was higher in the skin than in the blood at 24 and 96 hours after administration. The results show the possibility that orally administered hyaluronic acid migrated into the skin. No excessive accumulation was observed and more than 90% of the hyaluronic acid was excreted in expired air or urine.

A hand-held robotic device for peripheral intravenous catheterization.

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Cheng, Zhuoqi; Davies, Brian L; Caldwell, Darwin G; Barresi, Giacinto; Xu, Qinqi; Mattos, Leonardo S

2017-12-01

Intravenous catheterization is frequently required for numerous medical treatments. However, this process is characterized by a high failure rate, especially when performed on difficult patients such as newborns and infants. Very young patients have small veins, and that increases the chances of accidentally puncturing the catheterization needle directly through them. In this article, we present the design, development and experimental evaluation of a novel hand-held robotic device for improving the process of peripheral intravenous catheterization by facilitating the needle insertion procedure. To our knowledge, this design is the first hand-held robotic device for assisting in the catheterization insertion task. Compared to the other available technologies, it has several unique advantages such as being compact, low-cost and able to reliably detect venipuncture. The system is equipped with an electrical impedance sensor at the tip of the catheterization needle, which provides real-time measurements used to supervise and control the catheter insertion process. This allows the robotic system to precisely position the needle within the lumen of the target vein, leading to enhanced catheterization success rate. Experiments conducted to evaluate the device demonstrated that it is also effective to deskill the task. Naïve subjects achieved an average catheterization success rate of 88% on a 1.5 mm phantom vessel with the robotic device versus 12% with the traditional unassisted system. The results of this work prove the feasibility of a hand-held assistive robotic device for intravenous catheterization and show that such device has the potential to greatly improve the success rate of these difficult operations.

Evaluation of the causes and cost impact of returned intravenous ...

African Journals Online (AJOL)

Purpose: To evaluate the main reasons for returning intravenous (IV) medications and ... Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus, ... was conducted at a tertiary university teaching.

Enzymuria in neonates receiving continuous intravenous infusion of gentamicin

DEFF Research Database (Denmark)

Colding, H; Brygge, K; Brendstrup, L

1992-01-01

with non-treatment periods in the same newborn infant (33 infants). The same tendency applied to AAP. Newborn infants receiving continuous intravenous infusion of gentamicin were not found to be at greater risk of nephrotoxicity than those receiving intermittent gentamicin treatment, using NAG and AAP...

Intravenous Carbamazepine for Adults With Seizures.

Science.gov (United States)

Vickery, P Brittany; Tillery, Erika E; DeFalco, Alicia Potter

2018-03-01

To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions, and place in therapy of the intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of seizures in adult patients. A comprehensive PubMed and EBSCOhost search (1945 to August 2017) was performed utilizing the keywords carbamazepine, Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and seizure disorder. Additional data were obtained from literature review citations, manufacturer's product labeling, and Lundbeck website as well as Clinicaltrials.gov and governmental sources. All English-language trials evaluating IV carbamazepine were analyzed for this review. IV carbamazepine is FDA approved as temporary replacement therapy for treatment of adult seizures. Based on a phase I trial and pooled data from 2 open-label bioavailability studies comparing oral with IV dosing, there was no noted indication of loss of seizure control in patients switched to short-term replacement antiepileptic drug therapy with IV carbamazepine. The recommended dose of IV carbamazepine is 70% of the patient's oral dose, given every 6 hours via 30-minute infusions. The adverse effect profile of IV carbamazepine is similar to that of the oral formulation, with the exception of added infusion-site reactions. IV carbamazepine is a reasonable option for adults with generalized tonic-clonic or focal seizures, previously stabilized on oral carbamazepine, who are unable to tolerate oral medications for up to 7 days. Unknown acquisition cost and lack of availability in the United States limit its use currently.

Candida costochondritis associated with recent intravenous drug use

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Simeon J. Crawford

2016-01-01

Full Text Available Candida osteoarticular infections are being reported with increasing frequency, possibly due to an expanding population at risk. However, Candida costochondritis is uncommon. We report two cases of Candida costochondritis in patients who presented with subacute-onset chest wall swelling and whose only identifiable risk factor was a history of recent intravenous drug use.

DISTINGUISHED CHARACTERISTICS OF INFECTIVE ENDOCARDITIS IN HIV/AIDS AMONG INTRAVENOUS DRUGS ABUSED

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E. Y. Ponomareva

2011-01-01

Full Text Available The aim – definition of distinguished characteristics of the right-sided infective endocarditis (IE inintravenous drugs abused with human immunodeficiency virus (HIV/acquired immunodeficiency syndrome (AIDS.Materials and methods. The study included 10 patients with right-sided IE in conjunction with HIV/AIDS. All patients were male, age – from 28to 36 years.Results. Course of the IE in HIV/AIDS among intravenous drugs abused in general corresponds to features specific to IE in intravenous drug users without HIV infection. Distinctive features of IE in these patients are a large burden of lung disease, its disseminated character, more tissue oxygenation disorders and marked pulmonary hypertension and haematological disorders (lymphopenia, anemia, and late diagnosis of IE.Conclusion. Features of the current right-sided IE in intravenous drugs abused with HIV/AIDS are distinguished . Difficulties in diagnosis of IE inHIV infection are due to variety of causes of prolonged fever, which should guide doctors to more frequent use of transthoracic echocardiography during prolonged fever in HIV-infected patients.

Feasibility of using intravenous contrast-enhanced computed tomography (CT) scans in lung cancer treatment planning

International Nuclear Information System (INIS)

Xiao Jianghong; Zhang Hong; Gong Youling; Fu Yuchuan; Tang Bin; Wang Shichao; Jiang Qingfeng; Li Ping

2010-01-01

Background and purpose: To investigate the feasibility of using intravenous contrast-enhanced computed tomography (CT) scans in 3-dimensional conformal radiotherapy (3D-CRT), stereotactic body radiation therapy (SBRT) and intensity-modulated radiotherapy (IMRT) treatment planning for lung cancers, respectively. Materials and methods: Twelve patients with bulky lung tumors and 14 patients with small lung tumors were retrospectively analyzed. Each patient took two sets of CT in the same position with active breathing control (ABC) technique before and after intravenous contrast agent (CA) injections. Bulky tumors were planned with 3D-CRT, while SBRT plans were generated for patients with small tumors based on CT scans with intravenous CA. In addition, IMRT plans were generated for patients with bulky tumors to continue on a planning study. All plans were copied and replaced on the scans without intravenous CA. The radiation doses calculated from the two sets of CTs were compared with regard to planning volumes (PTV), the organ at-risk (OAR) and the lungs using Wilcoxon's signed rank test. Results: In comparisons for 3D-CRT plans, CT scans with intravenous CA reduced the mean dose and the maximum dose of PTV with significant differences (p 95 ) for targets, respectively (p < 0.05). There was no statistical significance for lung parameters between two sets of scans in SBRT plans and IMRT plans. Conclusions: The enhanced CT scans can be used for both target delineation and treatment planning in 3D-CRT. The dose difference caused by intravenous CA is small. But for SBRT and IMRT, the minimum irradiation dose in targets may be estimated to be increased up to 2.71% while the maximum dose may be estimated to be decreased up to 1.36%. However, the difference in dose distribution in most cases were found to be clinical tolerable.

Intravenous ibuprofen: the first injectable product for the treatment of pain and fever

Directory of Open Access Journals (Sweden)

P Brandon Bookstaver

2010-05-01

Full Text Available P Brandon Bookstaver, April D Miller, Celeste N Rudisill, LeAnn B NorrisDepartment of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, University of South Carolina Campus, Columbia, South Carolina, USAAbstract: This paper reviews the current data on the use of the first approved intravenous ibuprofen product for the management of post-operative pain and fever in the United States. The management of acute and post-operative pain and fever with nonsteroidal anti-inflammatory agents (NSAIDs is well documented. A search in Medline and International Pharmaceutical Abstracts of articles until the end of November 2009 and references of all citations were conducted. Available manufacturer data on file were also analyzed for this report. Several randomized controlled studies have demonstrated the opioid-sparing and analgesic effects of 400 and 800 mg doses of intravenous ibuprofen in a series of post-operative patient populations. Two recent studies have also noted the improvement in fever curves in critically ill and burn patients. These data, along with pharmacokinetic and pharmacologic properties, are explored in this review, which addresses the clinical utility of a parenteral NSAID in a hospitalized patient for post-operative pain management and fever reduction. Further data on intravenous ibuprofen are needed to define long-term utilization, management of acute pain, and use in special populations.Keywords: ibuprofen, intravenous, injectable, nonsteroidal anti-inflammatory drug

[Sedation with intravenous midazolam during upper gastrointestinal endoscopy--changes in hemodynamics, oxygen saturation and memory].

Science.gov (United States)

Mizuno, Ju; Matsuki, Michiko; Gouda, Yoshinori; Nishiyama, Tomoki; Hanaoka, Kazuo

2003-09-01

Cardiorespiratory adverse effects are often observed in patients undergoing upper gastrointestinal endoscopy with sedation. In this study, we examined hemodynamics, oxygen saturation and memory during upper gastrointestinal endoscopy under sedation with intravenous midazolam. Eight healthy outpatients without any obvious complications received intravenous midazolam 5 mg for sedation for upper gastrointestinal endoscopy. Blood pressure, heart rate and percutaneous arterial oxygen saturation (SpO2) were measured before, during and after endoscopy. After the arousal by intravenous flumazenil, we inquired the patients about the level of memory during the endoscopy. Blood pressure decreased significantly two minutes after midazolam administration, but increased significantly after the insertion of an endoscope which was not different from the control value. Heart rate increased significantly one and three minutes after the insertion of the endoscope. SpO2 decreased significantly after midazolam administration and stayed at around 95%. No patients remembered the procedure. Sedation with intravenous midazolam during upper gastrointestinal endoscopy is useful to control the cardiovascular responses, and to obtain amnesia. However, a decrease in SpO2 should be watched carefully.

Intravenous lipid infusion affects dry matter intake, methane yield, and rumen bacteria structure in late-lactating Holstein cows.

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Lamp, Ole; Reyer, Henry; Otten, Winfried; Nürnberg, Gerd; Derno, Michael; Wimmers, Klaus; Metges, Cornelia C; Kuhla, Björn

2018-03-28

Increasing the dietary fat content of ruminant diets decreases methane (CH 4 ) production. This effect is caused by the toxic properties of fatty acids on rumen microbial populations, coating of feed particles diminishing the accessibility for microbes, and a reduction in dry matter intake (DMI). The latter effect is caused by postabsorptive long-chain fatty acids eliciting anorexic signaling; however, whether circulating long-chain fatty acids affect rumen CH 4 production alike is unknown. To approach this question, 5 rumen-cannulated Holstein cows in late lactation received 2 jugular catheters and were kept in respiration chambers to measure CH 4 production and DMI for 48 h. In a crossover design, cows were intravenously infused with a 20% lipid emulsion (LIPO) or 0.9% NaCl (CON). The LIPO cows received 2.1 kg of triglycerides/d [0.152 ± 0.007 g of triglycerides/(kg of BW × h) -1 ] consisting of 12.1% palmitic acid, 4.2% stearic acid, 31.1% oleic acid, and 52.7% linoleic acid. Blood and rumen fluid samples were taken hourly during the day. Results showed that LIPO compared with CON infusion increased plasma triglyceride as well as free fatty acid and serotonin concentrations but reduced the proportion of de novo synthesized milk fatty acids (sum of C6 to C16). Daily CH 4 production and DMI were lower, whereas daily CH 4 yield (CH 4 /DMI) was greater in LIPO than CON cows, although CH 4 yield decreased from d 1 to d 2 by 2 to 14% in LIPO-infused cows only. This effect was associated with a higher (acetate + butyrate)/propionate ratio, tending lower propionate concentrations between 24 and 34 h of infusion, reduced relative abundances of genera belonging to Succinivibrio, Ruminococcaceae, and Ruminiclostridium, and greater relative Bacteroidetes genus abundances in the rumen. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Efficacy of tranexamic acid on surgical bleeding in spine surgery: a meta-analysis.

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Cheriyan, Thomas; Maier, Stephen P; Bianco, Kristina; Slobodyanyuk, Kseniya; Rattenni, Rachel N; Lafage, Virginie; Schwab, Frank J; Lonner, Baron S; Errico, Thomas J

2015-04-01

Spine surgery is usually associated with large amount of blood loss, necessitating blood transfusions. Blood loss-associated morbidity can be because of direct risks, such as hypotension and organ damage, or as a result of blood transfusions. The antifibrinolytic, tranexamic acid (TXA), is a lysine analog that inhibits activation of plasminogen and has shown to be beneficial in reducing surgical blood loss. To consolidate the findings of randomized controlled trials (RCTs) investigating the use of TXA on surgical bleeding in spine surgery. A metaanalysis. Randomized controlled trials investigating the effectiveness of intravenous TXA in reducing blood loss in spine surgery, compared with a placebo/no treatment group. MEDLINE, Embase, Cochrane controlled trials register, and Google Scholar were used to identify RCTs published before January 2014 that examined the effectiveness of intravenous TXA on reduction of blood loss and blood transfusions, compared with a placebo/no treatment group in spine surgery. Metaanalysis was performed using RevMan 5. Weighted mean difference with 95% confidence intervals was used to summarize the findings across the trials for continuous outcomes. Dichotomous data were expressed as risk ratios with 95% confidence intervals. A pTranexamic acid reduced intraoperative, postoperative, and total blood loss by an average of 219 mL ([-322, -116], pTranexamic acid led to a reduction in proportion of patients who received a blood transfusion (risk ratio 0.67 [0.54, 0.83], pTranexamic acid reduces surgical bleeding and transfusion requirements in patients undergoing spine surgery. Tranexamic acid does not appear to be associated with an increased incidence of pulmonary embolism, DVT, or MI. Copyright © 2015 Elsevier Inc. All rights reserved.