A comparison of the analgesic efficacy of transforaminal methylprednisolone alone and with low doses of clonidine in lumbo-sacral radiculopathy.

Science.gov (United States)

Tauheed, Nazia; Usmani, Hammad; Siddiqui, Anwar Hasan

2014-01-01

Although transforaminal epidural steroid injections under fluoroscopic guidance have become a common mode of treatment of lumbosacral radiculopathy due to herniated disc, the efficacy of steroid with low doses of clonidine has not been compared yet. Comparison of the analgesic efficacy of methylprednisolone alone and with low doses of clonidine for transforaminal injection in lumbosacral radiculopathy. A randomized, double-blind trial. This study was performed at the Pain Clinic under the Department of Anaesthesiology, Jawaharlal Nehru Medical College Hospital, Aligarh Muslim University, Aligarh, India. One hundred and eighty ASA grade I and II patients aged between 18 and 55 years were allocated into groups I, II and III to receive methylprednisolone 60 mg alone or methylprednisolone 60 mg with or without low doses of clonidine (0.5 mcg/kg or 1 mcg/kg) as transforaminal epidural injection. Pain relief and patient's satisfaction were evaluated with the global pain scale. Follow-up visits were advised at 1, 2, 4, 6 and 12 weeks and then at 6 months after injection. Associated complications were recorded. Maximum pain relief was observed at 2 weeks after injection in all the three groups, with no difference in complication rate among the three groups. The most common complication observed was paresthesia in the nerve distribution. Greater than 60% improvement in pain scores was seen in 40% of the patients in group I, 50% of the patients in group II and 75% of the patients in group III. This study is limited by the lack of a placebo group. Adding 1 mcg/kg clonidine to 60 mg methylprednisolone in transforaminal epidural injections provided better pain relief than 60 mg methylprednisolone with 0.5 mcg/kg clonidine or 60 mg methylprednisolone alone in patients suffering from lumbosacral radiculopathy, with practically no significant side-effects.

[Adult-onset Still's disease with pulmonary and cardiac involvement and response to intravenous immunoglobulin].

Science.gov (United States)

Neto, Nilton Salles Rosa; Waldrich, Leandro; de Carvalho, Jozélio Freire; Pereira, Rosa Maria Rodrigues

2009-01-01

Cardiopulmonary manifestations of adult-onset Still's disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.

Brain protection by methylprednisolone in rats with spinal cord injury.

Science.gov (United States)

Chang, Chia-Mao; Lee, Ming-Hsueh; Wang, Ting-Chung; Weng, Hsu-Huei; Chung, Chiu-Yen; Yang, Jen-Tsung

2009-07-01

Traumatic spinal cord injury is clinically treated by high doses of methylprednisolone. However, the effect of methylprednisolone on the brain in spinal cord injury patients has been little investigated. This experimental study examined Bcl-2 and Bax protein expression and Nissl staining to evaluate an apoptosis-related intracellular signaling event and final neuron death, respectively. Spinal cord injury produced a significant apoptotic change and cell death not only in the spinal cord but also in the supraventricular cortex and hippocampal cornu ammonis 1 region in the rat brains. The treatment of methylprednisolone increased the Bcl-2/Bax ratio and prevented neuron death for 1-7 days after spinal cord injury. These findings suggest that rats with spinal cord injury show ascending brain injury that could be restricted through methylprednisolone management.

α-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy

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Jungyeon Hwang

2008-10-01

Full Text Available Jungyeon Hwang1, Kathleen Rodgers2, James C Oliver3, Thomas Schluep11Insert Therapeutics, Inc., Pasadena, CA, USA; 2Livingston Research Institute, Los Angeles, CA, USA; James C Oliver, Peptagen, Inc., Raleigh, NC USAAbstract: A glycinate derivative of α-methylprednisolone (MP was prepared and conjugated to a linear cyclodextrin polymer (CDP with a loading of 12.4% w/w. The polymer conjugate (CDP-MP self-assembled into nanoparticles with a size of 27 nm. Release kinetics of MP from the polymer conjugate showed a half-life (t1/2 of 50 h in phosphate buffer solution (PBS and 19 h in human plasma. In vitro, the proliferation of human lymphocytes was suppressed to a similar extent but with a delayed effect when CDP-MP was compared with free MP. In vivo, CDP-MP was administered intravenously to mice with collagen-induced arthritis and compared with free MP. CDP-MP was administered weekly for six weeks (0.07, 0.7, and 7 mg/kg/week and MP was administered daily for six weeks (0.01, 0.1, and 1 mg/kg/day. Body weight changes were minimal in all animals. After 28 days, a significant decrease in arthritis score was observed in animals treated weekly with an intermediate or high dose of CDP-MP. Additionally, dorsoplantar swelling was reduced to baseline in animals treated with CDP-MP at the intermediate and high dose level. Histological evaluation showed a reduction in synovitis, pannus formation and disruption of architecture at the highest dose level of CDP-MP. MP administered daily at equivalent cumulative doses showed minimal efficacy in this model. This study demonstrates that conjugation of MP to a cyclodextrin-polymer may improve its efficacy, leading to lower doses and less frequent administration for a safer and more convenient management of rheumatoid arthritis.Keywords: α-methylprednisolone (MP, cyclodextrin polymer (CDP, polymer conjugate (CDP-MP, rheumatoid arthritis (RA, enhanced permeability and retention effect (EPR

Whole-brain radiotherapy and high-dose methylprednisolone for elderly patients with primary central nervous system lymphoma: Results of North Central Cancer Treatment Group (NCCTG) 96-73-51

International Nuclear Information System (INIS)

Laack, Nadia N.; Ballman, Karla V.; Brown, Paul B.; O'Neill, Brian Patrick

2006-01-01

Purpose: The aim of this study was to evaluate the efficacy, toxicity, and survival of whole-brain radiotherapy-treated (WBRT) and high-dose methylprednisolone (HDMP)-treated in elderly patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients with PCNSL who were 70 years and older received 1 g of methylprednisolone daily for 5 days, 30 days after WBRT. Patients then received 1 g of methylprednisolone every 28 days until progression. The primary endpoint was overall survival (OS) at 6 months. Results were compared with those in patients on the previous North Central Cancer Treatment Group (NCCTG) trial who received pre-WBRT cytoxan, adriamycin, vincristine, prednisone (CHOP) and high-dose cytarabine (CHOP-WBRT). A planned interim analysis was performed. The current regimen would be considered inactive if survival was not improved from patients treated with CHOP-WBRT. Results: Nineteen patients were accrued between 1998 and 2003. Median age was 76 years. Interim analysis revealed a 6-month survival of 33%, resulting in closure of the trial. Toxicity, OS, and event-free survival (EFS) were similar to those in patients more than 70 years of age who received CHOP-WBRT. The subgroup of patients who received HDMP had longer OS (12.1 vs. 7.0 months, p = 0.76) and EFS (11.7 vs. 4.0 months, p = 0.04) compared with the CHOP-WBRT patients alive 60 days after the start of treatment. Conclusions: Patients on-study long enough to receive HDMP had prolongation of OS and EFS compared to patients receiving CHOP-WBRT. Although the numbers of patients are too small for statistical conclusions, the HDMP regimen deserves further study

Suppressive effect of glucocorticoids on TNF-alpha production is associated with their clinical effect in multiple sclerosis

NARCIS (Netherlands)

van Winsen, L.M.L.; Polman, C.H.; Dijkstra, C.D.; Tilders, F.J.H.; Uitdehaag, B.M.J.

2010-01-01

A reduced sensitivity to glucocorticoids can affect the clinical effect of treatment with high-dose intravenous methylprednisolone in multiple sclerosis. We prospectively studied 27 multiple sclerosis patients who were treated with intravenous methylprednisolone. Before and after treatment in vitro

Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders

DEFF Research Database (Denmark)

Markvardsen, Lars Høj; Christiansen, I; Harbo, Thomas

2014-01-01

High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship...

Methylprednisolone for prevention of ovarian hyperstimulation syndrome in patients with polycystic ovarian syndrome undergoing in-vitro fertilisation: a randomised controlled trial.

Science.gov (United States)

Mohammadi Yeganeh, Ladan; Moini, Ashraf; Shiva, Marzieh; Mirghavam, Naimeh; Bagheri Lankarani, Narges

2018-02-01

This study aimed to evaluate the effect of methylprednisolone on prevention of ovarian hyperstimulation syndrome (OHSS) in polycystic ovarian syndrome (PCOS) patients undergoing in-vitro fertilisation (IVF). This randomised controlled trial was carried out between November 2009 and December 2013. A total of 219 eligible patients were randomly allocated for treatment (n = 108) or control groups (n = 111). The treatment group received oral methylprednisolone starting from the first day of stimulation. These patients also received an intravenous dose of methylprednisolone on the days of egg collection and embryo transfer. The control group received no glucocorticoid treatment to prevent OHSS. Nineteen percent of patients (18/93) who received methylprednisolone developed OHSS compared with 16.5% (15/91) in the control group and no significant difference was found (p = .61). There were no significant differences between treatment and control groups in the rates of implantation (10% versus 11%, p = .77) and clinical pregnancy (23.2% versus 17.7%, p = .46). Methylprednisolone did not reduce the incidence and severity of OHSS in PCOS patients undergoing IVF and no improvement in clinical outcomes was observed. Impact statement No significant differences were found in OHSS incidence and clinical outcomes between women who received methylprednisolone and control group. There seems to be no benefit for the routine use of glucocorticoids in IVF/ICSI treatments.

Intravenous high-dose immunotherapy: practical recommendations for use in the treatment of neurological disimmune diseases

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N. A. Suponeva

2015-01-01

Full Text Available Current publication summarizes main indications and benefits of intravenous high-dose immunotherapy (IHI in the treatment of various autoimmune diseases of the peripheral nervous system. Available products of intravenous immunoglobulin (IVIG on the Russian market are reviewed. Tactics for choosing optimal medication for IHI based on its effectiveness and safety are analyzed. Dosage calculation and way of administration of IVIG are described, beeing of a high practical value in neurologist’s daily work.

High-dose methylprednisolone in video-assisted thoracoscopic surgery lobectomy

DEFF Research Database (Denmark)

Bjerregaard, Lars S; Jensen, Per F; Bigler, Dennis R

2018-01-01

equally to 125 mg MP or placebo before the start of their elective video-assisted thoracoscopic surgery lobectomy. Group allocation was blinded to patients, investigators and caregivers, and all patients received standardized multimodal, opioid-sparing analgesia. Our primary outcome was area under...... the curve on a numeric rating scale from 0 to 10, for pain scores on the day of surgery and on postoperative days 1 and 2. Clinical follow-up was 2-3 weeks, and telephone follow-up was 12 weeks after surgery. RESULTS: Ninety-six patients were included in the primary analysis. Methylprednisolone...... significantly reduced pain at rest and after mobilization to a sitting position on the day of surgery, without later analgesic effects. Nausea and fatigue were improved without side effects, except transient higher postoperative blood glucose levels. CLINICAL TRIAL REGISTRATION: Registered...

24-hour immunologic assessment of CD4+ and CD8+ lymphocytes in renal transplant recipients receiving chronic methylprednisolone.

Science.gov (United States)

Tornatore, K M; Reed, K; Venuto, R

1995-11-01

Glucocorticoids are commonly prescribed in the post transplant period as a component of combination immunosuppressive regimens. However, the daily 24-hour pattern of helper lymphocytes (CD4+) and suppressor cells (CD8+) during chronic methylprednisolone therapy has not been examined in renal transplant recipients in relation to glucocorticoid exposure and time post-transplant. The response of total lymphocytes, CD4+ and CD8+ lymphocytes was examined in 23 stable renal transplant recipients who received methylprednisolone for at least 8 months post-transplant. The patient's prescribed oral methylprednisolone dose (mean daily dose = 9.7 +/- 2.6 mg) was given intravenously and whole blood was sampled periodically over 24 h for lymphocyte counts and methylprednisolone concentrations. A complete blood count with differential was determined via an automated hemocytometer with CD4+ and CD8+ lymphocytes determined using flow cytometry. Methylprednisolone area under the concentration versus time curve (AUC) was determined and normalized for each patient's respective dose. A general lymphopenia resulted in all patients with a mean decrease of 61 +/- 15% and an average nadir time occurring at 6 h. The decline from baseline was 76 +/- 17% for absolute number of CD4+ and 59 +/- 18% for CD8+ lymphocytes with an average nadir time at 6 h. Twelve patients exhibited a baseline CD4+ count to be less than 688 cells/mm3 (the low end of the reference range) and the lymphocyte count of all the patients fell below this value at the nadir. Six patients had a CD8+ lymphocyte count below 380 cells/mm3 (low end of the reference range) at baseline with 21 of the 23 patients exhibiting less than 380 cells/mm3 at the nadir time. At the time of nadir, the mean CD4+ and CD8+ counts were 156 +/- 105 cells/mm3 and 256 +/- 270 cells/mm3, respectively. In 17 of the 23 patients, the CD4+ count was below 200 cells/mm3 at the time of nadir. The dose-normalized AUC of methylprednisolone ranged from 22

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.

Review of high-dose intravenous vitamin C as an anticancer agent.

Science.gov (United States)

Wilson, Michelle K; Baguley, Bruce C; Wall, Clare; Jameson, Michael B; Findlay, Michael P

2014-03-01

In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate, ascorbic acid). These studies were criticized for their retrospective nature and lack of standardization of key prognostic factors including performance status. Subsequently, several well-designed randomized controlled trials failed to demonstrate a significant survival benefit, although these trials used high-dose oral vitamin C. Marked differences are now recognized in the pharmacokinetics of vitamin C with oral and IV administration, opening the issue of therapeutic efficacy to question. In vitro evidence suggests that vitamin C functions at low concentrations as an antioxidant but may have pro-oxidant activity at high concentrations. The mechanism of its pro-oxidant action is not fully understood, and both intra- and extracellular mechanisms that generate hydrogen peroxide have been proposed. It remains to be proven whether vitamin C-induced reactive oxygen species occur in vivo and, if so, whether this will translate to a clinical benefit. Current clinical evidence for a therapeutic effect of high-dose IV vitamin C is ambiguous, being based on case series. The interpretation and validation of these studies is hindered by limited correlation of plasma vitamin C concentrations with response. The methodology exists to determine if there is a role for high-dose IV vitamin C in the treatment of cancer, but the limited understanding of its pharmacodynamic properties makes this challenging. Currently, the use of high-dose IV vitamin C cannot be recommended outside of a clinical trial. © 2014 Wiley Publishing Asia Pty Ltd.

A randomised comparative study of the short term clinical and biological effects of intravenous pulse methylprednisolone and infliximab in patients with active rheumatoid arthritis despite methotrexate treatment

OpenAIRE

Durez, P; Nzeusseu, T; Lauwerys, B; Manicourt, D; Verschueren, P; Westhovens, R; Devogelaer, J; Houssiau, F

2004-01-01

OBJECTIVES: To compare the short term clinical and biological effects of intravenous (i.v.) pulse methylprednisolone (MP) and infliximab (IFX) in patients with severe active rheumatoid arthritis (RA) despite methotrexate (MTX) treatment. METHODS: Patients with active RA despite MTX treatment were randomly allocated to receive a single i.v. infusion of MP (1 g) or three i.v. infusions of IFX (3 mg/kg) on weeks 0, 2, and 6. Patients were "blindly" evaluated for disease activity measures. Qualit...

Early Angiographic Resolution of Cerebral Vasospasm with High Dose Intravenous Milrinone Therapy

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F. A. Zeiler

2015-01-01

Full Text Available Background. Treatment of symptomatic delayed cerebral ischemia (DCI after subarachnoid hemorrhage (SAH is difficult. Recent studies suggest intravenous (IV high dose milrinone as a potential therapy. The timing to angiographic response with this is unclear. Methods. We reviewed the chart of one patient admitted for SAH who developed symptomatic DCI and was treated with high dose IV milrinone. Results. A 66-year-old female was admitted with a Hunt and Hess clinical grade 4, World Federation of Neurological Surgeons (WFNS clinical grade 4, and SAH secondary to a left anterior choroidal artery aneurysm which was clipped. After bleed day 6, the patient developed symptomatic DCI. We planned for angioplasty of the proximal segments. We administered high dose IV milrinone bolus followed by continuous infusion which led to clinical improvement prior to angiography. The angiogram performed 1.5 hours after milrinone administration displayed resolution of the CT angiogram and MRI based cerebral vasospasm such that further intra-arterial therapy was aborted. She completed 6 days of continuous IV milrinone therapy, was transferred to the ward, and subsequently rehabilitated. Conclusions. High dose IV milrinone therapy for symptomatic DCI after SAH can lead to rapid neurological improvement with dramatic early angiographic improvement of cerebral vasospasm.

Effect of high-dose intravenous vitamin C on inflammation in cancer patients

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Mikirova Nina

2012-09-01

Full Text Available Abstract Background An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP are associated with poor prognosis and decreased survival in many types of cancer. Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels. Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients. Methods 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g after standard treatments by conventional methods. CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests. Results According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment. There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3 and changes in the levels of C-reactive protein. Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments. Conclusions The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases

Corneal Allograft Rejection: Topical Treatment Vs. Pulsed Intravenous Methylprednisolone - Ten Years' Result [rejeição De Transplantes De Córnea: Tratamento Tópico Vs. Pulsoterapia - Resultados De 10 Anos

OpenAIRE

Costa D.C.; de Castro R.S.; Ferraz de Camargo M.S.; Kara-Jose N.

2008-01-01

Purpose: To evaluate the efficacy of intravenous 500 mg methylprednisolone in addition to topical treatment with 1% prednisolone in the treatment of the first episode of corneal endothelial rejection in patients that were submitted to corneal allograft transplantation. Methods: Retrospective casecontrol study with 81 patients that presented the first episode of corneal endothelial rejection and were treated within the first 15 days of the onset of symptoms. Results: 67 patients were treated w...

The radioprotective effects of methylprednisolone and Sho-Saikoto on mouse lung

Energy Technology Data Exchange (ETDEWEB)

Kure, Fumio [Kyoto Prefectural Univ. of Medicine (Japan)

1992-01-01

The radioprotective effects of methylprednisolone and Sho-Saikoto (a herbal medicine) on radiation damage to lung tissue were evaluated in four main groups of female Slc-ICR mice, one control group and three groups irradiated with single doses (6 Gy, 12 Gy, 18 Gy) of {sup 60}Co gamma rays. Subgroups were established with administration of methylprednisolone and Sho-Saikoto, alone and together. Direct quantitative measurements of collagen accumulation in lung (lung fibrosis) were made by analysis of digitally processed microscopic images of Azan-Mallory stained sections 24 weeks after irradiation. Administration of methylprednisolone supressed the expected development of fibrotic lung tissue in each of the irradiated groups. In a further study, peplomycin, a lung fibrosis enhancing agent, was administered to all four groups in addition to methylprednisolone and Sho-Saikoto, alone and together. Methylprednisolone was demonstrated to be effective only in 12 Gy group. Overall, Sho-Saikoto showed a lesser degree of effect in the prevention of the fibrosis than methylprednisolone, but the administration of both was demonstrated to be more effective than either alone. (author).

Effect of methylprednisolone use on the rotator cuff in rats: biomechanical and histological study

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Gustavo Vinícius Ghellioni

2015-06-01

Full Text Available OBJECTIVE: To evaluate the influence of treatment with different doses of methylprednisolone on the mechanical resistance and possible histological alterations of the rotator cuff tendon in rats.METHODS: Male Wistar rats were divided randomly into four treatment groups: sham, vehicle or 0.6 mg/kg or 6.0 mg/kg of methylprednisolone. Changes to mechanical resistance (in N and histological parameters (fibrillar appearance, presence of collagen, edema and vascular proliferation of the rotator cuff tendon were evaluated. The analyses were conducted after administration of one treatment (24 h afterwards, two treatments (7 days afterward or three treatments (14 days afterwards, into the subacromial space.RESULTS: Seven and fourteen days after the treatments were started, it was found that in a dose-dependent manner, methylprednisolone reduced the mechanical resistance of the rotator cuff tendon (p < 0.05 in relation to the vehicle group. Modifications to the histological parameters were observed on the 7th and 14th days after the first infiltration, especially regarding the presence of collagen and vascular proliferation, for the dose of 0.6 mg/kg of methylprednisolone, and also regarding the presence of collagen, edema and vascular proliferation for the dose of 6.0 mg/kg of corticoid.CONCLUSION: The results obtained demonstrated a relationship between methylprednisolone use through infiltration into the subacromial space and reduction of the mechanical resistance of and histological modifications to the rotator cuff tendon in rats.

Prophylactic CNS therapy in childhood leukemia. Randomized controlled study of high-dose intravenous methotrexate and cranial irradiation

Energy Technology Data Exchange (ETDEWEB)

Yokoyama, Takashi; Hiyoshi, Yasuhiko [Kurume Univ., Fukuoka (Japan). School of Medicine; Fujimoto, Takeo

1982-12-01

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

Rejeição de transplantes de córnea: tratamento tópico vs. pulsoterapia - resultados de 10 anos Corneal allograft rejection: topical treatment vs. pulsed intravenous methylprednisolone - ten years' result

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Dácio Carvalho Costa

2008-02-01

Full Text Available OBJETIVOS: Avaliar a eficácia da associação de pulsoterapia com 500 mg de metilprednisolona intravenosa ao acetato de prednisolona 1% tópico no tratamento do primeiro episódio de rejeição endotelial de transplantes de córnea. MÉTODOS: Estudo caso-controle retrospectivo com 81 sujeitos que apresentaram o primeiro episódio de rejeição endotelial e submetidos à terapia nos primeiros quinze dias dos sintomas. RESULTADOS: 67 sujeitos foram tratados com acetato de prednisolona 1% tópico de 1 em 1 hora e pulsoterapia com 500 mg de metilprednisolona intravenosa no dia do diagnóstico e 14 sujeitos foram submetidos apenas ao tratamento com acetato de prednisolona 1% tópico formando o grupo controle. Dos 67 sujeitos submetidos a corticoterapia venosa e tópica, 41 (61,19% evoluíram satisfatoriamente e 26 (38,8% apresentaram falência endotelial. Dos 14 sujeitos submetidos apenas à corticoterapia tópica, 4 (28,57% evoluíram com enxerto transparente e os 10 restantes (71,43% com falência endotelial. O teste do qui-quadrado apontou maior taxa de sucesso (pPURPOSE: To evaluate the efficacy of intravenous 500 mg methylprednisolone in addition to topical treatment with 1% prednisolone in the treatment of the first episode of corneal endothelial rejection in patients that were submitted to corneal allograft transplantation. METHODS: Retrospective case-control study with 81 patients that presented the first episode of corneal endothelial rejection and were treated within the first 15 days of the onset of symptoms. RESULTS: 67 patients were treated with 1% topical prednisolone acetate and pulsed intravenous methylprednisolone 500 mg at the diagnosis of corneal allograft rejection. Fourteen patients were submitted to topical treatment only, thus forming the control group. Forty-one of 67 patients (61.2% that were submitted to pulsed steroid had good outcome and 26 (38.8% presented corneal graft failure while only 4 of 14 patients (28.57% that

Effect of methylprednisolone on the oxidative burst activity, adhesion molecules and clinical outcome following open heart surgery

DEFF Research Database (Denmark)

Toft, P; Christiansen, K; Tønnesen, Else Kirstine

1997-01-01

on granulocytes and improve clinical outcome. Sixteen patients undergoing open heart surgery participated in the study. Eight were randomized to receive methylprednisolone (30 mg/kg intravenously) at the start of anaesthesia while eight patients served as a control group. The oxidative burst was measured flow...... not improve the weaning from the ventilator or reduce the stay in the intensive-care unit. In conclusion, treatment with steroids prevented hyperthermia following open heart surgery with CPB and reduced capillary leak during ECC. Methylprednisolone, however, did not reduce the oxidative burst activity...

The effect of aqueous extract of Kalanchoe Folium on methylprednisolone pharmacokinetic profile

Science.gov (United States)

Indriyanti, Niken; Garmana, Afrillia Nuryanti; Setiawan, Finna; Sukandar, Elin Yulinah; Adnyana, I. Ketut

2016-03-01

Aqueous extract of Kalanchoe pinnata leaves had immunosupressant effect on lupus nephritis model. When it combined with methylprednisolone, there is a risk of interaction. In this study rats divided into two groups, a group that received methylprednisolone (MP) (0.72 mg/kgBW) and a group that received MP in combination with extract (0.36 mg/kg BW MP and 140 mg/kg BW extract). These treatment were given everyday for 4 weeks. Methylprednisolone concentration in rats serum was measured using HPLC with extraction method according to Lawson method (1985). The column used was Inertsil C-18 using mobile phase KH2PO4 : metanol (15:85) buffer, flow rate 0.6 mL/minutes, UV detector (λ = 230 nm) and pressure 1319 psi. The result showed that there was an interaction occurred. The combination of MP and aqueous extract of K. pinnata leaves showed interaction which causing methylprednisolone level comparable with methylprednisolone level in MP group. Mean of decreasing MP level in serum was 0.285 ppm. It means that aqueous extract of Kalanchoe Folium could elevate methylprednisolone concentration in plasma. Adjustment of the dose must be considered in this combination.

Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage

DEFF Research Database (Denmark)

Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid

2015-01-01

1000 with standard medical care on physical fatigue in women with postpartum haemorrhage. METHODS/DESIGN: In a single centre, open-labelled, randomised trial, women with postpartum haemorrhage exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron isomaltoside 1000 or standard...... Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant...... randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside...

Comparative evaluation of megadose methylprednisolone with dexamethasone for treatment of primary typical optic neuritis

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Menon Vimala

2007-01-01

Full Text Available Aim: To compare the efficacy of intravenous methylprednisolone and intravenous dexamethasone on visual recovery and evaluate their side-effects for the treatment of optic neuritis. Materials and Methods: Prospective, randomized case-controlled study including 21 patients of acute optic neuritis presenting within eight days of onset and with visual acuity less then 20/60 in the affected eye who were randomly divided into two groups. Group I received intravenous dexamethasone 200 mg once daily for three days and Group II received intravenous methylprednisolone 250 mg/six-hourly for three days followed by oral prednisolone for 11 days. Parameters tested were pupillary reactions, visual acuity, fundus findings, color vision, contrast sensitivity, Goldmann visual fields and biochemical investigations for all patients at presentation and follow-up. Results: Both groups were age and sex-matched. LOGMAR visual acuity at presentation was 1.10 ± 0.52 in Group I and 1.52 ± 0.43 in Group II. On day 90 of steroid therapy, visual acuity improved to 0.28 ± 0.33 in Group I and 0.36 ± 0.41 in Group II ( P =0.59. At three months there was no statistically significant difference in the color vision, contrast sensitivity, stereoacuity, Goldman fields and the amplitude and latency of visually evoked response between the two groups. The concentration of vitamin C, glucose, sodium, potassium, urea and creatinine were within the reported normal limits. Conclusion: Intravenous dexamethasone is an effective treatment for optic neuritis. However, larger studies are required to establish it as a safe, inexpensive and effective modality for the treatment of optic neuritis.

Treatment of early AIDS dementia in intravenous drug users : High versus low dose peptide T

NARCIS (Netherlands)

Kosten, TR; Rosen, MI; McMahon, TL; Bridge, TP; OMalley, SS; Pearsall, R; OConnor, PG

1997-01-01

This placebo-controlled, double blind, cross-over study tested the efficacy of two different doses of Peptide T in the treatment of nine intravenous drug users with early AIDS dementia who were also receiving methadone and AZT. Subjects received Peptide T doses of either 15 or 1.5 mg daily for four

Pharmacokinetics and pharmacodynamics of high doses of pharmaceutically prepared heroin, by intravenous or by inhalation route in opioid-dependent patients

NARCIS (Netherlands)

Rook, Elisabeth J.; van Ree, Jan M.; van den Brink, Wim; Hillebrand, Michel J. X.; Huitema, Alwin D. R.; Hendriks, Vincent M.; Beijnen, Jos H.

2006-01-01

A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by "chasing the dragon"

Intravenous methylprednisolone in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP Metilprednisolona endovenosa na mielopatia associada ao HTLV-I/Paraparesia Espástica Tropical (MAH/PET

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Abelardo Q-C Araújo

1993-09-01

Full Text Available HTLV-I (Human T-lymphotropic virus type I associated myelopathy/tropical spastic paraparesis (HAM/TSP is an immunomediated myelopathy induced by the HTLV-I. Some patients, specially those from Japan, seem to have a good response to steroid treatment. However, this has not been found in other regions of the world. High dose intravenous methylprednisolone has been used with success in patients with relapses of multiple sclerosis (MS, another autoimmune disease of the central nervous system. To test the effectiveness of methylprednisolone in patients with HAM/TSP, we devised an open trial in 23 patients. We found a very limited benefit of this form of treatment in these patients. Only one patient, who had the shortest disease duration (five months in the whole group, showed a sustained benefit. We speculate that those patients with a shorter history, with presumably less demye-lination and more inflammatory lesions, would show a better response to immunossupressive treatments.A mielopatia associada ao protovírus T-linfotrópico humano (HTLV-I, também conhecida como paraparesia espástica tropical associada ao HTLV-I (MAH/PET, constitui enfermidade imunomediada desencadeada pela infecção pelo HTLV-I. Nesta condição tem sido demonstrada, particularmente em pacientes japoneses, boa resposta clínica à terapêutica com corticosteróides. Este efeito benéfico todavia não foi encontrado em todas as regiões do mundo. Pulsoterapia com metilprednisolona endovenosa tem sido utilizada com sucesso em pacientes com esclerose múltipla, outro exemplo de doença auto-imune do sistema nervoso central, especialmente durante as fases de exacerbação da doença. Objetivando testar a eficácia da pulsoterapia com metilprednisolona em pacientes com MAH/PET, conduzimos estudo aberto em 23 doentes. Não constatamos efeito benéfico significativo desta forma de tratamento na maioria dos enfermos estudados. Apenas um dos pacientes, o qual exibia o menor tempo de

Low-dose intravenous lidocaine as treatment for proctalgia fugax.

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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.

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

A Comparative Analysis of Saffron and Methylprednisolone on Bleomycin-Induced Pulmonary Fibrosis in Rats

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Mehrzad Bahtouee

2018-04-01

Full Text Available Background: The purpose of this study was to compare the effects of saffron and methylprednisolone on bleomycin-induced pulmonary fibrosis in rats. Methods: This study was conducted in Bushehr, southern Iran in 2017.The animals were divided into four groups of five rats each. Three groups were injected with a single intratracheal dose of bleomycin (5 mg/kg. The fourth group was administered with normal saline at the same volume (200 µl. Saffron extract dissolved in water was given to one group (100 mg /body weight orally while intraperitoneal injection of methylprednisolone (2.5 mg/kg injected to another one for 16 days. The rats were sacrificed 28 days following surgery and their right and left lungs were removed and washed for measuring lung indices, myeloperoxidase activities and finally histopathological examination. Results: Injection of bleomycin caused decrement of body weight aggravated by intraperitoneal methylprednisolone treatment. Lung indices were increased in the bleomycin-treated group compared with the control, while methylprednisolone, unlike saffron, had no preventive effects on it. Both saffron and methylprednisolone treatment prevented the increase in lung myeloperoxidase as a destructive enzyme. In addition, excessive collagen deposition and thickening of alveolar septa were significantly prevented with saffron treatment as compared to methylprednisolone injection following hematoxylin and eosin staining. Conclusion: Saffron with established antioxidant properties could prevent some detrimental effects in bleomycin-induced pulmonary fibrosis even more than methylprednisolone injection known as a standard therapy in this murine model. More investigations must be carried out to examine the beneficial or harmful effects of this remedy.

Comparing the effect of preoperative administration of methylprednisolone and its administration before and during surgery on the clinical outcome in pediatric open heart surgeries.

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Soltani, Ghasem; Abbasi Tashnizi, Mohammad; Moeinipour, Ali Asghar; Ganjifard, Mahmoud; Esfahanizadeh, Jamil; Sepehri Shamloo, Alireza; Purafzali Firuzabadi, Seyed Javad; Zirak, Nahid

2013-06-01

Cardiac surgery under Cardiopulmonary bypass causes a systemic inflammatory response with a multifactorial etiology including direct tissue damage, ischemia and stimulation of immune system induced by cardiopulmonary bypass. This study was designed due to the high prevalence and complications of this stimulated immune system in mortality, morbidity, length of ICU stay, and mechanical ventilation. This study was aimed to compare preoperative and intraoperative methylprednisolone (MP) to intraoperative MP alone with respect to postbypass inflammation and clinical outcome. Sixty pediatric patients (age 0.05). No significant difference in amount of inotropic medications used for hemodynamic supports, duration of mechanical ventilation, peak and average temperature and length of ICU stay was observed. Among the laboratory tests (WBC, BUN, creatinine, CRP) only WBC counts raised more in group 2 when compared to group 1(P < 0.05). There was no difference in clinical outcome after cardiac surgery when we administered an additional dose of methylprednisolone compared to a single dose of methylprednisolone.

Effect of methylprednisolone on the oxidative burst activity, adhesion molecules and clinical outcome following open heart surgery

DEFF Research Database (Denmark)

Toft, P; Christiansen, K; Tønnesen, Else Kirstine

1997-01-01

Following cardiac surgery with cardiopulmonary bypass (CPB), activated granulocytes may be involved with ischaemia/ reperfusion injury. The purpose of this study was to investigate whether steroids could reduce the oxidative burst activity of granulocytes, the expression of adhesion molecules...... on granulocytes and improve clinical outcome. Sixteen patients undergoing open heart surgery participated in the study. Eight were randomized to receive methylprednisolone (30 mg/kg intravenously) at the start of anaesthesia while eight patients served as a control group. The oxidative burst was measured flow...... not improve the weaning from the ventilator or reduce the stay in the intensive-care unit. In conclusion, treatment with steroids prevented hyperthermia following open heart surgery with CPB and reduced capillary leak during ECC. Methylprednisolone, however, did not reduce the oxidative burst activity...

Radiation dose measurements in intravenous pyelography

International Nuclear Information System (INIS)

Egeblad, M.; Gottlieb, E.

1975-01-01

Intravenous pyelography (IVP) and micturition cystourethrography (MCU) are the standard procedures in the radiological examination of children with urinary tract infections and in the control of these children. Gonad protection against radiation is not possible in MCU, but concerning the girls partly possible in IVP. It is of major importance to know the radiation dose in these procedures, especially since the examination is often repeated in the same patients. All IVP were done by means of the usual technique including possible gonad protection. The thermoluminescence dosimeter was placed rectally in the girls and fixed on the scrota in the boys. A total of 50 children was studied. Gonad dose ranged from 140 to 200mR in the girls and from 20 to 70mR in the boys (mean values). The radiation dose in IVP is very low compared to that of MCU, and from this point of view IVP is a dose saving examination in the control of children with urinary tract infections [fr

[Late sequelae of central nervous system prophylaxis in children with acute lymphoblastic leukemia: high doses of intravenous methotrexate versus radiotherapy of the central nervous system--review of literature].

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Zając-Spychała, Olga; Wachowiak, Jacek

2012-01-01

Acute lymphoblastic leukemia is the most common malignancy in children. All current therapy regimens used in the treatment of childhood acute lymphoblastic leukemia include prophylaxis of the central nervous system. Initially it was thought that the best way of central nervous system prophylaxis is radiotherapy. But despite its effectiveness this method, may cause late sequelae and complications. In the programme currently used in Poland to treat acute lymphoblastic leukemia, prophylactic radiotherapy has been reduced by 50% (12 Gy) and is used only in patients stratified into the high risk group and in patients diagnosed as T-cell ALL (T-ALL). Complementary to radiotherapy, intrathecal methotrexate is given alone or in combination with cytarabine and hydrocortisone is given, as well as systemic chemotherapy with intravenous methotrexate is administered in high or medium doses (depending on risk groups and leukemia immunophenotype). Recent studies have shown that high dose irradiation of the central nervous system impairs cognitive development causing memory loss, visuomotor coordination impairment, attention disorders and reduction in the intelligence quotient. It has been proved that the degree of cognitive impairment depends on the radiation dose directed to the medial temporal lobe structures, particularly in the hippocampus and the surrounding cortex. Also, methotrexate used intravenously in high doses, interferes with the metabolism of folic acid which is necessary for normal development and the optimal functioning of neurons in the central nervous system. It has been proved that patients who have been treated with high doses of methotrexate are characterized by reduced memory skills and a lower intelligence quotient. The literature data concerning long term neuroanatomical abnormalities and neuropsychological deficits are ambiguous, and there is still no data concerning current methods of central nervous system prophylaxis with low doses of irradiation in

Treatment of multiple sclerosis relapses with high-dose methylprednisolone reduces the evolution of contrast-enhancing lesions into persistent black holes.

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Di Gregorio, Maria; Gaetani, Lorenzo; Eusebi, Paolo; Floridi, Piero; Picchioni, Antonella; Rosi, Giovanni; Mancini, Andrea; Floridi, Chiara; Baschieri, Francesca; Gentili, Lucia; Sarchielli, Paola; Calabresi, Paolo; Di Filippo, Massimiliano

2018-03-01

The MRI evidence of persistent black holes (pBHs) on T1-weighted images reflects brain tissue loss in multiple sclerosis (MS). The evolution of contrast-enhancing lesions (CELs) into pBHs probably depends on the degree and persistence of focal brain inflammation. The aim of our retrospective study was to evaluate the effect of a single cycle of intravenous methylprednisolone (IVMP), as for MS relapse treatment, on the risk of CELs' evolution into pBHs. We selected 57 patients with CELs on the baseline MRI scan. We evaluated the evolution of CELs into pBHs on a follow-up MRI scan performed after ≥ 6 months in patients exposed and not exposed to IVMP for the treatment of relapse after the baseline MRI. In our cohort, 182 CELs were identified in the baseline MRI and 57 of them (31.3%) evolved into pBHs. In the multivariate analysis, the exposure of CELs to IVMP resulted to be a significant independent protective factor against pBHs' formation (OR 0.28, 95% CI 0.11-0.766, p = 0.005), while ring enhancement pattern and the fact of being symptomatic were significant risk factors for CELs' conversion into pBHs (OR 6.42, 95% CI 2.55-17.27, p < 0.001 and OR 13.19, 95% CI 1.56-288.87, p = 0.037). The exposure of CELs to a cycle of IVMP as for relapse treatment is associated with a lower risk of CELs' evolution into pBHs. Future studies are required to confirm the potential independent protective effect of IVMP on CELs' evolution into pBHs.

Polymeric implant of methylprednisolone for spinal injury ...

African Journals Online (AJOL)

Polymeric implant of methylprednisolone for spinal injury: preparation and characterization. Bo Yin, Jian-Jun Ji, Ming Yang. Abstract. Purpose: To improve the effectiveness and reduce the systemic side effects of methylprednisolone in traumatic spinal injuries, its polymeric implants were prepared using chitosan and sodium ...

Usefulness of high-dose intravenous human immunoglobulins treatment for refractory recurrent pericarditis.

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Moretti, Michele; Buiatti, Alessandra; Merlo, Marco; Massa, Laura; Fabris, Enrico; Pinamonti, Bruno; Sinagra, Gianfranco

2013-11-01

The management of refractory recurrent pericarditis is challenging. Previous clinical reports have noted a beneficial effect of high-dose intravenous human immunoglobulins (IvIgs) in isolated and systemic inflammatory disease-related forms. In this article, we analyzed retrospectively our clinical experience with IvIg therapy in a series of clinical cases of pericarditis refractory to conventional treatment. We retrospectively analyzed 9 patients (1994 to 2010) with refractory recurrent pericarditis, who received high-dose IvIg as a part of their medical treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine treatment was not discontinued during IvIg treatment. No patients had a history of autoimmune or connective tissue diseases. During an average period of 11 months from the first recurrence, patients had experienced a mean of 5 relapses before the first IvIg treatment. In 4 cases, patients showed complete clinical remission with no further relapse after the first IvIg cycle. Two patients experienced a single minor relapse, responsive to short-term nonsteroidal anti-inflammatory drugs. In 2 patients, we performed a second cycle of IvIg after a recurrence of pericarditis, with subsequent complete remission. One patient did not respond to 3 cycles of IvIg and subsequently underwent pericardial window and long-term immunosuppressive treatment. No major adverse effect was observed in consequence of IvIg administration in all the cases. In conclusion, although IvIg mode of action is still poorly understood in this setting, this treatment can be considered as an option in patients with recurrent pericarditis refractory to conventional medical treatment and, in our small series, has proved to be effective in 8 of 9 cases. Copyright © 2013 Elsevier Inc. All rights reserved.

Intravenous administration of high-dose Paclitaxel reduces gut-associated lymphoid tissue cell number and respiratory immunoglobulin A concentrations in mice.

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Moriya, Tomoyuki; Fukatsu, Kazuhiko; Noguchi, Midori; Okamoto, Koichi; Murakoshi, Satoshi; Saitoh, Daizoh; Miyazaki, Masaru; Hase, Kazuo; Yamamoto, Junji

2014-02-01

Chemotherapy remains a mainstay of treatment for cancer patients. However, anti-cancer drugs frequently cause a wide range of side effects, including leukopenia and gastrointestinal toxicity. These adverse effects can lead to treatment delays or necessitate temporary dose reductions. Although chemotherapy-related changes in gut morphology have been demonstrated, the influences of chemotherapeutic regimens on gut immunity are understood poorly. This study aimed to examine whether the anti-cancer drug paclitaxel (PTX) impairs gut immunity in mice. Male ICR mice were randomized into three groups: Control, low-dose PTX (low PTX; 2 mg/kg), or high-dose PTX (high PTX; 4 mg/kg). A single intravenous dose was given. On day seven after the injection, lymphocytes from Peyer patches (PP), intraepithelial (IE) spaces, and the lamina propria (LP) were counted and analyzed by flow cytometry (CD4(+), CD8(+), αβTCR(+), γδTCR(+), B220(+)). Immunoglobulin A (IgA) concentrations were measured in small intestinal and respiratory tract washings. Total, CD4(+) and γδTCR(+) lymphocyte numbers in PPs were significantly lower in the high PTX than in the control group. The CD4(+) lymphocyte numbers in the IE spaces were significantly lower in both PTX groups than in the control group. Respiratory tract IgA concentrations were lower in the high PTX than in the control group. The present data suggest high-dose PTX impairs mucosal immunity, possibly rendering patients more vulnerable to infection. Careful dose selection and new therapies may be important for maintaining mucosal immunity during PTX chemotherapy.

Compatibility of ondansetron hydrochloride and methylprednisolone sodium succinate in multilayer polyolefin containers.

Science.gov (United States)

Bougouin, Christelle; Thelcide, Chloë; Crespin-Maillard, Fabienne; Maillard, Christian; Kinowski, Jean Marie; Favier, Mireille

2005-10-01

The compatibility of ondansetron hydrochloride and methylprednisolone sodium succinate in 5% dextrose injection and 0.9% sodium chloride injection was studied. Test solutions of ondansetron hydrochloride 0.16 mg/mL and methylprednisolone sodium succinate 2.4 mg/mL were prepared in triplicate and tested in duplicate. Total volumes of 4 and 2 mL of ondansetron hydrochloride solution and methylprednisolone sodium succinate solution, respectively, were added to 50-mL multilayer polyolefin bags containing 5% dextrose injection or 0.9% sodium chloride injection. Bags were stored for 24 hours at 20-25 degrees C and for 48 hours at 4-8 degrees C. Chemical compatibility was measured with high-performance liquid chromatography, and physical compatibility was determined visually. Ondansetron hydrochloride was stable for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C. Methylprednisolone sodium succinate was stable for up to 48 hours at 4-8 degrees C. When stored at 20-25 degrees C, methylprednisolone sodium succinate was stable for up to 7 hours in 5% dextrose injection and up to 24 hours in 0.9% sodium chloride injection. Compatibility data for solutions containing ondansetron hydrochloride plus methylprednisolone sodium succinate revealed that each drug was stable for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C. Ondansetron 0.16 mg/mL (as the hydrochloride) and methylprednisolone 2.4 mg/mL (as the sodium succinate) mixed in 50-mL multilayer polyolefin bags were stable in both 5% dextrose injection and 0.9% sodium chloride injection for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C.

Effect of Intravenous High Dose Vitamin C on Postoperative Pain and Morphine Use after Laparoscopic Colectomy: A Randomized Controlled Trial

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Younghoon Jeon

2016-01-01

Full Text Available Background and Objective. Vitamin C has antioxidant, neuroprotective, and neuromodulating effects. Recently, it showed antinociceptive effect as a result of the antioxidant properties. Therefore, we designed this study to assess the effect of intravenous vitamin C on opiate consumption and pain in patients undergoing laparoscopic colectomy. Methods. A total of 100 patients were enrolled and allocated to receive 50 mg/kg vitamin C or placebo by intravenous infusion immediately after induction of anesthesia. Morphine consumption and scores of pain were assessed at 2, 6, and 24 h after completion of surgery. Results. There were 97 patients included in the analysis. Patients who received vitamin C had higher plasma concentrations of vitamin C at the end of surgery, significantly lower morphine consumption at the 2 h after end of surgery, and significantly lower pain scores at rest during first 24 h postoperatively. There was no significant difference between groups in side effects, fatigue score, or pain score during cough. Conclusion. This study shows high dose vitamin C infusion decreased postoperative pain during the first 24 h and reduced morphine consumption in the early postoperative period. Additional research needed to examine whether higher doses of vitamin C and longer infusion times can amplify these effects.

Pharmacodynamic/Pharmacogenomic Modeling of Insulin Resistance Genes in Rat Muscle After Methylprednisolone Treatment: Exploring Regulatory Signaling Cascades

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Zhenling Yao

2008-01-01

Full Text Available Corticosteroids (CS effects on insulin resistance related genes in rat skeletal muscle were studied. In our acute study, adrenalectomized (ADX rats were given single doses of 50 mg/kg methylprednisolone (MPL intravenously. In our chronic study, ADX rats were implanted with Alzet mini-pumps giving zero-order release rates of 0.3 mg/kg/h MPL and sacrificed at various times up to 7 days. Total RNA was extracted from gastrocnemius muscles and hybridized to Affymetrix GeneChips. Data mining and literature searches identified 6 insulin resistance related genes which exhibited complex regulatory pathways. Insulin receptor substrate-1 (IRS-1, uncoupling protein 3 (UCP3, pyruvate dehydrogenase kinase isoenzyme 4 (PDK4, fatty acid translocase (FAT and glycerol-3-phosphate acyltransferase (GPAT dynamic profiles were modeled with mutual effects by calculated nuclear drug-receptor complex (DR(N and transcription factors. The oscillatory feature of endothelin-1 (ET-1 expression was depicted by a negative feedback loop. These integrated models provide test- able quantitative hypotheses for these regulatory cascades.

Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis

DEFF Research Database (Denmark)

Ratzer, Rikke; Iversen, Pernille; Börnsen, Lars

2016-01-01

BACKGROUND: There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments. OBJECTIVE: To evaluate the effect of monthly oral...... methylprednisolone pulse treatment on intrathecal inflammation in progressive MS. METHODS: In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin...... no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone. CONCLUSION: Monthly methylprednisolone pulse treatment was safe, but had...

Effects of oral methylprednisolone and inhaled salbutamol in the decrease of wheezing in patients with asthma after tracheal intubation

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2008-08-01

Full Text Available Background: Airway instrumentation in patients with bronchial hyperreactivity, may evoke life-threatening asthma attack and a good strategy for the prevention of bronchospasm"nhas not been defined. In a randomized, prospective, placebo-controlled study, it was determined whether prophylaxis with either inhaled salbutamol-or combined inhaled salbutamol and oral methylprednisolone improves lung functions and prevents wheezing after intubation. Methods: Thirty one patients with partially reversible airway obstruction (airway resistance> 180%, forced expiratory volume in 1 second [FEV1] < 70% of predicted value, and FEV1 increase> 12% after two puffs of salbutamol were randomized to receive daily either 3-2 puffs (0.2 mg of salbutamol (n =16 or 3-2 puffs (0.2 mg of salbutamol and 40 mg of methylprednisolone (n = 15 orally for 5 days. In all patients lung function was evaluated daily and wheezing changes was assessed before and 5 minutes after tracheal intubation. Results: Both salbutamol and combined inhaled salbutamol and oral methylprednisolone treatment significantly improved airway resistance and FEV1 to a steady state, with no difference between groups. When a single-dose of salbutamol pre-induction or prolonged salbutamol treatment was employed, most patients (8 of 10 and 7 of 9 experienced wheezing after intubation. In contrast, only one patient of those who received both salbutamol and methylprednisolone experienced wheezing (P = 0.0058. Conclusions: Pretreatment with either salbutamol or combined inhaled salbutamol and oral methylprednisolone significantly improves lung function and decreases the incidence of wheezing after tracheal intubation. Methylprednisolone decreases incidence of wheezing more than salbutamol. Therefore, in patients with bronchial hyper reactivity, preoperative treatment with both methylprednisolone and salbutamol minimizes intubation-evoked broncho-constriction.

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

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Rui-Rui Peng

2017-03-01

Full Text Available Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai.Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13% and 0.35% (95% CI: 0.06-1.39%, respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients, fatigue (2 patients, cough (1 patient, sore throat (1 patient, diarrhea (1 patient and erythematous rash (1 patient. The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05. Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia.Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for

Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice

Science.gov (United States)

Tanaka, Emi; Ogawa, Yuko; Mukai, Takeo; Sato, Yoshiaki; Hamazaki, Takashi; Nagamura-Inoue, Tokiko; Harada-Shiba, Mariko; Shintaku, Haruo; Tsuji, Masahiro

2018-01-01

Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs) have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs) in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12), and low-dose (1 × 104) or high-dose (1 × 105) UC-MSCs were administered intravenously 48 h after the insult (P14). To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF) measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by modulating

Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice

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Emi Tanaka

2018-03-01

Full Text Available Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12, and low-dose (1 × 104 or high-dose (1 × 105 UC-MSCs were administered intravenously 48 h after the insult (P14. To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by

Immunological effects of methylprednisolone pulse treatment in progressive multiple sclerosis

DEFF Research Database (Denmark)

Ratzer, R; Romme Christensen, J; Romme Nielsen, B

2014-01-01

phenotypes investigated, 25 changed at nominal significance from baseline to week 12 (pmultiple comparisons, we found 5 subpopulations that changed compared to baseline. No pattern were suggesting modulation of Th17 or TFH cells. CONCLUSION: Methylprednisolone pulse treatment has......OBJECTIVE: To investigate the effect of monthly oral methylprednisolone pulse treatment in progressive MS. METHODS: 30 progressive MS patients were treated with oral methylprednisolone every month. Peripheral blood mononuclear cells were analyzed by flow cytometry. RESULTS: Out of 102 leukocyte...

Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage

DEFF Research Database (Denmark)

Holm, C; Thomsen, L L; Norgaard, A

2017-01-01

BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open-label, ran......BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open...

Methylprednisolone and its related substances in freeze-dried powders for injections

OpenAIRE

LJILJANA SOLOMUN; SVETLANA IBRIĆ; VLATKA VAJS; IVAN VUČKOVIĆ; ZORICA VUJIĆ

2010-01-01

In this work, the behavior of the active pharmaceutical substances methylprednisolone (in a form of methylprednisolone sodium succinate) in finished pharmaceutical dosage form, i.e., freeze-dried powder for injections was examined. The goal was to evaluate the chemical stabilities of methyl-prednisolone sodium succinate packaged in a dual chamber vial, as a specific container closure system. The effect of different parameters: temperature, moisture and light were monitored. The method propose...

Sustained trilineage recovery and disappearance of abnormal chromosome clone in a patient with myelodysplastic syndrome following combination therapy with cytokines (granulocyte colony-stimulating factor and erythropoietin) and high-dose methylprednisolone.

Science.gov (United States)

Imai, Y; Fukuoka, T; Nakatani, A; Ohsaka, A; Takahashi, A

1996-04-01

We report a case of hypoplastic myelodyplastic syndrome (MDS) (refractory anemia (RA)) in which sustained trilineage haematological response and persistent disappearance of an abnormal chromosome clone were achieved after treatment with combination therapy of cytokines (granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Epo)) and methylprednisolone (mPSL) pulse dose. The patient's haematological recovery was rapid and maintained even after cessation of the therapy. In addition, the predominant chromosome clone 13q- in bone marrow cells disappeared in the fourth week. The patient's improved bone marrow haemopoiesis and disappearance of the abnormal chromosome has continued to the present, 13 months after treatment. The occurrence of both trilineage response and abnormal chromosome disappearance in MDS patients treated with cytokine(s) or steroids is rare. Combination therapy might therefore be advantageous in MDS.

High dose Intravenous Anti-D Immune Globulin is More Effective and Safe in Indian Paediatric Patients of Immune Thrombocytopenic Purpura.

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Swain, Trupti Rekha; Jena, Rabindra Kumar; Swain, Kali Prasanna

2016-12-01

Immune Thrombocytopenia (ITP) is characterised by an autoimmune antibody-mediated destruction of platelets and impaired platelet production. Few controlled trials exist to guide management of patients with ITP in Indian scenario for which patients require an individualized approach. Anti-D (Rho (D) immune globulin) at a higher dose can prove to be a cost effective and safe alternative for Indian patients with ITP. To compare the safety and efficacy of higher dose (75μg/kg) intravenous Anti-D immune globulin against the standard dose of 50μg/kg for the management of ITP in Indian patients. One hundred and sixty four children with newly diagnosed ITP between 4-14 years were randomly selected for inclusion and were treated with 50μg/kg (standard dose) or 75μg /kg (higher dose) of Anti-D to compare the efficacy and safety of higher dose intravenous anti-D immune globulin. Efficacy of Anti-D was measured in terms of rate of response and median time to response for increase in platelet counts. Any adverse event was noted. A decrease in haemoglobin concentration suggested accompanying haemolysis. Seventy one out of 84 patients treated with Anti-D at 75μg/kg produced complete response (85%) with median time of response being 2.5 days. On the contrary, 45 patients (70%) patients treated with 50μg/kg had complete response. However, there was no significant increase in haemolysis with higher dose. A significant correlation was found between dose and peak increase in platelet count measured at 7 th day following administration. However, there was no relationship between the decrease in haemoglobin and the dose given, or between the increase in platelet count and fall in haemoglobin. A 75μg/kg dose of Anti-D is more effective with acceptable side effect in comparison to 50μg dose for treatment of newly diagnosed Indian patients of ITP.

High dose intravenous iron, mineral homeostasis and intact FGF23 in normal and uremic rats

DEFF Research Database (Denmark)

Gravesen, Eva; Hofman-Bang, Jacob; Mace, Maria L.

2013-01-01

High iron load might have a number of toxic effects in the organism. Recently intravenous (iv) iron has been proposed to induce elevation of fibroblast growth factor 23 (FGF23), hypophosphatemia and osteomalacia in iron deficient subjects. High levels of FGF23 are associated with increased...

Absorbed Doses to Embryo from Intravenous Urography at Selected Radiological Departments in Slovakia

International Nuclear Information System (INIS)

Karkus, R.; Nikodemova, D.; Horvathova, M.

2003-01-01

Actual legislation used in radiological protection requires quality assurance program for decreasing radiation load of patients from radiological examinations. The information about irradiation of pregnant women is very important, because the embryo is more radiosensitive as adult organism. On the basis of absence of unified calculations or measurements of absorbed doses to embryo from various radiological examinations in Slovakia we present in this study the values of absorbed doses to embryo from intravenous urography at selected radiological departments in Slovakia. Absorbed doses to embryo were obtained by measurement and calculation using the simulation of irradiation of pregnant woman by intravenous urography. The results of our study indicate, that absorbed doses to embryo were at various radiological departments considerably different, depending on type of X-ray machine and different settings of technical parameters of X-ray machine. In accordance with worldwide trend it is necessary to decrease radiation load of patients as low as possible level. Differences in radiation load between radiological departments indicate, that it is necessary to continue in solving of this problem and perform measurements and calculations of absorbed doses to embryo at different types of X-ray machines and at different examinations, where the embryo is in direct beam of X-ray. (author)

Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis.

Science.gov (United States)

Ratzer, Rikke; Iversen, Pernille; Börnsen, Lars; Dyrby, Tim B; Romme Christensen, Jeppe; Ammitzbøll, Cecilie; Madsen, Camilla Gøbel; Garde, Ellen; Lyksborg, Mark; Andersen, Birgit; Hyldstrup, Lars; Sørensen, Per Soelberg; Siebner, Hartwig R; Sellebjerg, Finn

2016-06-01

There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments. To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS. In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin. Secondary outcomes were other CSF biomarkers of inflammation, axonal damage and demyelination; clinical scores; magnetic resonance imaging measures of disease activity, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI); motor evoked potentials; and bone density scans. We found no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone. Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS. © The Author(s), 2015.

Dose-ranging pharmacokinetics of colistin methanesulphonate (CMS) and colistin in rats following single intravenous CMS doses.

Science.gov (United States)

Marchand, Sandrine; Lamarche, Isabelle; Gobin, Patrice; Couet, William

2010-08-01

The aim of this study was to evaluate the effect of colistin methanesulphonate (CMS) dose on CMS and colistin pharmacokinetics in rats. Three rats per group received an intravenous bolus of CMS at a dose of 5, 15, 30, 60 or 120 mg/kg. Arterial blood samples were drawn at 0, 5, 15, 30, 60, 90, 120, 150 and 180 min. CMS and colistin plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of CMS and colistin were calculated by non-compartmental analysis. Linear relationships were observed between CMS and colistin AUCs to infinity and CMS doses, as well as between CMS and colistin C(max) and CMS doses. CMS and colistin pharmacokinetics were linear for a range of colistin concentrations covering the range of values encountered and recommended in patients even during treatment with higher doses.

Radiation Doses in Intravenous Urography And Potentials For Optimization

International Nuclear Information System (INIS)

Halato, M.A.; Badawi, A.; Gassom, G.A.; Barsham, M.A.; Ibrahim, A.F.; Suliman, I.I.; Sulieman, A.A.

2011-01-01

In this study radiation doses in IVU clinical examinations were measured in three public hospitals and a sample of 44 patients. In each room the machine output was measured for different peak tube voltages. Patient's data such as (age and weight) and exposure parameters (kVp) and mAs) were recorded. Entrance Surface Air Kerma (ESAK) for patients was determined by using the tube output and the patient exposure parameters. The ESAK ranged from 0.76 to 6.75 mGy. The cumulative ESAK ranged from 3.5 to 34.6 mGy. In conclusion, the obtained results are in agreement with the standard reference ESAK levels. The study showed that the cumulative ESAK can approach a level known to increase the probability of stochastic effect. Keywords: Patient dose, intravenous Urography, radiation protection

Hyperosmolar nonketotic hyperglycemic coma induced by methylprednisolone pulse therapy for acute rejection after liver transplantation: a case report and review of the literature

Directory of Open Access Journals (Sweden)

Zhou J

2014-12-01

Full Text Available Jian Zhou,* Weiqiang Ju,* Xiaopeng Yuan, Xiaofeng Zhu, Dongping Wang, Xiaoshun HeOrgan Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contributed equally to this work Abstract: Hyperosmolar nonketotic hyperglycemic coma (HNKHC is a serious, rare complication induced by methylprednisolone (MP pulse therapy for acute rejection after orthotopic liver transplantation (OLT. Herein, we report an unusual case of a 58-year-old woman who experienced acute rejection at 30 months after OLT, only one case in which HNKHC resulted in MP pulse therapy for acute rejection in all 913 recipients in our center. The general morbidity of HNKHC was 1.09‰ in this study. HNKHC is characterized by rapid onset, rapid progression, and a lack of specific clinical manifestations. High-dose MP management was a clear risk factor. The principle of treatment included rapid rehydration, low-dose insulin infusion, and correcting disorders of electrolytes and acidosis. In conclusion, clinicians considering MP pulse therapy after OLT should be alert to the occurrence of HNKHC. Keywords: liver transplantation, complications, hyperosmolar nonketotic hyperglycemic coma, methylprednisolone pulse therapy, principle of treatment

Intravenous paracetamol with a lower dose is also effective for the treatment of patent ductus arteriosus in pre-term infants.

Science.gov (United States)

Tekgündüz, Kadir Şerafettin; Ceviz, Naci; Caner, İbrahim; Olgun, Haşim; Demirelli, Yaşar; Yolcu, Canan; Şahin, İrfan Oğuz; Kara, Mustafa

2015-08-01

Haemodynamically significant patent ductus arteriosus is a significant cause of morbidity and mortality in pre-term infants. This retrospective study was conducted to investigate the usefulness of lower-dose paracetamol for the treatment of patent ductus arteriosus in pre-term infants. A total of 13 pre-term infants who received intravenous paracetamol because of contrindications or side effects to oral ibuprofen were retrospectively enrolled. In the first patient, the dose regimen was 15 mg/kg/dose, every 6 hours. As the patient developed significant elevation in transaminase levels, the dose was decreased to 10 mg/kg/dose, every 8 hours in the following 12 patients. Echocardiographic examination was conducted daily. In case of closure, it was repeated after 2 days and when needed thereafter in terms of reopening. A total of 13 patients received intravenous paracetamol. Median gestational age was 29 weeks ranging from 24 to 31 weeks and birth weight was 950 g ranging from 470 to 1390 g. The median postnatal age at the first intravenous paracetamol dose was 3 days ranging from 2 to 9 days. In 10 of the 13 patients (76.9%), patent ductus arteriosus was closed at the median 2nd day of intravenous paracetamol ranging from 1 to 4 days. When the patient who developed hepatotoxicity was eliminated, the closure rate was found to be 83.3% (10/12). Intravenous paracetamol may be a useful treatment option for the treatment of patent ductus arteriosus in pre-term infants with contrindication to ibuprofen. In our experience, lower-dose paracetamol is effective in closing the patent ductus arteriosus in 83.3% of the cases.

Distribution and excretion after intravenous dosing of [{sup 14}C]micafungin to rats

Energy Technology Data Exchange (ETDEWEB)

Yamato, Yasuhiro; Kaneko, Hayato; Yamasaki, Sachiko; Fujiwara, Tomoichi; Katashima, Masataka; Kawamura, Akio; Terakawa, Masato; Kagayama, Akira [Fujisawa Pharmaceutical Co., Ltd., Osaka (Japan). Biopharmaceutical and Pharmacokinetic Research Lab.

2002-12-01

In this study, distribution and excretion after intravenous dosing of [{sup 14}C] micafungin (1 mg/kg) to rats and in vitro serum protein binding and distribution to blood cells in mouse, rat, dog and human were investigated. The concentration of radioactivity in plasma at 5 min, which was the first observation point, was 3,396 ng eq./mL and decreased triexponentially. At 24 h, the concentration had decreased to approximately 12.4% of that at 5 min, and thereafter it deceased with a half-time of 39.3 h. The blood to plasma radioactivity concentration ratios were in the range of 0.80 to 1.00 for up to 7 day after dosing, and were 1.00 or more thereafter. The radioactivity was widely distributed immediately after dosing. The highest radioactivity concentrations were observed in the lungs at 5 min and were 1.86 times higher than that in plasma, followed by the kidneys (1.09). The relative radioactivity concentrations in brain, eyeball, white fat and testis were less than 0.08 of that in plasma, and those in other tissues were in the range of 0.17 to 0.86. The radioactivity concentrations in all tissues examined at 24 h had decreased compared with those at 5 min or 6 h, and decreased almost in parallel with plasma radioactivity concentrations from 72 h with the exception of concentrations for white fat. Up to 240 h after intravenous dosing, 83.5% and 14.4% of the radioactivity had been excreted in feces and urine, respectively. At 240 h, 2.8% and 0.3% of the radioactivity were detected in carcass and gut, respectively. In the expired air, no radioactivity was detected up to 72 h. Up to 48 h after intravenous dosing, 43.9%, 13.2% and 8.3% of the radioactivity had been excreted in bile, urine and feces, respectively. At 48 h, 32.2% and 4.4% of radioactivity were detected in carcass and gut, respectively. (author)

Randomized Clinical Trial of Intraosseous Methylprednisolone Injection for Acute Pulpitis Pain.

Science.gov (United States)

Bane, Khaly; Charpentier, Emmanuel; Bronnec, François; Descroix, Vianney; Gaye-N'diaye, Fatou; Kane, Abdoul Wahabe; Toledo, Rafael; Machtou, Pierre; Azérad, Jean

2016-01-01

The present study reports the results of a randomized clinical trial comparing local intraosseous methylprednisolone injection and emergency pulpotomy in the management of acute pulpitis on efficacy, safety, and efficiency end points. After providing prior informed written consent, 94 patients consulting for acute irreversible pulpitis pain at university-affiliated teaching hospital dental clinics in Dakar, Senegal were randomly assigned to either the methylprednisolone treatment group (n = 47) or the pulpotomy treatment group (n = 47). Patients were followed up at 1 week and assessed 6 months later to evaluate the therapeutic outcome of their treatment. At day 7 the patients in the methylprednisolone group reported less intense spontaneous and percussion pain in the day 0-day 7 period than the patients in the pulpotomy group. Methylprednisolone treatment took approximately 7 minutes (4.6-9.3) less to accomplish than pulpotomy (or about half the time). No difference in the therapeutic outcome was found between the 2 treatment groups at 6 months (all credible intervals span 0). This study establishes that methylprednisolone injection for acute pulpitis is relieved by a minimally invasive pharmacologic approach more effectively than by the reference pulpotomy and conserves scarce dental resources (ie, endodontic equipment and supplies, dental surgeon's time). Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The incidence of phlebitis with intravenous amiodarone at guideline dose recommendations.

Science.gov (United States)

Slim, Ahmad M; Roth, Jason E; Duffy, Benjamin; Boyd, Sheri Y N; Rubal, Bernard J

2007-12-01

Postoperative atrial fibrillation following cardiothoracic surgery is common and frequently managed with intravenous (IV) amiodarone. Phlebitis is the most common complication with peripheral infusion of this agent. Current practice guidelines for peripheral IV administration of phlebitis. The present study examines the incidence of phlebitis in a postoperative patient population given current dose recommendations. A total of 273 patient charts were reviewed. The incidence of phlebitis in patients given IV amiodarone (n = 36) was 13.9% (95% confidence interval, 2.6-25.2%; p = 0.001). Logistic regression analysis with backward elimination of other therapeutic risk factors suggests that the odds ratio for phlebitis using current dose regimens without IV filters is 19-fold greater than baseline risk in this population. Phlebitis remains a significant complication associated with peripheral infusion of amiodarone within recommended dosing limits.

Saving radiation dose and contrast media in intravenous digital subtraction angiography by use of bolus chasing

International Nuclear Information System (INIS)

Rueckforth, J.; Schuermann, K.; Vorwerk, D.; Guenther, R.W.

1998-01-01

Purpose: This study evaluates the dose area product, the amount of contrast media and the examination quality of the bolus chasing technique compared to the single-step technique in intravenous digital subtraction angiography. Material and Methods: 15 examinations each with bolus chasing and single-step technique were compared. The dose area product and the volume of contrast media were recorded. The examination quality was scored by two examiners. Results: With bolus chasing the volume of the administered contrast media could be decreased on average by 114 ml (43%). The difference between the dose area product of bolus chasing (722 dGy/cm 2 ) and single-step technique (1910 dGy/cm 2 ) was significant. No significant difference in examination quality was found. Conclusions: The intravenous bolus chasing technique is a practicable method. Compared to the single-step technique it allows a remarkable dose reduction and a low consumption of contrast media without restriction of examination quality. (orig.) [de

Efficacy of Single-dose and 2-dose Intravenous Administration of Ramosetron in Preventing Postoperative Nausea and Vomiting After Laparoscopic Gynecologic Operation: A Randomized, Double-blind, Placebo-controlled, Phase 2 Trial.

Science.gov (United States)

Lee, Banghyun; Kim, Kidong; Suh, Dong Hoon; Shin, Hyun-Jung; No, Jae Hong; Lee, Jung Ryeol; Jee, Byung Chul; Hwang, Jung Won; Do, Sang Hwan; Kim, Yong Beom

2017-06-01

This randomized trial investigated whether a 2-dose administration of intravenous ramosetron (5-hydroxytryptamine type 3 receptor antagonist) is more effective than a single-dose administration in preventing postoperative nausea and vomiting (PONV) in 89 patients who were scheduled to undergo laparoscopic operation for benign gynecologic diseases and to receive intravenous patient-controlled analgesia for relief of postoperative pain. After assignment at a ratio of 1:1, intravenous ramosetron (0.3 mg) was initially administered at the end of skin closure in all patients. Thereafter, ramosetron (0.3 mg) and placebo were administered to the study and control groups, respectively, at 4 hours after the operation. The baseline and operative characteristics were similar between the groups. The incidence of PONV during the 24-hour period after operation which was assessed as the primary endpoint did not differ between the groups. No serious adverse events occurred in either group. A 2-dose administration of intravenous ramosetron may not be superior to a single-dose administration in preventing PONV in patients undergoing laparoscopic operation for benign gynecologic diseases.

Development of biodegradable methylprednisolone microparticles for treatment of articular pathology using a spray-drying technique

Science.gov (United States)

Tobar-Grande, Blanca; Godoy, Ricardo; Bustos, Paulina; von Plessing, Carlos; Fattal, Elias; Tsapis, Nicolas; Olave, Claudia; Gómez-Gaete, Carolina

2013-01-01

In this work, microparticles were prepared by spray-drying using albumin, chondroitin sulfate, and hyaluronic acid as excipients to create a controlled-release methylprednisolone system for use in inflammatory disorders such as arthritis. Scanning electron microscopy demonstrated that these microparticles were almost spherical, with development of surface wrinkling as the methylprednisolone load in the formulation was increased. The methylprednisolone load also had a direct influence on the mean diameter and zeta potential of the microparticles. Interactions between formulation excipients and the active drug were evaluated by x-ray diffraction, differential scanning calorimetry, and thermal gravimetric analysis, showing limited amounts of methylprednisolone in a crystalline state in the loaded microparticles. The encapsulation efficiency of methylprednisolone was approximately 89% in all formulations. The rate of methylprednisolone release from the microparticles depended on the initial drug load in the formulation. In vitro cytotoxic evaluation using THP-1 cells showed that none of the formulations prepared triggered an inflammatory response on release of interleukin-1β, nor did they affect cellular viability, except for the 9.1% methylprednisolone formulation, which was the maximum test concentration used. The microparticles developed in this study have characteristics amenable to a therapeutic role in inflammatory pathology, such as arthritis. PMID:23737670

Effect of Admission Oral Diuretic Dose on Response to Continuous versus Bolus Intravenous Diuretics in Acute Heart Failure: An Analysis from DOSE-AHF

Science.gov (United States)

Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.

2014-01-01

Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486

Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department

OpenAIRE

Motov, Sergey; Drapkin, Jefferson; Likourezos, Antonios; Beals, Tyler; Monfort, Ralph; Fromm, Christian; Marshall, John

2018-01-01

Introduction: Our objective was to describe dosing, duration, and pre- and post-infusion analgesic administration of continuous intravenous sub-dissociative dose ketamine (SDK) infusion for managing a variety of painful conditions in the emergency department (ED).  Methods: We conducted a retrospective chart review of patients aged 18 and older presenting to the ED with acute and chronic painful conditions who received continuous SDK infusion in the ED for a pe...

Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

NARCIS (Netherlands)

P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

2005-01-01

textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

A Comparative Study on the Efficacy of Submucosal Injection of Dexamethasone Versus Methylprednisolone in Reducing Postoperative Sequelae After Third Molar Surgery.

Science.gov (United States)

Lim, Daniel; Ngeow, Wei Cheong

2017-11-01

To compare the efficacy of preoperative submucosal injection of 4 mg of dexamethasone versus 40 mg of methylprednisolone in reducing postoperative sequelae after surgical removal of impacted mandibular third molars. This prospective, randomized, double-blind study included 65 patients who required surgical removal of impacted mandibular third molars with Class II or position B impaction (Pell and Gregory classification). Patients were randomly assigned to 1 of 3 groups: dexamethasone, methylprednisolone, or placebo (control). Surgery was performed with patients under local anesthesia. Baseline measurements were obtained preoperatively, and subsequent assessments were made on postoperative day 1, 2, 5, and 7 to measure postoperative facial swelling by use of 2 linear measurements: interincisal mouth opening width and visual analog scale score for pain. The amount of analgesics consumed was recorded. Wound healing also was assessed on postoperative day 7. Descriptive and multivariate statistics were computed, and significance was set at P Kruskal-Wallis test), whereas the methylprednisolone group had significantly less pain (P Kruskal-Wallis test) and consumed a lower amount of analgesics (P test) during the early postoperative days. The study findings suggest that a single preoperative dose of dexamethasone versus methylprednisolone was equally effective in reducing postoperative swelling and trismus. Pain control by these corticosteroids, however, was variable. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Clonidine as an adjunct to intravenous regional anesthesia: A randomized, double-blind, placebo-controlled dose ranging study

Directory of Open Access Journals (Sweden)

Clarence S Ivie

2011-01-01

Full Text Available Background : The addition of clonidine to lidocaine intravenous regional anesthesia (IVRA has been previously reported to improve postoperative analgesia in patients undergoing upper extremity surgery. Our objective was to perform a dose ranging study in order to determine the optimal dose of clonidine used with lidocaine in IVRA. Design & Setting : We performed a double-blinded randomized placebo-controlled study with 60 patients scheduled for elective endoscopic carpal tunnel release under IVRA with 50 ml lidocaine 0.5%. University-affiliated outpatient surgery center. Data collected in operating rooms, recovery room, and by telephone after discharge from surgery center. Materials & Methods : Sixty adult ASA I or II patients undergoing outpatient endoscopic carpal tunnel release under intravenous regional anesthesia.Patients were randomized into five study groups receiving different doses of clonidine in addition to 50 ml 0.5% lidocaine in their IVRA. Group A received 0 mcg/kg, group B 0.25 mcg/kg, group C 0.5 mcg/kg, group D 1.0 mcg/kg and group E 1.5 mcg/kg of clonidine.Intraoperative fentanyl, recovery room pain scores, time to first postsurgical analgesic, total number of acetaminophen/codeine tablets consumed postsurgery, incidence of sedation, hypotension and bradycardia. Results & Conclusions : There was no benefit from any dose of clonidine compared to placebo. There were no clonidine-related side effects seen within the dose range studied. In short duration minor hand surgery, the addition of clonidine to lidocaine-based intravenous regional anesthesia provides no measurable benefit.

Split high-dose oral levothyroxine treatment as a successful therapy option in myxedema coma.

Science.gov (United States)

Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

2017-10-01

High-dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69-year-old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high-dose oral LT4 as a therapeutic option in myxedema coma.

Physical and chemical stability of palonosetron hydrochloride with dacarbazine and with methylprednisolone sodium succinate during simulated y-site administration.

Science.gov (United States)

Trissel, Lawrence A; Zhang, Yanping; Xu, Quanyun A

2006-01-01

The objective of this study was to evaluate the physical and chemical stability of mixtures of undiluted palonosetron hydrochloride 50 micrograms/mL with dacarbazine 4 mg/mL and with methylprednisolone sodium succinate 5 mg/mL in 5% dextrose injection during simulated Y-site administration. Triplicate test samples were prepared by admixing 7.5 mL of palonosetron hydrochloride with 7.5 mL of dacarbazine solution and, separately, methylprednisolone sodium succinate solution. Physical stability was assessed by using a multistep evaluation procedure that included both turbidimetric and particulate measurement as well as visual inspection. Chemical stability was assessed by using stability-indicating high-performance liquid chromatographic analytical techniques that determined drug concentrations. Evaluations were performed immediately after mixing and 1 and 4 hours after mixing. The palonosetron hydrochloride-dacarbazine samples were clear and colorless when viewed in normal fluorescent room light and when viewed with a Tyndall beam. Measured turbidities remained unchanged; particulate contents were low and exhibited little change. High-performance liquid chromatography analysis revealed that palonosetron hydrochloride and dacarbazine remained stable throughout the 4-hour test with no drug loss. Palonosetron hydrochloride is, therefore, physically compatible and chemically stable with dacarbazine during Y-site administration. Within 4 hours, the mixtures of palonosetron hydrochloride and methylprednisolone sodium succinate developed a microprecipitate that became a white precipitate visible to the unaided eye. The precipitate was analyzed and identified as methylprednisolone. Palonosetron hydrochloride is incompatible with methylprednisolone sodium succinate.

Prolonged high-dose intravenous magnesium therapy for severe tetanus in the intensive care unit: a case series

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Fligou Fotini

2010-03-01

Full Text Available Abstract Introduction Tetanus rarely occurs in developed countries, but it can result in fatal complications including respiratory failure due to generalized muscle spasms. Magnesium infusion has been used to treat spasticity in tetanus, and its effectiveness is supported by several case reports and a recent randomized controlled trial. Case presentations Three Caucasian Greek men aged 30, 50 and 77 years old were diagnosed with tetanus and admitted to a general 12-bed intensive care unit in 2006 and 2007 for respiratory failure due to generalized spasticity. Intensive care unit treatment included antibiotics, hydration, enteral nutrition, early tracheostomy and mechanical ventilation. Intravenous magnesium therapy controlled spasticity without the need for additional muscle relaxants. Their medications were continued for up to 26 days, and adjusted as needed to control spasticity. Plasma magnesium levels, which were measured twice a day, remained in the 3 to 4.5 mmol/L range. We did not observe hemodynamic instability, arrhythmias or other complications related to magnesium therapy in these patients. All patients improved, came off mechanical ventilation, and were discharged from the intensive care unit in a stable condition. Conclusion In comparison with previous reports, our case series contributes the following meaningful additional information: intravenous magnesium therapy was used on patients already requiring mechanical ventilation and remained effective for up to 26 days (significantly longer than in previous reports without significant toxicity in two patients. The overall outcome was good in all our patients. However, the optimal dose, optimal duration and maximum safe duration of intravenous magnesium therapy are unknown. Therefore, until more data on the safety and efficacy of magnesium therapy are available, its use should be limited to carefully selected tetanus cases.

Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

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Gabardi, Steven; Catella, Jennifer; Martin, Spencer T; Perrone, Ronald; Chandraker, Anil; Magee, Colm C; McDevitt-Potter, Lisa M

2011-09-01

To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation. The first patient is a 52-year-old female with a history of intolerance to calcineurin inhibitors (CNIs) and sirolimus. Following her second transplant, the patient received mycophenolate mofetil 100 mg twice daily, a tapering corticosteroid regimen (initial dose of methylprednisolone 500 mg tapered over 1 week to prednisone 30 mg/day), and biweekly intravenous daclizumab 1-1.2 mg/kg/dose; 33 months after transplant the IL-2RA was changed to intravenous basiliximab 40 mg once a month. At 40 months after transplant, the patient continued to have stable renal function (estimated glomerular filtration rate 48 mL/min/1.73 m²) with excellent tolerability. The second patient is a 59-year-old female also intolerant to CNIs and sirolimus who required intermittent maintenance therapy with intravenous basiliximab 20 mg/dose. Despite an initial rejection episode, the patient tolerated more than 2 years of basiliximab therapy with good renal function (estimated glomerular filtration rate 103 months after transplant 69 mL/min/1.73 m²) and no adverse events. The IL-2RAs basiliximab and daclizumab possess several characteristics of ideal maintenance immunosuppressive agents (ie, nondepleting, long half-lives, limited adverse events). Based on a MEDLINE search (through December 31, 2010) using the search terms basiliximab, daclizumab, organ transplant, immunosuppression, and/or maintenance immunosuppression, and an advanced search in the published abstracts from the American Transplant Congress and World Transplant Congress (2000-2010), it appears that IL-2RAs have been used successfully as short-term therapy in both renal and extrarenal transplant recipients to allow for renal recovery following CNI-induced nephrotoxicity. In heart transplant recipients, the IL-2

Experimental study of effectiveness of local application of electroneurostimulation, cortexin and methylprednisolone in acute spinal cord injury

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Tsymbaliuk V.I.

2014-09-01

Full Text Available The tasks were to investigate the effect of topical electroneurostimulation, cortexin and methy¬lprednisolone in acute spinal cord injury in electrophysiological experiments on laboratory rats. The animals un¬derwent half transection of the spinal cord in the lower-thoracic area to simulate Brown-Sequard’s syndrome. Drugs were administered subdurally once daily in the dose of 0.03 mg for cortexin and 0.7 mg for methylprednisolone during 72 hours. Electrophysiological studies were carried out using standard electrophysiological apparatus. Reliable changes of bioelectric indicators in neuromuscular complex during topical application of electrical stimulation, as well as in administered methylprednisolone, failed to be found. However, local application of cortexin in terms of traumatic spinal cord injury due the antioxidant and neurotrophic effect results in improvement of bioelectrical indicators; this is manifested in reliable (p<0.05 increase of amplitude of the background electromyogram impulses at rest by 33% and increase of spontaneous oscillations frequency by 29.82%.

Effect of pre-operative methylprednisolone on orthostatic hypotension during early mobilization after total hip arthroplasty

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Lindberg-Larsen, V; Petersen, P B; Jans, Ø

2018-01-01

a standardized mobilization protocol pre-operatively, 6, and 24 h after surgery. Systolic and diastolic arterial pressure and heart rate were measured non-invasively (Nexfin® ). The systemic inflammation was monitored by the C-reactive protein (CRP) response. RESULTS: At 6 h post-operatively, 11 (38%) versus 11......BACKGROUND: Orthostatic hypotension (OH) and intolerance (OI) are common after total hip arthroplasty (THA) and may delay early mobilization. The pathology of OH and OI includes a dysregulated post-operative vasopressor response, by a hitherto unknown mechanism. We hypothesized that OI could...... be related to the inflammatory stress response which is inhibited by steroid administration. Consequently, this study evaluated the effect of a pre-operative high-dose methylprednisolone on OH and OI early after THA. METHODS: Randomized, double-blind, placebo-controlled study in 59 patients undergoing...

[Directions for use of corticosteroids and calcineurin inhibitors against generalized myasthenia gravis: therapeutic strategies that can lead to early improvements and veer away from high-dose oral corticosteroids].

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Utsugisawa, Kimiaki; Nagane, Yuriko; Suzuki, Shigeaki; Suzuki, Norihiro

2012-01-01

The advent of effective immune treatment has meant that myasthenia gravis (MG) is most often not lethal. However, many MG patients still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of medication, since full remission without immune treatment is not common. Our analysis demonstrated that disease severity, dose of oral corticosteroids, and depressive state are the major independent factors negatively associated with self-reported QOL (MG-QOL15-J score). It is noteworthy that oral corticosteroid, the first-line agent for MG, is negatively associated with patients' QOL. When the analysis took into account MGFA postintervention status and dose of oral prednisolne (PSL), the MG-QOL15-J score of MM status patients taking ≤ 5 mg PSL per day is identically low (i.e., just as good QOL) as that seen in CSR and is a target of treatment. In order to veer away from high-dose oral corticosteroids and to achieve early MM or better status with PSL ≤ 5 mg/day, we advocate the early aggressive treatment strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved clinical status using low-dose oral corticosteroids and calcineurin inhibitors (cyclosporine microemulsion and tacrolimus). The early stages of MG are susceptible to treatment with calcineurin inhibitors. When using cyclosporine microemulsion for MG, blood concentrations 2 h after administration (C2) correlate with clinical improvement and immediately before administration (C0) with side effects (increased serum creatinine and/or hypertension). Monitoring of C2 and C0 levels is useful to estimate efficacy and safety of the drug.

Effect of high-dose preoperative methylprednisolone on pain and recovery after total knee arthroplasty: a randomized, placebo-controlled trial

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Lunn, Troels; Kristensen, Billy Bjarne; Andersen, Lasse

2011-01-01

Total knee arthroplasty (TKA) is associated with severe pain and inflammation despite an extensive multimodal analgesic approach, but the effect of high-dose glucocorticoid administration has not been studied.......Total knee arthroplasty (TKA) is associated with severe pain and inflammation despite an extensive multimodal analgesic approach, but the effect of high-dose glucocorticoid administration has not been studied....

A randomised comparative study of the short term clinical and biological effects of intravenous pulse methylprednisolone and infliximab in patients with active rheumatoid arthritis despite methotrexate treatment.

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Durez, P; Nzeusseu Toukap, A; Lauwerys, B R; Manicourt, D H; Verschueren, P; Westhovens, R; Devogelaer, J-P; Houssiau, F A

2004-09-01

To compare the short term clinical and biological effects of intravenous (i.v.) pulse methylprednisolone (MP) and infliximab (IFX) in patients with severe active rheumatoid arthritis (RA) despite methotrexate (MTX) treatment. Patients with active RA despite MTX treatment were randomly allocated to receive a single i.v. infusion of MP (1 g) or three i.v. infusions of IFX (3 mg/kg) on weeks 0, 2, and 6. Patients were "blindly" evaluated for disease activity measures. Quality of life (QoL) was evaluated through the SF-36 health survey. Serum matrix metalloproteinase-3 (MMP-3) titres were measured at baseline, weeks 2 and 6. Compared with baseline, significant improvement was noted in all activity measures, including serum C reactive protein (CRP) titres, in the IFX group only. At week 14, 6/9 (67%) and 4/9 (44%) IFX patients met the ACR20 and 50 response criteria, while this was the case in only 1/12 (8%) and 0/12 (0%) MP patients, respectively (ptreatment, whereas some did so in the IFX group. Serum MMP-3 titres significantly decreased (41% drop) at week 6 in the IFX group, while no changes were seen in patients given MP. This short term randomised comparative study demonstrates that TNF blockade is better than MP pulse therapy in a subset of patients with severe refractory RA, with improvement in not only clinical parameters of disease activity but also biological inflammatory indices, such as serum CRP and MMP-3 titres.

The route of administration (oral vs intravenous) does not influence dose or outcome in Graves' disease and unifocal autonomy

International Nuclear Information System (INIS)

Schneider, Peter; Biko, Johannes; Haenscheid, Heribert; Hilliger, Stephan; Koutsampelas, Christos; Kranzfelder, Michael; Ladner, Stephan; Reiners, Christoph

2005-01-01

In a prospective randomised study, we investigated the influence of the route of administration of radioiodide on dosimetry and therapy outcome. Fifty-four patients suffering from Graves' disease (GD) and 60 patients with unifocal autonomy (UA) participated in the study and were randomly treated with either orally or intravenously administered radioiodide. Pretherapeutic dosimetry was based on single uptake measurements with a calibrated uptake probe system. The radioiodine kinetics during hospitalisation was assessed by daily bedside uptake measurements. Therapeutic dose was determined by half-life and thyroid uptake at the time of discharge using the same uptake probe as for the radioiodine test. No improvement in accuracy of dosimetry was achieved when radioiodide was administered intravenously. Mean therapeutic doses were identical following intravenous or oral administration. Variation in the achieved dose was slightly higher in the patients receiving oral administration, this being attributable to larger deviations in discrete activities of the capsules administered as compared with the values determined by dosimetry. No differences according to treatment modality were found with regard to therapeutic outcome. Eighty-seven patients attended 6-month follow-up after therapy. In the UA group, successful treatment, defined as a normal or elevated TSH level, was observed in 94% of patients after oral administration and in 80% after intravenous administration; corresponding figures in the GD group were 68% and 65%. The causes of individual differences between targeted and therapeutically achieved doses remain undetermined. Variations in the bioavailability of radioiodide or other parameters affecting thyroid status may be involved, and further investigations are needed to clarify this. (orig.)

Development of biodegradable methylprednisolone microparticles for treatment of articular pathology using a spray-drying technique

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Tobar-Grande B

2013-05-01

Full Text Available Blanca Tobar-Grande,1 Ricardo Godoy,1 Paulina Bustos,2 Carlos von Plessing,1 Elias Fattal,3,4 Nicolas Tsapis,3,4 Claudia Olave,1 Carolina Gómez-Gaete11Departamento de Farmacia, Facultad de Farmacia, Universidad de Concepción, Concepción, Chile; 2Departamento de Bioquímica Clínica e Inmunología, Facultad de Farmacia, Universidad de Concepción, Concepción, Chile; 3Univ Paris-Sud, Institut Galien Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France; 4CNRS, UMR 8612, Faculté de Pharmacie, Châtenay-Malabry, FranceAbstract: In this work, microparticles were prepared by spray-drying using albumin, chondroitin sulfate, and hyaluronic acid as excipients to create a controlled-release methylprednisolone system for use in inflammatory disorders such as arthritis. Scanning electron microscopy demonstrated that these microparticles were almost spherical, with development of surface wrinkling as the methylprednisolone load in the formulation was increased. The methylprednisolone load also had a direct influence on the mean diameter and zeta potential of the microparticles. Interactions between formulation excipients and the active drug were evaluated by x-ray diffraction, differential scanning calorimetry, and thermal gravimetric analysis, showing limited amounts of methylprednisolone in a crystalline state in the loaded microparticles. The encapsulation efficiency of methylprednisolone was approximately 89% in all formulations. The rate of methylprednisolone release from the microparticles depended on the initial drug load in the formulation. In vitro cytotoxic evaluation using THP-1 cells showed that none of the formulations prepared triggered an inflammatory response on release of interleukin-1ß, nor did they affect cellular viability, except for the 9.1% methylprednisolone formulation, which was the maximum test concentration used. The microparticles developed in this study have characteristics amenable to a therapeutic role in

Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department

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Jefferson Drapkin

2018-03-01

Full Text Available Introduction: Our objective was to describe dosing, duration, and pre- and post-infusion analgesic administration of continuous intravenous sub-dissociative dose ketamine (SDK infusion for managing a variety of painful conditions in the emergency department (ED. Methods: We conducted a retrospective chart review of patients aged 18 and older presenting to the ED with acute and chronic painful conditions who received continuous SDK infusion in the ED for a period over six years (2010–2016. Primary data analyses included dosing and duration of infusion, rates of pre- and post-infusion analgesic administration, and final diagnoses. Secondary data included pre- and post-infusion pain scores and rates of side effects. Results: A total of 104 patients were enrolled in the study. Average dosing of SDK infusion was 11.26 mg/hr, and the mean duration of infusion was 135.87 minutes. There was a 38% increase in patients not requiring post-infusion analgesia. The average decrease in pain score was 5.04. There were 12 reported adverse effects, with nausea being the most prevalent. Conclusion: Continuous intravenous SDK infusion has a role in controlling pain of various etiologies in the ED with a potential to reduce the need for co-analgesics or rescue analgesic administration. There is a need for more robust, prospective, randomized trials that will further evaluate the analgesic efficacy and safety of this modality across a wide range of pain syndromes and different age groups in the ED.

Atorvastatin calcium in combination with methylprednisolone for the treatment of multiple sclerosis relapse.

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Li, Xiao-ling; Zhang, Zhen-chang; Zhang, Bo; Jiang, Hua; Yu, Chun-mei; Zhang, Wen-jing; Yan, Xiang; Wang, Man-xia

2014-12-01

This study aimed to investigate the efficacy of combined atorvastatin calcium and methylprednisolone for the treatment of multiple sclerosis relapse. Patients with multiple sclerosis (MS) at the relapse phase were randomized to receive either combined treatment of atorvastatin calcium and methylprednisolone (n = 19) or methylprednisolone alone (n = 19). Expanded Disability Status Scale (EDSS) was administered at baseline, 1 week, 2 weeks, 4 weeks, 3 months, and 6 months after treatment initiation. The number and volume of brain lesions were evaluated using magnetic resonance imaging at baseline and 6 months. The levels of IL-13, IL-35, IFN-γ, and IL-10 in the cerebrospinal fluid were examined using the enzyme-linked immunosorbent assay method. There was no significant difference in EDSS scores at 1, 2, and 4 weeks. At 3 and 6 months, the combined treatment group showed significantly lower EDSS scores than the monotherapy group (P atorvastatin calcium and methylprednisolone can improve the outcomes of MS relapse compared with glucocorticosteroid alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate.

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Jia, Minghong; Coats, Bonnie; Chadha, Monisha; Frentzen, Barbara; Perez-Rodriguez, Javier; Chadik, Paul A; Yost, Richard A; Henderson, George N; Stacpoole, Peter W

2006-12-01

Dichloroacetate (DCA) is a putative environmental hazard, owing to its ubiquitous presence in the biosphere and its association with animal and human toxicity. We sought to determine the kinetics of environmentally relevant concentrations of 1,2-(13)C-DCA administered to healthy adults. Subjects received an oral or intravenous dose of 2.5 microg/kg of 1,2-(13)C-DCA. Plasma and urine concentrations of 1,2-(13)C-DCA were measured by a modified gas chromatography-tandem mass spectrometry method. 1,2-(13)C-DCA kinetics was determined by modeling using WinNonlin 4.1 software. Plasma concentrations of 1,2-(13)C-DCA peaked 10 minutes and 30 minutes after intravenous or oral administration, respectively. Plasma kinetic parameters varied as a function of dose and duration. Very little unchanged 1,2-(13)C-DCA was excreted in urine. Trace amounts of DCA alter its own kinetics after short-term exposure. These findings have important implications for interpreting the impact of this xenobiotic on human health.

Effect of treatment with single total-dose intravenous iron versus daily oral iron(III-hydroxide polymaltose on moderate puerperal iron-deficiency anemia

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Iyoke CA

2017-05-01

Full Text Available Chukwuemeka Anthony Iyoke,1 Fausta Chioma Emegoakor,1 Euzebus Chinonye Ezugwu,1 Lucky Osaheni Lawani,2 Leonard Ogbonna Ajah,1 Jude Anazoeze Madu,3 Hyginus Uzo Ezegwui,1 Frank Okechukwu Ezugwu4 1Department of Obstetrics and Gynaecology, University of Nigeria, Enugu Campus, 2Department of Obstetrics and Gynaecology, Federal Teaching Hospital, Abakaliki, 3Department of Haematology, University of Nigeria, Nsukka, 4Department of Obstetrics and Gynaecology, College of Medicine, Enugu State University, Enugu, Nigeria Background: Iron-deficiency anemia is the most common nutritional cause of anemia in pregnancy and is often responsible for puerperal anemia. Puerperal anemia can impair postpartum maternal and neonatal well-being. Objective: To determine the effect of treatment of moderate puerperal iron-deficiency anemia using a single intravenous total-dose iron dextran versus daily single dose oral iron(III-hydroxide polymaltose. Methodology: A randomized controlled study in which postpartum women with moderate iron-deficiency anemia were randomized into treatment with either a single total-dose intravenous iron dextran or with daily single doses of oral iron(III-hydroxide polymaltose tablets for 6 weeks. Effects on hemoglobin concentration using either method were compared at 6 weeks postpartum. Analysis was per protocol using SPSS version 17 for windows. P-values ≤0.05 were considered significant. Results: Two hundred eighty-four women were recruited for the study: 142 women received single total dose intravenous infusion of iron dextran while 142 received daily oral iron(III-hydroxide polymaltose tablets. Approximately 84.0% (237/282 completed the study and were analyzed including 81% (115/142 of those randomized to injectable iron therapy compared to 85.9% (122/142 of those randomized to oral treatment. The proportions of women who had attained hemoglobin concentration of at least 10 g/dL by the 6 weeks postpartum visit did not differ

Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage: study protocol for a randomised controlled trial.

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Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid; Langhoff-Roos, Jens

2015-01-14

Postpartum haemorrhage can lead to iron deficiency with and without anaemia, the clinical consequences of which include physical fatigue. Although oral iron is the standard treatment, it is often associated with gastrointestinal side effects and poor compliance. To date, no published randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside 1000 with standard medical care on physical fatigue in women with postpartum haemorrhage. In a single centre, open-labelled, randomised trial, women with postpartum haemorrhage exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron isomaltoside 1000 or standard medical care. Healthy parturients with a singleton pregnancy will be included within 48 hours after delivery.Participants will complete structured questionnaires that focus on several dimensions of fatigue and mental health (Multidimensional Fatigue Inventory, Edinburgh Postnatal Depression Scale and the Postpartum Questionnaire), at inclusion and at follow-up visits after three days, one week, three weeks, eight weeks, and 12 weeks postpartum. The primary endpoint is the aggregated change in physical fatigue score within 12 weeks postpartum, as measured by a subscale of the Multidimensional Fatigue Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant difference between the mean scores at 1.8, and the assumed standard deviation at 4.2. Hence, 87 participants per treatment group are needed in order to demonstrate superiority; to provide an extra margin

Influence of intravenous contrast agent on dose calculations of intensity modulated radiation therapy plans for head and neck cancer

International Nuclear Information System (INIS)

Choi, Youngmin; Kim, Jeung-Kee; Lee, Hyung-Sik; Hur, Won-Joo; Hong, Young-Seoub; Park, Sungkwang; Ahn, Kijung; Cho, Heunglae

2006-01-01

Background and purpose: To evaluate the effect of an intravenous contrast agent (CA) on dose calculations and its clinical significance in intensity modulated radiation therapy (IMRT) plans for head and neck cancer. Materials and methods: Fifteen patients with head and neck cancer and involved neck nodes were enrolled. Each patient took two sets of computerized tomography (CT) in the same position before and after intravenous CA injections. Target volumes and organs at risk (OAR) were contoured on the enhanced CT, and then an IMRT plan of nine equiangular beams with a 6 MV X-ray was created. After the fusion of non-enhanced and enhanced CTs, the contours and the IMRT plan created from the enhanced CT were copied and placed to the non-enhanced CT. Doses were calculated again from the non-enhanced CT by the same IMRT plan. The radiation doses calculated from the two sets of CTs were compared with regard to planning target volumes (PTV) and the three OARs, both parotid glands and the spinal cord, by Wilcoxon's signed rank test. Results: The doses (maximum, mean, and the dose of 95% of PTV received (D 95% )) of PTV70 and PTV59.4 calculated from the enhanced CTs were lower than those from the non-enhanced CTs (p < 0.05), but the dose differences were less than 1% compared to the doses calculated from the enhanced CTs. The doses of PTV50.4, parotid glands, and spinal cord were not significantly different between the non-enhanced and enhanced CTs. Conclusions: The difference between the doses calculated from the CTs with and without CA enhancement was tolerably small, therefore using intravenous CA could be recommended for the planning CT of head and neck IMRT

Dose-dependent effects of intravenous lorazepam on cardiovascular activity, plasma catecholamines and psychological function during rest and mental stress

NARCIS (Netherlands)

J.H.M. Tulen (Joke); P. Moleman (Peter); F. Boomsma (Frans); H.G. van Steenis (H.); V.J.H.M. van den Heuij (Venantius)

1991-01-01

textabstractDose-dependent effects of intravenously administered lorazepam on psychophysiological activity during rest and mental stress were studied in order to examine differential responses to doses which may induce anxiolysis or sedation. In a double-blind randomized cross-over study, nine male

Iron concentration in breast milk normalised within one week of a single high-dose infusion of iron isomaltoside in randomised controlled trial

DEFF Research Database (Denmark)

Holm, Charlotte; Thomsen, Lars Lykke; Nørgaard, Astrid

2017-01-01

AIM: We compared the iron concentration in breast milk after a single high-dose of intravenous iron isomaltoside or daily oral iron for postpartum haemorrhage. METHODS: In this randomised controlled trial, the women were allocated a single dose of intravenous 1,200mg iron isomaltoside or oral iron...... deviation) iron concentration in breast milk in the intravenous and oral groups were 0.72 ± 0.27 mg/L and 0.40 ± 0.18 mg/L at three days (p birth. CONCLUSION: A single high...

Disability Surveillance in multiple sclerosis patients before and after methylprednisolone treatment

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Ghabaae M

2007-10-01

Full Text Available Background: Multiple sclerosis (MS is a chronic inflammatory disease of the central nervous system resulting from demyelination and axonal loss. Although treatment of MS has progressed, patients continue to have attacks and treatment for such episodes remains a subject of ongoing study. The object of this study is to determine the effect of intravenous methylprednisolone (IVMP on the degree of disability in MS patients."nMethods: This cross-sectional study involved 63 patients with a definite diagnosis of MS, based on the MacDonald criteria, at the Iranian Center for Neurological Research at Imam Khomeini Hospital, Tehran, Iran, from March 2004 through March 2005. After obtaining informed consent, investigators gathered data including each patient's age, gender, pyramidal activity status, cortical, cerebellar and brain stem activity status, sensory signals in the extremities, including vibration, touch, pain, position, visual status, as well as bladder and intestinal activity, and Expanded Disability Status Scale (EDSS score. SPSS version 11 was used for data analysis."nResults: A five-day regimen of IVMP (5g significantly reduced the immediate post-treatment score from 4.595 to 3.635, which represents a 96% improvement in the EDSS. The greatest change in functional system disability was seen in the pyramidal system with a mean score of 1.13. After treatment, the rate of disability reduction in the sensory system, cerebellum, vision, bladder and intestinal activity was 0.57, 0.49, 0.46, 0.4, and 0.38, respectively. Patients who had experienced fewer relapses responded better to treatment. There was no statistically significant relationship between patient age and the level of response to treatment. However, the rate of disability reduction after treatment was greater in males than females (p=0.05."nConclusion: These results show that IVMP treatment induces an immediate post-treatment effect that could partly account for clinical and

Pharmacokinetics of [14C]teicoplanin in male rats after single intravenous dose

International Nuclear Information System (INIS)

Bernareggi, A.; Cavenaghi, L.; Assandri, A.

1986-01-01

The pharmacokinetic profile of [ 14 C]teicoplanin was studied in male Sprague-Dawley rats given a single 10,000-U/kg intravenous dose. The disposition of the antimicrobial activity in the body was estimated by a three-compartment open model. Plasma concentration data were fitted to a three-exponent equation. The profile of total 14 C in plasma was similar to that of the microbiological activity. The cumulative recovery of total 14 C 5 days after drug administration averaged 76.3% of the administered dose in the urine and 8.7% in the feces. The residual dose remaining in the animal carcasses was 11.1%. Teicoplanin was widely distributed in the body. In almost all organs, the maximum concentration of [ 14 C]teicoplanin was already reached at the first time of killing, which was 0.25 h after the administration of drug. The liver, kidneys, skin, and fat contained most of the residual dose found in the animal carcasses 120 h after administration and behaved as a deep compartment with the adrenal glands and spleen

Pharmacokinetic Effects of Antidrug Antibodies Occurring in Healthy Subjects After a Single Dose of Intravenous Infliximab.

Science.gov (United States)

Ehrenpreis, Eli D

2017-12-01

Infliximab pharmacokinetic studies have been performed in patients receiving chronic infliximab therapy. In these patients, infliximab antidrug antibodies (ADAs) increase infliximab clearance and decrease serum levels and drug efficacy. This study analyzed the pharmacokinetic effect of infliximab ADAs in healthy subjects receiving a single dose of intravenous infliximab. Data were obtained from a single-blind, parallel-group, single-dose study of healthy subjects receiving 5 mg/kg of intravenous SB2 (infliximab biosimilar), EU-sourced Remicade (EU-IFX) or US-sourced Remicade (US-IFX). Serum infliximab was measured at 1, 2, 3, 6, 12, 24, 48, and 72 h and at 5, 7, 14, 21, 28, 42, 56, and 70 days after administration. ADAs were measured pre-dose and at 29 and 71 days. Data from the first ten subjects randomized to each treatment arm were utilized for this study. A two-compartment model of the serum infliximab vs. time curve was developed using nonlinear regression. At 10 weeks, 11 subjects (37%) developed ADAs. ADAs were detected in four subjects after SB2, one subject after EU-IFX, and six subjects after US-IFX infusion. Of these, neutralizing antibodies occurred in one subject after SB2, in no subjects after EU-IFX, and in three subjects after US-IFX infusion. Infliximab clearance was increased in subjects with ADAs vs. those without ADAs (12.89 ± 2.69 vs. 9.90 ± 1.74 ml/h; p ADAs (282.4 ± 56.4 vs. 343.3 ± 61.9 h; p ADAs are common in healthy subjects after a single intravenous dose of infliximab and result in faster infliximab clearance, shorter elimination time, and lower serum infliximab levels. These data confirm that ADAs are common with biologic therapy and significantly impact the efficacy of these drugs.

Granulocyte Colony-Stimulating Factor Combined with Methylprednisolone Improves Functional Outcomes in Rats with Experimental Acute Spinal Cord Injury

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William Gemio Jacobsen Teixeira

2018-02-01

Full Text Available OBJECTIVES: To evaluate the effects of combined treatment with granulocyte colony-stimulating factor (G-CSF and methylprednisolone in rats subjected to experimental spinal cord injury. METHODS: Forty Wistar rats received a moderate spinal cord injury and were divided into four groups: control (no treatment; G-CSF (G-CSF at the time of injury and daily over the next five days; methylprednisolone (methylprednisolone for 24 h; and G-CSF/Methylprednisolone (methylprednisolone for 24 h and G-CSF at the time of injury and daily over the next five days. Functional evaluation was performed using the Basso, Beattie and Bresnahan score on days 2, 7, 14, 21, 28, 35 and 42 following injury. Motor-evoked potentials were evaluated. Histological examination of the spinal cord lesion was performed immediately after euthanasia on day 42. RESULTS: Eight animals were excluded (2 from each group due to infection, a normal Basso, Beattie and Bresnahan score at their first evaluation, or autophagy, and 32 were evaluated. The combination of methylprednisolone and G-CSF promoted greater functional improvement than methylprednisolone or G-CSF alone (p<0.001. This combination also exhibited a synergistic effect, with improvements in hyperemia and cellular infiltration at the injury site (p<0.001. The groups displayed no neurophysiological differences (latency p=0.85; amplitude p=0.75. CONCLUSION: Methylprednisolone plus G-CSF promotes functional and histological improvements superior to those achieved by either of these drugs alone when treating spinal cord contusion injuries in rats. Combining the two drugs did have a synergistic effect.

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.

Intravenous Iron Therapy in Patients with Iron Deficiency Anemia: Dosing Considerations

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Todd A. Koch

2015-01-01

Full Text Available Objective. To provide clinicians with evidence-based guidance for iron therapy dosing in patients with iron deficiency anemia (IDA, we conducted a study examining the benefits of a higher cumulative dose of intravenous (IV iron than what is typically administered. Methods. We first individually analyzed 5 clinical studies, averaging the total iron deficit across all patients utilizing a modified Ganzoni formula; we then similarly analyzed 2 larger clinical studies. For the second of the larger studies (Study 7, we also compared the efficacy and retreatment requirements of a cumulative dose of 1500 mg ferric carboxymaltose (FCM to 1000 mg iron sucrose (IS. Results. The average iron deficit was calculated to be 1531 mg for patients in Studies 1–5 and 1392 mg for patients in Studies 6-7. The percentage of patients who were retreated with IV iron between Days 56 and 90 was significantly (p<0.001 lower (5.6% in the 1500 mg group, compared to the 1000 mg group (11.1%. Conclusions. Our data suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in a majority of patients with IDA and a dose of 1500 mg is closer to the actual iron deficit in these patients.

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

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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.

Distribution of 14C-lindane in the rat after a single dose intraperitoneal and intravenous injection

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Lievremont, Maurice; Le Flohic, J.-F.; Pascaud, Marc

1981-01-01

14 C-Lindane retentions in rat tissues were studied until 24 hrs after a single dose pesticide administration. Each organ shows particular kinetics. Adipose tissue is the most active in pesticide fixation but the lungs retain momentarily a large fraction of Lindane after intravenous injection [fr

Megadose Methylprednisolone (MDMP Treatment in a Patient with Autoimmune Hemolytic Anemia (AIHA Resistant to Conventional Corticosteroid Administration: A Case Report

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Şinasi Özsoylu

2013-06-01

Full Text Available A female in the Netherlands with severe autoimmune hemolytic anemia (AIHA was treated with conventional corticosteroid (2 mg/kg/d in divided doses and blood transfusions for 18 months without improvement. The presented patient responded to megadose methylprednisolone (MDMP 30 mg/kg/d for 3 d, followed by 20 mg/kg for 4 d, and subsequently 10, 5, 2, and 1 mg/kg/d each for 1 week.

Methylprednisolone promotes recovery of neurological function after spinal cord injury: association with Wnt/β-catenin signaling pathway activation

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Lu, Gong-biao; Niu, Fu-wen; Zhang, Ying-chun; Du, Lin; Liang, Zhi-yuan; Gao, Yuan; Yan, Ting-zhen; Nie, Zhi-kui; Gao, Kai

2016-01-01

Some studies have indicated that the Wnt/β-catenin signaling pathway is activated following spinal cord injury, and expression levels of specific proteins, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β, are significantly altered. We hypothesized that methylprednisolone treatment contributes to functional recovery after spinal cord injury by inhibiting apoptosis and activating the Wnt/β-catenin signaling pathway. In the current study, 30 mg/kg methylprednisolone was injected into rats with spinal cord injury immediately post-injury and at 1 and 2 days post-injury. Basso, Beattie, and Bresnahan scores showed that methylprednisolone treatment significantly promoted locomotor functional recovery between 2 and 6 weeks post-injury. The number of surviving motor neurons increased, whereas the lesion size significantly decreased following methylprednisolone treatment at 7 days post-injury. Additionally, caspase-3, caspase-9, and Bax protein expression levels and the number of apoptotic cells were reduced at 3 and 7 days post-injury, while Bcl-2 levels at 7 days post-injury were higher in methylprednisolone-treated rats compared with saline-treated rats. At 3 and 7 days post-injury, methylprednisolone up-regulated expression and activation of the Wnt/β-catenin signaling pathway, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β phosphorylation. These results indicate that methylprednisolone-induced neuroprotection may correlate with activation of the Wnt/β-catenin signaling pathway. PMID:28123427

Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs

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Ronaldo Lopes Torres

2014-06-01

Full Text Available Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO and total reactive antioxidant potential (TRAP, in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.; acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days; and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels.

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

Methylprednisolone as a memory enhancer in rats: Effects on aversive memory, long-term potentiation and calcium influx.

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de Vargas, Liane da Silva; Gonçalves, Rithiele; Lara, Marcus Vinícius S; Costa-Ferro, Zaquer S M; Salamoni, Simone Denise; Domingues, Michelle Flores; Piovesan, Angela Regina; de Assis, Dênis Reis; Vinade, Lucia; Corrado, Alexandre P; Alves-Do-Prado, Wilson; Correia-de-Sá, Paulo; da Costa, Jaderson Costa; Izquierdo, Ivan; Dal Belo, Cháriston A; Mello-Carpes, Pâmela B

2017-09-01

It is well recognized that stress or glucocorticoids hormones treatment can modulate memory performance in both directions, either impairing or enhancing it. Despite the high number of studies aiming at explaining the effects of glucocorticoids on memory, this has not yet been completely elucidated. Here, we demonstrate that a low daily dose of methylprednisolone (MP, 5mg/kg, i.p.) administered for 10-days favors aversive memory persistence in adult rats, without any effect on the exploring behavior, locomotor activity, anxiety levels and pain perception. Enhanced performance on the inhibitory avoidance task was correlated with long-term potentiation (LTP), a phenomenon that was strengthen in hippocampal slices of rats injected with MP (5mg/kg) during 10days. Additionally, in vitro incubation with MP (30-300µM) concentration-dependently increased intracellular [Ca 2+ ] i in cultured hippocampal neurons depolarized by KCl (35mM). In conclusion, a low daily dose of MP for 10days may promote aversive memory persistence in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

A case of recurrent encephalopathy with SCN2A missense mutation.

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Fukasawa, Tatsuya; Kubota, Tetsuo; Negoro, Tamiko; Saitoh, Makiko; Mizuguchi, Masashi; Ihara, Yukiko; Ishii, Atsushi; Hirose, Shinichi

2015-06-01

Voltage-gated sodium channels regulate neuronal excitability, as well as survival and the patterning of neuronal connectivity during development. Mutations in SCN2A, which encodes the Na(+) channel Nav1.2, cause epilepsy syndromes and predispose children to acute encephalopathy. Here, we report the case of a young male with recurrent acute encephalopathy who carried a novel missense mutation in the SCN2A gene. He was born by normal delivery and developed repetitive apneic episodes at 2days of age. Diffusion-weighted imaging revealed high-intensity areas in diffuse subcortical white matter, bilateral thalami, and basal nuclei. His symptoms improved gradually without any specific treatment, but he exhibited a motor milestone delay after the episode. At the age of 10months, he developed acute cerebellopathy associated with a respiratory syncytial viral infection. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy and seemed to have no obvious sequelae after the episode. He then developed severe diffuse encephalopathy associated with gastroenteritis at the age of 14months. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy but was left with severe neurological sequelae. PCR-based analysis revealed a novel de novo missense mutation, c.4979T>G (p.Leu1660Trp), in the SCN2A gene. This case suggests that SCN2A mutations might predispose children to repetitive encephalopathy with variable clinical and imaging findings. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

High-Dose Vitamin C Injection to Cancer Patients May Promote Thrombosis Through Procoagulant Activation of Erythrocytes.

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Kim, Keunyoung; Bae, Ok-Nam; Koh, Sung-Hee; Kang, Seojin; Lim, Kyung-Min; Noh, Ji-Yoon; Shin, Sue; Kim, Inho; Chung, Jin-Ho

2015-10-01

Potential risk of high-dose vitamin C consumption is often ignored. Recently, gram-dose vitamin C is being intravenously injected for the treatment of cancer, which can expose circulating blood cells to extremely high concentrations of vitamin C. As well as platelets, red blood cells (RBCs) can actively participate in thrombosis through procoagulant activation. Here, we examined the procoagulant and prothrombotic risks associated with the intravenous injection of gram-dose vitamin C. Vitamin C (0.5-5 mM) increased procoagulant activity of freshly isolated human RBCs via the externalization of phosphatidylserine (PS) to outer cellular membrane and the formation of PS-bearing microvesicles. PS exposure was induced by the dysregulation of key enzymes for the maintenance of membrane phospholipid asymmetry, which was from vitamin C-induced oxidative stress, and resultant disruption of calcium and thiol homeostasis. Indeed, the intravenous injection of vitamin C (0.5-1.0 g/kg) in rats in vivo significantly increased thrombosis. Notably, the prothrombotic effects of vitamin C were more prominent in RBCs isolated from cancer patients, who are at increased risks of thrombotic events. Vitamin C-induced procoagulant and prothrombotic activation of RBCs, and increased thrombosis in vivo. RBCs from cancer patients exhibited increased sensitivity to the prothrombotic effects of vitamin C, reflecting that intravenous gram-dose vitamin C therapy needs to be carefully revisited. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial.

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Tsuji, Daiki; Kim, Yong-Il; Taku, Keisei; Nakagaki, Shigeru; Ikematsu, Yoshito; Tsubota, Hiromi; Maeda, Masato; Hashimoto, Naoya; Kimura, Masayuki; Daimon, Takashi

2012-05-01

A single 3 mg or 40 μg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 μg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.

Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose.

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Sesé, L; Gaouar, H; Autegarden, J-E; Alari, A; Amsler, E; Vial-Dupuy, A; Pecquet, C; Francès, C; Soria, A

2016-03-01

The diagnosis of HSR to iodinated contrast media (ICM) is challenging based on clinical history and skin tests. This study evaluates the negative predictive value (NPV) of skin tests and intravenous provocation test (IPT) with low-dose ICM in patients with suspected immediate hypersensitivity reaction (HSR) to ICM. Thirty-seven patients with suspected immediate hypersensitivity reaction to ICM were included retrospectively. Skin tests and a single-blind placebo-controlled intravenous provocation test (IPT) with low-dose iodinated contrast media (ICM) were performed. Skin tests with ICM were positive in five cases (one skin prick test and five intradermal test). Thirty-six patients were challenged successfully by IPT, and only one patient had a positive challenge result, with a grade I reaction by the Ring and Messmer classification. Ten of 23 patients followed up by telephone were re-exposed to a negative tested ICM during radiologic examination; two experienced a grade I immediate reaction. For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44-97%). © 2016 John Wiley & Sons Ltd.

The changes in renal function after a single dose of intravenous furosemide in patients with compensated liver cirrhosis

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Mejirisky Yoram

2006-11-01

Full Text Available Abstract Background Patients with compensated Child-A cirrhosis have sub clinical hypovolemia and diuretic treatment could result in renal impairment. Aim To evaluate the changes in renal functional mass as reflected by DMSA uptake after single injection of intravenous furosemide in patients with compensated liver cirrhosis. Methods Eighteen cirrhotic patients were divided in two groups; eight patients (group 1, age 56 ± 9.6 yrs, Gender 5M/3F, 3 alcoholic and 5 non alcoholic were given low intravenous 40 mg furosemide and ten other patients (group 2, age 54 ± 9.9, Gender 6M/4F, 4 alcoholic and 6 non alcoholic were given high 120 mg furosemide respectively. Renoscintigraphy with 100MBq Of Tc 99 DMSA was given intravenously before and 90 minutes after furosemide administration and SPECT imaging was determined 3 hours later. All patients were kept under low sodium diet (80mEq/d and all diuretics were withdrawn for 3 days. 8-hours UNa exertion, Calculated and measured Creatinine clearance (CCT were performed for all patients. Results Intravenous furosemide increased the mean renal DMSA uptake in 55% of patients with compensated cirrhosis and these changes persist up to three hours after injection. This increase was at the same extent in either low or high doses of furosemide. (From 12.8% ± 3.8 to 15.2% ± 2.2, p 40%, as compared to normal calculated creatinine clearance (CCT 101 ± 26, and measured CCT of 87 ± 30 cc/min (P Conclusion A single furosemide injection increases renal functional mass as reflected by DMSA in 55% of patients with compensated cirrhosis and identify 45% of patients with reduced uptake and who could develop renal impairment under diuretics. Whether or not albumin infusion exerts beneficial effect in those patients with reduced DMSA uptake remains to be determined.

The impact on coagulation of an intravenous loading dose in addition to a subcutaneous regimen of low-molecular-weight heparin in the initial treatment of acute coronary syndromes

NARCIS (Netherlands)

Bijsterveld, Nick R.; Moons, Arno H.; Meijers, Joost C. M.; Levi, Marcel; Büller, Harry R.; Peters, Ron J. G.

2003-01-01

OBJECTIVES We sought to quantify the impact of adding an intravenous loading dose to a subcutaneous regimen of enoxaparin in patients with an acute coronary syndrome (ACS). BACKGROUND It is unclear whether an intravenous (M loading dose of enoxaparin should be added to a subcutaneous (SQ) regimen in

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.

Specific dose-dependent damage of Lieberkuehn crypts promoted by large doses of type 2 ribosome-inactivating protein nigrin b intravenous injection to mice

International Nuclear Information System (INIS)

Gayoso, M.J.; Munoz, R.; Arias, Y.; Villar, R.; Rojo, M.A.; Jimenez, P.; Ferreras, J.M.; Aranguez, I.; Girbes, T.

2005-01-01

Nigrin b is a non-toxic type 2 ribosome-inactivating protein as active as ricin at ribosomal level but 10 5 and 5 x 10 3 times less toxic for animal cell cultures and mice, respectively, than ricin. The purpose of the present study was to analyze the effects of intravenous injection of large amounts of nigrin b to the mouse. Injection through the tail vein of 16 mg/kg body weight killed all mice studied before 2 days. Analysis of several major tissues by light microscopy did not reveal gross nigrin b-promoted changes, except in the intestines which appeared highly damaged. As a consequence of the injury, the villi and crypt structures of the small intestine disappeared, leading to profuse bleeding and death. In contrast, intravenous injection of 5 mg/kg body weight was not lethal to mice but did trigger reversible toxic effects. In both cases, lethal and sub-lethal doses, the target of nigrin b appeared to be the highly proliferating stem cells of the intestinal crypts, which had undergone apoptotic changes. In contrast to nigrin b, the injection of 3 μg/kg of ricin kills all mice in 5 days but does not trigger apoptosis in the crypts. Therefore, the effect seen with sub-lethal nigrin b concentrations seems to be specific. Nigrin b killed COLO 320 human colon adenocarcinoma cells with an IC 50 of 3.1 x 10 -8 M and the effect was parallel to the extent of DNA fragmentation of these cells. Accordingly, despite the low general toxicity exerted by nigrin b as compared with ricin, intravenous injection of large amounts of nigrin b is able to kill mouse intestinal stem cells without threatening the lives of the animals, thereby opening a door for its use for the targeting of intestinal stem cells

Preoperative steroid in abdominal wall reconstruction

DEFF Research Database (Denmark)

Jensen, Kristian Kiim; Brøndum, Tina Lee; Belhage, Bo

2016-01-01

INTRODUCTION: Preoperative administration of high-dose glucocorticoid leads to improved recovery and decreased length of stay after abdominal surgery. Even so, studies on administration of glucocorticoids for patients undergoing abdominal wall reconstruction (AWR) for giant ventral hernia repair...... defect exceeding 10 cm will be randomised for intravenous administration of either 125 mg methylprednisolone or saline at the induction of anaesthesia. The primary endpoint is pain at rest on the first post-operative day. Patients will be followed until 30 days post-operatively, and secondary outcomes...

A combination of methylprednisolone and quercetin is effective for the treatment of cardiac contusion following blunt chest trauma in rats

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Demir, F. [Department of Pediatric Cardiology, Faculty of Medicine, Dicle University, Diyarbakır (Turkey); Güzel, A. [Department of Pediatrics, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Katı, C. [Department of Emergency Medicine, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Karadeniz, C. [Pediatric Cardiology Services, Behçet Uz Children' s Hospital, İzmir (Turkey); Akdemir, U. [Department of Emergency Medicine, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Okuyucu, A. [Department of Medical Biochemistry, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Gacar, A. [Department of Pathology, Faculty of Veterinary Medicine, Ondokuz Mayıs University, Samsun (Turkey); Özdemir, S. [Department of Pediatrics, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Güvenç, T. [Department of Pathology, Faculty of Veterinary Medicine, Ondokuz Mayıs University, Samsun (Turkey)

2014-08-01

Cardiac contusion is a potentially fatal complication of blunt chest trauma. The effects of a combination of quercetin and methylprednisolone against trauma-induced cardiac contusion were studied. Thirty-five female Sprague-Dawley rats were divided into five groups (n=7) as follows: sham, cardiac contusion with no therapy, treated with methylprednisolone (30 mg/kg on the first day, and 3 mg/kg on the following days), treated with quercetin (50 mg·kg{sup −1}·day{sup −1}), and treated with a combination of methylprednisolone and quercetin. Serum troponin I (Tn-I) and tumor necrosis factor-alpha (TNF-α) levels and cardiac histopathological findings were evaluated. Tn-I and TNF-α levels were elevated after contusion (P=0.001 and P=0.001). Seven days later, Tn-I and TNF-α levels decreased in the rats treated with methylprednisolone, quercetin, and the combination of methylprednisolone and quercetin compared to the rats without therapy, but a statistical significance was found only with the combination therapy (P=0.001 and P=0.011, respectively). Histopathological degeneration and necrosis scores were statistically lower in the methylprednisolone and quercetin combination group compared to the group treated only with methylprednisolone (P=0.017 and P=0.007, respectively). However, only degeneration scores were lower in the combination therapy group compared to the group treated only with quercetin (P=0.017). Inducible nitric oxide synthase positivity scores were decreased in all treatment groups compared to the untreated groups (P=0.097, P=0.026, and P=0.004, respectively). We conclude that a combination of quercetin and methylprednisolone can be used for the specific treatment of cardiac contusion.

Preoperative methylprednisolone does not reduce loss of knee-extension strength after total knee arthroplasty

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Lindberg-Larsen, Viktoria; Bandholm, Thomas Q; Zilmer, Camilla K

2017-01-01

tests, rescue analgesic requirements, and plasma C-reactive protein (CRP) changes. Results - 61 patients completed the follow-up. The loss in quadriceps muscle strength was similar between groups; group MP 1.04 (0.22-1.91) Nm/kg (-89%) vs. group C 1.02 (0.22-1.57) Nm/kg (-88%). Also between......-265) mg/L (p loss of knee-extension strength or other functional outcomes at discharge after fast-track TKA despite a reduced systemic inflammatory response.......Background and purpose - Patients undergoing total knee arthroplasty (TKA) face challenges related to postoperative reduction in knee-extension strength. We evaluated whether inhibition of the inflammatory response by a single preoperative dose of methylprednisolone (MP) reduces the pronounced loss...

Pharmacokinetics of colistin methanesulfonate (CMS) in healthy Chinese subjects after single and multiple intravenous doses.

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Zhao, Miao; Wu, Xiao-Jie; Fan, Ya-Xin; Zhang, Ying-Yuan; Guo, Bei-Ning; Yu, Ji-Cheng; Cao, Guo-Ying; Chen, Yuan-Cheng; Wu, Ju-Fang; Shi, Yao-Guo; Li, Jian; Zhang, Jing

2018-05-01

The high prevalence of extensively drug-resistant Gram-negative pathogens has forced clinicians to use colistin as a last-line therapy. Knowledge on the pharmacokinetics of colistin methanesulfonate (CMS), an inactive prodrug, and colistin has increased substantially; however, the pharmacokinetics in the Chinese population is still unknown due to lack of a CMS product in China. This study aimed to evaluate the pharmacokinetics of a new CMS product developed in China in order to optimise dosing regimens. A total of 24 healthy subjects (12 female, 12 male) were enrolled in single- and multiple-dose pharmacokinetic (PK) studies. Concentrations of CMS and formed colistin in plasma and urine were measured, and PK analysis was conducted using a non-compartmental approach. Following a single CMS dose [2.36 mg colistin base activity (CBA) per kg, 1 h infusion], peak concentrations (C max ) of CMS and formed colistin were 18.0 mg/L and 0.661 mg/L, respectively. The estimated half-life (t 1/2 ) of CMS and colistin were 1.38 h and 4.49 h, respectively. Approximately 62.5% of the CMS dose was excreted via urine within 24 h after dosing, whilst only 1.28% was present in the form of colistin. Following multiple CMS doses, colistin reached steady-state within 24 h; there was no accumulation of CMS, but colistin accumulated slightly (R AUC  = 1.33). This study provides the first PK data in the Chinese population and is essential for designing CMS dosing regimens for use in Chinese hospitals. The urinary PK data strongly support the use of intravenous CMS for serious urinary tract infections. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

[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.

Randomized clinical trial of prevention of seroma formation after mastectomy by local methylprednisolone injection

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Qvamme, G; Axelsson, C. K.; Lanng, C

2015-01-01

: This was a double-blind randomized placebo-controlled intervention study of a single dose of 80 mg methylprednisolone versus saline on seroma formation after mastectomy. Patients were further classified according to the surgical axillary procedure: mastectomy with sentinel lymph node biopsy (M + SLNB) or mastectomy......BACKGROUND: Seroma formation, the most prevalent postoperative complication after mastectomy, is an inflammatory process that is potentially preventable via local steroid administration. This study investigated the effect of local steroid administration on seroma formation. METHODS...... with level I-II axillary lymph node dissection (M + ALND). Treatments were administered into the wound cavity via the drain orifice following removal of the drain on the first day after surgery. The primary endpoint was seroma formation; secondary endpoints included the frequency of side...

Non-ST Elevation Myocardial Infraction after High Dose Intravenous Immunoglobulin Infusion

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Meir Mizrahi

2009-01-01

Full Text Available Intravenous immunoglobulins (IVIgs are used for several indications, including autoimmune conditions. IVIg treatment is associated with several possible adverse reactions including induction of a hypercoagulable state. We report a 76-year-old woman treated with IVIg for myasthenia gravis, which developed chest pain and weakness following IVIg infusion. The symptoms were associated with ST segment depression in V4–6 and elevated troponin levels. The patient was diagnosed with non-ST elevation myocardial infarction (NSTEMI. The patient had no significant risk factor besides age and a cardiac perfusion scan was interpreted as normal (the patient refused to undergo cardiac catheterization. This case is compatible with IVIg-induced hypercoagulability resulting in NSTEMI. Cardiac evaluation should therefore be considered prior to initiation of IVIg treatment especially in patients with multiple cardiovascular risks.

Randomized controlled trial comparing different single doses of intravenous paracetamol for placement of peripherally inserted central catheters in preterm infants

NARCIS (Netherlands)

D.W.E. Roofthooft (Daniella); S.H. Simons (Sinno); R.A. Lingen (Richard); D. Tibboel (Dick); J.N. van den Anker (John); I.K.M. Reiss (Irwin); M. van Dijk (Monique)

2017-01-01

markdownabstract__Background:__ The availability of a safe and effective pharmacological therapy to reduce procedural pain in preterm infants is limited. The effective analgesic single dose of intravenous paracetamol in preterm infants is unknown. Comparative studies on efficacy of different

Limited duration of the effect of methylprednisolone on changes on MRI in multiple sclerosis

International Nuclear Information System (INIS)

Barkhof, F.; Tas, M.W.; Frequin, S.T.F.M.; Scheltens, P.; Hommes, O.R.; Nauta, J.J.P.; Valk, J.

1994-01-01

We performed serial MRI imaging after methylprednisolone treatment to see whether suppression of enhancement persists and whether related abnormalities on T2-weighted images disappear at follow-up. Thirteen patients with definite MS received a total of 31 courses of methylprednisolone over an average period of 50 weeks. Gadolinium-enhanced MRI was obtained before and after treatment, then at monthly intervals, using a standardised repositioning and imaging protocol. We detected 609 active lesions on 195 examinations. Directly after treatment the reduction in the number of enhancing lesions was 78%, indicating restoration of the BBB and suppression of inflammation. It was uncommon for a lesion which stopped enhancing to show enhancement on a subsequent examination. No beneficial effect was observed on the rate of disappearance of related abnormalities on T2-weighted images. Moreover, in 89% of cases, an increase in the number of active lesions was observed before new clinical activity, if any, was observed (on average 52% earlier). MRI enabled us to demonstrate that the duration of the effect of methylprednisolone treatment is temporary (on average 9.7 weeks). (orig./MG)

[Therapeutic strategies against myasthenia gravis].

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Utsugisawa, Kimiaki; Nagane, Yuriko

2013-05-01

Many patients with myasthenia gravis (MG) still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of oral corticosteroids, since full remission is not common. Our analysis demonstrated that disease severity, oral corticosteroids, and depressive state are the major factors negatively associated with QOL, and that QOL of MM status patients taking CSR and is a target of treatment. In order to achieve early MM or better status with prednisolne strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved status using low-dose oral corticosteroids and calcineurin inhibitors.

Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg.

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Wark, J D; Bensen, W; Recknor, C; Ryabitseva, O; Chiodo, J; Mesenbrink, P; de Villiers, T J

2012-02-01

Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms. Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen. In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia (n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol (n = 135), ibuprofen (n = 137) or placebo (n = 137), or placebo + placebo (n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion. The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p paracetamol or ibuprofen. Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.

Cellular internalization and morphological analysis after intravenous injection of a highly hydrophilic octahedral rhenium cluster complex - a new promising X-ray contrast agent.

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Krasilnikova, Anna A; Solovieva, Anastasiya O; Trifonova, Kristina E; Brylev, Konstantin A; Ivanov, Anton A; Kim, Sung-Jin; Shestopalov, Michael A; Fufaeva, Maria S; Shestopalov, Alexander M; Mironov, Yuri V; Poveshchenko, Alexander F; Shestopalova, Lidia V

2016-11-01

The octahedral cluster compound Na 2 H 8 [{Re 6 Se 8 }(P(C 2 H 4 CONH 2 )(C 2 H 4 COO) 2 ) 6 ] has been shown to be highly radio dense, thus becoming a promising X-ray contrast agent. It was also shown that this compound had low cytotoxic effect in vitro, low acute toxicity in vivo and was eliminated rapidly from the body through the urinary tract. The present contribution describes a more detailed cellular internalization assay and morphological analysis after intravenous injection of this hexarhenium cluster compound at different doses. The median lethal dose (LD 50 ) of intravenously administrated compound was calculated (4.67 ± 0.69 g/kg). Results of the study clearly indicated that the cluster complex H n [{Re 6 Se 8 }(P(C 2 H 4 CONH 2 )(C 2 H 4 COO) 2 ) 6 ] n-10 was not internalized into cells in vitro and induced only moderate morphological alterations of kidneys at high doses without any changes in morphology of liver, spleen, duodenum, or heart of mice. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Effect of Preoperative Intra-Articular Methylprednisolone on Pain After TKA

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Luna, Iben E; Kehlet, Henrik; Jensen, Claus M

2017-01-01

In a randomized, double-blind, placebo controlled trial, we investigated the postoperative analgesic effect of a single intra-articular injection of 40 mg methylprednisolone acetate (MP) administered 1 week before total knee arthroplasty (TKA). Forty-eight patients with high pain osteoarthritis (≥5...... groups in postoperative sensitization was found (P > .4) despite reduced preoperative intra-articular inflammation (IL-6) in the MP group versus placebo (median change in IL-6 = -70 pg/mL, interquartile range = -466 to 0 vs. 32 pg/mL, interquartile range = -26 to 75, P = .029). Alternative central...

Prehospital high-dose sublingual nitroglycerin rarely causes hypotension.

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Clemency, Brian M; Thompson, Jeffrey J; Tundo, Gina N; Lindstrom, Heather A

2013-10-01

High-dose intravenous nitroglycerin is a common in-hospital treatment for respiratory distress due to congestive heart failure (CHF) with hypertension. Intravenous (IV) nitroglycerin administration is impractical in the prehospital setting. In 2011, a new regional Emergency Medical Services (EMS) protocol was introduced allowing advanced providers to treat CHF with high-dose oral nitroglycerin. The protocol calls for patients to be treated with two sublingual tabs (0.8 mg) when systolic blood pressure (SBP) was >160 mm Hg, or three sublingual tabs (1.2 mg) when SBP was >200 mm Hg, every five minutes as needed. Hypothesis/Problem To assess the protocol's safety, the incidence of hypotension following prehospital administration of multiple simultaneous nitroglycerin (MSN) tabs by EMS providers was studied. This study was a retrospective cohort study of patients from a single commercial EMS agency over a 6-month period. Records from patients with at least one administration of MSN were reviewed. For each administration, the first documented vital signs pre- and post-administration were compared. Administrations were excluded if pre- or post-administration vital signs were missing. One hundred case-patients had at least one MSN administration by an advanced provider during the study period. Twenty-five case-patients were excluded due to incomplete vital signs. Seventy-five case-patients with 95 individual MSN administrations were included for analysis. There were 65 administrations of two tabs, 29 administrations of three tabs, and one administration of four tabs. The mean change in SBP following MSN was -14.7 mm Hg (SD = 30.7; range, +59 to -132). Three administrations had documented systolic hypotension in the post-administration vital signs (97/71, 78/50 and 66/47). All three patients were over 65 years old, were administered two tabs, had documented improved respiratory status, and had repeat SBP of at least 100. The incidence of hypotension following MSN

Dosing of Intravenous Tocilizumab in a Real-World Setting of Rheumatoid Arthritis: Analyses from the Corrona Registry.

Science.gov (United States)

Pappas, Dimitrios A; John, Ani; Curtis, Jeffrey R; Reed, George W; Karki, Chitra; Magner, Robert; Kremer, Joel M; Shewade, Ashwini; Greenberg, Jeffrey D

2016-06-01

In the United States, the recommended starting dose of intravenous tocilizumab (TCZ) is 4 mg/kg every 4 weeks, with an increase to 8 mg/kg based on clinical response for patients with moderate to severe rheumatoid arthritis; however, data on how TCZ dose is escalated in real life are missing. The objective of this analysis was to describe patterns of early intravenous TCZ dose escalation in a real-world setting using data from the Corrona registry. All patients enrolled in the comparative effectiveness substudy (CERTAIN) nested within Corrona who initiated TCZ and completed 3- and 6-month study visits were eligible for inclusion. Patients who initiated TCZ 4 mg/kg were categorized into 1 of 2 groups: those who remained on TCZ 4 mg/kg at 3 months (Group 1) and those who escalated to TCZ 8 mg/kg by or at 3 months (Group 2). Changes in clinical disease activity measures were provided. Of the 213 patients who were eligible for analysis, 86 (40.4%) remained on their initial dose of TCZ 4 mg/kg (Group 1) and 110 (51.6%) were escalated to TCZ 8 mg/kg by or at 3 months (Group 2). Baseline demographic and clinical characteristics were similar between the 2 groups; except in Group 2, patients were older (58.3 vs. 54.0 years) and a lower proportion was female (75.5% vs. 89.4%) than in Group 1. Significant improvements in disease activity measures were observed at 3 and 6 months in both groups, with the majority of patients in both groups achieving moderate or good European League Against Rheumatism response. Real-world data demonstrated that physicians escalate TCZ dose at varying frequencies. The ability to administer TCZ in varying doses allows physicians to tailor TCZ therapy to disease activity. ClinicalTrials.gov identifier, NCT01625650.

Urinary iron excretion induced by intravenous infusion of deferoxamine in ß-thalassemia homozygous patients

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Boturão-Neto E.

2002-01-01

Full Text Available The purpose of the present study was to identify noninvasive methods to evaluate the severity of iron overload in transfusion-dependent ß-thalassemia and the efficiency of intensive intravenous therapy as an additional tool for the treatment of iron-overloaded patients. Iron overload was evaluated for 26 ß-thalassemia homozygous patients, and 14 of them were submitted to intensive chelation therapy with high doses of intravenous deferoxamine (DF. Patients were classified into six groups of increasing clinical severity and were divided into compliant and non-compliant patients depending on their adherence to chronic chelation treatment. Several methods were used as indicators of iron overload. Total gain of transfusion iron, plasma ferritin, and urinary iron excretion in response to 20 to 60 mg/day subcutaneous DF for 8 to 12 h daily are useful to identify iron overload; however, urinary iron excretion in response to 9 g intravenous DF over 24 h and the increase of urinary iron excretion induced by high doses of the chelator are more reliable to identify different degrees of iron overload because of their correlation with the clinical grades of secondary hemochromatosis and the significant differences observed between the groups of compliant and non-compliant patients. Finally, the use of 3-9 g intravenous DF for 6-12 days led to a urinary iron excretion corresponding to 4.1 to 22.4% of the annual transfusion iron gain. Therefore, continuous intravenous DF at high doses may be an additional treatment for these patients, as a complement to the regular subcutaneous infusion at home, but requires individual planning and close monitoring of adverse reactions.

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

Science.gov (United States)

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.

Single and 2-week repeated intravenous dose toxicity studies of disodium mercaptoundecahydro-closo-dodecaborate in rats

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Itoh, Fumio; Yabuuchi, Kazuya; Ohno, Kouji; Muraoka, Yoshihiro [Shionogi and Co. Ltd., Toyonaka, Osaka (Japan). Developmental Research Lab.; Ikeuchi, Isao

1998-10-01

Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is a boron compound used in Boron Neutron Capture Therapy for malignant brain tumors. Intravenous single and 2-week repeated dose toxicity studies of BSH were performed in Sprague-Dawley rats. In the single-dose study, BSH was administered at doses of 100, 300 or 600 mg/kg. Death occurred within 10 min (acute type) or from 5 hr to 2 days (delayed type) after dosing in the 600 mg/kg group. No differences in mortality by sex and dosing speed were observed. Major causes of death were considered to be circulatory disorder in acute death and renal injury in delayed death. The renal injury was observed in the 300 and 600 mg/kg groups. In the 2-week repeated dose study, BSH was administered at doses of 30, 100 or 300 mg/kg/day for 14 days. Body weight gain was suppressed in the 100 and 300 mg/kg groups. One male in the 300 mg/kg group died due to renal and pulmonary lesions at day 8. Slight anemia was observed in the 300 mg/kg group. Pathologically, the kidney showed tubular regeneration with increase of weight in the 300 mg/kg. From these results, the NOAEL of BSH is 30 mg/kg/day. (author)

Cytophagic histiocytic panniculitis, hemophagocytic lymphohistiocytosis and undetermined autoimmune disorder: reconciling the puzzle.

Science.gov (United States)

Pasqualini, Claudia; Jorini, Mauro; Carloni, Ines; Giangiacomi, Mirella; Cetica, Valentina; Aricò, Maurizio; de Benedictis, Fernando Maria

2014-02-13

Cytophagic histiocytic panniculitis is a rare disease, associated with either nonmalignant conditions or subcutaneous panniculitis-like T-cell lymphoma, and often also associated with hemophagocytic lymphohistiocytosis (HLH). We report the case of a 11-year-old boy with a history of secondary HLH who, after a local trauma, developed a painful, indurated plaque over the right thigh associated with relapsing HLH. Histopathologic findings from skin biopsy specimens revealed significant lobular panniculitis with benign histiocytes showing hemophagocytosis. High-dose intravenous methylprednisolone and cyclosporine A treatment was highly effective. A genetic study after a new, relapsing episode of HLH revealed an heterozygous missense mutation on STX 11 gene inherited from the mother.

Quality of life assessment in patients with Graves' disease and progressive infiltrative ophthalmopathy during combined treatment with methylprednisolone and orbital radiotherapy

International Nuclear Information System (INIS)

Kulig, G.; Andrysiak-Mamos, E.

2009-01-01

Introduction: The aim of the study was to assess quality of life (QoL) in patients with infiltrative form of Graves' ophthalmopathy (GO) during the combined pulse treatment with methylprednisolone and orbital radiotherapy, and also to search for the relation between the results of ophthalmopathy treatment and changes in QoL. Material and methods: The study involved 29 patients aged 25-74 (the mean age: 52 ±6 years) with infiltrative form of GO. They were classified for ophthalmopathy treatment on the basis of the following factors: the obtained euthyreosis, progressive character of eye changes, the level of eye changes determined on the basis of NO SPECS classification (at least class 3c), ophthalmopathy index (OI) according to Donaldson. 4. GO was diagnosed as active if CAS (clinical activity score) . 4. During the treatment, the patients received 6 cycles of methylprednisolone sodium succinate in doses of 1,0 g/24 h given as one-hour-long intravenous infusions for three successive days in a week. Between the 2 nd and 4 th cycle of Solu-Medrol, orbital radiotherapy with 10 MeV X-rays was performed. The control group was made up of healthy volunteers selected with regard to sex, age, educational background and nicotine addiction so as they corresponded with the study group. It involved 53 individuals aged 21-75 (the mean age: 52,4 ±14 years). QoL was assessed by means of the MOS SF-36 estionnaire. Results: Patients with GO evaluated their QoL lower than healthy individuals, which referred to physical functioning, physical and emotional role functioning, general health, vitality, social functioning, mental health and bodily pain. No correlation was found between quality of life and such factors as age, sex, or duration time of Graves disease and ophthalmopathy. Analogically, no relation was observed between the activity and stage of clinical development of eye changes and QoL. The use of the combined GO therapy contributed to a considerable decrease in the

[Multiple sclerosis. Therapeutic nihilism is the wrong approach here].

Science.gov (United States)

Voltz, R; Goebels, N; Jarius, S; Hohlfeld, R

2002-05-06

The standard treatment for acute multiple sclerosis relapses continues to be the intravenous administration of high-dose methylprednisolone. For prophylactic purposes, immunomodulatory therapy with interferon beta or glatiramer acetate, immunoglobulins or azathioprine. Studies have shown that interferon beta not only reduces the frequency of relapses by one-third, but also significantly delays the second relapse, provided it is administrated early, that is, immediately following the first relapse. The reduction in the patient's quality of life caused by the illness can be appreciably improved by a whole series of symptomatic treatments. The ideal situation is a cooperative effort by an interdisciplinary team.

Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered

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Decramer Marc

2010-12-01

Full Text Available Abstract Background High dose of corticosteroids has been previously shown to protect against controlled mechanical ventilation (CMV-induced diaphragmatic dysfunction while inhibiting calpain activation. Because literature suggests that the calpain inhibiting effect of corticosteroid depends on the dose administered, we determined whether lower doses of corticosteroids would also provide protection of the diaphragm during CMV. This may be important for patients undergoing mechanical ventilation and receiving corticosteroids. Methods Rats were assigned to controls or to 24 hours of CMV while being treated at the start of mechanical ventilation with a single intramuscular administration of either saline, or 5 mg/kg (low MP or 30 mg/kg (high MP of methylprednisolone. Results Diaphragmatic force was decreased after CMV and this was exacerbated in the low MP group while high MP rescued this diaphragmatic dysfunction. Atrophy was more severe in the low MP group than after CMV while no atrophy was observed in the high MP group. A significant and similar increase in calpain activity was observed in both the low MP and CMV groups whereas the high dose prevented calpain activation. Expression of calpastatin, the endogenous inhibitor of calpain, was decreased in the CMV and low MP groups but its level was preserved to controls in the high MP group. Caspase-3 activity increased in all CMV groups but to a lesser extent in the low and high MP groups. The 20S proteasome activity was increased in CMV only. Conclusions Administration of 30 mg/kg methylprednisolone during CMV protected against CMV-induced diaphragm dysfunction while 5 mg/kg was more deleterious. The protective effect is due mainly to an inhibition of the calpain system through preservation of calpastatin levels and to a lesser extent to a caspase-3 inhibition.

Single Intravenous Dose of Novel Flurbiprofen-Loaded Proniosome Formulations Provides Prolonged Systemic Exposure and Anti-inflammatory Effect.

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Verma, Preeti; Prajapati, Sunil K; Yadav, Rajbharan; Senyschyn, Danielle; Shea, Peter R; Trevaskis, Natalie L

2016-11-07

Vesicular and colloidal delivery systems can be designed to control drug release spatially and temporally to improve drug efficacy and side effect profiles. Niosomes (vesicles prepared from nonionic surfactants in aqueous media) are gaining interest as an alternative vesicular delivery system as they offer advantages such as biocompatibility, chemical stability, low cost, high purity, and versatility. However, the physical stability of niosomes, like other vesicular systems, is limited by vesicle fusion, aggregation, and leakage. Proniosomes (dehydrated powder or gel formulations that spontaneously form niosomes on hydration with aqueous media) can overcome these physical stability problems and are more convenient for sterilization, storage, transport, distribution, and dosing. Proniosomes have mostly been explored for their potential to enhance transdermal and oral absorption. In this study we assess, for the first time, the potential for hydrated proniosomes to sustain systemic exposure and therapeutic effect after intravenous delivery. Proniosomes carrying the anti-inflammatory drug, flurbiprofen, were prepared by spraying different nonionic surfactants (span 20, span 40, and span 60 in varying ratios with span 80) and cholesterol onto a sorbitol carrier. The proniosome powders were characterized for surface morphology and flow properties. Niosome formation was assessed at three different hydration temperatures (25, 37, and 45 °C), and the niosomes were assessed for vesicle size, entrapment efficiency, and sterility. OLP proniosomes prepared with a high ratio of span 80 to span 20 were found to spontaneously form vesicles of small size and high drug loading on hydration with aqueous media. The OLP derived niosomes successfully sustained in vitro drug release, in vivo pharmacokinetics, and the anti-inflammatory effect of flurbiprofen in an acute (rat paw edema) model of inflammation when compared to a control solution formulation. The study demonstrates that

A Complication after Intralesional Methylprednisolone Acetate Application to Oral Mucosa: A Case Report

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Borahan Mehmet Oguz

2014-11-01

Full Text Available Objectives: The purpose of this case report is to evaluate an abscess formation due to intralesional methylprednisolone acetate application to a patient with erosive oral lichen planus.

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

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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 intra-articular hyaluronic acid and methylprednisolone for pain management in knee osteoarthritis: A meta-analysis of randomized controlled trials.

Science.gov (United States)

Ran, Jian; Yang, Xiaohui; Ren, Zheng; Wang, Jian; Dong, Hui

2018-05-01

We performed a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of intra-articular methylprednisolone and hyaluronic acid (HA) in term of pain reduction and improvements of knee function in patients with knee osteoarthritis (OA). The PubMed, EMBASE, ScienceDirect, and Cochrane Library databases were systematically searched for literature up to January 2018. RCTs involving HA and methylprednisolone in knee OA were included. Two independent reviewers performed independent data abstraction. The I 2 statistic was used to assess heterogeneity. A fixed or random effects model was adopted for meta-analysis. All meta-analyses were performed by using STATA 14.0. Five RCTs with 1004 patients were included in the meta-analysis. The present meta-analysis indicated that there were no significant differences in terms of WOMAC pain, physical function and stiffness at 4 week, 12 weeks and 26 weeks between HA and methylprednisolone groups. No increased risk of adverse events were identified in both groups. Both HA and methylprednisolone injections were effective therapies for patients with knee OA. Methylprednisolone showed comparable efficacy in reducing pain and improving functional recovery to HA. And no significant difference was found in long-term of follow-up in terms of adverse effects. Copyright © 2018 IJS Publishing Group Ltd. All rights reserved.

Acute toxicity of intravenously administered titanium dioxide nanoparticles in mice.

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Jiaying Xu

Full Text Available 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 biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment. RESULTS: Death of mice in the highest dose (1387 mg/kg group was observed at day two after TiO₂ NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW coefficients, and lower liver and kidney coefficients in the TiO₂ NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO₂ NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO₂ NPs treated mice. CONCLUSIONS: Intravenous injection of TiO₂ NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed.

Estimation of absorbed doses in humans due to intravenous administration of fluorine-18-fluorodeoxyglucose in PET studies

International Nuclear Information System (INIS)

Mejia, A.A.; Nakamura, T.; Masatoshi, I.; Hatazawa, J.; Masaki, M.; Watanuki, S.

1991-01-01

Radiation absorbed doses due to intravenous administration of fluorine-18-fluorodeoxyglucose in positron emission tomography (PET) studies were estimated in normal volunteers. The time-activity curves were obtained for seven human organs (brain, heart, kidney, liver, lung, pancreas, and spleen) by using dynamic PET scans and for bladder content by using a single detector. These time-activity curves were used for the calculation of the cumulative activity in these organs. Absorbed doses were calculated by the MIRD method using the absorbed dose per unit of cumulated activity, 'S' value, transformed for the Japanese physique and the organ masses of the Japanese reference man. The bladder wall and the heart were the organs receiving higher doses of 1.2 x 10(-1) and 4.5 x 10(-2) mGy/MBq, respectively. The brain received a dose of 2.9 x 10(-2) mGy/MBq, and other organs received doses between 1.0 x 10(-2) and 3.0 x 10(-2) mGy/MBq. The effective dose equivalent was estimated to be 2.4 x 10(-2) mSv/MBq. These results were comparable to values of absorbed doses reported by other authors on the radiation dosimetry of this radiopharmaceutical

Supra-recommendation Treatment of Super-refractory Status Epilepticus.

Science.gov (United States)

Vyas, Devashish Dhiren; Dash, Gopal Krishna

2016-06-01

A 28-year old female was admitted with recurrent seizures following 2 days of febrile illness, after which she developed status epilepticus. Midazolam and later thiopentone infusions were started after failure of regular intravenous antiepileptics. Burst suppression was achieved at doses of 3 mg/kg/hr for midazolam and 6 mg/kg/hr of thiopentone. Adjunctive medications included methylprednisolone, intravenous immunoglobulin and acyclovir. Imaging and biochemical parameters were normal. She required 3 cycles of midazolam and 2 cycles of thiopentone for complete cessation of seizures. She recovered with mild attentional and recent memory deficits on follow up. Treatment of super-refractory status epilepticus requires individualized regimens and may need doses beyond conventional limits. To the best of our knowledge, there is no such reported case from India.

Optimization of initial propofol bolus dose for EEG Narcotrend Index-guided transition from sevoflurane induction to intravenous anesthesia in children.

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Dennhardt, Nils; Boethig, Dietmar; Beck, Christiane; Heiderich, Sebastian; Boehne, Martin; Leffler, Andreas; Schultz, Barbara; Sümpelmann, Robert

2017-04-01

Sevoflurane induction followed by intravenous anesthesia is a widely used technique to combine the benefits of an easier and less traumatic venipuncture after sevoflurane inhalation with a recovery with less agitation, nausea, and vomiting after total intravenous anesthesia (TIVA). Combination of two different anesthetics may lead to unwanted burst suppression in the electroencephalogram (EEG) during the transition phase. The objective of this prospective clinical observational study was to identify the optimal initial propofol bolus dose for a smooth transition from sevoflurane induction to TIVA using the EEG Narcotrend Index (NI). Fifty children aged 1-8 years scheduled for elective pediatric surgery were studied. After sevoflurane induction and establishing of an intravenous access, a propofol bolus dose range 0-5 mg·kg -1 was administered at the attending anesthetist's discretion to maintain a NI between 20 and 64, and sevoflurane was stopped. Anesthesia was continued as TIVA with a propofol infusion dose of 15 mg·kg -1 ·h -1 for the first 15 min, followed by stepwise reduction according to McFarlan's pediatric infusion regime, and remifentanil 0.25 μg·kg -1 ·min -1 . Endtidal concentration of sevoflurane, NI, and hemodynamic data were recorded during the whole study period using a standardized case report form. Propofol plasma concentrations were calculated using the paedfusor dataset and a TIVA simulation program. Median endtidal concentration of sevoflurane at the time of administration of the propofol bolus was 5.1 [IQR 4.7-5.9] Vol%. The median propofol bolus dose was 1.2 [IQR 0.9-2.5] mg·kg -1 and median NI thereafter was 33 [IQR 23-40]. Nine children presented with a NI 13-20 and three children with burst suppression in the EEG (NI 0-12); all of them received an initial propofol bolus dose >2 mg·kg -1 . Regression equation demonstrated that NI 20-64 was achieved with a 95% probability when using a propofol bolus dose of 1 mg·kg -1 after

[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.

Treatment of severe aplastic anaemia with total lymphoid irradiation and methylprednisolone

International Nuclear Information System (INIS)

Mehta, J.; Singhal, S.; Huilgol, N.; Merchant, R.; Mehta, B.C.

1992-01-01

This case report briefly summarizes the treatment of aplastic anaemia with total lymphoid irradiation and methylprednisolone and recommends that this procedure should be considered a therapeutic option in patients who are not candidates for bone marrow transplantation or antithymocyte globulin, or those who have failed one course of the latter. (Author)

Systemic high-dose methotrexate plus ifosfamide is highly effective for central nervous system (CNS) involvement of lymphoma

OpenAIRE

2008-01-01

Abstract Patients with malignant central nervous system (CNS) involvement of lymphoma have a poor prognosis with intrathecal chemotherapy and radiation. In this paper, we report the results we obtained in such patients by intravenous chemotherapy with high-dose methotrexate and ifosfamide (HDMTX/IFO). The study involved a review of all patients who received HDMTX/IFO for CNS involvement of malignant lymphoma at our hospital. Therapy consisted of 4 g/m2 of MTX (4 h infu...

Evaluation of N-acetylcysteine and methylprednisolone as therapies for oxygen and acrolein-induced lung damage

Energy Technology Data Exchange (ETDEWEB)

Critchley, J.A.J.H. (Univ. of Edinburgh (England)); Beeley, J.M.; Clark, R.J.; Buchanan, J.D. (Royal Naval Hospital Hoslar, Gosport (England)); Summerfield, M.; Bell, S. (Admiralty Research Establishment, Alverstoke (England)); Spurlock, M.S.; Edginton, J.A.G. (Chemical Defence Establishment, Porton Down (England))

1990-04-01

Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. The authors evaluated NAC and methylprednisolone in two rats models of inhalation injury: 40-hr exposure to >97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). The increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. They caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.

Comparison of two doses of intravenous temsirolimus in patients with relapsed/refractory mantle cell lymphoma.

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Jurczak, Wojciech; Ramanathan, Sundra; Giri, Pratyush; Romano, Alessandra; Mocikova, Heidi; Clancy, Jill; Lechuga, Mariajose; Casey, Michelle; Boni, Joseph; Giza, Agnieszka; Hess, Georg

2018-03-01

Temsirolimus 175 mg once-weekly for 3 weeks, followed by 75 mg once-weekly intravenously dosed (175/75 mg) is approved in the European Union for treatment of relapsed/refractory mantle cell lymphoma (MCL). A phase IV study explored whether similar efficacy, but improved safety could be achieved with 75 mg without 175 mg loading doses (ClinicaTrials.gov: NCT01180049). Patients with relapsed/refractory MCL were randomized to once-weekly temsirolimus 175/75 mg (n = 47) or 75 mg (n = 42). Treatment continued until objective disease progression. Primary endpoint: progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Median PFS was 4.3 versus 4.5 months (hazard ratio [HR] 0.731; 80% confidence interval [CI], 0.520-1.027), and median OS 18.7 versus 11.0 months (HR 0.681; 80% CI, 0.472-0.982) with 175/75 mg versus 75 mg. There were fewer patients with serious AEs, dose reduction, or death with 175/75 mg (57.4%, 48.9%, and 48.9%) versus 75 mg (73.8%, 64.3%, and 65.1%). Temsirolimus 175/75 mg remains the preferred dosing regimen for relapsed/refractory MCL.

Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects.

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Munjal, Sagar; Gautam, Anirudh; Okumu, Franklin; McDowell, James; Allenby, Kent

2016-01-01

In a randomized, parallel-group, single-center study in 42 healthy adults, the safety and pharmacokinetic parameters of an intravenous formulation of 18.75 and 37.5 mg diclofenac sodium (DFP-08) following single- and multiple-dose bolus administration were compared with diclofenac potassium 50 mg oral tablets. Mean AUC0-inf values for a 50-mg oral tablet and an 18.75-mg intravenous formulation were similar (1308.9 [393.0]) vs 1232.4 [147.6]). As measured by the AUC, DFP-08 18.75 mg and 37.5 mg demonstrated dose proportionality for extent of exposure. One subject in each of the placebo and DFP-08 18.75-mg groups and 2 subjects in the DFP-08 37.5-mg group reported adverse events that were considered by the investigator to be related to the study drug. All were mild in intensity and did not require treatment. Two subjects in the placebo group and 1 subject in the DFP-08 18.75-mg group reported grade 1 thrombophlebitis; no subjects reported higher than grade 1 thrombophlebitis after receiving a single intravenous dose. The 18.75- and 37.5-mg doses of intravenous diclofenac (single and multiple) were well tolerated for 7 days. Additional efficacy and safety studies are required to fully characterize the product. © 2015, The American College of Clinical Pharmacology.

Intravenous immunoglobulin therapy leading to dramatic improvement in a patient with systemic juvenile idiopathic arthritis and severe pericarditis resistant to steroid pulse therapy.

Science.gov (United States)

Aizawa-Yashiro, Tomomi; Oki, Eishin; Tsuruga, Kazushi; Nakahata, Tohru; Ito, Etsuro; Tanaka, Hiroshi

2012-05-01

A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.

Single-dose and multiple-dose pharmacokinetics and dose proportionality of intravenous and intramuscular HPβCD-diclofenac (Dyloject) compared with other diclofenac formulations.

Science.gov (United States)

Mermelstein, Fred; Hamilton, Douglas A; Wright, Curtis; Lacouture, Peter G; Ramaiya, Atulkumar; Carr, Daniel B

2013-10-01

To evaluate single- and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. Clinical research center. Healthy adult volunteers. Study 1: Subjects received HPβCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPβCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. Study 1: IV HPβCD-diclofenac had a higher peak plasma concentration (Cmax ) and earlier time to reach maximum plasma concentration (Tmax ), but equivalent plasma exposure (area under the curve from time zero to t [AUC0-t ]) to IV Voltarol. The geometric mean ratio of HPβCD-diclofenac (IV) to Voltarol (IV) for AUC0-t was 106.27%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IM) for AUC0-t was 110.91%. The geometric mean ratio of HPβCD-diclofenac (IV) to HPβCD-diclofenac (IM) for AUC0-t was 101.25%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IV) for AUC0-t was 104.96%. Study 2: Cmax for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPβCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ng·hour/ml) and 37.5 mg (1843 ng·hour/ml) IV HPβCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ng·hour/ml). Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPβCD-diclofenac compared with Voltarol and after IM administration of HPβCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPβCD-diclofenac was equivalent to IV administration of HP�

Intratunical bupivacaine and methylprednisolone instillation for scrotal pain after testicular sperm retrieval procedures

Institute of Scientific and Technical Information of China (English)

GulK.Talu; TibetErdogru; TanselKaplancan; MustafaBahceci

2003-01-01

Aim：To investigate the effect of intratunical instillation of bupivacaine and methylprednisolone for scrotal pain,swelling and peritesticular fibrosis due to testicular sperm retrieval procedures.Methods:A total of 65 patients were randomly divided into two groups.In the instillation group(GI),34 patients were administered 2.5mL of 0.5% bupivacaine combined with 10 mg/mL methylprednisolone before closure of the tunica vaginalis.In the control group (GC),31 patients only received analgesics postoperatively by intramuscular route.The pain(by visual analogue scale,VAS)and duration of pain-free period after surgery between the two groups were evaluated at 2 and 4 h and at days 2 and 7 postoperatively.Results:The mean pain scores were significantly lower in the GI than in the GC group at 2 and 4 h after surgery(P<0.05 and P<0.01,respectively).The mean duration of pain free interval after the procedure was 47.8±16.9(12-76)h in GI,which was significantly longer than that in GC[(9.9±3.6;4-20)h].Besides,in the GI,29% of patients were completely free from pain and 67% had no scrotal swelling,but in the GC,all the patients required additional NSAID injection due to pain and only 3 % had no scrotal swelling.Conclusion:This study confirms that direct intratunical instillation of bupivacaine and methylprednisolone around the testis reduces the postoperative pain,scrotal swelling and peritesticular fibrosis.

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.

Do intravenous N-acetylcysteine and sodium bicarbonate prevent high osmolal contrast-induced acute kidney injury? A randomized controlled trial.

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Antonio Jose Inda-Filho

Full Text Available N-acetylcysteine (NAC or sodium bicarbonate (NaHCO3, singly or combined, inconsistently prevent patients exposed to radiographic contrast media from developing contrast-induced acute kidney injury (CI-AKI.We asked whether intravenous isotonic saline and either NaHCO3 in 5% dextrose or else a high dose of NAC in 5% dextrose prevent CI-AKI in outpatients exposed to high-osmolal iodinated contrast medium more than does saline alone.This completed prospective, parallel, superiority, open-label, controlled, computer-randomized, single-center, Brazilian trial (NCT01612013 hydrated 500 adult outpatients (214 at high risk of developing CI-AKI exposed to ioxitalamate during elective coronary angiography and ventriculography. From 1 hour before through 6 hours after exposure, 126 patients (group 1 received a high dose of NAC and saline, 125 (group 2 received NaHCO3 and saline, 124 (group 3 received both treatments, and 125 (group 4 received only saline.Groups were similar with respect to age, gender, weight, pre-existing renal dysfunction, hypertension, medication, and baseline serum creatinine and serum cystatin C, but diabetes mellitus was significantly less prevalent in group 1. CI-AKI incidence 72 hours after exposure to contrast medium was 51.4% (257/500, measured as serum creatinine > (baseline+0.3 mg/dL and/or serum cystatin C > (1.1 · baseline, and 7.6% (38/500, measured as both serum creatinine and serum cystatin C > (baseline+0.3 mg/dL or > (1.25 · baseline. CI-AKI incidence measured less sensitively was similar among groups. Measured more sensitively, incidence in group 1 was significantly (p<0.05 lower than in groups 2 and 3 but not group 4; adjustment for confounding by infused volume equalized incidence in groups 1 and 3.We found no evidence that intravenous isotonic saline and either NaHCO3 or else a high dose of NAC prevent CI-AKI in outpatients exposed to high osmolal iodinated contrast medium more than does saline alone

Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects.

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Sebastian J Padayatty

2010-07-01

Full Text Available Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM practitioners. The scale of such use in the U.S. and associated side effects are unknown.We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U.S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA's Adverse Events Database. Of 199 survey respondents (out of 550, 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25 g/50 ml vials were 318,539 in 2006 and 354,647 in 2008. Manufacturers' yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue. Of 9,328 patients for whom data is available, 101 had side effects, mostly minor, including lethargy/fatigue in 59 patients, change in mental status in 21 patients and vein irritation/phlebitis in 6 patients. Publications documented serious adverse events, including 2 deaths in patients known to be at risk for IV vitamin C. Due to confounding causes, the FDA Adverse Events Database was uninformative. Total numbers of patients treated in the US with high dose vitamin C cannot be accurately estimated from this study.High dose IV vitamin C is in unexpectedly wide use by CAM practitioners. Other than the known complications of IV vitamin C in those with renal impairment or glucose 6 phosphate dehydrogenase deficiency, high dose intravenous vitamin C appears to be remarkably safe. Physicians should inquire about IV vitamin C use in patients with cancer, chronic, untreatable, or intractable conditions and be observant of unexpected harm, drug interactions, or benefit.

Sustained Local Release of Methylprednisolone From a Thiol-Acrylate Poly(Ethylene Glycol) Hydrogel for Treating Chronic Compressive Radicular Pain.

Science.gov (United States)

Slotkin, Jonathan R; Ness, Jennifer K; Snyder, Kristin M; Skiles, Amanda A; Woodard, Eric J; OʼShea, Timothy; Layer, Rick T; Aimetti, Alex A; Toms, Steven A; Langer, Robert; Tapinos, Nikos

2016-04-01

A preclinical animal model of chronic ligation of the sciatic nerve was used to compare the effectiveness of a slow-release hydrogel carrying methylprednisolone to methylprednisolone injection alone, which simulates the current standard of care for chronic compressive radiculopathy (CR). To extend the short-term benefits of steroid injections by using a nonswelling, biodegradable hydrogel as carrier to locally release methylprednisolone in a regulated and sustained way at the site of nerve compression. CR affects millions worldwide annually, and is a cause of costly disability with significant societal impact. Currently, a leading nonsurgical therapy involves epidural injection of steroids to temporarily alleviate the pain associated with CR. However, an effective way to extend the short-term effect of steroid treatment to address the chronic component of CR does not exist. We induced chronic compression injury of the sciatic nerves of rats by permanent ligation. Forty-eight hours later we injected our methylprednisolone infused hydrogel and assessed the effectiveness of our treatment for 4 weeks. We quantified mechanical hyperalgesia using a Dynamic Plantar Aesthesiometer (Ugo Basile, Stoelting Co., IL, USA), whereas gait analysis was conducted using the Catwalk automated gait analysis platform (Noldus, Leesburg, VA, USA). Macrophage staining was performed with immunohistochemistry and quantification of monocyte chemoattractant protein-1 in sciatic nerve lysates was performed with multiplex immunoassay using a SECTOR Imager 2400A (Meso Scale Discovery, Rockville, MA, USA). We demonstrate that using the hydrogel to deliver methylprednisolone results in significant (P pain in an animal model of chronic CR. Our steroid-infused hydrogel could be an effective extender of the short-term benefits of epidural steroid injections for patients with chronic compression-induced radicular pain. N/A.

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.

High dose, fast delivery magnesium sulphate in a 3-year-old acute severe asthmatic

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John R Elton

2017-09-01

Full Text Available Acute severe asthma when respiratory failure is imminent is not addressed in world asthma guidelines. Intravenous magnesium sulphate, salbutamol and aminophylline all have advocates but what order, speed of delivery or dosage is left up to the individual physician treating the patient. A child in respiratory failure was given a large, fast dose of intravenous magnesium sulphate before intravenous salbutamol which relaxed bronchial smooth muscle immediately and tracheal intubation and lung ventilation was avoided. Justification for this treatment is discussed.

Dr Michaels® product family (also branded as Soratinex®) versus Methylprednisolone aceponate - a comparative study of the effectiveness for the treatment of plaque psoriasis.

Science.gov (United States)

Hercogovấ, J; Fioranelli, M; Gianfaldoni, S; Chokoeva, A A; Tchernev, G; Wollina, U; Tirant, M; Novotny, F; Roccia, M G; Maximov, G K; França, K; Lotti, T

2016-01-01

As one of the most common dermatologic chronic-recurrent disease, variable therapeutic options are available today for management of psoriasis. Although topical high potency corticosteroids, alone or in association with salicylic acid or vitamin D analogues, are still considered the best treatment, they do not seem to possess the capability for a long-term control of the disease or prevent recurrences, as their side effects are major contraindications for continuative use. The aim of this study was to investigate whether Dr. Michaels® product family is comparable to methylprednisolone aceponate (MPA) as a viable alternative treatment option for the treatment and management of stable chronic plaque psoriasis. Thirty adults (13 male, 17 female, mean age 40 years) with mild to severe stable chronic plaque psoriasis, were included in the study. Patients were advised to treat the lesions of the two sides of their body (left and right) with two different unknown modalities for 8 weeks; the pack of Dr. Michaels® products on the left side (consisting of a cleansing gel, an ointment and a skin conditioner) and a placebo pack on the right side, consisting of a cleansing gel, methylprednisolone ointment and a placebo conditioner. Assessment was done using the Psoriasis Activity Severity Index (PASI) scores before treatment and after 2, 4, 6 and 8 weeks. The results achieved with the Dr. Michaels® (Soratinex®) product family for the treatment of chronic plaque psoriasis were better than the results achieved with methylprednisolone aceponate (MPA), even though quicker resolution was achieved with the steroid with 45% of patients achieving resolution within 8-10 days in comparison to 5-6 weeks in the Dr. Michaels® (Soratinex®) group. Before therapy, the mean PASI score of the LHS in Dr. Michaels® (Soratinex®) group was 13.8±4.1 SD and 14.2±4.2 SD in the RHS methylprednisolone aceponate (MPA) group. After 8 weeks of treatment 62% of the Dr. Michaels® (Soratinex

Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant

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Abdulla Alawadhi

2018-03-01

Full Text Available BackgroundAcute hemorrhagic encephalomyelitis (AHEM is considered as a rare form of acute disseminated encephalomyelitis characterized by fulminant encephalopathy with hemorrhagic necrosis and most often fatal outcome.ObjectiveTo report the association with Ran Binding Protein (RANBP2 gene variant and the response to decompressive craniectomy and high-dose intravenous methylprednisolone (IVMP in life-threatening AHEM.DesignSingle case study.Case reportA 6-year-old girl known to have sickle cell disease (SCD presented an acquired demyelinating syndrome (ADS with diplopia due to sudden unilateral fourth nerve palsy. She received five pulses of IVMP (30 mg/kg/day. Two weeks after steroid weaning, she developed right hemiplegia and coma. Brain magnetic resonance imaging showed a left frontal necrotico-hemorrhagic lesion and new multifocal areas of demyelination. She underwent decompressive craniotomy and evacuation of an ongoing left frontoparietal hemorrhage. Comprehensive investigations ruled out vascular and infectious process. The neurological deterioration stopped concomitantly with combined neurosurgical drainage of the hematoma, decompressive craniotomy, IVMP, and intravenous immunoglobulins (IVIG. She developed during the following months Crohn disease and sclerosing cholangitis. After 2-year follow-up, there was no new neurological manifestation. The patient still suffered right hemiplegia and aphasia, but was able to walk. Cognitive/behavioral abilities significantly recovered. A heterozygous novel rare missense variant (c.4993A>G, p.Lys1665Glu was identified in RANBP2, a gene associated with acute necrotizing encephalopathy. RANBP2 is a protein playing an important role in the energy homeostasis of neuronal cells.ConclusionIn any ADS occurring in the context of SCD and/or autoimmune condition, we recommend to slowly wean steroids and to closely monitor the patient after weaning to quickly treat any recurrence of neurological symptom

A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury.

Science.gov (United States)

Coleman, W P; Benzel, D; Cahill, D W; Ducker, T; Geisler, F; Green, B; Gropper, M R; Goffin, J; Madsen, P W; Maiman, D J; Ondra, S L; Rosner, M; Sasso, R C; Trost, G R; Zeidman, S

2000-06-01

From the beginning, the reporting of the results of National Acute Spinal Cord Injury Studies (NASCIS) II and III has been incomplete, leaving clinicians in the spinal cord injury (SCI) community to use or avoid using methylprednisolone in acute SCI on the basis of faith rather than a publicly developed scientific consensus. NASCIS II was initially reported by National Institutes of Health announcements, National Institutes of Health facsimiles to emergency room physicians, and the news media. The subsequent report in the New England Journal of Medicine implied that there was a positive result in the primary efficacy analysis for the entire 487 patient sample. However, this analysis was in fact negative, and the positive result was found only in a secondary analysis of the subgroup of patients who received treatment within 8 hours. In addition, that subgroup apparently had only 62 patients taking methylprednisolone and 67 receiving placebo. The NASCIS II and III reports embody specific choices of statistical methods that have strongly shaped the reporting of results but have not been adequately challenged or or even explained. These studies show statistical artifacts that call their results into question. In NASCIS II, the placebo group treated before 8 hours did poorly, not only when compared with the methylprednisolone group treated before 8 hours but even when compared with the placebo group treated after 8 hours. Thus, the positive result may have been caused by a weakness in the control group rather than any strength of methylprednisolone. In NASCIS III, a randomization imbalance occurred that allocated a disproportionate number of patients with no motor deficit (and therefore no chance for recovery) to the lower dose control group. When this imbalance is controlled for, much of the superiority of the higher dose group seems to disappear. The NASCIS group's decision to admit persons with minor SCIs with minimal or no motor deficit not only enables statistical

Low-Dose versus Standard-Dose Intravenous Immunoglobulin to Prevent Fetal Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia: A Randomized Trial.

Science.gov (United States)

Paridaans, Noortje P; Kamphuis, Marije M; Taune Wikman, Agneta; Tiblad, Eleonor; Van den Akker, Eline S; Lopriore, Enrico; Challis, Daniel; Westgren, Magnus; Oepkes, Dick

2015-01-01

Pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are commonly treated using weekly intravenous immunoglobulin (IVIG) at 1 g/kg maternal weight. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to evaluate the effectiveness of IVIG at a lower dose, i.e., 0.5 g/kg. This was a randomized controlled multicenter trial conducted in Sweden, the Netherlands and Australia. Pregnant women with human platelet antigen alloantibodies and an affected previous child without intracranial hemorrhage (ICH) were enrolled. The participants were randomized to IVIG at 0.5 or 1 g/kg per week. The analyses were per intention to treat. The primary outcome was fetal or neonatal ICH. Secondary outcomes were platelet count at birth, maternal and neonatal IgG levels, neonatal treatment and bleeding other than ICH. A total of 23 women were randomized into two groups (low dose: n = 12; standard dose: n = 11). The trial was stopped early due to poor recruitment. No ICH occurred. The median newborn platelet count was 81 × 10(9)/l (range 8-269) in the 0.5 g/kg group versus 110 × 10(9)/l (range 11-279) in the 1 g/kg group (p = 0.644). The risk of adverse outcomes in FNAIT pregnancies treated with IVIG at 0.5 g/kg is very low, similar to that using 1 g/kg, although our uncompleted trial lacked the power to conclusively prove the noninferiority of using the low dose.

Gadolinium-enhanced magnetic resonance imaging predicts response to methylprednisolone in multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, F; Jensen, C.V.; Larsson, H.B.W.

2003-01-01

underwent lumbar puncture before treatment. The odds ratio (OR) of improvement after methylprednisolone treatment (a one point change in the visual function system score of the Kurtzke Expanded Disability Status Scale (EDSS) in ON or in the EDSS score in attacks of MS) was higher in patients with enhancing...

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

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Berkó S

2016-05-01

Full Text Available Szilvia Berkó,1,* Kálmán F Szűcs,2,* Boglárka Balázs,1,3 Erzsébet Csányi,1 Gábor Varju,4 Anita Sztojkov-Ivanov,2 Mária Budai-Szűcs,1 Judit Bóta,2 Róbert Gáspár2 1Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 2Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 3Gedeon Richter Plc., Budapest, 4Dr Derm Clinic of Anti-Aging Dermatology, Aesthetic Laser and Plastic Surgery, Budapest, Hungary *These authors contributed equally to this work Purpose: 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. Methods: The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Results: 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. Conclusion: 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. Keywords: transdermal

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

Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination.

Science.gov (United States)

Schneider, M; Paulin, A; Dron, F; Woehrlé, F

2014-12-01

The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl(®) ). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4-16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

VISUAL OUTCOME OF TRAUMATIC OPTIC NEUROPATHY IN PATIENTS TREATED WITH INTRAVENOUS MEGADOSE OF STEROIDS

Directory of Open Access Journals (Sweden)

A. Sadeghi-Tari

2005-05-01

Full Text Available Although uncommon, traumatic optic neuropathy (TON is an important cause of visual loss. Different therapeutic approaches including different dosages of steroids, surgical decompression of optic canal and observation alone have been suggested but there has been no conclusive evidence to establish a standard approach to this devastating cause of visual loss. To determine the effectiveness of intravenous (IV steroids in the treatment of these patients, the medical records of patients with TON, including one bilateral case, treated with IV steroids were reviewed. Twenty-eight patients (22 males, 6 females with mean age of 24.1 (11 to 41 years were enrolled. All patients had received 30 mg/kg loading dose of methylprednisolone succinate followed by 5.4 mg/kg/ hour for 48 hours. Visual acuity (VA was improved by ≥ 1 line in 8 eyes (28.6% immediately after treatment and in 10 eyes (37% after 3 months; however, most of them (6 and 8, respectively were in the range of initial VA of no light perception to hand motion. After adjustment for the baseline VA, these improvements in visual acuities were not considered significant. Neither different orbital fractures, nor various extraocular muscle palsies had any significant effect on the prognosis of ultimate VA. Regarding the natural course of TON, this investigation showed that IV megadose steroids had no clear benefit on the visual outcome of patients with TON.

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.

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...

High-dose erythropoietin in patients with progressive multiple sclerosis

DEFF Research Database (Denmark)

Schreiber, Karen; Magyari, Melinda; Sellebjerg, Finn

2017-01-01

BACKGROUND: Erythropoietin (EPO) is a part of an endogenous neuroprotective system in the brain and may address pathophysiological mechanisms in progressive multiple sclerosis (MS). OBJECTIVE: To evaluate a treatment effect of EPO on progressive MS. METHODS: This was a single-center, randomized......, double-blind, placebo-controlled phase 2 trial, in which 52 patients with secondary or primary progressive MS were allocated to treatment with recombinant EPO (48,000 IU) or placebo, administered intravenously 17 times during 24 weeks. Patients had an Expanded Disability Status Score (EDSS) from 4 to 6......: This study provides class II evidence that treatment with high-dose EPO is not an effective treatment in patients with moderately advanced progressive MS....

Asthma: non-responsiveness to conventional therapy.

Science.gov (United States)

Rebuck, A S

1986-01-01

Despite regular inhalation of beta-agonists, topical steroids and anticholinergic aerosols and the achievement of therapeutic blood levels of theophylline, some asthmatics have rapidly fluctuating levels of peak flow measurements throughout the day. Often little or no improvement is obtained with larger doses of corticosteroids. Before embarking on more intense drug therapy, attention should be paid to conscientious adherence to the prescribed regimen and avoidance of aspirin and tartrazine, as well as to exposure to allergens such as those associated with household pets. A number of newer therapeutic options are related to the use of air jet or ultrasonic nebulizers, that allow liquid forms of inhalation agents to be taken slowly in the home environment. In this regard, combination therapy with a beta-agonist and the anticholinergic ipratropium has been shown to have bronchodilating properties superior to either agent used alone. Secondly, sodium cromoglycate in its liquid form appears to have bronchodilator properties; taken on a regular basis, four times per day, it appears to have a steroid-sparing effect. Two alternatives are available for increasing the intensity of corticosteroid therapy, other than by prolonged, high-dose prednisone. The first is that of high-dose inhaled beclomethasone (up to 2000 micrograms/day) using the 250 micrograms/puff inhaler. The second is that of intravenous therapy with methylprednisolone, recently shown to have lung permeability superior to that of prednisolone. Office patients can be treated with occasional or even regular 'pulse' doses of methylprednisolone, an approach that is now finding acceptance in the management of the inflammatory alveolitides.

Successful outcome after intravenous gasoline injection.

Science.gov (United States)

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.

Association between low-dose pulsed intravenous cyclophosphamide therapy and amenorrhea in patients with systemic lupus erythematosus: A case-control study

Science.gov (United States)

2011-01-01

Background The risk for amenorrhea following treatment of systemic lupus erythematosus (SLE) patients with low-dose intravenous cyclophosphamide (IVCY) has not been fully explored. Our objective was to ascertain the incidence of amenorrhea following treatment with low-dose IVCY and the association between amenorrhea and the clinical parameters of SLE. Methods A case-control retrospective study of premenopausal women ≤ 45 years old who had been treated for SLE with low-dose IVCY (500 mg/body/pulse) plus high-dose glucocorticoids (0.8-1.0 mg/kg/day of prednisolone; IVCY group) or glucocorticoids alone (0.8-1.0 mg/kg/day of prednisolone; steroid group) in our hospital from 2000 through 2009 was conducted using a questionnaire survey and medical record review. Results Twenty-nine subjects in the IVCY group and 33 subjects in the steroid group returned the questionnaire. A multivariate analysis revealed that age at initiation of treatment ≥ 40 years old was significantly associated with amenorrhea [p = 0.009; odds ratio (OR) 10.2; 95% confidence interval (CI) 1.8-58.7]. IVCY treatment may display a trend for association with amenorrhea (p = 0.07; OR 2.9; 95% CI 0.9-9.4). Sustained amenorrhea developed in 4 subjects in the IVCY group and 1 subject in the steroid group; all of these patients were ≥ 40 years old. Menses resumed in all subjects amenorrhea, our data suggest that patients amenorrhea with low-dose IVCY treatment. A higher risk for sustained amenorrhea following treatment with IVCY is a consideration for patients ≥ 40 years old. PMID:21663683

Cyclosporin-Methotrexate Compared with Cyclosporin-Methotrexate-Methylprednisolone Therapy for the Prophylaxis of Acute Graft-Versus Host Disease

International Nuclear Information System (INIS)

Khattab, N.F.

2010-01-01

Acute graft-versus host (GVHD) disease is a common immunologic complication, which occurs in 40-50% of the recipients of allogenic stem cell transplantation (SCT). The role of corticosteroid in the prevention of GVHD is not well established. We report here a study to determine whether the addition of methylprednisolone to the combination of cyclosporine (CSA) and methotrexate (MTX), methylp-rednisolone (MP) for the prophylaxis of acute GVHD would further decrease the incidence of acute GVHD. A group of patients (25 patients with acute myeloid leukemia (AML) and 12 patients with acute lymphocytic leukemia (ALL) that received CSA/MTX/MP started from 2004 to 2008, were compared to a historical group of patients (19 patient with acute myeloid leukemia (AML) and 12 patients with acute lymphocytic leukemia (ALL) that received GVHD prophylaxis in the form of CSA/MTX only from 1999 to 2003). The primary endpoint in this study was the develop-ment of GVHD and the secondary end point was overall and disease free survival. Both groups of patients were matched for age, sex, donor recipient sex, low risk patients and high risk patients. Although the incidence of acute GVHD in the MP -ve group was 35% versus 24% in the MP+ve group, there was no significant difference between them. The overall survival showed a significant difference between the 2 groups (p<0.05). It was 48% for the 2 drug regimen (CSA/MTX) vs. 81% for the three drug regimen (CSA/MTX/MP). There was a significant decrease in the relapse rate in patients on CSA/MTX/MP (p<0.05). In conclusion, the addition of MP (methylprednis-olone) to the combination of CSA/MTX did not affect the incidence of acute GVHD significantly in allogeneic SCT but surprisingly the incidence of survival and relapse was markedly increased and decreased respectively

Comparison of the pharmacokinetics of imipenem after intravenous and intrathecal administration in rabbits.

Science.gov (United States)

Wang, Y; Qiu, L; Dong, J; Wang, B; Shi, Z; Liu, B; Wang, W; Zhang, J; Cai, S; Ye, G; Cai, X

2013-03-01

Intrathecal administration of antibiotics has potentially high effectiveness for the treatment for severe intracranial infections, particularly nosocomial meningitis. The use of intrathecal injection of antibiotics has been reported mostly in case reports. However, there is sparse data regarding the pharmacokinetics of antibiotics after intrathecal administration. This study investigated whether intrathecal injection is an effective method for the administration of imipenem. The pharmacokinetics of imipenem after intrathecal and intravenous administration of 1:1 imipenem: cilastatin (IMI/CIL) to rabbits were compared. The AUC0-t in the cerebrospinal fluid for intrathecal administration was approximately twice that of an equal dose of intravenous administration at doses of 0.35, 0.7, and 1.4 mg/kg. Brain concentrations of imipenem after intrathecal injection were three times greater than observed after intravenous injection and remained high for at least 8 hours post-injection. Elimination of imipenem after administration by either route was primarily via urine, but a transient surge of imipenem in bile and intestinal tissue was observed. Results indicate that there is a clinical potential for intrathecally administered IMI/CIL. Further studies are warranted to investigate the potential for seizure and to assess the translatability of the rabbit model to human treatment.

The new generation of intravenous iron: chemistry, pharmacology, and toxicology of ferric carboxymaltose.

Science.gov (United States)

Funk, Felix; Ryle, Peter; Canclini, Camillo; Neiser, Susann; Geisser, Peter

2010-01-01

An ideal preparation for intravenous iron replacement therapy should balance effectiveness and safety. Compounds that release iron rapidly tend to cause toxicity, while large molecules can induce antibody formation and cause anaphylactic reactions. There is therefore a need for an intravenous iron preparation that delivers appropriate amounts of iron in a readily available form but with minimal side effects and thus with an excellent safety profile. In this paper, a review is given on the chemistry, pharmacology, and toxicology of ferric carboxymaltose (FCM, Ferinject), a stable and robust complex formulated as a colloidal solution with a physiological pH. The complex is gradually taken up mainly from the hepatic reticulo-endothelial system (RES), followed by effective delivery of iron to the endogeneous transport system for the haem synthesis in new erythrocytes, as shown in studies on the pharmacodynamics and pharmacokinetics with radio-labelled FCM. Studies with radio-labelled FCM also demonstrated a barrier function of the placenta and a low transfer of iron into the milk of lactating rats. Safety pharmacology studies indicated a favourable profile with regard to cardiovascular, central nervous, respiratory, and renal toxicity. A high maximum non-lethal dose was demonstrated in the single-dose toxicity studies. Furthermore, based on the No-Observed-Adverse-Effect-Levels (NOAELs) found in repeated-dose toxicity studies and on the cumulative doses administered, FCM has good safety margins. Reproductive and developmental toxicity studies did not reveal any direct or indirect harmful effects. No genotoxic potential was found in in vitro or in vivo studies. Moreover, antigenicity studies showed no cross-reactivity of FMC with anti-dextran antibodies and also suggested that FCM does not possess sensitizing potential. Lastly, no evidence of irritation was found in local tolerance studies with FCM. This excellent toxicity profile and the high effectiveness of FCM allow

Rapid Inpatient Titration of Intravenous Treprostinil for Pulmonary Arterial Hypertension: Safe and Tolerable.

Science.gov (United States)

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.

Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

Energy Technology Data Exchange (ETDEWEB)

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

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.

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

Does intravenous induction dosing among patients undergoing gastrointestinal surgical procedures follow current recommendations: a study of contemporary practice.

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Akhtar, Shamsuddin; Liu, Jia; Heng, Joseph; Dai, Feng; Schonberger, Robert B; Burg, Matthew M

2016-09-01

It is recommended to correct intravenous induction doses by up to 50% for patients older than 65 years. The objectives were to determine (a) the degree to which anesthesia providers correct induction doses for age and (b) additionally adjust for American Society of Anesthesiologists physical status (ASA-PS) class (severity of illness) and (c) whether postinduction hypotension is more common among patients aged >65. Retrospective chart review. Academic medical center. A total of 1869 adult patients receiving general anesthesia for GI surgical procedures from February 2013 to January 2014. Patients were divided into 3 age groups (age 80, which was still in less than the recommendations. An inverse relationship was observed between propofol dosing and ASA-PS class, but no consistent relationship was noted for fentanyl and midazolam. There were a significantly larger drop in mean arterial pressure and a greater likelihood of hypotension following induction in patients aged 65-79 years and >80 years as compared with those aged <65 years. This study shows that the administered dose of anesthetic induction agents is significantly higher than that recommended for patients older than 65 years. This failure to age-adjust dose may contribute to hypotensive episodes. Copyright © 2016 Elsevier Inc. All rights reserved.

Intravenous iron sucrose therapy for moderate to severe anaemia in pregnancy.

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Kriplani, Alka; Mahey, Reeta; Dash, Biswa Bhusan; Kulshreshta, Vidushi; Agarwal, Nutan; Bhatla, Neerja

2013-01-01

Iron deficiency anaemia (IDA) is the most common nutritional deficiency in pregnancy. Prophylactic oral iron is recommended during pregnancy to meet the increased requirement. In India, women become pregnant with low baseline haemoglobin level resulting in high incidence of moderate to severe anaemia in pregnancy where oral iron therapy cannot meet the requirement. Pregnant women with moderate anaemia are to be treated with parentral iron therapy. This study was undertaken to evaluate the response and effect of intravenous iron sucrose complex (ISC) given to pregnant women with IDA. A prospective study was conducted (June 2009 to June 2011) in the department of Obstetrics & Gynecology, All India Institute of Medical Sciences, New Delhi. One hundred pregnant women with haemoglobin between 5-9 g% with diagnosed iron deficiency attending antenatal clinic were given intravenous iron sucrose complex in a dose of 200 mg twice weekly schedule after calculating the dose requirement. The mean haemoglobin raised from 7.63 ± 0.61 to 11.20 ± 0.73 g% (Panaemia. Intravenous iron sucrose can be used in hospital settings and tertiary urban hospitals where it can replace intramuscular therapy due to injection related side effects. Further, long-term comparative studies are required to recommend its use at peripheral level.

A randomized, double-blinded, controlled trial of the effects of fluid rate and/or presence of dextrose in intravenous fluids on the labor course of nulliparas.

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Fong, Alex; Serra, Allison E; Caballero, Deysi; Garite, Thomas J; Shrivastava, Vineet K

2017-08-01

Prolonged labor has been demonstrated to increase adverse maternal and neonatal outcome. A practice that may decrease the risk of prolonged labor is the modification of fluid intake during labor. Several studies demonstrated that increased hydration in labor as well as addition of dextrose-containing fluids may be associated with a decrease in length of labor. The purpose of our study was to characterize whether high-dose intravenous fluids, standard-dose fluids with dextrose, or high-dose fluids with dextrose show a difference in the duration of labor in nulliparas. Nulliparous subjects with singletons who presented in active labor were randomized to 1 of 3 groups of intravenous fluids: 250 mL/h of normal saline, 125 mL/h of 5% dextrose in normal saline, or 250 mL/h of 2.5% dextrose in normal saline. The primary outcome was total length of labor from initiation of intravenous fluid in vaginally delivered subjects. Secondary outcomes included cesarean delivery rate and length of second stage of labor, among other maternal and neonatal outcomes. In all, 274 subjects who met inclusion criteria were enrolled. There were no differences in baseline characteristics among the 3 groups. There was no difference in the primary outcome of total length of labor in vaginally delivered subjects among the 3 groups. First stage of labor duration, second stage of labor duration, and cesarean delivery rates were also equivalent. There were no differences identified in other secondary outcomes including clinical chorioamnionitis, postpartum hemorrhage, blood loss, Apgar scores, or neonatal intensive care admission. There is no difference in length of labor or delivery outcomes when comparing high-dose intravenous fluids, addition of dextrose, or use of high-dose intravenous fluids with dextrose in nulliparous women who present in active labor. Copyright © 2017 Elsevier Inc. All rights reserved.

[Anti-Ma2, anti-NMDA-receptor and anti-GluRε2 limbic encephalitis with testicular seminoma: short-term memory disturbance].

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Kubota, Akihiro; Tajima, Takashi; Narukawa, Shinya; Yamazato, Masamizu; Fukaura, Hikoaki; Takahashi, Yukitoshi; Tanaka, Keiko; Shimizu, Jun; Nomura, Kyoichi

2012-01-01

A 36-year-old man presented with cognitive impairment and disturbance of short-term memory functions with character change. Cerebrospinal fluid analysis revealed no abnormalities; however, brain MRI revealed high-signal intensity from bilateral hippocampus lesions on fluid attenuated inversion recovery (FLAIR) images and T(2) weighted images. The 18F-fluorodeoxyglucose PET demonstrated high glucose uptake in the bilateral hippocampus lesions. He was diagnosed as limbic encephalitis, and was administered high-dose intravenous methylprednisolone and immune adsorption plasma therapy followed by intravenous immunoglobulin therapy. MRI abnormalities improved after treatment but recent memory disturbance remained. Ma2 antibody, NMDA-receptor antibody, and GluRε2 antibody were positive. Eleven months atter the onset of disease, the tumor was identified in left testicle by ultrasound and removed the tumor. The pathological findings were seminoma. We experienced a case of paraneoplastic limbic encephalitis associated with seminoma with short-term memory disturbance. The occurrence of paraneoplastic limbic encephalitis with antibodies against cell membrane (NMDA-receptor antibody and GluRε2 antibody) and intracellular (Ma2 antibody) is rare even in the literature.

Characterization of ornidazole metabolites in human bile after intraveneous doses by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry

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Jiangbo Du

2012-04-01

Full Text Available Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS was used to characterize ornidazole metabolites in human bile after intravenous doses. A liquid chromatography tandem mass spectrometry (LC–MS/MS assay was developed for the determination of the bile level of ornidazole. Bile samples, collected from four patients with T-tube drainage after biliary tract surgery, were prepared by protein precipitation with acetonitrile before analysis. A total of 12 metabolites, including 10 novel metabolites, were detected and characterized. The metabolites of ornidazole in human bile were the products of hydrochloride (HCl elimination, oxidative dechlorination, hydroxylation, sulfation, diastereoisomeric glucuronation, and substitution of NO2 or Cl atom by cysteine or N-acetylcysteine, and oxidative dechlorination followed by further carboxylation. The bile levels of ornidazole at 12 h after multiple intravenous infusions were well above its minimal inhibitory concentration for common strains of anaerobic bacteria.

Urinary profile of methylprednisolone and its metabolites after oral and topical administrations.

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Matabosch, Xavier; Pozo, Oscar J; Monfort, Núria; Pérez-Mañá, Clara; Farré, Magi; Marcos, Josep; Segura, Jordi; Ventura, Rosa

2013-11-01

Methylprednisolone (MP) is prohibited in sports competitions when administered by systemic routes; however its use by topical administration is allowed. Therefore, analytical approaches to distinguish between these different administration pathways are required. A reporting level of 30ng/mL was established for this purpose. However, the suitability of that reporting level for MP is not known. In the present work, excretion profiles of MP and different metabolites after oral and topical administrations have been compared. A method for the quantification of MP and the qualitative detection of fifteen previously reported metabolites has been validated. The method involved an enzymatic hydrolysis, liquid-liquid extraction and analysis by liquid chromatography coupled to tandem mass spectrometry. The method was found to be linear, selective, precise and accurate. The high sensitivity (limit of detection 0.1ng/mL) and linear range (0.1-250ng/mL) achieved allowed for the quantification of MP at both the low concentrations present after topical administration and the high concentrations detected after oral intake. The method was applied to samples collected after oral (4 or 40mg) and topical administration (10mg of MP aceponate/day for 5 consecutive days) to healthy volunteers. After oral administration, MP and all metabolites were detected in urines collected up to at least 36h. Only MP and five metabolites were detected in samples obtained after topical treatment. As expected, concentrations of MP after topical administration were well below current reporting level (30ng/mL), however 3 out of 4 samples in range 8-24h after the low oral dose (4mg) were also below that concentration. Taking into account metabolites detected after both administration routes, metabolites 16β,17α,21-trihydroxy-6α-methylpregna-1,4-diene-3,11,20-trione (M8) and 17α,20α,21-trihydroxy-6α-methylpregna-1,4-diene-3,11-dione (M11) are best markers to differentiate between topical and oral

[Conscious sedation and amnesic effect of intravenous low-dose midazolam prior to spinal anesthesia].

Science.gov (United States)

Koyama, Shinichi; Ohashi, Naotsugu; Kurita, Satoshi; Nakatani, Keiji; Nagata, Noboru; Toyoda, Yoshiroh

2008-06-01

The pain associated with spinal puncture is severe, and the memory of this uncomfortable procedure often deters patients from undergoing the procedure again. Therefore, it is important to make the patient as comfortable as possible when this procedure is performed. We administrated a low-dose (1-2.5 mg) of midazolam intravenously several minutes before conducting a spinal-tap in 200 patients undergoing elective surgery of the lower limb. The dose of midazolam used was based on the patient's age and weight, and we investigated remaining of a memory concerning the spinal-tap procedure and side effects of midazolam at the end of surgery. Memory of the spinal-tap procedure remained in 14.0%, 1.9%, and 32.7% of the patients who had received benzodiazepine preoperatively and in 25.0%, 40.0%, and 60.9% of the patients who hadn't received benzodiazepine preoperatively in the age group or =70 years, respectively. No patient experienced severe respiratory depression, but an excessive sedation or restlessness was experienced in 1.6%, 4.8%, and 5.2% of the patients. In the patients aged memory concerning the spinal-tap procedure; however, it is important to note that the number of side effects associated with this procedure increases in patients aged > or =60 years.

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

Successful Desensitization of T cell Flow Cytometry Crossmatch Positive Renal Transplant Recipients Using Plasmapheresis and Super High-Dose Intravenous Immunoglobulin

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Yoichi Kakuta, MD, PhD

2018-01-01

Full Text Available Background. High-dose IVIG (2 g/kg alone or low-dose IVIG (100 mg/kg in conjunction with plasma exchange is typically administered as a renal transplantation desensitization therapy. Herein, we monitored changes in T cell and B cell flow cytometry crossmatch (FCXM to assess the effects of short-term super high-dose IVIG (4 g/kg administration with plasmapheresis before living-donor renal transplantation. Methods. Seventeen patients, each showing positive T cell FCXM (median ratio, ≥ 1.4 after 2 rounds of double-filtration plasmapheresis, received 4-day regimens of IVIG (1 g/kg per day over 1-week periods. T cell and B cell FCXM determinations were obtained after every IVIG dose and again up to 4 weeks after initiating IVIG to ascertain negative conversion of T cell FCXM (median ratio < 1.4. The primary study endpoint was the percentage of patients achieving T cell FCXM-negative status after the 4-dose IVIG regimen. Results. Upon completion (4 g/kg total or discontinuation of IVIG administration, 8 (47.1% of 17 patients displayed negative T cell FCXM. Based on Kaplan-Meier estimates, the cumulative T cell FCXM-negative conversion rate 4 weeks after IVIG administration initiation was 60.3%. The T cell FCXM-negative conversion rates after cumulative doses of 1, 2, 3, and 4 g/kg IVIG were 29.4%, 35.3%, 56.3%, and 46.7%, respectively. Conclusions. Desensitization of donor-specific antibody-positive renal transplant recipients seems achievable in only a subset of recipients through IVIG dosing (1 g/kg × 4 within 1 week after double-filtration plasmapheresis. The T cell FCXM-negative conversion rate resulting from a cumulative IVIG dose of 3 g/kg or greater surpassed that attained via conventional single-dose IVIG (2 g/kg protocol. This short-term high-dose IVIG desensitization protocol may be an alternative to conventional protocols for recipients with donor-specific antibody.

Intravenous digital subtraction angiography contrast media time-concentration curves

International Nuclear Information System (INIS)

Burbank, F.H.; Brody, W.R.

1985-01-01

At any specified radiation dose and system signal-to-noise ratio, temporal (masked-mode) intravenous digital subtraction angiography (IV-DSA) image quality is dependent upon the shape of the arterial time-concentration curve produced by the intravenous injection of iodinated contrast media. If contrast media appears in the arterial circulation as a compact bolus and reaches a high peak, images containing low or no iodine (the mask image or images) and high iodine concentration (the enhanced image or images) can be obtained close together in time, maximizing contrast media enhancement and minimizing the potential for spatial movement (misregistration). However, if the contrast media bolus is broad, rising slowly to a low concentration peak, sufficient time may pass for movement to occur and the opacification difference between the mask image and the enhanced image may be too small to visualize vessels of interest. Consequently, knowledge of the rules which govern the formation of time-concentration curves is central to IV-DSA

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

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L John Hoffer

Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

Science.gov (United States)

Hoffer, L John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H

2015-01-01

Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy

The efficacy of low and high dose (99m)Tc-MIBI protocols for intraoperative identification of hyperplastic parathyroid glands in secondary hyperparathyroidism.

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Gencoglu, Esra Arzu; Aktas, Ayse

2014-01-01

The aim of this study was to compare the efficacy of low- and high-dose (99m)Tc-MIBI protocols for intraoperative identification of hyperplastic parathyroid glands via gamma probe in secondary hyperparathyroidism. This retrospective study was conducted using a prospective database of 59 patients who had undergone radioguided subtotal parathyroidectomy between 2004-2012. The patients were studied in 2 groups. Group 1 (n=31) received 37 MBq (99m)Tc-MIBI intravenously in the surgical room approximately 10 min before the beginning of the intervention and surgery was performed under gamma probe guidance. Group 2 (n=28) received 555 MBq (99m)Tc- MIBI intravenously 2h before surgery, which was also performed under gamma probe guidance. Intraoperative gamma probe findings, laboratory findings, and histopathological findings were evaluated together. Using acceptance of the histopathological findings as gold standard, sensitivity and specificity of intraoperative gamma probe for identifying hyperplastic parathyroid glands was 98% and 100%, respectively, in both groups. In the light of these findings, it is concluded that the low-dose (99m)Tc-MIBI protocol might be preferable for intraoperative identification of hyperplastic parathyroid glands in secondary hyperparathyroidism patients because it was observed to be as effective as the high-dose (99m)Tc-MIBI protocol. Furthermore, the low-dose protocol does not have the disadvantages that are associated with the high-dose protocol. Copyright © 2014 Elsevier España, S.L. and SEMNIM. All rights reserved.

[Comparative study on the tolerance and efficacy of high doses of metoclopramide and clebopride in vomiting induced by cisplatin].

Science.gov (United States)

Martín, M; Díaz-Rubio, E

1989-06-10

Forty-one patients treated with cisplatin (100-120 mg/m2), alone or associated with vindesine (3 mg/m2), were included in a randomized crossover pilot study which compared 3 different doses of intravenous clebopride with intravenous metoclopramide. The patients were randomly assigned to receive clebopride in the first chemotherapy course in one of the three dose levels used (0.5 mg/kg, 21 patients; 0.75 mg/kg, 11 patients; 1 mg/kg, 10 patients) or metoclopramide (10 mg/kg). In the second course of the same chemotherapy the patients received the alternative antiemetic, and thus each patient was his own control. The total dose of both antiemetic drugs was infused in 5 intravenous fractions given every 2 hours. The antiemetic activity of clebopride was moderately lower to that of metoclopramide with the first two tested doses (overall doses of 0.5 and 0.75 mg/kg) and similar with the last dose (1 mg/kg). Clebopride was reasonably well tolerated at the used dosages, inducing sedation in 20% of cases (versus 24% with metoclopramide) and diarrhea in 37% (versus 20% with metoclopramide). Extrapyramidal reactions developed in 17% of the courses which included metoclopramide and in none including clebopride. This difference was statistically significant.

Pharmacokinetics of lansoprazole and its main metabolites after single and multiple intravenous doses in healthy Chinese subjects.

Science.gov (United States)

Zhang, Dan; Zhang, Yanan; Liu, Man; Wang, Xiaolin; Yang, Man; Han, Jing; Liu, Huichen

2013-09-01

The aim of the study was to evaluate and compare the pharmacokinetics of lansoprazole (LPZ) and its main metabolites, 5'-hydroxy lansoprazole (HLPZ) and lansoprazole sulfone (LPZS), after single and multiple intravenous (i.v.) doses of LPZ in healthy Chinese subjects. Twelve subjects (six males and six females) were given a single dose of LPZ by i.v. infusion on day 1, and multiple doses from day 2 to day 6. Blood samples were collected at designated time points for analysis of plasma concentrations of LPZ, HLPZ and LPZS by an LC-MS/MS method. LPZ was generally well tolerated in healthy Chinese subjects. After single and multiple i.v. doses of 30 mg LPZ, the C max values of LPZ, HLPZ and LPZS were 1490 ± 290 and 1450 ± 280, 175 ± 71 and 154 ± 56, and 51.3 ± 82.9 and 74.1 ± 158.7 ng/mL, with the AUC0-t values 3280 ± 2550 and 4260 ± 3880, 381 ± 128 and 389 ± 111, and 389 ± 1204 and 700 ± 2255 ng h/mL, respectively. The t 1/2 and CL values of LPZ after single and multiple i.v. doses were 1.48 ± 1.03 and 2.19 ± 1.03 h, and 11.67 ± 4.49 and 9.56 ± 4.08 L/h, respectively. Compared with the pharmacokinetics of LPZ after a single dose, t 1/2 increased markedly, CL decreased significantly and AUC increased by over 20 % after multiple doses. The results indicated that there was drug accumulation of LPZ after multiple i.v. doses, and there was no gender-related difference in pharmacokinetics of LPZ and its two metabolites.

Corneal endothelial rejection after penetrating keratoplasty treated with intravenous and topic corticosteroid: one year follow up

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Ricardo Yuji Abe

2013-02-01

Full Text Available OBJECTIVE: To analyze the recovery of visual acuity (VA and graft survival after first episode of endothelial rejection in penetrating keratoplasty (PKP treated with intravenous (IV and topic corticosteroid. METHODS: Interventional, prospective, non-comparative case series study evolving 32 PKP patients in one year follow up, who presented first episode of corneal endothelial rejection. The patients were submitted to 500 mg IV injection of methylprednisolone in association with topical prednisolone. Main outcome measures included VA recovery and corneal edema regression. Second outcome included new rejections and graft failure. Multivariate analysis techniques were used to estimate rates of graft outcome events and the impact of risk factors. RESULTS: A total of 32 eyes from 32 patients (13 male and 19 female were included in the study. The mean VA (in number of letters before rejection was 48 (22 to 88 letters. Patients treated within 7 days or less of initial symptoms had better VA recovery, corneal edema regression and less graft failure (p<0.001. Patients with previous ocular surgery had worse VA recovery and more graft failure (p<0.047. CONCLUSION: The association between the other risk factors and the outcomes did not reach statistical significance in the multivariate model because of the small numbers of patients. Methylprednisolone in association with topical prednisolone is an alternative treatment for graft rejection. Our study showed that patients treated within 7 days of symptoms and no previous anterior segment surgery had better visual outcome and graft survival after treatment.

Effects of iloprost on bleomycin-induced pulmonary fibrosis in rats compared with methyl-prednisolone

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Z.A. Aytemur

2012-11-01

Full Text Available Objective: Prostacyclin (PGI2 has been shown to inhibit the expression of pro-inflammatory and pro-fibrotic mediators in pulmonary fibrosis. In this study, we aimed to test the preventive effects of intraperitoneally administered iloprost, a stable PGI2 analog, on bleomycin-induced pulmonary fibrosis in rats and to compare the effects of iloprost with the effects of methyl-prednisolone, a traditional therapy. Methods: Rats were randomly allocated into four groups: 1. Saline alone (n = 6; 2. Bleomycin + placebo (n = 7; 3. Bleomycin + methyl-prednisolone (n = 7; 4. Bleomycin + iloprost (n = 7. Fibrotic changes in the lungs were demonstrated by analyzing the cellular composition of bronchoalveolar lavage fluid, histological evaluation and lung hydroxyproline content. Results: Fibrosis was made in the lungs of rats by bleomycin experimentally. Fibrosis scores in the methyl-prednisolone and the iloprost groups were significantly lower than in the placebo group (p < 0.05. Furthermore, the score of the iloprost group was significantly lower than the score of the methyl-prednisolone group. The hydroxyproline content was significantly less in the methyl-prednisolone and the iloprost groups (p < 0.05. In the placebo group, the neutrophil percentage in bronchoalveolar lavage was significantly higher than in the other groups, whereas the macrophage percentage in placebo group was significantly lower (p < 0.05. Conclusion: Iloprost has protective effect on the pulmonary fibrosis induced by bleomycin and it may be more effective in decreasing fibrotic changes than methyl-prednisolone. Resumo: Objetivo: A prostaciclina (PGI2 é conhecida por inibir a expressão de mediadores pró-inflamatórios e pró-fibróticos na fibrose pulmonar. Neste estudo, procurou-se testar os efeitos preventivos do iloprost administrado por via intraperitoneal, um análogo estável do PGI2, na fibrose

Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of 14C-propofol.

Science.gov (United States)

Simons, P J; Cockshott, I D; Douglas, E J; Gordon, E A; Hopkins, K; Rowland, M

1988-04-01

1. An intravenous dose of 14C-propofol (0.47 mg/kg) administered to six male volunteers was rapidly eliminated with 88% recovered in the urine in 5 days and less than 2% in faeces. 2. The dose was cleared by metabolism with less than 0.3% excreted unchanged. The major metabolites were the glucuronic acid conjugate of propofol and the glucuronic acid and sulphate conjugates of its hydroxylated derivative, 2,6-diisopropyl-1,4-quinol. Propofol glucuronide accounted for about 53% of the urinary radioactivity and was the major metabolite in plasma from 30 min post dose. 3. The blood concentration of propofol declined in a biphasic manner from a maximum mean value of 0.44 microgram/ml, 2 min after injection. The half-lives of the first and second exponential phases, mean values 5 min and 97 min respectively, varied widely among subjects. A proportion of the dose was cleared slowly, probably due to slow release from less well perfused tissues. Propofol accounted for 94% of the total blood radioactivity at 2 min but only about 6% from 3 to 8 h post dose. 4. Propofol has a volume of distribution equivalent to about 3 to 4 times body weight, and a mean total body clearance of 2.2 1/min.

Comparative toxicity of 4 commonly used intravitreal corticosteroids on rat retina.

Science.gov (United States)

Citirik, Mehmet; Dilsiz, Nihat; Batman, Cosar; Zilelioglu, Orhan

2009-06-01

To investigate the effects of 4 commonly used steroids (dexamethasone, triamcinolone, betamethasone, and methylprednisolone) on 50 retinas of 25 adult pigmented rats. Experimental animal study. Twenty-five pigmented Long-Evans male rats. Each steroid drug with 2 different doses (0.025 mL and 0.050 mL) was injected into the vitreous of each eye of 5 rats. The low drug dose was injected into the right eye and the high dose was injected into the left eye. Ten eyes of 5 randomly selected rats were used as a control group and intravitreal saline was injected into these eyes. Oxidative damage and intrinsic antioxidative capacity were determined by measuring retinal malondialdehyde (MDA) and glutathione (GSH) levels, respectively. No statistically meaningful difference was observed in retinal GSH and MDA measurements in the low- and high-dose triamcinolone (1 and 2 mg), low-dose betamethasone (0.075 mg), and low-dose dexamethasone (0.1 mg) groups, compared with the control group. Both doses of methylprednisolone (1.6 mg and 3.2 mg), high-dose betamethasone (0.15 mg), and high-dose dexamethasone (0.2 mg) markedly altered retinal GSH and MDA levels. The results of our study show that the toxicity of triamcinolone is not evident even in high doses. It may be used safely. We also suggest that intravitreal use of low doses of betamethasone and dexamethasone is safer than higher doses of these drugs and both doses of methylprednisolone.

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)

NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis (NORMIMS study): a randomised, placebo-controlled trial

DEFF Research Database (Denmark)

Sorensen, Per Soelberg; Mellgren, Svein Ivar; Svenningsson, Anders

2009-01-01

BACKGROUND: Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective, and new more effective and safe strategies are needed. Our aim was to assess the efficacy of oral methylprednisolone as an add-on therapy to subcutaneous interferon beta-1a to reduce...... was 0.22 for methylprednisolone compared with 0.59 for placebo (62% reduction, 95% CI 39-77%; pSleep disturbance and neurological and psychiatric symptoms were the most frequent adverse events recorded in the methylprednisolone group. Bone mineral density had not changed after 96 weeks......, these findings need to be corroborated in larger cohorts....

Comparison of postoperative analgesic efficacy of intraoperative single-dose intravenous administration of dexketoprofen trometamol and diclofenac sodium in laparoscopic cholecystectomy.

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Anıl, Ali; Kaya, Fatma Nur; Yavaşcaoğlu, Belgin; Mercanoğlu Efe, Esra; Türker, Gürkan; Demirci, Abdurrahman

2016-08-01

The aim of this study is to compare the effects of intravenous single-dose dexketoprofen trometamol and diclofenac sodium 30 minutes before the end of the surgery on relief of postoperative pain in patients undergoing laparoscopic cholecystectomy. A randomized fashion. Sixty (American Society of Anesthesiologist class I-II) patients undergoing laparoscopic cholecystectomy were divided into 2 groups Patients in group DT received 50 mg dexketoprofen trometamol, whereas patients in group DS received 75 mg diclofenac sodium, intravenously 30 minutes before the end of surgery. Postoperative pain intensity, morphine consumption with patient-controlled analgesia, time to first analgesic requirement, complications, rescue analgesic (intravenous tenoxicam 20 mg) requirement, and duration of hospital stay were recorded. Postoperative pain visual analog scale scores were similar in the follow-up periods (P > .05). Patient-controlled analgesia morphine consumption was significantly less in group DT compared with group DS in all postoperative follow-up periods (2 and 4 hours: P dexketoprofen trometamol 30 minutes before the end of surgery provided effective analgesia with reduced consumption of opioids and requirement for rescue analgesic compared with diclofenac sodium in patients undergoing laparoscopic cholecystectomy. For this reason, we believe that, as a part of multimodal analgesia, dexketoprofen trometamol provides more effective analgesia than diclofenac sodium in patients undergoing laparoscopic cholecystectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of high doses of intracoronary adenosine on the assessment of fractional flow reserve

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Ahmed Khashaba

2014-03-01

Conclusions: Intracoronary adenosine, at doses higher than currently suggested, lows obtaining FFR values similar to IV adenosine. Intravenous adenosine, which remains the gold standard, might thus be reserved for those lesions with equivocal FFR values.

Early intravenous immunoglobin (two-dose regimen) in the management of severe Rh hemolytic disease of newborn--a prospective randomized controlled trial.

Science.gov (United States)

Elalfy, Mohsen Saleh; Elbarbary, Nancy Samir; Abaza, Heba Wegdan

2011-04-01

Phototherapy is the standard treatment in moderately severe hemolytic disease of newborn (HDN), whereas exchange transfusion (ET) is the second line in progressive cases. Intravenous immunoglobin (IVIG) has been suggested to decrease the need for ET. We aimed at assessing the efficacy of early two-dose regimens of IVIG to avoid unnecessary ET in severe Rh HDN. The study included 90 full-term neonates with Rh incompatibility unmodified by antenatal treatment and not eligible for early ET and which were randomly assigned into one of three groups: group (I), treated by conventional method; groups IIa and IIb received IVIG once at 12 h postnatal age if PT was indicated, in a dose of 0.5 and 1 g/kg, respectively. Analysis revealed 11 neonates (22%) in the conventional group and 2 (5%) in the intervention group who administered low-dose IVIG at 12 h, while none in group IIb required exchange transfusion (p = 0.03). Mean bilirubin levels were significantly lower during the first 96 h in the intervention group compared to the conventional group (p < 0.0001). Shorter duration of phototherapy (52.8 ± 12.39 h) and hospital stay (3.25 ± 0.71 days) in the IVIG group compared to conventional group (84 ± 12.12 h and 4.72 ± 0.78 days, p < 0.0001, respectively) were observed. We conclude that IVIG administration at 12 h was effective in the treatment of severe Rh HDN; the low-dose IVIG (0.5 g/kg) was as effective as high dose (1 g/kg) in reducing the duration of phototherapy and hospital stay, but less effective in avoiding exchange transfusion.

Single-shot, high-dose rabbit ATG for rejection prophylaxis after kidney transplantation

NARCIS (Netherlands)

R. Zietse (Bob); E.P.M. van Steenberge (E. P M); C.J. Hesse (Cees); L.B. Vaessen (L.); J.N.M. IJzermans (Jan); W. Weimar (Willem)

1993-01-01

textabstractWe studied the effects of a single intravenous injection of rabbit ATG (RIVM, Bilthoven, The Netherlands) in a dose of 8 mg/kg body weight administered 6 h after kidney transplantation on graft survival, rejection incidence, T-cell subsets, and cost-effectiveness. A total of 58 (37

Thallium-201 myocardial imaging during pharmacologic coronary vasodilation: comparison of oral and intravenous administration of dipyridamole

International Nuclear Information System (INIS)

Taillefer, R.; Lette, J.; Phaneuf, D.C.; Leveille, J.; Lemire, F.; Essiambre, R.

1986-01-01

Although the diagnostic utility of thallium-201 myocardial imaging after dipyridamole infusion is well established, the intravenous form of the drug is not yet commercially available in North America. Fifty patients referred for coronary angiography were prospectively studied. Within a 2 week period, each patient underwent cardiac catheterization and thallium-201 myocardial imaging after both oral and intravenous dipyridamole administration. For the oral protocol, patients were randomly assigned to treatment with either 200 or 400 mg of dipyridamole in tablet form. Coronary artery stenoses of 70% or greater were considered significant. For the 25 patients who received a 200 mg oral dose of dipyridamole, the scintigraphic study showed perfusion defects in 65% of patients with significant coronary artery disease after the oral dose and in 85% of patients after the intravenous dose. For the 25 patients who received a 400 mg oral dose, the sensitivity of the scintigram was 84% after the oral dose and 79% after the intravenous dose. Except for headache and nausea, side effects were less severe and less frequent with oral (either 200 or 400 mg) than with intravenous dipyridamole. Because of the delayed and variable absorption of dipyridamole tablets, the oral studies required a longer period of medical supervision (45 to 60 minutes), and aminophylline was empirically administered after completion of the first set of thallium-201 images. It is concluded from this study that thallium-201 myocardial imaging after coronary vasodilation with a 400 mg oral dose of dipyridamole is a safe, widely available and reliable alternative for the evaluation of coronary artery disease in patients unable to achieve an adequate exercise level on stress testing

Use of high-flow nasal cannula in obese patients receiving colonoscopy under intravenous propofol sedation: A case series

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Chi Chan Lee

Full Text Available Intravenous sedation during colonoscopy has become the standard practice in the United States given its higher patient satisfaction and procedural quality. This practice is not free of side effects as a significant proportion of patients undergoing this procedure tend to have respiratory depression and desaturation events. Obesity, as it relates to higher levels of body mass index (BMI has a positive correlation with the incidence of hypoxemia. During colonoscopy High flow nasal cannula (HFNC may potentially improve oxygen performance in patients receiving colonoscopy under intravenous sedation. Here we present 3 cases of patients undergoing adjunctive oxygen therapy with HFNC during colonoscopy with intravenous sedation. We found patients to have lower number of desaturation events and were satisfied with their experience. Keywords: High BMI (body mass index, HFNC (high-flow nasal cannula, Colonoscopy, Intravenous sedation, Obesity

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

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

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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.

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.

Randomised controlled trial comparing oral and intravenous paracetamol (acetaminophen) plasma levels when given as preoperative analgesia.

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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.

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...

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

Science.gov (United States)

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.

Successful treatment of azole-resistant invasive aspergillosis in a bottlenose dolphin with high-dose posaconazole

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Paulien E. Bunskoek

2017-06-01

Full Text Available Invasive aspergillosis due to azole-resistant Aspergillus fumigatus is difficult to manage. We describe a case of azole-resistant invasive aspergillosis in a female bottlenose dolphin, who failed to respond to voriconazole and posaconazole therapy. As intravenous therapy was precluded, high dose posaconazole was initiated aimed at achieving trough levels exceeding 3 mg/l. Posaconazole serum levels of 3–9.5 mg/l were achieved without significant side-effects. Follow-up bronchoscopy and computed tomography showed complete resolution of the lesions.

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

Effects of Intrarenal and Intravenous Infusion of the Phosphodiesterase 3 Inhibitor Milrinone on Renin Secretion

Science.gov (United States)

Kumagai, Kazuhiro; Reid, Ian A.

1994-01-01

We have reported that administration of the phosphodiesterase III inhibitor milrinone increases renin secretion in conscious rabbits. The aim of the present study was to determine if the increase in renin secretion results from a direct renal action of milrinone, or from an indirect extrarenal effect of the drug. This was accomplished by comparing the effects of intrarenal and intravenous infusion of graded doses of milrinone on plasma renin activity in unilaterally nephrectomized conscious rabbits. Milrinone was infused into the renal artery in doses of 0.01, 0.1 and 1.0 micro-g/kg/min, and intravenously in the same rabbits in doses of 0.01, 0.1, 1.0 and 10 micro-g/kg/min. Each dose was infused for 15 min. No intrarenal dose of milrinone altered plasma renin activity or arterial pressure, although at the highest dose, there was a small increase in heart rate. Intravenous infusion of milrinone at 1.0 micro-g/kg/min increased plasma renin activity to 176 +/- 55% of the control value (P less than 0.05). Heart rate increased but arterial pressure did not change. Intravenous infusion of milrinone at 1O micro-g/kg/min increased plasma renin activity to 386 +/- 193% of control in association with a decrease in arterial pressure and an increase in heart rate. These results confirm that milrinone increases renin secretion, and indicate that the stimulation is due to an extrarenal effect of the drug.

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...

Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2g starting dose following third molar surgery

DEFF Research Database (Denmark)

Juhl, Gitte Irene; Nørholt, Sven E.; Tønnesen, Else Kirstine

2006-01-01

BACKGROUND: The recommended dose for intravenous (IV) paracetamol injection in adults is 1g, however pharmacokinetic and pharmacodynamic findings suggest that a better analgesia could be obtained with a 2g starting dose. METHODS: A single-centre, randomised, double-blind, placebo-controlled, 3......-parallel group study was performed to demonstrate the analgesic efficacy and safety of IV paracetamol 2g. Following third molar surgery, patients reporting moderate to severe pain received a single 15-min infusion of either IV paracetamol 2g, IV paracetamol 1g or placebo. Efficacy and safety were evaluated...... over 8h. Laboratory tests were performed before and 48h after drug administration. RESULTS: Two hundred and ninety seven patients (132=IV paracetamol 2g; 132=IV paracetamol 1g; 33=placebo) were randomised and completed the study. The summed pain relief over 6h (TOTPAR6) was significantly superior...

Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans

Science.gov (United States)

D'Souza, Deepak Cyril; Fridberg, Daniel J; Skosnik, Patrick D; Williams, Ashley; Roach, Brian; Singh, Nagendra; Carbuto, Michelle; Elander, Jacqueline; Schnakenberg, Ashley; Pittman, Brian; Sewell, R Andrew; Ranganathan, Mohini; Mathalon, Daniel

2012-01-01

Cannabinoids induce a host of perceptual alterations and cognitive deficits in humans. However, the neural correlates of these deficits have remained elusive. The current study examined the acute, dose-related effects of delta-9-tetrahydrocannabinol (Δ9-THC) on psychophysiological indices of information processing in humans. Healthy subjects (n=26) completed three test days during which they received intravenous Δ9-THC (placebo, 0.015 and 0.03 mg/kg) in a within-subject, double-blind, randomized, cross-over, and counterbalanced design. Psychophysiological data (electroencephalography) were collected before and after drug administration while subjects engaged in an event-related potential (ERP) task known to be a valid index of attention and cognition (a three-stimulus auditory ‘oddball' P300 task). Δ9-THC dose-dependently reduced the amplitude of both the target P300b and the novelty P300a. Δ9-THC did not have any effect on the latency of either the P300a or P300b, or on early sensory-evoked ERP components preceding the P300 (the N100). Concomitantly, Δ9-THC induced psychotomimetic effects, perceptual alterations, and subjective ‘high' in a dose-dependent manner. Δ9-THC -induced reductions in P3b amplitude correlated with Δ9-THC-induced perceptual alterations. Lastly, exploratory analyses examining cannabis use status showed that whereas recent cannabis users had blunted behavioral effects to Δ9-THC, there were no dose-related effects of Δ9-THC on P300a/b amplitude between cannabis-free and recent cannabis users. Overall, these data suggest that at doses that produce behavioral and subjective effects consistent with the known properties of cannabis, Δ9-THC reduced P300a and P300b amplitudes without altering the latency of these ERPs. Cannabinoid agonists may therefore disrupt cortical processes responsible for context updating and the automatic orientation of attention, while leaving processing speed and earlier sensory ERP components intact

Direct effect of methylprednisolone on renal sodium and water transport via the principal cells in the kidney

DEFF Research Database (Denmark)

Lauridsen, Thomas G; Vase, Henrik; Bech, Jesper N

2010-01-01

Glucocorticoids influence renal concentrating and diluting ability. We tested the hypothesis that methylprednisolone treatment increased renal water and sodium absorption by increased absorption via the aquaporin-2 (AQP2) water channels and the epithelial sodium channels (ENaCs) respectively....

Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy.

Science.gov (United States)

Letko, Erik; Yeh, Steven; Foster, C Stephen; Pleyer, Uwe; Brigell, Mitchell; Grosskreutz, Cynthia L

2015-05-01

safe and was well tolerated. Intravenous secukinumab was effective and well tolerated in noninfectious uveitis requiring systemic corticosteroid-sparing immunosuppressive therapy. Greater activity with IV dosing suggests that patients may not receive sufficient drug with SC administration. High-dose IV secukinumab may be necessary to deliver secukinumab in therapeutic concentrations. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Effects of caffeine on fractional flow reserve values measured using intravenous adenosine triphosphate.

Science.gov (United States)

Nakayama, Masafumi; Chikamori, Taishiro; Uchiyama, Takashi; Kimura, Yo; Hijikata, Nobuhiro; Ito, Ryosuke; Yuhara, Mikio; Sato, Hideaki; Kobori, Yuichi; Yamashina, Akira

2018-04-01

We investigated the effects of caffeine intake on fractional flow reserve (FFR) values measured using intravenous adenosine triphosphate (ATP) before cardiac catheterization. Caffeine is a competitive antagonist for adenosine receptors; however, it is unclear whether this antagonism affects FFR values. Patients were evenly randomized into 2 groups preceding the FFR study. In the caffeine group (n = 15), participants were given coffee containing 222 mg of caffeine 2 h before the catheterization. In the non-caffeine group (n = 15), participants were instructed not to take any caffeine-containing drinks or foods for at least 12 h before the catheterization. FFR was performed in patients with more than intermediate coronary stenosis using the intravenous infusion of ATP at 140 μg/kg/min (normal dose) and 170 μg/kg/min (high dose), and the intracoronary infusion of papaverine. FFR was followed for 30 s after maximal hyperemia. In the non-caffeine group, the FFR values measured with ATP infusion were not significantly different from those measured with papaverine infusion. However, in the caffeine group, the FFR values were significantly higher after ATP infusion than after papaverine infusion (P = 0.002 and P = 0.007, at normal and high dose ATP vs. papaverine, respectively). FFR values with ATP infusion were significantly increased 30 s after maximal hyperemia (P = 0.001 and P < 0.001 for normal and high dose ATP, respectively). The stability of the FFR values using papaverine showed no significant difference between the 2 groups. Caffeine intake before the FFR study affected FFR values and their stability. These effects could not be reversed by an increased ATP dose.

Evaluation of an every-other-day palonosetron schedule to control emesis in multiple-day high-dose chemotherapy.

Science.gov (United States)

Mirabile, Aurora; Celio, Luigi; Magni, Michele; Bonizzoni, Erminio; Gianni, Alessandro Massimo; Di Nicola, Massimo

2014-12-01

Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.

Low-Dose Intravenous Paracetamol for Patent Ductus Arteriosus in Indomethacin-Resistant or Contraindicated Preterm Infants: Three Cases Reports.

Science.gov (United States)

Matsumura, Shun; Oshima, Ayumi; Fujinuma, Sumie; Tanaka, Kosuke; Nagano, Nobuhiko; Miyake, Fuyu; Masutani, Satoshi; Tamura, Masanori; Ueda, Keiko; Namba, Fumihiko

2017-10-01

Background  Although indomethacin (IND) is the standard treatment for hemodynamically significant patent ductus arteriosus (hsPDA) in Japan, it may be associated with renal impairment and gastrointestinal complications. The use of paracetamol for hsPDA closure has recently increased. Unlike IND, paracetamol does not have a peripheral vasoconstrictive effect and can be given to infants with contraindications to IND. Based on limited data available from randomized trials, paracetamol and IND seem to have similar effects. However, there have been no reports of the use of paracetamol for hsPDA in Japan. Cases  Our drug administration protocol was approved by the institutional ethics committee after purchasing a clinical trial insurance. In three premature infants in whom IND was contraindicated or ineffective, a 7.5 mg/kg of paracetamol was intravenously administered every 6 hour for 3 days after obtaining parental consents. A temporary hsPDA closure was observed in two of the three infants. However, all three infants eventually needed surgical closure. No side effects, such as hepatic and renal dysfunctions, and adverse events were reported. Conclusion  The intravenous administration of paracetamol was safe and feasible in premature infants with hsPDA. Future clinical trials with optimized dose and timing of administration are needed.

Inversion-based propofol dosing for intravenous induction of hypnosis

Science.gov (United States)

Padula, F.; Ionescu, C.; Latronico, N.; Paltenghi, M.; Visioli, A.; Vivacqua, G.

2016-10-01

In this paper we propose an inversion-based methodology for the computation of a feedforward action for the propofol intravenous administration during the induction of hypnosis in general anesthesia. In particular, the typical initial bolus is substituted with a command signal that is obtained by predefining a desired output and by applying an input-output inversion procedure. The robustness of the method has been tested by considering a set of patients with different model parameters, which is representative of a large population.

Relapse after methylprednisolone oral minipulse therapy in childhood vitiligo: A 12-month follow-up study

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Imran Majid

2013-01-01

Full Text Available Background: Oral minipulse (OMP therapy with methylprednisolone is presently one of the most common oral treatments used for progressive vitiligo in children. The treatment is usually given for a period of 6 months during which majority of patients are reported to go into remission. However, there are no follow-up studies to comment upon what happens to the disease after OMP therapy is withdrawn. Aim of the study: To document the incidence of relapse over a period of 1 year after OMP therapy is stopped in children with vitiligo. Materials and Methods: The study was conducted in 180 patients of childhood vitiligo (<15 years of age who had been on OMP therapy with oral methylprednisolone for at least 6 months and who had achieved a complete remission of their disease during the treatment period. The enrolled patients were followed up for a period of 1 year and examined clinically for any sign of reactivation of their disease over either the old lesions or at any new area of the body. Results: Forty-two patients were lost and could not complete the follow-up period of 1 year. Out of the 138 patients available at the end of 1 year, relapse was observed in 48 patients (34.8%. Rest of 90 patients remained in remission over the follow-up period of 1 year. Relapse was more common in patients below 10 years of age (47.4% as compared with older children (25.9%. Conclusion: Relapse after using methylprednisolone OMP therapy in children with vitiligo is quite common especially in younger age groups. Studies are needed to see whether these relapses could be avoided by giving the treatment for a period longer than 6 months.

Short-term intravenous antimicrobial prophylaxis for elective rectal cancer surgery: results of a prospective randomized non-inferiority trial.

Science.gov (United States)

Ishibashi, Keiichiro; Ishida, Hideyuki; Kuwabara, Kouki; Ohsawa, Tomonori; Okada, Norimichi; Yokoyama, Masaru; Kumamoto, Kensuke

2014-04-01

To investigate the non-inferiority of postoperative single-dose intravenous antimicrobial prophylaxis to multiple-dose intravenous antimicrobial prophylaxis in terms of the incidence of surgical site infections (SSIs) in patients undergoing elective rectal cancer surgery by a prospective randomized study. Patients undergoing elective surgery for rectal cancer were randomized to receive a single intravenous injection of flomoxef (group 1) or five additional doses (group 2) of flomoxef after the surgery. All the patients had received preoperative oral antibiotic prophylaxis (kanamycin and erythromycin) after mechanical cleansing within 24 h prior to surgery, and had received intravenous flomoxef during surgery. A total of 279 patients (including 139 patients in group 1 and 140 in group 2) were enrolled in the study. The incidence of SSIs was 13.7% in group 1 and 13.6% in group 2 (difference [95% confidence interval]: -0.2% [-0.9 to 0.7%]). The incidence of SSIs was not significantly different in patients undergoing elective rectal surgery who were treated using a single dose of postoperative antibiotics compared to those treated using multiple-dose antibiotics when preoperative mechanical and chemical bowel preparations were employed.

Safety and Efficacy of Intravenous Clevidipine for the Perioperative Control of Acute Hypertension in Neurosurgical Patients: A Dose Update

Directory of Open Access Journals (Sweden)

Kristin I Brower

2017-06-01

Full Text Available Clevidipine is a third-generation dihydropyridine calcium channel blocker approved in 2008 by the Food and Drug Administration for parenteral therapy of arterial hypertension. The high degree of lipophilicity of clevidipine provides a rapid onset of action and ease of titration to reach the desired clinical effect. Since its introduction into clinical practice, clevidipine has been shown to be safe and effective for perioperative use in patients undergoing procedures in which rapid and effective blood pressure control is essential. In 2011, clevidipine received institutional approval for intraoperative use during neurosurgical procedures and for postoperative blood pressure control in the Post-Anesthesia Care Unit and Surgical Intensive Care Unit during the first 24 hours after surgery. This review describes the efficacy and safety of intravenous clevidipine in intraoperative blood pressure management during neurosurgical procedures in 11 patients over a period of 3 months. The evaluation revealed that lower rates of clevidipine infusion than previously documented in the literature achieved blood pressure control within the desired limits during surgery while avoiding dose-related adverse reactions.

Buprenorphine Maintenance Subjects Are Hyperalgesic and Have No Antinociceptive Response to a Very High Morphine Dose.

Science.gov (United States)

Athanasos, Peter; Ling, Walter; Bochner, Felix; White, Jason M; Somogyi, Andrew A

2018-03-05

Acute pain management in opioid-dependent persons is complicated because of tolerance and opioid-induced hyperalgesia. Very high doses of morphine are ineffective in overcoming opioid-induced hyperalgesia and providing antinociception to methadone-maintained patients in an experimental setting. Whether the same occurs in buprenorphine-maintained subjects is unknown. Randomized double-blind placebo-controlled. Subjects were tested on two occasions, at least five days apart, once with intravenous morphine and once with intravenous saline. Subjects were tested at about the time of putative trough plasma buprenorphine concentrations. Ambulatory. Twelve buprenorphine-maintained subjects: once daily sublingual dose (range = 2-22 mg); no dose change for 1.5-12 months. Ten healthy controls. Intravenous morphine bolus and infusions administered over two hours to achieve two separate pseudo-steady-state plasma concentrations one hour apart. Pain tolerance was assessed by application of nociceptive stimuli (cold pressor [seconds] and electrical stimulation [volts]). Ten blood samples were collected for assay of plasma morphine, buprenorphine, and norbuprenorphine concentrations until three hours after the end of the last infusion; pain tolerance and respiration rate were measured to coincide with blood sampling times. Cold pressor responses (seconds): baseline: control 34 ± 6 vs buprenorphine 17 ± 2 (P = 0.009); morphine infusion-end: control 52 ± 11(P = 0.04), buprenorphine 17 ± 2 (P > 0.5); electrical stimulation responses (volts): baseline: control 65 ± 6 vs buprenorphine 53 ± 5 (P = 0.13); infusion-end: control 74 ± 5 (P = 0.007), buprenorphine 53 ± 5 (P > 0.98). Respiratory rate (breaths per minute): baseline: control 17 vs buprenorphine 14 (P = 0.03); infusion-end: control 15 (P = 0.09), buprenorphine 12 (P < 0.01). Infusion-end plasma morphine concentrations (ng/mL): control 23 ± 1

Intravenous Esomeprazole for Prevention of Peptic Ulcer Rebleeding: A Randomized Trial in Chinese Patients.

Science.gov (United States)

Bai, Yu; Chen, Dong-Feng; Wang, Rong-Quan; Chen, You-Xiang; Shi, Rui-Hua; Tian, De-An; Chen, Huifang; Eklund, Stefan; Li, Zhao-Shen

2015-11-01

High-dose intravenous esomeprazole is the only approved pharmacological treatment for the prevention of peptic ulcer rebleeding (currently approved in over 100 countries worldwide), but has not yet been approved in China. This study aimed to evaluate a high-dose esomeprazole intravenous regimen vs. an active control (cimetidine) for the prevention of rebleeding in Chinese patients with a high risk of peptic ulcer rebleeding who had undergone primary endoscopic hemostatic treatment. This was a parallel-group study conducted at 20 centers in China. The study comprised a randomized, double-blind, intravenous treatment phase of 72 h in which 215 patients received either high-dose esomeprazole (80 mg + 8 mg/h) or cimetidine (200 mg + 60 mg/h), followed by an open-label oral treatment phase in which all patients received esomeprazole 40 mg tablets once daily for 27 days. The primary outcome was the rate of clinically significant rebleeding within the first 72 h after initial endoscopic hemostatic therapy. Secondary outcomes included the rates of clinically significant rebleeding within 7 and 30 days; proportions of patients who had endoscopic retreatment and other surgery due to rebleeding; and number of blood units transfused. The rate of clinically significant rebleeding within 72 h was low overall (3.3%) and numerically lower in patients treated with esomeprazole compared with cimetidine (0.9% vs. 5.6%). Overall, the results of the secondary outcomes also showed a numerical trend towards superiority of esomeprazole over cimetidine. All treatments were well tolerated. In this phase 3, multicenter, randomized trial conducted in China, esomeprazole showed a numerical trend towards superior clinical benefit over cimetidine in the prevention of rebleeding in patients who had successfully undergone initial hemostatic therapy of a bleeding peptic ulcer, with a similar safety and tolerability profile. These findings suggest that esomeprazole may be an

Oral pyridoxine can substitute for intravenous pyridoxine in managing patients with severe poisoning with isoniazid and rifampicin fixed dose combination tablets: a case report.

Science.gov (United States)

Dilrukshi, M D S A; Ratnayake, C A P; Gnanathasan, C A

2017-08-08

Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka. A 22 year old, Sri Lankan female presented to a local hospital 1 h after self-ingestion of 28 tablets of fixed drug combination of isoniazid and rifampicin which contained 4.2 g of standard isoniazid and 7.2 g of rifampicin. One and half hours after ingestion she developed generalized tonic-clonic seizure with loss of consciousness. She was given intravenous diazepam 5 mg immediately and transferred to national hospital of Sri Lanka, for further care. Upon arrival to tertiary care hospital in 3.5 h of poisoning she had persistent vomiting, dizziness and headache. On examination, she was drowsy but arousable, orange-red discoloration of the body was noted even with the dark skin complexion. She also had orange-red colour urine and vomitus. Pulse rate was 104 beats/min, blood pressure 130/80 mmHg, respiratory rate was 20 breaths/min. The arterial blood gas analysis revealed compensated metabolic acidosis and mildly elevated lactic acid level. Considering the clinical presentation with neurological toxicity and the large amount of isoniazid dose ingested, crushed oral tablets of pyridoxine 4.2 g (equal to standard isoniazid dose ingested) administered immediately via a nasogastric tube since intravenous preparation was not available in the hospital. Simultaneously forced diuresis using intravenous 0.9% saline was commenced in order to enhance excretion of toxic metabolites via kidneys. She had no recurrence of seizures but had

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...

Comparison of the Concentrations of Lidocaine in Different Body Fluids/Tissues after Subarachnoid Space and Intravenous Administration of a Lethal Dose of Lidocaine

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Nan Zhang

2015-01-01

Full Text Available The objective of the study was to compare the concentration of lidocaine in different body fluids/tissues after subarachnoid space and intravenous administrations of a lethal dose of lidocaine. Totally 18 dogs were used in the experiment. Six dogs were given subarachnoid anesthesia, another were given an intravenous injection of a dose of 75 mg/kg weight of lidocaine hydrochloride in 5 min and the last 6 dogs were used as the blank control dogs and given a subarachnoid space injection or a femoral artery injection of the same volume of sodium chloride. As soon as its vital signs disappeared, each dog was dissected and the specimen, such as brain, cerebrospinal fluid (CSF in lateral ventricle, CSF in subarachnoid space, spinal cord (cervical spinal cord, thoracic spinal cord, lumbar spinal cord, and waist spinal cord, heart, lung, liver, spleen, kidney, bile, urine, heart blood, peripheral blood, muscle in injection location, and muscle in no injection location, were collected for analysis of lidocaine immediately. Analysis was performed with gas chromatography-mass spectrometry (GC-MS. From the maximum to the minimum, the order of lidocaine concentration detected in the subarachnoid space-administered dogs was as follows: CSF in subarachnoid space, waist spinal cord, thoracic spinal cord, CSF in lateral ventricle, lumbar spinal cord, cervical spinal cord, lung, kidney, muscle in injection location, heart, brain, spleen, heart blood, liver, peripheral blood, bile, muscle in no injection location, and urine. The order of lidocaine concentration detected in the intravenously administered dogs was as followed: Kidney, heart, lung, spleen, brain, liver, peripheral blood, bile, heart blood, cervical spinal cord, thoracic spinal cord, muscle in injection location, lumbar spinal cord, muscle in no injection location, CSF in subarachnoid space, urine, and CSF in lateral ventricle. The maximum concentration of lidocaine was detected in the subarachnoid

Population pharmacokinetics of intravenous Erwinia asparaginase in pediatric acute lymphoblastic leukemia patients.

Science.gov (United States)

Sassen, Sebastiaan D T; Mathôt, Ron A A; Pieters, Rob; Kloos, Robin Q H; de Haas, Valérie; Kaspers, Gertjan J L; van den Bos, Cor; Tissing, Wim J E; Te Loo, Maroeska; Bierings, Marc B; Kollen, Wouter J W; Zwaan, Christian M; van der Sluis, Inge M

2017-03-01

Erwinia asparaginase is an important component in the treatment of pediatric acute lymphoblastic leukemia. A large variability in serum concentrations has been observed after intravenous Erwinia asparaginase. Currently, Dutch Childhood Oncology Group protocols dose alterations are based on trough concentrations to ensure adequate asparaginase activity (≥100 IU/L). The aim of this study was to describe the population pharmacokinetics of intravenous Erwinia asparaginase to quantify and gather insight into inter-individual and inter-occasion variability. The starting dose was evaluated on the basis of the derived population pharmacokinetic parameters. In a multicenter prospective observational study, a total of 714 blood samples were collected from 51 children (age 1-17 years) with acute lymphoblastic leukemia. The starting dose was 20,000 IU/m 2 three times a week and adjusted according to trough levels from week three onwards. A population pharmacokinetic model was developed using NONMEM ® A 2-compartment linear model with allometric scaling best described the data. Inter-individual and inter-occasion variability of clearance were 33% and 13%, respectively. Clearance in the first month of treatment was 14% higher ( P <0.01). Monte Carlo simulations with our pharmacokinetic model demonstrated that patients with a low weight might require higher doses to achieve similar concentrations compared to patients with high weight. The current starting dose of 20,000 IU/m 2 might result in inadequate concentrations, especially for smaller, lower weight patients, hence dose adjustments based on individual clearance are recommended. The protocols were approved by the institutional review boards. (Registered at NTR 3379 Dutch Trial Register; www.trialregister.nl). Copyright© Ferrata Storti Foundation.

High Dose Oral Calcium Treatment in Patients with Vitamin D-dependent Rickets Type II

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R Vakili

2017-02-01

Full Text Available BACKGROUND AND OBJECTIVE: Vitamin D-dependent rickets type II (VDDR2 is a rare genetic disorder caused by mutations in vitamin D receptor (VDR and leads to resistance to biological effects of calcitriol. Based on the type of mutation, this disease is resistant to calcitriol even at high doses of calcitriol and successful treatment of these patients requires hypocalcemic modification through administration of high doses of calcium and bypassing the intestinal defect in VDR signaling. In addition to the need for frequent hospitalization and high costs, intravenous administration of calcium is associated with complications and problems such as arrhythmia and sepsis, venous catheter infection and hypercalciuria. This study aims to report the positive treatment effects of high doses of oral calcium in 4 patients with vitamin D-dependent rickets type II. CASE REPORT: In this study, 4 patients with vitamin D-dependent rickets type II, diagnosed based on clinical and biochemical symptoms of rickets with alopecia, underwent therapy using high doses of oral calcium (300 mg/kg/day in pediatric endocrinology and metabolism center of Imam Reza hospital. After a short period, increased growth rate in height, strength and elasticity of muscles was observed in addition to biochemical improvements without serious side effects and even one patient started walking independently within the first week of therapy for the first time. Patients were regularly followed up in terms of height and weight, growth rate and biochemical factors including calcium, phosphorus and alkaline phosphatase every 3 months for one year. CONCLUSION: Regardless of the type of mutation in vitamin D receptor, it is suggested that a 3-6 months trial of high dose oral calcium be started in each patient with vitamin D-dependent rickets type II, particularly for patients whose disease was diagnosed at lower ages.

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

Science.gov (United States)

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.

Comparative study of clindamycin concentration in the cerebrospinal fluid after intravenous and intrathecal administration in patients with toxoplasmic meningoencephalitis

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Сергій Петрович Борщов

2015-07-01

Full Text Available Aim of the work: to study the difference of clindamycin concentration in CSF at the intravenous and combined (intrathecal + intravenous ways of administration of preparation.Materials and methods: study was carried out at the treatment of 11 HIV-positive patients 27-63 years old (men and women with toxoplasmic meningoencephalitises.There was measured the clindamycin concentration in CSF of every patient after intravenous and combined (intrathecal + intravenous ways of administration of preparation. The determinations of concentration were done by the way of the reverse-phase high-performance liquid chromatography (HPLC with ultraviolet (UV detection. Statistic processing of the received data was carried out using the Wilcoxon criterion.Results of research. There was received the statistically significant increase of clindamycin concentration in CSF of patients in a day after combined (intrathecal + intravenous administration of preparation comparing with an intravenous administration.Conclusions. 1. Intrathecal administration of 150 mg. of clindamycin with 8 mg. of dexamethasone is safe.2. Intrathecal administration of 150 mg. of clindamycin with 8 mg. of dexamethasone in combination with an intravenous administration of preparation leads to statistically significant increase of clindamycin concentration in CSF at least during a day after injection.3. Intrathecal administration of clindamycin with dexamethasone in offered doses can be recommended for treatment of meningoencephalitises that caused by microorganisms susceptible to clindamycin.4. If the therapy of toxoplasmic meningoencephalitis was started with an intravenous prescription of clindamycin it is recommended an additional treatment with an intrathecal administration of clindamycin with dexamethasone in offered doses to increase efficiency by creating an effective concentration of preparation in the nidus of infection.5. Intrathecal methods of therapy must be used by the specialists of

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

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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

The importance of active learning and practice on the students' mastery of pharmacokinetic calculations for the intermittent intravenous infusion dosing of antibiotics

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Mehvar Reza

2012-11-01

Full Text Available Abstract Background Estimation of pharmacokinetic parameters after intermittent intravenous infusion (III of antibiotics, such as aminoglycosides or vancomycin, has traditionally been a difficult subject for students in clinical pharmacology or pharmacokinetic courses. Additionally, samples taken at different intervals during repeated dose therapy require manipulation of sampling times before accurate calculation of the patient-specific pharmacokinetic parameters. The main goal of this study was to evaluate the effectiveness of active learning tools and practice opportunities on the ability of students to estimate pharmacokinetic parameters from the plasma samples obtained at different intervals following intermittent intravenous infusion. Methods An extensive reading note, with examples, and a problem case, based on a patient’s chart data, were created and made available to students before the class session. Students were required to work through the case before attending the class. The class session was devoted to the discussion of the case requiring active participation of the students using a random participation program. After the class, students were given additional opportunities to practice the calculations, using online modules developed by the instructor, before submitting an online assignment. Results The performance of students significantly (P P  Conclusions Despite being a difficult subject, students achieve mastery of pharmacokinetic calculations for the topic of intermittent intravenous infusion when appropriate active learning strategies and practice opportunities are employed.

Cardiovascular effects, induction and recovery characteristics and alfaxalone dose assessment in alfaxalone versus alfaxalone-fentanyl total intravenous anaesthesia in dogs.

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Dehuisser, Virginie; Bosmans, Tim; Kitshoff, Adriaan; Duchateau, Luc; de Rooster, Hilde; Polis, Ingeborgh

2017-11-01

To compare cardiovascular effects and anaesthetic quality of alfaxalone alone or in combination with a fentanyl constant rate infusion (CRI) when used for total intravenous anaesthesia (TIVA) in dogs. Prospective, blinded, randomized, experimental study. A group of 12 intact female dogs. Following intramuscular dexmedetomidine (10 μg kg -1 ) and methadone (0.1 mg kg -1 ) administration, anaesthesia was induced intravenously with alfaxalone (2 mg kg -1 ) (group AP) or alfaxalone (2 mg kg -1 ) preceded by fentanyl (2 μg kg -1 ) (group AF). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg -1 minute -1 (group AP) or an alfaxalone VRI (same starting rate) combined with a CRI of fentanyl (10 μg kg -1 hour -1 ) (group AF). The alfaxalone VRI was adjusted every 5 minutes, based on clinical assessment. Cardiovascular parameters (recorded every 5 minutes) and recovery characteristics (using a numerical rating scale) were compared between groups. A mixed model statistical approach was used to compare the mean VRI alfaxalone dose and cardiovascular parameters between groups; recovery scores were analysed using the Wilcoxon rank-sum test (α = 0.05). The mean CRI alfaxalone dose for anaesthetic maintenance differed significantly between treatments [0.16 ± 0.01 mg kg -1 minute -1 (group AP) versus 0.13 ± 0.01 mg kg -1 minute -1 (group AF)]. Overall heart rate, systolic, mean and diastolic arterial pressures were lower in group AF than in group AP (p < 0.0001, p = 0.0058, p < 0.0001 and p < 0.0001, respectively. Recovery quality scores did not differ significantly and were poor in both groups. In combination with a fentanyl CRI, an alfaxalone TIVA provides a cardiovascular stable anaesthesia in dogs. The addition of fentanyl results in a significant dose reduction. The quality of anaesthetic recovery remains poor. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia

The Value of Intravenous Prostaglandin E2 after Intra-uterine Death

African Journals Online (AJOL)

1974-09-21

Sep 21, 1974 ... ficantly smaller doses of prostaglandins can achieve deli- very of the fetus and an intravenous route will be the method of choice. However, in cases of rhesus iso- immunisation, where larger doses of prostaglandin are required, with correspondingly more severe side-effects, the extra-amniotic route may be ...

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

Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia.

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Elefritz, Jessica L; Bauer, Karri A; Jones, Christian; Mangino, Julie E; Porter, Kyle; Murphy, Claire V

2017-09-01

Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

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

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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.

Comparison of two dose regimens of ibuprofen for the closure of patent ductus arteriosus in preterm newborns,

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Laura Vargas Dornelles

2016-06-01

Full Text Available Abstract Objective: To compare the efficacy of intravenous ibuprofen at high (20-10-10 mg/kg/dose and low doses (10-5-5 mg/kg/dose the closure of patent ductus arteriosus in preterm newborns. Methods: A cohort study with historical control of newborns that received high- and low-dose intravenous ibuprofen, from 2010 to 2013 in a neonatal intensive care unit, for closure of the patent ductus arteriosus, documented by echocardiography. Secondary outcomes included the number of ibuprofen cycles, incidence of bronchopulmonary dysplasia, necrotizing enterocolitis, changes in renal function, and death. Results: Seventy-seven patients received three doses of ibuprofen for the treatment of patent ductus arteriosus, with 33 receiving high-dose and 44 low-dose therapy. The ductus closed after the first cycle in 25 (56.8% low-dose patients and in 17 (51.5% high-dose patients (p > 0.99. Sixteen patients received a second cycle of ibuprofen, and the ductus closed in 50% after low-dose and in 60% after high-dose therapy (p > 0.99. Seven patients required surgery for ductus closure, 13.6% in the low-dose group and 3% in the high-dose group (p = 0.22. Thirty-nine patients developed bronchopulmonary dysplasia, 50% in the low-dose group and 51.5% in the high-dose group (p > 0.99. Twenty-two (50% low-dose patients died vs. 15 (45.5% high-dose patients (p = 0.86. Conclusions: There was no difference in closure of the ductus arteriosus or occurrence of adverse effects between the two dose regimens.

Intravenous Carbamazepine for Adults With Seizures.

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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.

Central venous catheter insertion problem solving using intravenous catheter: technical communication

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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.

Self-assembled nanoformulation of methylprednisolone succinate with carboxylated block copolymer for local glucocorticoid therapy.

Science.gov (United States)

Kamalov, Marat I; Đặng, Trinh; Petrova, Natalia V; Laikov, Alexander V; Luong, Duong; Akhmadishina, Rezeda A; Lukashkin, Andrei N; Abdullin, Timur I

2018-04-01

A new self-assembled formulation of methylprednisolone succinate (MPS) based on a carboxylated trifunctional block copolymer of ethylene oxide and propylene oxide (TBC-COOH) was developed. TBC-COOH and MPS associated spontaneously at increased concentrations in aqueous solutions to form almost monodisperse mixed micelles (TBC-COOH/MPS) with a hydrodynamic diameter of 19.6 nm, zeta potential of -27.8 mV and optimal weight ratio ∼1:6.3. Conditions for the effective formation of TBC-COOH/MPS were elucidated by comparing copolymers and glucocorticoids with different structure. The micellar structure of TBC-COOH/MPS persisted upon dilution, temperature fluctuations and interaction with blood serum components. TBC-COOH increased antiradical activity of MPS and promoted its intrinsic cytotoxicity in vitro attributed to enhanced cellular availability of the mixed micelles. Intracellular transportation and hydrolysis of MPS were analyzed using optimized liquid chromatography tandem mass spectrometry with multiple reaction monitoring which showed increased level of both MPS and methylprednisolone in neuronal cells treated with the formulated glucocorticoid. Our results identify TBC-COOH/MPS as an advanced in situ prepared nanoformulation and encourage its further investigation for a potential local glucocorticoid therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Diffuse alveolar hemorrhage in a patient with acute poststreptococcal glomerulonephritis caused by impetigo.

Science.gov (United States)

Yoshida, Masahiro; Yamakawa, Hideaki; Yabe, Masami; Ishikawa, Takeo; Takagi, Masamichi; Matsumoto, Kei; Hamaguchi, Akihiko; Ogura, Makoto; Kuwano, Kazuyoshi

2015-01-01

We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure.

Pharmacokinetics of intravenous and oral tramadol in the bald eagle (Haliaeetus leucocephalus).

Science.gov (United States)

Souza, Marcy J; Martin-Jimenez, Tomas; Jones, Michael P; Cox, Sherry K

2009-12-01

Analgesia is becoming increasingly important in veterinary medicine, and little research has been performed that examined pain control in avian species. Tramadol is a relatively new drug that provides analgesia by opioid (mu), serotonin, and norepinephrine pathways, with minimal adverse effects. To determine the pharmacokinetics of tramadol and its major metabolite O-desmethyltramadol (M1) in eagles, 6 bald eagles (Haliaeetus leucocephalus) were each dosed with tramadol administered intravenously (4 mg/kg) and orally (11 mg/kg) in a crossover study. Blood was collected at various time points between 0 and 600 minutes and then analyzed with high-performance liquid chromatography to determine levels of tramadol and M1, the predominate active metabolite. The terminal half-life of tramadol after intravenous dosing was 2.46 hours. The maximum plasma concentration, time of maximum plasma concentration, and terminal half life for tramadol after oral dosing were 2156.7 ng/ml, 3.75 hours, and 3.14 hours, respec vely. In addition, the oral bioavailability was 97.9%. Although plasma concentrations of ramadol and M1 associated with analgesia in any avian species is unknown, based on the obtained data and known therapeutic levels in humans, a dosage of 5 mg/kg PO q12h is recommended for bald eagles. Pharmacodynamic studies are needed to better determine plasma levels of tramadol and M1 associated with analgesia in birds.

Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose.

Science.gov (United States)

Viscardi, Rose M; Othman, Ahmed A; Hassan, Hazem E; Eddington, Natalie D; Abebe, Elias; Terrin, Michael L; Kaufman, David A; Waites, Ken B

2013-05-01

Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)(0.75) [WT(kg)(0.75) indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)(0.75); central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥ 96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial

Low-dose intravenous alpha-2 agonists as adjuvants to spinal levobupivacaine: A randomized study

Directory of Open Access Journals (Sweden)

Pranav Jetley

2017-01-01

Full Text Available Background: Alpha-2 agonists have been used with spinal anesthesia for anxiolysis, analgesia, and hypnosis and for postoperative pain relief. These beneficial effects may, however, be offset by their propensity to prolong the duration of motor block and adversely affect hemodynamics when used in higher doses. This study compares the effects of low-dose premedication with intravenous (IV dexmedetomidine and IV clonidine with placebo, on spinal blockade duration, analgesia, and sedation with intrathecal levobupivacaine. Materials and Methods: In this prospective, randomized, double-blinded, placebo-controlled study, ninety American Society of Anesthesiologists Status I and II patients were randomly allocated into three groups: Group A (control received 10 ml normal saline IV, Group B received IV dexmedetomidine 0.6 μg/kg, and Group C received IV clonidine 1.2 μg/kg over 10 min, before spinal anesthesia with 0.5% levobupivacaine. Hemodynamics, total duration of analgesia, onset and duration of sensory and motor block, visual analog scale score, and sedation score were assessed. Complications, if any, were noted. Results: The level of sensory block achieved was higher with dexmedetomidine (T4.2 ± 0.8 and clonidine (T4.4 ± 0.7 as compared to control (T5.1 ± 0.7; P< 0.001. Time to two segment regression was greater with dexmedetomidine (146.5 ± 12.5 min and clonidine (138.9 ± 17.4 min compared to control (90.1 ± 9.4; P< 0.001. Dexmedetomidine maximally prolonged the duration to first patient request for analgesia (245.2 ± 26.8 min, followed by clonidine (175.3 ± 20.1 min, P< 0.001 and control (121.3 ± 16.1 min, P< 0.001. The duration of motor block was similar in all three groups. Incidence of bradycardia was significantly greater with both dexmedetomidine and clonidine compared to saline (P < 0.05. Conclusion: Premedication with low-dose IV dexmedetomidine and clonidine prolonged sensory blockade and analgesic duration and provided

Intravenous Lacosamide in Pediatric Status Epilepticus: An Open-Label Efficacy and Safety Study.

Science.gov (United States)

Poddar, Karan; Sharma, Rohan; Ng, Yu-Tze

2016-08-01

Lacosamide is an antiepilepsy drug approved by the Food and Drug Administration for patients aged 17 years and older for partial-onset seizures as monotherapy or adjunctive therapy. We reviewed the use of intravenous lacosamide in children aged less than 17 years with status epilepticus. Children who received at least one dose of intravenous lacosamide for status epilepticus at our tertiary care children's hospital from December 2011 to March 2014 were studied. Status epilepticus was defined as continuous seizure activity for longer than 20 minutes or two or more recurrent seizures without regaining baseline level of awareness. Efficacy was defined as seizure freedom or more than 50% reduction of seizures within 24 hours of administering lacosamide. Nine children with a mean age of 5.7 years (range: three months to 16 years) were included. The mean initial or loading dose was 8.7 mg/kg, with seven of nine patients receiving a dose of 10 mg/kg. The average total amount of intravenous lacosamide administered within the initial 24 hours was 13.8 mg/kg. Lacosamide was found to be efficacious in seven of nine (77.8%) patients. Four patients (44.4%) became seizure free. Two patients continued to have status epilepticus within 24 hours of lacosamide administration. Bradycardia was observed in one patient. In children with status epilepticus, intravenous lacosamide was efficacious in 78% of the patients and 44% become seizure free. In addition, no significant adverse reactions were observed. An appropriate safe, effective initial, or loading dose may be 10 mg/kg. Copyright © 2016 Elsevier Inc. All rights reserved.

The Effect of Local Irradiation in Prevention and Reversal of Acute Rejection of Transplanted Kidney with High-dose Steroid Pulse

International Nuclear Information System (INIS)

Kim, I. H.; Ha, S. W.; Park, C. I.; Kim, S. T.

1986-01-01

From 1979 to 1984, 39 local allograft irradiations were given to 29 patients: 10 irradiations were administered for prevention and 29 for reversal of acute rejection of transplanted kidney. Three doses of 150 cGy every other day were combined with high-dose of methylprednisolone pulse (1 gm/day) for 3 days. For prevention of acute rejection, local irradiation was delivered on the days 1, 3, and 5 after the transplantation, and for reversal, irradiation started after the diagnosis of acute rejection. Eight out of 10 patients irradiated for prevention had acute allograft rejection, and, what is more, there was no surviving graft at 15 months after transplantation. Reversal of acute rejection was achieved in 71%. When the pre-irradiation level of serum creatinine was below 5.5 mg%, the reversal rate was 93%, but above 5.5 mg% the reversal rate was only 17% (p<0.01). Reirradiation after failure was not successful. Among 15 reversed patients, 7 (47%) had subsequent rejection (s). The functional graft survivals at 6 month, 1, 2, and 3 year were 70%, 65%, 54%, and 65%, respectively. Therapeutic irradiation resulted in better graft survival when serum creatinine was below 5.5 mg% (p<0.001) or when irradiation started within 15 days after the diagnosis of acute rejection (p<0.001)

Gamma dosimetry of high doses

International Nuclear Information System (INIS)

Martinez C, T.; Galvan G, A.; Canizal, G.

1991-01-01

The gamma dosimetry of high doses is problematic in almost all the classic dosemeters either based on the thermoluminescence, electric, chemical properties, etc., because they are saturated to very high dose and they are no longer useful. This work carries out an investigation in the interval of high doses. The solid system of heptahydrate ferrous sulfate, can be used as solid dosemeter of routine for high doses of radiation. The proposed method is simple, cheap and it doesn't require sophisticated spectrophotometers or spectrometers but expensive and not common in some laboratories

An 8-year old boy with continuous spikes and waves during slow sleep presenting with positive onconeuronal antibodies.

Science.gov (United States)

Hu, Lin-Yan; Shi, Xiu-Yu; Feng, Chen; Wang, Jian-Wen; Yang, Guan; Lammers, Stephen H T; Yang, Xiao Fan; Ebrahimi-Fakhari, Darius; Zou, Li-Ping

2015-03-01

To determine the etiology of epilepsy with continuous spikes and waves during slow sleep (CSWS)/electrical status epilepticus during sleep (ESES) in an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus. A combination of clinical characterization and follow-up, video EEG and laboratory investigations. We report the case of an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus, who presented with intellectual disability, pharmacotherapy-resistant epilepsy and CSWS/ESES. Although the patient's neuroblastoma had been successfully treated 8 years prior to presentation and an extensive workup did not show a tumor reoccurrence, testing for onconeuronal antibodies was positive for anti-Ma2 and anti-CV2/CRMP5 antibodies. High-dose intravenous methylprednisolone and a taper of oral methylprednisolone were given, leading to a significant clinical improvement. During the taper the patient's condition and EEG manifestations deteriorated again necessitating another cycle of steroid therapy, which lead to a stable improvement. During a 6-month follow-up no CSWS/ESES was seen on EEG and anti-Ma2 and anti-CV2/CRMP5 antibodies remained undetectable. This case suggests that onconeuronal antibodies may be involved in the pathogenesis of CSWS/ESES. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The analgesic efficacy of intravenous versus oral tramadol for preventing postoperative pain after third molar surgery

NARCIS (Netherlands)

Ong, Cliff K. S.; Lirk, Phillip; Tan, Juliana M. H.; Sow, Belle W. Y.

2005-01-01

The aim of this study was to compare the analgesic efficacy of single-dose preoperative intravenous versus oral tramadol for preventing pain after third molar surgery. Seventy-two patients undergoing elective third molar surgery were randomized to receive either intravenous (n = 36) or oral (n = 36)

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

Directory of Open Access Journals (Sweden)

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

Comparison of two dose regimens of ibuprofen for the closure of patent ductus arteriosus in preterm newborns.

Science.gov (United States)

Dornelles, Laura Vargas; Corso, Andréa Lúcia; Silveira, Rita de Cássia; Procianoy, Renato Soibelmann

2016-01-01

To compare the efficacy of intravenous ibuprofen at high (20-10-10mg/kg/dose) and low doses (10-5-5mg/kg/dose) the closure of patent ductus arteriosus in preterm newborns. A cohort study with historical control of newborns that received high- and low-dose intravenous ibuprofen, from 2010 to 2013 in a neonatal intensive care unit, for closure of the patent ductus arteriosus, documented by echocardiography. Secondary outcomes included the number of ibuprofen cycles, incidence of bronchopulmonary dysplasia, necrotizing enterocolitis, changes in renal function, and death. Seventy-seven patients received three doses of ibuprofen for the treatment of patent ductus arteriosus, with 33 receiving high-dose and 44 low-dose therapy. The ductus closed after the first cycle in 25 (56.8%) low-dose patients and in 17 (51.5%) high-dose patients (p>0.99). Sixteen patients received a second cycle of ibuprofen, and the ductus closed in 50% after low-dose and in 60% after high-dose therapy (p>0.99). Seven patients required surgery for ductus closure, 13.6% in the low-dose group and 3% in the high-dose group (p=0.22). Thirty-nine patients developed bronchopulmonary dysplasia, 50% in the low-dose group and 51.5% in the high-dose group (p>0.99). Twenty-two (50%) low-dose patients died vs. 15 (45.5%) high-dose patients (p=0.86). There was no difference in closure of the ductus arteriosus or occurrence of adverse effects between the two dose regimens. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Comparative study of intravenous urographic bolus (I.U.B.) and intravenous urographic infusion (I.U.I.) in dogs

International Nuclear Information System (INIS)

Thibaut L, Julio; Ditzel, G.; Vargas, L; Born, R; Deppe G, Rodolfo

1996-01-01

Two urographic methods were compared: the intravenous urographic bolus (i.u.b.) and the intravenous urographic infusion (i.u.i.). In both methods, two groups of seven healthy adult dogs of both sexes, weighing7.0 to 16.5 kg were used and were anaesthesized with 2% thiopentone sodium in doses of 20 mg/kg via cephalica. In the i.u.b., meglumine diatrizoate (Hypaque-M, 60%) was injected via saphena with a concentration of 282 mg of iodine per mi in doses of 564 mg of iodine per kg. In the i.u.i., meglumine diatrizoate was injected via saphena by drip infusion with a concentration of 200 mg of iodine per mi in doses of 500 mg of iodine per kg. Three series of two X-rays each were taken in ventrodorsal projection 1, 4 and 8 min and left lateral recumbency 30 sec after administering the contrast medium. The X-ray plates obtained were analyzed and compared intra and inter group considering the advance speed of the contrast medium, the radiographic density and outline, and kidney size. The advance speed of the contrast medium was higher in the i.u.i., reaching the kidney, ureter and bladder 1 min after administration in both projections; in ventrodorsal projections in the i.u.b. only the kidneys were reached while in the left lateral recumbency, the kidney and ureters were reached [es

Intra-articular injection of methylprednisolone for reducing pain in knee osteoarthritis: A systematic review and meta-analysis.

Science.gov (United States)

Tian, Kewei; Cheng, Huiguang; Zhang, Jiangtao; Chen, Ke

2018-04-01

To evaluate the efficacy and safety of intra-articular methylprednisolone for reducing pain in patients with knee osteoarthritis. We conduct electronic searches of Medline (1966-2017.11), PubMed (1966-2017.11), Embase (1980-2017.11), ScienceDirect (1985-2017.11), and the Cochrane Library (1900-2017.11) for randomized clinical trials comparing the use of methylprednisolone to treat knee osteoarthritis. The primary outcomes are Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores and WOMAC function scores. Each outcome was combined and calculated using the statistical software STATA 12.0. Fixed/random effect model was adopted based on the heterogeneity tested by I statistic. A total of 739 patients were analyzed across 4 randomized controlled trials (RCTs). The present meta-analysis revealed that there were significant differences between groups regarding the WOMAC pain scores at 4 weeks (WMD = -1.384, 95% CI: -1.975 to -0.793, P = .000), 12 weeks (WMD = -1.587, 95% CI: -2.489 to -0.685, P = .001), and 24 weeks (WMD = -1.563, 95% CI: -2.245 to -0.881, P = .000). Significant differences were identified in terms of physical function at 4 weeks (WMD = -7.925, 95% CI: -13.359 to -2.491, P = .004), 12 weeks (WMD = -7.314, 95% CI: -13.308 to -1.320, P = .117), and 24 weeks (WMD = -6.484, 95% CI: -11.256 to -1.711, P = .008). Intra-articular methylprednisolone injection was associated with an improved pain relief and physical function in patients with knee osteoarthritis. Additionally, no severe adverse effects were observed. Due to the limited quality of the evidence currently available, higher quality RCTs were required.

Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics.

Science.gov (United States)

Heuberger, Jules A A C; Guan, Zheng; Oyetayo, Olubukayo-Opeyemi; Klumpers, Linda; Morrison, Paul D; Beumer, Tim L; van Gerven, Joop M A; Cohen, Adam F; Freijer, Jan

2015-02-01

Δ(9)-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized through more accurate predictions of the dosing sequence and the wash-out between occasions in a crossover setting, which is mainly determined by the terminal half-life of the compound. The purpose of this study is to better quantify the long-term pharmacokinetics of THC. A population-based PK model for THC was developed describing the profile up to 48 h after an oral, intravenous, and pulmonary dose of THC in humans. In contrast to earlier models, the current model integrates all three major administration routes and covers the long terminal phase of THC. Results show that THC has a fast initial and intermediate half-life, while the apparent terminal half-life is long (21.5 h), with a clearance of 38.8 L/h. Because the current model characterizes the long-term pharmacokinetics, it can be used to assess the accumulation of THC in a multiple-dose setting and to forecast concentration profiles of the drug under many different dosing regimens or administration routes. Additionally, this model could provide helpful insights into the THC challenge test used for the development of (novel) compounds targeting the cannabinoid system for different therapeutic applications and could improve decision making in future clinical trials.

Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses.

Science.gov (United States)

Serrano-Rodríguez, Juan Manuel; Gómez-Díez, Manuel; Esgueva, María; Castejón-Riber, Cristina; Mena-Bravo, Antonio; Priego-Capote, Feliciano; Ayala, Nahúm; Caballero, Juan Manuel Serrano; Muñoz, Ana

2017-10-01

Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50mg/kg and PO at doses 0 (placebo), 0.25, 0.50 and 1.00mg/kg. Blood pressures (BP) were measured and blood samples were obtained at different times in order to measure serum drug concentrations and serum ACE activity, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of benazeprilat after PO benazepril was 3-4%. Maximum ACE inhibitions from baseline were 99.63% (IV benazepril), 6.77% (placebo) and 78.91%, 85.74% and 89.51% (for the three PO benazepril doses). Significant differences in BP were not found. Although oral availability was low, benazeprilat 1.00mg/kg, reached sufficient serum concentrations to induce long lasting serum ACE inhibitions (between 88 and 50%) for the first 48h. Additional research on benazepril administration in equine patients is indicated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial

DEFF Research Database (Denmark)

Ravnborg, Mads; Sørensen, Per Soelberg; Andersson, Magnus

2010-01-01

status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets....... Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained...

A 12-week dose-escalating study of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese hemodialysis patients
.

Science.gov (United States)

Yokoyama, Keitaro; Fukagawa, Masafumi; Shigematsu, Takashi; Akiba, Takashi; Fujii, Akifumi; Odani, Motoi; Akizawa, Tadao

2017-08-01

To evaluate dose-escalation of etelcalcetide (ONO-5163/AMG 416), a novel, intravenous (IV), long-acting calcium-sensing receptor agonist, for treatment of secondary hyperparathyroidism (SHPT) in Japanese hemodialysis patients. In this multicenter study, IV injections of etelcalcetide (3 times a week for 12 weeks) were administered, with dose escalation every 4 weeks depending on changes in serum intact parathyroid hormone (iPTH) and corrected calcium (cCa). A total of 24 patients participated in this study. Serum iPTH was reduced in a time- and dose-dependent manner, with reductions (in pg/mL) at 12 weeks of -226.1 ± 125.3, -362.5 ± 161.5, and -412.4 ± 130.2, respectively, for maximum doses of 5, 10, and 15 mg. At the end of the treatment, 50% of patients had serum iPTH levels within the target range (60 - 240 pg/mL). Serum cCa and phosphorus were reduced in parallel with iPTH. Adverse events (AEs) occurred in 20 patients (83.3%). The most frequently observed AEs (> 10%) were either mild or moderate nasopharyngitis (29.2%), decreased serum calcium (16.7%), and vomiting (12.5%). Dose-escalated triweekly etelcalcetide was effective for SHPT in Japanese hemodialysis patients and was satisfactorily tolerated.
.

Safety and Efficacy of Intravenous Ferric Carboxy Maltose in Iron Deficiency Anaemia During Post-partum Period.

Science.gov (United States)

Mishra, Vineet; Roy, Priyankar; Gandhi, Khushali; Choudhary, Sumesh; Aggarwal, Rohina; Sokabaj, Shaheen

2018-01-01

Iron deficiency is the commonest treatable cause of postpartum anaemia. Parenteral iron therapy results in faster and higher replenishment of iron stores and correction of haemoglobin levels with better compliance. Ferric Carboxy Maltose is an effective and a safe option which can be administered intravenously in single total correction dose without any serious adverse effects.The study was done to evaluate the efficacy and safety of Ferric Carboxy Maltose in the treatment of iron deficiency anaemia in post-natal patients. It was an open, single arm study including 615 women with diagnosis of Iron deficiency anaemia and haemoglobin (Hb) levels between 4gm% and 11gm% from January 2013 to December 2016. Intravenous Ferric Carboxy Maltose(500-1500mg) was administered and the improvement in haemoglobin levels and iron stores were assessed after three weeks of total dose infusion. Out of the 615 women, 595 women were included in the analysis. Most of the women were in the age group of 27-30 years. Most of the women had mild anaemia as per World Health Organisation guidelines. Mean hemoglobin levels significantly increased over a period of three weeks after Ferric Carboxy Maltose administration. Other parameters like total iron binding capacity, Ferritin and Iron also had a significant improvement after Ferric Carboxy Maltose administration. No serious adverse events were observed after Ferric Carboxy Maltose. Intravenous Ferric Carboxy Maltose was an effective and a safe treatment option for iron deficiency anaemia and has an advantage of single administration of high doses without serious adverse effects.

The Value of Intravenous Prostaglandin E2 after Intra-uterine Death

African Journals Online (AJOL)

1974-09-21

Sep 21, 1974 ... using different routes of administration of the prosta- glandin. Given by ..... The disadvantages of intravenous prostaglandins are the systemic ... advantage of this method is that labour can be accurately monitored and the dose ...

Successful Treatment of Antiepileptic Drug-Induced DRESS Syndrome with Pulse Methylprednisolone

Directory of Open Access Journals (Sweden)

Celebi Kocaoglu

2013-01-01

Full Text Available Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome is a rare but potentially life-threatening syndrome characterized by skin rash, fever, lymph node enlargement, and involvement of internal organs. It is most commonly induced by aromatic anticonvulsants and antibiotics. Nonaromatic anticonvulsants are rarely encountered as the causes of DRESS syndrome. In the present report, three discrete cases with DRESS syndrome developing due to three antiepileptic drugs, including valproic acid (nonaromatic, carbamazepine (aromatic, and lamotrigine (aromatic, and their treatment modalities were aimed to be discussed in light of the literature. To the best of our knowledge, our cases are the first children to be treated with pulse methylprednisolone in the literature.

Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin.

Science.gov (United States)

Richter, C; Schnabel, A; Csernok, E; De Groot, K; Reinhold-Keller, E; Gross, W L

1995-07-01

In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality.

Magnetic resonance imaging of the femoral head to detect avascular necrosis in active rheumatoid arthritis treated with methylprednisolone pulse therapy

Energy Technology Data Exchange (ETDEWEB)

Vugt, R.M. van; Sijbrandij, E.S.; Bijlsma, J.W.J. [Univ. Hospital Utrecht (Netherlands)

1996-03-01

Efficacious management of patients with avascular necrosis of bone (AVN) necessitates the identification of patients with a high risk of collapse of the femoral head. In this prospective study we imaged both hips of 10 patients with active rheumatoid arthritis, who were treated with methylprednisolone pulse therapy. MRI and conventional radiography were performed before MP-pulse therapy and 6 and 12 months thereafter. Two patients showed unilateral changes compatible with AVN. One patient became symptomatic and revealed characteristic radiographic abnormalities. The other patient remained asymptomatic and the MRI appearance returned to normal after 6 months. 18 refs., 2 figs., 1 tab.

Magnetic resonance imaging of the femoral head to detect avascular necrosis in active rheumatoid arthritis treated with methylprednisolone pulse therapy

International Nuclear Information System (INIS)

Vugt, R.M. van; Sijbrandij, E.S.; Bijlsma, J.W.J.

1996-01-01

Efficacious management of patients with avascular necrosis of bone (AVN) necessitates the identification of patients with a high risk of collapse of the femoral head. In this prospective study we imaged both hips of 10 patients with active rheumatoid arthritis, who were treated with methylprednisolone pulse therapy. MRI and conventional radiography were performed before MP-pulse therapy and 6 and 12 months thereafter. Two patients showed unilateral changes compatible with AVN. One patient became symptomatic and revealed characteristic radiographic abnormalities. The other patient remained asymptomatic and the MRI appearance returned to normal after 6 months. 18 refs., 2 figs., 1 tab

Effect of methylprednisolone upon technetium-99m pyrophosphate assessment of myocardial necrosis in the canine countershock model

International Nuclear Information System (INIS)

Schneider, R.M.; Hayslett, J.P.; Downing, S.E.; Berger, H.J.; Donabedian, R.K.; Zaret, B.L.

1977-01-01

RRepeat DC countershock reproducibly results in myocardial necrosis in dogs. In this model, myocardial technetium-/sup 99m/ pyrophosphate (PYP) uptake correlates linearly with tissue creatine kinase depletion (r = -0.83). The effect of pretreatment with methylprednisolone (MP) was studied with PYP in 25 dogs. In myocardium damaged by countershock, 12 MP dogs had higher tissue radioactivity sample:normal (S:N) ratios than control (P < 0.05), suggesting increased tissue injury. However, by several other measures of tissue damage, the two groups did not differ. MP-elevated PYP S:N ratios were explained by reduced PYP activity in normal myocardium of MP dogs. Further experiments in 21 dogs revealed that renal PYP clearance, which correlated with glomerular filtration rate (GFR) as measured by creatinine clearance, was increased in MP dogs, resulting in accelerated urinary excretion of PYP (46.9 +- 3.6 vs 35.8 +- 2.4 percent injected dose in one hour, P < 0.01), and reduced blood PYP. Thus, MP does not modify countershock-induced myocardial injury. However, by increasing GFR, MP increased PYP excretion, resulting in lowered blood and normal zone myocardial PYP, thereby spuriously affecting myocardial PYP tissue uptake data

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

Paediatric dose display

International Nuclear Information System (INIS)

Griffin, D.W.; Derges, S.; Hesslewood, S.

1984-01-01

A compact, inexpensive unit, based on an 8085 microprocessor, has been designed for calculating doses of intravenous radioactive injections for children. It has been used successfully for over a year. The dose is calculated from the body surface area and the result displayed in MBq. The operator can obtain the required dose on a twelve character alphanumeric display by entering the age of the patient and the adult dose using a hexadecimal keyboard. Circuit description, memory map and input/output, and firmware are dealt with. (U.K.)

Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.

Science.gov (United States)

Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

2016-02-01

Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±  16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.

Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251.

Science.gov (United States)

Andrews, Chasity D; Bernard, Leslie St; Poon, Amanda Yee; Mohri, Hiroshi; Gettie, Natanya; Spreen, William R; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Hong, Zhi; Ho, David D; Markowitz, Martin

2017-02-20

We evaluated the effectiveness of cabotegravir (CAB; GSK1265744 or GSK744) long acting as preexposure prophylaxis (PrEP) against intravenous simian immunodeficiency virus (SIV) challenge in a model that mimics blood transfusions based on the per-act probability of infection. CAB long acting is an integrase strand transfer inhibitor formulated as a 200 mg/ml injectable nanoparticle suspension that is an effective PrEP agent against rectal and vaginal simian/human immunodeficiency virus transmission in macaques. Three groups of rhesus macaques (n = 8 per group) were injected intramuscularly with CAB long acting and challenged intravenously with 17 animal infectious dose 50% SIVmac251 on week 2. Group 1 was injected with 50 mg/kg on week 0 and 4 to evaluate the protective efficacy of the CAB long-acting dose used in macaque studies mimicking sexual transmission. Group 2 was injected with 50 mg/kg on week 0 to evaluate the necessity of the second injection of CAB long acting for protection against intravenous challenge. Group 3 was injected with 25 mg/kg on week 0 and 50 mg/kg on week 4 to correlate CAB plasma concentrations at the time of challenge with protection. Five additional macaques remained untreated as controls. CAB long acting was highly protective with 21 of the 24 CAB long-acting-treated macaques remaining aviremic, resulting in 88% protection. The plasma CAB concentration at the time of virus challenge appeared to be more important for protection than sustaining therapeutic plasma concentrations with the second CAB long acting injection. These results support the clinical investigation of CAB long acting as PrEP in people who inject drugs.

Distribution and pharmacokinetics of radiolabeled monoclonal antibody OC 125 after intravenous and intraperitoneal administration in gynecologic tumors

International Nuclear Information System (INIS)

Haisma, H.J.; Moseley, K.R.; Battaile, A.; Griffiths, T.C.; Knapp, R.C.

1988-01-01

Radiolabeled monoclonal antibodies may be useful for radioimmunotherapy of gynecologic tumors. Iodine 131-labeled F(ab')2 fragments of a monoclonal antibody, OC 125, with specificity for ovarian carcinoma, were used to study the distribution and pharmacokinetics of this antibody in patients with gynecologic tumors. The radiolabeled antibody was injected intravenously or intraperitoneally into 10 patients suspected of having ovarian cancer. Blood and urine samples were used for pharmacokinetic studies, and biopsy specimens were examined for the uptake of antibody. The serum half-life of the labeled antibody was 30 hours after intravenous administration, with 20% of the injected dose per liter detected at 24 hours. After intraperitoneal injection, the appearance of antibody in serum was slow, with a maximum level of 1.4% of the injected dose per liter at 24 hours. Urinary excretion of the radiolabeled antibody was similar for intravenous and intraperitoneal administration, with approximately 50% of the injected dose excreted after 48 hours. Intraperitoneal administration of the radiolabeled antibody resulted in a higher uptake of antibody in the tumor and a lower uptake of antibody in normal tissues. On the basis of this limited study, intraperitoneal administration of radiolabeled antibody is preferred over intravenous administration for radioimmunotherapy of ovarian cancer

Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers.

Science.gov (United States)

Jung, Caroline; Greco, Santo; Nguyen, Hanh H T; Ho, Jui T; Lewis, John G; Torpy, David J; Inder, Warrick J

2014-11-26

Glucocorticoid replacement is essential in patients with primary and secondary adrenal insufficiency, but many patients remain on higher than recommended dose regimens. There is no uniformly accepted method to monitor the dose in individual patients. We have compared cortisol concentrations in plasma, saliva and urine achieved following "physiological" and "stress" doses of hydrocortisone as potential methods for monitoring glucocorticoid replacement. Cortisol profiles were measured in plasma, saliva and urine following "physiological" (20 mg oral) or "stress" (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to endogenous cortisol levels (12 subjects). Total plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5 h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5 h, and hourly from time 0 to 5 h following administration of oral or intravenous hydrocortisone. Plasma free cortisol was calculated using Coolens' equation. Plasma, salivary and urine cortisol at 2 h after oral hydrocortisone gave a good indication of peak cortisol concentrations, which were uniformly supraphysiological. Intravenous hydrocortisone administration achieved very high 30 minute cortisol concentrations. Total plasma cortisol correlated significantly with both saliva and urine cortisol after oral and intravenous hydrocortisone (P cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in hypoadrenal patients.

Regional cerebral energy metabolism during intravenous anesthesia with etomidate, ketamine or thiopental

International Nuclear Information System (INIS)

Davis, D.W.

1987-01-01

Regional brain glucose utilization (rCMRglc) was measured in rats during steady-state levels of intravenous anesthesia to determine if alterations in brain function due to anesthesia could provide information on the mechanisms of anesthesia. Intravenous anesthetics from three different chemical classes were studied: etomidate, ketamine and thiopental. All rCMRglc experiments were conducted in freely moving rats in isolation chambers, with the use of [6- 14 C] glucose and guantitative autoradiography. Etomidate caused a rostral-to-caudal gradient of depression of rCMRglc. The four doses of etomidate did not differ in their effects on energy metabolism. Sub-anesthetic (5 mg kg -1 ) and anesthetic (30 mg kg -1 ) doses of ketamine produced markedly different patterns of behavior. Brain energy metabolism during the sub-anesthetic dose was stimulated in most regions, while the anesthetic dose selectively stimulated the hippocampus, leaving most brain regions unaffected. Thiopental produced a dose-dependent reduction of rCMRglc in all gray matter regions. No brain region was selectively affected. Comparison of the drug-specific alterations of cerebral energy metabolism suggests these anesthetics do not act through a common mechanism. The hypothesis that each acts by binding to specific cell membrane receptors is consistent with these observations

Low-dose intravenous ketamine for postcardiac surgery pain: Effect on opioid consumption and the incidence of chronic pain.

Science.gov (United States)

Cogan, Jennifer; Lalumière, Geneviève; Vargas-Schaffer, Grisell; Deschamps, Alain; Yegin, Zeynep

2017-01-01

Recent meta-analyses have concluded that low-dose intravenous ketamine infusions (LDKIs) during the postoperative period may help to decrease acute and chronic postoperative pain after major surgery. This study aims to evaluate the level of pain at least 3 months after surgery for patients treated with a postoperative LDKI versus patients who were not treated with a postoperative LDKI. Administrative and Ethics Board approval were obtained for this study. We performed a retrospective chart review for all patients receiving LDKI, and equal number of age-, sex-, and surgery-matched patients who did not receive LDKI. Low-dose ketamine was prepared using 100 mg of ketamine in 100 ml of normal saline and run between 50 and 200 mcg/kg/h. We reviewed 115 patients with LDKI and 115 without LDKI. The average age was 63.1 years, 73% of the patients were men and sex was evenly distributed between LDKI and non-LDKI. The average duration of the ketamine infusions was 26.8 h with the average dose being 169.9 mg. At an average of 9 months after surgery, 42% of the ketamine group and 38% of the nonketamine group stated that they had had pain on discharge. Of these patients, 30% of the ketamine group and 26% of the nonketamine group still had pain at the time of the phone call. Women in both groups had more acute and chronic pain than men. These results show that LDKI does not promote a decrease in long-term postoperative pain.

Biological dose estimation for accidental supra-high dose gamma-ray exposure

International Nuclear Information System (INIS)

Chen, Y.; Yan, X.K.; Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K.

2011-01-01

To correctly estimate the biological dose of victims accidentally exposed to a very high dose of 60 Co gamma-ray, a new dose-effect curve of chromosomal dicentrics/multicentrics and rings in the supra-high dose range was established. Peripheral blood from two healthy men was irradiated in vitro with doses of 60 Co gamma-rays ranging from 6 to 22 Gy at a dose rate of 2.0 Gy/min. Lymphocytes were concentrated, cultured and harvested at 52 h, 68 h and 72 h. The numbers of dic + r were counted. The dose-effect curves were established and validated using comparisons with doses from the Tokai-mura accident and were then applied to two victims of supra-high dose exposure accident. The results indicated that there were no significant differences in chromosome aberration frequency among the different culture times from 52 h to 72 h. The 6-22 Gy dose-effect curve was fitted to a linear quadratic model Y = -2.269 + 0.776D - 7.868 x l0 -3 D 2 . Using this mathematic model, the dose estimates were similar to data from Tokai-mura which were estimated by PCC ring. Whole body average doses of 9.7 Gy and 18.1 Gy for two victims in the Jining accident were satisfactorily given. We established and successfully applied a new dose-effect curve of chromosomal dicentrics plus ring (dic + r) after 6-22 Gy γ-irradiation from a supra-high dose 60 Co gamma-ray accident.

INTRAVENOUS IMMUNOGLOBULIN ADMINISTRATION FOR DESENSITIZATION BEFORE RENAL TRANSPLANTATION AND MANAGING ANTIBODY-MEDIATED REJECTION

Directory of Open Access Journals (Sweden)

A. I. Sushkov

2011-01-01

Full Text Available Much attention has been placed recently in transplantation in highly HLA-sensitized patients. In attempts to remove these antibodies and enable successful renal transplantation, several approaches have been developed. Intravenous immunoglobulin (IVIG was found to be effective in the treatment of autoimmune and inflammatory disorders (e. g. Kawasaki disease, Guillain-Barre syndrome. Recently, a beneficial effect of IVIG on the reduc- tion of anti-HLA antibodies was described. The anti-inflammatory effect of IVIG provides hopeful opportunities in antibody-mediated rejection (AMR management. There are several protocols of IVIG administration for pre-transplant desensitization and AMR treatment: high-dose IVIG, low-dose IVIG + plasmapheresis, IVIG + plasmapheresis + rituximab. These advancements have enabled transplantation in patients previously considered untransplantable and in concert with new diagnostic techniques has resulted in new approaches to management of AMR. 

Pharmacokinetics of lansoprazole and its main metabolites after single intravenous doses in healthy Chinese subjects.

Science.gov (United States)

Zhang, Dan; Yang, Man; Liu, Man; Zhang, Yanan; Wang, Xiaolin; Xiao, Xue; Liu, Huichen

2012-11-01

The aim of the study was to evaluate the pharmacokinetics (PK) of lansoprazole (LPZ) and its main metabolites 5'-hydroxy lansoprazole (HLPZ) and lansoprazole sulphone (LPZS) after single intravenous (i.v.) doses of LPZ in healthy Chinese subjects, and the relationship between the cytochrome P450 (CYP) 2C19 phenotypes and the plasma concentrations of LPZS at the time-points in the elimination phase of LPZ. Twelve subjects were given lansoprazole by i.v. infusion. Blood samples were collected at designated time points up to 24 h. Plasma concentrations of LPZ, HLPZ and LPZS were quantified by a selective and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. After single i.v. doses of 15, 30 and 60 mg LPZ, C(max) and area under the plasma concentration-time curve (AUC(0-t)) of LPZ were 725 ± 151, 1480 ± 190, 3130 ± 480 µg · L(-1) and 1690 ± 1210, 3630 ± 2530, 8080 ± 4550 µg · h · L(-1), respectively. LPZ was generally well tolerated in healthy Chinese subjects, and displayed linear PK in the range of 15-60 mg. There were significant differences in the elimination of LPZ and the formation of LPZS between the single CYP2C19 poor metabolizer (PM) and the CYP2C19 extensive metabolizers (EM). The concentration of LPZS at the time-points in the elimination phase of LPZ could be monitored for CYP2C19 phenotyping. As a probe drug for CYP2C19 phenotyping, LPZ for injection might be more suitable than LPZ oral formulations.

Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study.

Science.gov (United States)

Zhang, Ting; Tang, Meng; Zhang, Shanshan; Hu, Yuanyuan; Li, Han; Zhang, Tao; Xue, Yuying; Pu, Yuepu

2017-01-01

The numerous increasing use of carbon nanotubes (CNTs) derived from nanotechnology has raised concerns about their biosafety and potential toxicity. CNTs cause immunologic dysfunction and limit the application of CNTs in biomedicine. The immunological responses induced by pristine multi-walled carbon nanotubes (p-MWCNTs) and PEGylated multi-walled carbon nanotubes (MWCNTs-PEG) on BALB/c mice via an intravenous administration were investigated. The results reflect that the p-MWCNTs induced significant increases in spleen, thymus, and lung weight. Mice treated with p-MWCNTs showed altered lymphocyte populations (CD3 + , CD4 + , CD8 + , and CD19 + ) in peripheral blood and increased serum IgM and IgG levels, and splenic macrophage ultrastructure indicated mitochondria swelling. p-MWCNTs inhibited humoral and cellular immunity function and were associated with decreased immune responses against sheep erythrocytes and serum hemolysis level. Natural killer (NK) activity was not modified by two types of MWCNTs. In comparison with two types of MWCNTs, for a same dose, p-MWCNTs caused higher levels of inflammation and immunosuppression than MWCNTs-PEG. The results of immunological function suggested that after intravenous administration with p-MWCNTs caused more damage to systemic immunity than MWCNTs-PEG. Here, we demonstrated that a surface functional modification on MWCNTs reduces their immune perturbations in vivo. The chemistry-modified MWCNTs change their preferred immune response in vivo and reduce the immunotoxicity of p-MWCNTs.

Median Lethal Doses Associated with Intravenous Exposure to the Optically Pure Enantiomers of VX in Guinea Pigs

Science.gov (United States)

2017-03-01

in Guinea Pigs 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Wright, Linnzi K. M.; Forster, Jeffry S...intravenous exposure of adult, male guinea pigs to the individual VX enantiomers, and we compared those potencies to that for a racemic mixture. The P...highly toxic based on the U.S. Environmental Protection Agency’s Acute Toxicity Categories for Pesticide Products. 15. SUBJECT TERMS Guinea pig

Evidence-based postoperative pain management after laparoscopic colorectal surgery

DEFF Research Database (Denmark)

Joshi, G P; Bonnet, F; Kehlet, H

2013-01-01

transferable evidence from other relevant procedures. Results  Of the 170 randomized studies identified, 12 studies were included. Overall, all approaches including ketorolac, methylprednisolone, intraperitoneal instillation of ropivacaine, intravenous lidocaine infusion, intrathecal morphine and epidural...

Initial experience with intravenous pentobarbital sedation for children undergoing MRI at a tertiary care pediatric hospital: the learning curve

International Nuclear Information System (INIS)

Greenberg, S.B.; Adams, R.C.; Aspinall, C.L.

2000-01-01

Objective. Our purpose is to describe the initial experience with intravenous pentobarbital sedation in children undergoing MRI at a tertiary pediatric hospital to identify errors associated with inexperience. Subjects and methods. The study included the first 100 children sedated with intravenous pentobarbital prior to magnetic resonance examination at a tertiary pediatric hospital. The protocol included a maximum dose of 6 mg/kg administered in three divided doses with the total dose not to exceed 200 mg. Flow sheets documenting vital signs, administered drug doses, and adverse reactions were maintained contemporaneous to sedation. Results. Sedation was successful in 92 children. Of the eight children who failed sedation, three were at least 12 years old and three weighed more than 50 kg. χ 2 tests identified significantly greater failure rates in children older than 11 years or weight greater than 50 kg. Two children had prolonged sedation after the maximum suggested dose was exceeded. Conclusions. The success rate was good, but could have been improved by restricting the use of pentobarbital to children less than 12 years of age and weighing less than 50 kg. Radiologists inexperienced with intravenous sedation should strictly observe the maximum suggested dose of pentobarbital to prevent prolonged sedation. (orig.)

Intravenous superoxide dismutase as a protective agent to prevent impairment of lung function induced by high tidal volume ventilation.

Science.gov (United States)

Wu, Nan-Chun; Liao, Fan-Ting; Cheng, Hao-Min; Sung, Shih-Hsien; Yang, Yu-Chun; Wang, Jiun-Jr

2017-07-26

Positive-pressure mechanical ventilation is essential in assisting patients with respiratory failure in the intensive care unit and facilitating oxygenation in the operating room. However, it was also recognized as a primary factor leading to hospital-acquired pulmonary dysfunction, in which pulmonary oxidative stress and lung inflammation had been known to play important roles. Cu/Zn superoxide dismutase (SOD) is an important antioxidant, and possesses anti-inflammatory capacity. In this study, we aimed to study the efficacy of Cu/Zn SOD, administered intravenously during high tidal volume (HTV) ventilation, to prevent impairment of lung function. Thirty-eight male Sprague-Dawley rats were divided into 3 groups: 5 h ventilation with (A) low tidal volume (LTV; 8 mL/kg; n = 10), (B) high tidal volume (HTV; 18 mL/kg; n = 14), or (C) HTV and intravenous treatment of Cu/Zn SOD at a dose of 1000 U/kg/h (HTV + SOD; n = 14). Lung function was evaluated both at baseline and after 5-h ventilation. Lung injury was assessed by histological examination, lung water and protein contents in the bronchoalveolar lavage fluid (BALF). Pulmonary oxidative stress was examined by concentrations of methylguanidine (MG) and malondialdehyde (MDA) in BALF, and antioxidative activity by protein expression of glutathione peroxidase-1 (GPx-1) in the lung. Severity of lung inflammation was evaluated by white blood cell and differential count in BALF, and protein expression of inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), and mRNA expression of nuclear factor-κB (NF-κB) in the lung. We also examined protein expression of surfactant protein (SP)-A and D and we measured hourly changes in serum nitric oxide (NO) level. Five hours of LTV ventilation did not induce a major change in lung function, whereas 5 h of HTV ventilation induced apparent combined restrictive and

Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial.

Science.gov (United States)

Lv, Jicheng; Zhang, Hong; Wong, Muh Geot; Jardine, Meg J; Hladunewich, Michelle; Jha, Vivek; Monaghan, Helen; Zhao, Minghui; Barbour, Sean; Reich, Heather; Cattran, Daniel; Glassock, Richard; Levin, Adeera; Wheeler, David; Woodward, Mark; Billot, Laurent; Chan, Tak Mao; Liu, Zhi-Hong; Johnson, David W; Cass, Alan; Feehally, John; Floege, Jürgen; Remuzzi, Giuseppe; Wu, Yangfeng; Agarwal, Rajiv; Wang, Hai-Yan; Perkovic, Vlado

2017-08-01

Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain. To evaluate the efficacy and safety of corticosteroids in patients with IgA nephropathy at risk of progression. The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate [eGFR] of 20 to 120 mL/min/1.73 m2 after at least 3 months of blood pressure control with renin-angiotensin system blockade] and to provide follow-up until 335 primary outcomes occurred. Patients were randomized 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/d; maximum, 48 mg/d) (n = 136) or matching placebo (n = 126) for 2 months, with subsequent weaning over 4 to 6 months. The primary composite outcome was end-stage kidney disease, death due to kidney failure, or a 40% decrease in eGFR. Predefined safety outcomes were serious infection, new diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular events. The mean required follow-up was estimated to be 5 years. After randomization of 262 participants (mean age, 38.6 [SD, 11.1] years; 96 [37%] women; eGFR, 59.4 mL/min/1.73 m2; urine protein excretion, 2.40 g/d) and 2.1 years' median follow-up, recruitment was discontinued because of excess serious adverse events. Serious events occurred in 20 participants (14.7%) in the methylprednisolone group vs 4 (3.2%) in the placebo group (P = .001; risk difference, 11.5% [95% CI, 4.8%-18.2%]), mostly due to excess serious infections (11 [8.1%] vs 0; risk difference, 8.1% [95% CI, 3.5%-13.9%]; P < .001), including 2 deaths. The primary renal outcome occurred in 8 participants (5.9%) in the methylprednisolone group vs 20 (15.9%) in the placebo group (hazard ratio, 0.37 [95% CI, 0.17-0.85]; risk difference, 10.0% [95% CI, 2

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)

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

Directory of Open Access Journals (Sweden)

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.

Optimized dose distribution of a high dose rate vaginal cylinder

International Nuclear Information System (INIS)

Li Zuofeng; Liu, Chihray; Palta, Jatinder R.

1998-01-01

Purpose: To present a comparison of optimized dose distributions for a set of high-dose-rate (HDR) vaginal cylinders calculated by a commercial treatment-planning system with benchmark calculations using Monte-Carlo-calculated dosimetry data. Methods and Materials: Optimized dose distributions using both an isotropic and an anisotropic dose calculation model were obtained for a set of HDR vaginal cylinders. Mathematical optimization techniques available in the computer treatment-planning system were used to calculate dwell times and positions. These dose distributions were compared with benchmark calculations with TG43 formalism and using Monte-Carlo-calculated data. The same dwell times and positions were used for a quantitative comparison of dose calculated with three dose models. Results: The isotropic dose calculation model can result in discrepancies as high as 50%. The anisotropic dose calculation model compared better with benchmark calculations. The differences were more significant at the apex of the vaginal cylinder, which is typically used as the prescription point. Conclusion: Dose calculation models available in a computer treatment-planning system must be evaluated carefully to ensure their correct application. It should also be noted that when optimized dose distribution at a distance from the cylinder surface is calculated using an accurate dose calculation model, the vaginal mucosa dose becomes significantly higher, and therefore should be carefully monitored

High-dose superselective intra-arterial cisplatin and concomitant radiation therapy for carcinoma of the oral cavity

International Nuclear Information System (INIS)

Suzuki, Gen; Tanaka, Norimitsu; Ogo, Etuyo

2007-01-01

The purpose of this study was to evaluate the effect of high-dose superselective intra-arterial cisplatin and concomitant radiation therapy for carcinoma of the oral cavities. The subjects consisted of 18 patients with carcinoma of the oral, and cavity treated with superselective intra-arterial infusion of high dose cisplatin (100 mg/body) concomitant with delivery of external beam radiotherapy (median total dose, 60.8 Gy) between 2001 and 2004. Sodium thiosulfate was administered intravenously to provide effective cisplatin neutlization. They were International Union Against Cancer (UICC)1997 stage II-IV (stage II: 4 patients, stage III: 4 patients, stage IV: 10 patients). Patients ranged from 43-81 years of age, with a median of 60 years, and included 14 men and 4 women. A follow-up period was 6 months minimum from the atart of the radiation therapy, the median follow up period at 28 months. The three-year overall survival rate was 71%. The three-year disease free rate and local control rate were 60% and 65%, respectively. Three-year local control rate of the T2-3 was achieved at 83%, and that for T4 at 50%. There was borderline significant difference in local control rate between T2-3 and T4 (p=0.05). We conclude that the high-dose superselective intra-arterial cisplatin and concomitant radiation therapy provides effective results in organ preservation for cancer of oral cavities. Further studies are also required to determine the validity of this method. (author)

Population pharmacokinetics of intravenous Erwinia asparaginase in pediatric acute lymphoblastic leukemia patients

NARCIS (Netherlands)

Sassen, Sebastiaan D. T.; Mathôt, Ron A. A.; Pieters, Rob; Kloos, Robin Q. H.; de Haas, Valérie; Kaspers, Gertjan J. L.; van den Bos, Cor; Tissing, Wim J. E.; te Loo, Maroeska; Bierings, Marc B.; Kollen, Wouter J. W.; Zwaan, Christian M.; van der Sluis, Inge M.

2017-01-01

Erwinia asparaginase is an important component in the treatment of pediatric acute lymphoblastic leukemia. A large variability in serum concentrations has been observed after intravenous Erwinia asparaginase. Currently, Dutch Childhood Oncology Group protocols dose alterations are based on trough

Population pharmacokinetics of intravenous Erwinia asparaginase in pediatric acute lymphoblastic leukemia patients

NARCIS (Netherlands)

Sassen, Sebastiaan D. T.; Mathot, Ron A. A.; Pieters, Rob; Kloos, Robin Q. H.; de Haas, Valerie; Kaspers, Gertjan J. L.; van den Bos, Cor; Tissing, Wim J. E.; te Loo, D. Maroeska W. M.; Bierings, Marc B.; Kollen, Wouter J. W.; Zwaan, Christian M.; van der Sluis, Inge M.

Erwinia asparaginase is an important component in the treatment of pediatric acute lymphoblastic leukemia. A large variability in serum concentrations has been observed after intravenous Erwinia asparaginase. Currently, Dutch Childhood Oncology Group protocols dose alterations are based on trough

Intravenous application of an anticalin dramatically lowers plasma digoxin levels and reduces its toxic effects in rats

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Eyer, Florian, E-mail: Florian.Eyer@mac.com [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Steimer, Werner [Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Munich (Germany); Nitzsche, Thomas [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany); Jung, Nicole; Neuberger, Heidi [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Müller, Christine [Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Munich (Germany); Schlapschy, Martin [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany); Zilker, Thomas [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Skerra, Arne [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany)

2012-09-15

Lipocalins tailored with high affinity for prescribed ligands, so-called anticalins, constitute promising candidates as antidotes. Here, we present an animal study to investigate both pharmacokinetic and clinical effects of an anticalin specific for the digitalis compound digoxin. Intravenous digoxin (2.5–50 μg/kg/min) was administered to rats until first changes in the ECG occurred (dose finding study) or a priori for 30 min (kinetic study). The anticalin DigA16(H86N), dubbed DigiCal, was administered intravenously at absolute doses of 1, 5, 10 and 20 mg, while the control group received isotonic saline. Hemodynamic changes, several ECG parameters and digoxin concentration in plasma were monitored at given time intervals. After DigiCal administration free digoxin concentration in plasma ultrafiltrate declined dramatically within 1 min to the presumably non-toxic range. There was also a significant and DigiCal dose-dependent effect on longer survival, less ECG alterations, arrhythmia, and improved hemodynamics. Infusion of a lower digoxin dose (2.5 μg/kg/min) resulted in a more sustained reduction of free digoxin in plasma after DigiCal administration compared to a higher digoxin dose (25 μg/kg/min), whereas ECG and hemodynamic parameters did not markedly differ, reflecting the known relative insensitivity of rats towards digoxin toxicity. Notably, we observed a re-increase of free digoxin in plasma some time after bolus administration of DigiCal, which was presumably due to toxin redistribution from tissue in combination with the relatively fast renal clearance of the rather small protein antidote. We conclude that anticalins with appropriately engineered drug-binding activities and, possibly, prolonged plasma half-life offer prospects for next-generation antidotal therapy. -- Highlights: ► We provide an advanced model of digoxin toxicity in rats. ► We report on binding of digoxin to a novel designed anticalin. ► We report on pharmacokinetics of digoxin

Progress in high-dose radiation dosimetry

International Nuclear Information System (INIS)

Ettinger, K.V.; Nam, J.W.; McLaughlin, W.L.; Chadwick, K.H.

1981-01-01

The last decade has witnessed a deluge of new high-dose dosimetry techniques and expanded applications of methods developed earlier. Many of the principal systems are calibrated by means of calorimetry, although production of heat is not always the final radiation effect of interest. Reference systems also include a number of chemical dose meters: ferrous sulphate, ferrous-cupric sulphate, and ceric sulphate acidic aqueous solutions. Requirements for stable and reliable transfer dose meters have led to further developments of several important high-dose systems: amino acids and saccharides analysed by ESR or lyoluminescence, thermoluminescent materials, radiochromic dyes and plastics, ceric-cerous solutions analysed by potentiometry, and ethanol-chlorobenzene solutions analysed by high-frequency oscillometry. A number of other prospective dose meters are also treated in this review. In addition, an IAEA programme of high-dose standardization and intercomparison for industrial radiation processing is described. (author)

Intubation following high-dose rocuronium in a cat with protracted laryngospasm

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Graeme M Doodnaught

2017-10-01

Full Text Available Case summary An 11-year-old spayed female domestic shorthair cat with a history of laryngospasm at induction of general anesthesia presented for dental evaluation and treatment. The cat was premedicated with hydromorphone (0.05 mg/kg and alfaxalone (0.5 mg/kg intravenously, pre-oxygenated for 5 mins (3 l/min, face mask and anesthesia was induced with alfaxalone (to effect intravenously. Lidocaine (0.1 ml, 2% was applied topically to the arytenoid cartilages following loss of jaw tone. Laryngospasm was not noted during or immediately following lidocaine application. However, after waiting 60 s for the onset of effect of the topical lidocaine, laryngospasm was apparent. Orotracheal intubation by direct visualization was unsuccessful after four attempts by three anesthetists (with increasing levels of experience. At this point, a failed intubation was declared and the non-depolarising neuromuscular blocking agent rocuronium (1 mg/kg IV given, resulting in arytenoid abduction and appropriate conditions for intubation. Successful intubation occurred 9 mins after induction of anesthesia. Oxygen was continuously supplemented throughout and arterial hemoglobin saturation with oxygen was never <94%. Relevance and novel information To the authors’ knowledge, this is the first report of the use of high-dose rocuronium to successfully resolve prolonged laryngospasm at induction of general anesthesia in a cat. Despite laryngospasm and a delay in achieving orotracheal intubation, low values for arterial hemoglobin saturation with oxygen (indicative of hypoxemia were not observed, highlighting the benefits of pre-oxygenation and apneic oxygenation. The principles of the Difficult Airway Society 2015 guidelines were followed in managing this difficult intubation.

Intravenous and inhalation toxicokinetics of sarin stereoisomers in atropinized guinea pigs

NARCIS (Netherlands)

Spruit, W.E.T.; Langenberg, J.P.; Trap, H.C.; Wiel, H.J. van der; Helmich, R.B.; Helden, H.P.M. van; Benschop, H.P.

2000-01-01

We report the first toxicokinetic studies of (±)-sarin. The toxicokinetics of the stereoisomers of this nerve agent were studied in anesthetized, atropinized, and restrained guinea pigs after intravenous bolus administration of a dose corresponding to 0.8 LD50 and after nose-only exposure to vapor

Effect of high-dose lidocaine treatment on superoxide dismutase and malon dialdehyde levels in seven diabetic patients.

Science.gov (United States)

Celebi, H; Bozkirli, F; Günaydin, B; Bilgihan, A

2000-01-01

We report on the use of intravenous (IV) high-dose lidocaine to relieve diabetic neuropathic pain, and the technique's effects on clinical measures of lipid peroxidation. Under continuous electrocardiogram monitoring, IV lidocaine (5 mg kg(-1) in 100 mL saline) was administered over 30 minutes to 7 non-insulin-dependent diabetic patients suffering from neuropathic pain who reported increased pain within the preceding 6 months. This treatment was performed once a week for 1 month. Blood samples were collected from the contralateral limb to determine plasma superoxide dismutase (SOD) and malondialdehyde (MDA) levels on admission and following the final lidocaine administration. Plasma MDA concentrations significantly decreased after the final IV lidocaine treatment (P < .05, paired t-test), whereas SOD levels did not show a statistically significant difference compared with baseline levels. High-dose lidocaine treatment lessens MDA levels, a marker of free-radical-mediated cell damage. This suggests that one of lidocaine's mechanism of action may be its effect on oxygen free radicals, which in turn impacts lipid peroxidation.

Disseminated nocardiosis in a patient on infliximab and methylprednisolone for treatment-resistant Sweet′s syndrome

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Elizabeth R Drone

2014-01-01

Full Text Available A 62-year-old white man with a 10-year history of treatment-refractory Sweet′s syndrome was admitted to the hospital with the onset of purpuric lesions. Methylprednisolone and infliximab were administered. Our patient developed disseminated Nocardia infection and eventually succumbed. Opportunistic infections such as Nocardia have been associated with infliximab and other tumour necrosis factor (TNF-α inhibitors. The astute clinician should be aware of the risk of rare opportunistic infections, particularly in patients on TNF-α inhibitors and systemic corticosteroids.

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.

Impact of intravenous contrast used in computed tomography on radiation dose to carotid arteries and thyroid in intensity-modulated radiation therapy planning for nasopharyngeal carcinoma

Energy Technology Data Exchange (ETDEWEB)

Lee, Victor Ho Fun, E-mail: vhflee@hku.hk; Ng, Sherry Chor Yi; Kwong, Dora Lai Wan; Lam, Ka On; Leung, To Wai

2017-07-01

The aim of this study was to investigate if intravenous contrast injection affected the radiation doses to carotid arteries and thyroid during intensity-modulated radiation therapy (IMRT) planning for nasopharyngeal carcinoma (NPC). Thirty consecutive patients with NPC underwent plain computed tomography (CT) followed by repeated scanning after contrast injection. Carotid arteries (common, external, internal), thyroid, target volumes, and other organs-at-risk (OARs), as well as IMRT planning, were based on contrast-enhanced CT (CE-CT) images. All these structures and the IMRT plans were then copied and transferred to the non–contrast-enhanced CT (NCE-CT) images, and dose calculation without optimization was performed again. The radiation doses to the carotid arteries and the thyroid based on CE-CT and NCE-CT were then compared. Based on CE-CT, no statistical differences, despite minute numeric decreases, were noted in all dosimetric parameters (minimum, maximum, mean, median, D05, and D01) of the target volumes, the OARs, the carotid arteries, and the thyroid compared with NCE-CT. Our results suggested that compared with NCE-CT planning, CE-CT scanning should be performed during IMRT for better target and OAR delineation, without discernible change in radiation doses.

Intravenous nitroglycerin as an experimental model of vascular headache. Basic characteristics

DEFF Research Database (Denmark)

Iversen, Helle Klingenberg; Olesen, J; Tfelt-Hansen, P

1989-01-01

To develop a reliable experimental model of vascular headache, we studied the dose-response relationship between headache and i.v. nitroglycerin (NTG) in 10 healthy subjects. NTG was infused intravenously over periods of 10 min separated by wash-out periods. Doses of 0.25, 0.50, 1.00 and 2......) at various doses and declined rapidly after NTG discontinuation. Wash-out periods of 10-20 min were sufficient. The reproducibility of headache intensity and character was satisfactory in the retest experiment. There were no unpleasant side effects and no visible flushing. Thus blindness was maintained. I...

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)

[Experimental study on avascular necrosis of femoral head in chickens induced by different glucocorticoides].

Science.gov (United States)

Xiao, Chun-Sheng; Lin, Na; Lin, Shi-Fu; Wan, Rong; Chen, Wei-Heng

2010-03-01

To study the effects of Methylprednisolone and Dexamethasone on the avascular necrosis of femoral head in chickens. Thirty-six chickens were randomly divided into 6 groups (n = 6): control group (group A), Methylprednisolone low dose group (group B), Methylprednisolone large dose group (group C), small dose Dexamethasone and horse serum group (group D), middle dose Dexamethasone and horse serum group (group E), and Dexamethasone large dose group (group F). On the 6th and 12th weeks, blood samples were obtained to determine the level of total cholesterol triglyeride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL). On the 12th week, femoral heads were taken off. Paraffin tissue sections were prepared to detect histopathologic change with hematoxylin and eosin staining. On the 6th week, compared with group A, the level of CHO increased significantly in group C and group F (P < 0.05), and TG increased in group B, C and group E, while HDL decreased in group B, C and group E. On the 12th week, the level of TG and CHO increased in group B, C, E and group F, and HDL decreased in group C, D and group E (P < 0.05). LDL was not detected in most chickens. The ratio of empty lacuna was higher in group C and group E compared with those of the control group (P < 0.05). Methylprednisolone is easier to induce osteonecrosis of femoral head than Dexamethasone. The condition of metabolic disorder in blood may be the basic pathomechanism of steroid-induced necrosis of femoral head.

Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers.

Science.gov (United States)

Zuurman, Lineke; Passier, Paul C C M; de Kam, Marieke L; Kleijn, Huub J; Cohen, Adam F; van Gerven, Joop M A

2010-11-01

An ideal drug for outpatient treatments under conscious sedation would have both sedative and analgesic properties. CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties of intravenous Org 26828. In addition, pharmacokinetics, amnestic properties, postural stability, and behavioural and cardiovascular effects were studied. Midazolam intravenous 0.1 mg/kg and placebo were used as controls. The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose. No effects were observed after doses up to 0.3 μg/kg of Org 26828. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 26828 at 3 and 6 μg/kg, the observed sedation was considerably less than after midazolam. Doses higher than the maximum tolerated dose of 1 μg/kg of Org 26828 caused unpleasant central nervous system effects (anxiety, paranoia, hallucinations). Therefore, Org 26828 is not suitable for providing sedation for outpatient surgical procedures.

Intracranial meningiomas after high-dose irradiation

International Nuclear Information System (INIS)

Soffer, D.; Gomori, J.M.; Siegal, T.; Shalit, M.N.

1989-01-01

Three patients who presented with intracranial meningiomas 12, 15, and 20 years, respectively, after therapeutic high-dose irradiation of a primary brain tumor are described. Analysis of these cases and similar documented cases suggests that meningiomas after high-dose irradiation constitute a recognizable entity. Patients with such tumors received radiation therapy at a young age (mean age, 9.4 years). After a latent period of 2 to 47 years (mean, 19.8 years) they developed meningiomas at the site of irradiation, at a much younger age than patients with ''spontaneous'' meningiomas. Similar to the situation with meningiomas after low-dose irradiation, a relatively high proportion of meningiomas induced by high-dose irradiation tend to be malignant and biologically aggressive. A very young age at the time of irradiation seems to predispose to the induction of malignant meningiomas, rather than benign tumors. These unusual features provide indirect evidence that high-dose radiation may play a role in the pathogenesis of meningiomas.41 references

Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers.

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Ryszard M Pluta

Full Text Available BACKGROUND: Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion. METHODOLOGY: Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075 between July 2007 and August 2008. All subjects provided written consent to participate. Twelve subjects (5 males, 7 females; mean age, 38.8±9.2 years (range, 21-56 years were intravenously infused with increasing doses of sodium nitrite for 48 hours (starting dose at 4.2 µg/kg/hr; maximal dose of 533.8 µg/kg/hr. Clinical, physiologic and laboratory data before, during and after infusion were analyzed. FINDINGS: The maximal tolerated dose for intravenous infusion of sodium nitrite was 267 µg/kg/hr. Dose limiting toxicity occurred at 446 µg/kg/hr. Toxicity included a transient asymptomatic decrease of mean arterial blood pressure (more than 15 mmHg and/or an asymptomatic increase of methemoglobin level above 5%. Nitrite, nitrate, S-nitrosothiols concentrations in plasma and whole blood increased in all subjects and returned to preinfusion baseline values within 12 hours after cessation of the infusion. The mean half-life of nitrite estimated at maximal tolerated dose was 45.3 minutes for plasma and 51.4 minutes for whole blood. CONCLUSION: Sodium nitrite can be safely infused intravenously at defined concentrations for prolonged intervals. These results should be valuable for developing studies to investigate new NO treatment paradigms for a variety of clinical disorders, including cerebral vasospasm after subarachnoid hemorrhage, and ischemia of the heart, liver, kidney and brain, as well as organ transplants, blood-brain barrier modulation and pulmonary hypertension. CLINICAL TRIAL REGISTRATION INFORMATION: http

Intravenous lidocaine for postmastectomy pain treatment: randomized, blind, placebo controlled clinical trial

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Tania Cursino de Menezes Couceiro

2015-06-01

Full Text Available BACKGROUND AND OBJECTIVE: Postoperative pain treatment in mastectomy remains a major challenge despite the multimodal approach. The aim of this study was to investigate the analgesic effect of intravenous lidocaine in patients undergoing mastectomy, as well as the postoperative consumption of opioids. METHODS: After approval by the Human Research Ethics Committee of the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, a randomized, blind, controlled trial was conducted with intravenous lidocaine at a dose of 3 mg/kg infused over 1 h in 45 women undergoing mastectomy under general anesthesia. One patient from placebo group was. RESULTS: Groups were similar in age, body mass index, type of surgery, and postoperative need for opioids. Two of 22 patients in lidocaine group and three of 22 patients in placebo group requested opioid (p = 0.50. Pain on awakening was identified in 4/22 of lidocaine group and 5/22 of placebo group (p = 0.50; in the post-anesthetic recovery room in 14/22 and 12/22 (p = 0.37 of lidocaine and placebo groups, respectively. Pain evaluation 24 h after surgery showed that 2/22 and 3/22 patients (p = 0.50 of lidocaine and placebo groups, respectively, complained of pain. CONCLUSION: Intravenous lidocaine at a dose of 3 mg/kg administered over a period of an hour during mastectomy did not promote additional analgesia compared to placebo in the first 24 h, and has not decreased opioid consumption. However, a beneficial effect of intravenous lidocaine in selected and/or other therapeutic regimens patients cannot be ruled out.

Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

International Nuclear Information System (INIS)

Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

1987-01-01

Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82 Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity

Intravenous immunoglobulin therapy in a patient with lupus serositis and nephritis.

Science.gov (United States)

Meissner, M; Sherer, Y; Levy, Y; Chwalinska-Sadowska, H; Langevitz, P; Shoenfeld, Y

2000-01-01

The use of intravenous immunoglobulin (IVIg) has been reported as an immunomodulating agent in several autoimmune diseases, including systemic lupus erythematosus (SLE). Herein we report a SLE patient with severe clinical presentation that included pericarditis, pleural effusion, nephrotic range proteinuria, leukopenia, and lymphopenia. The patient received one course of high-dose IVIg (2.8 g/kg body weight), and within a week of post-IVIg therapy, her condition significantly improved. One-month post-IVIg there were decreased proteinuria, elevated leukocytes and lymphocytes count, decrease in antinuclear and anti-dsDNA antibodies, and disappearance of pericarditis and pleuritis. This case demonstrates the efficacy of IVIg in severe SLE with various clinical manifestations.

Single-dose intravenous iron infusion versus red blood cell transfusion for the treatment of severe postpartum anaemia

DEFF Research Database (Denmark)

Holm, C; Thomsen, L L; Norgaard, A

2017-01-01

BACKGROUND AND OBJECTIVES: There are no randomized trials comparing intravenous iron to RBC transfusion for the treatment of severe postpartum anaemia. The objectives of this study were to evaluate the feasibility of randomizing women with severe postpartum anaemia secondary to postpartum...... haemorrhage to RBC transfusion or intravenous iron, and to describe patient-reported outcomes, and haematological and iron parameters. MATERIALS AND METHODS: Women with a postpartum haemorrhage exceeding 1000 ml and an Hb between 5·6 and 8·1 g/dl were randomized to 1500 mg of intravenous iron (n = 7......) isomaltoside or RBC transfusion (n = 6). Participants completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and blood samples were drawn at inclusion, daily during the first week and at weeks 3, 8 and 12. RESULTS: We screened 162 women and included 13 (8...

Efficacy of reduced dose of intravitreal triamcinolone acetonide in a case of active serpiginous choroiditis

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Avirupa Ghose

2016-01-01

Full Text Available Active serpiginous choroiditis (SC is a vision-threatening condition which requires intensive treatment using corticosteroids and/or immunosuppressives, especially if the lesions are involving or encroaching on the macula. Use of oral and intravenous high-dose steroids are contraindicated in uncontrolled diabetics. Intravitreal steroid delivers a localized dose in such situations. This case report highlights the efficacy of reduced dose of intravitreal triamcinolone acetonide (2 mg in the treatment of active SC.

Don’t live in a town where there are no doctors: toxic epidermal necrolysis initially misdiagnosed as oral thrush

Science.gov (United States)

Wani, Abdul Majid; Hussain, Waleed Mohd; Fatani, Mohamad Ibrahim; Ali, Khaled Shawkat; Khoujah, Amer Mohd; Akhtar, Mubeena; Maimani, Ghassan Adnan Al; Raja, Sadeya Hanif; Basraheel, Ashraf; Fareed, Khurram

2009-01-01

Toxic epidermal necrolysis (TEN) is a rare but life threatening skin disease that is most commonly drug induced. The exact pathogenesis of TEN is still unknown and many drugs, including prednisolone, cyclosporin and intravenous immunoglobulin (IVIG), have been used in an attempt to halt the disease process. The use of IVIG in particular is controversial. Recently, the US Food and Drug Administration (FDA) has made a labelling change to the drug information for carbamazepine. Owing to recent data implicating the HLA allele B*1502 as a marker for carbamazepine induced Stevens–Johnson syndrome and TEN in Han Chinese, the FDA recommends genotyping all Asians for the allele. We present an interesting case of carbamazepine induced TEN which was confused with oral thrush, had no skin lesions on presentation, and had an excellent response to a 5 day course of methylprednisolone and high dose IVIG in combination. PMID:22207871

High-dose irradiation of food

International Nuclear Information System (INIS)

Diehl, J.F.

1999-01-01

Studies performed on behalf of the International Project on Food Irradiation in the period from 1971 until 1980 resulted in the concluding statement that ''.the irradiation of any food commodity up to an overall average dose of 10 kGy presents no toxicological hazard; hence, toxicological testing of foods so treated is no longer required.'' Since then, licenses for food irradiation have been restricted to this maximum dose in any country applying this technology. Further testing programmes have been carried out investigating the wholesomeness or hazards of high-dose irradiation, but there has been little demand so far by the food industry for licensing of high-dose irradiation, as there is only a small range of products whose irradiation at higher doses offers advantages for given, intended use. These include eg. spices, dried herbs, meat products in flexible pouch packagings for astronauts, or patients with immune deficiencies. (orig./CB) [de

Intravenous Vitamin C administration reduces fatigue in office workers: a double-blind randomized controlled trial

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Suh Sang-Yeon

2012-01-01

Full Text Available Abstract Background Studies of the efficacy of vitamin C treatment for fatigue have yielded inconsistent results. One of the reasons for this inconsistency could be the difference in delivery routes. Therefore, we planned a clinical trial with intravenous vitamin C administration. Methods We evaluated the effect of intravenous vitamin C on fatigue in office workers. A group of 141 healthy volunteers, aged 20 to 49 years participated in this randomized, double-blind, controlled clinical trial. The trial group received 10 grams of vitamin C with normal saline intravenously, while the placebo group received normal saline only. Since vitamin C is a well-known antioxidant, oxidative stress was measured. Fatigue score, oxidative stress, and plasma vitamin C levels were measured before intervention, and again two hours and one day after intervention. Adverse events were monitored. Results The fatigue scores measured at two hours after intervention and one day after intervention were significantly different between the two groups (p = 0.004; fatigue scores decreased in the vitamin C group after two hours and remained lower for one day. Trial also led to higher plasma vitamin C levels and lower oxidative stress compared to the placebo group (p Conclusion Thus, intravenous vitamin C reduced fatigue at two hours, and the effect persisted for one day. There were no significant differences in adverse events between two groups. High dose intravenous vitamin C proved to be safe and effective against fatigue in this study. Trial Registration The clinical trial registration of this trial is http://ClinicalTrials.govNCT00633581.

Low-Dose Intravenous Immunoglobulin Treatment for Long-Standing Complex Regional Pain Syndrome: A Randomized Trial.

Science.gov (United States)

Goebel, Andreas; Bisla, Jatinder; Carganillo, Roy; Frank, Bernhard; Gupta, Rima; Kelly, Joanna; McCabe, Candy; Murphy, Caroline; Padfield, Nick; Phillips, Ceri; Sanders, Mark; Serpell, Mick; Shenker, Nick; Shoukrey, Karim; Wyatt, Lynne; Ambler, Gareth

2017-10-03

Two small trials suggest that low-dose intravenous immunoglobulin (IVIg) may improve the symptoms of complex regional pain syndrome (CRPS), a rare posttraumatic pain condition. To confirm the efficacy of low-dose IVIg compared with placebo in reducing pain during a 6-week period in adult patients who had CRPS from 1 to 5 years. 1:1 parallel, randomized, placebo-controlled, multicenter trial for 6 weeks, with an optional 6-week open extension. Patients were randomly assigned to 1 of 2 study groups between 27 August 2013 and 28 October 2015; the last patient completed follow-up on 21 March 2016. Patients, providers, researchers, and outcome assessors were blinded to treatment assignment. (ISRCTN42179756). 7 secondary and tertiary care pain management centers in the United Kingdom. 111 patients with moderate or severe CRPS of 1 to 5 years' duration. IVIg, 0.5 g/kg of body weight, or visually indistinguishable placebo of 0.1% albumin in saline on days 1 and 22 after randomization. The primary outcome was 24-hour average pain intensity, measured daily between days 6 and 42, on an 11-point (0- to 10-point) rating scale. Secondary outcomes were pain interference and quality of life. The primary analysis sample consisted of 108 eligible patients, 103 of whom had outcome data. Mean (average) pain scores were 6.9 points (SD, 1.5) for placebo and 7.2 points (SD, 1.3) for IVIg. The adjusted difference in means was 0.27 (95% CI, -0.25 to 0.80; P = 0.30), which excluded the prespecified, clinically important difference of -1.2. No statistically significant differences in secondary outcomes were found between the groups. In the open extension, 12 of the 67 patients (18%) who received 2 IVIg infusions had pain reduction of at least 2 points compared with their baseline score. Two patients in the blinded phase (1 in the placebo and 1 in the IVIg group) and 4 in the open IVIg phase had serious events. Results do not apply to patients who have had CRPS for less than 1 year or more

Problems in radiation absorbed dose estimation from positron emitters

International Nuclear Information System (INIS)

Powell, G.F.; Harper, P.V.; Reft, C.S.; Chen, C.T.; Lathrop, K.A.

1986-01-01

The positron emitters commonly used in clinical imaging studies for the most part are short-lived, so that when they are distributed in the body the radiation absorbed dose is low even though most of the energy absorbed is from the positrons themselves rather than the annihilation radiation. These considerations do not apply to the administration pathway for a radiopharmaceutical where the activity may be highly concentrated for a brief period rather than distributed in the body. Thus, high local radiation absorbed doses to the vein for an intravenous administration and to the upper airways during administration by inhalation can be expected. For these geometries, beta point source functions (FPS's) have been employed to estimate the radiation absorbed dose in the present study. Physiologic measurements were done to determine other exposure parameters for intravenous administration of O-15 and Rb-82 and for administration of O-15-CO 2 by continuous breathing. Using FPS's to calculate dose rates to the vein wall from O-15 and Rb-82 injected into a vein having an internal radius of 1.5 mm yielded dose rates of 0.51 and 0.46 (rad x g/μCi x h), respectively. The dose gradient in the vein wall and surrounding tissues was also determined using FPS's. Administration of O-15-CO 2 by continuous breathing was also investigated. Using ultra-thin thermoluninescent dosimeters (TLD's) having the effective thickness of normal tracheal mucosa, experiments were performed in which 6 dosimeters were exposed to known concentrations of O-15 positrons in a hemicylindrical tracheal phantom having an internal radius of 0.96 cm and an effective length of 14 cm. The dose rate for these conditions was 3.4 (rads/h)/(μCi/cm 3 ). 15 references, 7 figures, 6 tables

''Low dose'' and/or ''high dose'' in radiation protection: A need to setting criteria for dose classification

International Nuclear Information System (INIS)

Sohrabi, M.

1997-01-01

The ''low dose'' and/or ''high dose'' of ionizing radiation are common terms widely used in radiation applications, radiation protection and radiobiology, and natural radiation environment. Reading the title, the papers of this interesting and highly important conference and the related literature, one can simply raise the question; ''What are the levels and/or criteria for defining a low dose or a high dose of ionizing radiation?''. This is due to the fact that the criteria for these terms and for dose levels between these two extreme quantities have not yet been set, so that the terms relatively lower doses or higher doses are usually applied. Therefore, setting criteria for classification of radiation doses in the above mentioned areas seems a vital need. The author while realizing the existing problems to achieve this important task, has made efforts in this paper to justify this need and has proposed some criteria, in particular for the classification of natural radiation areas, based on a system of dose limitation. (author)

[Effect of intravenous dexketoprofen use on postoperative analgesic consumption in patients with lumbar disc surgery].

Science.gov (United States)

Kelsaka, Ebru; Güldoğuş, Fuat; Cetinoğlu, Erhan

2014-01-01

The objective of this study was to evaluate the postoperative analgesic effect of a preemptive, single-dose intravenous dexketoprofen administration in patients undergoing lumbar microdiscectomy. A total of 50 ASA I-II patients candidate to laminectomy were included in this study. They were divided in two groups. Patients in Group A were given 50 mg (2 mL) dexketoprofen and those in Group K 2 mL normal saline intravenously by a blinded anesthesia physician, 10 minutes before the start of intervention. All cases underwent general anesthesia. All patients received postoperative patient-controlled analgesia with tramadol. The VAS scores 1, 4, 8, 16 and 24 hours following the operation, sedation and patient satisfaction scores and tramadol consumption were evaluated. VAS scores recorded during the first 8 postoperative hours and total tramadol amounts were lower, and the patient satisfaction scores higher, in patients given dexketoprofen than control group. Sedation scores and side effects were similar in both groups. Single-dose preemptive intravenous dexketoprofen provides effective analgesia especially in the first 8 postoperative hours, reducing tramadol use.

REVIEW ARTICLE – Intravenous paracetamol in pediatrics: A global perspective

Directory of Open Access Journals (Sweden)

Muzammil Irshad, MBBS

2012-12-01

Full Text Available Intravenous (IV Paracetamol is an excellent post operative analgesic and antipyretic in children. Efficacy and tolerability of IV Propacetamol have been established in pediatric practice. It is believed that paracetamol works by inhibiting cyclooxygenase-2 (COX-2 enzymes. Studies bring to light that therapeutic doses of IV acetaminophen are effective and tolerable in children with least chances of hepatotoxicity. However, overdose toxicity has been reported in children and drug induced hypotension in febrile critically ill patients. Therapeutic doses according to body weight of neonates and children can be administered in hospital settings. Special education of health care staff regarding precise dose and solution is necessary to assess the role of IV paracetamol preparation in pediatric practice.

Disposition kinetics of long acting moxifloxacin following intravenous administration in Sheep

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Chirag M. Modi

Full Text Available Aim: The objective of the present study was to study the disposition kinetics and dosage regimens of long acting moxifloxacin following intravenous administration at the dose rate of 7.5 mg/kg-1 b. wt. in six male sheep and to calculate dosage regimens of the same in sheep. Materials and Methods: The study was conducted using six healthy male sheep. Long acting Moxifloxacin solution (10 % moxifloxacin in solution with L- arginine, N-butyl alcohol and benzyl alcohol was injected in jugular vein and periodical blood samples were collected from contra-lateral jugular vein in test tubes containing 30-50 IU heparin (anticoagulant at 0.083 (5 min, 0.166 (10 min, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 60, 72 and up to 96 h post administration of drug. Drug concentration in plasma was determined using High Performance Liquid Chromatography (HPLC with Fluorescence Detector. The blood concentrations versus time data were analyzed using software. Results: After single dose intravenous administration of long acting moxifloxacin the plasma concentration of 0.016 ± 0.001 μg/ml-1 was maintained for up to 72 h. Distribution half-life (t and elimination half-life (t were 1.637 ± 0.053 h, and 1/2 1/2 12.130 ± 0.202 h, following IV administration. The mean values of apparent volume of distribution V 5.436 ± 0.135 L/kg-1 d(area as well as mean residence time 10.02 ± 4.787 minute were detected with IV administration. Conclusion: The long acting Moxifloxacin @ the dose 7.5 mg/kg IV maintains the effective therapeutic concentration in the plasma of sheep for up to 72 hours. The long acting Moxifloxacin at this dose rate can be used to treat sensitive bacteria causing infectious diseases in sheep. [Vet World 2012; 5(9.000: 517-521

Effect of antiarrhythmic therapy with intravenous loading dose of amiodarone: evidence for an altered response in diabetic patients.

Science.gov (United States)

Iervasi, G; Clerico, A; Bonini, R; Nannipieri, M; Manfredi, C; Sabatino, L; Biagini, A; Donato, L

1998-01-01

Amiodarone, a potent class III antiarrhythmic agent with adrenergic antagonism properties, is administered increasingly to diabetic patients with cardiac arrhythmias refractory to all other available forms of therapy. Because a large percentage of diabetic patients show a perturbed autonomic regulation of the cardiovascular system, including a pertubed regulation of heart rate, we studied the antiarrhythmic response as well as the early effects (within 5 days) on heart rate of an intravenous amiodarone loading dose in diabetic patients. Seven type II (noninsulin-dependent) diabetic patients (age 64.7 +/- 9.7 years), affected by uncontrolled atrial fibrilation or atrial flutter, were enrolled for the study and a group of 12 well-matched (for age, sex and arrhythmia) nondiabetic patients served as a control group. It was found that before amiodarone administration, nondiabetic patients showed significantly wider variations in the circadian rhythm of heart rate values than diabetic patients (p = 0.0062, unpaired t-test). In all patients but one (who was nondiabetic), amiodarone treatment resulted in a cardioversion to sinus rhythm. After amiodarone administration, nondiabetic patients showed a significantly greater decrease (p = 0.0011) in heart rate values in comparison with the diabetic group (-35% vs. -20% on average, at the end of the study). Furthermore, in nondiabetic patients there was also an earlier significant fall (within the first 4 h after the start of treatment with amiodarone, p atrial fibrilation or atrial flutter may be delayed in comparison with nondiabetic patients. This altered response may be (at least in part) due to the diabetic autonomic neuropathy. Our study indicates that the presence of diabetes mellitus always must be taken into account when patients are enrolled for large, prospective, randomized trials, planned to evaluate the antiarrhythmic effects of amiodarone given intravenously.

Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a multiple ascending dose study in opioid-naïve healthy volunteers.

Science.gov (United States)

Rauck, Richard L; Oh, D Alexander; Singla, Neil; Koch, Christian; Parikh, Neha; Nalamachu, Srinivas; Wilson, Daniel; Yu, Jin; Vetticaden, Santosh

2017-11-01

Fentanyl sublingual spray, with its rapid onset for pain relief, may be efficacious in the management of acute or post-operative pain. Because patients in these settings may be opioid-naïve, the study was conducted to determine the safety, tolerability, and pharmacokinetics of multiple dose administration of fentanyl sublingual spray in an opioid-naïve population. Fentanyl sublingual spray (100 mcg, 200 mcg, and 400 mcg) and fentanyl citrate intravenous (IV; 50 mcg) were administered every 0.5, 1.0, 2.0, and 4.0 h for up to three doses per cohort in opioid-naïve subjects (ClinicalTrials.gov identifier: NCT02641340). Eight subjects in each cohort were randomly assigned (six subjects received fentanyl sublingual spray; two subjects received fentanyl citrate IV). Pharmacokinetic and safety-related pharmacodynamic assessments were performed through 24 h post-first dose. Safety assessments were collected through Day 7. Ninety-six opioid-naïve subjects, aged 20-55 years, with a body mass index of 18.7-31.5 kg/m 2 , participated in the study. Multiple doses of fentanyl sublingual spray (100, 200, and 400 mcg) were generally well tolerated. Hypoxia, observed in the 200-mcg and 400-mcg dose groups, increased with increasing doses and higher dosing frequency, but was readily managed by nasal cannula oxygenation. Overall, nausea increased with increasing doses, and ∼52.6% (10 out of 19) cases of nausea that occurred at the highest dose of 400 mcg were treated with concomitant medication. Overall, the reported adverse events were consistent with the known safety profile of fentanyl. Fentanyl sublingual spray (100 mcg, 200 mg, and 400 mcg) administered every 0.5, 1, 2, and 4 h was generally well tolerated in an opioid-naïve population. The results suggest that doses of 200 mcg or lower may be safe for use in an opioid-naïve population.

Phase I dose escalation pharmacokinetic assessment of intravenous humanized anti-MUC1 antibody AS1402 in patients with advanced breast cancer.

Science.gov (United States)

Pegram, Mark D; Borges, Virginia F; Ibrahim, Nuhad; Fuloria, Jyotsna; Shapiro, Charles; Perez, Susan; Wang, Karen; Schaedli Stark, Franziska; Courtenay Luck, Nigel

2009-01-01

MUC1 is a cell-surface glycoprotein that establishes a molecular barrier at the epithelial surface and engages in morphogenetic signal transduction. Alterations in MUC1 glycosylation accompany the development of cancer and influence cellular growth, differentiation, transformation, adhesion, invasion, and immune surveillance. A 20-amino-acid tandem repeat that forms the core protein of MUC1 is overexpressed and aberrantly glycosylated in the majority of epithelial tumors. AS1402 (formerly R1550) is a humanized IgG1k monoclonal antibody that binds to PDTR sequences within this tandem repeat that are not exposed in normal cells. AS1402 is a potent inducer of antibody-dependent cellular cytotoxicity (ADCC), specifically against MUC1-expressing tumor cells. The objective of this study was to determine the safety, tolerability, and pharmacokinetic (PK) characteristics of AS1402 monotherapy in patients with locally advanced or metastatic MUC1-positive breast cancer that had progressed after anthracyclines- and taxane-based therapy. Patients received AS1402 over a 1- to 3-hour intravenous (i.v.) infusion at doses between 1 and 16 mg/kg, with repeated dosing every 1 to 3 weeks (based on patient-individualized PK assessment) until disease progression. Serum AS1402 levels were measured at multiple times after i.v. administration. Human anti-human antibody (HAHA) responses were measured to determine the immunogenicity of AS1402. Noncompartmental pharmacokinetic parameters were determined and were used to assess dose dependency across the dose range studied. Twenty-six patients were treated. AS1402 was generally well tolerated. Two grade 3/4 drug-related adverse events were reported, both at the 3-mg/kg dose. Neither was observed in expanded or subsequent dosing cohorts. No anti-human antibodies were detected. Plasma concentrations of AS1402 appeared to be proportional to dose within the 1- to 16-mg/kg dose range assessed, with a mean terminal half-life of 115.4 +/- 37.1 hours

Clinical observation of alprostadil combined with glucocorticoids on acute optic neuritis

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Ke-Shun Fan

2015-09-01

Full Text Available AIM: To study the clinical effect of alprostadil combined with glucocorticoids in the treatment of acute optic neuritis(AON.METHODS: Seventy patients(70 eyeswith AON from January, 2012 to June, 2014 were randomly divided into two groups. 35 patients in observation group were used 10ug alprostadil with 10mL normal saline(NSby intravenous injection, once/d for 7d/one treatment course, and 10mL NS was used by intravenous injection in 35 patients of control group. Besides, the two groups were treated with the combined therapy as follows: 20mg methylprednisolone was injected periglomerularly beside the eyeballs, once /3d for 3 times; 800～1 000mg of methylprednisolone through intravenous drip for 3d, once/d; after 3d, oral administration of prednisone acetate for 1wk, 1mg/(kg·d; after 1wk, the dose decreased to 5mg/wk until withdraw. Simultaneously, oral administration of ranitidine capsules, calcium carbonate and vitamin D3 tablets were combined in the supportive treament. The differences of curative effect between two groups were comparatively analyzed.RESULTS: In the observation group, 25 eyes(71.4%were markedly effective, 7 eyes(20.0%were valid and 3 eyes(8.6%were invalid, and the total effective rate was 91.4%. In the control group, 15 eyes(42.9%were markedly effective, 14 eyes(40.0%were valid and 6 eyes(17.1%were invalid, and the total effective rate was 82.9%. The difference of total effective rate between the two groups was not statistically significant(P=0.477, but there was a significant difference in markedly effective rate between the two groups(χ2=5.833, P=0.016.CONCLUSION: Alprostadil combined with glucocorticoids is effective for AON, and it is worth of advocation.

Remifentanil Prevents Withdrawal Movements Caused by Intravenous Injection of Rocuronium

Science.gov (United States)

Choi, Byung In; Choi, Seung Ho; Shin, Yang-Sik; Lee, Sung Jin; Yoon, Kyung Bong; Shin, Seo Kyung

2008-01-01

Purpose The incidence of pain induced withdrawal movement following intravenous injection of rocuronium is high. This randomized, double-blind, placebo-controlled study was designed to evaluate the effect of pretreatment of remifentanil on the withdrawal movements due to intravenous injection of rocuronium during anesthetic induction. Materials and Methods Ninety adult female patients undergoing thyroidectomy were randomly allocated to three groups. Each patient intravenously received one of three solutions of equal volume (4 mL): normal saline (Group I, n = 30), 0.5 µg/kg remifentanil (Group II, n = 30) or 1 µg/kg remifentanil (Group III, n = 30). Thirty seconds after remifentanil administration, anesthesia was induced with 5 mg/kg IV thiopental. Twenty seconds after thiopental injection, 0.6 mg/kg IV rocuronium was administered (injection rate of 0.5 mL/sec) and patients' withdrawal movements were assessed. Mean arterial pressure (MAP) and heart rate were assessed on arrival in the operation room, before the tracheal intubation and immediately, 1 and 2 min after the tracheal intubation. Results The incidence of withdrawal movements was significantly lower in both of the remifentanil groups (3 and 0% in Group II and III, respectively) than in the saline group (70%). Remifentanil attenuated the increase of heart rate and MAP immediately and 1 min after the tracheal intubation. Conclusion The pretreatment with 0.5 and 1.0 µg/kg remifentanil of bolus doses prevented the withdrawal movements caused by rocuronium injection, and effectively blunted cardiovascular activation following tracheal intubation. PMID:18452256

Intravenous iron sucrose therapy for moderate to severe anaemia in pregnancy

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Alka Kriplani

2013-01-01

Full Text Available Background & objectives: Iron deficiency anaemia (IDA is the most common nutritional deficiency in pregnancy. Prophylactic oral iron is recommended during pregnancy to meet the increased requirement. In India, women become pregnant with low baseline haemoglobin level resulting in high incidence of moderate to severe anaemia in pregnancy where oral iron therapy cannot meet the requirement. Pregnant women with moderate anaemia are to be treated with parentral iron therapy. This study was undertaken to evaluate the response and effect of intravenous iron sucrose complex (ISC given to pregnant women with IDA. Methods: A prospective study was conducted (June 2009 to June 2011 in the department of Obstetrics & Gynecology, All India Institute of Medical Sciences, New Delhi. One hundred pregnant women with haemoglobin between 5-9 g% with diagnosed iron deficiency attending antenatal clinic were given intravenous iron sucrose complex in a dose of 200 mg twice weekly schedule after calculating the dose requirement. Results: The mean haemoglobin raised from 7.63 ± 0.61 to 11.20 ± 0.73 g% (P<0.001 after eight wk of therapy. There was significant rise in serum ferritin levels (from 11.2 ± 4.7 to 69 ± 23.1 μg/l (P<0.001. Reticulocyte count increased significantly after two wk of starting therapy (from 1.5 ± 0.6 to 4.6±0.8%.Other parameters including serum iron levels and red cell indices were also improved significantly. Only one woman was lost to follow up. No major side effects or anaphylactic reactions were noted during study period. Interpretation & conclusions: Parentral iron therapy was effective in increasing haemoglobin, serum ferritin and other haematological parameters in pregnant women with moderate anaemia. Intravenous iron sucrose can be used in hospital settings and tertiary urban hospitals where it can replace intramuscular therapy due to injection related side effects. Further, long-term comparative studies are required to recommend its

Intrathecal morphine is superior to intravenous PCA in patients undergoing minimally invasive cardiac surgery

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Chirojit Mukherjee

2012-01-01

Full Text Available Aim of our study was to evaluate the beneficial effect of low dose intrathecal morphine on postoperative analgesia, over the use of intravenous patient controlled anesthesia (PCA, in patients undergoing fast track anesthesia during minimally invasive cardiac surgical procedures. A randomized controlled trial was undertaken after approval from local ethical committee. Written informed consent was obtained from 61 patients receiving mitral or tricuspid or both surgical valve repair in minimal invasive technique. Patients were assigned randomly to 2 groups. Group 1 received general anesthesia and intravenous patient controlled analgesia (PCA pump with Piritramide (GA group. Group 2 received a single shot of intrathecal morphine (1.5 μg/kg body weight prior to the administration of general anesthesia (ITM group. Site of puncture was confined to lumbar (L1-2 or L2-3 intrathecal space. The amount of intravenous piritramide used in post anesthesia care unit (PACU and the first postoperative day was defined as primary end point. Secondary end points included: time for tracheal extubation, pain and sedation scores in PACU upto third postoperative day. For statistical analysis Mann-Whitney-U Test and Fishers exact test (SPSS were used. We found that the demand for intravenous opioids in PACU was significantly reduced in ITM group (P <0.001. Pain scores were significantly decreased in ITM group until second postoperative day (P <0.01. There was no time delay for tracheal extubation in ITM group, and sedation scores did not differ in either group. We conclude that low dose single shot intrathecal morphine provides adequate postoperative analgesia, reduces the intravenous opioid consumption during the early postoperative period and does not defer early extubation.

Effect of interleukin-2 and methylprednisolone on in vitro transformation of uremic lymphocytes

DEFF Research Database (Denmark)

Langhoff, E; Ladefoged, J; Ødum, Niels

1986-01-01

The functional relationship in vitro between mitogen-induced lymphocyte transformation, lymphocyte response to interleukin-2 (IL-2) and steroid, and production of IL-2 was examined in patients with chronic renal failure on hemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD......). The lymphocyte responses to optimal stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen were depressed in lymphocyte cultures from HD patients, while CAPD lymphocyte cultures responded normally. However, at suboptimal phytohemagglutinin stimulation both CAPD lymphocyte and HD lymphocyte...... responses were subnormal. Uremic lymphocyte cultures were more sensitive to the immunosuppressive effect of methylprednisolone. Addition of IL-2 normalized the phytohemagglutinin responses of suboptimally stimulated CAPD lymphocyte cultures and clearly improved the mitogen responses of the HD lymphocyte...

An analysis of acute complications and perioperative morbidity from high dose rate brachytherapy in the treatment of gynecological malignancies

International Nuclear Information System (INIS)

Sarkaria, Jann N.; Petereit, Daniel G.; Kinsella, Timothy J.; Buchler, Dolores A.

1995-01-01

Purpose: To evaluate the acute morbidity and mortality for high dose-rate (HDR) brachytherapy performed in an outpatient setting in the treatment of gynecological malignancies, and to identify possible risk factors for adverse outcomes. Materials and Methods: One hundred seventy-one patients with cervical (n=129) or uterine (n=42) carcinoma with an intact uterus were evaluated and treated from August 1989 through December 1994, with at least part of their therapy delivered with intracavitary HDR 192 Ir radiation. A total of 830 ICR insertions were performed with greater than 95% done on an outpatient basis under heavy intravenous sedation using fentanyl and midazolam. Perioperative morbidity and mortality were recorded for any event occurring within 30 days of the completion of therapy. Anesthesia risk was evaluated retrospectively in all patients based on the American Society of Anesthesiologists' (ASA) Physical Class System. Results: The uterine patients, many treated with radiation alone because of morbid obesity or medical inoperability, had a significantly higher perioperative morbidity and mortality rate as compared to the cervix patient cohort. Thirteen of the 42 (31%) uterine patients and 8 of the 129 (6%) cervix patients required hospitalization within 30 days of treatment completion (p 2) experienced greater morbidity and mortality, while the best predictor of complications in the cervix patients was age greater than 70 years. For the entire cohort of patients, no correlation was found between the 30 day morbidity and mortality and the doses of fentanyl and midazolam used or the length of the procedure. Conclusions: The acute complication rate from HDR brachytherapy performed on an outpatient basis with heavy intravenous sedation is acceptable for the great majority of patients who present for treatment. However, the high morbidity and mortality experienced by certain patient cohorts suggests that careful assessment of the risk/benefit ratio for treatment

Dose-reduction techniques for high-dose worker groups in nuclear power plants

International Nuclear Information System (INIS)

Khan, T.A.; Baum, J.W.; Dionne, B.J.

1991-03-01

This report summarizes the main findings of a study of the extent of radiation dose received by special work groups in the nuclear power industry. Work groups which chronically get large doses were investigated, using information provided by the industry. The tasks that give high doses to these work groups were examined and techniques described that were found to be particularly successful in reducing dose. Quantitative information on the extent of radiation doses to various work groups shows that significant numbers of workers in several critical groups receive doses greater than 1 and even 2 rem per year, particularly contract personnel and workers at BWR-type plants. The number of radiation workers whose lifetime dose is greater than their age is much less. Although the techniques presented would go some way in reducing dose, it is likely that a sizeable reduction to the high-dose work groups may require development of new dose-reduction techniques as well as major changes in procedures. 10 refs., 26 tabs

Performance of thermoluminescent materials for high dose dosimetry

International Nuclear Information System (INIS)

Texeira, Maria I.; Cecatti, Sonia G.P.; Caldas, Linda V.E.

2008-01-01

Cases involving high-doses of ionizing radiation are becoming increasingly common.The objective of this work was to characterize thermoluminescent materials for the dosimetry of workers exposed to high doses. Samples of TLD-200, TLD-400 and TLD-800 pellets from Thermo Electron Corporation were studied in gamma high-doses. Dose-response curves were obtained for doses between 100 mGy and 100 Gy. The reproducibility, the lower detection limits and dose-response curves were obtained for all three materials. The different kinds of detectors show usefulness for dosimetry of workers exposed accidentally to high doses. (author)

Successfully Treated Calcific Uremic Arteriolopathy: Two Cases of a High Anion Gap Metabolic Acidosis with Intravenous Sodium Thiosulfate

Science.gov (United States)

Rein, Joshua L.; Miyata, Kana N.; Dadzie, Kobena A.; Gruber, Steven J.; Sulica, Roxana; Winchester, James F.

2014-01-01

Calcific uremic arteriolopathy (CUA) is a rare and potentially fatal disorder of calcification involving subcutaneous small vessels and fat in patients with renal insufficiency. We describe the successful use of intravenous sodium thiosulfate (STS) for the treatment of CUA in two patients. The first case was complicated by the development of a severe anion gap metabolic acidosis, which was accompanied by a seizure. Both patients had complete wound healing within five months. Although STS should be considered in the treatment of CUA, little is known about pharmacokinetics and additional studies are required to determine dosing strategies to minimize severe potential side effects. PMID:25506005

Phase I and pharmacokinetic study of the combination of topotecan and ifosfamide administered intravenously every 3 weeks

NARCIS (Netherlands)

Kerbusch, T.; Groenewegen, G.; Mathôt, R. A. A.; Herben, V. M. M.; ten Bokkel Huinink, W. W.; Swart, M.; Ambaum, B.; Rosing, H.; Jansen, S.; Voest, E. E.; Beijnen, J. H.; Schellens, J. H. M.

2004-01-01

To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetics of topotecan administered as a 30-min intravenous (i.v.) infusion over 5 days in combination with a 1-h i.v. infusion of ifosfamide (IF) for 3 consecutive days every 3 weeks. Patients with advanced

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

Science.gov (United States)

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.

The analgesic efficacy of intravenous lidocaine infusion after laparoscopic fundoplication: a prospective, randomized, double-blind, placebo-controlled trial

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Dale GJ

2016-12-01

Full Text Available Gregory J Dale,1 Stephanie Phillips,2 Gregory L Falk3 1Westmead Hospital Clinical School, The University of Sydney, 2Sydney Adventist Hospital Clinical School, The University of Sydney, 3Concord Clinical School, The University of Sydney, Sydney, Australia Abstract: This study aimed to determine if intravenous lidocaine infusion reduces postoperative pain intensity following laparoscopic fundoplication surgery and to also validate the safety of intravenous lidocaine at the dose tested. This was an equally randomized, double-blind, placebo-controlled, parallel-group, single center trial. Adult patients undergoing laparoscopic fundoplication were recruited. The intervention group received 1 mg/kg intravenous lidocaine bolus prior to induction of anesthesia, then an intravenous infusion at 2 mg/kg/h for 24 hours. The primary outcome was pain, measured using a numeric rating scale for 30 hours postoperatively. Secondary outcomes were nausea and vomiting, opioid requirements, adverse events, serum lidocaine concentration, and length of hospital stay. The study was terminated after an interim analysis of 24 patients showed evidence of futility. There was no difference in postoperative pain scores (lidocaine versus control, mean ± standard deviation at rest (2.0 ± 2.7 vs 2.1 ± 2.4, P=0.286 or with movement (2.0 ± 2.6 vs 2.6 ± 2.7, P=0.487. Three adverse events occurred in the lidocaine group (25% of patients. Intravenous lidocaine did not provide clinically significant analgesia to patients undergoing laparoscopic fundoplication. The serum lidocaine concentration of patients who experienced adverse events were within the therapeutic range. This trial cannot confirm the safety of intravenous lidocaine at the dose tested. Keywords: analgesia, local anesthetics, intravenous infusions, pharmacokinetics

[Toxicity studies of landiolol hydrochloride (ONO-1101) (2). 4-week repeated dose intravenous toxicity study in rats with 4-week recovery test].

Science.gov (United States)

Yamaguchi, K; Yanagi, H; Shimizu, K; Sakai, M; Nishibata, K; Oida, H; Shinomiya, K; Suzuki, Y; Yonezawa, H; Fujita, T

1997-12-01

4-week repeated dose toxicity study with 4-week recovery test of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley (SD) rats. ONO-1101 was administered intravenously to rats of both sexes at a dose level of 0 (control), 12.5, 25, 50 or 100 mg/kg/day. In the 100 mg/kg/day group, bradypnea or dyspnea was seen in all animals, pale in ear, eye and foot, tremor, reddish lacrimation and loss of righting reflex were also observed in some animals right after administration, and then those signs disappeared within 1 min after administration. During the treatment period, 3/20 animals of each sex in the 100 mg/kg/day showed clonic convulsion and died within 2 min after administration. No clinical changes were seen in the 50 mg/kg/day group or lower. Histopathological findings showed atrophy of the submaxillary gland in females and vessel-wall thickening and perivascular fibrosis of the injection site (tail) in both sexes at 100 mg/kg/day, however those changes were reversible. ONO-1101 did not effect on body weight, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights or necropsy at any doses. These results indicate that the no-adverse-effect level of ONO-1101 in rats is 50 mg/kg/day for both sexes in this study.

Fiber optics in high dose radiation fields

International Nuclear Information System (INIS)

Partin, J.K.

1985-01-01

A review of the behavior of state-of-the-art optical fiber waveguides in high dose (greater than or equal to 10 5 rad), steady state radiation fields is presented. The influence on radiation-induced transmission loss due to experimental parameters such as dose rate, total dose, irradiation history, temperature, wavelength, and light intensity, for future work in high dose environments are given

Choice of intravenous contrast material for CT

International Nuclear Information System (INIS)

Cohen, M.D.; Herman, E.; Herron, D.; White, S.T.; Smith, J.A.; Cory, D.A.

1989-01-01

For CT, minor side effects (e.g., nausea, vomiting, pain) following intravenous administration of contrast medium may degrade image quality by causing patient motion or by delaying scanning. The objective of this study was to see if nonionic contrast agents offer advantages in reducing the incidence of such side effects. One hundred five pediatric patients randomly received iohexol (Omnipaque), Iopamidol (Isovue), or diatrizoate sodium (Hypaque). Contrast medium was given in doses of 2 mL/kg body weight (300 mg of iodine per milliliter). The results are presented in the paper

Effect of high-dose dexamethasone on the outcome of acute encephalitis due to Japanese encephalitis virus.

Science.gov (United States)

Hoke, C H; Vaughn, D W; Nisalak, A; Intralawan, P; Poolsuppasit, S; Jongsawas, V; Titsyakorn, U; Johnson, R T

1992-04-01

Death due to Japanese encephalitis usually occurs in the first 5 days of hospitalization as a result of deepening coma with respiratory arrest. Death may result from edema-induced increases in intracranial pressure that might be reduced by the administration of steroids. Sixty-five patients presenting in Thailand to four hospitals with a diagnosis of acute Japanese encephalitis were randomized in a double-masked fashion and stratified by initial mental status into a placebo group (saline) or a treatment group (dexamethasone 0.6 mg/kg intravenously as a loading dose followed by 0.2 mg/kg every 6 h for 5 days). Fifty-five of the 65 had confirmed Japanese encephalitis as demonstrated by detection of virus or by Japanese encephalitis virus-specific IgM antibody. Important outcome measures included mortality (24%, treatment group; 27%, control group), days to alert mental status (3.9 vs. 6.2), and neurologic status 3 months after discharge (45% abnormal in each group). No statistically significant benefit of high-dose dexamethasone could be detected.

Induction of annexin-1 at transcriptional and posttranscriptional level in rat brain by methylprednisolone and the 21-aminosteroid U74389F

NARCIS (Netherlands)

Voermans, PH; Go, KG; TerHorst, GJ; Ruiters, MHJ; Solito, E; Parente, L

1996-01-01

BRAIN tissue of rats pretreated with methylprednisolone or with the 21-aminosteroid U74389F, and that of untreated control rats, was assessed for the expression of annexin-l (Anx-1) and the transcription of its mRNA. For this purpose Anx-1 cDNA was amplified and simultaneously a T7-RNA-polymerase

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

Radiophotoluminescence light scope for high-dose dosimetry

International Nuclear Information System (INIS)

Sato, Fuminobu; Zushi, Naoki; Sakiyama, Tomoki; Kato, Yushi; Murata, Isao; Shimizu, Kikuo; Yamamoto, Takayoshi; Iida, Toshiyuki

2015-01-01

A radiophotoluminescence (RPL) light scope is a remote-sensing technique for measuring in situ the radiation dose in an RPL detector placed at a distance. The RPL light scope is mainly composed of an ultraviolet (UV) pulse laser, telescopic lenses, a photomultiplier tube, and camera modules. In a performance test, some RPL detectors were placed at distances up to 30 m and were illuminated with a pulsed UV laser beam. The photoluminescence responses of the RPL detectors were analyzed using this scope. Their radiation doses were determined from the amplitude of the given component of the photoluminescence responses. The RPL readout could be repeated without fading, and its amplitude exhibited good linearity at a dose ranging from 0.1 to 60 Gy. Furthermore, a two-dimensional distribution of radiation dose was obtained by laser scanning on an RPL detector. It was confirmed that the RPL light scope was a useful remote-sensing tool for high-dose dosimetry. - Highlights: • A radiophotoluminescence (RPL) light scope was developed for high-dose dosimetry. • The RPL light scope has high sensitivity and accuracy in high-dose dosimetry. • Two-dimensional radiation dose distribution was obtained by the RPL light scope.

Exposure doses of the patient and the medical staff during urological X-ray examens

International Nuclear Information System (INIS)

Vogel, H.; Loehr, H.; Haug, P.; Schuett, B.

1977-01-01

During 32 intravenous urografies and 48 angiografies of the kidney and the suprarenal glands the X-ray doses at the patient's skin and gonades were determined. During the angiografies the doses were mesured at the hands. the gonades and the front (eyes) of the medical staff. The results are discussed. Because the X-ray doses are relatively high, the number of the pictures and the exposure time is to be reduced to the minimum. Clinical experience and special knowledge is the best X-ray protection. (orig.) [de

High-dose dosimetry using natural silicate minerals

International Nuclear Information System (INIS)

Carmo, Lucas S. do; Mendes, Leticia; Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina; Barbosa, Renata F.

2015-01-01

In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

High-dose dosimetry using natural silicate minerals

Energy Technology Data Exchange (ETDEWEB)

Carmo, Lucas S. do; Mendes, Leticia, E-mail: isatiro@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina, E-mail: lacifid@if.usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Fisica. Departamento de Fisica Nuclear; Barbosa, Renata F., E-mail: profcelta@hotmail.com [Universidade Federal de Sao Paulo (UNIFESP), Santos, SP (Brazil). Departamento de Ciencias do Mar

2015-07-01

In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

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

Hypersensitivity reaction with intravenous GnRH after pulsatile subcutaneous GnRH treatment in male hypogonadotrophic hypogonadism.

OpenAIRE

Popović, V.; Milosević, Z.; Djukanović, R.; Micić, D.; Nesović, M.; Manojlović, D.; Djordjević, P.; Mićić, J.

1988-01-01

Chronic pulsatile subcutaneous administration of low doses of gonadotrophin releasing hormone (GnRH) is an effective therapy for men with hypogonadotrophic hypogonadism. Hypersensitivity reactions to GnRH are rare. We wish to report hypersensitivity reactions with intravenous GnRH after low dose subcutaneous pulsatile GnRH treatment in two men with hypogonadotrophic hypogonadism due to suprasellar disease.

Treatment of radiation enteritis: a comparison study

International Nuclear Information System (INIS)

Loiudice, T.A.; Lang, J.A.

1983-01-01

Twenty-four patients with severe radiation injury to the small bowel seen over a 4-year period were randomized to four treatment groups: 1) methylprednisolone 80 mg intravenously plus Vivonex-HN, 2 L/day po, 2) methylprednisolone 80 mg intravenously plus total parenteral nutrition, 2.5 L/day, 3) total parenteral nutrition, 2.5 L/day, and 4) Vivonex-HN, 2 L/day po. Patients received nothing by mouth except water in groups II and III, and only Vivonex-HN in groups I and IV. Patients were treated for 8-wk periods. Improvement was gauged by overall nutritional assessment measurements, nitrogen balance data and by radiological and clinical parameters. No significant difference between groups I, II, III, and IV could be found for age, sex, mean radiation dosage, time of onset after radiation therapy, or initial nutritional assessment data. Differences statistically could be found between groups II and III and I and IV regarding nutritional assessment data, nitrogen balance, radiographic and clinical parameters after therapy, with marked improvement noted in groups II and III. We conclude that a treatment regimen consisting of total parenteral nutrition and bowel rest is beneficial in the treatment of radiation enteritis. Methylprednisolone appears to enhance this effect and indeed, may be responsible for a longer lasting response

Nonclinical Safety Assessment of SYN-004: An Oral β-lactamase for the Protection of the Gut Microbiome From Disruption by Biliary-Excreted, Intravenously Administered Antibiotics.

Science.gov (United States)

Kokai-Kun, John F; Bristol, J Andrew; Setser, John; Schlosser, Michael

2016-05-01

SYN-004 is a first in class, recombinant β-lactamase that degrades β-lactam antibiotics and has been formulated to be administered orally to patients receiving intravenous β-lactam antibiotics including cephalosporins. SYN-004 is intended to degrade unmetabolized antibiotics excreted into the intestines and thus has the potential to protect the gut microbiome from disruption by these antibiotics. Protection of the gut microbiome is expected to protect against opportunistic enteric infections such as Clostridium difficile infection as well as antibiotic-associated diarrhea. In order to demonstrate that oral SYN-004 is safe for human clinical trials, 2 Good Laboratory Practice-compliant toxicity studies were conducted in Beagle dogs. In both studies, SYN-004 was administered orally 3 times per day up to the maximum tolerated dose of the formulation. In the first study, doses of SYN-004 administered over 28 days were safe and well tolerated in dogs with the no-observed-adverse-effect level at the high dose of 57 mg/kg/day. Systemic absorption of SYN-004 was minimal and sporadic and showed no accumulation during the study. In the second study, doses up to 57 mg/kg/day were administered to dogs in combination with an intravenous dose of ceftriaxone (300 mg/kg) given once per day for 14 days. Coadministration of oral SYN-004 with intravenous ceftriaxone was safe and well tolerated, with SYN-004 having no noticeable effect on the plasma pharmacokinetics of ceftriaxone. These preclinical studies demonstrate that SYN-004 is well tolerated and, when coadministered with ceftriaxone, does not interfere with its systemic pharmacokinetics. These data supported advancing SYN-004 into human clinical trials. © The Author(s) 2015.

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.

Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

Directory of Open Access Journals (Sweden)

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

High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism

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Tahereh Safari

2015-01-01

Full Text Available Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R- mediated vasodilatation. However, the effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy in postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of estrogen (0.5 mg/kg/week for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30–300 ng/kg/min were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined by pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF decreased in a dose-related manner in response to Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kg−1 min−1, Ang II reduced RBF by 45.7±1.9% in estradiol-treated rats but only by 27.3±5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted the response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with estradiol. We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism could potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using high-dose estrogen.

Systematic review of the use of intravenous amiodarone and nifekalant for cardiopulmonary resuscitation in Japan

Directory of Open Access Journals (Sweden)

Mari Amino, MD, PhD

2014-06-01

Conclusions: Amiodarone and nifekalant were equivalent in their prophylactic and defibrillation efficacy. Concerning the initial amiodarone dose, the 125 mg intravenous [i.v.] over 10 min seemed to be more appropriate for the Japanese population.

The impact of using an intravenous workflow management system (IVWMS) on cost and patient safety.

Science.gov (United States)

Lin, Alex C; Deng, Yihong; Thaibah, Hilal; Hingl, John; Penm, Jonathan; Ivey, Marianne F; Thomas, Mark

2018-07-01

The aim of this study was to determine the financial costs associated with wasted and missing doses before and after the implementation of an intravenous workflow management system (IVWMS) and to quantify the number and the rate of detected intravenous (IV) preparation errors. A retrospective analysis of the sample hospital information system database was conducted using three months of data before and after the implementation of an IVWMS System (DoseEdge ® ) which uses barcode scanning and photographic technologies to track and verify each step of the preparation process. The financial impact associated with wasted and missing >IV doses was determined by combining drug acquisition, labor, accessory, and disposal costs. The intercepted error reports and pharmacist detected error reports were drawn from the IVWMS to quantify the number of errors by defined error categories. The total number of IV doses prepared before and after the implementation of the IVWMS system were 110,963 and 101,765 doses, respectively. The adoption of the IVWMS significantly reduced the amount of wasted and missing IV doses by 14,176 and 2268 doses, respectively (p system was $144,019 over 3 months. The total number of errors detected was 1160 (1.14%) after using the IVWMS. The implementation of the IVWMS facilitated workflow changes that led to a positive impact on cost and patient safety. The implementation of the IVWMS increased patient safety by enforcing standard operating procedures and bar code verifications. Published by Elsevier B.V.

In an animal model nephrogenic systemic fibrosis cannot be induced by intraperitoneal injection of high-dose gadolinium based contrast agents

Energy Technology Data Exchange (ETDEWEB)

Langer, R.D., E-mail: rlanger@uaeu.ac.ae [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Lorke, D.E. [Florida International University, Miami, FL (United States); Neidl van Gorkom, K.F. [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Petroianu, G. [Florida International University, Miami, FL (United States); Azimullah, S.; Nurulain, S.M.; Singh, S. [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Fuchsjäger, M. [Al Ain Hospital, MUV-VAMED, Al Ain (United Arab Emirates)

2012-10-15

Aim and objective: Nephrogenic systemic fibrosis (NSF) has been reported in humans to be most likely induced by gadolinium based contrast agents (GBCA), namely by gadodiamide, gadopentetate dimeglumine, and gadoversetamide, rarely by other GBCA. The pathogenesis of NSF remains unclear; different hypotheses are under discussion. The objective of the study is to assess if in the animal model human-like NSF changes can be induced by high-dose, intraperitoneal GBCA injections over four weeks. Materials and methods: After approval by the institutional animal ethics committee, six rats each were randomly assigned to groups, and treated with seven different GBCA. Intraperitoneal (IP) injections – proven in the animal model to be effective – were chosen to prolong the animals’ exposure to the respective GBCA. GBCA doses of previous intravenous (IV) animal studies were applied. After five weeks all rats were sacrificed. Sham controls were treated with IP saline injections, employing the same regimen. Results: No findings comparable with human NSF were observed in all animals after IP treatment with all seven GBCA at daily doses of 2.5 and 5.0 mmol/kg body weight (BW). No histopathological abnormalities of all examined organs were noted. Weight loss was stated in weeks three and four with GBCA injections at doses of 5.0 mmol/kg BW, but rats regained weight after cessation of GBCA treatment. Conclusions: NSF-comparable pathological findings could not be induced by high dose intraperitoneal injection of seven GBCA.

In an animal model nephrogenic systemic fibrosis cannot be induced by intraperitoneal injection of high-dose gadolinium based contrast agents

International Nuclear Information System (INIS)

Langer, R.D.; Lorke, D.E.; Neidl van Gorkom, K.F.; Petroianu, G.; Azimullah, S.; Nurulain, S.M.; Singh, S.; Fuchsjäger, M.

2012-01-01

Aim and objective: Nephrogenic systemic fibrosis (NSF) has been reported in humans to be most likely induced by gadolinium based contrast agents (GBCA), namely by gadodiamide, gadopentetate dimeglumine, and gadoversetamide, rarely by other GBCA. The pathogenesis of NSF remains unclear; different hypotheses are under discussion. The objective of the study is to assess if in the animal model human-like NSF changes can be induced by high-dose, intraperitoneal GBCA injections over four weeks. Materials and methods: After approval by the institutional animal ethics committee, six rats each were randomly assigned to groups, and treated with seven different GBCA. Intraperitoneal (IP) injections – proven in the animal model to be effective – were chosen to prolong the animals’ exposure to the respective GBCA. GBCA doses of previous intravenous (IV) animal studies were applied. After five weeks all rats were sacrificed. Sham controls were treated with IP saline injections, employing the same regimen. Results: No findings comparable with human NSF were observed in all animals after IP treatment with all seven GBCA at daily doses of 2.5 and 5.0 mmol/kg body weight (BW). No histopathological abnormalities of all examined organs were noted. Weight loss was stated in weeks three and four with GBCA injections at doses of 5.0 mmol/kg BW, but rats regained weight after cessation of GBCA treatment. Conclusions: NSF-comparable pathological findings could not be induced by high dose intraperitoneal injection of seven GBCA

Relative safety profiles of high dose statin regimens

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Carlos Escobar

2008-06-01

Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.Keywords: statins, high doses, tolerability, liver, muscle

Disposition of nasal, intravenous, and oral methadone in healthy volunteers.

Science.gov (United States)

Dale, Ola; Hoffer, Christine; Sheffels, Pamela; Kharasch, Evan D

2002-11-01

Nasal administration of many opioids demonstrates rapid uptake and fast onset of action. Nasal administration may be an alternative to intravenous and oral administration of methadone and was therefore studied in human volunteers. The study was approved by the Institutional Review Board of the University of Washington, Seattle. Eight healthy volunteers (6 men and 2 women) aged 19 to 33 years were enrolled after informed written consent was obtained. Subjects received 10 mg methadone hydrochloride nasally, orally, or intravenously on 3 separate occasions in a crossover design. Nasal methadone (50 mg/mL in aqueous solution) was given as a 100-microL spray in each nostril (Pfeiffer BiDose sprayer). Blood samples for liquid chromatography-mass spectrometry analyses of methadone and the metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium were drawn for up to 96 hours. The methadone effect was measured by noninvasive infrared pupilometry coincident with blood sampling. Nasal uptake of methadone was rapid, with maximum plasma concentrations occurring within 7 minutes. The maximum effects of intravenous, nasal, and oral methadone, on the basis of dark-adapted pupil diameter, were reached in about 15 minutes, 30 minutes, and 2 hours, respectively. The respective durations were 24, 10, and 8 hours. Both nasal and oral bioavailabilities were 0.85. Subjects reported that nasal methadone caused a burning sensation. Nasal administration of methadone results in rapid absorption and onset of effect and high bioavailability, which was greater than that reported for other nasal opioids, with a similar duration of effect. Nasal administration may be an alternative route of methadone administration; however, improved formulations are desirable to reduce nasal irritation.

Segmental lichen aureus: a report of two cases treated with methylprednisolone aceponate.

Science.gov (United States)

Moche, John; Glassman, Steven; Modi, Deepak; Grayson, Wayne

2011-05-01

Two cases of segmental lichen aureus with a response to topical 0.1% methylprednisolone aceponate ointment are reported. A 9-year-old child and a 23-year-old man showed complete resolution of their lesions following treatment with the latter after 7 months and 4 months, respectively. Lichen aureus is a rare form of the pigmented purpuric dermatoses characterized by golden-brown and lichenoid macules and papules, most often on the lower extremities. Segmental presentations have seldom been described. Histology showed a lichenoid infiltrate with extravasation of red blood cells and haemosiderin deposition. The aetiology is unclear and treatment is disappointing. We report an uncommon segmental presentation of lichen aureus with resolution of the lesions after treatment with a topical corticosteroid. © 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.

High Efficiency of Human Normal Immunoglobulin for Intravenous Administration in a Patient with Kawasaki Syndrome Diagnosed in the Later Stages

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Tatyana V. Sleptsova

2016-01-01

Full Text Available The article describes a case of late diagnosis of mucocutaneous lymphonodular syndrome (Kawasaki syndrome. At the beginning of the therapy, the child had fever, conjunctivitis, stomatitis, rash, solid swelling of hands and feet, and coronaritis with the development of aneurysms. The article describes the successful use of normal human immunoglobulin for intravenous administration at a dose of 2 g/kg body weight per course in combination with acetylsalicylic acid at the dose of 80 mg/kg per day. After 3 days of treatment, the rash disappeared; limb swelling and symptoms of conjunctivitis significantly reduced; and laboratory parameters of disease activity became normal (erythrocyte sedimentation rate, C-reactive protein concentration. After 3 months, inflammation in the coronary arteries was stopped. After 6 months, a regression of coronary artery aneurysms was recorded. No adverse effects during the immunoglobulin therapy were observed.

High dose gamma-ray standard

International Nuclear Information System (INIS)

Macrin, R.; Moraru, R.

1999-01-01

The high gamma-ray doses produced in a gamma irradiator are used, mainly, for radiation processing, i.e. sterilization of medical products, processing of food, modifications of polymers, irradiation of electronic devices, a.s.o. The used absorbed doses depend on the application and cover the range 10 Gy to 100 MGy. The regulations in our country require that the response of the dosimetry systems, used for the irradiation of food and medical products, be calibrated and traceable to the national standards. In order to be sure that the products receive the desired absorbed dose, appropriate dosimetric measurements must be performed, including the calibration of the dosemeters and their traceability to the national standards. The high dose gamma-ray measurements are predominantly based on the use of reference radiochemical dosemeters. Among them the ferrous sulfate can be used as reference dosemeter for low doses (up to 400 Gy) but due to its characteristics it deserves to be considered a standard dosemeter and to be used for transferring the conventional absorbed dose to other chemical dosemeters used for absorbed doses up to 100 MGy. The study of the ferrous sulfate dosemeter consisted in preparing many batches of solution by different operators in quality assurance conditions and in determining for all batches the linearity, the relative intrinsic error, the repeatability and the reproducibility. The principal results are the following: the linear regression coefficient: 0.999, the relative intrinsic error: max.6 %, the repeatability (for P* = 95 %): max.3 %, the reproducibility (P* = 95%): max.5 %. (authors)

Comparison of oral and intravenous Ibuprofen for medical closure of patent ductus arteriosus: which one is better?

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Olukman, Ozgur; Calkavur, Sebnem; Ercan, Gulten; Atlihan, Fusun; Oner, Taliha; Tavli, Vedide; Kultursay, Nilgun

2012-01-01

Intravenous ibuprofen is an expensive drug that is being used currently for treating and preventing patent ductus arteriosus. Although oral ibuprofen is much cheaper, there is limited data published about its safety and efficacy. The aim of this study was to compare two forms of ibuprofen in terms of safety and efficacy in closure of patent ductus arteriosus. This is a single-center retrospective study. Data were collected from patients' files of preterm infants who were hospitalized at the Neonatal Intensive Care Unit of Dr. Behcet Uz Children's Hospital between April 2009 and June 2010. Six hundred sixty infants were evaluated by echocardiography between 24 and 48 postnatal hours. Clinically and hemodynamically significant ductus arteriosus was defined in 66 infants with gestational age less than 32 weeks and birth weight less than 1500 g. Oral or intravenous ibuprofen (loading dose: 10 mg/kg on day 1, followed by maintenance dose: 5 mg/kg on days 2 and 3) was administered. Treatment success was defined as a completely closed duct without reopening on follow-up. Drug-associated renal, gastrointestinal, cerebral, hematological, and metabolic side effects were monitored and compared between treatment groups. Ductal closure rates were 100% and 97.6%, respectively, in the oral and intravenous groups. Hypernatremia was the remarkable side effect in the intravenous group, whereas bronchopulmonary dysplasia and septicemia were prominent in the oral group. No statistically significant difference could be demonstrated between the groups in terms of mortality rates. Oral ibuprofen therapy is as efficacious as intravenous ibuprofen with some concerns about increased sepsis and bronchopulmonary dysplasia incidence. However, comprehensive and large-scale pharmacokinetic studies are required in order to prove this efficacy. On the other hand, intravenous ibuprofen still remains to be the drug of choice for patent ductus arteriosus but only with meticulous control of serum

[Value of intravenous immunoglobulins. A case of Guillain-Barré syndrome].

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Hidou, M; Olivier, J; Vivant, J F

1992-01-01

A case of severe Guillain-Barré syndrome (GBS) was treated with high dose intravenous immunoglobulin (IVIG), 400 mg.kg-1.days-1, over three consecutive days. The treatment was repeated once. We observed a time-related response between immunoglobulins administration and clinical improvement. The pathologic lesions of the GBS suggest that this syndrome has an immunologic basis: a humoral factor is probably not the only immunological mechanism and cellular mechanisms are also likely to be of importance. Specific mechanisms might also be present in GBS, such as anti-idiotypic suppression of autoantibodies, and elimination of circulating immune complexes. Treatment with IVIG might have several therapeutic advantages over plasmapheresis: IVIG is easily infused without any delay, is easily available and has been used widely without serious complications.

Case with high cervical intramedullary hemangioblastoma associated with arteriovenous fistula. CT with simultaneous intravenous and intrathecal injection of contrast medium

Energy Technology Data Exchange (ETDEWEB)

Hashimoto, Takao; Shoji, Shin-ichi; Yanagisawa, Nobuo; Tada, Tsuyoshi; Kobayashi, Naoki

1988-02-01

A 34-year-old woman complained of right hemiparesis and pain in the right hand. Routine X-ray of the cervical portion failed to reveal abnormal findings. CT with intravenous contrast medium showed a large high-density mass in the spinal canal at the level of C2. Right vertebral angiography showed a hypervascular mass. With simultaneous intravenous and intrathecal injections of contrast medium, the tumor was shown as a moderately high-density area and the parenchyma of cord as a thin low-density area surrounding the tumor stain on CT. These CT appearances led to the final diagnosis of high cervical intramedullary hemangioblastoma associated with arteriovenous fistulae. Pathological findings are typical of hemangioblastoma. The usefulness of CT in detecting the localization of hypervascular spinal cord lesions is stressed. (Namekawa, K.).

A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

International Nuclear Information System (INIS)

Mason, Jay W; Moon, Thomas E; O’Boyle, Erin; Dietz, Albert

2014-01-01

Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO), intravenous (IV), and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC) injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals. This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF) for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated. The upper one-sided 95% confidence interval (CI) for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36) at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours) and slow elimination (mean half-life 18.6 hours; systemic clearance 20.2 L/hour) of granisetron versus the expected early peak concentration and elimination of granisetron IV. APF530 SC was well tolerated. Adverse events, most commonly constipation and SC injection-site reactions, were generally mild and quickly resolved. APF530 1 g SC did

Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells has a neutral effect on obesity-induced diabetic cardiomyopathy

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Sebastián D Calligaris

2013-01-01

Full Text Available Obesity is a major global health issue. Obese patients develop metabolic syndrome, which is a cluster of clinical features characterized by insulin resistance and dyslipidemia. Its cardiac manifestation, diabetic cardiomyopathy, leads to heart failure. Bone marrow-derived multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSC are envisioned as a therapeutic tool not only for cardiovascular diseases but also for other degenerative conditions. Our aim was to evaluate whether the intravenous administration of MSC modifies cardiac dysfunction in obese mice. To this end, C57BL/6 mice were fed a regular (normal or high-fat diet (obese. Obese animals received the vehicle (obese, a single dose (obese + 1x MSC or three doses (obese + 3x MSC of 0.5x10(6 syngeneic MSC. Two to three months following MSC administration, cardiac function was assessed by cardiac catheterization, at basal condition and after a pharmacological stress. Compared to normal mice, obese mice presented hyperglycemia, hyperinsulinemia, hypercholesterolemia and cardiac dysfunction after stress condition. Exogenous MSC neither improved nor impaired this cardiac dysfunction. Thus, intravenous administration of MSC has neutral effect on obesity-induced diabetic cardiomyopathy

Estimation of the transit dose component in high dose rate brachytherapy

International Nuclear Information System (INIS)

Garcia Romero, A.; Millan Cebrian, E.; Lozano Flores, F.J.; Lope Lope, R.; Canellas Anoz, M.

2001-01-01

Current high dose rate brachytherapy (HDR) treatment planning systems usually calculate dose only from source stopping positions (stationary component), but fails to account for the administered dose when the source is moving (dynamic component or transit dose). Numerical values of this transit dose depends upon the source velocity, implant geometry, source activity and prescribed dose. In some HDR treatments using particular geometry the transit dose cannot be ignored because it increases the dose at the prescriptions points and also could increase potential late tissue complications as predicted by the linear quadratic model. International protocols recommend to verify this parameter. The aim of this paper has been to establish a procedure for the transit dose calculation for the Gammamed 12i equipment at the RT Department in the Clinical University Hospital (Zaragoza-Spain). A numeric algorithm was implemented based on a dynamic point approximation for the moving HDR source and the calculated results for the entrance-exit transit dose was compared with TLD measurements made in some discrete points. (author) [es

Combined treatment of methylprednisolone pulse and memantine hydrochloride prompts recovery from neurological dysfunction and cerebral hypoperfusion in carbon monoxide poisoning: a case report.

Science.gov (United States)

Iwamoto, Konosuke; Ikeda, Ken; Mizumura, Sunao; Tachiki, Kazuhiro; Yanagihashi, Masaru; Iwasaki, Yasuo

2014-03-01

A 49-year-old healthy man developed sudden unconsciousness under inadequate ventilation. Blood gas analysis showed carboxyhemoglobin of 7.3%. After normobaric oxygen therapy, he recovered completely 7 days later. At 3 weeks after carbon monoxide (CO) exposures, memory and gait disturbances appeared. Neurological examination revealed Mini-Mental State Examination (MMSE) score of 5 of 30 points, leg hyper-reflexia with Babinski signs, and Parkinsonism. Brain fluid-attenuated inversion recovery imaging disclosed symmetric hypointense lesions in the thalamus and the globus pallidus, and hyperintense lesions in the cerebral white matter. Brain single-photon emission tomography (SPECT) scanning with (99m)Technesium-ethyl cysteinate dimer displayed marked hypoperfusion in the cerebellum, the thalamus, the basal ganglia, and the entire cerebral cortex. He was diagnosed as CO poisoning and treated with hyperbaric oxygen therapy. The neurological deficits were not ameliorated. At 9 weeks after neurological onset, methylprednisolone (1000 mg/day, intravenous, 3 days) and memantine hydrochloride (20 mg/day, per os) were administered. Three days later, MMSE score was increased from 3 to 20 points. Neurological examination was normal 3 weeks later. Brain SPECT exhibited 20% increase of regional cerebral blood flows in the cerebellum, the thalamus, the basal ganglia, and the entire cerebral cortex. These clinicoradiological changes supported that the treatment with steroid pulse and memantine hydrochloride could prompt recovery from neurological dysfunction and cerebral hypoperfusion. Further clinical trials are warranted whether such combined therapy can attenuate neurological deficits and cerebral hypoperfusion in patients with CO poisoning. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

ELDRS Characterization for a Very High Dose Mission

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Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

2010-01-01

Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

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.

Rationale and design of the Aquapheresis Versus Intravenous Diuretics and Hospitalization for Heart Failure (AVOID-HF) trial.

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Costanzo, Maria Rosa; Negoianu, Daniel; Fonarow, Gregg C; Jaski, Brian E; Bart, Bradley A; Heywood, J Thomas; Nabut, Jose L; Schollmeyer, Michael P

2015-09-01

In patients hospitalized with acutely decompensated heart failure, unresolved signs and symptoms of fluid overload have been consistently associated with poor outcomes. Regardless of dosing and type of administration, intravenous loop diuretics have not reduced heart failure events or mortality in patients with acutely decompensated heart failure. The results of trials comparing intravenous loop diuretics to mechanical fluid removal by isolated venovenous ultrafiltration have yielded conflicting results. Studies evaluating early decongestive strategies have shown that ultrafiltration removed more fluid and was associated with fewer heart failure-related rehospitalization than intravenous loop diuretics. In contrast, when used in the setting of worsening renal function, ultrafiltration was associated with poorer renal outcomes and no reduction in heart failure events. The AVOID-HF trial seeks to determine if an early strategy of ultrafiltration in patients with acutely decompensated heart failure is associated with fewer heart failure events at 90 days compared with a strategy based on intravenous loop diuretics. Study subjects from 40 highly experienced institutions are randomized to either early ultrafiltration or intravenous loop diuretics. In both treatment arms, fluid removal therapies are adjusted according to the patients' hemodynamic condition and renal function. The study was unilaterally terminated by the sponsor in the absence of futility and safety concerns after the enrollment of 221 subjects, or 27% of the originally planned sample size of 810 patients. The AVOID-HF trial's principal aim is to compare the safety and efficacy of ultrafiltration vs that of intravenous loop diuretics in patients hospitalized with acutely decompensated heart failure. Because stepped treatment approaches are applied in both ultrafiltration and intravenous loop diuretics groups and the primary end point is time to first heart failure event within 90 days, it is hoped that

Comparative evaluation of prophylactic single-dose intravenous antibiotic with postoperative antibiotics in elective urologic surgery

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Mohammad K Moslemi

2010-11-01

site infection rates of categories A and B in Group 1 were 0 and two (0.86%, respectively, while those in Group 2 were 0 and five (0.92%, respectively. There was no significant difference in infection rates in terms of remote infection and surgical site infection between Group 1 and Group 2 (P = 0.670. The amounts, as well as the prices, for intravenously administered antibiotics decreased to approximately one quarter.Conclusion: Our protocol effectively decreased the amount of antibiotics used without increasing perioperative infection rates. Thus, our protocol of prophylactic antibiotic therapy can be recommended as an appropriate method for preventing perioperative infection in urologic surgery. Keywords: surgical site infection, antibiotic prophylaxis, single dose, urologic surgery

Haloperidol dose combined with dexamethasone for PONV prophylaxis in high-risk patients undergoing gynecological laparoscopic surgery: a prospective, randomized, double-blind, dose-response and placebo-controlled study.

Science.gov (United States)

Joo, Jin; Park, Yong Gyu; Baek, Jungwon; Moon, Young Eun

2015-07-08

Low-dose haloperidol is known to be effective for the prevention of postoperative nausea and vomiting (PONV). However, precise dose-response studies have not been completed, especially in patients at high risk for PONV who require combination therapy. This study sought to identify which dose of haloperidol 1mg or 2mg could be combined with dexamethasone without adverse effects in high-risk patients undergoing gynecological laparoscopic surgery. Female adults (n = 150) with three established PONV risk factors based on Apfel's score were randomized into one of three study groups. At the end of anesthesia, groups H0, H1, and H2 were given intravenous (IV) saline, haloperidol 1 mg, and haloperidol 2 mg, respectively. All patients were given dexamethasone 5 mg during the induction of anesthesia. The overall early (0-2 h) and late (2-24 h) incidences of nausea, vomiting, rescue anti-emetic administration, pain, and adverse effects (cardiac arrhythmias and extrapyramidal effects) were assessed postoperatively. The sedation score was recorded in the postanesthesia care unit (PACU). The total incidence of PONV over 24 h was significantly lower in groups H1 (29 %) and H2 (24 %) than in group H0 (54 %; P = 0.003), but there was no significant difference between groups H1 and H2. In the PACU, group H2 had a higher sedation score than groups H1 and H0 (P haloperidol was equally effective as 2 mg in terms of preventing PONV with the less sedative effect. ClinicalTrials.gov ( NCT01639599 ).

Radioimmunotherapy for liver micrometastases in mice. Pharmacokinetics, dose estimation, and long-term effect

International Nuclear Information System (INIS)

Saga, Tsuneo; Sakahara, Harumi; Nakamoto, Yuji; Sato, Noriko; Zhao, Songji; Iida, Yasuhiko; Konishi, Junji; Kuroki, Masahide; Endo, Keigo

1999-01-01

The pharmacokinetics of a therapeutic dose of 131 I-labeled antibody and the absorbed dose in liver micrometastases of human colon cancer LS174T in female BALB/c nu/nu mice were investigated, along with the long-term therapeutic effect. Mice with liver micrometastases were given an intravenous injection of 131 I-labeled anti-carcinoembryonic antigen (CEA) antibody F33-104 (8.88 MBq/40 μg). The biodistribution of the antibody was determined 1, 2, 4, 6, and 10 days later. The absorbed dose was estimated for three hypothetical tumor diameters; 1,000, 500, and 300 μm. Autoradiography showed a homogeneous distribution of radioactivity in the micrometastases, and a high uptake was maintained until day 6 (24.0% injected dose (ID)/g on day 1 to 17.8% ID/g on day 6), but decreased thereafter. The absorbed doses in the 1,000-, 500-, and 300-μm tumors were calculated to be 19.1, 12.0, and 8.2 Gy, respectively. The intravenous injection of the 131 I-labeled antibody also showed a dose-dependent therapeutic effect (all mice of the nontreated group died, with a mean survival period of 4 weeks; 3 of the 8 mice that received 9.25 MBq survived up to 120 days with no sign of liver metastasis). These data give further evidence that micrometastasis is a good target of radioimmunotherapy, and that an absorbed dose of less than 20 Gy can effectively control small metastatic lesions. (author)

Comparing the effects of epidural methylprednisolone acetate injected in patients with pain due to lumbar spinal stenosis or herniated disks: a prospective study

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Gharibi F

2011-12-01

Full Text Available Jafar Mobaleghi1, Faramarz Allahdini2, Karim Nasseri3, Behzad Ahsan3, Shoaleh Shami4, Mansour Faizi5, Fardin Gharibi51Department of Surgery, 2Department of Neurosurgery, 3Department of Anesthesia, 4Faculty of Nursing, 5Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Kurdistan, IranObjective: Satisfactory results have been seen with epidural steroid injections (ESI in patients with herniated disks (HD, but the role in lumbar spinal stenosis (LSS has been less investigated. We compared long-term effects of ESI in HD and LSS patients.Methods: In a prospective, single-blind uncontrolled study, 60 patients with radicular pain due to HD (n = 32 or LSS (n = 28 were enrolled over a 9-month period. Methylprednisolone acetate 80 mg plus 0.5% bupivacaine 10 mg were diluted in normal saline up to a total volume of 10 mL, and injected into the epidural space. The amount of pain based on numeric pain score, level of activity, and subjective improvement were reported by patients after 2 and 6 months by telephone. Demographic data were analyzed with the chi-square test. The differences in numeric pain scale scores between the two groups at different times were analyzed with the t-test.Results: There were no differences between HD and LSS patients regarding age, sex, and average duration of pain prior to ESI. The degree of pain was significantly higher in LSS patients in comparison with HD patients in the pre-injection period. The amount of pain was significantly reduced in both groups 2 months after injection. This pain reduction period lasted for 6 months in the HD group, but to a lesser extent in LSS patients (P < 0.05.Discussion: Epidural methylprednisolone injection has less analgesic effect in LSS, with less permanent effect in comparison with HD.Keywords: methylprednisolone acetate, lumbar spinal stenosis, herniated disk

Pharmacokinetics and skin concentrations of lincomycin after intravenous and oral administration to cats

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Gabriela A. Albarellos

2013-10-01

Full Text Available The aim of the present study was to describe the plasma pharmacokinetic profile and skin concentrations of lincomycin after intravenous administration of a 15% solution and oral administration of 300 mg tablets at a dosing rate of 15 mg/kg to cats. Susceptibility of staphylococci (n = 31 and streptococci (n = 23 strains isolated from clinical cases was also determined. Lincomycin plasma and skin concentrations were determined by microbiological assay using Kocuria rhizophila ATCC 9341 as test microorganism. Susceptibility was established by the antimicrobial disc diffusion test. Individual lincomycin plasma concentration–time curves were analysed by a non-compartmental approach. After intravenous administration, volume of distribution, body clearance and elimination half-life were 0.97 L/kg ± 0.15 L/kg, 0.17 L/kg ± 0.06 L/h.kg and 4.20 h ± 1.12 h, respectively. After oral administration, peak plasma concentration, time of maximum plasma concentration and bioavailability were 22.52 µg/mL ± 10.97 µg/mL, 0.80 h ± 0.11 h and 81.78% ± 24.05%, respectively. Two hours after lincomycin administration, skin concentrations were 17.26 µg/mL ± 1.32 µg/mL (intravenous and 16.58 µg/mL ± 0.90 µg/mL (oral. The corresponding skin: plasma ratios were 2.08 ± 0.47 (intravenous and 1.84 ± 0.97 (oral. The majority of staphylococci and streptococci tested in this study were susceptible to lincosamides (87.09% and 69.56%, respectively. In conclusion, lincomycin administered orally at the assayed dose showed a good pharmacokinetic profile, with a long elimination half-life and effective skin concentration. Therefore, it could be a good first option for treating skin infections in cats.

Quality control of 192Ir high dose rate after loading brachytherapy dose veracity

International Nuclear Information System (INIS)

Feng Zhongsu; Xu Xiao; Liu Fen

2008-01-01

Recently, 192 Ir high dose rate (HDR) afterloading are widely used in brachytherapy. The advantage of using HDR systems over low dose rate systems are shorter treatment time and higher fraction dose. To guarantee the veracity of the delivery dose, several quality control methods are deseribed in this work. With these we can improve the position precision, time precision and dose precision of the brachytherapy. (authors)

Administrative risk quantification of subcutaneous and intravenous therapies in Italian centers utilizing the Failure Mode and Effects Analysis approach

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Ponzetti C

2016-08-01

Full Text Available Clemente Ponzetti,1 Monica Canciani,2 Massimo Farina,2 Sara Era,3 Stefan Walzer4,5 1Gruppo Policlinico di Monza, Alessandria, ANMDO National Association of Hospital Physicians, Bologna, 2Studio EmmEffe Srl, Milan, 3Roche Spa, Monza, Italy; 4MArS Market Access & Pricing Strategy GmbH, Weil am Rhein, 5State University Baden-Wuerttemberg, Health Care Management, Loerrach, Germany Background: In oncology, an important parameter of safety is the potential treatment error in hospitals. The analyzed hypothesis is that of subcutaneous therapies would provide a superior safety benefit over intravenous therapies through fixed-dose administrations, when analyzed with trastuzumab and rituximab.Methods: For the calculation of risk levels, the Failure Mode and Effect Analysis approach was applied. Within this approach, the critical treatment path is followed and risk classification for each individual step is estimated. For oncology and hematology administration, 35 different risk steps were assessed. The study was executed in 17 hematology and 16 breast cancer centers in Italy. As intravenous and subcutaneous were the only injection routes in medical available for trastuzumab and rituximab in oncology at the time of the study, these two therapies were chosen.Results: When the risk classes were calculated, eight high-risk areas were identified for the administration of an intravenous therapy in hematology or oncology; 13 areas would be defined as having a median-risk classification and 14 areas as having a low-risk classification (total risk areas: n=35. When the new subcutaneous formulation would be applied, 23 different risk levels could be completely eliminated (65% reduction. Important high-risk classes such as dose calculation, preparation and package labeling, preparation of the access to the vein, pump infusion preparation, and infusion monitoring were included in the eliminations. The overall risk level for the intravenous administration was estimated

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.

The Role of Intravenous Immunoglobulin Preparations in the Treatment of Systemic Sclerosis

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Marta Baleva

2011-01-01

Full Text Available Scleroderma is progressive autoimmune disease associated with severe disability. The major underlying pathological process in scleroderma is progressive development of fibrous tissue and obliteration of the microvasculature. Currently, there are no medical products for the treatment of scleroderma that provide both sufficient immunosuppression and low-risk side safety profile with negligible side effects. There are a large number of experimental data showing that intravenous immunoglobulin (IVIG has multiple clinical and morphological effects. On the other hand, some authors report good effect of intravenous immune globulins in patients with scleroderma. The less frequent side effects of IVIG in doses below or equal to 2 g/kg/month divided in 5 consecutive days make IVIG a promising treatment of choice in scleroderma.

Pharmacokinetically guided dosing of (high-dose) chemotherapeutic agents

NARCIS (Netherlands)

Attema-de Jonge, M.E. (Milly Ellen)

2004-01-01

Due to variation in drug distribution, metabolism and elimination processes between patients, systemic exposure to chemotherapeutic agents may be highly variable from patient to patient after administration of similar doses. This pharmacokinetic variability may explain in part the large variability

Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose-Response Curves in Worsening Refractory Congestive Heart Failure.

Science.gov (United States)

Paterna, Salvatore; Di Gaudio, Francesca; La Rocca, Vincenzo; Balistreri, Fabio; Greco, Massimiliano; Torres, Daniele; Lupo, Umberto; Rizzo, Giuseppina; di Pasquale, Pietro; Indelicato, Sergio; Cuttitta, Francesco; Butler, Javed; Parrinello, Gaspare

2015-10-01

Diuretic responsiveness in patients with chronic heart failure (CHF) is better assessed by urine production per unit diuretic dose than by the absolute urine output or diuretic dose. Diuretic resistance arises over time when the plateau rate of sodium and water excretion is reached prior to optimal fluid elimination and may be overcome when hypertonic saline solution (HSS) is added to high doses of furosemide. Forty-two consecutively hospitalized patients with refractory CHF were randomized in a 1:1:1 ratio to furosemide doses (125 mg, 250 mg, 500 mg) so that all patients received intravenous furosemide diluted in 150 ml of normal saline (0.9%) in the first step (0-24 h) and the same furosemide dose diluted in 150 ml of HSS (1.4%) in the next step (24-48 h) as to obtain 3 groups as follows: Fourteen patients receiving 125 mg (group 1), fourteen patients receiving 250 mg (group 2), and fourteen patients receiving 500 mg (group 3) of furosemide. Urine samples of all patients were collected at 30, 60, and 90 min, and 3, 4, 5, 6, 8, and 24 h after infusion. Diuresis, sodium excretion, osmolality, and furosemide concentration were evaluated for each urine sample. After randomization, 40 patients completed the study. Two patients, one in group 2 and one in group 3 dropped out. Patients in group 1 (125 mg furosemide) had a mean age of 77 ± 17 years, 43% were male, 6 (43%) had heart failure with a preserved ejection fraction (HFpEF), and 64% were in New York Heart Association (NYHA) class IV; the mean age of patients in group 2 (250 mg furosemide) was 80 ± 8.1 years, 15% were male, 5 (38%) had HFpEF, and 84% were in NYHA class IV; and the mean age of patients in group 3 (500 mg furosemide) was 73 ± 12 years, 54% were male, 6 (46%) had HFpEF, and 69% were in NYHA class IV. HSS added to furosemide increased total urine output, sodium excretion, urinary osmolality, and furosemide urine delivery in all patients and at all time points. The percentage increase was 18,14, and

The effects of increasing doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs.

Science.gov (United States)

Honkavaara, J M; Restitutti, F; Raekallio, M R; Kuusela, E K; Vainio, O M

2011-08-01

Different doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, with or without dexmedetomidine were compared in conscious dogs. Eight animals received either dexmedetomidine (10 μg/kg [D]), MK-467 (250 μg/kg [M250] or dexmedetomidine (10 μg/kg) with increasing doses of MK-467 (250 μg/kg [DM250], 500 μg/kg [DM500] and 750 μg/kg [DM750], respectively). Treatments were given intravenously (i.v.) in a randomized, crossover design with a 14-day washout period. Systemic hemodynamics and arterial blood gas analyses were recorded at baseline and at intervals up to 90 min after drugs administration. Dexmedetomidine alone decreased heart rate, cardiac index and tissue oxygen delivery and increased mean arterial pressure and systemic vascular resistance 5 min after administration. DM250 did not completely prevent these early effects, while DM750 induced a decrease in mean arterial pressure. With DM500, systemic hemodynamics remained stable throughout the observational period. MK-467 alone increased cardiac index and tissue oxygen delivery and had no deleterious adverse effects. No differences in arterial blood gases were observed between treatments that included dexmedetomidine. It was concluded that MK-467 attenuated or prevented dexmedetomidine's systemic hemodynamic effects in a dose-dependent manner when given simultaneously i.v. but had no effect on the pulmonary outcome in conscious dogs. A 50:1 dose ratio (MK-467:dexmedetomidine) induced the least alterations in cardiovascular function. © 2010 Blackwell Publishing Ltd.

Acute Changes in Mentation in a Patient with Hepatic Cirrhosis Treated with High Doses of Dexamethasone.

Science.gov (United States)

Dabul, Luis; Droney, Andrew; Oms, Juan; Sanchez-Gonzalez, Marcos A

2017-09-10

Despite the anti-inflammatory benefits of steroids in the management of multiple medical conditions, they are associated with undesired metabolic and psychiatric side effects. We present a case of a 57-year-old Hispanic man with hepatic cirrhosis due to hepatitis C and no past medical history of psychiatric illnesses who became delirious after treatment with high doses of intravenous Dexamethasone. The patient presented to Larkin Community Hospital, USA with complaints of lower back pain requiring treatment with steroids for severe lumbar central canal stenosis. After three days of treatment, the patient became disoriented to time and place, grossly psychotic with auditory hallucinations and disorganized behavior, manic, aggressive, combative, restless, hard to redirect, and unable to follow commands. He met the criteria for a diagnosis of substance-induced psychotic disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM) V. Furthermore, the patient had worsening hepatic profile, a high ammonia level of 125 umol/L, and clinical findings consistent with West Haven classification grade 2 encephalopathy. Head computed tomography (CT) scan was normal. He was treated with discontinuation of steroids, lactulose, and Haloperidol returning to baseline mental status after 48 hours. The patient's hospitalization was complicated with a prolonged hospital stay after lumbar surgery. This case illustrates that treatment with high doses of Dexamethasone in a patient with hepatic cirrhosis can cause acute changes in mental status by (i) inducing delirium, and (ii) precipitating hepatic encephalopathy.

Dynamics of morphofunctional erythrocyte properties during intravenous glucose injection in patients with coronary heart disease

Science.gov (United States)

Malinova, Lidia I.; Simonenko, Georgy V.; Denisova, Tatyana P.; Tuchin, Valery V.

2007-02-01

Dynamics of glucose concentration in human organism is an important diagnostic characteristic for it's parameters correlate significantly with the severity of metabolic, vessel and perfusion disorders. 36 patients with stable angina pectoris of II and III functional classes were involved in this study. All of them were men in age range of 45-59 years old. 7 patients hospitalized with acute myocardial infarction (aged from 49 to 59 years old) form the group of compare. Control group (n = 5) was of practically healthy men in comparable age. To all patients intravenous glucose solution (40%) in standard loading dose was injected. Capillary and vein blood samples were withdrawn before, and 5, 60, 120, 180 and 240 minutes after glucose load. At these time points blood pressure and glucose concentration were measured. In prepared blood smears shape, deformability and sizes of erythrocytes, quantity and degree of shear stress resistant erythrocyte aggregates were studied. Received data were approximated by polynomial of high degree to receive concentration function of studied parameters, which first derivative elucidate velocity characteristics of morphofunctional erythrocyte properties during intravenous glucose injection in patients with coronary heart disease and practically healthy persons. Received data show principle differences in dynamics of morphofunctional erythrocyte properties during intravenous glucose injection in patients with coronary heart disease as a possible mechanism of coronary blood flow destabilization.

Role of Intravenous Ferric Carboxy-maltose in Pregnant Women with Iron Deficiency Anaemia.

Science.gov (United States)

Mishra, Vineet; Gandhi, Khusaili; Roy, Priyankur; Hokabaj, Shaheen; Shah, Kunur N

2017-09-08

Iron deficiency is a common nutritional deficiency amongst women of childbearing age. Peri-partum iron deficiency anaemia is associated with significant maternal, foetal and infant morbidity. Current options for treatment include oral iron, 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 modern treatment option. The study was designed to assess the safety and efficacy of intravenous ferric carboxymaltose for correction of iron deficiency anaemia in pregnant women. A prospective study was conducted at Institute of Kidney Disease and Research Centre, Ahmedabad from January 2014 to December 2016. Antenatal women (108) with iron deficiency anaemia were the study subjects. Socio-demographic profile was recorded and anaemia was assessed based on recent haemoglobin reports. Iron deficiency was diagnosed on basis of serum ferritin value. Intravenous ferric carboxymaltose as per total correction dose (maximum 1500mg) was administered to all women; the improvement in haemoglobin levels were assessed after 3 weeks of total dose infusion. Most of the women(n= 45, 41.7%), were in the age group of 27-30 years. Most of the women (n = 64, 59.3%) had moderate anaemia as per WHO guidelines. Mean haemoglobin levels significantly increased over a period of 3 weeks after Ferric carboxymaltose administrationand no serious life threatening adverse events were observed. Intravenous ferric carboxymaltose was safe and effective in pregnent women with iron deficiency anaemia.

Repeated intravenous doxapram induces phrenic motor facilitation.

Science.gov (United States)

Sandhu, M S; Lee, K Z; Gonzalez-Rothi, E J; Fuller, D D

2013-12-01

Doxapram is a respiratory stimulant used to treat hypoventilation. Here we investigated whether doxapram could also trigger respiratory neuroplasticity. Specifically, we hypothesized that intermittent delivery of doxapram at low doses would lead to long-lasting increases (i.e., facilitation) of phrenic motor output in anesthetized, vagotomized, and mechanically-ventilated rats. Doxapram was delivered intravenously in a single bolus (2 or 6mg/kg) or as a series of 3 injections (2mg/kg) at 5min intervals. Control groups received pH-matched saline injections (vehicle) or no treatment (anesthesia time control). Doxapram evoked an immediate increase in phrenic output in all groups, but a persistent increase in burst amplitude only occurred after repeated dosing with 2mg/kg. At 60min following the last injection, phrenic burst amplitude was 168±24% of baseline (%BL) in the group receiving 3 injections (Pphrenic response to doxapram (2mg/kg) was reduced by 68% suggesting that at low doses the drug was acting primarily via the carotid chemoreceptors. We conclude that intermittent application of doxapram can trigger phrenic neuroplasticity, and this approach might be of use in the context of respiratory rehabilitation following neurologic injury. © 2013.

"Time sequential high dose of Cytarabine in acute myelocytic leukemia "

Directory of Open Access Journals (Sweden)

Ghavamzadeh A

2003-05-01

Full Text Available Given preliminary evidence of timed, sequential chemotherapy of high dose cytosine arabinoside the current study was initiated to assess the side effects and efficacy of this regimen in patients with newly acute myelocytic leukemia (AML. Nineteen adults who referred to Hematology-Oncology and Bone Marrow Transplantation (BMT research center of Tehran University of Medical Sciences were enrolled in a trial from Aug 1999 to Nov 2000. All patients had a Karnofski classification above 60%. At this time induction therapy consisted of daunorubicin or idarubicin given at a dose of 60 mg/m² and 12 mg/m² IV respectively on days 1-3, and cytarabine (Ara-C 100 mg/m² intravenously by continuous infusion on days 1-7, followed by Ara-C 1000 mg/m² given on day 8-10 every 12 hours by IV infusion. Consolidation therapy started after 35th day. Of 19 fully evaluable patients, 10 patients achieved a complete remission, whereas 36.6% patients succumbed to death due to regeneration failure. The clinical data show that the overall survival rate from diagnosis 55.5% (95% CI, 30.8-78.5 at 6 months for the entire cohort of the patients. Disease free survival is also 50% (95% CI, 26-74. Mean duration of death due to treatment was 20 days (range 17-29 after beginning the regimen. Presenting WBC counts, French-American-British (FAB classification, sex and age were not useful prognostic variables. Fever, diarrhea, nausea and vomiting and GI hemorrhage were seen in 19, 6, 4, 7 patients respectively. It seems the 3+7+3 regimen is a promising approach for the AML patients regarding to high complete remission rate, but more supportive care should be considered. Furthermore any, benefit in long-term outcome can’t be determined regardless to the choice of post remission therapy (e.g., GCSF, appropriate antibiotics and etc.

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 ...

Intraoperative use of epidural methylprednisolone or bupivacaine for postsurgical lumbar disectomy pain relief: A randomized, placebo-controlled trial

International Nuclear Information System (INIS)

Lotfinia, I.; Khallaghi, E.; Meshkini, A.; Shakeri, M.; Shima, M.; Safaeian, A.

2007-01-01

Many patients with lumbar disc surgery experience postoperative back and radicular pain, delaying hospital discharge and resumption of normal activity. Some surgeons have used intraoperative epidural corticosteroids and local anesthetics to decrease pain following surgery for a herniated lumbar disc. Controversies still exist regarding the benefits of these drugs. The present study was meant to compare the effects of the intraoperative administration of epidural methylprednisolone and bupivacaine with that of normal saline (placebo) in lumbar disc surgery for postoperative pain control. One hundred fifty patients with single level herniated nucleus pulposus (L4-L5 or L5-S1), which was refractory to 6 weeks of conservative management, were divided randomly in three groups. A standard hemipartial lamimectomy and discectomy was performed on all patients. At the end of the surgery, before the closure of fascia, 40 mg methylprednisoslone with 3 mL normal saline for group1, 2 mL bupivacaine 5% with 2mL normal saline for group 2 and 4 mL normal saline for group 3 were stilled on to the epidural and exposed nerve root. Postoperative back and radicular pain intensity was assessed by a visual analogue scale (VAS) before and at 24, 48, 72 and 96 hours after surgery. There was no significant difference in back and radicular pain intensity between the three groups. Introperative administration of epidural methylprednisolone or bupivacaine does not relieve postoperative back and radicular pain. (author)

CHARACTERIZATION OF AN INTRAVENOUS LIPOPOLYSACCHARIDE INFLAMMATION MODEL IN BROILER CHICKENS

OpenAIRE

De Boever , Sandra; Croubels , Siska; Meyer , Evelyne; Sys , Stanislas; Beyaert , Rudi; Ducatelle , Richard; De Backer , Patrick

2009-01-01

Abstract Intravenous administration of lipopolysaccharide (LPS) from Escherichia coli O127:B8 at a dose of 1,500,000 units/kg BW evoked a hypothermic response followed by a fever phase in five week old broiler chickens. The hypothermic phase coincided with a severe decrease in blood pressure. We assume that this decrease in blood pressure is, at least partly, responsible for the hypothermic phase of the body temperature curve. LPS administration also caused a decrease in circulatin...

Radiation absorbed doses from iron-52, iron-55, and iron-59 used to study ferrokinetics

International Nuclear Information System (INIS)

Robertson, J.S.; Price, R.R.; Budinger, T.F.; Fairbanks, V.F.; Pollycove, M.

1983-01-01

Biological data obtained principally with Fe-59 citrate are used with physical data to calculate radiation absorbed doses for ionic or weak chelate forms of Fe-52, Fe-55, and Fe-59, administered by intravenous injection. Doses are calculated for normal subjects, primary hemochromatosis (also called idiopathic or hereditary hemochromatosis), pernicious anemia in relapse, iron-deficiency anemia, and polycythemia vera. The Fe-52 doses include the dose from the Mn-52m daughter generated after injection of Fe-52. Special attention has been given to the dose to the spleen, which has a relatively high concentration of RBCs and therefore of radioiron, and which varies significantly in size in both health and disease

Plasma concentrations of fenbendazole (FBZ and oxfendazole in alpacas (Lama pacos after single intravenous and oral dosing of FBZ

Directory of Open Access Journals (Sweden)

Lakritz J

2015-02-01

Full Text Available Jeffrey Lakritz,1 Daniel Linden,2 David E Anderson,3 Terri A Specht4 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; 2Department of Agriculture and Engineering Technologies, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Wooster, OH, USA; 3Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA; 4Four Star Veterinary Service, Chickasaw, OH, USA Abstract: The objective of this study was to determine plasma pharmacokinetics and bioavailability of fenbendazole (FBZ and oxfendazole (OFZ after intravenous (iv and oral administrations of FBZ (5 mg/kg to alpacas. Plasma concentrations of FBZ and OFZ after administration of FBZ iv and orally (5 mg/kg were determined by high-performance liquid chromatography with ultraviolet detection. Total clearance (CL of FBZ was 16.5±4 mL/kg/min (range: 4–31 mL/kg/min, and steady-state volume of distribution (Vdss was 3.3±1 L/kg (range: 1.7–7.4 L/kg. The terminal phase half-life of FBZ after iv administration was 5.9±3.8 hours (range: 0.8–20 hours. After oral administration, the FBZ terminal phase half-life was 23±5 hours (range: 9–37 hours and the systemic bioavailability of FBZ was 16%±6% (range: 1%–41%. Peak FBZ concentrations after oral administration were 0.13±0.05 µg/mL (range: 0.05–0.28 µg/mL at 10 hours (range: 8–12 hours. Peak plasma OFZ concentrations after oral dosing with FBZ (5 mg/kg were 0.14±0.05 µg/mL (0.05–0.3 µg/mL at 24±7 hours (range: 12–48 hours. FBZ clearance is lower in comparison to that of other species. Systemic availability of FBZ after oral administration is low after oral dosing. Metabolites of FBZ produced by alpacas are similar to those observed in other species. Keywords: bioavailability, benzimidazoles, camelid, pharmacokinetics

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

Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate.

Science.gov (United States)

Bowers, Christian A; Kundu, Bornali; Hawryluk, Gregory W J

2016-06-01

Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS's status as a historical standard of care.

Open-label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study of intravenously administered CNF1010 (17-(allylamino)-17-demethoxygeldanamycin [17-AAG]) in patients with solid tumors.

Science.gov (United States)

Saif, M W; Erlichman, C; Dragovich, T; Mendelson, D; Toft, D; Burrows, F; Storgard, C; Von Hoff, D

2013-05-01

17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin that binds to and inhibits the Hsp90 family of molecular chaperones leading to the proteasomal degradation of client proteins critical in malignant cell proliferation and survival. We have undertaken a Phase 1 trial of CNF1010, an oil-in-water nanoemulsion of 17-AAG. Patients with advanced solid tumors and adequate organ functions received CNF1010 by 1-h intravenous (IV) infusion, twice a week, 3 out of 4 weeks. Doses were escalated sequentially in single-patient (6 and 12 mg/m(2)/day) and three-to-six-patient (≥25 mg/m(2)/day) cohorts according to a modified Fibonacci's schema. Plasma pharmacokinetic (PK) profiles and biomarkers, including Hsp70 in PBMCs, HER-2 extracellular domain, and IGFBP2 in plasma, were performed. Thirty-five patients were treated at doses ranging from 6 to 225 mg/m(2). A total of 10 DLTs in nine patients (2 events of fatigue, 83 and 175 mg/m(2); shock, abdominal pain, ALT increased, increased transaminases, and pain in extremity at 175 mg/m(2); extremity pain, atrial fibrillation, and metabolic encephalopathy at 225 mg/m(2)) were noted. The PK profile of 17-AAG after the first dose appeared to be linear up to 175 mg/m(2), with a dose-proportional increase in C max and AUC0-inf. Hsp70 induction in PBMCs and inhibition of serum HER-2 neu extracellular domain indicated biological effects of CNF1010 at doses >83 mg/m(2). The maximum tolerated dose was not formally established. Hsp70 induction in PBMCs and inhibition of serum HER-2 neu extracellular domain indicated biological effects. The CNF1010 clinical program is no longer being pursued due to the toxicity profile of the drug and the development of second-generation Hsp90 molecules.

Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial.

Science.gov (United States)

Ladenstein, Ruth; Pötschger, Ulrike; Pearson, Andrew D J; Brock, Penelope; Luksch, Roberto; Castel, Victoria; Yaniv, Isaac; Papadakis, Vassilios; Laureys, Geneviève; Malis, Josef; Balwierz, Walentyna; Ruud, Ellen; Kogner, Per; Schroeder, Henrik; de Lacerda, Ana Forjaz; Beck-Popovic, Maja; Bician, Pavel; Garami, Miklós; Trahair, Toby; Canete, Adela; Ambros, Peter F; Holmes, Keith; Gaze, Mark; Schreier, Günter; Garaventa, Alberto; Vassal, Gilles; Michon, Jean; Valteau-Couanet, Dominique

2017-04-01

High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan. We did an international, randomised, multi-arm, open-label, phase 3 cooperative group clinical trial of patients with high-risk neuroblastoma at 128 institutions in 18 countries that included an open-label randomised arm in which high-dose chemotherapy regimens were compared. Patients (age 1-20 years) with neuroblastoma were eligible to be randomly assigned if they had completed a multidrug induction regimen (cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide with or without topotecan, vincristine, and doxorubicin) and achieved an adequate disease response. Patients were randomly assigned (1:1) to busulfan and melphalan or to carboplatin, etoposide, and melphalan by minimisation, balancing age at diagnosis, stage, MYCN amplification, and national cooperative clinical group between groups. The busulfan and melphalan regimen comprised oral busulfan (150 mg/m 2 given on 4 days consecutively in four equal doses); after Nov 8, 2007, intravenous busulfan was given (0·8-1·2 mg/kg per dose for 16 doses according to patient weight). After 24 h, an intravenous melphalan dose (140 mg/m 2 ) was given. Doses of busulfan and melphalan were modified according to bodyweight. The carboplatin, etoposide, and melphalan regimen consisted of carboplatin continuous infusion of area under the plasma concentration-time curve 4·1 mg/mL per min per day for 4 days, etoposide continuous infusion of 338 mg/m 2 per day for 4 days, and melphalan 70 mg/m 2 per day for 3 days, with doses for all three drugs modified according to bodyweight and glomerular filtration rate. Stem-cell rescue was given after the last dose of

Physiological and immunological changes following exposure to low versus high-dose ionizing irradiation; comparative analysis with dose rate and cumulative dose

International Nuclear Information System (INIS)

Heesun, Kim; Heewon, Jang; Soungyeon, Song; Shinhye, Oh; Cukcheul, Shin; Meeseon, Jeong; Chasoon, Kim; Kwnaghee, Yang; Seonyoung, Nam; Jiyoung, Kim; Youngwoo, Jin; Changyoung, Cha

2008-01-01

Full text: While high-dose of ionizing radiation is generally harmful and causes damage to living organisms some reports suggest low-dose of radiation may not be as damaging as previously thought. Despite increasing evidence regarding the protective effect of low-dose radiation, no studies have directly compared the exact dose-response pattern by high- and low-dose of radiation exposed at high-and low-dose rate. This study aims to explore the cellular and molecular changes in mice exposed to low- and high-dose of radiation exposed at low- and high-dose rate. When C57BL/6 mice (Female, 6 weeks) were exposed at high-dose rate, 0.8 Gy/min, no significant change on the level of WBC, RBC, or platelets was observed up to total dose of 0.5 Gy. However, 2 Gy of radiation caused dramatic reduction in the level of white blood cells (WBC) and platelets. This reduction was accompanied by increased DNA damage in hematopoietic environments. The reduction of WBC was mainly due to the reduction in the number of CD4+ T cells and CD19+ B cells. CD8+ T cells and NK cells appeared to be relatively resistant to high-dose of radiation. This change was also accompanied by the reduction of T- and B- progenitor cells in the bone marrow. In contrast, no significant changes of the number of CD4+ T, CD8+ T, NK, and B cells were observed in the spleen of mice exposed at low-dose-rate (0.7 m Gy/h or 3.95 mGy/h) for up to 2 Gy, suggesting that low-dose radiation does not alter cellular distribution in the spleen. Nevertheless, mice exposed to low-dose radiation exhibited elevation of VEGF, MCP-1, IL-4, Leptin, IL-3, and Tpo in the peripheral blood and slight increases in MIP-2, RANTES, and IL-2 in the spleen. This suggests that chronic γ-radiation can stimulate immune function without causing damage to the immune components of the body. Taken together, these data indicate hormesis of low-dose radiation, which could be attributed to the stimulation of immune function. Dose rate rather than total

Dose volume assessment of high dose rate 192IR endobronchial implants

International Nuclear Information System (INIS)

Cheng, B. Saw; Korb, Leroy J.; Pawlicki, Todd; Wu, Andrew

1996-01-01

Purpose: To study the dose distributions of high dose rate (HDR) endobronchial implants using the dose nonuniformity ratio (DNR) and three volumetric irradiation indices. Methods and Materials: Multiple implants were configured by allowing a single HDR 192 Ir source to step through a length of 6 cm along an endobronchial catheter. Dwell times were computed to deliver a dose of 5 Gy to points 1 cm away from the catheter axis. Five sets of source configurations, each with different dwell position spacings from 0.5 to 3.0 cm, were evaluated. Three-dimensional (3D) dose distributions were then generated for each source configuration. Differential and cumulative dose-volume curves were generated to quantify the degree of target volume coverage, dose nonuniformity within the target volume, and irradiation of tissues outside the target volume. Evaluation of the implants were made using the DNR and three volumetric irradiation indices. Results: The observed isodose distributions were not able to satisfy all the dose constraints. The ability to optimally satisfy the dose constraints depended on the choice of dwell position spacing and the specification of the dose constraint points. The DNR and irradiation indices suggest that small dwell position spacing does not result in a more homogeneous dose distribution for the implant. This study supports the existence of a relationship between the dwell position spacing and the distance from the catheter axis to the reference dose or dose constraint points. Better dose homogeneity for an implant can be obtained if the spacing of the dwell positions are about twice the distance from the catheter axis to the reference dose or dose constraint points

Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgery

NARCIS (Netherlands)

Prins, Sandra A.; Van Dijk, Monique; Van Leeuwen, Pim; Searle, Susan; Anderson, Brian J.; Tibboel, Dick; Mathot, Ron A. A.

Background: The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. Methods: During surgery all infants (6 months-2 years) received a rectal loading dose of 40

Braquiterapia de alta taxa de dose no Brasil High-dose rate brachytherapy in Brazil

Directory of Open Access Journals (Sweden)

Sérgio Carlos Barros Esteves

2004-10-01

Full Text Available A braquiterapia de alta taxa de dose foi introduzida em nosso meio em janeiro de 1991. Desde então, houve uma mudança significativa na abordagem das neoplasias malignas em relação às vantagens do novo método, e também resolução da demanda reprimida de braquiterapia para as neoplasias ginecológicas. Nos primeiros dez anos de atividade, o Brasil tratou, em 31 serviços, 26.436 pacientes com braquiterapia, sendo mais de 50% das pacientes portadoras de neoplasias do colo uterino. Este estudo mostra o número e o perfil de pacientes tratados com esse método e a sua distribuição no território nacional, deixando explícito o benefício da braquiterapia de alta taxa de dose para o Brasil.High-dose rate brachytherapy was first introduced in Brazil in January 1991. Significant changes in the management of malignant neoplasms were observed since utilization of high-dose rate brachytherapy. The high number of gynecological patients awaiting for brachytherapy also decreased during this period. In the first ten years 26,436 patients were treated with high-dose rate brachytherapy. More than 50% of these patients presented neoplasms of the uterine cervix. In this study we present the number and profile of the patients treated with high-dose rate brachytherapy as well as the distribution of these patients in the Brazilian territory, proving the benefit of the use of high-dose rate brachytherapy in Brazil.

Perineural versus intravenous clonidine as an adjuvant to Bupivacaine in supraclavicular Brachial plexus block

Directory of Open Access Journals (Sweden)

Vikram Bedi

2017-07-01

Conclusion: Addition of clonidine 2mcg/kg to 28 ml of 0.5% bupivacaine in brachial plexus blocks results in a faster onset, increased duration of block and longer postoperative pain relief when compared to bupivacaine alone. These advantages are not observed when the same dose of clonidine is injected intravenously.

Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection

Directory of Open Access Journals (Sweden)

Steven Rockman

2017-05-01

Full Text Available Influenza is a highly contagious, acute, febrile respiratory infection that can have fatal consequences particularly in individuals with chronic illnesses. Sporadic reports suggest that intravenous immunoglobulin (IVIg may be efficacious in the influenza setting. We investigated the potential of human IVIg to ameliorate influenza infection in ferrets exposed to either the pandemic H1N1/09 virus (pH1N1 or highly pathogenic avian influenza (H5N1. IVIg administered at the time of influenza virus exposure led to a significant reduction in lung viral load following pH1N1 challenge. In the lethal H5N1 model, the majority of animals given IVIg survived challenge in a dose dependent manner. Protection was also afforded by purified F(ab′2 but not Fc fragments derived from IVIg, supporting a specific antibody-mediated mechanism of protection. We conclude that pre-pandemic IVIg can modulate serious influenza infection-associated mortality and morbidity. IVIg could be useful prophylactically in the event of a pandemic to protect vulnerable population groups and in the critical care setting as a first stage intervention.

Randomised Phase I/II trial assessing the safety and efficacy of radiolabelled anti-carcinoembryonic antigen I131 KAb201 antibodies given intra-arterially or intravenously in patients with unresectable pancreatic adenocarcinoma

International Nuclear Information System (INIS)

Sultana, Asma; Garvey, Conall; Sutton, Robert; Neoptolemos, John P; Ghaneh, Paula; Shore, Susannah; Raraty, Michael GT; Vinjamuri, Sobhan; Evans, Jonathan E; Smith, Catrin Tudur; Lane, Steven; Chauhan, Seema; Bosonnet, Lorraine

2009-01-01

Advanced pancreatic cancer has a poor prognosis, and the current standard of care (gemcitabine based chemotherapy) provides a small survival advantage. However the drawback is the accompanying systemic toxicity, which targeted treatments may overcome. This study aimed to evaluate the safety and tolerability of KAb201, an anti-carcinoembryonic antigen monoclonal antibody, labelled with I 131 in pancreatic cancer (ISRCTN 16857581). Patients with histological/cytological proven inoperable adenocarcinoma of the head of pancreas were randomised to receive KAb 201 via either the intra-arterial or intravenous delivery route. The dose limiting toxicities within each group were determined. Patients were assessed for safety and efficacy and followed up until death. Between February 2003 and July 2005, 25 patients were enrolled. Nineteen patients were randomised, 9 to the intravenous and 10 to the intra-arterial arms. In the intra-arterial arm, dose limiting toxicity was seen in 2/6 (33%) patients at 50 mCi whereas in the intravenous arm, dose limiting toxicity was noted in 1/6 patients at 50 mCi, but did not occur at 75 mCi (0/3). The overall response rate was 6% (1/18). Median overall survival was 5.2 months (95% confidence interval = 3.3 to 9 months), with no significant difference between the intravenous and intra-arterial arms (log rank test p = 0.79). One patient was still alive at the time of this analysis. Dose limiting toxicity for KAb201 with I 131 by the intra-arterial route was 50 mCi, while dose limiting toxicity was not reached in the intravenous arm

Desensitization protocol in highly HLA-sensitized and ABO-incompatible high titer kidney transplantation.

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Uchida, J; Machida, Y; Iwai, T; Naganuma, T; Kitamoto, K; Iguchi, T; Maeda, S; Kamada, Y; Kuwabara, N; Kim, T; Nakatani, T

2010-12-01

A positive crossmatch indicates the presence of donor-specific alloantibodies and is associated with a graft loss rate of >80%; anti-ABO blood group antibodies develop in response to exposure to foreign blood groups, resulting in immediate graft loss. However, a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation has not yet been established. We treated 6 patients with high (≥1:512) anti-A/B antibody titers and 2 highly HLA-sensitized patients. Our immunosuppression protocol was initiated 1 month before surgery and included mycophenolate mofetil (1 g/d) and/or low-dose steroid (methylprednisolone 8 mg/d). Two doses of the anti-CD20 antibody rituximab (150 mg/m(2)) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6-12 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation, combined with 2 doses of basiliximab. Of the 8 patients, 7 subsequently underwent successful living-donor kidney transplantation. Follow-up of our recipients showed that the patient and graft survival rates were 100%. Acute cellular rejection and antibody-mediated rejection episodes occurred in 1 of the 7 recipients. These findings suggest that our immunosuppression regimen consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression may prove to be effective as a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation. Copyright © 2010 Elsevier Inc. All rights reserved.

Comparison between preoperative administration of methylprednisolone with its administration before and during congenital heart surgery on serum levels of IL-6 and IL-10.

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Abbasi Tashnizi, Mohammad; Soltani, Ghasem; Moeinipour, Ali Asghar; Ayatollahi, Hossein; Tanha, Amir Saber; Jarahi, Lida; Sepehri Shamloo, Alireza; Zirak, Nahid

2013-02-01

Steroid administration during cardiopulmonary bypass is considered to improve cardiopulmonary function by modulating inflammations caused by bypass. This study was performed to compare effectiveness of preoperative and intraoperative methylprednisolone (MP) to preoperative methylprednisolone alone in post bypass inflammatory (IL-6) and anti-inflammatory (IL-10) factors. Fifty pediatric patients undergoing cardiopulmonary bypass surgery from August 2011 to 2012 in the cardiac surgery department of Imam Reza Hospital, the major center for CPB, in Mashhad, Iran were randomly assigned to receive preoperative and intraoperative MP (30 mg/kg, 4 hours before bypass and in bypass prime, number 25) or preoperative MP only (30 mg/kg, number 25). Before and after bypass, four and 24 hours after bypass, serum IL-6 and IL-10 were measured by ELISA. In both groups, no significant difference with variation of expression for IL-6 (inflammatory factor) and IL-10 (anti-inflammatory factor) in different times after bypass was observed. No significant difference in reducing post bypass inflammation between preoperative steroid treatment and combined preoperative and intraoperative steroid administration reported and they had the same effects.

Methylprednisolone acetate induces, and Δ7-dafachronic acid suppresses, Strongyloides stercoralis hyperinfection in NSG mice.

Science.gov (United States)

Patton, John B; Bonne-Année, Sandra; Deckman, Jessica; Hess, Jessica A; Torigian, April; Nolan, Thomas J; Wang, Zhu; Kliewer, Steven A; Durham, Amy C; Lee, James J; Eberhard, Mark L; Mangelsdorf, David J; Lok, James B; Abraham, David

2018-01-02

Strongyloides stercoralis hyperinfection causes high mortality rates in humans, and, while hyperinfection can be induced by immunosuppressive glucocorticoids, the pathogenesis remains unknown. Since immunocompetent mice are resistant to infection with S. stercoralis , we hypothesized that NSG mice, which have a reduced innate immune response and lack adaptive immunity, would be susceptible to the infection and develop hyperinfection. Interestingly, despite the presence of large numbers of adult and first-stage larvae in S. stercoralis -infected NSG mice, no hyperinfection was observed even when the mice were treated with a monoclonal antibody to eliminate residual granulocyte activity. NSG mice were then infected with third-stage larvae and treated for 6 wk with methylprednisolone acetate (MPA), a synthetic glucocorticoid. MPA treatment of infected mice resulted in 50% mortality and caused a significant >10-fold increase in the number of parasitic female worms compared with infected untreated mice. In addition, autoinfective third-stage larvae, which initiate hyperinfection, were found in high numbers in MPA-treated, but not untreated, mice. Remarkably, treatment with Δ7-dafachronic acid, an agonist of the parasite nuclear receptor Ss -DAF-12, significantly reduced the worm burden in MPA-treated mice undergoing hyperinfection with S. stercoralis Overall, this study provides a useful mouse model for S. stercoralis autoinfection and suggests a therapeutic strategy for treating lethal hyperinfection.

An analysis of acute complications and perioperative morbidity from high dose rate brachytherapy in the treatment of gynecological malignancies

Energy Technology Data Exchange (ETDEWEB)

Sarkaria, Jann N; Petereit, Daniel G; Kinsella, Timothy J; Buchler, Dolores A

1995-07-01

Purpose: To evaluate the acute morbidity and mortality for high dose-rate (HDR) brachytherapy performed in an outpatient setting in the treatment of gynecological malignancies, and to identify possible risk factors for adverse outcomes. Materials and Methods: One hundred seventy-one patients with cervical (n=129) or uterine (n=42) carcinoma with an intact uterus were evaluated and treated from August 1989 through December 1994, with at least part of their therapy delivered with intracavitary HDR {sup 192}Ir radiation. A total of 830 ICR insertions were performed with greater than 95% done on an outpatient basis under heavy intravenous sedation using fentanyl and midazolam. Perioperative morbidity and mortality were recorded for any event occurring within 30 days of the completion of therapy. Anesthesia risk was evaluated retrospectively in all patients based on the American Society of Anesthesiologists' (ASA) Physical Class System. Results: The uterine patients, many treated with radiation alone because of morbid obesity or medical inoperability, had a significantly higher perioperative morbidity and mortality rate as compared to the cervix patient cohort. Thirteen of the 42 (31%) uterine patients and 8 of the 129 (6%) cervix patients required hospitalization within 30 days of treatment completion (p<0.001). Four of these uterine patients (10%) died of medical complications related to therapy or disease progression within 30 days, while 2 of the cervix patients (1.5%) died: one from disease progression and the other due to radiation enteritis (p=0.05). Preliminary analysis suggests that uterine patients with a high anesthesia risk score (ASA>2) experienced greater morbidity and mortality, while the best predictor of complications in the cervix patients was age greater than 70 years. For the entire cohort of patients, no correlation was found between the 30 day morbidity and mortality and the doses of fentanyl and midazolam used or the length of the procedure

Bradycardia Associated with Steroid Use for Laryngeal Edema in an Adult: A Case Report and Literature Review

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Preeti R. John

2016-01-01

Full Text Available Steroids are used for specific indications in the perioperative period to reduce laryngeal or spinal cord edema, or for prophylaxis and treatment of postoperative nausea and vomiting. Given the other potential causes for hemodynamic alterations in the perioperative setting, it is important for physicians to be aware of cardiovascular side effects of short term steroids. Changes in blood pressure and heart rate, cardiac dysrhythmias, and even death have been described in patients receiving short term intravenous steroids. Bradycardia has been reported following short term methylprednisolone and dexamethasone therapy in both adult and pediatric patients. There are only two case reports in the literature of bradycardia following short term intravenous dexamethasone use in adult patients. This is the first case report that describes bradycardia following the use of dexamethasone in the postoperative setting for management of laryngeal edema in an adult. Telemetry and twelve lead electrocardiograms revealed sinus bradycardia and correlated directly with administration of dexamethasone in our patient. Bradycardia resolved following discontinuation of dexamethasone. We advocate for hemodynamic monitoring in patients receiving more than one dose of intravenous steroid therapy in the perioperative period, especially those with known cardiac and hepatic comorbidities and those taking medications with negative chronotropic effects.

Endorectal high dose rate brachytherapy quality assurance

International Nuclear Information System (INIS)

Devic, S.; Vuong, T.; Evans, M.; Podgorsak, E.

2008-01-01

We describe our quality assurance method for preoperative high dose rate (HDR) brachytherapy of endorectal tumours. Reproduction of the treatment planning dose distribution on a daily basis is crucial for treatment success. Due to the cylindrical symmetry, two types of adjustments are necessary: applicator rotation and dose distribution shift along the applicator axis. (author)

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer

International Nuclear Information System (INIS)

Martinez, Alvaro A.; Gustafson, Gary; Gonzalez, Jose; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

2002-01-01

Purpose: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Methods and Materials: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level ≥10.0 ng/mL, Gleason score ≥7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. Results: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p<0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p=0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Conclusion: Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause

Acute Dysphasia and Reversible Cognitive Decline in a Patient with Probable Cerebral Amyloid Angiopathy-Related Inflammation

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Louise Rigney

2015-01-01

Full Text Available Cerebral amyloid angiopathy related inflammation (CAAri is becoming increasingly recognised as a subset of cerebral amyloid angiopathy (CAA. CAAri generally presents with subacute cognitive decline, headaches, seizures, behavioral changes, and focal neurological deficits. We describe a patient who developed acute dysphasia and reversible cognitive decline due to probable CAAri. CT brain showed bilateral vasogenic edema in the cerebral hemispheres, predominantly involving the parietal and temporal lobes, left greater than right without enhancement. Magnetic resonance brain imaging showed extensive multifocal areas of subcortical white matter T2 hyperintensity in the frontal and temporal regions with associated mass effect, negligible enhancement, and multiple foci of microhemorrhage on susceptibility weighted imaging sequences consistent with a diagnosis of probable CAAri. She responded dramatically to a course of intravenous methylprednisolone followed by further immunosuppression with pulse intravenous cyclophosphamide. Her dysphasia resolved within 5 days of intravenous methylprednisolone therapy. Her MMSE improved from 11/30 at day 5 of admission to 28/30 at 6-month follow-up. The notable features of our case were the unusual CT findings, which were inconsistent with stroke and diagnostic utility of susceptibility-weighted magnetic resonance imaging in confirming the diagnosis which allowed for prompt institution of immunosuppression.

Low dose radiation enhance the anti-tumor effect of high dose radiation on human glioma cell U251

International Nuclear Information System (INIS)

Wang Chang; Wang Guanjun; Tan Yehui; Jiang Hongyu; Li Wei

2008-01-01

Objective: To detect the effect on the growth of human glioma cell U251 induced by low dose irradiation and low dose irradiation combined with large dose irradiation. Methods: Human glioma cell line U251 and nude mice carried with human glioma were used. The tumor cells and the mice were treated with low dose, high dose, and low dose combined high dose radiation. Cells growth curve, MTT and flow cytometry were used to detect the proliferation, cell cycle and apoptosis of the cells; and the tumor inhibition rate was used to assess the growth of tumor in vivo. Results: After low dose irradiation, there was no difference between experimental group and control group in cell count, MTT and flow cytometry. Single high dose group and low dose combined high dose group both show significantly the suppressing effect on tumor cells, the apoptosis increased and there was cell cycle blocked in G 2 period, but there was no difference between two groups. In vivo apparent anti-tumor effect in high dose radiation group and the combining group was observed, and that was more significant in the combining group; the prior low dose radiation alleviated the injury of hematological system. There was no difference between single low dose radiation group and control. Conclusions: There is no significant effect on human glioma cell induced by low dose radiation, and low dose radiation could not induce adaptive response. But in vivo experience, low dose radiation could enhance the anti-tumor effect of high dose radiation and alleviated the injury of hematological system. (authors)

Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgery

NARCIS (Netherlands)

Prins, Sandra A.; van Dijk, Monique; van Leeuwen, Pim; Searle, Susan; Anderson, Brian J.; Tibboel, Dick; Mathot, Ron A. A.

2008-01-01

The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. During surgery all infants (6 months-2 years) received a rectal loading dose of 40 mg.kg(-1) paracetamol 2 h

[Correction of anemia in hemodialysis, effect of intravenous iron without erythropoietin].