Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to compare the effects of the University of Wisconsin solution plus butanedione monoxime, the University of Wisconsin solution without butanedione monoxime, and saline on the preservation of muscle tissue. Forty-nine rat hindlimbs were amputated and replanted. The study population was subdivided into four groups according to flushing solution, storage, and replantation protocols. The limbs of the control group (n = 12) were flushed with 20 ml University of Wisconsin solution and immediately replanted onto the same rat. In the remaining three groups, the limbs were immersed in solution, stored in a refrigerator at 4 degrees C for 24 hours, and then replanted onto a fresh rat. The limbs in the no flushout group (n = 7) were placed into storage in cold saline solution without being flushed. The limbs in the University of Wisconsin solution group (n = 17) were flushed with 20 ml of University of Wisconsin solution prior to storage, and those in the University of Wisconsin solution plus butanedione monoxime group (n = 13) were flushed with 20 ml University of Wisconsin solution plus 20 mM butanedione monoxime. Limb survival rate was 100 percent for the control and University of Wisconsin solution plus butanedione monoxime groups, 87 percent for the University of Wisconsin solution group, and 71 percent for the no flushout group. Seven days after replantation, ATP levels were 71 percent of control in the University of Wisconsin solution plus butanedione monoxime group, 33 percent in the University of Wisconsin solution group, and 29 percent in the no flushout group. Tissue K+/Na+ ratio showed that the University of Wisconsin solution plus butanedione monoxime group maintained electrolyte balance, whereas the balance was significantly lowered in University of Wisconsin solution and no flushout groups. The University of Wisconsin solution plus butanedione monoxime limbs did not exhibit cell swelling, whereas total tissue water values for the University of Wisconsin solution and no flushout groups increased significantly. Serum creatinine kinase, measured 24 hours after replantation, was 120 percent of control in the University of Wisconsin solution plus butanedione monoxime group, 550 percent in the University of Wisconsin solution group, and 772 percent in the no flushout group. Limbs in the University of Wisconsin solution plus butanedione monoxime group had more flexible ankle joints and pliable muscle (i.e., less contracture) than those in the University of Wisconsin solution and no flushout groups. In conclusion, rat hindlimbs can be preserved hypothermically for 24 hours using the University of Wisconsin solution, the University of Wisconsin solution plus butanedione monoxime, or saline. However, the University of Wisconsin solution plus butanedione monoxime limbs had better ATP levels and less cellular injury after replantation. Based on these results, we believe that, biochemically, flushing and storage of muscle tissue in the University of Wisconsin solution plus butanedione monoxime are the most effective means of those studied for preserving composite tissue grafts for 24 hours.
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PMID:Improved preservation of rat hindlimbs with the University of Wisconsin solution and butanedione monoxime. 929 Jun 64

Herpes infections continue to be prevalent, especially in immunocompromised patients. Some of these patients will develop resistant HSV infections. Therefore, it is important to explore new treatment options. Animal studies have shown cidofovir to be effective in the treatment and prevention of HSV infections. Human data are limited, with only one randomized, double-blind, placebo-controlled trial performed to date. The results from this study look promising; however, due to the small sample size, a larger clinical trial is warranted. The human data available as case reports are suboptimal in the quality of reporting time frames for resolution of lesions/symptoms and outcomes of therapy. Another problem with the case report data is that the TK status of the herpes simplex isolates was not reported. This would have helped substantiate the acyclovir resistance seen in these patients. It was evident in these case reports that acyclovir resistance can be overcome, as acyclovir-resistant strains became sensitive following cidofovir therapy. This may be because TK(+) viruses have been shown to establish latency more readily than do TK(-) viruses. This pattern suggests that alternating between acyclovir and cidofovir therapies may provide a strategy to manage the emergence of alternatively acyclovir-sensitive and -resistant infections. At present, only the intravenous formulation of cidofovir is commercially available. Advantages of the intravenous formulation include weekly dosing and efficacy. Disadvantages are the complexity of administration and the adverse effect profile. The most common adverse effects with this formulation include nephrotoxicity manifested as proteinuria (12%), and increased creatinine (5%) and neutropenia (15%). Administration of probenecid and NaCl 0.9% hydration are used to reduce the incidence and severity of nephrotoxicity in patients who are receiving cidofovir. Probenecid also has toxicities, including nausea, vomiting, headache, fever, and flushing. The topical formulation of cidofovir looks promising for mucocutaneous HSV infection because it is usually undetectable in the blood following topical administration. Therefore, systemic adverse effects should be minimized. A cidofovir gel product (Forvade, Gilead Sciences) is currently being reviewed by the Food and Drug Administration for the treatment of refractory HSV. Ultimately, more controlled clinical studies are necessary to determine whether routine cidofovir use can be justified in patients with acyclovir-resistant HSV infection.
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PMID:Cidofovir use in acyclovir-resistant herpes infection. 941 91

Andes virus was identified in 1995 as the etiologic agent of Hantavirus Pulmonary Syndrome (HPS) in Southern Argentina. We describe herein the main clinical characteristics of 25 HPS confirmed cases acquired in this area between 1993 and September 1999. The mean age was 34 years (range 11-70), with 72% males. Clinical characteristics were similar to those previously reported for Sin Nombre virus (SNV) cases. However, in this group of patients we also observed conjuntival injection in 10/25 (42%), facial flushing in 8/25 (33%), pharyngeal congestion in 7/25 (29%) and petechiae in 3/25 (12%). On the other hand, BUN was increased in 83% of cases (mean 0.77 g/l range 0.31-2.01). Mean serum creatinine concentration was 26.8 mg/l (range: 8.1-110 mg/l) with serum creatinine being higher than 20 mg/l in 8/15 patients (53%). Urinalysis was abnormal in 12/12 cases and was characterized by presence of proteins, red blood cells and granular casts. Aminotransferases were increased in 90% of cases with levels 5-10 times over normal values in 50% of cases. Serum creatine kinase concentration was elevated in 11/14 cases. Two patients required hemodialysis. Case fatality rate was 44% (11/25) and 10 of these cases died among the first 10 days of illness. Mononuclear myocarditis was observed in two cases, a finding that has not been reported for SNV cases. During the 1996 HPS outbreak in Southern Argentina due to Andes virus, there were epidemiological and molecular evidences of person-to-person transmission, a feature not previously shown for other members of the hantavirus genus. These data would also be indicative of some distinctive clinical characteristics of HPS caused by Andes virus, with more frequent renal involvement than in SNV cases.
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PMID:[Hantavirus pulmonary syndrome in southern Argentina]. 1105 Aug 3

In adults the calcium antagonist amlodipine given once a day has proved to be an attractive addition to the antihypertensive armamentarium. The present report describes our experience in 43 paediatric outpatients (26 boys and 17 girls, aged between 1.1 and 19, median 9.8 years) with chronic kidney diseases. The patients were given amlodipine for 16 weeks as part of their antihypertensive treatment. Before amlodipine arterial pressure was 150 (142-163)/90 (84-95) mm Hg (median and interquartile range). Six patients withdrew from amlodipine because of oedema, flushing or headache. In the remaining patients amlodipine 7.7 (6.9-9.4) mg/m(2) body surface area once a day significantly decreased arterial pressure by 17 (13-22)/10 (7-13) mm Hg. The efficacy of amlodipine was more pronounced in girls than in boys. No changes in heart rate, body weight and circulating haemoglobin, sodium, potassium and creatinine were noted. In none of the patients circulating potassium, sodium or creatinine changed by more than 0.5 mmol/l, 5 mmol/l respectively 20%. In 11 patients concomitantly treated with cyclosporine the dosage and the trough-level of this agent were stable throughout the trial. In conclusion the present experience in paediatric outpatients with chronic kidney diseases supports the view that amlodipine is an effective and rather well tolerated antihypertensive drug when given once a day.
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PMID:Antihypertensive efficacy of amlodipine in children with chronic kidney diseases. 1143 13

This paper describes a new iodine-125 radioimmunoassay of 9alpha ,11beta-PGF2, and its use for the determination of urinary 9alpha,11beta-prostaglandin F2 after a selective one-step solid-phase extraction. The newly reported immunoassay is based on the use of 125I-tyrosyl methyl ester derivative of 9alpha,11beta-PGF2 and specific polyclonal antibody raised in rabbits. The assay detected as lowas 0.85 pg/tube 9alpha,11beta-PGF2, and the antibodyshowed lessthan 0.01 cross-reaction with PGF-ring metabolites (e.g., 8-iso-PGF2alpha, PGF2alpha 2,3-dinor-6-keto-PGF1alpha, and 5 more PGF-ring compounds). Both the intra-assay, and inter-assay CVs were lessthan 20% for internal controls containing low, medium and high concentrations of 9alpha,11beta-PGF2. Immuno-HPLC analysis showed a very low ratio of specific immunoreactivity in both non-extracted urine (6.5%), and in urine extracted on C18-silicacartridge (14.8%). By contrast, approximately 80% specific immunoreactivity could be achieved by using C2-silicaas the sorbent, acetonitrile: water (15:85, v/v) as wash solvent, and ethyl acetate as eluent of 9alpha,11beta-PGF2. This extraction procedure enabled a reasonably high extraction efficiency of 80.4 +/- 0.855 (mean +/- SEM, n=82), as determined by 3H-9alpha,11beta-PGF2. The new SPE/RIA method was applied for the determination of urinary 9alpha,11beta-PGF2 values in 50 healthy human volunteers. For the concentration and for the excretion rate 37.52 +/- 4.61 pg/ml (mean +/- SEM), and 3.50 + 0.35 ng/mmol creatinine (mean +/- SEM), respectively, was measured. The specificity of the SPE/RIA method was supported by the observed 69% decrease in 9alpha, 11beta-PGF2 excretion rate after acetylsalicylic acid treatment. The effect of nicotinic acid, a PGD2-stimulatory agent, was monitored by the urinary excretion of 9alpha ,11beta-PGF2 in 6 patients, by using the new SPE/RIA method. In patients responding with flushing symptoms nicotinic acid induced an increase of the urinary excretion of 9alpha,11beta-PGF2 in the range between 11% and 187%. In summary, the combination of the newly developed specific [125I] radioimmunoassay with solid-phase extraction on C2-silica cartridges enables the specific, sensitive, and reliable determination of 9alpha,11beta-PGF2 in human urine without the need for further laborious chromatographic purification before radioimmunoassay.
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PMID:Determination of 9alpha, 11beta prostaglandin F2 in human urine. combination of solid-phase extraction and radioimmunoassay. 1199 20

Despite extensive efforts in the fields of donor selection and management, standardisation of organ retrieval procedures, storage solutions, and novel immunosuppressive protocols, the rates of delayed graft function (DGF) after renal transplantation have been stagnating between 30% and 50%. As DGF exerts negative influences on acute rejection episodes and long-term organ function, the early phase of transplantation immediately following reperfusion deserves special interest. Several studies on machine-controlled reperfusion showed promising results in various organs, in experimental and clinical settings. Moreover, the flushing of organs with Carolina rinse solution (CR) immediately prior to reperfusion has been proven beneficial and is being clinically applied in human liver transplantation in recognised departments. In our study, we set up an autogenic porcine kidney transplantation model and assessed the normal values (control group) for creatinine clearance (ClCr) and urine output per hour (U/h) after "standard" reperfusion similar to clinical transplantation. Subsequently, kidneys of the experimental group 1 were reperfused at a blood pressure (RR) under the systemic level by means of a roller pump. Group 2 kidneys were rinsed with CR before controlled reperfusion, analogous to group 1. Both groups were compared with each other and with the assessed normal values. Our findings for Group 1 are that pressure-reduced reperfusion negatively affected immediate graft function. ClCr was reduced from 9.9 (control group) to 3.4 ml/min, U/h from 233 to 132 ml ( P<0.05). Group 2 showed that rinsing the kidneys with CR before reperfusion improved functional parameters highly significantly, compared with group 1 (ClCr: 13.5 vs 3.4 ml/min, U/h: 384 vs 132 ml; P<0.05) and even showed a positive trend compared with the control group (ClCr: 13.5 vs 9.9 ml/min, U/h: 384 vs 233 ml; P=0.0546). We can conclude that in a model of porcine renal autotransplantation, pressure-reduced reperfusion via a roller pump is detrimental to early kidney graft function. The flushing of organs with CR prior to controlled reperfusion significantly improves ClCr as well as urine output.
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PMID:Detrimental effects of controlled reperfusion on renal function after porcine autotransplantation are fully compensated by the use of Carolina rinse solution. 1266 15

Y-90-DOTA-Phe1-Tyr3-Octreotide (90Y-SMT 487, OctreoTher) has shown potential for effectively treating patients with neuroendocrine tumors. The dose-limiting organ for this agent is the kidney. The purpose of this work is to assess the effectiveness of a commercially available amino acid solution on reducing renal uptake of 90Y-SMT 487 and determine the safety profile of this solution. Subjects with In-111 pentetreotide positive tumors and normal creatinine levels were treated with 3 cycles of 90Y-SMT 487, 120 mCi/cycle, at 6-9 week intervals. During each treatment two liters of an amino acid solution containing arginine and lysine (Aminosyn II 7%, Abbott Laboratories, Abbott Park, IL) were infused IV over 4 hours. Adverse events were recorded. To assess the effect of Aminosyn II on renal uptake of 90Y-SMT 487, a subgroup of subjects underwent bremsstrahlung imaging 24 hours following infusion. Kidney to liver (K/L) count density ratios were generated from the baseline In-111 pentetreotide images (performed without amino acid infusion) and the 90Y bremsstrahlung images. Follow-up creatinine levels were obtained. Thirty-seven subjects received a total of 89 90Y-SMT 487 treatments. The number of amino-acid infusions associated with one or more episodes of emesis was 53 (62%). During 13 (15%) of these infusions, the Aminosyn II rate had to be reduced because of severe nausea and vomiting. Symptomatic flushing occurred during 16 (18%) of the infusions. One subject experienced a near syncopal event shortly after completing the infusion. Creatinine levels remained normal in 34 of 36 subjects during a mean follow-up period of 9.8 months. Fourteen subjects underwent bremsstrahlung imaging following infusion of 90Y-SMT 487. Kidney uptake appeared to decrease with administration of the amino acid solution in 13 of 14 subjects. For the 28 individual kidneys, the mean percent decrease in the Kidney/Liver uptake ratio with the amino acid solution was found to be 32%. We conclude that 2 L of Aminosyn II 7% infused over 4 hours appears to notably reduce renal uptake of 90Y-SMT 487. Aminosyn is generally well tolerated, particularly at lower infusion rates with occasional moderate to severe nausea and vomiting at higher rates.
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PMID:Effects of intravenous amino acid administration with Y-90 DOTA-Phe1-Tyr3-Octreotide (SMT487[OctreoTher) treatment. 1506 9

Surgical management of juxtarenal aortic (JR-Ao) aneurysms and occlusive disease may include supraceliac aortic clamping, a retroperitoneal approach, or medial visceral rotation. The authors report their results using preferential direct suprarenal aortic clamping via a midline transperitoneal incision. Between July 1, 1992, and July 31, 2001, they treated 58 patients with JR-Ao disease (44 aneurysmal, 14 occlusive) via a midline incision without medial visceral rotation. Preferential suprarenal aortic clamping was used in 53 cases (42 proximal to both renal arteries, 11 proximal to the left renal artery only) and supraceliac or supramesenteric clamping in 5 cases when there was insufficient space for an aortic clamp between the superior mesenteric artery and renal arteries. This strategy avoided mesenteric ischemia associated with supraceliac clamping in the majority of cases and afforded better exposure of the right renal artery than obtainable with a left retroperitoneal approach or medial visceral rotation. Eleven patients underwent concomitant renal revascularization. Critical adjuncts included the following: (1) selective left renal vein (LRV) division if the vein stump pressure was < 35 mm Hg (suggesting sufficient renal venous collaterals existed), (2) bilateral renal artery occlusion during aortic clamping to prevent thromboembolism, (3) flushing of aortic debris before restoring renal perfusion, and (4) routine administration of perioperative intravenous mannitol and renal-dose dopamine. Patients with type IV thoracoabdominal aneurysms, ruptured aneurysms, or JR-Ao disease approached via a retroperitoneal incision (severely obese patients, re-do aortic surgery) were excluded. No patients died or required dialysis during their hospital stay. The LRV was divided in 12 (21%) cases and reanastomosed in 2 cases (elevated stump pressures). The average suprarenal clamp time was 26 minutes (range, 10-60). Postoperative serum creatinine remained > 0.5 ng/dL above baseline in 3 (5%) patients. These results support suprarenal aortic clamping with a midline transperitoneal incision as the optimal strategy for treating juxtarenal aortic aneurysms and occlusive disease. The authors believe that selective left renal vein division enhances juxtarenal aortic exposure, and routine administration of renal protective agents, along with occlusion of both renal arteries during suprarenal aortic clamping, are critical adjuncts in performing these operations.
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PMID:Management of juxtarenal aortic aneurysms and occlusive disease with preferential suprarenal clamping via a midline transperitoneal incision: technique and results. 1549 38

Bosentan, a dual endothelin receptor antagonist, is indicated for the treatment of patients with pulmonary arterial hypertension (PAH). Following oral administration, bosentan attains peak plasma concentrations after approximately 3 hours. The absolute bioavailability is about 50%. Food does not exert a clinically relevant effect on absorption at the recommended dose of 125 mg. Bosentan is approximately 98% bound to albumin and, during multiple-dose administration, has a volume of distribution of 30 L and a clearance of 17 L/h. The terminal half-life after oral administration is 5.4 hours and is unchanged at steady state. Steady-state concentrations are achieved within 3-5 days after multiple-dose administration, when plasma concentrations are decreased by about 50% because of a 2-fold increase in clearance, probably due to induction of metabolising enzymes. Bosentan is mainly eliminated from the body by hepatic metabolism and subsequent biliary excretion of the metabolites. Three metabolites have been identified, formed by cytochrome P450 (CYP) 2C9 and 3A4. The metabolite Ro 48-5033 may contribute 20% to the total response following administration of bosentan. The pharmacokinetics of bosentan are dose-proportional up to 600 mg (single dose) and 500 mg/day (multiple doses). The pharmacokinetics of bosentan in paediatric PAH patients are comparable to those in healthy subjects, whereas adult PAH patients show a 2-fold increased exposure. Severe renal impairment (creatinine clearance 15-30 mL/min) and mild hepatic impairment (Child-Pugh class A) do not have a clinically relevant influence on the pharmacokinetics of bosentan. No dosage adjustment in adults is required based on sex, age, ethnic origin and bodyweight. Bosentan should generally be avoided in patients with moderate or severe hepatic impairment and/or elevated liver aminotransferases. Ketoconazole approximately doubles the exposure to bosentan because of inhibition of CYP3A4. Bosentan decreases exposure to ciclosporin, glibenclamide, simvastatin (and beta-hydroxyacid simvastatin) and (R)- and (S)-warfarin by up to 50% because of induction of CYP3A4 and/or CYP2C9. Coadministration of ciclosporin and bosentan markedly increases initial bosentan trough concentrations. Concomitant treatment with glibenclamide and bosentan leads to an increase in the incidence of aminotransferase elevations. Therefore, combined use with ciclosporin and glibenclamide is contraindicated and not recommended, respectively. The possibility of reduced efficacy of CYP2C9 and 3A4 substrates should be considered when coadministered with bosentan. No clinically relevant interaction was detected with the P-glycoprotein substrate digoxin. In healthy subjects, bosentan doses >300 mg increase plasma levels of endothelin-1. The drug moderately reduces blood pressure, and its main adverse effects are headache, flushing, increased liver aminotransferases, leg oedema and anaemia. In a pharmacokinetic-pharmacodynamic study in PAH patients, the haemodynamic effects lagged the plasma concentrations of bosentan.
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PMID:Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. 1556 89

The aim of this study was to evaluate the efficacy of the Celsior (C) solution for flushing and cold storage of cadaveric renal allografts. Among 177 cadaveric renal allografts harvested and transplanted in our unit, 138 were preserved with the University of Wisconsin (W) solution and 39 with the C solution. The mean age of the recipients was 48.1 +/- 13.5 years, including 107 men and 70 women. The immunosuppressive regimens were tacrolimus-based (n = 118) or cyclosporine-based (n = 59). Grafts perfused with W solution were obtained from older donors than those perfused with C solution (42.3 +/- 16.9 vs 38.1 +/- 12.5 years; P = .017) and had been transplanted to older recipients (49.5 +/- 14.4 vs 43.3 +/- 13.0 years; P = .017). The prevalence of delayed graft function (DGF) was similar in the 2 groups (39.1% in the W group vs 23.7% in the C group; P = .097), as well as the incidence of primary nonfunction grafts (5.8% vs 2.7%; P = .427). The serum creatinine value at 1 month was significantly higher among grafts preserved with W versus solution (1.9 +/- 0.9 vs 1.5 +/- 0.5 mg/dL; P = .000) as well as at 12 months (1.63 +/- 0.5 vs 1.35 +/- 0.4 mg/dL; P = .003). There were no differences in graft survival at 12 months (97% C group vs 88% W group; P = .069). Our results showed that C solution was equivalent to W solution with respect to DGF and primary function of kidneys. The differences in renal function may have been due to differences in donor and recipient ages.
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PMID:Wisconsin and Celsior solutions in renal preservation: a comparative preliminary study. 1586 22


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