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1.
Dig Dis Sci ; 62(9): 2455-2463, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28589238

RESUMO

BACKGROUND: Rifaximin has demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D). AIM: To determine the rifaximin repeat treatment effect on fecal bacterial antibiotic susceptibility. METHODS: Patients with IBS in Trial 3 (TARGET 3) study who responded to open-label rifaximin 550 mg three times daily for 2 weeks, with symptom recurrence within 18 weeks, were randomized to double-blind treatment: two 2-week repeat courses of rifaximin or placebo, separated by 10 weeks. Prospective stool sample collection occurred before and after open-label rifaximin, before and after the first repeat course, and at the end of the study. Susceptibility testing was performed with 11 antibiotics, including rifaximin and rifampin, using broth microdilution or agar dilution methods. RESULTS: Of 103 patients receiving open-label rifaximin, 73 received double-blind rifaximin (n = 37) or placebo (n = 36). A total of 1429 bacterial and yeast isolates were identified, of which Bacteroidaceae (36.7%) and Enterobacteriaceae (33.9%) were the most common. In the double-blind phase, Clostridium difficile was highly susceptible to rifaximin [minimum inhibitory concentration (MIC) range 0.008-1 µg/mL] and rifampin (MIC range 0.004-0.25 µg/mL). Following double-blind rifaximin treatment, Staphylococcus isolates remained susceptible to rifaximin at all visits (MIC50 range ≤0.06-32 µg/mL). Rifaximin exposure was not associated with long-term cross-resistance of Bacteroidaceae, Enterobacteriaceae, and Enterococcaceae to rifampin or nonrifamycin antibiotics tested. CONCLUSIONS: In this study, short-term repeat treatment with rifaximin has no apparent long-term effect on stool microbial susceptibility to rifaximin, rifampin, and nonrifamycin antibiotics. CLINICALTRIALS. GOV IDENTIFIER: NCT01543178.


Assuntos
Antibacterianos/administração & dosagem , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Fezes/microbiologia , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/tratamento farmacológico , Rifamicinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/administração & dosagem , Diarreia/diagnóstico , Diarreia/tratamento farmacológico , Método Duplo-Cego , Resistência Microbiana a Medicamentos/fisiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Rifaximina , Adulto Jovem
2.
Am J Gastroenterol ; 110(7): 956-62, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25803401

RESUMO

OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME) emphasizes the importance of medical trainees meeting specific performance benchmarks and demonstrating readiness for unsupervised practice. The aim of this study was to examine the readiness of Gastroenterology (GI) fellowship programs for competency-based evaluation in endoscopic procedural training. METHODS: ACGME-accredited GI program directors (PDs) and GI trainees nationwide completed an online survey of domains relevant to endoscopy training and competency assessment. Participants were queried about current methods and perceived quality of endoscopy training and assessment of competence. Participants were also queried about factors deemed important in endoscopy competence assessment. Five-point Likert items were analyzed as continuous variables by an independent t-test and χ(2)-test was used for comparison of proportions. RESULTS: Survey response rate was 64% (94/148) for PDs and 47% (546/1,167) for trainees. Twenty-three percent of surveyed PDs reported that they do not have a formal endoscopy curriculum. PDs placed less importance (1­very important to 5­very unimportant) on endoscopy volume (1.57 vs. 1.18, P<0.001), adenoma detection rate (2.00 vs. 1.53, P<0.001), and withdrawal times (1.96 vs. 1.68, P=0.009) in determining endoscopy competence compared with trainees. A majority of PDs report that competence is assessed by procedure volume (85%) and teaching attending evaluations (96%). Only a minority of programs use skills assessment tools (30%) or specific quality metrics (28%). Specific competencies are mostly assessed by individual teaching attending feedback as opposed to official documentation or feedback from a PD. PDs rate the overall quality of their endoscopy training and assessment of competence as better than overall ratings by trainees. CONCLUSIONS: Although the majority of PDs and trainees nationwide believe that measuring specific metrics is important in determining endoscopy competence, most programs still rely on procedure volume and subjective attending evaluations to determine overall competence. As medical training transitions from an apprenticeship model to competency-based education, there is a need for improved endoscopy curricula which are better suited to demonstrate readiness for unsupervised practice.


Assuntos
Competência Clínica , Educação Baseada em Competências , Currículo , Educação de Pós-Graduação em Medicina , Endoscopia do Sistema Digestório/educação , Bolsas de Estudo , Gastroenterologia/educação , Acreditação , Adulto , Benchmarking , Educação Baseada em Competências/métodos , Educação Baseada em Competências/normas , Educação Baseada em Competências/tendências , Coleta de Dados , Educação de Pós-Graduação em Medicina/métodos , Educação de Pós-Graduação em Medicina/normas , Educação de Pós-Graduação em Medicina/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Estados Unidos
5.
Endoscopy ; 43(4): 325-30, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21455872

RESUMO

BACKGROUND: Temporary prophylactic pancreatic duct stenting effectively reduces post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk patients, but the optimal stent remains unclear. We compared rate of spontaneous passage, and technical difficulty of placement for 3-Fr and 5-Fr stents. METHODS: A randomized controlled trial at a single academic medical center. Patients deemed high risk for PEP randomly received 5-Fr or 3-Fr pancreatic duct stents. Primary outcome was spontaneous stent passage by 2 weeks. Secondary outcomes were ease and time for stent placement, and number of guide wires required for the entire procedure. RESULTS: Patients (69 female [89 %]; mean age 44.9 years, standard deviation [SD] 16.8) were randomly assigned to receive 5-Fr (n = 38) and 3-Fr (n = 40) stents. Indications for stenting were similar. Seven patients in the 3-Fr group actually received a 5-Fr stent, and two in the 5-Fr group had a 3-Fr stent. Spontaneous passage or non-passage was confirmed in 64 (83 %). No statistically significant difference in spontaneous passage rates was seen (5-Fr group, 68.4 %; 3-Fr group 75.0 %; P = 0.617). Non-passage rates were 10.5 % (5-Fr group) and 10.0 % (3-Fr group) ( P = 1.00). The study was stopped after a futility analysis for the primary end point. Placement of 5-Fr stents was rated easier, at a mean score of 1.8 (5-Fr) vs. 3.4 (3-Fr), P < 0.001, with a trend towards being faster, 9.2 vs. 11.1 minutes ( P = 0.355). Fewer guide wires were required for 5-Fr stent placement, 1.5 vs. 1.9 ( P = 0.002). PEP rates did not differ ( P = 0.519). CONCLUSION: Placement of 5-Fr compared to 3-Fr pancreatic duct stents for PEP prophylaxis is easier, faster, and requires fewer wires. No statistically significant difference in spontaneous passage was found between the two sizes.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Ductos Pancreáticos/cirurgia , Pancreatite/etiologia , Pancreatite/prevenção & controle , Stents , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Stents/efeitos adversos
6.
Gut ; 58(3): 367-78, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19001059

RESUMO

OBJECTIVE: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence for treatment of the condition with antidepressants and psychological therapies is conflicting. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). MEDLINE, EMBASE and the Cochrane Controlled Trials Register were searched (up to May 2008). SETTING: RCTs based in primary, secondary and tertiary care. PATIENTS: Adults with IBS. INTERVENTIONS: Antidepressants versus placebo, and psychological therapies versus control therapy or "usual management". MAIN OUTCOME MEASURES: Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. RESULTS: The search strategy identified 571 citations. Thirty-two RCTs were eligible for inclusion: 19 compared psychological therapies with control therapy or "usual management", 12 compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Study quality was generally good for antidepressant but poor for psychological therapy trials. The RR of IBS symptoms persisting with antidepressants versus placebo was 0.66 (95% CI, 0.57 to 0.78), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms persisting with psychological therapies was 0.67 (95% CI, 0.57 to 0.79). The NNT was 4 for both interventions. CONCLUSIONS: Antidepressants are effective in the treatment of IBS. There is less high-quality evidence for routine use of psychological therapies in IBS, but available data suggest these may be of comparable efficacy.


Assuntos
Antidepressivos/uso terapêutico , Terapia Cognitivo-Comportamental/métodos , Síndrome do Intestino Irritável/terapia , Adulto , Terapia Combinada/métodos , Feminino , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/psicologia , Masculino , Placebos/uso terapêutico , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
7.
J Clin Invest ; 77(4): 1071-83, 1986 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3082933

RESUMO

Plasma cholesterol metabolism was investigated in normotriglyceridemic patients with end-stage renal disease treated by hemo- or continuous ambulatory peritoneal dialysis (CAPD), and compared with that in a control group with normal renal function. A reversed net transport of free cholesterol from plasma to cultured fibroblasts, as well as greatly reduced levels of plasma cholesterol esterification and cholesterol ester transfer rates to low and very low density lipoproteins (LDL and VLDL), was found in the hemodialysis group compared to the controls. The LDL and VLDL contained increased amounts of free cholesterol and inhibited cholesterol ester transfer when recombined with control plasma. The LDL triglyceride content was doubled in the hemodialysis group, whereas cholesterol esters were decreased. Patients treated by CAPD, in marked contrast, had cholesterol metabolic rates that were within the normal range, as well as normal lipoprotein composition.


Assuntos
Colesterol/sangue , Falência Renal Crônica/sangue , Diálise Peritoneal Ambulatorial Contínua , Diálise Renal , Apolipoproteína A-I , Apolipoproteína A-II , Apolipoproteínas/sangue , Apolipoproteínas A/sangue , Apolipoproteínas B/sangue , Apolipoproteínas D , Apolipoproteínas E/sangue , Células Cultivadas , Ésteres do Colesterol/sangue , Humanos , Falência Renal Crônica/terapia , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Triglicerídeos/sangue
8.
Aliment Pharmacol Ther ; 26(2): 183-93, 2007 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-17593064

RESUMO

BACKGROUND: Chronic abdominal pain syndromes may increase the risk of suicidal behaviour - a feature well described in non-visceral pain syndromes. AIM: To perform a systematic review to summarize and interpret published data linking chronic abdominal pain syndromes and suicidal behaviour. METHODS: We performed a structured search to identify studies pertaining to the following questions: (i) What is the prevalence of suicidal behaviour in patients with chronic abdominal pain syndromes, including bowel syndrome (IBS)? (ii) Is the prevalence of suicidal behaviour in chronic abdominal pain syndromes higher than in matched controls? And (iii) is suicidal behaviour in abdominal pain syndromes simply due to psychiatric co-morbidities? RESULTS: Thirty-two relevant titles were identified, of which six manuscripts, describing eight studies, met inclusion criteria. Patients with non-IBS syndromes were 3-11 times more likely to demonstrate suicidal behaviour vs. controls, while patients with IBS were two to four times more likely to have suicidal behaviour. Chronic abdominal pain was an independent predictor of suicidal behaviour after adjusting for co-morbid psychiatric conditions. CONCLUSIONS: Chronic abdominal pain syndromes increase the risk for suicidal behaviours. This relationship may exist independently of co-morbid depression, although additional research is needed to better understand this link. These data indicate that clinicians should survey for suicidal behaviour in chronic abdominal pain patients.


Assuntos
Dor Abdominal/psicologia , Síndrome do Intestino Irritável/psicologia , Suicídio/psicologia , Dor Abdominal/complicações , Doença Crônica , Humanos , Síndrome do Intestino Irritável/complicações , Fatores de Risco
9.
Rev Med Brux ; 28(4): 315-9, 2007 Sep.
Artigo em Francês | MEDLINE | ID: mdl-17958027

RESUMO

The epidemiologic observations show that atrial fibrillation is a major challenge of public health. This article underlines the central role of the general practitioner to detect and treat the arrhythmia precociously, and to follow attentively the treatment (in particular, but not only, anticoagulant and antiarrhythmic therapies). The choice between various therapeutic strategies is reviewed. The family practitioner is also placed best to educate the patient to manage his pathology and his treatment in an optimal way. Pharmacological prospects exceeding the antiarrhythmic ones are evoked, as well as the contribution of nonpharmacological strategies, either already accepted in current practice, or under development.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Medicina de Família e Comunidade , Antiarrítmicos/uso terapêutico , Anticoagulantes/uso terapêutico , Fibrilação Atrial/reabilitação , Fibrilação Atrial/terapia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cardioversão Elétrica , Humanos
10.
Arch Intern Med ; 139(7): 801-5, 1979 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-454069

RESUMO

Twenty patients who had evidence of myoglobinuria were treated with intravenous infusions of mannitol and sodium bicarbonate. Nine patients (group 1) responded with higher urine output, and continued infusion improved renal function; none required dialysis and all survived. Eleven patients (group 2) did not respond to the infusion, and required an average of 5.3 (range, 0 to 11) dialyses; one patient died. There was no significant difference in initial BUN level, creatinine level, BUN/creatinine ratio, or fractional sodium excretion level between the two groups. However, group 2 patients had a significantly higher creatine phosphokinase (CPK) level, serum phosphate level, and hematocrit reading initially than did group 1, indicative of more severe muscle injury and hemoconcentration. These results demonstrate that some patients with myoglobinuria will respond to infusion of mannitol and sodium bicarbonate. This treatment may be effective in altering the clinical course of myoglobinuric acute renal failure.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Bicarbonatos/uso terapêutico , Manitol/uso terapêutico , Mioglobinúria/tratamento farmacológico , Adulto , Bicarbonatos/administração & dosagem , Feminino , Humanos , Infusões Parenterais , Testes de Função Renal , Masculino , Manitol/administração & dosagem , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
J Clin Endocrinol Metab ; 62(6): 1227-31, 1986 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3084536

RESUMO

Previous studies in several animal species have demonstrated that the kidneys are the primary site of mevalonate metabolism by the oxidative or shunt pathway. To determine the role of the human kidney in mevalonate oxidation, we studied mevalonate shunt activity in patients undergoing hemodialysis for varying degrees of renal failure. Surprisingly, at least half of the uremic patients and even anephric patients had normal ability to oxidize mevalonate by the shunt pathway. In addition, we found a strong negative correlation (R = -0.94) between mevalonate shunt activity and serum phosphorus levels in uremic patients. The resulting inhibition of mevalonate oxidation by high serum phosphorus levels was reversed by lowering the serum phosphorus in one patient. Finally, a positive correlation was found between mevalonate oxidation and serum PTH levels. The results of this study suggest that, in humans, extrarenal tissues can be major contributors to mevalonate oxidation. It is therefore probable that in humans, in contrast to other animals, the kidney is not the primary site of mevalonate metabolism by this oxidative pathway. Finally, the strong negative correlation between serum phosphorus levels and the ability of uremic patients to oxidize mevalonate suggests a regulatory role for the phosphate ion in the mevalonate shunt pathway.


Assuntos
Rim/metabolismo , Ácido Mevalônico/metabolismo , Adulto , Dióxido de Carbono/metabolismo , Feminino , Humanos , Masculino , Ácido Mevalônico/sangue , Pessoa de Meia-Idade , Oxirredução , Fósforo/sangue , Uremia/sangue
12.
Clin Pharmacol Ther ; 45(5): 527-34, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2721108

RESUMO

The pharmacokinetic disposition of cefotaxime, desacetyl cefotaxime, and mezlocillin after the administration of each drug singly and in combination was examined in eight healthy volunteers and in five anuric patients with end-stage renal disease (ESRD). In the presence of ESRD, the total body clearance of cefotaxime decreased from 256.7 +/- 41.5 to 65.4 +/- 42.0 ml/min, and its elimination half-life (t1/2) increased from 1.1 to 3.6 hours as compared with healthy volunteers. Concomitant administration of mezlocillin in healthy volunteers decreased the total body clearance of cefotaxime by 42% and increased its steady-state volume of distribution. This reduction in clearance was reflected by a decrease in both renal and nonrenal clearances. In the presence of ESRD, coadministration of mezlocillin increased the t1/2 of cefotaxime to 5.8 hours. Desacetyl cefotaxime accumulated in ESRD with a prolongation of its elimination t1/2 to 18.7 hours from 1.7 hours in healthy volunteers. Desacetyl cefotaxime peak plasma concentrations occurred later with the combination regimen in the presence of ESRD. The clearance of mezlocillin was reduced and t1/2 prolonged in ESRD from 194.6 +/- 31.9 to 76.4 +/- 38.8 ml/min and 1.4 to 2.3 hours, respectively. Concomitant administration of cefotaxime did not alter the pharmacokinetics of mezlocillin. These data suggest that in the presence of normal renal function, lower doses of cefotaxime may be adequate to maintain similar cefotaxime plasma concentrations when mezlocillin is coadministered compared to when cefotaxime is given alone. Additional pharmacodynamic and clinical studies with this combination are warranted to further elucidate the clinical impact of this pharmacokinetic interaction.


Assuntos
Cefotaxima/farmacocinética , Falência Renal Crônica/metabolismo , Mezlocilina/farmacocinética , Adulto , Cefotaxima/administração & dosagem , Cromatografia Líquida de Alta Pressão , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Meia-Vida , Humanos , Falência Renal Crônica/tratamento farmacológico , Masculino , Taxa de Depuração Metabólica , Mezlocilina/administração & dosagem , Mezlocilina/farmacologia , Pessoa de Meia-Idade , Distribuição Aleatória
13.
Clin Pharmacol Ther ; 27(2): 236-42, 1980 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7353346

RESUMO

An 18-yr-old male with a severe ethchlorvynol (ECV) overdose was treated with Amberlite XAD-4 resin hemoperfusion. Plasma ECV concentration declined 33% during a 3.5-hr hemoperfusion, but rebounded substantially, peaking 6 hr later. It was estimated that 16% of ECV in the body was removed. Following hemoperfusion, plasma ECV concentrations declined linearly at a rate of 13 mg/1/day. Hemoperfusion clearance was estimated by both the traditional method, using extraction ratios across the column and column blood flow (Cl = 270 ml/min), and an alternative method, using blood concentrations during hemoperfusion and recovery of drug from the resin (Cl = 184 ml/min). The latter may provide a better estimate of hemoperfusion clearance because it is not subject to error (which can be substantial) in measurement of column blood flow. The resin completely extracted ECV from plasma, resulting in a rate of elimination 10 times that expected from endogenous processes. To aid in kinetic analysis, blood:plasma partition and protein binding of ECV in 3 normal subjects were also examined. Blood:plasma ratio averaged 0.88 +/- 0.04 and fraction free in plasma, 0.38 +/- 0.02; neither changed as a function of blood concentration between 27 and 108 mg/1. Our data indicate that removal of ECV from the overdosed patient by hemoperfusion is limited by extensive distribution in and slow redistribution from body tissues, but because of the extremely slow rate of removal by the body and the severe nature of the ECV overdose, Amberlite XAD-4 hemoperfusion may be clinically useful.


Assuntos
Etclorvinol/intoxicação , Hemoperfusão/métodos , Intoxicação/terapia , Resinas Sintéticas , Adolescente , Etclorvinol/sangue , Humanos , Cinética , Masculino , Fatores de Tempo
14.
Clin Pharmacol Ther ; 45(6): 674-81, 1989 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2525081

RESUMO

The pharmacokinetics of teicoplanin in serum and dialysate were examined in a crossover study after intravenous and intraperitoneal administration of a 3 mg/kg dose to five anuric patients who were undergoing continuous ambulatory peritoneal dialysis (CAPD). Blood and dialysate samples were obtained for 30 and 15 days, respectively, and were assayed microbiologically. The principal pharmacokinetic parameters after intravenous administration were as follows: total body clearance, 2.76 +/- 1.08 ml/min; elimination half-life, 377 +/- 109 hours; volume of distribution at steady state, 1.04 +/- 0.18 L/kg. Only 9% +/- 6% of the intravenous dose was recovered in the dialysate and the net peritoneal clearance was 0.25 +/- 0.21 ml/min. Bioavailability values, which were assessed by use of three methods after intraperitoneal administration and while dialysate was retained in the peritoneal cavity for 5 hours (dwell time), were 0.77 +/- 0.21, 0.78 +/- 0.05, and 0.76 +/- 0.08. Changes in bioavailability with dwell time were also examined. A dosing guide, which accounts for changes in bioavailability with dwell time, is presented.


Assuntos
Antibacterianos/farmacocinética , Diálise Peritoneal Ambulatorial Contínua , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Disponibilidade Biológica , Feminino , Glicopeptídeos/administração & dosagem , Glicopeptídeos/sangue , Glicopeptídeos/farmacocinética , Humanos , Infusões Intravenosas , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Teicoplanina
15.
Clin Pharmacol Ther ; 65(1): 21-8, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9951427

RESUMO

BACKGROUND: Cidofovir is an antiviral agent used for the treatment of cytomegalovirus infection in patients with acquired immunodeficiency syndrome. Because cidofovir is primarily eliminated by the kidneys and because its main adverse effect is nephrotoxicity, an understanding of the pharmacokinetic disposition of cidofovir in patients with renal insufficiency is necessary. METHODS: Twenty-four subjects were enrolled into this study and were divided into 6 groups depending on their degree of renal dysfunction, including subjects receiving maintenance continuous ambulatory peritoneal dialysis and high-flux hemodialysis. The creatinine clearance (CLCR) for subjects not receiving dialysis ranged from 12 to 164 mL/min. Each subject received a single 0.5 mg/kg intravenous dose of cidofovir over 1 hour. Subjects not receiving dialysis were given intravenous hydration with 1 L normal saline solution and concomitant oral probenecid. Serial serum and urine samples were collected to determine pharmacokinetic parameters with use of noncompartmental methods. RESULTS: Mean +/- SD cidofovir clearance (CL) in control subjects (normal renal function; n = 5) was 1.7 +/- 0.1 mL/min/kg, which decreased with declining renal function as indicated by the regression equation: CL (mL/min/kg) = 0.94 x CLCR (mL/min/kg) + 0.064 (r2 = 0.91). Mean volume of distribution at steady state did not change significantly in subjects with kidney disease and cidofovir serum elimination half-life was significantly increased in subjects with severe renal impairment. Cidofovir was not significantly cleared during continuous ambulatory peritoneal dialysis, but high-flux hemodialysis resulted in the removal of 52% +/- 11% of the dose administered. CONCLUSION: The significant (P < .001) correlation observed between CLCR and CL in subjects with varying degrees of renal insufficiency indicates that aggressive dosage reduction of cidofovir would be necessary in subjects with kidney disease to ensure comparable drug exposure based on serum levels.


Assuntos
Fármacos Anti-HIV/farmacocinética , Citosina/análogos & derivados , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Organofosfonatos , Compostos Organofosforados/farmacocinética , Diálise Peritoneal Ambulatorial Contínua , Diálise Renal , Adulto , Idoso , Fármacos Anti-HIV/administração & dosagem , Cidofovir , Creatinina/sangue , Citosina/administração & dosagem , Citosina/farmacocinética , Esquema de Medicação , Feminino , Meia-Vida , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/urina , Masculino , Pessoa de Meia-Idade , Compostos Organofosforados/administração & dosagem , Índice de Gravidade de Doença
16.
Am J Med ; 107(6A): 48S-54S, 1999 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-10628593

RESUMO

This article provides a systematic review of the frequency and severity of adverse gastrointestinal (GI) events among patients using meloxicam, a cyclooxygenase (COX)-2-selective nonsteroidal anti-inflammatory drug (NSAID). A MEDLINE search of English language articles from 1990-1998, a manual search of citations from primary trials and review articles, and a manual search of proceedings from international gastroenterology meetings were conducted. Randomized clinical trials comparing the frequency of GI adverse events for meloxicam versus non-COX-2-selective NSAIDs were selected. Specific data about the frequency of dyspepsia; perforations, ulcers, and bleeds (PUBs); and withdrawal of medication because of adverse GI events was also extracted. From a pool of 62 potentially relevant citations, 12 randomized trials were identified. All trials concerning symptomatic GI adverse events used the World Health Organization's Adverse Reaction Terminology List (WHO-ARTL) to code adverse events. Patients using meloxicam had fewer GI adverse events compared with non-COX-2-selective NSAIDs (odds ratio = 0.64; 95% confidence interval [CI], 0.59-0.69). Patients using meloxicam experienced less dyspepsia (odds ratio = 0.73; 95% CI, 0.64-0.84), fewer PUBs (odds ratio = 0.52; 95% CI, 0.28-0.96), and less frequent discontinuation of NSAID because of adverse GI events (odds ratio = 0.59; 95% CI, 0.52-0.67) compared with non-COX-2 selective NSAIDs. Meloxicam, a COX-2-selective NSAID, appears to cause fewer adverse GI events than standard, non-COX-2-selective NSAIDs. However, the generalizability of these data may be limited by the low dose of meloxicam used in most trials and the use of the WHO-ARTL to code adverse events.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase/efeitos adversos , Sistema Digestório/efeitos dos fármacos , Isoenzimas/farmacologia , Prostaglandina-Endoperóxido Sintases/farmacologia , Tiazinas/efeitos adversos , Tiazóis/efeitos adversos , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Humanos , Meloxicam , Proteínas de Membrana , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Am J Med ; 68(1): 59-65, 1980 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7350806

RESUMO

Ten patients with proved disease caused by Myocobacterium tuberculosis were identified over a 10 year period in a population of 172 adult patients undergoing long-term dialysis. The incidence of tuberculosis was 12 times greater than that prevailing in the general community during the period of the study and could not be accounted for solely by demographic factors. Diagnosis was obscured because the symptoms were nonspecific and attributable to uremia, intermediate strength (5 TU) tuberculin tests were often negative, the roentgenographic appearance of pulmonary disease was often atypical, and there was more frequent extrapulmonary involvement. Impaired cellular immunity due to advanced renal failure may predispose to the increased incidence of tuberculosis and the greater frequency of extrapulmonary disease observed. Treatment was safe and effective in these patients using 300 mg of isoniazid and 8 to 10 mg/kg of ethambutol daily. Eight patients survived longer than one year following the diagnosis of tuberculosis, and all were clinically cured. No deaths were directly attributed to tuberculosis. A high index of suspicion and aggressive evaluation may be necessary to diminish the significant mortality described previously in association with disseminated disease.


Assuntos
Falência Renal Crônica/complicações , Tuberculose/complicações , Adulto , Idoso , Etambutol/uso terapêutico , Feminino , Humanos , Imunidade Celular , Isoniazida/uso terapêutico , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Pirazinamida/uso terapêutico , Diálise Renal , Rifampina/uso terapêutico , Risco , Tuberculose/tratamento farmacológico , Tuberculose/imunologia
18.
Am J Med ; 61(5): 641-9, 1976 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-984067

RESUMO

Sinus nod recovery time (SNRT) at paced atrial rates of 100 (SNRT100) and 120 (SNRT120) beats/min, atrial effective refractory periods at spontaneous heart rates (AERP) and at paced rates of 100 (AERP100) and 120 (AERP120) beats/min, and premature atrial stimulation were among the studies in evaluating 33 patients with symptomatic sinus node disease and 42 normal subjects. Although mean SNRT100 and SNRT120 were statistically significantly greater in patients than in control subjects, there was a significant overlap between patient and control groups, and SNRT100 or SNRT120 was associated with a 30.3 per cent false-negative and 5 per cent false-positive incidence. Correction for heart rate (SNRT-spontaneous cycle length) failed to improve the sensitivity or specificity of this test. There was no significant difference in mean AERP, AERP100 or AERP120, or in sinoatrial conduction time in patients compared with control subjects. Analyses of curves derived from plots of test and return cycles showed abnormal curves in only five of the 24 patients studied by progressively premature atrial stimulation. Two of these five patients showed normal zone I and II phenomena followed by a progressive linear increase in the return cycle that was thought to be due to abnormal refractoriness of the perinodal fibers.


Assuntos
Arritmia Sinusal/fisiopatologia , Marca-Passo Artificial , Adulto , Idoso , Eletrocardiografia , Frequência Cardíaca , Humanos , Pessoa de Meia-Idade , Período Refratário Eletrofisiológico , Nó Sinoatrial/fisiopatologia
19.
J Hypertens ; 12(12): 1395-403, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7706700

RESUMO

OBJECTIVE: To explore the repercussion of cardiac denervation on the short-term blood pressure variability in humans, in order to assess the extent to which the variability of blood pressure is linked to the variability of heart rate. METHODS: Beat-to-beat blood pressure and RR interval time were recorded in 16 heart-transplanted patients and were compared with those of 10 healthy control subjects in the resting supine, sitting and standing positions. Blood pressure and RR interval variabilities were assessed by spectral analysis. RESULTS: The total blood pressure power and the sitting very low-frequency, low-frequency, low-frequency and high-frequency blood pressure variability were similar in the heart-transplanted patients and in the controls, despite a marked reduction in the RR interval variability in the heart-transplanted patients. However, the heart-transplanted patients had lower standing low-frequency blood pressure variability than the control subjects. Moreover, very low-frequency and low-frequency RR interval variabilities reappeared in the long-term heart-transplanted patients but not in the short-term heart-transplanted patients (range of time after transplantation 53-124 and 3-25 months, respectively). CONCLUSIONS: Short-term RR interval fluctuations are not mandatory for the maintenance of normal blood pressure variability in the supine and sitting positions, but may contribute to the increase in the low-frequency blood pressure variability which occurs normally in the standing position. Moreover, the long-term heart-transplanted patients had increased RR interval variability, which may have been caused by the reappearance of limited autonomic cardiac modulation. However, this increased RR interval variability did not affect the corresponding blood pressure variability.


Assuntos
Pressão Sanguínea , Transplante de Coração , Coração/inervação , Denervação , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Pediatrics ; 91(4): 726-9, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8464658

RESUMO

The etiology and management of critical illness and injury in a pediatric emergency department were reviewed to survey the use of cardiopulmonary and trauma resuscitation and to compare these data with the educational content of Pediatric Advanced Life Support (PALS) courses. The emergency department records of 183 patients treated in the cardiopulmonary/trauma resuscitation room of a pediatric emergency department over a 17-month period were reviewed for data on diagnosis, morbidity, presence of apnea or pulselessness, and utilization of several resuscitation skills: intubation, cardioversion, tibial interosseous line placement, and other resuscitation techniques. Apneic and pulseless pediatric patients had poor survival (10.3%), but apneic patients had excellent survival (96.9%). Endotracheal intubation (57.9%), bag-valve-mask ventilation (63.9%), and medications for rapid-sequence induction of anesthesia prior to endotracheal intubation (25.7%) were used frequently. Inasmuch as asystole was the most common rhythm in pulseless patients, cardioversion and defibrillation were rarely used (2.2%). Specialized vascular access techniques, tibial interosseous lines (24.0%), and femoral intravenous lines (19.7%), were used frequently in pediatric patients. The frequent use of airway management skills and the excellent survival of apneic pediatric patients supports the current emphasis on airway management in PALS courses. Cardioversion/defibrillation should receive less emphasis in PALS courses. The frequent use of rapid-sequence induction of anesthesia prior to endotracheal intubation indicates that these techniques might warrant increased emphasis in the training of pediatric emergency department personnel and in PALS courses.


Assuntos
Ressuscitação , Ferimentos e Lesões/terapia , Apneia/terapia , Reanimação Cardiopulmonar , Criança , Cuidados Críticos , Medicina de Emergência/educação , Serviço Hospitalar de Emergência , Parada Cardíaca/terapia , Humanos , Pediatria , Ressuscitação/educação , Ressuscitação/métodos
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