RESUMO
BACKGROUND: Cannabis is the most frequently used illegal substance in the United States and Europe. There is a dramatic increase in the demand for treatment for cannabis dependence. Cannabis users frequently have co-morbid mood symptoms, especially depression and anxiety, and regular cannabis users may self-medicate for such symptoms. OBJECTIVES: We report a double-blind, placebo-controlled treatment study, for the prevention of cannabis use in cannabis-dependent individuals. METHOD: Regular cannabis-dependent users (n = 52) were treated for 9 weeks with weekly cognitive-behavior and motivation-enhancement therapy sessions together with escitalopram 10 mg/day. Urine samples were collected to monitor delta-9 tetrahydrocannabinol (THC) during treatment and questionnaires were administered to assess anxiety and depression. RESULTS: We observed a high rate of dropout (50%) during the 9-week treatment program. Fifty-two patients were included in the intention-to-treat analysis. Of these, ten (19%) remained abstinent after 9 weeks of treatment as indicated by negative urine samples for THC. Escitalopram provided no advantage over placebo in either abstinence rates from cannabis or anxiety and depression scores during the withdrawal and abstinent periods. CONCLUSIONS: Escitalopram treatment does not provide an additional benefit either for achieving abstinence, or for the treatment of the cannabis withdrawal syndrome. Due to limitations of our study, namely, a high dropout rate and effects of low abstinence rates on measures of anxiety, depression and withdrawal, it is premature to conclude that selective serotonin reuptake inhibitors are not effective for treatment of the cannabis withdrawal syndrome.
Assuntos
Citalopram/uso terapêutico , Terapia Cognitivo-Comportamental , Abuso de Maconha/tratamento farmacológico , Abuso de Maconha/terapia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Adulto , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Terapia Combinada , Depressão/complicações , Depressão/tratamento farmacológico , Método Duplo-Cego , Dronabinol/urina , Feminino , Humanos , Masculino , Abuso de Maconha/complicações , Abuso de Maconha/urina , Pessoa de Meia-Idade , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/prevenção & controle , Adulto JovemRESUMO
Antibody to the antibiotic chloramphenicol was obtained by immunizing rabbits with a chloramphenicol derivative coupled to bovine gamma globulin. Production of antibody was demonstrated by the precipitin and complement fixation reactions with "reduced chloramphenicol" coupled to rabbit serum albumin as the test antigen. Specificity of the antibody was confirmed in that crystalline chloramphenicol completely inhibited complement fixation and precipitin reactions. "reduced chloramphenicol" coupled to human serum albumin provides an antigen for the detection of antibody to chloramphenicol, if it occurs in human serum in dyscrasias. With quantitative complement fixation, as little as 10(-5) microg (4 x 10(-14) mole) of chloramphenicol was detectable by the inhibition assay.
Assuntos
Anticorpos/imunologia , Cloranfenicol/imunologia , Animais , Anticorpos/sangue , Especificidade de Anticorpos , Cloranfenicol/análise , Testes de Fixação de Complemento , Células HeLa , Humanos , Imunização , Testes de Precipitina , CoelhosRESUMO
A pentapeptide was synthesized with the same amino acid sequence that occurs in a unique region of the chaim of immunoglobulin E near the cysteine residue participating in the linkage between the two heavy chains. This pentapeptide has the capacity to block a standard Prausnitz-Küstner reaction as well as to inhibit a known positive skin test reaction. Other similar synthetic polypeptides had less or no inhibitory activity. The likelihood that this pentapeptide amino acid sequence does in fact represent the structure of the specific immunoglobulin E binding site for the mast cell and basophil is considered.
Assuntos
Sítios de Ligação de Anticorpos , Hipersensibilidade Imediata/imunologia , Imunoglobulina E , Mastócitos/imunologia , Oligopeptídeos/imunologia , Testes Cutâneos , Sequência de Aminoácidos , Basófilos/imunologia , Ligação Competitiva , Depressão Química , Humanos , Fragmentos Fc das Imunoglobulinas , Oligopeptídeos/síntese química , Relação Estrutura-AtividadeRESUMO
AIM: To determine whether implementation of criteria for performing a toxicology screen and increasing staff awareness improve detection of substance abuse among adolescents presenting to the emergency department. METHODS: Patients 12 to 18 years of age presenting to one of three emergency departments in Israel were included in a prospective cohort study. In the 'study' hospital, a set of criteria for urine toxicology screen and measurements of ethanol serum level were implemented. No specific interventions were implemented in the two other hospitals. The main outcome measure was the rate of substance abuse detection. RESULTS: The number of adolescents seen in the participating centres was 3200 at the study hospital, and 3493 and 2792 at the two other hospitals. High blood ethanol concentrations were found in 49 patients at the study hospital compared with 30 and 19 patients at the two other hospitals (p < 0.001). Illicit drugs were detected in 13, 4 and 1 patients, respectively (p = 0.002). CONCLUSIONS: Introducing structured guidelines for ordering toxicological screening increases the detection of alcohol and drug of abuse among adolescents presenting to paediatric emergency departments.
Assuntos
Alcoolismo/diagnóstico , Serviço Hospitalar de Emergência , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adolescente , Comportamento do Adolescente , Intoxicação Alcoólica/diagnóstico , Alcoolismo/epidemiologia , Análise de Variância , Criança , Etanol/sangue , Etanol/toxicidade , Feminino , Humanos , Drogas Ilícitas/toxicidade , Israel/epidemiologia , Masculino , Guias de Prática Clínica como Assunto , Prevalência , Estudos Prospectivos , Detecção do Abuso de Substâncias/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Urina/químicaRESUMO
Heavy use of marijuana is claimed to damage critical skills related to short-term memory, visual scanning and attention. Motor skills and driving safety may be compromised by the acute effects of marijuana. The aim of this study was to investigate the acute effects of 13 mg and 17 mg Delta 9-tetrahydrocannabinol (THC) on skills important for coordinated movement and driving and on subjective and autonomic measures in regular users of marijuana. Fourteen regular users of marijuana were enrolled. Each subject was tested on two separate days. On each test day, subjects smoked two low-nicotine cigarettes, one with and the other without THC. Seventeen mg THC was included in the cigarette on one test day and 13 mg on the other day. The sequence of cigarette types was unknown to the subject. During smoking, heart rate and blood pressure were monitored, and the subjects performed a virtual reality maze task requiring attention and motor coordination, followed by 3 other cognitive tasks (Wisconsin Card Sorting Test (WCST), a "gambling" task and estimation of time and distance from an approaching car). After smoking a cigarette with 17 mg THC, regular marijuana users hit the walls more often on the virtual maze task than after smoking cigarettes without THC; this effect was not seen in patients after they smoked cigarettes with 13 mg THC. Performance in the WCST was affected with 17 mg THC and to a lesser extent with the use of 13 mg THC. Decision making in the gambling task was affected after smoking cigarettes with 17 mg THC, but not with 13 m THC. Smoking cigarettes with 13 and 17 mg THC increased subjective ratings of pleasure and satisfaction, drug "effect" and drug "high". These findings imply that smoking of 17 mg THC results in impairment of cognitive-motor skills that could be important for coordinated movement and driving, whereas the lower dose of 13 mg THC appears to cause less impairment of such skills in regular users of marijuana.
Assuntos
Nível de Alerta/efeitos dos fármacos , Atenção/efeitos dos fármacos , Condução de Veículo/psicologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Tomada de Decisões/efeitos dos fármacos , Dronabinol/toxicidade , Abuso de Maconha/fisiopatologia , Abuso de Maconha/psicologia , Memória de Curto Prazo/efeitos dos fármacos , Destreza Motora/efeitos dos fármacos , Testes Neuropsicológicos , Desempenho Psicomotor/efeitos dos fármacos , Adulto , Afeto/efeitos dos fármacos , Afeto/fisiologia , Nível de Alerta/fisiologia , Atenção/fisiologia , Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Tomada de Decisões/fisiologia , Percepção de Distância/efeitos dos fármacos , Percepção de Distância/fisiologia , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Fumar Maconha/efeitos adversos , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória de Curto Prazo/fisiologia , Destreza Motora/fisiologia , Orientação/efeitos dos fármacos , Orientação/fisiologia , Desempenho Psicomotor/fisiologia , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Jogos de VídeoRESUMO
The intrarenal gradient of renin activity was determined in rats by using superficial (S) and deep (D) cortical juxtaglomerular apparatuses (JGA's), identified and microdissected after silicone-rubber compound injection. Angiotensin generated from single JGA's using partially purified sheep renin substrate was quantified by rat bioassay. When, in rats on a normal NaCl diet, silicone-rubber was injected into a carotid artery, alone or with abdominal aorta catheterization, S:D renin activity ratios were 1.18+/-0.08 (SEM) and 1.21+/-0.12, respectively. The S:D renin activity ratios obtained when silicone-rubber was injected into the abdominal aorta (2.52+/-0.09) or a chronic carotid artery catheter (3.44+/-0.40) were significantly higher (P < 0.001). The lower S:D renin activity ratios after carotid artery manipulation were due to significantly higher D-JGA renin activities. This increased D-JGA renin activity and the lack of a renin gradient appear to be related to acute carotid artery manipulation. Alterations in JGA renin activity were examined relative to NaCl intake. 2 wk after high-NaCl diet the absolute net renin activity decreased (P < 0.001) more in S (5.84+/-0.11 ng AI.JGA(-1).h(-1)) than D (1.73+/-0.06 ng AI.JGA(-1).h(-1)) JGA's, and the intrarenal renin gradient was lost (S:D-JGA renin activity, 1.00+/-0.07), as compared to the regular NaCl diet. 2 wk of a low-NaCl diet resulted in a greater (P < 0.01) increase in S (14.28+/-1.47 ng AI.JGA(-1).h(-1)) than D (9.62+/-1.19 ng AI.JGA(-1).h(-1)) JGA renin activity and a renin gradient (S:D-JGA renin activity) of 1.75+/-0.12. These results demonstrate that NaCl intake clearly influences total JGA renin content and may also affect the relative intrarenal distribution of renin activity.
Assuntos
Sistema Justaglomerular/enzimologia , Renina/sangue , Cloreto de Sódio/farmacologia , Angiotensina II/análise , Angiotensina II/biossíntese , Animais , Aorta Abdominal , Bioensaio , Artérias Carótidas , Cateterismo , Dieta , Dieta Hipossódica , Dissecação , Sistema Justaglomerular/irrigação sanguínea , Sistema Justaglomerular/cirurgia , Masculino , Radioimunoensaio , Ratos , Ovinos , Cloreto de Sódio/administração & dosagemRESUMO
To determine the sites of tubular phosphate reabsorption in the nephron, microinjection studies were undertaken, utilizing isotonic electrolyte solutions, containing either 1.4 or 8.0 mM phosphate and radioactive PO(4)-(33)P and inulin-(3)H, in rats made mildly diuretic by infusion of mannitol. The injected sites were localized by the technique of latex dissection. The relation between proximal tubular length and per cent (33)P recovery for injections of 1.4 mM phosphate (physiological amounts) suggest that relatively little reabsorption of phosphate occurs in the distal 30% of the proximal tubule compared with the proximal portion of the tubule. The corresponding recoveries for proximal tubular microinjections of 8.0 mM phosphate fall along a smooth curve tending to plateau with essentially complete (33)P recovery (> 95%) beyond 50% of the tubule. Absolute reabsorption of injected phosphate for both concentrations (i.e., absolute efflux per unit tubular length in the proximal tubule) was independent of phosphate delivery, since the relationship between reabsorption and site of injection was no different for the two concentrations. Distal convoluted tubular microinjections for both phosphate concentrations showed complete recovery of (33)P from all injection sites. THE DATA INDICATE THAT: (a) no phosphate reabsorption occurs in the distal convoluted tubule or in the collecting duct, (b) phosphate efflux per unit tubular length is greater in the first one-third of the proximal tubule than in the remaining two-thirds, and (c) in the last two-thirds of the proximal tubule, absolute phosphate reabsorption is relatively small and might be limited by factors other than the amount or concentration of injected phosphate.
Assuntos
Túbulos Renais/fisiologia , Fosfatos/metabolismo , Animais , Bicarbonatos/administração & dosagem , Feminino , Taxa de Filtração Glomerular , Injeções Intravenosas , Inulina/administração & dosagem , Inulina/urina , Túbulos Renais Distais/fisiologia , Túbulos Renais Proximais/anatomia & histologia , Túbulos Renais Proximais/fisiologia , Manitol/administração & dosagem , Microinjeções , Fosfatos/administração & dosagem , Isótopos de Fósforo , Potássio/administração & dosagem , Ratos , Análise de Regressão , Cloreto de Sódio/administração & dosagem , Espectrofotometria , Trítio , Ureter , Cateterismo Urinário , Urina/fisiologiaRESUMO
Serial estimations of exchangeable (42)K showed that six volunteer subjects undergoing intensive physical conditioning in a hot climate sustained a mean deficit of 517 mEq. This deficit occurred despite a daily potassium intake of 100 mEq. Simultaneous values for lean body mass rose suggesting that potassium deficiency was not the result of catabolism. Although sweating was the major avenue by which the deficit occurred, daily excretion of potassium into the urine when each subject was maximally deficient ranged from 46 to 75 mEq and thus was inappropriately high for potassium-depleted subjects. Despite high intakes of sodium and excretion of corresponding quantities into the urine, Na/K ratios in sweat were low thus indicating unsuppressed activity of aldosterone on sweat glands. Moreover, excretion and secretion of aldosterone and in many instances, plasma renin activity, appeared to be high with respect to sodium intake. These findings suggest that intense physical work in the heat stimulates higher production of aldosterone than would occur in nonexercising subjects on similar sodium intakes. Similar to the phenomenon of mineralocorticoid escape, such overproduction of aldosterone in the presence of conditions permitting excretion of sodium into the urine could facilitate continued excretion of potassium by the kidney despite serious potassium depletion. As a consequence, the kidney played a role in the genesis of potassium depletion in these subjects. In contrast to subjects undergoing conditioning in the summer months, potassium depletion did not occur in 16 subjects during identical training under cooler environmental conditions.
Assuntos
Clima , Rim/fisiopatologia , Esforço Físico , Deficiência de Potássio/fisiopatologia , Sudorese , Aclimatação , Adulto , Aldosterona/metabolismo , Composição Corporal , Exaustão por Calor/etiologia , Exaustão por Calor/fisiopatologia , Humanos , Rim/metabolismo , Masculino , Medicina Militar , Educação Física e Treinamento , Potássio/metabolismo , Deficiência de Potássio/etiologia , Renina/metabolismo , Sódio/metabolismoRESUMO
Factor VIII antigen (VIII:CAg) exhibits molecular weight heterogeneity in normal plasma. We have compared the relative quantities of VIII:CAg forms present in normal individuals (n = 22) with VIII:CAg forms in renal dysfunction patients (n = 19) and in patients with disseminated intravascular coagulation (DIC; n = 7). In normal plasma, the predominant VIII: CAg form, detectable by sodium dodecyl sulfate polyacrylamide gel electrophoresis, was of molecular weight 2.4 X 10(5), with minor forms ranging from 8 X 10(4) to 2.6 X 10(5) D. A high proportion of VIII:CAg in renal dysfunction patients, in contrast, was of 1 X 10(5) mol wt. The patients' high 1 X 10(5) mol wt VIII: CAg level correlated with increased concentrations of serum creatinine, F1+2 (a polypeptide released upon prothrombin activation), and with von Willebrand factor. Despite the high proportion of the 1 X 10(5) mol wt VIII:CAg form, which suggests VIII:CAg proteolysis, the ratio of Factor VIII coagulant activity to total VIII:CAg concentration was normal in renal dysfunction patients. These results could be simulated in vitro by thrombin treatment of normal plasma, which yielded similar VIII:CAg gel patterns and Factor VIII coagulant activity to antigen ratios. DIC patients with high F1+2 levels but no evidence of renal dysfunction had an VIII:CAg gel pattern distinct from renal dysfunction patients. DIC patients had elevated concentrations of both the 1 X 10(5) and 8 X 10(4) mol wt VIII:CAg forms. We conclude that an increase in a particular VIII:CAg form correlates with the severity of renal dysfunction. The antigen abnormality may be the result of VIII:CAg proteolysis by a thrombinlike enzyme and/or prolonged retention of proteolyzed VIII:CAg fragments.
Assuntos
Coagulação Intravascular Disseminada/sangue , Fator VIII/análise , Nefropatias/sangue , Idoso , Creatinina/sangue , Coagulação Intravascular Disseminada/etiologia , Humanos , Falência Renal Crônica/sangue , Pessoa de Meia-Idade , Peso Molecular , Neoplasias/sangue , Neoplasias/complicações , Protrombina/análise , Diálise Renal , Fator de von Willebrand/análiseRESUMO
OBJECTIVES: The purpose of this study was to determine the effects of obesity and its interaction with age, race and the magnitude of blood pressure elevation in a large cohort of patients with mild to moderate hypertension and a high prevalence of left ventricular hypertrophy. BACKGROUND: Obesity, race and age each have important effects on the incidence and severity of hypertension and may contribute to the effects of blood pressure elevation on the cardiac manifestations of hypertension. METHODS: Left ventricular structure and function were assessed with two-dimensional targeted M-mode echocardiography in 692 men with mild to moderate hypertension (average blood pressure 153/100 mm Hg), and the data were compared in relation to obesity (determined from body mass index), age, race, blood pressure, physical activity, plasma renin activity, urinary sodium excretion, hematocrit, heart rate and serum lipids. RESULTS: Left ventricular hypertrophy was common (63% with increased left ventricular mass, 22% with left ventricular hypertrophy on the electrocardiogram [ECG]). On multivariable regression analysis, body mass index was the strongest predictor of left ventricular mass and magnified the slope relation of blood pressure to left ventricular mass. Despite a greater prevalence of ECG left ventricular hypertrophy in blacks (31%) than in whites (10%), left ventricular mass and echocardiographic prevalence of left ventricular hypertrophy did not differ by race. However, septal, posterior left ventricular and relative wall thickness were greater in black than in white men. CONCLUSIONS: Obesity is the strongest clinical predictor of left ventricular mass and left ventricular hypertrophy in men, even in those with mild to moderate hypertension of sufficient severity to be associated with a high prevalence of left ventricular hypertrophy. Moreover, independent effects of systolic blood pressure on left ventricular mass are amplified by obesity. Although race does not affect left ventricular mass or the prevalence of left ventricular hypertrophy, black race is associated with greater relative wall thickness, itself a predictor of unfavorable cardiovascular outcome.
Assuntos
População Negra , Hipertensão/patologia , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/complicações , Obesidade/complicações , Fatores Etários , Idoso , Análise de Variância , Índice de Massa Corporal , Ecocardiografia , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico por imagem , Obesidade/patologia , Obesidade/fisiopatologia , PrevalênciaRESUMO
BACKGROUND: Based on pre-clinical studies regarding the interaction of various antidepressant drugs with the opioid system, we designed a clinical study to be carried out in the 'in-patient detoxification unit' within a large community centre for treatment of drugs dependent people. We evaluated the effect of mianserin add-on, on the intensity of opioid withdrawal symptoms in opiate dependent subjects undergoing medication-supported physical detoxification and integrated psychosocial and psychotherapeutic intervention for the treatment of dependence. METHODS: Mianserin (or placebo) was added to the routine medication protocol, during the 3-week in-patient phase of detoxification in a prospective, randomized, double blind, placebo controlled study. Mianserin (or placebo) was continued after discharge and patients were followed up for 3 months in order to evaluate relapse rates. Opiate withdrawal symptoms were assessed during the first 10 days, while depression and anxiety were assessed throughout the 3 months of study. RESULTS: From day 2 onward, patients in the study group showed significantly lower withdrawal symptoms than the control group patients and reached this peak faster (study group 2.8 days, control group 3.2 days, p<0.001). However, drop out rates were higher in the study group throughout the study period and only 13% of the study group patients, compared to 30% of the control group patients reached the end point. CONCLUSION: Though adding mianserin to the medication treatment during detoxification of opiate-dependent persons attenuated significantly both the intensity and the duration of withdrawal symptoms, the overall drop out rate was negatively influenced in the study group compared to the control group and fewer patients completed the study. Further study is needed in order to establish the origin of the paradox of higher drop out rates in the presence of attenuated intensity and duration of opiate withdrawal symptoms in the study group, and the clinical implications that should be drown.
Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Mianserina/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/reabilitação , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Análise de Variância , Ansiedade/etiologia , Transtorno Depressivo/etiologia , Método Duplo-Cego , Humanos , Masculino , Cooperação do Paciente , Estudos Prospectivos , Análise de SobrevidaRESUMO
Polyarteritis nodosa developed in one of 34 patients undergoing long-term maintenance hemodialysis with persistent hepatitis B surface antigenemia. Exacerbation of the baseline hypertension and progressive peripheral neuropathy during the recovery phase of hepatitis B surface antigen hepatitis were the initial features. Poor response to aggressive corticosteroid and immunosuppressive therapy in this patient was in contrast to recent experience in patients undergoing long-term hemodialysis and the general population.
Assuntos
Hepatite B/complicações , Poliarterite Nodosa/etiologia , Diálise Renal , Corticosteroides/uso terapêutico , Idoso , Ciclofosfamida/uso terapêutico , Feminino , Hepatite B/imunologia , Hepatite B/terapia , Antígenos de Superfície da Hepatite B/análise , Humanos , Hipertensão/complicações , Neurite (Inflamação)/complicações , Poliarterite Nodosa/tratamento farmacológico , Vasculite/tratamento farmacológico , Vasculite/etiologiaRESUMO
The courses of 276 acute tubular necrosis patients referred for dialysis were reviewed in search for prognostic indicators. Sixty-three percent survived. Of 28 possible predictor variables, a posttoxic cause and nonoliguria were favorable, whereas myocardial infarction and peritonitis affected survival unfavorably. Total pareneral nutrition influenced survival favorably only in those with multiple complications or peritonitis. No single variable or combination predicted a lethal outcome. Since survivors were frequently restored to complete health, we advocate an aggressive therapeutic approach even in the face of multiple complications.
Assuntos
Injúria Renal Aguda/mortalidade , Necrose Tubular Aguda/mortalidade , Adolescente , Adulto , Idoso , Criança , Economia Hospitalar , Honorários e Preços , Feminino , Humanos , Necrose Tubular Aguda/complicações , Necrose Tubular Aguda/etiologia , Necrose Tubular Aguda/terapia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
The effectiveness of transdermally administered clonidine hydrochloride was evaluated in a multicenter study in 85 patients with mild essential hypertension. The drug was incorporated into small self-adhesive delivery systems (pliable skin patches, 3.5-sq-cm area) designed to continuously deliver 0.1 mg of clonidine hydrochloride per day. These devices were changed by the patients themselves at weekly intervals. Diastolic BP fell by at least 10% in 37 patients and was normalized (less than 90 mm Hg) in 54 patients (64%); 17 of these responding patients required only one skin patch, 27 required two, and the other ten responders required three. The antihypertensive action of the transdermal clonidine was sustained for the full three months of study. Side effects were similar to those during conventional oral treatment, but appeared to be milder.
Assuntos
Clonidina/administração & dosagem , Hipertensão/tratamento farmacológico , Fatores Etários , População Negra , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ensaios Clínicos como Assunto , Clonidina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Absorção Cutânea , População BrancaRESUMO
BACKGROUND: An important issue in clinical practice is how to treat patients whose blood pressure does not respond to the first antihypertensive drug selected. OBJECTIVE: To analyze the antihypertensive response of patients who had failed to achieve their diastolic blood pressure goal (< 90 mm Hg at the end of 8 to 12 weeks of titration) with one of six randomly allocated drugs or placebo to the random allocation of an alternate drug. METHODS: We initially randomized 1292 men with diastolic blood pressure of 95 to 109 mm Hg to treatment with hydrochlorothiazide, atenolol, captopril, clonidine hydrochloride, diltiazem hydrochloride (sustained release), prazosin hydrochloride, or placebo. Of 410 men in whom initial treatment failed, 352 qualified for randomization to the alternate drug. RESULTS: Of the 352 patients, 173 (49.1%) achieved their goal diastolic blood pressure, in 133 (37.8%) the alternate drug failed, and 46 (13.1%) left the study for various reasons. Overall response rates were as follows: diltiazem, 63%; clonidine, 59%; prazosin, 47%; hydrochlorothiazide, 46%; atenolol, 41%; and captopril, 37%. The best response rate for patients in whom hydrochlorothiazide failed was achieved with diltiazem (70%); after atenolol failure, clonidine (86%); after captopril failure, prazosin (54%); after clonidine failure, diltiazem (100%); after diltiazem failure, captopril (67%); and after prazosin failure, clonidine (53%). The combined response rate for patients initially randomized to an active treatment was 76.0%, which is similar to that achieved by the combination of two drugs in previous studies. CONCLUSIONS: We conclude that sequential single-drug therapy is a rational approach for treatment of hypertension in patients in whom initial drug therapy has failed.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Adulto , Idoso , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Falha de Tratamento , Resultado do TratamentoRESUMO
OBJECTIVE: To determine whether blood pressure is reduced for at least 6 months with an intervention to lower alcohol intake in moderate to heavy drinkers with above optimal to slightly elevated diastolic blood pressure, and whether reduction of alcohol intake can be maintained for 2 years. DESIGN: A randomized controlled trial. METHODS: Six hundred forty-one outpatient veterans with an average intake of 3 or more alcoholic drinks per day in the 6 months before entry into the study and with diastolic blood pressure 80 to 99 mm Hg were randomly assigned to a cognitive-behavioral alcohol reduction intervention program or a control observation group for 15 to 24 months. The goal of the intervention was the lower of 2 or fewer drinks daily or a 50% reduction in intake. A subgroup with hypertension was defined as having a diastolic blood pressure of 90 to 99 mm Hg, or 80 to 99 mm Hg if recently taking medication for hypertension. RESULTS: Reduction in average weekly self-reported alcohol intake was significantly greater (P<.001) at every assessment from 3 to 24 months in the intervention group vs the control group: levels declined from 432 g/wk at baseline by 202 g/wk in the intervention group and from 445 g/wk by 78 g/wk in the control group in the first 6 months, with similar reductions after 24 months. The intervention group had a 1.2/0.7-mm Hg greater reduction in blood pressure than the control group (for each, P = .17 and P = .18) for the 6-month primary end point; for the hypertensive stratum the difference was 0.9/0.7 mm Hg (for each, P = .58 and P = .44). CONCLUSIONS: The 1.3 drinks per day average difference between changes in self-reported alcohol intake observed in this trial produced only small nonsignificant effects on blood pressure. The results from the Prevention and Treatment of Hypertension Study (PATHS) do not provide strong support for reducing alcohol consumption in nondependent moderate drinkers as a sole method for the prevention or treatment of hypertension.
Assuntos
Consumo de Bebidas Alcoólicas , Hipertensão/terapia , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Etanol/farmacologia , Feminino , Humanos , Hipertensão/prevenção & controle , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
To assess cellular immune status and the hypothalamic-pituitary (HP) axis in patients with major depression, we examined peripheral blood mononuclear cells (PBMC) and measured the plasma levels of cortisol, adrenocorticotropin hormone (ACTH), growth hormone (GH), and prolactin (PRL). Twenty patients with major depression were compared with 20 control subjects matched for age, sex, and race. The dose-response curves for concanavalin-A (Con-A) and phytohemagglutinin (PHA) stimulation were not significantly different between the two groups. The patients had decreased Con-A-stimulated T-lymphocyte proliferation when compared to the control subjects, but only at the lowest suboptimal concentration of Con-A. None of the four concentrations of PHA-stimulated proliferation were different between the two groups, neither was PHA-induced interleukin-2 production. Within the patient group only, plasma prolactin (PRL) correlated significantly with stimulated lymphocyte proliferation using two optimal concentrations of PHA and one optimal concentration of Con-A, when the proliferation was expressed using the stimulation index.
Assuntos
Transtorno Depressivo/imunologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Interleucina-2/biossíntese , Ativação Linfocitária , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Transtorno Depressivo/psicologia , Hormônio do Crescimento/sangue , Humanos , Hidrocortisona/sangue , Pessoa de Meia-Idade , Prolactina/sangue , Testes Psicológicos , PsiconeuroimunologiaRESUMO
The efficacy of Naltrexone in preventing reabuse of heroin among heroin addicts in Israel was studied in a double-blind, controlled design. Naltrexone (or placebo) treatment was given as part of a general treatment plan that continued for 12 weeks. Thirty-two addicts who successfully completed a detoxification program and met research criteria, were included in the study. Fifty milligrams of Naltrexone were taken orally three times a week (25 mg twice a week for the first 2 weeks). The follow-up procedure included an interview, urine tests, and screening for possible adverse effects. In addition, social and psychological parameters were evaluated. Fewer heroin-positive urine tests were found the Naltrexone group than in the placebo group. Throughout the entire study, the number of drug-free patients in the Naltrexone group was higher than in the placebo group. The Naltrexone group showed a significant improvement in most psychological parameters as compared with the placebo group. No differences were found in compliance or ratio of adverse effects between the Naltrexone and placebo groups. The concept "heroin abuse load" based on daily heroin consumption and duration of addiction enabled us to predict which addicts would complete the treatment program. The results suggest that heroin addicts in Israel may benefit from treatment with Naltrexone.
Assuntos
Dependência de Heroína/reabilitação , Naltrexona/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Adulto , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/efeitos adversosRESUMO
We conducted a 7-month randomized, single, double, single-blind comparison of calcitriol (1,25(OH)2D3) with vitamin D3 in 22 hemodialysis patients to study the effects on the biochemical abnormalities associated with osteodystrophy. Calcitriol was given for 3 mo. All patients had initial prestudy calcium values less than or equal to 9.5 mg/100 ml, and phosphate values less than or equal to 4.5 mg/100 ml. Data were analyzed using the Normalized Trend Index (NTI). Calcitriol induced a rise in calcium (8.7 to 10.25 mg/100 ml) (p less than 0.001) and a fall in alkaline phosphatase (p less than 0.005), while D3 had no appreciable effect. The mean dose of calcitriol during treatment was 0.579 microgram/day while that for D3 was 706 IU/day. The effect on serum phosphate concentration was variable. Hypercalcemia as high as 13.2 mg/100 ml occurred in 2 of 13 patients on 1,25(OH)2D3, but in every instance promptly returned to normal with dose reduction. No other adverse effects were noted with therapy. We conclude that calcitriol reverses the biochemical abnormalities of osteodystrophy. Since its effects are rapidly reversed with discontinuation, the drug is probably safe as well as effective.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Di-Hidroxicolecalciferóis/uso terapêutico , Hidroxicolecalciferóis/uso terapêutico , Diálise Renal , Adulto , Idoso , Fosfatase Alcalina/sangue , Cálcio/sangue , Colecalciferol/uso terapêutico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Ensaios Clínicos como Assunto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
An immunochemical assay is described in which a radiolabelled antibody fragment, Fab', is bound specifically to immunoglobulin E (IgE), and precipitated with ammonium sulfate. The radioactivity in the precipitate is a measure of the amount of IgE in the sample. Results for six serum samples are compared using the double antibody and ammonium sulfate methods as well as the PRIST.