RESUMEN
STUDY OBJECTIVE: To evaluate the efficacy and safety of caffeine citrate for treatment of apnea of prematurity. DESIGN: Multicenter, parallel, randomized, double-blind, placebo-controlled trial with open-label rescue. SETTING: Nine neonatal intensive care units. PATIENTS: Eighty-five infants, 28-32 weeks postconception and 24 hours or more after birth who had six or more apnea episodes within 24 hours. INTERVENTION: Caffeine citrate 10 mg/kg (as caffeine base) administered intravenously, followed by 2.5 mg/kg/day orally or intravenously, or placebo, for up to 10 days. Infants failing double-blind therapy could receive open-label rescue. MEASUREMENTS AND MAIN RESULTS: Success was defined as 50% or greater reduction in apnea episodes and elimination of apnea. Caffeine citrate was significantly more effective than placebo in reducing apnea episodes by at least 50% in 6 days (p<0.05), and approached statistical significance (p<0.10) in 3 days. It was significantly better than placebo in eliminating apnea in 5 days (p<0.05), and approached significance (p<0.10) in 2 days. The number of infants with an aggregate of 7-10 days of at least a 50% reduction in apnea events or elimination of apnea was significantly higher in the caffeine citrate than in the placebo group. Adverse events did not differ significantly between groups. No correlations were found between success and mean daily plasma concentrations or baseline characteristics. Volume of distribution and clearance increased with weight, supporting weight-adjusted dosing of caffeine citrate. CONCLUSION: Caffeine citrate 10 mg/kg caffeine base (equivalent to 20 mg/kg caffeine citrate) intravenously followed by 2.5 mg/kg/day caffeine base (equivalent to 5 mg/kg/day caffeine citrate) either intravenously or orally for 10 days is safe and effective for treating apnea of prematurity in infants 28-32 weeks postconception.
Asunto(s)
Apnea/tratamiento farmacológico , Cafeína/uso terapéutico , Citratos/uso terapéutico , Cafeína/efectos adversos , Cafeína/farmacocinética , Citratos/efectos adversos , Citratos/farmacocinética , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
Two hundred six outpatients with panic disorder and agoraphobia were randomly assigned to receive 4 weeks of treatment with placebo or sustained-release adinazolam under double-blind conditions. Eighty-eight percent of patients receiving drug and 85% of patients receiving placebo remained in the study at week 4. This report describes the "intent-to-treat" analysis of 202 patients who made at least one follow-up visit after randomization at baseline. On the basis of the Clinical Global Impressions-Improvement Scale, 69.7% of the adinazolam-treated patients were much or very much improved compared with 39.6% of the placebo-treated patients at week 4 or end-point (p = 0.0001). At week 4, panic attacks were completely blocked in 57.1% of adinazolam-treated patients and in 39.2% of the placebo-treated patients (p = 0.009). Adinazolam sustained-release treatment was statistically more effective than placebo treatment on measures of global improvement, number of panic attacks, SCL-90 phobia severity, main phobia severity, and anticipatory and general anxiety. No drug-placebo differences were found for overall self-rated phobia severity, unexpected or situational panic attacks, or for work, family, or social disability.
Asunto(s)
Agorafobia/tratamiento farmacológico , Ansiolíticos , Antidepresivos/administración & dosificación , Benzodiazepinas/administración & dosificación , Trastorno de Pánico/tratamiento farmacológico , Adulto , Agorafobia/psicología , Antidepresivos/efectos adversos , Benzodiazepinas/efectos adversos , Preparaciones de Acción Retardada , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno de Pánico/psicología , Determinación de la Personalidad/estadística & datos numéricos , Inventario de Personalidad/estadística & datos numéricos , Psicometría , Resultado del TratamientoRESUMEN
Twenty-four nonsmoking male volunteers took 50 mg atenolol or 10 mg betaxolol orally once a day for 9 days in a two-period, four-sequence, randomized, crossover study. Plasma concentrations reached steady state after day 5. Percent fluctuation in plasma concentration defined as (Cmax-Cmin)/Cavg (% fluctuation 1) was 97% on day 9 for betaxolol and 343% for atenolol; thus atenolol fluctuation was more than threefold that of betaxolol. A 10-fold difference in plasma level fluctuation was observed when fluctuation was defined as (Cmax-Cmin)/Cmin (% fluctuation 2). The intersubject variances for % fluctuation 1 and % fluctuation 2 were 4.1 and 85.5 times greater for atenolol than for betaxolol; these differences were marginally statistically significant for % fluctuation 1 and significant for % fluctuation 2. The intrasubject variabilities for area under the curve and plasma level fluctuations were statistically greater for atenolol than for betaxolol. Atenolol intrasubject variances were 25 and 271 times greater than for betaxolol for % fluctuation 1 and % fluctuation 2, respectively. Thus, betaxolol exhibited less fluctuation in plasma levels with substantially less intersubject and intrasubject variability. These factors would be expected to provide a more consistent therapeutic response and more dependable dosage adjustment.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacocinética , Atenolol/farmacocinética , Betaxolol/farmacocinética , Antagonistas Adrenérgicos beta/sangre , Adulto , Atenolol/sangre , Betaxolol/sangre , Disponibilidad Biológica , Humanos , Individualidad , MasculinoRESUMEN
Twenty-six women were evaluated with both hysterosalpingography and laparoscopy. The hysterosalpingograms were reviewed independently by two radiologists. Postdrainage films were obtained in 19 of 26 patients. A high false-negative rate (44.9% overall) and low specificity (20.6%) were observed. The postdrainage film contributed to a correct diagnosis in only four of 38 tubes evaluated by the first radiologist and in none evaluated by the second radiologist. Hysterosalpingography is valuable as a screening procedure for identifying abnormals but is not specific in differentiating tubal adhesions from tubal obstructions. It is recommended that preliminary films not be obtained routinely and that postdrainage films be reserved for cases where fluoroscopic and spot-film findings are equivocal.
Asunto(s)
Histerosalpingografía , Laparoscopía , Estudios de Evaluación como Asunto , Pruebas de Obstrucción de las Trompas Uterinas/métodos , Trompas Uterinas/patología , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Humanos , Infertilidad Femenina/diagnóstico , Adherencias Tisulares/diagnósticoRESUMEN
The fate of [3H]thymidine ([3H]Tdr) pulse-labelled cells was followed in tracheal epithelium of young male rats. The time course for cell differentiation, and the relation of events to tissue composition were studied. In vivo labelling and light microscope autoradiography of epoxy embedded sections were used. Labelled and total nuclei for each cell type, and combinations of labelled cells which were adjacent to one another, were tallied. Hierarchical analyses of variance were performed on the several data sets. All cell types, except ciliated, were labelled at 1 hr. A few labelled ciliated cells were seen 24 hr post-label. The frequency of labelled intermediate cells peaked at day 2; goblet and ciliated cells at day 3. No significant changes occurred in the labelling index, but at 24 hr the frequency of adjacent labelled cells (ALC) had increased greater than 5-fold, and changes had occurred in patterns of ALC combinations. The labelled ciliated cells which were seen at 24 hr were adjacent to labelled intermediate cells. No labelled basal-ciliated cell combinations were seen at any time. Data indicated that ciliated cells can develop from S-phase intermediate cells within 24 hr, and neither basal nor superficial goblet cells are progenitors of ciliated cells. It is proposed that both superficial goblet cell and ciliated cell development is preceded by two divisions: a basal cell division followed by an intermediate cell division.
Asunto(s)
Células Epiteliales , Tráquea/crecimiento & desarrollo , Análisis de Varianza , Animales , Autorradiografía , Diferenciación Celular , División Celular , ADN/biosíntesis , Cinética , Masculino , Ratas , Timidina/metabolismo , Tráquea/análisisRESUMEN
The observed inverse relationship between smoking and Parkinson disease has prompted suggestions that nicotine, a centrally active agent, might protect against the disease. In this case-control study, cases were found to have ever regularly smoked cigarettes significantly less frequently than sex-, race-, and age-matched neighbors. This report analyzes the detailed smoking histories of cases and neighbors to see if these histories support the nicotine protection hypothesis. Estimated nicotine exposure before age at onset of symptoms for smoking cases was 186.1 g; for smoking controls it was 208.3 g (p = 0.34). Among the cases, severity of disease was not related to the extent of nicotine exposure before disease onset. Age at onset of symptoms for smoking cases (52.7 years) was not delayed (57.8 years for nonsmoking cases). Since the study was unable th find further support for the nicotine protection hypothesis, it is concluded that the observed inverse relationship between smoking and Parkinson disease is likely explainable by other factors, such as selective mortality or pre-morbid behavioral and/or constitutional changes.
Asunto(s)
Enfermedad de Parkinson/prevención & control , Fumar , Adulto , Anciano , Femenino , Humanos , Kentucky , Masculino , Persona de Mediana Edad , Nicotina , Estudios RetrospectivosAsunto(s)
Dopamina/efectos adversos , Hipotensión/inducido químicamente , Fenitoína/efectos adversos , Simpatomiméticos/efectos adversos , Animales , Presión Sanguínea/efectos de los fármacos , Perros , Interacciones Farmacológicas , Isoproterenol/uso terapéutico , Contracción Miocárdica/efectos de los fármacos , Choque/tratamiento farmacológico , Resistencia Vascular/efectos de los fármacosRESUMEN
The in vitro effects of the water-soluble fraction of whole cigarette smoke (WSF) and two alpha, beta-unsaturated aldehydes of cigarette smoke (acrolein and crotonaldehyde) on polymorphonuclear leukocyte (PMNL) adherence were determined with nylon fiber columns. Each of these cigarette smoke constituents caused a dose-dependent inhibition of PMNL adherence. However, at least fivefold higher concentrations of these agents were necessary to inhibit adherence as compared with those necessary to achieve the same level of inhibition of PMNL chemotaxis. Furthermore, inhibition of adherence by WSF could be differentiated from its effects on chemotaxis in that reduced glutathione completely protected chemotaxis from the effects of WSF but only afforded partial protection to PMNL adherence. These data suggest that the inhibitory effects of WSF, acrolein, and crotonaldehyde on PMNL chemotaxis are not due to their inhibition of adherence. Finally, although PMNL adherence is considered to be an integral part of the chemotactic mechanism, differentiation between these two PMNL functions may be possible, since some inhibitors of chemotaxis do not have corresponding inhibitory effects on adherence.
Asunto(s)
Neutrófilos/inmunología , Humo , Acroleína/farmacología , Adulto , Aldehídos/farmacología , Adhesión Celular/efectos de los fármacos , Quimiotaxis de Leucocito/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Glutatión/farmacología , Humanos , Hidroximercuribenzoatos/farmacología , MasculinoRESUMEN
In previous studies, there were fewer cigarette smokers among persons with Parkinson disease than among other patients. We reinvestigated this phenomenon, using nonpatient controls. In home interviews with 237 Parkinson patients and 474 age-, sex-, and race-matched neighbors, we inquired about consumption of tobacco, coffee, tea, and alcohol. All Parkinson patients were diagnosed by a neurologist, had two or more cardinal features of parkinsonism, and had not received chronic phenothiazine therapy. One hundred fifty (63%) of 237 cases and 224 (47%) of 474 controls never smoked cigarettes (p < 0.0001). Significantly different smoking rates were also preset at 10 and 20 years before the onset of parkinsonism.