Evidence for an Interaction Between the β-Blocker Pafenolol and Bile Salts in the Intestinal Lumen of the Rat Leading to Dose-Dependent Oral Absorption and Double Peaks in the Plasma Concentration–Time Profile

Pafenolol is a -blocker with unusual oral absorption properties. The blood concentration–time profile exhibits two peaks, and the bioavailability is low and dose dependent because of incomplete and nonlinear intestinal uptake. We addressed the question whether the intestinal absorption of pafenolol was affected by bile depletion in the gut lumen of rats. Further, the hypothesis that variable gastric emptying accounts for double peaks in blood was tested by duodenal administration of pafenolol. Following intraduodenal administration to rats with intact bile secretion, double peaks were observed in the blood concentration–time curve. The bioavailability was 6.8 ± 0.7% for the low dose (1 µmol/kg) and increased significantly to 28 ± 10% following the high duodenal dose (25 µmol/kg). These blood concentration–time profiles exclude interrupted gastric emptying as cause of the twin peaks. In bile duct-cannulated rats the intestinal absorption of the low dose (1 µmol/kg) was still poor (F = 10.7 ± 5.5%) and the blood concentration–time profile contained two peaks. Following administration of a high duodenal dose (25 µmol/kg) to rats with an almost bile-free small intestine, the absorption rate increased and the double-peak phenomenon disappeared in five of seven rats, while the bioavailability increased significantly, to 62 ± 27%. These results suggest that the low bioavailability of pafenolol is due to a complexation between bile and pafenolol in the gut lumen, preventing intestinal uptake in the major part of the small intestine. Further, such complex formation in the intestinal lumen may be the underlying mechanism of the double peaks observed in the blood concentration–time profile.     

Androgen treatment of abdominally obese men

Middle-aged men with abdominal obesity were treated in a double-blind study with moderate doses of transdermal preparations of testosterone (T), dihydrotestosterone (DHT), or placebo. This resulted in moderately elevated T concentrations and marked decreases in follicle stimulating and luteinizing hormones in the group treated with T, while the DHT group showed elevated DHT, markedly lower T values, and less diminution of gonadotropin concentrations. In the group treated with T visceral fat mass decreased (measured by computerized tomography) without significant changes in other depot fat regions. Lean body mass did not change. In the group treated with T, glucose disposal rate, measured with the euglycemic hyperinsulinemic clamp method, was markedly augmented. Plasma triglycerides, cholesterol, and fasting blood glucose concentrations as well as diastolic blood pressure decreased. There were no such changes in the DHT or placebo treatment groups. The men treated with T reported increased well-being and energy. In none of the groups did prostate volume, specific prostate antigen concentration, genito-urinary history, or urinary flow measurement change. It is suggested that supplementation of abdominal obese men with moderate doses of T might have several beneficial effects.     

Diagnostic outcome of repeated mammography screening

Mammographic screening for breast cancer within health service routines was evaluated for the years 1987–1992, with special focus on repeated screening during 1989–1992. The overall attendance rate by women aged 40 to 74 years was 82.8%. During 1989–1992 malignancy was found in 2.6/1000 screened women, giving a 87.4% positive predictive rate at surgery and 95.9% efficiency. Among women aged 45, the positive predictive rate was >94%. Fine-needle aspiration (FNA) biopsy showed invasive cancers in 84% and highly suspected cancer in another 15%; 60% of the lesions were nonpalpable. For first-time (prevalence) screening (1987–1988) the positive predictive rate was 86% and the malignancy yield 6.4/1000. In women aged 40–44 years there were few surgical referrals (1.6%), but the positive predictive rate at surgery was only 48.3%, indicating diagnostic difficulties in young women. The median size of all invasive cancers was 12 mm: 84% were classified as pT1, and 23% had lymph node involvement. Stage II disease was found in 27% of all malignancies. The use of FNA in the diagnostic workup for breast cancer screening is of crucial importance to the maintenance of high positive predictive rates at surgery. Moreover, regular analysis is important even when mammographic screening is incorporated into the routine work of health services.

---

Resumen El tamizaje mamográfico para cáncer del seno como parte de las rutinas de los servicios de salud fue evaluado para los años 1987–1992, con especial énfasis en el tamizaje repetido en el período 1989–1992. La tasa de cumplimiento por parte de las pacientes en las edades 40–74 años fue de 82.8%. En 1989–92 se halló neoplasia maligna en 2.6/1000 mujeres tamizadas, lo cual significó un índice de predicción de positividad en la cirugía de 87.4% y de eficiencia de 95.9%. Entre las mujeres con edad 45 años el valor de predicción de positividad fue >94%. La biopsia por aspiración con aguja fina demostró cánceres invasores en 84% y alta sospecha de cáncer en un 15% adicional; 60% de las lesiones fueron no palpables. En el tamizaje de primera vez (prevalencia, 1987–1988) el valor de predicción de positividad fue de 86% y el rendimiento de 6.4/1000. En las mujeres con edades 40–44 años se hicieron menos referencias para cirugía (1.6%) pero el valor de predicción de positividad en la cirugía fue apenas de 48.3%, lo cual indica dificultades diagnósticas en las pacientes más jóvenes. El tamaño promedio de los cánceres invasores fue 12 mm; 84% fueron clasificados como pT1 y 25% presentaban invasión ganglionar; 27% de todos los tumores malignos fueron estado II. La aspiración con aguja fina en la evaluación diagnóstica del tamizaje para cáncer mamario es de importancia crucial para el mantenimiento de un alto valor de predicción de positividad en la cirugía y el análisis regular es importante aun cuando el tamizaje mamográfico quede incorporado en el trabajo rutinario de los servicios de salud.

---

Résumé Le dépistage systématique des cancers du sein par mammographie effectuée par les services de santé a été évalué entre 1987–1992, en particulier le dépistage répété pratiqué entre 1989–1992. Le taux de participation des femmes âgées entre 40–74 ans a été de 82.8%. Dans la période 1989–1992, une tumeur maligne a été retrouvée chez 2.6/1000 femmes, la chirurgie permettant de calculer une valeur prédictive positive de 87.4% et une efficacité de 95.9%. Chez les femmes âgées de plus de 45 ans, la valeur prédictive positive a dépassé 94%. La ponction biopsie a fourni la preuve de cancer invasif dans 84% des cas et celle d'une forte suspicion dans 15% des cas, alors que 60% des lésions n'étaient pas palpables. Par comparaison, la valeur prédictive positive pendant la période de dépistage entre 1987–88 a été de 96% pour une prévalence de cancer de 6.4/1000. Chez la femme âgée entre 40–44 ans, très peu de femmes ont été opérées, avec une valeur prédictive positive de 48.3%, ce qui démontre les difficultés de diagnostic chez la femme jeune. La taille médiane de tous les cancers invasifs était de 12 mm: 84% étaient classés comme pT1 et 23% avaient un envahissement lymphatique. On a trouvé un stade II chez 27% des patientes tous cancers confondus. L'utilisation de ponction biopsie est capitale pour le diagnostic de cancer de sein pour maintenir une valeur prédictive positive élevée lors de la chirurgie et une analyse régulière est nécessaire même lorsque le dépistage systématique par mammographie est inclu dans le programme des service de santé.

     

高校离退休老人躯体健康与心理状况的相关性研究

目的：了解离退休老人躯体健康和心理状况的关系。方法：采用ＣＭＩ和ＳＣＬ－９０对２２５名高校离退休老人进行调查,分析两者的关系。结果：既往健康状况、神经系统疾病和躯体化成正相关;强迫与呼吸系统疾病成正相关,与心血管系统疾病成负相关;疲劳感和敌对成负相关,和睡眠饮食障碍成负相关。结论：维持老人心身健康,主要在于防治慢性疾病和神经系统疾病,以及对躯体化障碍和强迫症状的干预     

血液制品丙肝病毒与艾滋病毒检测

目的了解１９９３～１９９５年度临床使用的新鲜冰冻血浆（ＦＦＰ）和血液制品中艾滋病毒（ＨＩＶ）、丙肝病毒（ＨＣＶ）的感染情况。方法用ＥＬＩＳＡ、ＷＢ和ＰＣＲ对１１０批ＦＦＰ、人血丙种球蛋白、人血白蛋白检测了抗ＨＣＶ、ＨＣＶＲＮＡ、抗ＨＩＶ（１＋２）、ＨＩＶ－１ＲＮＡ。结果所有血制品抗ＨＣＶ的平均阳性率为１９．１％,ＨＣＶＲＮＡ为１７．３％;１９９３～１９９４年度ＦＦＰ的抗ＨＣＶＨＣＶＲＮＡ阳性率比１９９５年度高（３０％、２６％和０．５％）;人血丙球的抗ＨＣＶ和ＨＣＶＲＮＡ阳性率明显高于人血白蛋白（３０％、２０％和０．５％）;８９批抗ＨＣＶ阴性血制品ＨＣＶＲＮＡ的阳性率为５．６％,所有血制品的抗ＨＩＶ（１＋２）和ＨＩＶ－１ＲＮＡ均阴性。结论１９９３～１９９５年度临床上所使用的血制品,特别是１９９３～１９９４年度的ＦＦＰ,有传播ＨＣＶ的危险,这与当时没有对所有供血者进行抗ＨＣＶ筛检有关。     

Within-day variability of magnetic fields among electric utility workers: consequences for measurement strategies

Occupational exposure to 50-Hz magnetic fields was surveyed among electric utility workers to investigate (1) components of exposure variability, (2) patterns of autocorrelation between short-term measurements, and (3) imprecision and misclassification due to short-term measurements. Spot measurements every 10 seconds during 81 working days were analyzed for 42 electric utility workers from 10 occupational subgroups and during 8 working days for 4 office workers from the same company. For the 8-hour time-weighted average (TWA) magnetic fields, the variability was partitioned into its components: within workers, between workers, and between groups. For spot measurements of magnetic fields, the within-day variance component also was examined. Autocorrelation functions were determined and numbers of short-term measurements necessary for reliable estimates of 8-hour TWA magnetic fields were assessed. Spot measurements of magnetic fields, as well as 8-hour TWA magnetic fields, were approximately log normally distributed among workers. The mean exposure to magnetic fields was 0.47 microT (n = 81 days) in electric utility workers and 0.12 microT (n = 8 days) in office workers. A large fraction, 76% of the spot measurements total variance, could be attributed to variability within days. For the 8-hour TWA magnetic fields, between-group variability was small and of the same magnitude as between-worker variability. Significant autocorrelations between short-term averages of 7.5, 15, and 30 minutes were present, when taken within periods of 30 minutes. One-hour averages showed no autocorrelation. Simulations showed that, due to high within-day variability and autocorrelation, a limited number of short-term measurements of magnetic fields in electric utility workers are likely to result in imprecise estimates of 8-hour TWA magnetic fields. Measurement strategies relying on short-term (spot) measurements are therefore likely to result in misclassification of exposure and consequently absent or spurious exposure-response relations.