妊娠性肝内胆汁淤积症：一项地塞米松和熊脱氧胆酸的随机、对照试验

妊娠性肝内胆汁淤积症（ICP）的主要特征是：母体难以忍受的瘙痒症，血清胆汁酸升高（≥10μmol／L）以及胎儿死亡风险的增加。最近，确定了一个与影响胎儿损害相关的界值，即血清胆汁酸≥40μmol／L。在一项双盲、安慰剂对照试验中，作研究了熊脱氧胆酸（UDCA）和地塞米松对瘙痒症、胆汁淤积的生化指标和胎儿并发症发生率的影响。为此，选取了130例患有ICP的妇女，随机分到UDCA组（1g／d，使用3周），地塞米松组（12mg／d使用1周，第2周、第3周使用安慰剂）和安慰剂组（使用3周）进行治疗。在治疗期间和治疗3周后对瘙痒症和胆汁淤积的生化指标进行分析。在分娩时记录胎儿的并发症（自发性早产，新生儿窒息，羊水、胎盘、胎膜的胎粪染色）。意向治疗分析显示仅在UDCA组中，丙氨酸转氨酶（ALT）（P=0．01）和胆红素（P=0．002）明显减少。在血清胆汁酸≥40μmol／L的ICP妇女的亚群分析中发现（n=34）UDCA对瘙痒症（减轻75％）、胆汁酸（下降79％）、ALT（降低80％）和胆红素（降低50％）也有明显效果，但对胎儿并发症发生率无影响。地塞米松并无减轻瘙痒症或降低ALT的作用，在降低胆汁酸和胆红素方面比UDCA效果差。     

First-pass effects of verapamil on the intestinal absorption and liver disposition of fexofenadine in the porcine model.

The aim of this study in pigs was to investigate the local pharmacokinetics of fexofenadine in the intestine and liver by using the pig as a model for drug transport in the entero-hepatobiliary system. A parallel group design included seven pigs (10-12 weeks, 22.2-29.5 kg) in three groups (G1, G2, G3), and a jejunal single-pass perfusion combined with sampling from the bile duct and the portal, hepatic, and superior caval veins was performed. Fexofenadine was perfused through the jejunal segment alone (G1: 120 mg/l, total dose 24 mg) or with two different verapamil doses (G2: 175 mg/l, total dose 35 mg; and G3: 1000 mg/l, total dose 200 mg). The animals were fully anesthetized and monitored throughout the experiment. Fexofenadine had a low liver extraction (E(H); mean +/- S.E.M.), and the given doses of verapamil did not affect the E(H) (0.13 +/- 0.04, 0.16 +/- 0.03, and 0.12 +/- 0.02 for G1, G2, and G3, respectively) or biliary clearance. The E(H) for verapamil and antipyrine agreed well with human in vivo data. Verapamil did not increase the intestinal absorption of fexofenadine, even though the jejunal permeability of fexofenadine, verapamil, and antipyrine showed a tendency to increase in G2. This combined perfusion and hepatobiliary sampling method showed that verapamil did not affect the transport of fexofenadine in the intestine or liver. In this model the E(H) values for both verapamil and antipyrine were similar to the corresponding values in vivo in humans.     

Variation in dietary fibre, beta-glucan, starch, protein, fat and hull content of oats grown in Sweden 1987-1989.

Samples of oat groat from cultivars grown in Sweden during 3 years (1987-1989, 50 samples/year) were investigated. On an average, the kernels contained 15.9% protein, 7.0% fat, 9.7% dietary fibre and 63.2% starch (% of dry matter). The coefficient of variation was highest for fat (26%) and lowest for starch (7%). The thousand kernel weight was on average 34.7 g. The content of dietary fibre and fat was significantly negatively correlated and the starch positively correlated with the thousand kernel weight. The samples contained mean (and range) 9.7% (5.0-13.4) total dietary fibre, 3.5% (2.0-5.0) soluble dietary fibre, and 4.6% (3.5-5.7) beta-glucan. The beta-glucan content was significantly positively correlated with insoluble and total dietary fibre as well as with the fat content, and significantly negatively correlated with starch.     

Muscle membrane polarisation after provocative tests, and after cooling: the normal CMAP changes to be expected.

OBJECTIVE: To know the range of changes of compound muscle action potentials (CMAPs) in the muscles innervated by the ulnar nerve after diverse provocative tests, 14 healthy patients were studied with the same protocol. METHODS: CMAPs were measured at rest, just after a short exercise test (SET), during short 5 and 10c/s repetitive nerve stimulation (RNS) trains, at approximately 32 and approximately 20 degrees C. RESULTS: At 32 degrees C, the SET induced a significant but transient enlargement of the CMAPs (amplitude increased by 8.3%, duration decreased by 9%) that was only partially reproduced by RNS trains, except for a significant shortening of the CMAPs at 10c/s. At 20 degrees C without exercise, CMAPs increased significantly by approximately 30% in amplitude, duration and area, and after the SET the inverse of what has been seen at 32 degrees C was observed (amplitude decreased by 1.7% and duration increased by 9%). RNS at 20 degrees C produced a marked interpatient heterogeneity except for a significant shortening of the CMAPs at 10c/s. In one pure autonomic failure patient, the infusion of norepinephrine induced potentiation of the responses at rest and a decrease in the expected changes after provocative tests. CONCLUSIONS: CMAP amplitude and duration are significantly modified just after the SET at 32 degrees C, at rest at 20 degrees C and after RNS at 10c/s but not at 5c/s. Although providing indirect evidence, these findings indicate that provocative tests make the muscle membrane hyperexcitable by the way of a direct influence on the electrical events and by an indirect local catecholamine spillover.     

A longitudinal population study of climacteric symptoms and their treatment in a random sample of Swedish women.

OBJECTIVES: To assess, first, the prevalence and severity of symptoms associated with the climacteric period and their treatment and, second, the prevalence of exercise, smoking and body weight in a population-based sample of Swedish women. MATERIAL AND METHODS: Prospective, longitudinal cohort study, initiated in 1992, in women aged 46, 50, 54, 58 and 62 years with a follow-up 6 years later. Information was obtained from the same women (n=3816) on both occasions using a postal questionnaire regarding sociodemographic variables, general and reproductive health, the occurrence of climacteric symptoms and their severity, and the use of hormone replacement therapy (HRT). RESULTS: The prevalences of climacteric symptoms were as follows (1992/1998): vasomotor symptoms, 52%/62%; depression/irritability, 57%/65%; sleeping disturbances, 51%/69%; muscle/joint pain, 55%/70%; and loss of libido, 38%/57%. HRT with medium-potency estrogens was currently being used by 34% (1992: 14%), and 12% (1992: 8%) were using low-potency estrogens. The maximum prevalence of HRT (medium-potency estrogens) use was found in the 56-year-old group, at 46% (1992: 25% in the 54-year-old group). Body mass for the whole group had increased from 66.3 to 68.9 kg. Exercise was more frequent in all age groups in 1998 compared to 1992. There was a decrease in current smokers from 32 to 26% between the two periods. Compared with 1992, the women in all five birth cohorts considered themselves to be less healthy and quality of life had decreased for the whole group. CONCLUSIONS: The prevalence of symptoms associated with the climacteric period and the use of HRT had increased markedly in this longitudinal study of the same women followed between 1992 and 1998. During the same period, smoking decreased, while body weight and exercise frequency increased.     

Effective dose from radiopharmaceuticals.

The effective dose, as defined by the International Commission on Radiological Protection (ICRP 1991), provides a possibility of expressing the radiation risk to patients undergoing different radiodiagnostic procedures by means of a single figure. This has been obtained by introducing organ or tissue weighting factors reflecting the radiation sensitivity of the organs. Such weighting factors were first published by the ICRP in publication 26 (1977), and have now been revised in publication 60 (1991). The effective dose for almost all radiopharmaceuticals in clinical use has been recalculated using the new weighting factors from ICRP 60 (1991) and compared with results from former calculations. A slight decrease in the numerical value for the effective dose has been observed, on average 11%. However, this does not correspond to a decrease in the estimated risk from the irradiation, since this has been re-evaluated and found to be higher than earlier believed (NAS 1990; ICRP 1991).     

Repeated quantitative bone scintigraphy in patients with prostatic carcinoma treated with orchiectomy

Bone scintigraphy was performed in 16 men with newly diagnosed prostatic carcinoma before orchiectomy as well as 2 weeks and 2 months after operation. The uptake in the lower thoracic and lumbar vertebrae was registered up to 240 min after injection of ^99mTc-MDP and was then calculated for each patient and vertebra. The relative standard deviation in measured uptake due to measuring technique was estimated to be±7%. In eight patients, who had normal bone scintigraphies before orchiectomy, there were no changes in the uptake values after operation. The remaining eight patients had widespread metastatic involvement prior to treatment. Six of these patients showed a so called flare phenomenon in the abnormal vertebrae which means an initial increase in uptake after operation followed by a decreased uptake in response to therapy. One patient had a continuously increased uptake in all the abnormal vertebrae which correlated well with the clinical progression of the disease, while in another patient both reactions were seen. Thus, repeated quantitative bone scintigraphies using ^99mTc-MDP can be made in a reproducible way and can be a useful tool to follow a patient's response to treatment.     

Induction of release of tumor necrosis factor from human monocytes by staphylococci and staphylococcal peptidoglycans.

The role of cytokines in gram-positive infections is still relatively poorly defined. The purpose of this study was to establish whether or not intact staphylococci and purified peptidoglycans and peptidoglycan components derived from staphylococci are capable of stimulating the release of tumor necrosis factor (TNF) by human monocytes. We show here that intact staphylococci and purified peptidoglycans, isolated from three Staphylococcus epidermidis and three S. aureus strains, were indeed able to induce secretion of TNF by human monocytes in a concentration-dependent fashion. TNF release was detected by both enzyme immunoassay and the L929 fibroblast bioassay. In the enzyme immunoassay, a minimal concentration of peptidoglycan of 1 micrograms/ml was required to detect TNF release by monocytes, whereas in the bioassay a peptidoglycan concentration of 10 micrograms/ml was needed to detect a similar amount of TNF release. Peptidoglycan components such as the stem peptide, tetra- and pentaglycine, and muramyl dipeptide were unable to induce TNF release from human monocytes.