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。     

Left main coronary artery stenosis no longer a risk factor for early and late death after coronary artery bypass surgery--an experience covering three decades.

OBJECTIVE: To analyse early and late mortality after coronary artery bypass grafting (CABG) in patients with and without left main coronary artery (LMCA) stenosis during the 30-year period 1970-1999. METHODS: A total of 1888 of 10,647 patients (18%) who underwent a first isolated CABG at the Karolinska Hospital in Stockholm, Sweden, during 1970-1999 had significant left main coronary artery stenosis. The Swedish National Cause of Death Register was used to determine mortality up to five years after the operation. RESULTS: The proportion of patients with LMCA stenosis of all CABG patients increased from 7% during the 1970s to 26% in 1999. During 1970-1984 early mortality was 5.8% in patients with LMCA stenosis compared with 1.5% in patients without LMCA stenosis (odds ratio (OR) 3.7 (95% confidence interval (CI) 1.8-7.6)). The corresponding rates during 1995-1999 were 2.0% versus 2.2% (OR 0.8 (95% CI 0.5-1.5)), respectively. The increased risk of early death in patients with LMCA stenosis was neutralised in males during 1985-1994 and in females during 1995-1999. Five-year survival in males was 88% after operations performed during 1994-1999 compared with 82% after CABG performed during 1970-1984. Five-year mortality, exclusive of early deaths, during 1970-1984 was higher in patients with LMCA stenosis (12.8%) than in those without (8.4%) (relative risk 1.7 (95% CI 1.1-2.5)). An increased risk of late mortality in patients with LMCA stenosis was neutralised in males during 1985-1994 and in females during 1995-1999. CONCLUSIONS: During 1970-1999 there was a decrease of early and five-year mortality in patients with LMCA stenosis after CABG despite increase of patient age and risk factors. There were gender differences so that the risk of death in patients with compared with in those without LMCA stenosis was neutralised in males during 1985-1994 and in females during 1994-1999. The continuous decline of mortality during three decades most likely reflects improvement of the peri- and postoperative management of patients undergoing CABG during this period.     

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.     

Infantile autism—fragile X: Molecular findings support genetic heterogeneity

Twenty-two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR-1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR-1 region in infantile autists negative for fragile X expression. © 1992 Wiley-Liss, Inc.     

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.     

Characterization of in vitro metabolites of the aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole by liquid chromatography-mass spectrometry and NMR.

The tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) exhibits the highest aryl hydrocarbon receptor (AhR) binding affinity reported so far. In different cells, in vitro, both extracts of UV-irradiated tryptophan and the synthesized pure compound FICZ induce a rapid and transient expression of AhR-regulated genes. The transient induction suggests that the biotransformation gene battery induced by AhR activation takes part in a metabolic degradation of the ligand, whereby a low steady-state level is regained. The down-regulation of AhR-regulated gene expression was previously shown to be dependent on cytochrome P450 1A1 (CYP1A1). Metabolism of FICZ generates five major metabolites, which appeared as three peaks (M1-M3) in the high performance liquid chromatography. The aim of the present study was to use rat liver S9 from Aroclor-pretreated rats to produce large enough quantities of FICZ metabolites for structure characterization and to determine their product precursor relationship. NMR analysis of large combined fractions of the metabolites indicated that M3 and M2 contained 2 isomers, respectively. By means of liquid chromatography-mass spectrometry (negative ion electrospray mode) and NMR spectroscopy (by (1)H-NMR, correlation spectroscopy, and nuclear Overhauser effect spectroscopy techniques) five metabolites of FICZ were identified, and their structures were elucidated. The molecular weights of the two M3 isomers were 300 and both M2 and M1 compounds demonstrated molecular weights of 316, corresponding to addition of one (M3) and of two oxygen (M2 and M1), respectively. The structures were assigned as 2- and 8-hydroxy (M3), 2,10- and 4,8-dihydroxy (M2) and 2,8-dihydroxy derivatives of indolo[3,2-b]carbazole-6-carboxaldehyde (6-formylindolo[3,2-b]carbazole).     

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.