Haematocrit, leukocyte and platelet counts and the severity of the ovarian hyperstimulation syndrome

Previous studies have shown that severe ovarian hyperstimulation syndrome (OHSS) is secondary to circulatory dysfunction due to the simultaneous occurrence of increased vascular permeability and marked arteriolar vasodilation which lead to an intense homeostatic stimulation of the renin-aldosterone and sympathetic nervous systems and antidiuretic hormone (ADH). In the present report, we have investigated the correlation between changes in haematocrit concentration, and white blood cell (WBC) and platelet counts and the severity of OHSS, as assessed by these markers of effective intra- arterial blood volume, in a series of 50 patients. In comparison with recovery values (4-5 weeks after hospital discharge), OHSS patients showed arterial hypotension, tachycardia, oliguria, very high plasma concentrations of renin, aldosterone, norepinephrine and ADH, and increased mean haematocrit values and WBC and platelet counts. The haematocrit concentration values were directly related to the plasma concentrations of vasoactive substances (plasma renin activity, aldosterone, norepinephrine and ADH) during OHSS (P < 0.001). In contrast, no correlation was evident between WBC or platelet counts and neurohormonal measurements during the syndrome. It is concluded that haematocrit, but not WBC or platelet counts, can act as a biological marker of the severity of OHSS as indicated by plasma measurement of volume-dependent endogenous vasoactive substances.      

A simple and objective approach to identifying human round spermatids

Although round spermatids have been studied extensively using staining techniques and electron microscopy, little information is available about their appearance in living conditions. We describe a method of collecting and identifying round spermatids from ejaculates and testicular biopsies. The validity of the selection procedure was confirmed by fluorescence in-situ hybridization. Based on cell size, morphological characteristics of nucleus and cytoplasm, and on the nucleus/cytoplasm ratio, we harvested a population of cells that was 84% haploid. This procedure can be applied to select spermatids for clinical or research purposes.      

A simplified serum-free method for preparation and cultivation of human granulosa-luteal cells

A simplified method for the preparation and long-term cultivation of granulosa-luteal cells in serum-free medium is described. The cells were harvested from women undergoing in-vitro fertilization, enriched by sedimentation and dissociated by enzymatic treatment. We demonstrated, by introducing a synthetic serum replacement (SSR2), that these primary cell cultures cultivated in monolayers on an extracellular matrix may be used in experiments exceeding 7 days with low cell loss and cell death. No adverse effect on progesterone production was found. There was a high diversity in progesterone production between cells from individual patients. After several days in culture, the cells were challenged with human chorionic gonadotrophin which revived the rapidly decreasing progesterone production. We were unable to demonstrate an increase in cell number after 7 days of cultivation when the cells were grown in medium supplemented with either serum or SSR2. The mitogens epidermal growth factor and basic fibroblast growth factor had no influence on proliferation. We also found that the present method prevents leukocyte contamination in the granulosa-luteal cell cultures. Compared with the common method based on the enrichment of granulosa-luteal cells on a density gradient (Ficoll/Percoll), this method saves time, labour and expense, in addition to augmenting purity.      

Unprofessional behavior in medical school is associated with subsequent disciplinary action by a state medical board.

PURPOSE: To determine if medical students who demonstrate unprofessional behavior in medical school are more likely to have subsequent state board disciplinary action. METHOD: A case-control study was conducted of all University of California, San Francisco, School of Medicine graduates disciplined by the Medical Board of California from 1990-2000 (68). Control graduates (196) were matched by medical school graduation year and specialty choice. Predictor variables were male gender, undergraduate grade point average, Medical College Admission Test scores, medical school grades, National Board of Medical Examiner Part 1 scores, and negative excerpts describing unprofessional behavior from course evaluation forms, dean's letter of recommendation for residencies, and administrative correspondence. Negative excerpts were scored for severity (Good/Trace versus Concern/Problem/Extreme). The outcome variable was state board disciplinary action. RESULTS: The alumni graduated between 1943 and 1989. Ninety-five percent of the disciplinary actions were for deficiencies in professionalism. The prevalence of Concern/Problem/Extreme excerpts in the cases was 38% and 19% in controls. Logistic regression analysis showed that disciplined physicians were more likely to have Concern/Problem/Extreme excerpts in their medical school file (odds ratio, 2.15; 95% confidence interval, 1.15-4.02; p =.02). The remaining variables were not associated with disciplinary action. CONCLUSION: Problematic behavior in medical school is associated with subsequent disciplinary action by a state medical board. Professionalism is an essential competency that must be demonstrated for a student to graduate from medical school.     

HPRT-APRT-deficient mice are not a model for lesch-nyhan syndrome

Complete hypoxanthine-guanine phosphoribosyl-transferase (HPRT) deficiency in humans results in the Lesch-Nyhan syndrome which is characterized, among other features, by compulsive self-injurious behavior. HPRT-deficient mice generated using mouse embryonic stem cells exhibit none of the behavioral symptoms associated with the Lesch- Nyhan syndrome. Administration of drugs that inhibit adenine phosphoribosyltransferase (APRT) in HPRT-deficient mice has produced the suggestion that deficiency of APRT in combination with HPRT- deficiency in mice may lead to self-mutilation behavior [C.L. Wu and D.W. Melton (1993) Nature Genet. 3, 235-240]. To test this proposition, we bred HPRT-APRT-deficient mice. Although the doubly-deficient mice excrete adenine and its highly insoluble derivative, 2,8- dihydroxyadenine, which are also associated with human APRT deficiency, additional abnormalities or any self-injurious behavior were not detected. Thus, APRT-HPRT-deficient mice, which are devoid of any purine salvage pathways, show no novel phenotype and are not a model for the behavioral abnormalities associated with the Lesch-Nyhan syndrome as previously suggested.      

Evaluation of the performance of hysterosalpingo contrast sonography in 500 consecutive, unselected, infertile women

The performance of hysterosalpingo contrast sonography (Hy Co Sy) as a first-line, outpatient investigation of tubal patency was examined in 500 consecutive, infertile women, at one centre. Hy Co Sy was completed in 463 (92.6%) cases, using a galactose microbubble contrast agent (Echovist-200) and transvaginal sonography. Initial plain scanning identified adnexal pathology in 198 women (39.6%). Examination with Echovist was attempted for 905 tubes and only 67 (7.4%) were not assessable; after the first 100 women this decreased to 35 tubes (4.8%). A sonographic appearance compatible with blocked tubes was found on 118 (14.1%) occasions but it was also possible to identify variations in the appearance/filling/spilling patterns of individual tubes which increased the number assessed as abnormal to 193 (23.0%). Comparison with laparoscopy and dye chromopertubation findings from the past three years was possible for 185 (37%) women, representing 282 tubes, which gave Hy Co Sy an overall concordance rate of 85.8%, sensitivity of 90.4%, specificity of 70.3%, positive predictive value of 91.2% and negative predictive value of 68.2%. Some 51.0% of women described only mild discomfort and there were no significant postprocedure complications. Hy Co Sy appears to be an acceptable first- line screen and may select out women in whom more invasive investigations are likely to reveal pathology.      

Linkage analysis of candidate regions for coeliac disease genes

A strong HLA association is seen in coeliac disease [specifically to the DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account for the increased risk seen in relatives of affected cases. One or more genes at HLA-unlinked loci also predispose to coeliac disease and are probably stronger determinants of disease susceptibility than HLA. A recent study has proposed a number of candidate regions on chromosomes 6p23 (distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3, 19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked susceptibility gene. We have examined these regions in 28 coeliac disease families by linkage analysis. There was excess sharing of chromosome 6p markers, but no support for a predisposition locus telomeric to HLA. No significant evidence in favour of linkage to coeliac disease was obtained for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or 22cen. There was, however, excess sharing close to D15S642. The maximum non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac disease to chromosome 15q26 is not strong, the well established association between coeliac disease and insulin dependent diabetes mellitus, together with the mapping of an IDDM susceptibility locus (IDDM3) to chromosome 15q26, provide indirect support for this as a candidate locus conferring susceptibility to coeliac disease in some families.      

Duchenne肌营养不良症的分子遗传学

分子生物学,特别是重组DNA技术的出现,使我们对人类遗传病有了更深入的认识。这一领域的进展是极其迅速的,其中最明显的例子就是对X-连锁遗传病Duchenne肌营养不良症(DMD)的研究。用基因组探针检测携带者和产前诊断已经证明XJ1.1和pERT基因组探针,及侧翼探针如C7、754和99.6对于发现DMD携带者和产前诊断具有不可估量的价值。受累患儿血清CK水平是正常儿童的100～200倍,但用于检测携带者却不可靠,因为有1/3的肯定携带者的CK水平在正常范围。而应用RFLP进行的连锁分析具有很高的可信