A controlled family history study of bulimia

Using the family history method, we assessed the morbid risk for psychiatric disorders in the first-degree relatives of 69 probands with bulimia, 24 probands with major depression, and 28 nonpsychiatric control probands. The morbid risk for major affective disorder among the first-degree relatives of the bulimic probands was 32%, significantly greater than that found in the nonpsychiatric control probands. The rate of familial major affective disorder was significantly greater in bulimic probands who had a history of major affective disorder themselves than in bulimic probands without such a history - but the latter group, in turn, displayed significantly higher rates than the nonpsychiatric control probands. Eating disorders were slightly, but not significantly, more prevalent in the families of bulimic probands than nonpsychiatric control probands. We present two alternative hypotheses which might explain these findings.     

Improvement in histological diagnosis of primary hyperparathyroidism with a monoclonal antiparathyroid antibody

The monoclonal antiparathyroid antibody E11 reacts with a glycoprotein of high molecular weight, which acts as a calcium receptor on the surface of parathyroid cells and mediates calcium regulation of parathyroid hormone (PTH) release. Reduced expression of the calcium receptor has been implicated as a cause of the defect in PTH regulation in the pathological parathyroid parenchyma of patients with hyperparathyroidism (HPT). The present study evaluated the efficacy of immunostainings with the E11 antibody in comparison with routine histopathological methods including staining by the oil red O technique for histological discrimination between normal and pathological parathyroid glands. Parathyroid tissue from euparathyroid individuals invariably presented intense and homogeneous surface staining, with the antibody on virtually all chief cells, while the pathological glands from patients with HPT consistently showed heterogeneous and reduced immunostaining. Even minimally enlarged pathological glands from individuals with mild hypercalcemia and the normal-sized glands associated with adenomas displayed parathyroid chief cells with reduced antibody reactivity. The monoclonal antiparathyroid antibody should constitute a useful tool in parathyroid histopathology not only by its ability to identify the parathyroid tissue, but also by directly demonstrating the functionally normal and abnormal cells within the parathyroid tissue.     

Serum lipids and lipoproteins in relation to endogenous and exogenous female sex steroids and age. The Women's Health in the Lund Area (WHILA) study

BACKGROUND: Different studies have presented conflicting results concerning the effect of menopause on lipid levels. AIMS: To describe the serum lipid profile and the prevalence of hyperlipidemia in women aged 50-60 and the perceived relation to endogenous and exogenous hormones and age. METHODS: Out of a total population of 10,766 women aged 50-59 years, 6908 (64%) participated in a health assessment program, including a lipid profile evaluation. The women were grouped according to hormonal status into pre-menopausal (PM), post-menopausal without hormone replacement therapy (PM0) (HRT) and post-menopausal with hormone replacement therapy (PMT). Age groups used were 50-54, 55-59 and >60 years. RESULTS: Serum cholesterol and triglycerides increased significantly by age in PM0 (P < 0.0001) and triglycerides also in PMT (P < 0.0001). Serum high-density lipoprotein cholesterol (HDL) levels decreased significantly by age in PMT (P = 0.002) and low-density lipoprotein cholesterol (LDL) increased in PM0 (P < 0.0001) and PMT (P = 0.007). The co-prevalence of levels of cholesterol >7 and triglycerides >2 mmol/l decreased by age in PM, but increased by age in PM0 and PMT. The prevalence of high-risk lipid levels and the prevalence of coexisting additional two metabolic risk factors were higher in the PM0 compared to the PMT group. The prevalence of serum triglycerides >1.5 and serum cholesterol >5 mmol/l were increasing by age in each of the hormonal groups. CONCLUSIONS: These data suggest that loss of endogenous sex steroids contribute substantially to an increased atherogenic lipid profile. Hormone replacement therapy may partly reverse these differences.     

Combined hormone therapy in postmenopausal women with features of metabolic syndrome. Results from a population-based study of Swedish women: Women's Health in the Lund Area study

OBJECTIVE: To delineate the influence of hormone therapy (HT) on features of metabolic syndrome with special reference to the composition and mode of administration of three specific HT regimens, all containing estradiol (E2) + norethisterone. DESIGN: The Women's Health in the Lund Area project screened all women (n = 10,766), born between 1935 and 1945. Complete data were obtained from 6,917 women. Those at or above defined cutoff limits were considered positively screened (n = 3,593) for metabolic syndrome. All of them were invited to undergo an oral glucose tolerance test; 2,923 women accepted. After excluding 200 women with impaired fasting glucose, 2,723 women were included in the present analysis. Serum lipids were determined by conventional standard methods at the department of clinical chemistry of Lund University Hospital. RESULTS: According to World Health Organization criteria, 2,123 women had normal glucose tolerance and 600 women had impaired glucose tolerance (IGT). IGT was less common (P = 0.001) among users of a transdermal patch [CYC-TRANS; E2 50 microg + norethisterone acetate (NETA) 250microg] compared with the two-combined oral regimen [CON-O (continuous oral E2 2 mg + NETA 1 mg) + CYC-O (sequential oral E2 2 mg + NETA 1 mg)]. Furthermore, IGT was more common among CON-O users when compared with either the CYC-O + CYC-TRANS group (P = 0.002) or the CYC-TRANS only group (P = 0.001). There were no significant differences between CYC-O versus CYC-TRANS or CON-O. Serum levels of total cholesterol were higher in the CYC-TRANS group than in the combined CON-O + CYC-O group (P < 0.05); they also were higher (P = 0.05) when comparing the CYC-O + CYC-TRANS versus CON-O as well as higher in CYC-TRANS versus CON-O (P < 0.05). Serum high-density lipoprotein cholesterol levels were higher in the CYC-O (P = 0.001), CYC-TRANS (P < 0.05), and the CYC-O + CYC-TRANS (P = 0.001) groups when compared with the CON-O users. There were no differences in the mean age, blood pressure (systolic and diastolic), body mass index, waste-hip ratio, or the rate of cigarette and alcohol consumption between the different hormone regimens. CONCLUSION: The risk of having a pathological glucose load was lower in transdermal versus oral users of HT. Transdermal HT could be regarded as first-line treatment in women at risk of developing diabetes.     

The University of Missouri-Kansas City School of Medicine: thirty-five years of experience with a nontraditional approach to medical education.

The University of Missouri-Kansas City (UMKC) School of Medicine is a public medical school that opened in 1971 in response to a need to train more physicians in Missouri. As a six-year, integrated, combined-degree program leading to the baccalaureate and medical degrees, the school offers an innovative, nontraditional approach to medical education. In the past 35 years, UMKC has graduated over 2,400 physicians who are successful according to outcomes measures used at other medical schools. With recent interest in reforming medical education to prepare physicians for a changing world, a review of alternative models may be especially instructive.UMKC's academic plan offers a blueprint for the curriculum plan and governance of the school. The plan is built on four hallmarks: (1) a combined baccalaureate/MD program, (2) early exposure to clinical medicine, (3) small-group learning through the docent system, and (4) a continuing ambulatory care clinic experience for four years.This article catalogs the results of this plan including student, faculty, and graduates' perceptions of and satisfaction with the school's educational approach, students' achievement on licensing examinations and in the residency match, graduates' performance in residency programs, and their subsequent career patterns. The authors also discuss lessons learned and adjustments made in response to local needs in the context of a changing environment in education, health care, and health care delivery while continually improving the school's nontraditional approach to medical education. These include changes in basic and clinical science instruction, student assessment, faculty development, and funding and governance.     

Sensitivity of a modified version of the ARCHITECT Anti-HCV test in detecting samples with immunoblot-confirmed, low-level antibody to hepatitis C virus.

BACKGROUND AND OBJECTIVES: Compliance with current regulations regarding the prevention of hepatitis C virus (HCV) transmission in the blood transfusion setting requires the use of sensitive assays for HCV antibody (anti-HCV) detection, which should, ideally, identify any donor having had prior contact with the virus. Therefore, low-level anti-HCV positive blood units should be detected by the screening assays, even those reflecting a past and resolved infection. To assess the sensitivity of two versions of an automated chemiluminescent microparticle immunoassay (CMIA) for anti-HCV screening (ARCHITECT Anti-HCV), 113 single serum samples containing low levels of anti-HCV, assessed by two immunoblot tests, were selected from 3686 samples received for confirmation of HCV infection by a reference laboratory over a 2-year period. MATERIALS AND METHODS: The panel included 17 samples with HCV RNA detected by the polymerase chain reaction (PCR) and 96 PCR negative samples with either positive or indeterminate (anti-Core and anti-NS3 alone) results by immunoblot. RESULTS: All but 13 specimens (100/113, 88.5%) were detected by the current version of the ARCHITECT Anti-HCV assay and 10 additional samples (110/113, 97.3%) tested positive in a modified version of the test. CONCLUSION: The results showed that the modification introduced in the ARCHITECT Anti-HCV assay achieves a significant sensitivity improvement including samples with low-level anti-HCV which are either PCR positive or negative.     

Optimal heparin surface concentration and antithrombin binding capacity as evaluated with human non-anticoagulated blood in vitro

Contact between blood and a biomaterial surface takes place in many applications and is known to activate the coagulation and complement systems. Heparin surface coatings have been shown to reduce blood activation upon contact with artificial surfaces. To establish the optimal heparin surface concentration, blood was incubated in a tubing loop model at 37 degrees C. The tubing was coated with different surface concentrations of heparin and rotated at three different velocities. We demonstrate that the blood compatibility of a surface with regard to coagulation, complement, and platelet activation can be improved by increasing the heparin surface concentration in the 6-12 pmol antithrombin/cm2 concentration interval. The binding of factor H is not influenced by the increased heparin surface concentration, suggesting that this factor is not the primary regulator of complement on heparin surfaces. In addition, the heparin coating has no effect on the complement activation that occurs on gas surfaces in extracorporeal circuits.     

c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression

c-Myc promotes cell growth and transformation by ill-defined mechanisms. c-myc(-/-) mice die by embryonic day 10.5 (E10.5) with defects in growth and in cardiac and neural development. Here we report that the lethality of c-myc(-/-) embryos is also associated with profound defects in vasculogenesis and primitive erythropoiesis. Furthermore, c-myc(-/-) embryonic stem (ES) and yolk sac cells are compromised in their differentiative and growth potential. These defects are intrinsic to c-Myc, and are in part associated with a requirement for c-Myc for the expression of vascular endothelial growth factor (VEGF), as VEGF can partially rescue these defects. However, c-Myc is also required for the proper expression of other angiogenic factors in ES and yolk sac cells, including angiopoietin-2, and the angiogenic inhibitors thrombospondin-1 and angiopoietin-1. Finally, c-myc(-/-) ES cells are dramatically impaired in their ability to form tumors in immune-compromised mice, and the small tumors that sometimes develop are poorly vascularized. Therefore, c-Myc function is also necessary for the angiogenic switch that is indispensable for the progression and metastasis of tumors. These findings support the model wherein c-Myc promotes cell growth and transformation, as well as vascular and hematopoietic development, by functioning as a master regulator of angiogenic factors.     

Asynchronous GABA release generates long-lasting inhibition at a hippocampal interneuron-principal neuron synapse

Hippocampal GABAergic interneurons show diverse molecular and morphological properties. The functional significance of this diversity for information processing is poorly understood. Here we show that cholecystokinin (CCK)-expressing interneurons in rat dentate gyrus release GABA in a highly asynchronous manner, in contrast to parvalbumin (PV) interneurons. With a gamma-frequency burst of ten action potentials, the ratio of asynchronous to synchronous release is 3:1 in CCK interneurons but is 1:5 in parvalbumin interneurons. N-type channels trigger synchronous and asynchronous release in CCK interneuron synapses, whereas P/Q-type Ca(2+) channels mediate release at PV interneuron synapses. Effects of Ca(2+) chelators suggest that both a long-lasting presynaptic Ca(2+) transient and a large distance between Ca(2+) source and sensor of exocytosis contribute to the higher ratio of asynchronous to synchronous release in CCK interneuron synapses. Asynchronous release occurs at physiological temperature and with behaviorally relevant stimulation patterns, thus generating long-lasting inhibition in the brain.     

Presynaptic short-term depression is maintained during regulation of transmitter release at a GABAergic synapse in rat hippocampus

To examine possible interactions between fast depression and modulation of inhibitory synaptic transmission in the hippocampus, we recorded from pairs of synaptically connected basket cells (BCs) and granule cells (GCs) in the dentate gyrus of rat brain slices at 34 °C. Multiple-pulse depression (MPD) was examined in trains of 5 or 10 inhibitory postsynaptic currents (IPSCs) evoked at frequencies of 10–00 Hz under several conditions that inhibit transmitter release: block of voltage-dependent Ca²⁺ channels by Cd²⁺ (10 μ m ), activation of γ-amino-butyric acid type B receptors (GABA_BRs) by baclofen (10 μ m ) and activation of muscarinic acetylcholine receptors (mAchRs) by carbachol (2 μ m ). All manipulations led to a substantial inhibition of synaptic transmission, reducing the amplitude of the first IPSC in the train (IPSC₁) by 72 %, 61 % and 29 %, respectively. However, MPD was largely preserved under these conditions (0.34 in control versus 0.31, 0.50 and 0.47 in the respective conditions at 50 Hz). Similarly, a theta burst stimulation (TBS) protocol reduced IPSC₁ by 54 %, but left MPD unchanged (0.40 in control and 0.39 during TBS). Analysis of both fractions of transmission failures and coefficients of variation (CV) of IPSC peak amplitudes suggested that MPD had a presynaptic expression site, independent of release probability. In conclusion, different types of presynaptic modulation of inhibitory synaptic transmission converge on a reduction of synaptic strength, while short-term dynamics are largely unchanged.