The retinal nerve fiber layer in normal and glaucomatous eyes. II. Correlations

The retinal nerve fiber layer is different in normal and glaucomatous eyes. We correlated semi-quantitative data of the retinal nerve fiber layer of 398 eyes with chronic primary open-angle glaucoma and of 234 normal eyes with the intra- and parapapillary morphometric signs and with the perimetric indices. The three parameters "sequence of the fundus sectors concerning the best visibility of the retinal nerve fiber bundles", "visibility of the nerve fiber bundles", and "localized defects" were significantly (p less than 0.001) correlated to 1) area of the neuroretinal rim as a whole and in four different optic disc sectors, 2) neuroretinal rim width determined every 30 degrees, 3) optic cup area, diameters and form, 4) horizontal and vertical cup/disc ratios and the quotient of the horizontal to vertical cup/disc ratio, 5) area and width of zone "Alpha", zone "Beta", and the total parapapillary chorio-retinal atrophy, 6) diameter of the retinal vessels, 7) grade of a "tesselated fundus", and 8) the visual field loss. If only the inferior temporal and the superior temporal sectors were considered, the retinal nerve fiber bundles were less visible in that sector with the largest notch in the neuroretinal rim, the smaller neuroretinal rim area and width, the thinner retinal vessels, and the larger zone "Alpha", zone "Beta", and total parapapillary chorio-retinal atrophy. The glaucomatous changes in the retinal nerve fiber layer are correlated in time and location with the intra- and parapapillary and the perimetric alterations. Evaluation of the retinal nerve fiber layer is a useful method to detect a glaucomatous optic nerve damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction.

Connective tissue growth factor (CTGF) is reported to be a target gene of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) in vitro. Its physiological role in angiogenesis and skeletogenesis during mouse development has been described recently. Here, we have mapped expression of CTGF mRNA during mouse heart development, postnatal adult life, and after experimental myocardial infarction. Furthermore, we investigated the relationship between CTGF and the BMP/TGFbeta signaling pathway in particular during heart development in mutant mice. Postnatally, CTGF expression in the heart became restricted to the atrium. Strikingly, 1 week after myocardial infarction, when myocytes have disappeared from the infarct zone, CTGF and TGFbeta expression as well as activated forms of TGFbeta but not BMP, Smad effector proteins are colocalized exclusively in the fibroblasts of the scar tissue, suggesting possible cooperation between CTGF and TGFbeta during the pathological fibrotic response.     

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.     

Serological markers to differentiate between ulcerative colitis and Crohn's disease.

AIM--To assess prospectively the value of three serological tests for differentiating between ulcerative colitis and Crohn's disease, used either alone or combined. METHODS--Coded serum samples from 63 patients with ulcerative colitis and 67 patients with Crohn's disease were analysed. Detection assays for the presence of perinuclear antineutrophil cytoplasmic antibodies (pANCA), serum agglutinating antibodies to anaerobic coccoid rods, and specific IgG antibodies against a Kd-45/48 immunological crossreactive mycobacterial antigen complex (ImCrAC) were studied. Sensitivity, specificity, pre- and post-test probabilities, likelihood ratios, and predictive values of each of these serological tests were determined. RESULTS--The sensitivity and specificity of the pANCA test for the diagnosis of ulcerative colitis were 61 and 79%, respectively. The serum agglutination test for anaerobic coccoid rods had a sensitivity of 42% and a specificity of 89% for a diagnosis of Crohn's disease. The sensitivity of specific IgG antibodies against Kd-45/48 ImCrAC in diagnosing Crohn's disease was 70% and specificity 60%. Although 100% specificity was achieved by combining all three tests in a small group of patients with Crohn's disease (n = 20), combining two or more tests had no additive clinical value. No correlation was found between the presence of any one of these antibodies and disease activity, duration, or localisation of disease. Surgery or medical treatment did not influence the presence of antibodies or the antibody titre. CONCLUSIONS--The value of these tests in the differential diagnosis between ulcerative colitis and Crohn's disease is limited, but the high predictive values and specificities of different tests for both diseases suggest that these tests may be of help in studying disease heterogeneity and in defining different subgroups of patients with different pathogenesis.     

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.     

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.     

Neutrophil cytoplasmic antibodies (p-ANCA) in ulcerative colitis.

AIMS--To study ulcerative colitis associated neutrophil cytoplasmic antibodies (p-ANCA) in respect of class and subclass distribution, antigen specificity, and (sub)cellular localisation of the antigen(s) to which these antibodies are directed. METHODS--p-ANCA positivity was determined using the standard indirect immunofluorescence test (IIFT). The immunoglobulin (Ig) subclass distribution of p-ANCA was investigated using monoclonal antibodies directed against IgG1, IgG2, IgG3, and IgG4. Intracellular antigen localisation studies were performed on (fractionated) neutrophils using antigen-specific antibodies. RESULTS--In contrast to vasculitis associated ANCA, ulcerative colitis p-ANCA are mainly of IgG1 and IgG3 subclass and lack IgG4. Ulcerative colitis p-ANCA are myeloid specific. IIFT data indicate that the related antigen(s) seem(s) to be located not in the cytosol, but in the granules (most likely the azurophil granules) of the neutrophil. CONCLUSIONS--p-ANCA in ulcerative colitis have a different immunoglobulin subclass distribution than the ANCA of systemic necrotising vasculitis and necrotising and crescentic glomerulonephritis. This may point to differences in immune regulation between these diseases. Both cathepsin G and lactoferrin are recognised by a subpopulation of ulcerative colitis p-ANCA. In our series, eight out of 36 (22%) of ulcerative colitis associated p-ANCA react with lactoferrin and seven (19.5%) other sera with cathepsin G. None of them recognised both antigens. The main target antigen(s) of ulcerative colitis p-ANCA still remain(s) to be identified.     

Incipient ovarian failure and premature ovarian failure show the same immunological profile

PROBLEM: Incipient ovarian failure (IOF) is characterized by regular menstrual cycles, infertility and a raised early-follicular FSH in women under 40. IOF might be a precursor or a mitigated form of premature ovarian failure (POF). Disturbances in the immune system may play a role in ovarian failure. METHOD OF STUDY: Autoantibodies and lymphocyte subsets were determined in 63 POF patients, 50 IOF patients, and 27 controls. RESULTS: The prevalence of autoantibodies did not differ between the groups. There was a statistically significant difference in lymphocyte subsets between the control group and the POF group, with the IOF group taking an intermediate position. We found a decrease in percentage of T-suppressor cells with a rise in T-helper/T-suppressor cell ratio, a decrease in natural killer cells, and an increase in B lymphocytes and HLA-DR positive T cells. CONCLUSIONS: These data support the concept that IOF is a mitigated form of POF. The question remains whether these changes are the cause or the consequence of the ovarian failure.