Alzheimer's disease lesions: from morphology to cell biology

Four different approaches to Alzheimer disease changes have been successively applied, and allowed a permanent feed forward-feed back enrichment of knowledge: morphologists described neurofibrillary tangles, senile plaques, amyloid angiopathy; with the help of immunohistochemical and biochemical techniques, they recognised A beta- and tau-associated pathologies; this, in turn, allowed more precise analysis of the lesions, and permitted recognising new ones such as neuropil threads; molecular genetics and molecular biology provided new insights, allowing the discovery of additional pathologic proteins, the relevance of which to physiology and pathology of the nervous system has now to be settled down. The increasingly intricate complex of lesions of Alzheimer syndrome is reviewed. A more comprehensive understanding is urgently needed for initiating efficient therapeutic researches. It will require together continuing a multidisciplinary approach, and a renewal of research in neuropathology.     

Early ultrastructural lesions of diphenylamine-induced renal papillary necrosis in Syrian hamsters

Wegener's granulomatosis (WG) is characterized by necrotizing granulomas and vasculitis that may affect any organ. The upper and lower respiratory tract and kidney usually are affected. WG is diagnosed by determination of anti-neutrophil cytoplasm antibody (ANCA), a highly sensitive and specific test that is particularly important in the early stages to achieve the best prognosis. We describe a case in a 28-year-old man that exemplifies some of the diagnostic features of WG.     

Serum progesterone at the time of human chorionic gonadotrophin does not predict pregnancy in in-vitro fertilization and embryo transfer

Controversy exists as to whether the serum concentration of progesterone on the day of human chorionic gonadotrophin (HCG) administration following ovarian stimulation for in-vitro fertilization (IVF) and embryo transfer can be used to predict the likelihood of success. This retrospective study was undertaken to answer this question by analysing a large population of IVF and embryo transfer cycles (n = 756). In addition to the concentration of progesterone on the day of HCG administration, all variables known to impact on IVF and embryo transfer success (such as patient age), indication for IVF and embryo transfer, number of oocytes retrieved and the number of embryos generated and transferred were examined. There was a significant increase in the number of oocytes retrieved with increasing progesterone concentration at the time of HCG administration. However, there was no correlation of progesterone concentration at HCG administration with pregnancy and implantation rates. It is concluded that previous reports associating a slight elevation of progesterone in gonadotrophin-releasing hormone agonist ovarian stimulation cycles for IVF and embryo transfer may be misleading because of a small sample size or the presence of confounding variables that affect IVF and embryo transfer success.     

Human immunodeficiency virus infection among high-risk seronegative prostitutes in Nairobi

To determine the frequency and duration of antibody-negative human immunodeficiency virus (HIV) infection among heterosexually exposed African women, 56 HIV-seronegative female prostitutes in Nairobi were studied. Polymerase chain reaction (PCR) was used to detect HIV DNA in peripheral blood at enrollment, and women were followed prospectively with serologic testing to determine HIV seroincidence. Six women (11%) were infected with HIV by PCR criteria at enrollment. Seroconversion occurred in 5 of these subjects within 1-12 months, while the sixth remained seronegative when last evaluated at 5 months. The cumulative annual seroconversion rate in the entire cohort was 38%. Using maximum likelihood analysis, the mean interval between HIV infection and seroconversion was estimated to be between 3 and 4 months, similar to that described for homosexual men and blood product recipients in the United States. Prolonged HIV infection in the absence of antibodies appears to be uncommon in this setting.     

Carcinoid tumour complicating inflammatory bowel disease. A study of two cases with review of the literature

Two cases of carcinoid tumour complicating inflammatory bowel disease (IBD) are presented. Both tumours were located in the appendiceal tip. The first case occurred in a man with Crohn's disease (CD), and the second one in a woman suffering from ulcerative colitis (UC). Histochemical and immunohistochemical studies were not allowed on case 1 because the tumour was not still present on serial sections of the appendix. On case 2, tumour cells were not reactive with Grimelius and Masson-Fontana stainings, but were strongly stained with anti-keratin and anti-chromogranin monoclonal antibodies (MAb), and faintly expressed neuron specific enolase (NSE), and Leu-7. Both cases occurred in inflammatory or damaged mucosa which exhibited Paneth cell metaplasia and hyperplasia and areas indefinite for dysplasia. Along with these lesions, hyperplasia of enteroendocrine cells was pointed out in the neighbouring appendiceal and colonic mucosa by means of anti-chromogranin MAb. These data suggest that the association of carcinoid tumour with IBD, albeit rare, is not coincidental and is the result of hyperplastic and dysplastic troubles that may involve enteroendocrine cells as well as such other derivatives of digestive stem cells as columnar cells, goblet cells and Paneth cells.     

Lipid mediators in the rat retina: light exposure and trauma elicit leukotriene B4 release in vitro

Light exposure not only elicits a visual response but may also alter functional and structural characteristics of the retina. Furthermore, light exposure can lead to reversible or irreversible lesions of photoreceptors and pigment epithelium. Previous studies in our laboratory have shown that light liberates arachidonic acid from retinal membrane phospholipids mainly by activating the phospholipase A2. In this study we show that light and trauma elicit the synthesis of leukotriene B4 in the isolated rat retina in vitro. Male albino rats were dark adapted for 36 h, isolated retinae were taken, incubated and exposed a) either to darkness or to 5,000 lux of cool white fluorescent light for 5, 10 or 15 min at 37 degrees C, b) either to darkness or to 5,000 lux of cool white fluorescent light for 15 min at 0 degrees C or c) either to darkness or to 5,000 lux of cool white fluorescent light for 15 min at 37 degrees C with a 5-lipoxygenase inhibitor (zileuton). Eicosanoids were extracted and leukotriene B4 levels were determined by radioimmunoassay. Removal of retinae and incubation in darkness caused a significant rise in leukotriene B4 levels with increasing incubation time. This rise was further augmented significantly after light exposure. The leukotriene B4 levels obtained when incubating the retinae either at 0 degree C or with the lipoxygenase inhibitor zileuton as well as the high specificity of the radioimmunoassay indicate that the light- and trauma-elicited synthesis of leukotriene B4 is mediated by activating the 5-lipoxygenase. Leukotriene B4 may be involved, at least in part, in the pathogenesis of retinal diseases including light damage. Curr. Eye Res. 14: 1001-1008, 1995.     

Core decompression versus nonoperative management for osteonecrosis of the hip

A complete review of the literature disclosed that there were 42 reports of 2025 hips treated by either core decompression (1206 hips) or nonoperative management (819 hips), excluding electrical stimulation, for osteonecrosis of the femoral head. The peer-reviewed published reports included general surveys, prospective studies, and multicenter studies, but excluded case reports. Satisfactory clinical results were reported in 63.5% of hips in 24 studies of core decompression and in 22.7% of hips in 21 studies of nonoperative management. When looking at only precollapse hips, there were 71% versus 34.5% good results, respectively. Recalculation excluding reports by the 4 centers that do the most core decompressions (and report the best results) showed a clinical success rate for core decompression of 53% versus 22.7% for the nonoperatively treated group. Investigators of multiple studies have reported that nonoperative management leads to extremely poor results. Core decompression has been reported to have a notable effect on the natural history and clinical progression in early stages of osteonecrosis of the femoral head. In view of the limitations of this data, further clarification of this effect only can be obtained by large prospective randomized studies.