Differential preservation of cognitive functions in geriatric patients with lifelong chronic schizophrenia: less impairment in reading compared with other skill areas.

BACKGROUND: Our study examined the differential performance of cognitive skills in geriatric, cognitively impaired schizophrenic patients (n = 165) with a lengthy course of institutional stay and a poor overall functional outcome. Their relative deficits were compared with a sample of healthy elderly individuals. METHODS: Schizophrenic patients were matched one-to-one with healthy individuals of the same age and education and compared on a number of measures of cognitive functioning. The schizophrenic patients' old-learning performance was also compared with their educational level only. RESULTS: Mini-Mental State Examination (Folstein et al 1975) scores of the patients were in the moderately demented range (M = 20.36), and these patients underperformed healthy control subjects by more than 1 to slightly less than 3 standard deviations on measures of memory, praxis, and verbal skills. Wide Range Achievement Test-Revised word-recognition reading scores were found to be at the 10th-grade level, although the patients on average had completed 11 years of formal education. CONCLUSIONS: These results suggest that even in schizophrenic patients with significant cognitive impairment, reading scores are relatively consistent with educational attainment. These data indicate that poor performance on measures of cognitive functioning in this population does not necessarily occur on measures of old learning.     

海马区星形胶质细胞培养上清液体外诱导人脂肪基质细胞向神经元样细胞的分化

目的:观察海马区星形胶质细胞培养上清液能否在体外诱导人脂肪基质细胞向神经元样细胞分化。方法:实验于2004-10/2005-06在华北煤炭医学院中心实验室完成。在无菌条件下从Wistar乳鼠分离出海马组织,从分离的海马组织中获得星形胶质细胞,并收集其培养上清液。取外科手术获得的人腹部皮下脂肪组织进行人脂肪基质细胞的原代培养。30例患者均知情同意。取第3代人脂肪基质细胞接种到培养孔中,预先放置无菌盖玻片的24孔培养板,制备细胞爬片或者接种到培养瓶中,细胞生长达50%～60%融合时,去除培养液,换为海马区星形胶质细胞培养上清诱导液进行诱导,对照组培养液为无血清培养基。倒置相差显微镜下连续观察细胞生长情况和形态变化,应用免疫细胞化学、鉴定神经前体细胞的特异性标志神经巢蛋白、神经细胞的特异性标志神经元特异性烯醇化酶、微管联合蛋白2和神经胶质细胞的特异性标志胶质纤维酸性蛋白的表达。结果:①诱导培养第3天,部分人脂肪基质细胞开始变形,从原先的细长梭状细胞变成神经元样细胞,可见细胞伸出突起,多为双极或多极细胞。②刚分离接种的人脂肪基质细胞镜下呈圆形,悬浮状态,接种后24h内贴壁,并开始伸展,多呈梭形。1周后细胞融合成单层,排列出现方向性,但有少量圆形及卵圆形细胞混杂生长。③第4,5代人脂肪基质细胞在诱导48h后形态即开始发生变化,扁平的胞体较预诱导后逐渐回缩,向外伸出突起,72h后扁平的胞浆向胞核收缩,突起继续延长,以后随时间进展,具有典型神经细胞形态特点的细胞数量逐渐增多,形成双极或多极细胞。④免疫细胞化学检测人脂肪基质细胞诱导5d后发现有(10.5±3.7)%神经巢蛋白、(38.4±5.2)%胶质纤维酸性蛋白、(15.7±2.3)%神经元特异性烯醇化酶表达,未见微管联合蛋白2的表达。结论:海马区星形胶质细胞培养上清液可以在体外诱导人脂肪基质细胞向神经元样细胞方向分化。     

Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden

Patients with inflammatory bowel disease have an increased frequency of thromboembolism, and microvascular thrombosis has been proposed as a contributory pathogenic factor. The mechanism of enhanced procoagulant activity is not understood. We examined the clinical setting of thromboembolic events in 52 patients with Crohn's disease or ulcerative colitis, and assessed the procoagulant laboratory profile, including Factor V Leiden, in a subset of 20 patients to identify procoagulant risk factors. Patients who developed thrombosis tended to be young; 60% of thrombotic events occurred in patients under 50 years. Multiple thromboembolic episodes occurred in 13% and unusual sites of thrombosis (e.g. intracardiac, cerebral, inominate veins) in 11%. No risk factor was identifiable in 52% of cases and two-thirds of thromboses occurred in an out-patient setting. The mortality rate was 8%. Evidence for inflammatory disease activity was found in only 45% of patients with ulcerative colitis at the time of the thromboembolic event, in contrast to 89% of those with Crohn's disease. Assays for specific coagulation defects were negative in all cases tested (protein S, C were normal in 17/17; anti-thrombin III, anti-phospholipid antibodies and activated protein C resistance were negative in 20/20, and only 1/20 patients was found to be heterozygous for Factor V leiden. Thrombosis in inflammatory bowel disease is important because it occurs in a young population, often in unusual sites, and has a high mortality. The development of thrombosis is related to active inflammatory disease in most patients with Crohn's disease but apparently not in those with ulcerative colitis. Since approximately half of the patients had no other identifiable risk factor, there remains a substantial group of patients with IBD who develop thrombosis for unknown reasons.      

Morphometric analysis of intestinal mucosa. V. Quantitative histological and immunocytochemical studies of rectal mucosae in gluten sensitivity.

To study changes in rectal mucosa that might be attributable to the effects of gluten, rectal biopsy specimens from untreated and treated gluten sensitised subjects were analysed morphometrically and by immunohistochemical techniques and were compared with a series of disease control mucosae. Although morphometry showed increased populations of plasma cells, lymphocytes, and mast cells in the mucosae of untreated patients, which were reduced (except for mast cells) by dietary gluten restriction, immunohistochemical techniques were far more sensitive in defining these changes. There were highly significant increases in CD3+ and gamma delta+ lymphocytes within both the lamina propria and the epithelium while neutrophils (CD15+ cells) were not at all prominent. Activated (CD25+) lymphocytes expressing interleukin (IL)-2 receptors were increased in lamina propria, usually subjacent to basal lamina, although a few IL-2R+ intraepithelial lymphocytes were found: other IL-2R+ cells were deemed to be macrophages (CD68+). These results clearly indicate that in untreated, gluten sensitised subjects the rectal mucosa shows a lymphoplasmacytoid reaction that is responsive to gluten restriction. The absence of neutrophilia suggests that this lesion is not a conventional inflammatory type proctitis, but rather one presumed to be induced by gluten antigen(s) present in the faecal stream--that is, a cell mediated form of response.     

Atypical teratoid/rhabdoid tumor of the spine

SUMMARY: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system neoplasm usually seen in young children and infants. Prognosis for AT/RT is poor, with most patients dying within 1 year of presentation. AT/RT most commonly occurs intracranially. Location in the spine, though previously reported, is rare, and imaging findings have not been emphasized in the past. We present a case of AT/RT occurring in the thoracolumbar spine of a child and review available clinical and imaging findings in previously reported cases of spinal AT/RT.     

Thalidomide attenuates nitric oxide-driven angiogenesis by interacting with soluble guanylyl cyclase

Background and purpose:

Nitric oxide (NO) promotes angiogenesis by activating endothelial cells. Thalidomide arrests angiogenesis by interacting with the NO pathway, but its putative targets are not known. Here, we have attempted to identify these targets.

Experimental approach:

Cell-based angiogenesis assays (wound healing of monolayers and tube formation in ECV304, EAhy926 and bovine arterial endothelial cells), along with ex vivo and in vivo angiogenesis assays, were used to explore interactions between thalidomide and NO. We also carried out in silico homology modelling and docking studies to elucidate possible molecular interactions of thalidomide and soluble guanylyl cyclase (sGC).

Key results:

Thalidomide inhibited pro-angiogenic functions in endothelial cell cultures, whereas 8-bromo-cGMP, sildenafil (a phosphodiesterase inhibitor) or a NO donor [sodium nitroprusside (SNP)] increased these functions. The inhibitory effects of thalidomide were reversed by adding 8-bromo-cGMP or sildenafil, but not by SNP. Immunoassays showed a concentration-dependent decrease of cGMP in endothelial cells with thalidomide, without affecting the expression level of sGC protein. These results suggested that thalidomide inhibited the activity of sGC. Molecular modelling and docking experiments revealed that thalidomide could interact with the catalytic domain of sGC, which would explain the inhibitory effects of thalidomide on NO-dependent angiogenesis.

Conclusion and implications:

Our results showed that thalidomide interacted with sGC, suppressing cGMP levels in endothelial cells, thus exerting its anti-angiogenic effects. These results could lead to the formulation of thalidomide-based drugs to curb angiogenesis by targeting sGC.     

Effect of low-density lipoprotein apheresis on inflammatory and noninflammatory high-density lipoprotein cholesterol

Low-density lipoprotein (LDL) apheresis, a treatment for familial hypercholesterolemia, significantly decreases LDL cholesterol and inflammatory markers such as C-reactive protein, CD40 ligand, and tissue factor. LDL apheresis also decreases high-density lipoprotein (HDL) cholesterol, which might be considered therapeutically counterproductive because HDL is known to be anti-inflammatory. However, recent studies have shown that HDL also possesses proinflammatory properties, as seen in its ability to alter LDL-induced monocyte chemotactic activity. We examined the acute effects of LDL apheresis on inflammatory HDL activity in 13 patients with familial hypercholesterolemia and cardiovascular disease who had been receiving bi-weekly LDL apheresis treatments. Immediately before and immediately after treatment, each patient's plasma was collected for analysis of inflammatory HDL and full lipid profile. LDL apheresis reduced LDL by 52% (from 208 +/- 89 to 99 +/- 48 mg/dl, p <0.002), and HDL decreased by 16% (49 +/- 15 to 41 +/- 13 mg/dl, p <0.003). At the same time, inflammatory HDL activity (in migrated monocytes per high-power field) decreased from 22 +/- 4 to 14 +/- 2, a 37% acute reduction (p <0.003). Moreover, inflammatory HDL before HDL apheresis was highly correlated with its acute reduction (r(s) = 0.85, p <0.001). In conclusion, our findings indicate that, in addition to decreasing LDL, LDL apheresis also decreases inflammatory HDL. The clinical significance of reducing inflammatory HDL is currently unknown, and further research is needed to examine its potential benefit for cardiovascular disease.     

Cigarette smoking and primary liver cancer: a population-based case–control study in US men

Objective Using the case–control data from the Selected Cancers Study, the authors assessed whether cigarette smoking increases the risk of primary liver cancer in the US. Methods Cases were men who were pathologically diagnosed with primary liver cancer during 1984–1988, were 31–59 years old, and lived in the areas covered by eight US cancer registries (n = 168). Controls were men without a history of primary liver cancer who were selected by random-digit telephone dialing (n = 1910). Results Relative to non-smokers, the risks of liver cancer were 1.85 (95% confidence interval (CI), 1.05–3.25) and 1.49 (95% CI, 0.83–2.68) for former and current smokers, respectively. The adjusted odds ratio (OR) estimates were 0.96, 1.43, 1.80, and 1.87 for smoking for less than 15, 15–24, 25–34 and 35 or more years, respectively (p for trend = 0.039). The OR estimates were 1.41 (95% CI, 0.74–2.68), 1.67 (95% CI, 0.93–2.98), and 1.83 (95% CI, 0.89–3.76) for less than 1, 1–2, and 2 or more packs smoked per day (p for trend = 0.068). Conclusions Cigarette smoking may be a factor that contributes somewhat to the occurrence of primary liver cancer among men in the United States, a country with low risk of liver cancer.     

Interventional radiology in the treatment of intracranial vascular injuries and fistulae

Traumatic intracranial vascular injuries are uncommon. However prompt diagnosis and management is essential because of the high morbidity and mortality associated with these conditions. The imaging evaluation and potential endovascular management of traumatic intracranial aneurysms and traumatic intracranial fistulae is discussed.