The influence of MK-801 on the hippocampal free arachidonic acid level and Na+,K+-ATPase activity in global cerebral ischemia-exposed rats

The influence of 20 min global cerebral ischemia on the free arachidonic acid (FAA) level and Na⁺,K⁺-ATPase activity in the rat hippocampus at different time points after ischemia was examined. In addition, the effect of MK-801 on mentioned parameters was studied. Animals were exposed to 20 min global cerebral ischemia and were sacrificed immediately, 0.5, 1, 2, 6, 24, 48, 72, and 168 h after ischemic procedure. The level of the FAA and the Na⁺,K⁺-ATPase activity was measured during all reperfusion periods examined. Various doses of MK-801 (0.3, 1.0, 3.0, and 5.0 mg/kg) had been injected 30 min before ischemic procedure started. It was found that 20 min global cerebral ischemia induces a statistically significant increase of the FAA level immediately after ischemia and during the first 0.5 h of reperfusion. After a transient decrease, the level of FAA level increased again after 24 and 168 h of recirculation. Treatment with 3.0 mg/kg of MK-801 significantly prevented the FAA accumulation immediately and 0.5 h after ischemic insult while application of 5.0 mg/kg of MK-801 exerted a protective effect during the first 24 h. Global cerebral ischemia induces the significant decline in the Na⁺,K⁺-ATPase activity in the hippocampus starting from 1 to 168 h of reperfusion. Maximal inhibition was obtained 24 h after the ischemic damage. Application of 3.0 mg/kg of MK-801 exerted statistically significant protection during the first 24 h while the treatment with 5.0 mg/kg of MK-801 prevented fall in enzymatic activity during all reperfusion periods examined. Our results suggest that, in spite of different and complex pathophysiological mechanisms involved in the increase of FAA level and the decrease of the Na⁺,K⁺-ATPase activity, blockade of NMDA receptor subtype provides a very important strategy for the treatment of the postischemic excitotoxicity.     

A randomized,placebo-controlled trial of the discontinuation of long-term antipsychotics in dementia

The objectives of this randomized clinical trial were to investigate the impact of the discontinuation of long-term antipsychotics in residents with dementia in chronic care institutions and to identify clinical predictors of safe discontinuation. Subjects included 34 residents with dementia who were on antipsychotics for more than 6 months and whose behavior was currently stable. Subjects were randomized to either continue receiving their regular dosage of antipsychotics or to receive placebo for 6 months. Early withdrawal from the study was not statistically different between the groups (relative risk [RR] = 1.57, 95% confidence interval [CI] 0.76-3.26), and though not significantly different, subjects in the placebo group were more likely to be withdrawn from the study because of worsening behavior (RR = 1.25, 95% Cl 0.33-4.76). Three subjects in the placebo group were withdrawn from the study due to worsening of extrapyramidal symptoms. The active treatment group had more behavioral problems (e.g., physical aggression towards others, p < .05) compared to the placebo group. The placebo group developed more apathy, but balancing this outcome was a relative improvement in cognitive functioning. Baseline antipsychotic dose was predictive of behavioral worsening upon discontinuation of long-term antipsychotic drugs. The primary limitation of the study was the small sample size. In conclusion, a trial of discontinuation of antipsychotics should be considered in this population.     

Cerebrospinal fluid fistula as a consequence of war head injury

Cerebrospinal fluid (CSF) fistula as a consequence of brain missile injury and following infectious complications has been recognized for years. Different methods of treatment have been advocated. Missiles used in war cause extensive destruction of the skull and brain as a result of their high kinetic energy. On its transfer through the skull, such high kinetic energy causes fractures called "discontinuous fractures," which are distant from the entry wound and not related to the fracture of the vault. The role of the timely diagnosis of CSF fistulas and their early repair in the management of these wounds is emphasized. Data on 312 patients with missile injuries of the brain inflicted during the war in Croatia were retrieved and analyzed, with special reference to the complications of CSF fistulas and infection. Forty-five patients developed CSF fistula, 15 (33%) of them at the wound site, 23 (51%) as CSF rhinorrhea, and seven (15%) as CSF otorrhea. Six patients developed infectious complications. The presented strategy and operative approach resulted in a low incidence of infectious complications in the study series.     

Complications and mortality in surgery of cerebral aneurysms

AIM: To establish the risk factors for complications and fatal outcome after the operative occlusion of cerebral aneurysms. METHODS: Retrospective study on 91 (lethality rate) and on 72 operated patients (complications). For survived and dead patients, as well as for patients with and without complications, following parameters were compared: gender, age, clinical condition, preoperative interval, use of temporary clips, vasospasm, outcome, as well as localization, size and intraoperative rupture of the aneurysm. RESULTS: Complications existed: in 54.5% of aneurysms of middle cerebral and 13.6% of aneurysms of internal carotid artery (p < 0.01); in 18.2% of patients in the first and 45.8% of patients in the third clinical Hunt and Hess group (p < 0.05); in 57.9% of patients with and 20.5% of patients without intraoperative rupture (p < 0.01); in 50% of patients with and 18.7% of patients without vasospasm (p < 0.05). Average aneurysmal size was 18 mm in group with complications and 10.8 mm in patients with no complications (p < 0.05), while average preoperative intervals in these two groups were 20 and 8.7 days (p < 0.05). Lethality rate was 25% for the third and 83.3% for the fourth and fifth clinical group (p < 0.01), and the existence of complications significantly increased mortality (from 15.7% to 50%, p < 0.01). Good outcome existed in 19.2% of operated patients with complications and in 78.3% of those without complications (p < 0.01). CONCLUSIONS: Incidence of complications depended significantly on preoperative clinical condition, duration of preoperative interval, size, localization and intraoperative rupture of aneurysm. Complications significantly minimized the surgical treatment outcome and increased the lethality rate mortality.     

Advanced prostatic carcinoma with low levels of serum prostate-specific antigen

The serum levels of prostate-specific antigen (PSA) represent a significant diagnostic and monitoring parameter of prostatic carcinoma (PC). The aim of the study was to establish correlation of serum PSA level in addition to grade, histological type, and clinical stage of PC in patients with normal or intermediary PSA serum level. In 37 untreated PC patients with preoperative serum PSA levels ranging between 0.1 and 9.6 ng/ml, paraffin-embedded tissue and serum samples were immunohistologically studied and immunoassay for PSA was done. The most representative was poorly differentiated PC with D stage. In serum samples from PC patients 27 (73.7%) normal (< or = 4.0 ng/ml), and 10 (27.3%) intermediate (4.1-10 ng/ml) PSA levels were found. Immunohistochemistry, in 36 PC (97.3%) had demonstrated the expression of PSA. Our study results had shown low serum PSA levels in some patients with advanced poorly differentiated PC.     

Effect of changes in fat distribution on the rates of change of insulin response in children

OBJECTIVE: To develop mixed models for examining longitudinal associations between rates of change in visceral, subcutaneous abdominal, and total body fat with rates of change in fasting insulin (FI) and insulin sensitivity (SI) over 3 years in children. RESEARCH METHODS AND PROCEDURES: Seventy-seven children (mean age, 8.3 years at baseline) from Birmingham, Alabama, with three or more annual measures of FI and SI were included. Abdominal fat was measured by computed tomography, and total body fat and lean tissue mass were measured by DXA. Mixed models examined the longitudinal associations between the baseline level/rate of change of different fat compartments and the rate of change in FI or SI. RESULTS: An annual increase of approximately 5% in FI was associated with 1 cm(2)/yr of visceral fat gain per year (p < 0.05), independent of subcutaneous abdominal fat. A 1-cm(2) difference in initial subcutaneous abdominal fat was associated with an approximately 0.2% increase per year in FI (p < 0.02), independent of visceral fat. None of the rates of change in any of the fat measures was associated with the rate of change of SI. DISCUSSION: The rate of change in visceral fat was positively associated with the rate of change in FI, independent of increasing subcutaneous abdominal fat; however, subcutaneous abdominal fat may be more predictive of the rate of change of FI than visceral or total fat. Therefore, growth-related increases in abdominal fat, particularly subcutaneous abdominal fat, may contribute to accelerating increases in FI, but have no effect on SI.     

Validity of body mass index compared with other body-composition screening indexes for the assessment of body fatness in children and adolescents

BACKGROUND: Validation studies of height- and weight-based indexes of body fatness in children and adolescents have examined only small samples of school-age children. OBJECTIVE: The objective was to validate the performance of age- and sex-specific body mass index (BMI) compared with the Rohrer index (RI) and weight-for-height in screening for both underweight and overweight in children aged 2-19 y. DESIGN: Data from the third National Health and Nutrition Examination Survey (n = 11096) and a pooled data set from 3 studies that used dual-energy X-ray absorptiometry (n = 920) were examined. The receiver operating characteristic curve was used to characterize the sensitivity and specificity of these 3 indexes in classifying both underweight and overweight. Percentage body fat and total fat mass were determined by dual-energy X-ray absorptiometry. Subcutaneous fat was assessed on the basis of the average of triceps and subscapular skinfold thicknesses. RESULTS: For children aged 2-19 y, BMI-for-age was significantly better than were weight-for-height and RI-for-age in detecting overweight when average skinfold thicknesses were used as the standard, but no differences were found in detecting underweight. When percentage body fat or total fat mass was used as the standard, BMI-for-age was significantly better than was RI-for-age in detecting overweight in children aged 3-19 y. No differences were found between BMI-for-age and weight-for-height in detecting overweight or underweight. CONCLUSION: For children and adolescents aged 2-19 y, the performance of BMI-for-age is better than that of RI-for-age in predicting underweight and overweight but is similar to that of weight-for-height.     

Expression pattern of lacZ reporter gene representing connexin36 in transgenic mice

Targeted deletion of the connexin36 (Cx36) gene in the mouse genome leads to visual transmission defects, weakened synchrony of rhythmic inhibitory potentials in the neocortex, and disruption of gamma-frequency network oscillations. We have generated transgenic mice in which a reporter protein consisting of the exon1 coded N-terminal part of Cx36 fused to beta-galactosidase (N36-beta-gal) is expressed instead of Cx36. Here, we have used these mice for a detailed analysis of the reporter gene expression. By beta-gal staining of adult retina, we found expression of the lacZ reporter gene in the ganglion cell layer, in two rows of the inner nuclear layer, and in the photoreceptor layer. In the brain, beta-gal staining was present in gamma-aminobutyric acid (GABA)ergic neurons of the cerebellar nuclei, in non-GABAergic neurons of the inferior olive, in mitral cells of the olfactory bulb, and in parvalbumin-positive cells of the cerebral cortex. Outside the central nervous system, N36-beta-gal signals were detected in insulin producing beta-cells of the pancreas and in the medulla of the adrenal gland of adult Cx36(+/del[LacZ]) mice. This expression pattern suggests that Cx36 fulfills functional roles not only in several types of neurons in the retina and central nervous system but also in excitable cells of the pancreas and adrenal gland.     

Differences in patient and transplant professional perceptions of immunosuppression-induced cosmetic side effects

BACKGROUND: A two-part study was initiated to compare kidney transplant patient and transplant professional perceptions regarding immunosuppression-related physical changes and their impact on transplant recipients. METHODS: Parallel surveys were developed and administered to transplant patients and active transplant clinicians. RESULTS: Eighty percent of surveyed patients reported immunosuppression-induced hirsutism, gingival hyperplasia, acne, alopecia, or cushingoid facies. Hirsutism (94%) and gingival hyperplasia (51%) occurred more frequently in cyclosporine patients (p < 0.01); alopecia (30%) occurred more frequently in tacrolimus patients (p < 0.01). Patient reported incidence of physical changes significantly exceeded observations by professionals for every condition (p < 0.01), however 84.4% of affected patients reported feeling "happy to endure" changes "for the sake of having a transplant." Patients also reported emotional and social effects due to physical changes, an outcome underestimated by transplant professionals (p < 0.01). Patients and professionals communicated about physical changes; however, more than half of affected patients believed communication occurred "rarely/never" while over half of the professionals believed communication occurred "every visit/most of the time." Although most physicians believed changes could be addressed, doctors recommended treatment for less than half of the affected patients. When recommended therapy changes were pursued, treatments were effective in the majority of cases. CONCLUSIONS: Incidence of immunosuppression-related physical changes is high and somewhat dependent on drug regimen. Although patients seem willing to accept cosmetic changes for the sake of having a transplant, physical changes have a psychosocial impact that is underestimated by clinicians. Immunosuppression-related physical changes remain underaddressed; effective interventions offer opportunities for improved care.