Temporary loss of perivascular aquaporin-4 in neocortex after transient middle cerebral artery occlusion in mice

The aquaporin-4 (AQP4) pool in the perivascular astrocyte membranes has been shown to be critically involved in the formation and dissolution of brain edema. Cerebral edema is a major cause of morbidity and mortality in stroke. It is therefore essential to know whether the perivascular pool of AQP4 is up- or down-regulated after an ischemic insult, because such changes would determine the time course of edema formation. Here we demonstrate by quantitative immunogold cytochemistry that the ischemic striatum and neocortex show distinct patterns of AQP4 expression in the reperfusion phase after 90 min of middle cerebral artery occlusion. The striatal core displays a loss of perivascular AQP4 at 24 hr of reperfusion with no sign of subsequent recovery. The most affected part of the cortex also exhibits loss of perivascular AQP4. This loss is of magnitude similar to that of the striatal core, but it shows a partial recovery toward 72 hr of reperfusion. By freeze fracture we show that the loss of perivascular AQP4 is associated with the disappearance of the square lattices of particles that normally are distinct features of the perivascular astrocyte membrane. The cortical border zone differs from the central part of the ischemic lesion by showing no loss of perivascular AQP4 at 24 hr of reperfusion but rather a slight increase. These data indicate that the size of the AQP4 pool that controls the exchange of fluid between brain and blood during edema formation and dissolution is subject to large and region-specific changes in the reperfusion phase.     

Reduced baroreflex effectiveness index in hypertensive patients with chronic renal failure

BACKGROUND: Impaired arterial baroreflex function has been associated with an increased risk of ventricular arrhythmia and sudden death. This has also been suggested for patients with chronic renal failure (CRF) who are at high risk for cardiovascular morbidity. The aim of this study was to investigate the arterial baroreflex function in CRF patients with emphasis on analyzing the time during which the arterial baroreflex is active, the baroreflex effectiveness index (BEI). METHODS: Beat-to-beat blood pressure (measured with Portapres) and electrocardiography were continuously registered during 30 min rest in 216 hypertensive CRF patients on hemodialysis (n=95), continuous ambulatory peritoneal dialysis (n=59), or conservative treatment (n=59). The spontaneous sequence method was used to calculate BRS and BEI. Age-matched healthy subjects (n=43) were examined for comparison. RESULTS: The BRS was reduced by 51% and the BEI by 49% in CRF patients compared with healthy subjects (P<.001 for both). In addition, CRF patients with diabetes showed further reductions compared with patients without diabetes (15% reduction of BRS and 44% of BEI, P<.01 for both). The treatment modality for renal failure had no effect on BRS or BEI. In a multivariate linear regression analysis, age, body mass index, and systolic blood pressure were independent predictors of BRS, whereas age and diabetes were independent predictors of BEI in patients with CRF. CONCLUSIONS: We conclude that BEI, which is markedly reduced in hypertensive patients with CRF, may convey information on arterial baroreflex function that is complementary to BRS.     

Alpha-mannosidosis and mutational analysis in a Turkish patient

We present a case of alpha-mannosidosis with its mutational analysis. She was referred to our hospital with the provisional diagnosis of mucolipidosis. She was the first child of second-degree relative parents. She had a coarse face with flat and wide nasal bridge, hepatosplenomegaly, umbilical hernia, lumbar gibbus, motor and mental retardation and deafness. On peripheral blood smear, lymphocytes revealed vacuoles and neutrophils contained some granules resembling Reilly bodies seen in mucopolysaccharidosis (MPS). Based on these findings, the diagnosis of alpha-mannosidosis was suspected. Her urine oligosaccharide chromatography showed an abnormal pattern with a heavy trisaccharide band. Enzyme studies on white cells confirmed a deficiency of alpha-mannosidase activity, which was 2.6 micromol/g/hr. Her DNA analysis showed a S453Y mutation.     

Incidence rates of progressive childhood encephalopathy in Oslo,Norway: a population based study

Background  

Progressive encephalopathy (PE) in children is a heterogeneous group of diseases mainly composed of metabolic diseases, but it consists also of neurodegenerative disorders where neither metabolic nor other causes are found. We wanted to estimate the incidence rate and aetiology of PE, as well as the age of onset of the disease.     

Baroreflex effectiveness index and baroreflex sensitivity predict all-cause mortality and sudden death in hypertensive patients with chronic renal failure

OBJECTIVES: Impaired arterial baroreflex sensitivity (BRS) has been associated with cardiac mortality and non-fatal cardiac arrests after a myocardial infarction. Patients with chronic renal failure (CRF) have a poor prognosis because of cardiovascular diseases, and sudden death is common. The aim of this study was to assess whether BRS or the baroreflex effectiveness index (BEI), a novel index reflecting the number of times the baroreflex is active in controlling the heart rate in response to blood pressure fluctuations, is associated with prognosis in CRF. METHODS: Hypertensive patients with CRF who were treated conservatively, by haemodialysis or peritoneal dialysis were studied. Electrocardiogram and beat-to-beat blood pressures were recorded continuously and BRS and BEI were calculated. Patients were then followed prospectively for 41 +/- 15 months (range 1-64). RESULTS: During follow-up 69 patients died. Cardiovascular diseases and uraemia accounted for the majority of deaths (60 and 20%, respectively), whereas sudden death occurred in 15 patients. In adjunct with established risk factors such as age, diabetes, congestive heart failure and diastolic blood pressure, reduced BEI was an independent predictor of all-cause mortality among CRF patients [relative risk (RR) 0.50, 95% confidence interval (CI) 0.33-0.71 for an increase of one standard deviation in BEI, P < 0.001]. Diabetes and reduced BRS were independent predictors of sudden death (RR 0.29, 95% CI 0.09-0.86 for an increase of one standard deviation in BRS, P=0.022). CONCLUSIONS: Both BEI and BRS convey prognostic information that may have clinical implications for patients with cardiovascular diseases in general.     

DNA microarray as a tool in establishing genetic relatedness--Current status and future prospects

In the past decades, microarray technology has definitely put an edge to the field of genetic research. Our aim was to determine whether single nucleotide polymorphism (SNP) microarrays could be used as a tool in establishing genetic relationships where current molecular genetic methods are not sufficient. We used the Genechip, Affymetrix GenomeWide SNP Array 6.0, which detects more than 900,000 SNP markers dispersed throughout the human genome. The intention was to find a good selection of SNP markers that could be used for statistical evaluation of relatedness in a forensic setting. We conducted pairwise comparisons in the R-package FEST as well as pedigree comparisons in Merlin. Our methods were applied on two separate families, where relationships as distant as 3rd cousins were known. In addition, a question about a possible common ancestry between the two families was tested. Relationships as distant as 2nd cousins could be readily distinguished both from unrelated and other, genetically, closer relationships. This was achieved with a selection of 5774 markers, where each pair of markers was separated by a genetic distance of at least 0.5cM (centiMorgan). When considering 3rd cousins, and more distant relationships, the number of markers needs to be extended, consequently decreasing the genetic distance between the markers. However, inclusion of a too large number of markers presents new challenges and our results imply that the use of too dense sets of markers always yields the highest probability for the genetically closest relationship hypothesis. Simulations confirm that this is most probably caused by the fact that the computational model assumes linkage equilibrium between markers, a problem that will be further evaluated. Our results do however suggest that SNP-data derived from microarrays are well suited for kinship determination provided linkage disequilibrium is properly accounted for.     

Patient satisfaction in a regular and after-hours dental clinic

To determine whether financial incentives would have an impact on the quality of care, we compared patient satisfaction in a "regular" daytime postdoctoral general dentistry clinic and an "after-hours" clinic, using a 14-item mail questionnaire to a randomly selected sample of adult patients, stratified by age and gender. The providers in both clinics were identical; however, the method of compensation was different. When residents treated patients in the regular clinic, they were paid a fixed stipend, while the "after-hours" clinic residents' compensation was fee-for-service. The percentage of patients giving very favorable or favorable responses was high in both clinics. However, the response of patients in the "after-hours" clinic was more favorable for total number of visits required for care to be completed, management of pain, and politeness of receptionists. This study demonstrated that the payment of financial incentives to residents did not reduce and may even have enhanced patient satisfaction.