The pathogenesis of diabetic retinopathy

Diabetic retinopathy remains a major cause of loss of vision. The Diabetes Control and Complications Trial (DCCT) has implicated hyperglycaemia as a probable major direct causative factor in the pathogenesis of diabetic retinopathy. There are several plausible mechanisms by which high glucose concentrations could lead to the functional and later structural changes characterising diabetic retinopathy. These include increased activity of the aldose reductase pathway, increase de novo synthesis of diacylglycerol from glucose, causing protein kinase C activation, increased non-enzymatic glycation and increased oxidative damage. The demonstration of the potential roles of these pathways and the subsequent effects of growth factors in enhancing angiogenesis provide potential new approaches to the prevention and treatment of diabetic retinopathy.     

Air pollution exposure estimation using dispersion modelling and continuous monitoring data in a prospective birth cohort study in the Netherlands

Background

High temperature and humidity conditions are associated with short-term elevations in the mortality rate in many United States cities. Previous research has quantified this relationship in an aggregate manner over large metropolitan areas, but within these areas the response may differ based on local-scale variability in climate, population characteristics, and socio-economic factors.

Methods

We compared the mortality response for 48 Zip Code Tabulation Areas (ZCTAs) comprising Philadelphia County, PA to determine if certain areas are associated with elevated risk during high heat stress conditions. A randomization test was used to identify mortality exceedances for various apparent temperature thresholds at both the city and local scale. We then sought to identify the environmental, demographic, and social factors associated with high-risk areas via principal components regression.

Results

Citywide mortality increases by 9.3% on days following those with apparent temperatures over 34°C observed at 7:00 p.m. local time. During these conditions, elevated mortality rates were found for 10 of the 48 ZCTAs concentrated in the west-central portion of the County. Factors related to high heat mortality risk included proximity to locally high surface temperatures, low socioeconomic status, high density residential zoning, and age.

Conclusions

Within the larger Philadelphia metropolitan area, there exists statistically significant fine-scale spatial variability in the mortality response to high apparent temperatures. Future heat warning systems and mitigation and intervention measures could target these high risk areas to reduce the burden of extreme weather on summertime morbidity and mortality.     

Mammography using an ultrahigh-strip-density, stationary, focused grid

A 1-mm-thick, stationary, ultrahigh-strip-density, focused grid was evaluated with respect to patient radiation dose and mammographic image quality as it affected the resolution of microcalcifications and masses. Radiographic technique was varied to determine the most useful alteration to improve image quality with the grid. Results from 89 patients demonstrated that no improvement in diagnostic ability was found in women with fatty breasts. As breast density increased, the advantage of the grid technique became more apparent. Grid mammography also often solved the problem of questionable microcalcifications with improved visualization of their number and geometry.     

垂全催乳素瘤的诊断和治疗指南

3.男性:高催乳素血症通常导致阳痿、不孕和性功能低下.男性患者通常为大腺瘤,有神经系统症状.其原因可能是对症状认识的延误或者肿瘤生物学行为的差异.     

Interaction of platelet factor four with cultured vascular endothelial cells

Platelets secrete a low-molecular-weight protein, platelet factor four (PF-4), which binds to and neutralizes heparin and related sulfated glycosaminoglycans (GAGs). To examine the interactions of PF-4 with the GAGs present on endothelial cell surfaces, we incubated 125I-PF-4 with cell suspensions derived from confluent monolayers of cultured bovine aortic endothelium. Binding of 125I-PF-4 was inhibited by a 100-fold excess of nonradioactive PF-4 and varied with duration and temperature of incubation. At 4 degrees C, binding reached equilibrium at 20 minutes with kd = 2.87 mumol/L and Bmax of 63.83 pmol/10(5) cells. Binding capacity was reduced 83.4% by brief incubation of endothelial cells with trypsin and 46.67% by incubation with Flavobacterium heparinase, but was unchanged by chondroitin-ABCase treatment. At 37 degrees C, PF-4 was internalized by confluent monolayer of bovine aortic endothelial cells primarily through low-affinity adsorptive endocytosis. The internalized PF-4 was degraded to amino acids and small peptides with 50% conversion after 18-hour incubation. These studies demonstrate that a secreted platelet protein can bind to and enter endothelial cells. Binding may explain the rapid clearance of released PF-4 from plasma and could have important local effects on endothelial structure and function.     

Immunoblotting characterization of neutrophil antigenic targets in autoimmune neutropenia

We characterized neutrophil autoantigens using an immunoblotting technique with antibodies obtained from patients with autoimmune neutropenia. These results were correlated with serologic characterization of the antibodies, using indirect immunofluorescence and leukoagglutination. Of the 17 sera immunoblotted, 16 showed discrete bands in the molecular weight range of 30 to 112. Three patients with Felty's syndrome reacted with an antigenic target of 80 to 84 Kd molecular mass, a finding not seen in any of the other patients studied. By serologic testing, none of the autoimmune sera showed serologic specificity for any known neutrophil-specific alloantigen. Using an anti-NA-1 serum, we identified antigenic targets at 40, 50, and 101 Kd in both NA-1-positive and NA-1-negative neutrophils. Ten of 17 autoimmune sera showed reactivity in this corresponding range. These studies demonstrate that immunoblotting may be used to identify antigenic targets in autoimmune neutropenia and may suggest a specificity of these antibodies not definable by serologic techniques. Correlation of immunoblot reactivity with disease states associated with immune neutropenia may be useful in the study of the pathogenesis of the different forms of autoimmune neutropenia.     

Carotid artery: percutaneous transbrachial selective arteriography with a 4-F catheter

Bilateral selective common carotid artery catheterization was attempted in 72 patients by means of percutaneous placement of a 4-F catheter from a right brachial artery puncture site in the antecubital fossa. The success rate was high (95.8%) and the complication rate low (6.9%), and there were no instances of brachial artery spasm or thrombosis. The experience, while small, suggests that selective common carotid arteriography can be done safely and efficaciously from the right brachial artery approach.     

Anxiety in patients undergoing MR imaging

To determine and quantify the major sources of anxiety for patients undergoing magnetic resonance (MR) imaging and to suggest means by which to eliminate or diminish their negative effects, the authors studied anxiety in 46 subjects. Of these, 20 randomly selected subjects who successfully completed the examination participated in exit interviews. Six subjects who terminated the examination before completion also completed exit interviews. Pre-imaging and postimaging questionnaires (state-trait anxiety inventory) were administered to measure anxiety in the 20 other subjects. Anxiety was associated with the constrictive dimensions of the magnet bore, examination duration, coil noise, and temperature within the bore. Preparation at the point of referral was consistently absent, incomplete, or misleading. Patients used identifiable strategies to cope with the examination: blinding, breathing relaxation techniques, visualization of pleasant images, and performance of mental exercises.     

Cerebrospinal fluid rhinorrhea: depiction with MR cisternography in dogs

Canine cerebrospinal fluid rhinorrhea, which occurs frequently in purebred beagles, was demonstrated in two dogs on magnetic resonance images after cisternal introduction of gadolinium-DTPA dimeglumine.     

An electronic stethoscope is judged better than conventional stethoscopes for anesthesia monitoring

A prototype electronic monitoring stethoscope was constructed from readily available, high-quality components. It consisted of a conventional precordial or esophageal probe connected to a microphone by a rubber adapter. The microphone was connected by lightweight wire to an amplifier and headphones. Twenty-one anesthesia clinicians evaluated the stethoscope and responded to a multiple-choice preference questionnaire. The electronic stethoscope was judged to perform better than the conventional stethoscope in most categories evaluated. The electronic device was perceived to be louder, clearer in sound reproduction, more efficacious for monitoring, and easier to use continuously, and its head-phones were considered more comfortable than the conventional carpiece. Based on our results, we conclude that amplified stethoscopes have the potential to improve monitoring. Further development of electronic stethoscope monitoring seems warranted and is continuing.