A mouse mutant strain highly resistant to methyl beta-carboline-3-carboxylate-induced seizures

It is believed that DOPA-negative melanocytes in the outer root sheath of the human hair follicle are activated, become identifiable by DOPA staining, and migrate into the epidermis during the repigmenting phase of vitiligo. These cells are difficult to identify, however, and otherwise have not been characterized. These cells are readily identified by immunofluorescence, immunohistochemistry, and immunoelectronmicroscopy using the antibodies NKI/beteb and A4F11, which recognize premelanosome-related antigens. The majority of the outer root sheath melanocytes were found in the mid to the upper portion of the hair follicle. Double staining revealed that these cells were distinct from HLA-DR-bearing dendritic cells. Further immunohistochemical investigation using alpha-PEP-7, alpha-PEP-1, or TMH-1 and alpha-PEP-8 antibodies revealed that outer root sheath melanocytes cannot be identified by antibodies to tyrosinase, TRP-1, or TRP-2, respectively. These cells also did not react with HMB45 antibody, which recognizes a melanosome-associated cytoplasmic antigen. We believe that the inactive outer root sheath melanocytes contain some of the early structural proteins but not any of the enzymatic proteins necessary for melanogenesis. Therefore, activation is the process whereby outer root sheath melanocytes acquire all of the structural and enzymatic proteins necessary for melanogenesis.     

Pharmacologic profile of survivors of acute myocardial infarction at United States academic hospitals

Optimal drug therapy for patients with acute myocardial infarction (AMI) is well described in the medical literature. However, data on the actual pharmacologic management of patients surviving AMI at academic hospitals is unavailable. The purpose of this study was to document treatment profiles in 500 patients surviving AMI at 12 academic hospitals in the United States. These profiles were compared with established guidelines and were evaluated for trends. Overall, thrombolytics (streptokinase > or = tissue-type plasminogen activator) were administered in 29% of the patients, with a greater proportion of patients receiving beta-blockers than calcium channel antagonists in the initial 72 hours (61% vs 40%; p < 0.005) and at discharge (51% vs 35%; p < 0.005). Further, women were less likely than men to receive thrombolytic therapy (odds ratio [OR] = 0.61; confidence interval [CI], 0.54 to 0.69) or beta-blocker therapy within the first 72 hours (OR = 0.61; CI, 0.55 to 0.67) or at hospital discharge (OR = 0.53; CI, 0.48 to 0.58). Overall, improvements could still be made in the number of patients who receive thrombolytic and acute and chronic beta-blocker therapies after AMI, particularly in women. Changes in treatment profiles may be a reflection of the publication of large clinical trials.     

Endoscopic surveillance of Barrett's esophagus: a cost-effectiveness comparison with mammographic surveillance for breast cancer

OBJECTIVE: Endoscopic surveillance of Barrett's esophagus is commonly practiced to detect malignancy in an early and curable stage. However, the cost-effectiveness of this practice has been questioned. To clarify this issue, we undertook a cost analysis of endoscopic surveillance to detect adenocarcinoma in Barrett's esophagus compared with mammography used to detect occult carcinoma of the breast, a widely accepted cancer surveillance technique. METHODS: The rate of esophageal adenocarcinoma detected by endoscopic surveillance was calculated for Duluth Clinic patients with Barrett's esophagus seen from 1980 to 1995 and compared with published rates. The rate of occult breast cancer detection was calculated for all women undergoing surveillance mammography at the Duluth Clinic for the year 1994 and compared with published rates. Costs for screening studies and therapy for cancer treatment for both cancers were calculated based on clinical results and assumptions regarding outcomes derived from published reports, and the costs were compared. RESULTS: Endoscopic surveillance of 149 patients with benign Barrett's esophagus was performed for a total of 510 patient-yr, during which time seven patients developed adenocarcinoma, an incidence of one case per 73 patient-yr of follow-up. Occult breast cancer was detected in 50 of 12,537 mammograms, a detection rate of 0.4%. The incidences in both cases were comparable to published figures. The costs of detecting a case of adenocarcinoma in Barrett's esophagus and occult breast cancer were $37,928 and $54,513, respectively, and those for treatment resulting in cure were $83,340 and $83,292. Cost per life-yr saved was $4,151 for adenocarcinoma in Barrett's esophagus and $57,926 for breast cancer. CONCLUSION: Endoscopic surveillance of patients with Barrett's esophagus compares favorably with the common practice of surveillance mammography to detect early breast cancer, and should therefore be considered to be as cost-effective as surveillance mammography.     

Wave-front curvature as a cause of slow conduction and block in isolated cardiac muscle

We have investigated the role of wave-front curvature on propagation by following the wave front that was diffracted through a narrow isthmus created in a two-dimensional ionic model (Luo-Rudy) of ventricular muscle and in a thin (0.5-mm) sheet of sheep ventricular epicardial muscle. The electrical activity in the experimental preparations was imaged by using a high-resolution video camera that monitored the changes in fluorescence of the potentiometric dye di-4-ANEPPS on the surface of the tissue. Isthmuses were created both parallel and perpendicular to the fiber orientation. In both numerical and biological experiments, when a planar wave front reached the isthmus, it was diffracted to an elliptical wave front whose pronounced curvature was very similar to that of a wave front initiated by point stimulation. In addition, the velocity of propagation was reduced in relation to that of the original planar wave. Furthermore, as shown by the numerical results, wave-front curvature changed as a function of the distance from the isthmus. Such changes in local curvature were accompanied by corresponding changes in velocity of propagation. In the model, the critical isthmus width was 200 microns for longitudinal propagation and 600 microns for transverse propagation of a single planar wave initiated proximal to the isthmus. In the experiments, propagation depended on the width of the isthmus for a fixed stimulation frequency. Propagation through an isthmus of fixed width was rate dependent both along and across fibers. Thus, the critical isthmus width for propagation was estimated in both directions for different frequencies of stimulation. In the longitudinal direction, for cycle lengths between 200 and 500 milliseconds, the critical width was < 1 mm; for 150 milliseconds, it was estimated to be between 1.3 and 2 mm; and for the maximum frequency of stimulation (117 +/- 15 milliseconds), it was > 2.5 mm. In the transverse direction, critical width was between 1.78 and 2.32 mm for a basic cycle length of 200 milliseconds. It increased to values between 2.46 and 3.53 mm for a basic cycle length of 150 milliseconds. The overall results demonstrate that the curvature of the wave front plays an important role in propagation in two-dimensional cardiac muscle and that changes in curvature may cause slow conduction or block.     

Cuticle chirality and body handedness in Caenorhabditis elegans

BACKGROUND AND PURPOSE: Norway has the highest reported incidence of hip fractures in western Europe. Little is known about the epidemiology of falls in Norway where the winter season is long and dark. The objective of this work was to study reported falls and their consequences among elderly Norwegians living at home. METHODS: A cross-sectional design was used for the study. Interviews were performed in the homes of 431 subjects, aged 67-97 years, living at home. Information on falling was gathered through six questions: whether the subject had fallen during the last six months, and if so, how many falls they had, where the last fall occurred, its perceived reason, the activity the subject had been engaged in when the fall occurred, and the resulting injury. RESULTS: In all, 24.1% of subjects reported falling during the last six months, and 9.5% had suffered more than one fall. Falls were most frequently linked to external events (63.1%). Outdoor falls were more frequent (59.0%; 95% CI = 51.2-82.0) than indoor falls. Older subjects were associated with more frequent indoor falls (p < 0.05), but gender was not significant. Fifty-one per cent of subjects had fallen while walking and 53% had suffered an injury from the last fall. In 13.4% of the women and 16.2% of the men, the last fall had resulted in a fracture. CONCLUSIONS: Compared to the results of other studies from industrialized Western countries, a similar crude fall rate, similar frequency and similar type of injury were found. However, in contrast to other studies, no gender difference was observed with regard to falling, place of falling and fracture rate.     

Quantitative measurement of a new synthetic hetrazepine derivative, BN50730, in human plasma and urine by combined liquid chromatography-negative chemical ionization mass spectrometry using a particle beam interface

A new simple and sensitive assay has been developed for the quantitative measurement of BN50730 at the picomole level in human plasma and urine. The drug and the internal standard (BN50765) were measured by combined liquid chromatography-negative chemical ionization mass spectrometry with methane as the reagent gas. A simple solid-liquid extraction procedure was used to isolate BN50730 from complex biological matrices. Mild operating conditions were required to assay the parent drug with a particle beam interface from Hewlett-Packard. The mass spectrometer was tuned to monitor the intense ion m/z 333, which was generated in the ion source by a dissociative capture process. This assay was performed with 1 ml of plasma or 0.1 ml of urine, and the quantification limit of the method was statistically calculated as 1 ng ml-1. The very low relative standard deviation and mean percentage of error calculated during the different within-day or between-day repeatability assays clearly demonstrate the ruggedness of the technique for the routine determination of BN50730 in the biological fluids. Some preliminary results on the pharmacokinetics of the drug are presented to illustrate the applicability of this new powerful LC-MS method.