A molecular mechanism for electrical tuning of cochlear hair cells

Cochlear frequency selectivity in lower vertebrates arises in part from electrical tuning intrinsic to the sensory hair cells. The resonant frequency is determined largely by the gating kinetics of calcium-activated potassium (BK) channels encoded by the slo gene. Alternative splicing of slo from chick cochlea generated kinetically distinct BK channels. Combination with accessory beta subunits slowed the gating kinetics of alpha splice variants but preserved relative differences between them. In situ hybridization showed that the beta subunit is preferentially expressed by low-frequency (apical) hair cells in the avian cochlea. Interaction of beta with alpha splice variants could provide the kinetic range needed for electrical tuning of cochlear hair cells.     

Incremental value of rubidium-82 positron emission tomography for prognostic assessment of known or suspected coronary artery disease

Myocardial perfusion imaging using positron emission tomography (PET) may be more accurate for the diagnosis of coronary artery disease (CAD) than conventional imaging. The purpose of this study was to evaluate the prognostic implications of perfusion abnormalities in 685 patients (age 62 +/- 11 years, 199 women) studied by PET, and to assess the incremental value of these data in relation to prognostic implications of clinical and angiographic findings. Rubidium (Rb)-82 PET was performed before and after dipyridamole stress. Transient defects were detected in 227 patients (33%), and were moderate or greater in severity (> 15% of the left ventricle) in 84 (12%). Resting defects were present in 435 (64%) and were moderate or greater in severity in 216 (32%). The total extent of abnormally perfused myocardium was small (< 15% of the left ventricle) in 198 (29%), moderate in 216 (32%), and extensive in 105 (15%). Clinic review or standardized phone interview in 657 patients (96%) identified 151 cardiac events, including 81 cardiac deaths, 16 patients with myocardial infarction, 7 with unstable angina, and 47 with late revascularization (> 3 months after PET). Normal scans had a 90% event-free survival, compared with 87% in patients with small, 75% with moderate, and 76% with extensive defects (log rank chi-square 30, p <0.0001). Functional class, extent of CAD, and the presence and extent of perfusion defects (both at rest and during stress) were independent predictors of cardiac death and total cardiac events. In sequential Cox proportional-hazards models, the results of PET were incremental to those of clinical and angiographic evaluation. Thus, the presence and extent of damaged and jeopardized myocardium are independent and incremental predictors of outcome in patients undergoing Rb-82 PET.     

Vasoactive intestinal peptide stimulation of human trabecular meshwork cell growth

PURPOSE: To demonstrate that vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide, is a growth factor of human trabecular meshwork (TM) cells in culture and in a corneoscleral explant organ culture treated with laser trabeculoplasty (LTP). METHODS: Proliferating human TM cells in cell cultures were incubated with VIP for 20 hours, followed by total cell number determination, using a Coulter counter. The percentage of proliferating TM cells was assessed, using an antibody against the proliferating cell nuclear antigen (PCNA). To test the growth effect of VIP on TM cells in situ, corneoscleral explants in organ cultures were first treated with argon LTP to initiate TM-cell proliferation and then were exposed to VIP for 48 hours. The mitotic TM cells were demonstrated immunocytochemically, using anti-PCNA in paraffin sections of the explants; and the total number of TM cells was determined after paraffin sections were counterstained by hematoxylin. RESULTS: Vasoactive intestinal peptide dose-dependently stimulated the proliferation of TM cells in cell culture. Treatment with 5 x 10(-10) M VIP resulted in a maximal increase of 40% in cell number. The effect of VIP was blocked by a VIP antagonist. The number of PCNA-stained TM cells and the total cell number in the TM in LTP-treated corneoscleral explants were increased by VIP. CONCLUSIONS: Exogenously applied VIP stimulated the proliferation of human TM cells in subconfluent cultures and in LTP-treated corneoscleral explants. In that LTP has been shown to increase the number of TM cells in situ, the growth stimulatory effect of VIP may help enhance this therapy.     

Successful cytologic diagnosis of cholangiocarcinoma from within a recently placed biliary Wallstent

A six year old boy with an epicardial pacing lead since infancy presented with thoracic pain triggered by movement. The pain was thought to be musculoskeletal, but two weeks later he collapsed and died in ventricular fibrillation. Necropsy showed strangulation of the ventricular apex by the epicardial lead.     

Benign and malignant esophageal strictures: treatment with a polyurethane-covered retrievable expandable metallic stent

PURPOSE: To evaluate the clinical effectiveness of a polyurethane-covered, retrievable, self-expandable metallic stent and hook catheter in the treatment of esophageal strictures. MATERIALS AND METHODS: Stents were constructed of 0.4-mm stainless steel wire in a cylindric zig-zag configuration of six to nine bends. Four to eight stents were connected in tandem by dipping in a polyurethane solution. A nylon loop was hooked inside to each bend of the proximal portion of the stent and strung with a thread. Under fluoroscopic guidance, 22 stents were placed in 16 patients with a malignant stricture and five patients with a benign stricture. The stent was removed with a hook catheter 2 months after placement in patients with a benign stricture and when complications occurred in patients with a malignant stricture. All patients had dysphagia with ingestion of soft foods or liquids. RESULTS: Stent placement was technically successful and well tolerated in 20 patients. In one patient, the stent was misplaced but relocated successfully. After stent placement, all patients were able to ingest solid and/or soft foods without dysphagia. After stent removal, strictures showed improvement but recurred in two patients. CONCLUSION: Use of polyurethane-covered, retrievable expandable stents seems to be a feasible and effective method of treatment of benign and malignant esophageal strictures.     

Developing a regional healthcare information network

The Internet and associated technology is transforming the dissemination of healthcare information. As this occurs, means must be developed to manage and coordinate it effectively. One approach is through community healthcare information networks (CHINs), which benefit both information providers and consumers. The paper reports on a regional CHIN operational in Scotland     

The role of histone acetylation in the allelic expression of the imprinted human insulin-like growth factor II gene

This study examines the relationship between the first cycle of in-vitro fertilization (IVF) and subsequent cycles. The results of all IVF cycles conducted at The Hammersmith Hospital or The Royal Masonic Hospital between 1988 and 1995 were studied including those cycles where egg recovery was abandoned due to poor ovarian response. All patients underwent a standardized treatment protocol. Of those women who achieved a clinical pregnancy during their first IVF attempt, 33% achieved a pregnancy during their second cycle, statistically significantly different from the 24% of patients conceiving during a second cycle who had failed to conceive during their first. 36% of those who achieved a biochemical pregnancy in their first cycle became pregnant in their second. Age was an important factor in the success of IVF treatment, with pregnancy rates of 48% in the 20-25 year age group falling to 8% in those aged > or =41 years. Cumulative pregnancy rates were 26% after one cycle, increasing to 43% after two cycles and reached 80% after seven cycles. A previous pregnancy significantly improved a couple's probability of conception in a later IVF cycle. Overall pregnancy rates per cycle were constant for the first three attempts. Cumulative pregnancy rates continued to rise to 72% after six cycles. Thus the more cycles a couple undergo (up to six) the greater their chance of a pregnancy.     

Prediction of fatigue screw loosening in anterior spinal fixation using dual energy x-ray absorptiometry

STUDY DESIGN: A biomechanical study was performed to investigate a relation between the bone mineral density of the vertebral body and the number of loading cycles to induce fatigue loosening of an anterior vertebral screw. OBJECTIVES: The objective of this study was to investigate the potential usefulness of dual energy x-ray absorptiometry of measuring bone mineral density of the vertebral body in predicting the fatigue loosening of th anterior vertebral screw. SUMMARY OF BACKGROUND DATA: Loosening of the vertebral body screw is a well know failure in spinal instrumentation, and more commonly observed than pullout failure. The relation between bone mineral density and pullout strength of the screw has been investigated previously, but no studies are available on the fatigue loosening in anterior spinal fixation. METHODS: Bone mineral density was measured using dual energy x-ray absorptiometry and the screw loosening was produce by a cyclic loading in the cephalad-caudal direction. Screw loosening was defined as 1 mm displacement of the screw relative to bone, and the number of loading cycles to induce the screw loosening was obtained and statistically correlated with bone mineral density. RESULTS: There was a positive correlation between the number of loading cycles to induce screw loosening and bone mineral density (R = 0.8, P < 0.01). The average number of loading cycles to induce screw loosening was significantly less for specimens with bone mineral density < 0.45 g/cm2 compared to those with bone mineral density > or = g/cm2. CONCLUSIONS: These findings suggest that bone mineral density may be a good predictor of anterior vertebral screw loosening. Bone mineral density < 0.45 g/cm2 may be critical value of loosening of the anterior vertebral body screw. However, further biomechanical and clinical studies are required before using threshold value clinically.