Solvent effects on the conformation of cyclo(-D-Trp-D-Asp-Pro-D-val-Leu-) An NMR spectroscopy and molecular modeling study

The conformations of cyclo(-D-Trp-D-Asp-Pro-D-val-Leu-) in dimethyl sulfoxide-d₆ (DMSO-d₆) and water were determined using two-dimensional nuclear magnetic resonance spectroscopy and restrained molecular dynamics. Comparisons were made between conformations of the cyclic pentapeptide in both solvents. The NMR study revealed that, while the backbone remained relatively unchanged in both solvents, the side-chains adopted distinctly different orientations in DMSO-d₆ vs. H₂O. A modeling study, minus NOE constraints, produced a set of low-energy conformers possessing agreement in backbone conformation with the NMR-derived structures; however, lowest-energy conformers did not have this agreement. These results show that different solvents can significantly affect the preferred side-chain conformation of small cyclic peptides in solution. This finding will impact the selection of solvent when determining structures for use as templates in rational drug design.     

Anti-hCG Vaccines are in Clinical Trials

Two vaccines inducing antibodies against human chorionic gonadotropin (hCG) have completed Phase I clinical trials, indicating the reversibility and safety of these vaccines. One is currently in Phase II efficacy trials in women in three major centres in India. The available data suggest that the vaccine prevents pregnancy above antibody titres of 50 ng/ml hCG bioneutralization capacity.     

Withdrawal of antihypertensive drug treatment: time-course for redevelopment of hypertension and effects upon left ventricular mass.

OBJECTIVES: To examine: (1) in how many treated hypertensive patients it was possible to discontinue drug treatment; (2) the time-course for redevelopment of hypertension after discontinuation of therapy; and (3) whether drug withdrawal was associated with an increase in left ventricular mass (LVM). DESIGN: Fifty-four men with primary hypertension treated for a mean period of 6 years (primarily beta 1-selective beta-blockade) were evaluated for withdrawal of treatment. Exclusion criteria were signs of organ damage, severe hypertension, other serious disease and unwillingness. Treatment was reinstituted if blood pressure increased above a safety level or if symptoms occurred. Echocardiographic estimations of LVM were obtained before withdrawal and 1, 4 and 8 weeks after withdrawal or before return to treatment. SETTING: Outpatient clinic in a city hospital. PATIENTS: A random sample of 56-year-old hypertensive men. INTERVENTION: Gradual discontinuation of treatment with close follow-up of blood pressure. MAIN OUTCOME MEASURES: Number of patients who could withdraw from treatment and who had to return to pharmacological therapy; time-courses for development of hypertension; absolute changes in LVM. RESULTS: Thirty-two patients withdrew from treatment for 1-1000 days. Therapy was reinstituted in all owing to hypertension or symptoms. Serial echocardiograms were obtained in 22 patients. During the drug-free period, relative wall thickness increased, but LVM did not. Patients with rapid redevelopment of hypertension had larger prewithdrawal LVM than patients whose blood pressure increased more slowly. CONCLUSION: It was possible to withdraw treatment and obtain readable echocardiograms in a minority of the patients. After drug-withdrawal, relative wall thickness increased, but not LVM. We suggest that previously treated patients should be avoided in studies examining reversal of left ventricular hypertrophy.     

Relationship between Myopia and Optical Components - A Study among Chinese Hong Kong Student Population

Purpose: To establish the prevalence and severity of myopia among the Chinese Hong Kong students and to study the relationship between myopia and optical components.Methods;One thousand and seventy-five freshmen of the 1993-1994 academic year in the Chinese University of Hong Kong underwent the eye examination including evaluation of refractive error, keratometry, and A-scan ultrasonic biometry. The data were analyzed with the SPSS/PC 4. 01 statistical package. Results: The prevalence of myopia was 91. 7% with the mean refraction being -4. 00 ± 2. 64D in this young adult population. The statistical analyses demonstrated a significant correlation between refractive value and axial length of the globe (r=-0. 78), vitreous length (r=-0. 76), anterior chamber depth (r=-0. 33), lens thickness (r = 0. 13) and corneal curvature (r = 0. 19). Conclusion: The refractive status is mainly dependent on the axial length. In general, the higher the myopia was, the longer the eyeball, the deeper the anterior chamber,     

Rates of claims for cumulative trauma disorder of the upper extremity in Ontario workers during 1997

Surveillance of work-related cumulative trauma disorder of the upper extremity (CTDUE) requires valid and reliable claim extraction strategies and should examine for confounding and interaction. This research estimated crude and specific rates of CTDUE claims in Ontario workers during 1997 while acknowledging misclassification and testing for confounding and interaction. Lower and upper limit event estimates were obtained by means of an algorithm applied to the Ontario Workplace Safety and Insurance Board (OWSIB) database and were combined with "at-risk" estimates obtained from the Canadian Labour Force Survey (LFS). Poisson regression was used to evaluate confounding and interaction. The method used to identify CTDUE claims had a substantial impact on the magnitude of rates, female to male rate ratios, the most commonly affected part of the upper extremity and the highest risk occupational categories. Poisson regression identified sex interactions. It allowed rigorous evaluation of the data and indicated that rates should be examined separately for men and women. Researchers should clearly define extraction strategies and examine the impact of misclassification.     

Biomechanical superiority of plate fixation for proximal tibial osteotomy

Proximal tibial osteotomies require secure and durable fixation to allow early range of motion; however, biomechanical data comparing commonly used fixation methods are lacking. The current study was done to quantify the dynamic biomechanical performance of blade staple fixation and plate fixation of simulated proximal tibial osteotomies. A 15 degrees proximal tibial osteotomy was done on each of 18 synthetic adult composite tibias. Blade staples were used as the means of fixation in nine tibias; plate fixation was used in the remaining nine tibias. The specimens were stressed cyclically in sinusoidal loading whose peak compression and tension loads imitate those measured during normal gait. Device performance was quantified by measuring displacement at the osteotomy site and the number of cycles to failure. Plate fixation had a greater fatigue life than staples (eight plates surviving past 200,000 cycles versus one blade staple) and showed a trend toward less displacement (0.69 mm versus 0.97 mm). Plate fixation of proximal tibial osteotomies offers better fixation and dynamic mechanical performance than blade staples.     

Growth hormone response to edrophonium in Alzheimer's disease

Neuropathologic data from patients with Alzheimer's disease indicate the presence of neurofibrillary tangles in hypothalamic regions associated with regulation of pituitary hormone release. The authors explored the hypothesis that cholinergic projections to hypothalamic nuclei controlling pituitary growth hormone (GH) release degenerate in Alzheimer's disease. Integrity of cholinergic regulation was tested by assaying the GH response to a presynaptic cholinergic challenge. After administration of the choline esterase inhibitor edrophonium, the peak GH response was 14 ng/ml in healthy elderly control subjects and only 2 ng/ml in Alzheimer's patients. The magnitude of GH blunting was correlated with cognitive and functional deficits. Possible implications of these data for enhanced accuracy in the diagnosis of dementia are discussed.     

Late arthroscopic debridement of metal fragments and synovectomy after penetrating knee joint injury by low-velocity missile: a report of two cases

Retained metal debris from intraarticular missile injury to the knee may produce mechanical symptoms and synovitis. Arthroscopic debridement and thorough synovectomy can relieve symptoms and allow early return of function.