Ablepharon macrostomia syndrome with associated cutis laxa: possible localization to 18q

The ablepharon-macrostomia (AMS) and Barber-Say syndromes (BSS) are rare disorders characterized by absence of the eyelids or ectropion, macrostomia, ambiguous genitalia, abnormal ears, rudimentary nipples, and dry, redundant skin. Patients with Barber-Say syndrome also have hypertrichosis. We present a patient with a phenotype similar to AMS who has a complex rearrangement of chromosome 18, involving both an inversion and interstitial deletion. Our patient lacks the typical features of the 18q deletion syndrome. We review AMS and BSS as compared with our patient, and recognize cutis laxa as a feature shared by all. We propose that the gene(s) for this phenotype may lie on chromosome 18 in the region of the deletion or inversion breakpoints.     

Measuring L-dopa in plasma and urine to monitor therapy of elderly patients with Parkinson disease treated with L-dopa and a dopa decarboxylase inhibitor

We have established a method for measuring L-dopa in plasma and urine, including the metabolites dopamine and L-dopac, using separation by ion-pair reversed-phase HPLC and quantification with an electrochemical detector. The assay was applied to the therapeutic monitoring of elderly patients with established Parkinson disease being treated with L-dopa plus a dopa decarboxylase inhibitor. Plasma L-dopa was evaluated in relation to dosage and postdose sampling time in 71 outpatients with Parkinson disease. L-Dopa concentrations were greatest in the patients taking the highest dosages prescribed and decreased significantly with increasing time after postdose sampling. Comparison of plasma L-dopa concentrations with a published therapeutic range established by intravenous administration of L-dopa was helpful in assessing the suitability of each patient's drug dosage, assessing patients' compliance, and avoiding overdosage but was not useful in the overall clinical assessment of progression of disease or of the long-term therapeutic response. Urine measurements confirmed the plasma concentrations but showed no further advantage. The recommended time for sample collection is between 1.5 and 3 h after the first morning dose. Plasma is the preferred matrix but if blood sampling is difficult, particularly from elderly/infirm individuals, an untimed urine collection could be used.     

Evidence for a 1,2-hydride shift in the microsomal metabolism of the heterocycle L-158,338, a nonpeptide angiotensin II receptor antagonist

L-158,338 is an imidazo[4,5-b]pyridine derivative that is a potent and highly selective angiotensin II receptor antagonist. Rat liver microsomal metabolism of [C6-3H]L-158,338 gave a major metabolite that was monohydroxylated at the C6 position of the imidazo-pyridine but showed partial retention of the radiolabel. This biotransformation necessitated a shift of the radiolabel from the C6 position to another site within the molecule. We have investigated the mechanism of this biotransformation using 3H-, 3H/14C-, and 2H-labeled L-158,338. Metabolites were identified by FAB/MS, LC/MS, and 1H-NMR. Results of these studies show that the microsomal metabolism of L-158,338 to its C6-monohydroxylated derivative was mediated by a 1,2 hydride shift.     

Fatigue performance of ultra-high-molecular-weight polyethylene: effect of gamma radiation sterilization

Ultra-high-molecular-weight polyethylene (UHMWPE) failure presents a significant materials concern in the orthopaedic community. Clinical failure following joint arthroplasty can result from the biological response to wear debris as well as structural failure owing to UHMWPE fatigue. In this study, cantilever rotating beam fatigue testing was conducted on GUR 415 UHMWPE in both the unsterilized and gamma radiation sterilized conditions. Calculations of flexural fatigue stresses were based on extreme fibre stresses and assumed negligible plastic deformation. Both material conditions exhibited similar fatigue strengths at 250,000 cycles (approximately 41 MPa) and at one million cycles (approximately 36 MPa), but a large difference developed after two million cycles. At ten million cycles, the unsterilized condition exhibited a fatigue strength of approximately 31 MPa, while the gamma-sterilized condition exhibited a reduced fatigue strength of approximately 18 MPa, an approximate decrease of 42%. High-cycle fatigue testing was necessary to fully characterize this behaviour owing to the pronounced difference in fatigue behaviour beyond two million cycles. These results suggest that gamma radiation sterilization of UHMWPE medical implants reduces their resistance to cyclic loading and, subsequently, may contribute to the associated fatigue-related failures which have been reported clinically.     

Infective endocarditis in adolescents. Analysis of risk factors for hospital mortality

PURPOSE: To study the epidemiological, clinical, therapeutic and evolutive aspects of endocarditis in a group of patients aging 12 to 20 years-old (mean 15.5). METHODS: Thirty-three consecutive patients (14 males, 19 females) admitted with infective endocarditis were retrospectively studied. RESULTS: Infective endocarditis mortality was 42%. Rheumatic heart disease was the predominant underlying condition in 63% of patients. Congenital heart disease (24%) and cardiac prosthesis (12%) were the other affections involved. The majority of patients (78%) were in functional class III and IV, with more deaths than the 22% who were in functional class I and II (p = 0.01). Staphylococcus aureus was the most frequently isolated agent (42% of the positive blood cultures, followed by Staphylococcus viridans, 21%). Multivariate analysis identified total leukocyte count above 10,000/mm3 and functional class, both at admission (p = 0.01 and p = 0.004, respectively), and the occurrence of embolic complications (p = 0.03) as independent predictors of in-hospital mortality. CONCLUSION: Rheumatic heart disease remains, as in adults, the main predisposing factor for infective endocarditis in adolescents, and S. aureus is, like in children, the leading agent. Mortality is high and functional class at hospital admission, embolic complications and leukocytosis are independent predictors of in-hospital mortality.