Current Status of Transcatheter Tricuspid Valve Therapies.

Tricuspid regurgitation is a complex disease that carries a poor prognosis, and surgical repair is associated with high mortality. In light of the success of other transcatheter-based valve interventions, transcatheter tricuspid therapy has recently seen exponential use both clinically and in innovation. Given the rapid development of many tricuspid systems and multiple on-going clinical trials, the aim of this review is to highlight the current state of transcatheter tricuspid therapeutics and to provide an up-to-date view of their clinical use, outcomes and future directions.

DNA sequence analysis for structure/function and mutation studies in Becker muscular dystrophy.

We systematically screened the whole coding region of 18 male muscular dystrophy patients whose clinical, histological and laboratory findings suggest Becker muscular dystrophy (present but abnormal dystrophin). No systematic mutation study of a cohort of patients with dystrophin of normal quality but abnormal quantity has been published. The complete coding sequence of the dystrophin gene (11 kb) of each patient was subjected to an automated sequence analysis by using muscle biopsy RNA; 535 bp of the gene promoter and 5'UTR were likewise sequenced. We identified seven disease-causing mutations (40%). Six were novel, including missense, nonsense, small deletion and splice site mutations. Sixty percent (11/18) of patients with decreased quantities of normal molecular weight dystrophin showed no mutation, but most of them had a family history highly suggestive of X-linked inheritance, suggesting transcription or translational deleterious affection, i.e. outside what was screened. Quantitative multiplex fluorescence polymerase chain studies of mutation-negative patients showed normal levels of dystrophin mRNA. In three patients, there was some reduction of the transcript suggesting a deleterious undetected gene change resulted in the reduction of RNA levels. Our data address important structure/function and genotype/phenotype correlations and it suggests that dystrophin protein studies must be interpreted with caution in deletion-negative male muscular dystrophy patients.

Evidence for TeV Emission from GRB 970417a.

Milagrito, a detector sensitive to very high energy gamma rays, monitored the northern sky from 1997 February through 1998 May. With a large field of view and a high duty cycle, this instrument was well suited to perform a search for TeV gamma-ray bursts (GRBs). We report on a search made for TeV counterparts to GRBs observed by BATSE. BATSE detected 54 GRBs within the field of view of Milagrito during this period. An excess of events coincident in time and space with one of these bursts, GRB 970417a, was observed by Milagrito. The excess has a chance probability of 2.8x10-5 of being a fluctuation of the background. The probability for observing an excess at least this large from any of the 54 bursts is 1.5x10-3. No significant correlations were detected from the other bursts.

Intern Prescribing for Common Clinical Conditions.

To examine the ability of interns to prescribe appropriately for common clinical conditions at the commencement and completion of the intern year. Interns' perceptions of their ability to prescribe and the perceived influences on their practices were also assessed. The study was conducted at a teaching hospital in urban New South Wales, Australia. A self-complete questionnaire was administered to 56 interns at the beginning and end of internship. At the beginning of the year respondents were asked to identify how equipped they felt they were to perform specific functions related to prescribing practice. Interns were also asked to write hospital prescriptions for four common clinical cases scenarios: post-operative pain, urinary tract infection, asthma, and community-acquired pneumonia. At the end of the year interns were asked to prescribe for the same clinical scenarios and also asked to identify the main influences on their practice. At the beginning of the year 54% of interns felt equipped to choose an appropriate drug for common clinical conditions, however, few felt they were able to determine the appropriate dose (23% of respondents) or dose frequency (25%). A previously validated four-point rating scale was used by two assessors to judge appropriateness of prescribing [Kappa = 0.6]. At the beginning of the year at least two-thirds of interns were prescribing 'inappropriately' for all clinical conditions. By the end of the year 75% were prescribing 'appropriately' for all conditions. The main perceived influences on prescribing practices were registrars, consultants, books and pharmacists.The use of hypothetical clinical cases to explore prescribing ability has shown that doctors are ill-equipped to perform various aspects of prescribing on graduating from medical school. Although our findings may not translate into practice directly they highlight the existence of a potential problem that warrants further study, especially in the areas of actual practice and the influences on it in the early postgraduate years.

TeV Observations of Markarian 501 with the Milagrito Water Cerenkov Detector.

The Milagrito water Cerenkov detector near Los Alamos, New Mexico, was operated as a sky monitor at energies of a few TeV between 1997 February and 1998 May, including the period of the strong, long-lasting 1997 flare of Markarian 501. Milagrito served as a test run for the full Milagro detector. An event excess with a significance of 3.7 sigma from Markarian 501 was observed, in agreement with expectations.