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Biomedical subjects

R R Wilson

Publications and source records attributed to R R Wilson.

At least 19 recordsLinked to original sources

A cautionary note when using pepsin as a probe for the formation of a collagen triple helix.

The ability of the collagen triple helix to resist digestion with proteases has been used as a conformational probe to ascertain whether a collagenous molecule has formed a correctly aligned helix during biosynthesis or during refolding of the protein in vitro. During our studies into the synthesis and folding of a variety of engineered procollagen polypeptide chains, we noted that resistance to digestion with proteases, in particular pepsin, could be misleading and does not necessarily indicate the formation of a collagen triple helix. These results clearly show that resistance to pepsin digestion alone should not be used to indicate correct folding and that preferably an alternative assay should be used to unequivocally demonstrate the formation of a correctly aligned triple helix.

Animals

Restriction digest of PCR-amplified mtDNA from fin clips is an assay for sequence genetic "tags" among hundreds of fish in wild populations.

We tested the feasibility of recovering from wild populations mitochondrial DNA genetic "tags" that might result from release of hatchery-reared fingerlings for marine stock enhancement. A practical, nondestructive method of genetic "tag" recovery would allow quantitative assessment of the efficacy of such programs. A rare mtDNA variant with two sites each instead of one for TaqI and RsaI in the control region was used as a mock genetic "tag" in snook (Centropomus undecimalis). We assayed for the variant among nearly 900 fish by restriction digests of DNA amplified by polymerase chain reaction (PCR) obtained from fin-clip extracts, finding only a single second example of the variant. Thus, mtDNA "tags" can be nondestructively assayed for with specificity among hundreds of individuals.

Animals

The quality of life and employment in panic disorder.

Our purpose was to measure quality of life (QOL) and work productivity (WP) in persons with panic disorder. Eighty-four panic disorder patients with limited psychiatric comorbidity for ten U.S. outpatient mental health centers were evaluated in a cross-sectional design. Patients self-administered the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and Work Productivity and Impairment (WPAI) questionnaire. The independent effects of psychiatric comorbidity were addressed through entry criteria, stratification, and regression analyses. QOL scores are significantly below age and sex-adjusted population norms on all SF-36 measures (p < .01). We note far greater impairment on measures of mental and emotional versus physical well-being. The unemployment rate among these patients is 25%, and only 57% are employed full-time. Those who are employed rated their WP as low. This sample of outpatients suffer marked QOL and employment impairment, which is only partially explained by the presence of psychiatric comorbidity.

Adult

Intermittent transdermal nitroglycerin therapy in angina pectoris. Clinically effective without tolerance or rebound. Minitran Efficacy Study Group.

BACKGROUND: The objectives of this study were to assess the antianginal and anti-ischemic effects of three dose levels of transdermal nitroglycerin patches applied for 12 hours daily for 30 days. The study also assessed the development of tolerance and rebound. Intermittent transdermal nitroglycerin therapy with a patch-free period of 10 to 12 hours each day has documented clinical benefits during the period of patch application, but studies have failed to clearly document prolonged exercise duration for the entire period of patch application. This study was designed to evaluate the efficacy and duration of action of a range of doses of nitroglycerin. The study also permitted the assessment of the maintenance of initial effects, the development of tolerance, and the presence of rebound. METHODS AND RESULTS: This study was a multicenter, randomized, double-blind, placebo-controlled parallel design trial with treadmill exercise tests at days 0, 1, 7, 15, and 30. Tests were carried out up to 12 hours after patch application. There was a statistically significant treatment effect with increases in treadmill walking time to moderate angina in each nitroglycerin patch group compared with placebo at various time points up to 12 hours throughout the 30-day study period. Secondary efficacy parameters, including the consistent increase in time to 1-mm ST-segment depression, supported the primary efficacy results. There was no evidence of tolerance or rebound. CONCLUSIONS: Intermittent transdermal nitroglycerin therapy increases exercise duration and maintains anti-ischemic effects for 12 hours after patch application, throughout 30 days of therapy, without significant evidence of nitrate tolerance or rebound phenomena.

Administration, Cutaneous

Salsalate cross-sensitivity in aspirin-sensitive patients with asthma.

Ten aspirin (ASA)-sensitive patients with asthma underwent double-blind, placebo-controlled oral challenges with salsalate followed by ASA-sensitive confirmatory challenges. All 10 patients sustained asthmatic reactions to ASA, but only two developed respiratory reactions to 2 gm of salsalate. In these two patients, repeat confirmatory challenges with 2 gm of salsalate reproduced the same asthmatic reactions. Both patients were desensitized to ASA, and cross-desensitization with 2 gm of salsalate was then achieved. We conclude that salsalate, a weak inhibitor of cyclooxygenase in vitro, is less likely than ASA to induce asthma in known ASA-sensitive patients with asthma but may occasionally cross-react in these patients. Such reactions were mild and easily treated with beta 2-agonists.

Acetaminophen

Improved comfort and patient acceptance in a novel transdermal nitroglycerin delivery system.

Sixty-three angina patients were recruited to participate in a two-week, randomized, open-label, crossover, multicenter trial to compare patient acceptance of two transdermal nitroglycerin delivery systems, Minitran and Transderm-Nitro (TDN). Patients were enrolled if they had stable angina and had been on a stabilized dose (5, 10, or 15 mg/24 hr) of Nitro-Dur II (ND II) for at least one month before entering the study. Patients with a bias against TDN or with any of the contraindications for transdermal nitroglycerin therapy were excluded. During the two consecutive one-week treatment periods, the patients received their prestudy dose regimen of Minitran and TDN in random order. Patients completed daily diaries, weekly questionnaires, and poststudy patient preference evaluation forms. Of the 63 patients who completed the study, 70% preferred Minitran overall (P less than or equal to 0.001), 24% preferred TDN, and 6% had no overall preference.

Adhesiveness

Improved skin adherence and patient acceptance in a new transdermal nitroglycerin delivery system.

Sixty-five patients with angina pectoris participated in a two-week, randomized, crossover, open-label, multicenter trial to compare patient preferences between two transdermal nitroglycerin delivery systems: Minitran and Nitro-Dur II (ND II). Patients were enrolled if they had stable angina pectoris and had been on a stabilized dose (5, 10, or 15 mg/24 hr) of Transderm-Nitro (TDN) for at least one month before entering the study. Patients with a bias against ND II or with any of the contraindications for transdermal nitroglycerin therapy were excluded. During the first one-week treatment period, the patients received their prestudy dose regimen of either Minitran or ND II. During the second week, the patients were crossed over to the transdermal delivery system that they had not received in the first week. Patients completed daily diaries, weekly questionnaires, and poststudy patient preference evaluation forms. Two patients, one in each treatment group, withdrew from the study because of increased angina, which was probably not related to the use of transdermal nitroglycerin. Fifty-seven percent of the patients preferred Minitran overall (P less than or equal to 0.05), 27% preferred ND II, and 16% had no overall preference.

Adhesiveness

Temperature adaptation of fish hemoglobins reflected in rates of autoxidation.

Observation of rapid autoxidation of oxyhemoglobin (HbO2) from a deep-sea fish (Co-ryphaenoides acrolepis) prompted a survey of rates of autoxidation of HbO2 to methemoglobin in vitro from fishes inhabiting vastly different depths (1 to 3800 m) in order to discover any relationship between autoxidation rates and different environmental temperatures and pressures to which hemoglobins may be adapted. The rate of autoxidation was found to be sensitive to temperature in both deep- and shallow-living fishes. Hemoglobin appears to be thermally adapted since autoxidation was 10 times faster at all temperatures tested with HbO2 obtained from a cold-adapted fish (Coryphaenoides armatus variabilis) than from a comparatively warm-adapted one (Paralabrax nebulifer). High hydrostatic pressure does not affect autoxidation rates in either deep- or shallow-dwelling species. Rates of autoxidation may be intimately related to hemoglobin function thus providing a means for studying hemoglobin adaptation in poikilothermic vertebrates, especially among cold-adapted species.

Adaptation, Physiological

Chymodiactin in patients with herniated lumbar intervertebral disc(s). An open-label, multicenter study.

To extent the safety information for Chymodiactin (chymopapain for injection), 37 neurologic and orthopedic surgeons conducted an open-label, multicenter, phase 3 clinical study. A total of 1,498 patients with one or two herniated lumbar intervertebral discs were enrolled. Therapeutic results were generally favorable, with the percentages of patients achieving either excellent or good (or successful) results ranging from 79.6% to 88.9%, depending on criteria employed in the tabulation. There were 13 cases of anaphylaxis, and 2 of these patients died of complications of anaphylaxis. Two additional patients experienced serious neurologic problems. The first of these two patients developed transverse myelitis and paraplegia approximately 3 weeks following chemonucleolysis. Transdural discograms at three levels had been done approximately 2 days prior to chemonucleolysis, in violation of the protocol. The second patient developed acute cauda equina syndrome, and, despite emergency laminectomy, had permanent neurologic sequelae. Back spasm and stiffness/soreness were the most frequently encountered adverse experiences.

Adolescent

The transdermal administration of nitrates: an overview.

Nitroglycerin has been the mainstay of the medical management of angina pectoris for over 100 years. The long-held clinical impression of the efficacy of nitroglycerin has now been clearly documented in controlled clinical trials designed to evaluate objective response to antianginal agents. Advances in scientific methodology and improved experimental design have contributed to continuing interest in nitrates. Newer uses of nitroglycerin and other nitrates in congestive heart failure and acute myocardial infarction are the result of a developing understanding of the pharmacology of nitrates.

Administration, Oral

Disopyramide: six years' experience.

Since its approval by the FDA six years ago, oral disopyramide has earned a recognized role in the treatment of ventricular arrhythmias. During this time, clinical experience has refined our knowledge of this agent, allowing revision of dosing guidelines and better selection of patients. This review explores the recent therapeutic experience with disopyramide.

Arrhythmias, Cardiac

A randomized, double-blind, parallel group comparison of disopyramide phosphate and quinidine in patients with cardiac arrhythmias.

This report summarizes the results of a randomized, double-blind, parallel group, multicenter study which compared the antiarrhythmic activity and safety of oral disopyramide phosphate and oral quinidine sulfate. A total of 124 outpatients, whose pretreatment rates of ventricular and/or supraventricular arrhythmias were documented by ambulatory ECG recordings, were randomly assigned to receive either oral disopyramide or oral quinidine for the eight-week course of the study. Every two weeks, ten-hour ambulatory ECG recordings were obtained from each patient and blood was drawn to determine serum concentrations of assigned drug.

Administration, Oral