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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

An isolated case of leprosy presenting in a migrant worker in Northern Ireland.

Leprosy was first recorded in 600 bc in India. Europe saw its first cases in the fourteenth century. The worldwide incidence is falling, but the disease can still present in the most unexpected places: this is a report of the first case of leprosy presenting to an emergency department in Northern Ireland. It is important for physicians in both community and hospital medicine to have a high index of suspicion for leprosy in patients with chronic skin conditions who were born outside the UK or other developed countries.

Adult↗

Molecular characterization and expression of p63 isoforms in human keloids.

Keloids are benign skin tumors that develop following wounding. A cDNA product from human keloid specimens was identified using the differential display technique. The full-length cDNA was cloned by RT-PCR using human keloid mRNA as template. The predicted product of the cDNA was found to be 99% identical to the DeltaN-p63 gamma isotype of p63, a transcription factor that belongs to the family that includes the structurally related tumor suppressor p53 and p73. The DeltaN-p63 isotype lacks the acidic N terminal region corresponding to the transactivation domain of p53. Since this can potentially block p53-mediated target gene transactivation, it may serve as a dominant-negative isoform. Real-Time RT-PCR analysis of RNAs from normal skin tissue and keloids showed that the DeltaN-p63 isotype is specifically expressed in keloids, but is virtually undetectable in normal skin. Immunostaining of p63 in normal skin revealed that only basal cells of the epithelium expressed the protein, while in keloid tissues the antigen was detected in the nuclei of cells scattered through all layers of the epithelium and in fibroblast-like cells in the dermis. These results may indicate that aberrant p63 expression plays a role not only in malignant tumors but also in benign skin diseases that show hyperproliferation of epidermal cells in vivo. Moreover, this isoform of p63 could serve as a specific molecular marker for this human disease.

DNA-Binding Proteins↗

A new species of Nezumia (Gadiformes: Macrouridae) from Fieberling Guyot, eastern North Pacific Ocean.

A new species of the macrourine genus Nezumia is described from specimens collected from the crest of Fieberling Guyot in the eastern North Pacific Ocean. The new species is distinguishable from all other Nezumia species chiefly on the basis of a high number of pelvic fin rays, a relatively high number of first dorsal fin soft rays, a steep blunt snout lacking scales ventrally, a relatively weak suborbital ridge, and a moderately long, thin barbel. Although possibly endemic to the Baja California Seamount Province, the new species appears to lack close relatives among the other Nezumia species of the eastern North Pacific Ocean. It might have arrived there either from a disjunct Tethyan distribution, thus retaining close relatives among the Atlantic Ocean species of Nezumia, or by way of stepping-stone dispersal from the Indo-west Pacific Ocean.

Animals↗

Amphi-panamic geminates of snook (Percoidei: Centropomidae) provide a calibration of the divergence rate in the mitochondrial DNA control region of fishes.

The mitochondrial DNA control region is one of the most frequently utilized sequences for both intra- and interspecific genetic studies of fishes, yet a tenable divergence rate specifically for fish control regions has not been established. We attempted to establish a rate through a comparative study of control region sequences and those of a protein-coding mitochondrial gene region from geminate species of snook (Centropomus) assumed to have been separated by the emergence of the Isthmus of Panama 3.5 million years ago. The divergence rate suggested from the control region alignments between the geminates was markedly higher than rates currently applied in many studies, as was the rate suggested from the ND 5/6 protein coding region alignments. However, the suggested ND 5/6 rate when applied to alignments with the outgroup species was not concordant with the scant centropomid fossil record and therefore the assumed separation time of 3.5 million years seemed implausible. An average control region divergence rate was then estimated based on separation times of snook species derived assuming a divergence rate of 1% per million years for transversion substitutions at third codon positions in the ND 5/6 region. Using these separation times, a tenable average divergence rate for fish control regions of approximately 3.6% per million years +/- 0.46% SE was calculated.

Animals↗

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↗