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Biomedical subjects

R J Lewis

Publications and source records attributed to R J Lewis.

At least 235 records · Page 13Linked to original sources

Sequential clinical trials in emergency medicine.

In a traditional clinical trial, a fixed number of patients are evaluated before the data are analyzed. This has the disadvantage that more patients may be enrolled than are necessary to achieve a statistically significant result. Sequential statistical techniques provide a method for the analysis of clinical trials so that a reliable result is obtained with a minimum number of patients. In a sequential trial, the data are analyzed after each patient's outcome is known, and the trial is halted as soon as treatment efficacy or lack thereof is demonstrated. This study was undertaken to confirm the advantages of sequential statistical techniques over conventional fixed-sample-size statistical techniques for the analysis of clinical trials. Using sequential techniques, we conducted computer simulations of two fixed-sample-size clinical studies from the literature - a trial of hepatitis B vaccine in homosexual men (N Engl J Med 1980;303:833-841) and a trial of the pneumatic antishock garment in hypotensive patients with penetrating abdominal trauma (Ann Emerg Med 1987;16:653-658). In the trial simulations, patients were randomly assigned to the control and test groups, their outcomes were determined randomly according to the frequency of outcomes observed in the actual studies, and the simulated sequential studies were continued until conclusions were reached. Thousands of possible realizations of each trial were simulated; thus, the distribution of required patient numbers was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

Ciguatera and mannitol: experience with a new treatment regimen.

Ciguatera is a distressing, hitherto-untreatable and not rare disease which results from the eating of ciguatoxin-contaminated fish from tropical and subtropical waters. We report here the results of a pilot study to assess the efficacy of mannitol therapy in ciguatera poisoning. Twelve adult patients (six men) have been treated, five of whom--who were ill acutely--experienced a significant benefit from this therapy, in three cases, with a hitherto-unexperienced dramatic reversal of symptoms. We conclude that an intravenous infusion of 1.0 g/kg of mannitol which is given over 45 minutes, after rehydration if required, can be of significant benefit to at least some acutely intoxicated victims. We postulate either a reduction of axonal oedema, or a scavenger effect, or both, as the mechanism of the beneficial effects of mannitol. Ciguatoxin is rich in hydroxyl groups, and causes microscopic oedema of neural tissue. If our conclusion of the beneficial effects of mannitol therapy is confirmed, this will offer the first effective therapy for acute phases of this disease, and has promise of preventing much long-term morbidity.

Acute Disease↗

Body-image disturbances in adolescent female binge-purgers: a brief report of the results of a national survey in the U.S.A.

A sample (N = 114) of adolescent female binge-purgers were among the respondents to a nationwide survey on body-image. Relative to female controls (N = 114) who were matched on age, height and weight, binge-purgers evaluated their physical appearance, fitness and health much less favourably. However, they reported being more appearance-oriented and fitness-oriented than controls. Regardless of actual weight, binge-purgers more often distorted their body size as heavier than did controls, displayed more anxious preoccupation about their weight and weight gain and reported much more frequent eating restraint to lose weight. Binge-purgers also considered themselves to be more poorly psychosocially adjusted, with a reported childhood history of appearance-related conflicts. Discriminant function analysis indicated that the above variables were very accurate in classifying the two groups.

Adolescent↗

The use of indium-111 labeled platelet scanning for the detection of asymptomatic deep venous thrombosis in a high risk population.

Five hundred indium-111 labeled platelet imaging studies (387 donor and 113 autologous) were performed postoperatively in 473 patients who had undergone total hip replacement, total knee replacement, or internal fixation of a hip fracture to detect occult deep venous thrombosis. All patients had been anticoagulated prophylactically with aspirin, warfarin sodium (Coumadin), or dextran. Thirty-four possible cases of proximal deep venous thrombosis were identified in 28 asymptomatic patients. To verify the scan results, 31 venograms were performed in 25 patients (three refused). In 21 of 31 cases, totally occlusive thrombi were detected; in 5 cases, partially occlusive thrombi were detected; in 5 cases, no thrombus was seen. No patient who had a negative scan nor any patient who had a verified positive scan (and received appropriate heparin therapy) subsequently developed symptoms or signs of pulmonary embolism. One hundred forty-one indium study patients also underwent Doppler ultrasonography/impedance plethysmography (Doppler/IPG) as a comparative non-invasive technique. In 137 cases, the results of the indium study and Doppler/IPG studies were congruent. The indium study had no false negative results that were detected by Doppler/IPG. No patient had any clinically evident toxicity. These results suggest that indium-111 labeled platelet scanning is a safe, noninvasive means for identifying DVT in high risk patients.

Adult↗

Alcohol, other drugs, and fatal work-related injuries.

The purpose of this study was to determine the proportion of fatal work-related injuries that involved alcohol and other drugs in Harris County, Texas (which includes most of the city of Houston) during 1984 and 1985. A total of 207 death certificates and 196 autopsy reports that classified deaths as occurring at work were identified, and the demographic and toxicologic information was reviewed. Tests for alcohol were conducted for 173 (88.3%) of the workers autopsied; 23 (13.3%) had a detectable blood alcohol content. Drug screens, in addition to tests for alcohol, were performed on 172 (87.8%) of the workers autopsied; 12 (7.0%) had detectable traces of drugs which had the potential to alter physiologic functions needed to avoid injury. Only one case of illicit drug use was detected. When substances were detected, alcohol and prescription drugs, not illicit drugs, were the ones most frequently found.

Accidents↗

The relationship between adult sexual adjustment and childhood experiences regarding exposure to nudity, sleeping in the parental bed, and parental attitudes toward sexuality.

The relationship between adult sexual functioning and childhood experiences with exposure to nudity, sleeping in the parents' bed, and parental attitudes toward sexuality was examined. Although a variety of experts have provided their opinion on this issue, empirical research on this topic has been lacking. In this study, male and female college students were asked to retrospectively report on the frequency of sleeping in the parental bed as a child, the frequency of seeing others nude during childhood, and parental attitudes regarding sexuality. Information on current sexual functioning and adjustment was also obtained. The results suggest that childhood experiences with exposure to nudity and sleeping in the parental bed are not adversely related to adult sexual functioning and adjustment. In fact, there is modest support that these childhood experiences are positively related to indices of adjustment. Results also suggest that a positive attitude toward sexuality can be beneficial for a child's comfort with his/her sexuality. Finally, examination of gender differences revealed that male and female experience paternal attitudes toward sexuality differently but are similar in their perceptions of maternal attitudes.

Adolescent↗

Negative inotropic and arrhythmic effects of high doses of ciguatoxin on guinea-pig atria and papillary muscles.

Ciguatoxin, the toxin present in fish responsible for ciguatera, at doses equal or above the maximum positive inotropic dose in atria (greater than 0.15 mouse units/ml) induced arrhythmias in atria and papillary muscles stimulated at 1 Hz and dose-dependent negative inotropy in atria. Negative inotropy was enhanced by ouabain or by an increase in stimulation to 3 Hz, little affected by procaine or increasing Ringer [Ca2+] and reversed by lidocaine and tetrodotoxin (TTX). Ciguatoxin caused negative inotropy associated with cell depolarisation in 1.2 mM Ca2+-Ringer and additionally caused signs of Ca overload in 3.2 mM Ca2+-Ringer. Ciguatoxin induced transient after-contractions and contracture in atria which were common in 3.2 mM but not 1.2 mM Ca2+-Ringer and which were enhanced by ouabain. TTX and lidocaine abolished after-contractions and contracture while procaine was less effective. Extrasystoles consisting of short bursts of 1-2 extra contractions per sec were seen in atria and papillary muscles within 45 min of ciguatoxin being added. The effect was observed in 3.2 mM but seldom in 1.2 mM Ca2+-Ringer and was absent when low doses of propranolol or TTX were added prior to ciguatoxin. Flutter was observed in a few papillary muscles after ciguatoxin. These results suggest that the toxic effects of ciguatoxin stem from its direct action of opening myocardial Na+ channels. Extrasystoles appeared to result mainly from its effect on neural Na+ channels causing an increased release of noradrenaline from the nerves associated with the myocardium.

Animals↗

Brain lesions in a Pacific white-sided dolphin (Lagenorhynchus obliquidens).

A young, male, free-ranging Pacific white-sided dolphin (Lagenorhynchus obliquidens) was found disoriented and died after being held in captivity for several months. Malacic lesions in several areas of the brain were associated with helminth eggs. The appearance and location of these eggs suggested they were of the genus Nasitrema.

Animals↗

Successful joint arthroplasty following Proteus morganii (Morganella morganii) septic arthritis: a four-year study.

Proteus morganii (Morganella morganii) is an uncommon cause of septic arthritis. We describe a 53-year-old woman with severely deforming rheumatoid arthritis, who developed an indolent septic arthritis secondary to infection with this organism. She was treated with antibiotics and closed drainage, and subsequently, underwent successful arthroplasty. She continues to do well 4.5 years later. This patient's disease course shows that gram-negative septic arthritis, effectively treated, does not preclude successful total joint arthroplasty.

Arthritis, Infectious↗

Processivity of T4 endonuclease V is sensitive to NaCl concentration.

We previously reported that endonuclease V of bacteriophage T4 reacts processively with pyrimidine dimers in UV-irradiated DNA, tending to react with all of the dimers on one DNA molecule before reacting with any dimers on another DNA molecule [Lloyd, R. S., Hanawalt, P. C., & Dodson, M. L. (1980) Nucleic Acids Res. 8, 5113-5127]. In this paper we show that this processivity depends upon salt concentration: it can be detected in 10 mM NaCl but not, by our methods, in 100 mM NaCl. In addition, we show that endonuclease V binds to unirradiated DNA in 10 mM NaCl but not in 100 mM NaCl. We conclude that T4 endonuclease V binds to pyrimidine dimers in a two-step process in 10 mM NaCl. It first binds electrostatically to undamaged sections of DNA, and it remains bound during the second step in which it "searches" for pyrimidine dimers. Our conclusion is analogous to the expanded target theory developed for Lac repressor [Berg, O. G., Winter, R. B., & von Hippel, P. H. (1981) Biochemistry 20, 6929-6948].

DNA Damage↗

Substrate range of the 40,000-dalton DNA-photoreactivating enzyme from Escherichia coli.

We determined the ability of the 40 000-dalton Escherichia coli photoreactivating enzyme to act on a variety of pyrimidine-pyrimidine photoproduct substrates in nucleic acids. The enzyme is at least as active on cis-syn-cyclobutylpyrimidine dimers in supercoiled DNA as in linear DNA, but inactive on dimers in RNA. Both the phosphodiester bond internal to the deoxyriboses of the pyrimidines of the dimer and the N-glycosyl bond joining the pyrimidine to deoxyribose must be intact for enzyme action. The enzyme has no activity toward (6-4) pyrimidine-cytosine products in DNA.

Base Sequence↗

Direct and indirect effects of ciguatoxin on guinea-pig atria and papillary muscles.

The mode of action of ciguatoxin (CTX) on the isolated atrial and papillary muscle of the guinea-pig heart was investigated using conventional methods for the measurement of mechanical and electrophysiological parameters. CTX induced positive inotropic and positive klinotropic responses in atrial and papillary muscles. Each response consisted of two phases. The initial positive inotropic response developed rapidly and resulted from the previously reported indirect action of CTX. The second phase of positive inotropy developed more slowly and was well maintained at doses of CTX up to 0.15 mouse units/ml in atria and up to 0.8 M.U./ml in papillary muscles. This phase was found to result from a direct action of CTX on the myocardium which was not reversed by washing. Tetrodotoxin (TTX) reversed the positive inotropic effects stemming from the direct action of CTX. The (-) and (+) enantiomers of propranolol were equally effective in inhibiting the direct effect of CTX. These antagonists did not displace CTX from the myocardium. CTX induced a TTX-sensitive depolarization of stimulated or quiescent atrial cells. All the effects of CTX on the atrial action potential were reversed by TTX. It was therefore concluded that CTX opens voltage dependent Na+ channels. CTX bound equally to resting and K+-depolarized Na+ channels but there were indications that electrical stimulation enhanced the rate of CTX binding. CTX overrides the positive staircase effect of increasing stimulation frequency. Na+ channels found in the atria which were particularly sensitive to TTX did not play a prominent role in mediating the CTX effect. CTX appeared to have little effect on the normal Na+ channel inactivation process. CTX did not restore contractions in the K+-depolarized cardiac muscles examined. The sensitivity of CTX action to TTX distinguished it from cardiac glycoside activity. Established mechanisms of Na+/Ca2+ exchange and Ca2+-induced release of Ca2+ can explain the link between CTX-induced increase of intracellular [Na+] and the positive inotropic response.

Action Potentials↗

Antidiuretic effect and pharmacokinetics of oral 1-desamino-8-D-arginine vasopressin. 1. Studies in adults and children.

The dose-response relationships and pharmacokinetics of orally administered 1-desamino-8-D-AVP (DDAVP) were investigated. In water-loaded normal subjects marked reductions in urine flow rate and increases in urinary osmolality occurred. The responses were maximal 2 h after ingestion of 50, 100, and 200 micrograms, and lasted at least 6 h. Plasma DDAVP levels increased in a dose-dependent fashion and its disappearance from the plasma followed an exponential time course, with a half-life 86 to 142 min. In water-loaded adults with central diabetes insipidus (CDI), 200 micrograms oral DDAVP caused marked antidiuresis and mean urinary osmolality increased from 107 mosm/kg to 554 mosm/kg after 3 h. In these patients the effect also lasted at least 6 h. Children with CDI were less sensitive than normal subjects to the 50-microgram dosage and required 100 micrograms orally to achieve a duration of action similar to that resulting from 200 micrograms in adults. Oral DDAVP may be useful for treating some patients with CDI.

Administration, Intranasal↗

Reversible total esophageal exclusion.

A 23-year-old man with miliary tuberculosis had severe esophageal hemorrhage secondary to eroding tuberculous nodes. Balloon tamponade and packing with gauze did not alter the profuse bleeding. Empyema of the right thorax, massive mediastinal nodes, an unknown site of bleeding in the esophagus, and diffuse pulmonary involvement with tuberculosis precluded a thoracotomy. Because of widespread peritoneal tuberculosis, permanent esophageal exclusion by ligation was rejected as bowel interposition would have been extremely difficult at a later time. Reversible total esophageal exclusion was successfully utilized.

Adult↗