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Biomedical subjects

R L Brown

Publications and source records attributed to R L Brown.

At least 109 records · Page 6Linked to original sources

Electrophysiological effects of anti-free radical interventions in canine Purkinje fibers.

To assess whether free radicals affect the characteristic sequence of events in an in vitro model of ischemia and reperfusion, isolated canine cardiac Purkinje fibers were exposed to anti-free radical agents, superoxide dismutase 50 U/ml; catalase 600 U/ml; mannitol 2 mM and 20 mM and combined superoxide dismutase, catalase, and mannitol 20 mM. Fibers were superfused for 60 min with altered Tyrode's solution which mimicked some conditions of ischemia (glucose-free, containing lactate, equilibrated with 90% N2-10% CO2), and then re-exposed to normal, oxygenated Tyrode's solution. Anti-free radical agents alone had no electrophysiological effects. Ischemic conditions resulted in moderate depolarization in most preparations (10 control; 43 treated) but in severe depolarization, to less than -60 mV, in some (3 control, 11 treated). Re-exposure to normal, oxygenated solution resulted in prompt initial hyperpolarization followed by marked depolarization, and finally by recovery to baseline maximum diastolic potential. Anti-free radical agents had not effect on maximum diastolic potential during exposure to ischemic conditions or on initial hyperpolarization following re-exposure to oxygenated solution. Preparations that became severely depolarized during exposure to ischemic conditions were not protected by anti-free radical interventions from developing marked depolarization following re-exposure to oxygenated solution. However, in fibers only moderately depolarized by the ischemic conditions, all anti-free radical interventions except mannitol, 2 mM significantly attenuated depolarization following re-exposure to oxygenated solution. Anti-free radical interventions significantly reduced the number of preparations that became markedly depolarized (to less than -65 mV) during re-exposure to oxygenated solution (except for mannitol, 2 mM). Agents had no effect on the occurrence of abnormal automaticity; the occurrence of inexcitability was reduced, but not significantly, except when all agents were used in combination. The results suggest that free radical production may contribute to electrophysiological abnormalities when Purkinje fibers are re-exposed to oxygenated Tyrode's solution after they have been exposed to ischemic conditions.

Action Potentials↗

Effects of naloxone on penile erection in cats.

Male cats were anesthetized with pentobarbital. A Foley catheter was placed in the urinary bladder and physiologic saline, under a head of pressure, was allowed to flow at a constant rate through the bladder. Naloxone, 0.2 mg, caused penile erection in 5 of 11 experiments. The onset of action was 0.5 to 4 minutes, and the duration of the erection was 5 to 36 minutes. In two of three experiments a second injection of naloxone caused a second erection. The erection caused by naloxone was not changed by pre- or posttreatment with morphine or by posttreatment with propranolol. It was suggested that the erection could be due either to altered levels of hormones released from the central nervous system or to removal of reflex inhibitory tone in the spinal cord or sacral parasympathetic ganglia.

Animals↗

Energy metabolism of the untrained muscle of elite runners as observed by 31P magnetic resonance spectroscopy: evidence suggesting a genetic endowment for endurance exercise.

The purpose of this study was to investigate whether genetically determined properties of muscle metabolism contribute to the exceptional physical endurance of world-class distance runners. ATP, phosphocreatine, inorganic phosphate, and pH were quantitatively determined by 31P nuclear magnetic resonance spectroscopy in the wrist flexor muscles of elite long-distance runners and sedentary control subjects. These muscles had not been exposed to any specific program of exercise training in either group of subjects. The "untrained" muscles were examined at rest, during two cycles of three grades of exercise, and in recovery. The flexor muscles of the athletes had higher concentrations of phosphocreatine and ATP than did those of the control subjects at rest and during exercise. The athletes' muscles possessed a higher capacity for generation of ATP by oxidative metabolism than did control subjects' muscles according to the following criteria: (i) high force output, 60% of maximum voluntary contraction, was more easily reached and better maintained in both exercise cycles; (ii) the ratio of inorganic phosphate to phosphocreatine rose less during exercise and recovered faster in the postexercise period; (iii) there was no loss of adenine nucleotides or total phosphate from the athletes' muscles but significant losses from the control subjects' muscles; and (iv) the pH decreased no more than 0.1 unit in the athletes' muscles during exercise, attesting to a relatively slow glycolysis and/or a rapid oxidation of lactate. In the muscles of the control subjects, on the other hand, the pH decreased nearly 0.4 unit early in the first exercise cycle, indicating a relatively fast glycolysis and/or slower oxidation of lactate. In the second exercise cycle, the pH returned to near normal in the control subjects' muscles, reflecting diminished lactate formation because of glycogen depletion and lactate washout by the high blood flow induced by exercise. By the end of the exercise program, the maximum voluntary contractile force for the control subjects had declined to less than 60% of the initial value. This decline could be explained best by exhaustion of the glycolytic contribution to muscle contraction. Therefore, the residual maximum strength provided a measure of the oxidative capacity to support contraction, as is discussed. In conclusion, we suggest that a greater oxidative capacity relative to glycolytic capacity for support of contraction in untrained muscle of world-class runners reflects a genetic endowment for physical endurance. Additional systemic effects of training cannot be completely excluded. 31P magnetic resonance spectroscopy provides a noninvasive method for assessing this endowment.

Adenine Nucleotides↗

Pressure-flow relations across the normal mitral valve.

The stenotic mitral valve area is a major determinant of the atrioventricular pressure-flow relation, and mean atrioventricular pressure gradient is proportionate to the square of mean flow rate. In the absence of obstruction, this relation is linear. The effect of the normal mitral valve area on this pressure-flow relation has not been previously examined. Pulsed Doppler studies of transmitral flow were performed simultaneously with thermodilution cardiac outputs in 25 patients in sinus rhythm and with no valvular disease. Mean flow rate was determined as thermodilution stroke volume/diastolic filling period measured by Doppler. Several instantaneous pressure gradients were estimated from multiple velocity measurements using the modified Bernoulli equation and were plotted against time. Mean pressure gradient was estimated by dividing the area under the pressure-time curve by the diastolic filling period. Average and standard deviation of mean flow rate and pressure gradient was 223 +/- 70 ml/s and 1.4 +/- 0.8 mm Hg, respectively. There was an excellent linear correlation between these 2 parameters (r = 0.91, SEE = 30 ml/s). This confirms the linear relation of mean pressure gradient to mean flow rate in the absence of obstruction. The excellent correlation, obtained without considerations of individual variations of valve area, suggests that this relation is independent of valve area, under normal physiologic conditions.

Blood Flow Velocity↗

Functional pools of oxidative and glycolytic fibers in human muscle observed by 31P magnetic resonance spectroscopy during exercise.

Quantitative probing of heterogeneous regions in muscle is feasible with phosphorus-31 magnetic resonance spectroscopy because of the differentiation of metabolic patterns of glycolytic and oxidative fibers. A differential recruitment of oxidative and glycolytic fibers during exercise was demonstrated in 4 of 10 untrained young men by following changes in phosphate metabolites. Concentrations of inorganic phosphate (Pi), phosphocreatine, and ATP were estimated in the wrist flexor muscles of the forearm at rest, during two cycles of three grades of exercise, and in recovery. At high work levels (40% of maximum strength), two distinct Pi peaks were observed and identified with Pi pools at pH 6.9 and pH 5.9-6.4, respectively. These could be accounted for as follows. At the lowest level of work (using 20% of maximum strength), early recruitment primarily of oxidative (type I) and possibly some intermediate (type IIA) muscle fibers occurs with relatively little net lactate production and consequently little decrease in pH. At higher work loads, however, primarily glycolytic (type IIB) muscle fibers are recruited, which have relatively high net lactate production and therefore generate a second pool of Pi at low pH. ATP depletion (35-54%) and Pi losses accompanied the reduction in ability to perform during the first exercise cycle. When the cycle of graded exercise was repeated immediately, the total Pi remained high but gave rise to only one peak at pH 6.8-7.0. These observations indicated exhaustion of glycolytic type IIB fibers, removal of lactate by high local blood flow, and sustained contractions largely by oxidative type I and IIA fibers. A functional differentiation of fiber types could also be demonstrated during recovery if exercise was stopped while two pools of Pi were still apparent. In the first 3 min of recovery, the Pi peak at pH 6.8-6.9 disappeared almost entirely, whereas the Pi peak at pH 6.0 remained unaltered, reflecting the faster recovery of oxidative type I fibers. The potential of magnetic resonance spectroscopy to characterize oxidative and glycolytic fibers, predict capacity for aerobic performance, and signal the presence of muscle pathology is discussed.

Adenine Nucleotides↗

Diagnosis of alcoholism in a simulated patient encounter by primary care physicians.

Although early detection and treatment of alcoholism have been shown to be efficacious, it is widely accepted that primary care physicians often fail to diagnose alcoholism. In this study, a computerized, simulated encounter with an alcoholic patient was used to assess the performance of a randomly selected sample of primary care physicians in diagnosing alcoholism. Of 95 physicians in this study, only 32 percent diagnosed alcoholism with maximal certainty. There was great variability among physicians in the threshold of information needed to diagnose alcoholism. One third of subjects misinterpreted symptoms of alcoholism and erroneously made other psychiatric diagnoses, chiefly anxiety or depression. Results of this pilot study were not associated with the physicians' age, sex, specialty, duration of training, or reported personal impact of alcoholism. This study provides further evidence of the need for additional education of primary care physicians if such physicians are to succeed in reducing the dramatic impact of alcoholism and alcohol abuse on public health.

Alcoholism↗

The use of a factor-analytic procedure for assessing the validity of an employee safety climate model.

This paper assesses the validity of a safety climate measure proposed by Zohar (Safety climate in industrial organizations: Theoretical and applied implications. J. Appl. Psychol. 65(1), 96-101, 1980.) on an American sample of production workers. Using LISREL, confirmatory factor analyses were carried out to test the hypothesis of similar variance-covariance structures (validation of the proposed model). The originally proposed climate model was not supported by the data. An exploratory factor analytic algorithm is then discussed as a means of refining the climate model. A smaller safety climate model was then extracted from the data, and comparisons were made for two groups of employees (accidents versus no accidents). Factorial invariance tests were conducted to test the hypotheses of similar factor patterns, equal units of measurement, equal accuracy of measurement, and equal covariance across factors, between the two groups. The results indicated that the climate structures did not differ between the two groups of interest, subsequently providing a valid and reliable climate measure across the groups. Groups were then compared on climate scores, with differences in climate perception being detected between the groups.

Accident Prevention↗

Arteriographic management of uterine arteriovenous fistula.

A 21-year-old woman had an arteriovenous fistula of the uterus diagnosed by arteriography after several episodes of profuse uterine bleeding. Arteriographic embolization of the uterine vessels was performed twice with the resumption of normal menses after the second procedure. 15-Methyl-prostaglandin F2 alpha was used effectively for short-term control of hemorrhage.

Adult↗

Competition and body size.

If being larger than competing conspecifics is important for fitness, then an unstable escalation of body size may result. In asexual populations, a cycling of sizes can occur but for sexual diploids, an irreversible size increase is more likely. Several factors can produce a stable distribution of sizes, but a single body size or even a narrow range of sizes cannot be stable. For example, enough environmental variance can produce stability without any genetic variability in the population. Or, with no environmental variance, a high cost of fighting between similar sizes or, for diploids, an increasing mortality with size may lead to a stable distribution of sizes. A game theory model is used to investigate the existence and form of a stable distribution of body sizes in a population.

Animals↗

Coxsackie virus B4 produces transient diabetes in nonhuman primates.

Cynomolgus, rhesus, and Cebus monkeys failed to show glucose tolerance or insulin secretion abnormalities after infection with encephalomyocarditis virus or Coxsackie virus B4. Patas monkeys also showed no abnormalities after infection with encephalomyocarditis virus. However, patas monkeys infected with Coxsackie virus B4 or treated first with a subdiabetogenic dose of streptozocin and then infected sequentially with Coxsackie viruses B4 and B3 showed transient elevation of glucose tolerance tests, depressed insulin secretion, and glucose in the urine. Our experiments in nonhuman primates support earlier studies in mice and humans that under certain circumstances, Coxsackie viruses can cause abnormalities in glucose homeostasis.

Animals↗

The proliferation and function of human mononuclear leukocytes and natural killer cells in serum-free medium.

We recently developed a serum-free (SF) culture medium that supports the growth of several established lymphoid cell lines. In an effort to develop a standardized medium for assay of human natural killer (NK) cell activity, we compared the cytotoxic activity of peripheral blood mononuclear leukocytes (PBL) and purified large granular lymphocytes (LGL) cultured in SF medium containing interleukin 2 (IL-2) or medium containing 10% fetal bovine serum (FBS) plus IL-2. The results indicated that PBL had a 30% increase in cumulative net cell growth and had as high or higher cytotoxic activity after growth in SF medium than in medium containing FBS. Purified LGL had a 50% increase in cumulative net cell growth and persisted approximately 2 weeks longer in culture in medium containing FBS than in SF medium. However, the cytotoxic activity of cells grown in SF medium persisted during the initial 3 weeks of culture. Purified LGL that were maintained and were subcultured at cell densities of 10(6) cells or greater per milliliter of either SF or FBS-containing medium had equivalent levels of cytotoxicity over a 44-day period in either medium compared with cells subcultured at a density of 5 X 10(5) cells per milliliter of medium. NK cells produced a cytotoxic factor (NKCF) in SF medium, and its cytotoxic activity was blocked by 10% FBS. We conclude that the SF medium supplemented with IL-2 can be used as an alternative to FBS-containing medium with IL-2 for the growth of NK cells and is advantageous for the production of NKCF.

Cell Division↗

Modulation of interleukin 2 release from a primate lymphoid cell line in serum-free and serum-containing media.

The ability to grow a clone of the cell line, MLA144, which is a constitutive producer of interleukin 2 (IL-2), in serum-free medium permitted the study of the direct effect of various agents on cell growth and IL-2 production in a homogeneous population. Bovine serum albumin (BSA) at 4 mg/ml was optimal for cell growth and IL-2 production. Selenium at 10 ng/ml enhanced IL-2 production nearly twofold and lithium at 42 ng/ml also enhanced IL-2 production by nearly twofold. Neither compound at these levels altered cellular proliferation. Two other compounds, iron and zinc, known to be associated with cellular proliferation and/or immunoregulation did not alter IL-2 production. Catalase or horseradish peroxidase was able to substitute for BSA and maintain the long-term growth of the MLA144 clone with only a 30% decrease in the rate of cellular proliferation and a 50% decrease in IL-2 production compared to cells maintained in the serum-free formulation with BSA. Addition of 0.5 mg of BSA to the catalase serum-free formulation increased the production of IL-2 to 70% of that of cells cultured in the BSA-containing serum-free formulation. The catalase-containing serum-free formulation has the advantage of consisting of only three proteins, catalase, insulin, and transferrin, at a very low protein content. The catalase-containing serum-free medium also supported the long-term growth of a human T-cell line, HSB-2.

Animals↗

Federally funded CMHCs: the effects of period of initial funding and hospital affiliation.

Previous research on federally funded community mental health centers has largely failed to recognize fundamental differences among different types of centers. Here we show that such basic factors as the arrangement for providing inpatient services and the period of initial federal funding have large effects on the development and organization of a center. Although the centers joining the federal program from 1965-1970 are the largest, those facilities funded between 1971-1975 are generally smaller than those funded later. The arrangement for providing inpatient services has an important effect on staffing. This work suggests the national norms may not be the most useful data for evaluating past performance or planning the future of a specific center.

Budgets↗

Bilateral fracture of the hook of the hamate.

Bilateral hamate fractures in a physician sportsman were treated successfully by surgical excision of the fracture fragment. This case demonstrates the importance of carpal tunnel roentgenograms and of a high index of suspicion in making an accurate diagnosis in wrist injuries.

Athletic Injuries↗

Comparison of short and long courses of ampicillin for vaginal hysterectomy.

Administering perioperative antibiotic to reduce the morbidity associated with vaginal hysterectomy has become well accepted. Although both short and long courses of antibiotics are effective, the optimal length of treatment has not been well established by clinical studies. Our prospective study compared two groups of patients, one receiving a short course and the other a long course of ampicillin. Patients having vaginal hysterectomy were randomly assigned to the short or long course. Febrile morbidity, as well as serious morbidity and hospital stays, in the two groups was compared. Of 212 patients receiving the short course, 21 had febrile morbidity, while 14 of 215 patients receiving the long course had febrile morbidity. These rates were not significantly different. Furthermore, serious morbidity and length of hospital stay were not significantly different.

Adult↗

The treatment of mucous cysts: long-term follow-up in sixty-two cases.

To determine the course of the so-called mucous cyst both after various modalities of treatment and without treatment, 56 patients with 62 cysts were contacted to participate in a study with an average follow-up of 6.2 years after initial evaluation. The mucous cysts primarily occurred in elderly women and were most prevalent in the index and long fingers. Longitudinal grooving of the nail was not uncommon and may hve preceded the appearance of the cyst. Degeneration of the distal interphalangeal joint was frequently found. The long-term results after treatment with simple aspiration or decapping, or by excision with skin grafts and flaps as needed or with observation only were similar. However, surgical excision or aspiration may eliminate earlier the cosmetic disfigurement and occasional discomfort that are associated with this lesion.

Adult↗