Biomedical subjects
Publications and source records attributed to M Brown.
A 28-year-old African-American man presented with constant, sometimes sharp, abdominal pain that was partially relieved by lying down. The pain had begun five days earlier, starting in his back and radiating to his epigastrium. He had had fever, chills, nausea, and loss of appetite for about two weeks, and constipation for four days. He had not had heartburn, bleeding, dysuria, or recent trauma.
A 41-year-old man who had tested positive for HIV infection presented with cough, yellow sputum, fever, and chills of 10 days' duration. He was short of breath at rest and had a poor appetite. He did not have chest pain, bloody sputum, or weight loss.
BACKGROUND: Attenuated vasodilation in response to the intra-arterial administration of the beta-adrenergic agonist isoproterenol (INN, isoprenaline), an endothelium-independent vasodilator, has previously been observed in normotensive black Americans. To determine whether this reflected a more generalized attenuation of responses to vasodilators, we compared forearm blood flow responses to the endothelium-dependent vasodilator methacholine and the endothelium-independent vasodilator sodium nitroprusside in young normotensive black men and white men. METHODS: Forearm blood flow responses to the intra-arterial administration of isoproterenol (10 to 400 ng/min), methacholine (0.25 to 8 micrograms/min), and sodium nitroprusside (0.25 to 8 micrograms/min) were measured with use of venous occlusion plethysmography in 11 normotensive black men (mean +/- SE age, 30.5 +/- 2.2 years) and nine normotensive white men (mean age, 28.0 +/- 3.2 years). RESULTS: Baseline characteristics, including baseline forearm blood flow, were similar in the black and the white subjects. Vasodilation in response to isoproterenol, sodium nitroprusside, and methacholine was significantly attenuated in black subjects, resulting respectively in a 3.7-fold, 3.6-fold, and 5.0-fold increase in forearm blood flow in black subjects and a 7.5-fold, 5.2-fold, and 6.9-fold increase in forearm blood flow in white subjects (ANOVA; isoproterenol, p < 0.0001; sodium nitroprusside, p < 0.0001; methacholine, p = 0.01). CONCLUSIONS: Our finding of attenuated nitric oxide-mediated vasodilation in response to methacholine and sodium nitroprusside in healthy black American men suggests that attenuated vasodilation in black subjects is a relatively generalized phenomenon, resulting in attenuated responses to multiple vasodilators that act through different receptor- and nonreceptor-mediated mechanisms.
The optimal management of arthropod bites is prevention, and many over-the-counter insect repellents are available. Since first marketed in 1956, deet has remained the most effective repellent against mosquitoes, biting fleas, gnats, and chiggers. Permethrin is applied to clothing rather than to skin, and it is a better repellent against ticks than deet. The risk of serious side effects with the use of deet is slight; nevertheless, the lowest effective concentration should be used. The current, popular repellent agents (for adults and children) and their active ingredients are discussed. In addition, the Environmental Protection Agency guidelines for the safe use of insect repellents are supplied.
BACKGROUND: Low-dose cyclosporine therapy for severe plaque psoriasis is effective. Most side effects can be controlled by patient monitoring, with appropriate dose adjustment or pharmacologic intervention, or both, if indicated. Prevention or reversibility of laboratory and chemical abnormalities may be achieved by discontinuation of therapy after the induction of clearing. However, relapse occurs rapidly on discontinuation. Maintenance therapy with cyclosporine after induction has not been fully evaluated. OBJECTIVE: Our purpose was to compare a regimen of 3.0 mg/kg per day of oral cyclosporine with placebo in maintaining remission or improvement in patients with psoriasis. METHODS: After a 16-week unblinded induction phase in which 181 patients received cyclosporine, 5.0 mg/kg per day (an increase up to 6.0 mg/kg per day and a decrease to 3.0 mg/kg per day were allowed, if required, to achieve efficacy or tolerability, respectively), those patients showing a 70% decrease or more in involved body surface area (BSA) entered the 24-week maintenance phase and were randomly assigned to either placebo, cyclosporine, 1.5 mg/kg per day, or cyclosporine, 3.0 mg/kg per day. Patients were considered to have had a relapse when BSA returned to 50% or more of the prestudy baseline value. Clinical efficacy, adverse effects, and laboratory values were monitored regularly throughout both study phases. RESULTS: During induction, cyclosporine at approximately 5.0 mg/kg per day produced a reduction in BSA of 70% or more in 86% of the patients. During maintenance, the median time to relapse was 6 weeks in both the placebo and cyclosporine 1.5 mg/kg per day groups, but was longer than the 24-week maintenance period in the 3.0 mg/kg per day group (p < 0.001 vs placebo). By the end of the maintenance period, 42% of the patients in the 3.0 mg/kg per day cyclosporine group had a relapse compared with 84% in the placebo group. Changes in laboratory values associated with the higher induction dosage generally exhibited partial or complete return toward mean prestudy baseline values during the maintenance phase, with the greatest degree of normalization in the placebo group. CONCLUSION: Cyclosporine, 3.0 mg/kg per day, adequately and safely maintained 58% of patients with psoriasis for a 6-month period after clearing of their psoriasis with doses of approximately 5.0 mg/kg per day.
Explore the source record for details and available documents.
The 3-dimensional (3-D) functional organization of the cat's inferior colliculus (IC) was examined using the 2-deoxyglucose method. Animals were dichotically stimulated with pure tone stimuli at an intensity of 80 dB SPL. Autoradiographic sections from these animals, cut in the three standard planes, were serially reconstructed to reveal the 3-D topography of the isofrequency sheets of labelling. In all 3-D reconstructions, the isofrequency sheets extend rostrocaudally through the IC with the rostral aspect of the sheet being situated more ventral than its caudal aspect. In the mediolateral dimensions, sheets are angled at between 40 degrees and 60 degrees to the horizontal, running from a dorsomedial to a ventrolateral position. The low-frequency sheets (0.5 and 2 kHz) are dorsolaterally convex and situated in the dorsolateral region of the IC. The 4 and 10 kHz isofrequency sheets have a helical structure and are situated in the mid-region of the IC. The high-frequency sheets (20 and 30 kHz) are dorsolaterally concaved and situated in the ventromedial region of the IC. The topography of these isofrequency sheets generally agree with, and extended our knowledge of, the tonotopic organization of the IC as derived from electrophysiological studies. The functional organization revealed by the 2-deoxyglucose method only partially correlated with the neural laminae in the anatomical models of the IC proposed by Rockel and Jones [J. Comp. Neurol. 147 (1973) 11-60] and Oliver and Morest [J. Comp. Neurol. 222 (1984) 237-264]. It is therefore concluded that the neural laminar organization of the IC may not be a necessary substrate for the tonotopic organization seen the IC.
The frequency organization of the central nucleus of the inferior colliculus (ICC) in the anesthetised cat was quantitatively mapped using [14C]2-deoxyglucose. From a standardised rostrocaudal region of the ICC, the position of peak selective labelling along the tonotopic axis closely conformed to the reported tonotopic organization of this nucleus. The position of the peak was found not to significantly change its position along the tonotopic axis with increasing stimulus intensity. However, the amplitude of peak uptake and width of selective labelling were shown to monotonically increase with increase in stimulus intensity. The increase in width of selective labelling, about the position of peak uptake, showed a slight asymmetry toward the high-frequency regions of the ICC. A 2-DG frequency-position function for the ICC, similar to that for the cochlea, enabled the width of 2-DG bands to be expressed in terms of their frequency spread along the tonotopic axis. This inturn enabled 2-DG tuning curves to be plotted which, when compared to electrophysiologically determined tuning curves, showed marked similarities. The minimum threshold and width (Q10) of these 2-DG tuning curves fell within the range reported for single units in the cat auditory pathway.
We investigated electro-mechanical transduction within the cochlea by comparing masking of the auditory nerve compound action potential (CAP) by acoustical and electrical maskers. Forward-masking of the CAP reflects the response to the masker of the cochlear location tuned to the probe. Electrical stimulation was delivered through bipolar stimulating electrodes within the basal turn of the scala tympani. The growth of masking of high-frequency probes which excite cochlear locations close to the stimulating electrodes was similar for both acoustic and electrical maskers, suggesting a linear transduction of electrical energy to mechanical energy. Exposure to intense acoustic stimulation caused an equal loss of sensitivity to acoustic and electrical maskers. Masking of lower-frequency probes by electrical maskers increased rapidly with masker current, suggesting the direct electrical stimulation of neural elements. This masking was reduced by the administration of strychnine suggesting a contribution by the efferents towards masking of these low-frequency probes.
This study estimated the mechanical response of the cochlea to pulsatile electrical stimulation of the scala tympani of the cat. The auditory nerve compound action potential evoked by an acoustic probe was forward-masked by a train of charge-balanced biphasic current pulses. Masking as a function of probe frequency reflected the excitation pattern of the response to the masker and resembled the spectrum of the electrical stimulus. Both pulse rate and pulse width influenced the degree of masking. The vibration of a region of the basilar membrane was estimated by recording the local cochlear microphonic evoked by biphasic pulses. The amplitude of the cochlear microphonic was proportional to the amplitude of the spectral component of the electrical stimulus to which the local cochlear microphonic was tuned. These results are consistent with the generation of a mechanical response to the electrical stimulus.
Prognosis and survival for patients diagnosed with melanoma depends on a number of interrelated factors, including histological, clinical, immunologic, and surgical parameters. Tumor thickness and depth of invasion is the most important prognostic factor, and helps to guide treatment and management plans. Besides tumor thickness, other histological criteria include melanoma growth phase (nodal v. vertical), host response, angiolymphatic invasion, mitotic rate, regression, satellitosis, and neurotropism. Important clinical prognostic factors include anatomic location of the melanoma and the patient's age and sex. Surgical factors to be examined involve excisional margin size, and elective lymph node dissection. Finally, the staging of patients with melanomas (nodal or visceral metastases) helps to define survival.
Explore the source record for details and available documents.
BACKGROUND: The technical skill of surgical trainees is not well assessed. This study aimed (1) to compare the reliability of three scoring systems, (2) to compare live and bench formats and (3) to assess construct validity of a test of operative skill. METHODS: Parallel examinations of operative skill, one using live animals and one using simulations, were developed. Performance was graded using operation-specific checklists, detailed global rating forms and pass/fail judgements. Twenty surgical residents each took both formats. RESULTS: Disattenuated correlations between live and bench scores were high (0.69-0.72). Mean interrater reliability across stations ranged from 0.64 to 0.72. Internal consistency was moderate to high (alpha: 0.61-0.74) for the live format using the checklist and for live and bench formats using global ratings. Global ratings discriminated between resident levels for both formats (bench: F(2,17) = 4.45, P < 0.05; live: F(2,17) = 3.55, P < 0.05), checklists did not. CONCLUSION: This preliminary study suggests that the Objective Structured Assessment of Technical Skill can reliably and validly assess surgical skills. Global ratings are a better method of assessment than task-specific checklists. Bench model simulation gives equivalent results to use of live animals for this test format.
Lower extremity strength and fat-free mass were examined in 58 postmenopausal women aged 60-72 yr. Subjects were studied before and after an 11-mo control period (n = 16) or before and after an 11-mo weight-bearing exercise training program designed to generate relatively high ground reaction forces (n = 42). Twenty-two of the exercisers initiated hormone replacement therapy (HRT) at the outset of exercise and continued HRT for 11 mo. Hip extension and abduction strength were assessed using a hand-held dynamometer. Force production during knee extension and flexion was evaluated on an isokinetic dynamometer at 60, 90, and 180 degrees/s. Simultaneous knee and hip extension strength was also assessed on a leg press machine. Total body and lower extremity fat-free mass were determined using dual-energy x-ray absorptiometry. There were no significant changes in muscle strength or body composition in control subjects. Both exercise groups had significant increases in fat-free mass and in all strength measures. Fat-free mass increased from 38.8 +/- 4.3 to 39.7 +/- 4.3 kg in the exercise group and from 37.7 +/- 3.9 to 38.9 +/- 4.6 kg in the exercise-plus-HRT group. The average relative increase in strength was 16.2 +/- 11.0% in the exercise group and 17.0 +/- 13.0% in the exercise-plus-HRT group. Women receiving HRT did not have a gain in fat-free mass or in strength over and above that demonstrated by the women not on HRT. Our results provide evidence that HRT does not augment the increases in muscle mass or strength that occur in response to weight-bearing exercise in older women.
Mitochondrial DNA haplotypes of humpback whales show strong segregation between oceanic populations and between feeding grounds within oceans, but this highly structured pattern does not exclude the possibility of extensive nuclear gene flow. Here we present allele frequency data for four microsatellite loci typed across samples from four major oceanic regions: the North Atlantic (two mitochondrially distinct populations), the North Pacific, and two widely separated Antarctic regions, East Australia and the Antarctic Peninsula. Allelic diversity is a little greater in the two Antarctic samples, probably indicating historically greater population sizes. Population subdivision was examined using a wide range of measures, including Fst, various alternative forms of Slatkin's Rst, Goldstein and colleagues' delta mu, and a Monte Carlo approximation to Fisher's exact test. The exact test revealed significant heterogeneity in all but one of the pairwise comparisons between geographically adjacent populations, including the comparison between the two North Atlantic populations, suggesting that gene flow between oceans is minimal and that dispersal patterns may sometimes be restricted even in the absence of obvious barriers, such as land masses, warm water belts, and antitropical migration behavior. The only comparison where heterogeneity was not detected was the one between the two Antarctic population samples. It is unclear whether failure to find a difference here reflects gene flow between the regions or merely lack of statistical power arising from the small size of the Antarctic Peninsula sample. Our comparison between measures of population subdivision revealed major discrepancies between methods, with little agreement about which populations were most and least separated. We suggest that unbiased Rst (URst, see Goodman 1995) is currently the most reliable statistic, probably because, unlike the other methods, it allows for unequal sample sizes. However, in view of the fact that these alternative measures often contradict one another, we urge caution in the use of microsatellite data to quantify genetic distance.
Explore the source record for details and available documents.
OBJECTIVE: It is common practice to measure serum ferritin levels in endurance athletes because of the belief that low iron stores may compromise performance. The direct relationship between endurance performance and iron deficiency anemia is well known, but there are theoretical reasons to believe that endurance performance may be adversely affected by low iron stores even in the absence of frank anemia. The purpose of this article is to provide a critical review of the scientific evidence relating low iron stores to endurance performance. DATA SOURCES: Medline was searched using MeSH for articles related to ferritin and endurance published since 1985. Additional references were reviewed from the bibliographies of the retrieved articles. STUDY SELECTION: All clinical study designs were reviewed as well as relevant animal studies. Conclusions regarding endurance performance in humans were limited to data from clinical studies. DATA EXTRACTION AND SYNTHESIS: In reviewing the literature, the relative strengths of the study designs were examined carefully. Particular attention of the effectiveness of each study in isolating ferritin as the key independent variable. Dependent measures of endurance capacity were also evaluated. MAIN RESULTS: Eight studies isolated serum ferritin as the experimental variable. Only one study reported a significant improvement in endurance performance (time to exhaustion) in subjects with low ferritin levels treated with oral iron, but this finding may have been magnified by an unexplained decrease in time to exhaustion in the control group. Iron dosages differed in the studies reviewed. Two additional studies that reported increases in performance parameters following increases in ferritin were confounded by concomitant increases in hemoglobin levels. CONCLUSIONS: Iron supplementation can raise serum ferritin levels, but increases in ferritin concentration, unaccompanied by increases in hemoglobin concentration, have not been shown to increase endurance performance. Of concern to the clinician is that athletes with low ferritin levels but hemoglobin in the low-normal range may have iron deficiency anemia responsive to iron supplementation. Low ferritin with hemoglobin in the mid- to upper normal range is at best a relative indication for iron supplementation: low ferritin with hemoglobin in the low normal range is a stronger, yet still relative, indication for iron supplementation in athletes.
Breast cancers lacking estrogen receptor (ER) expression have an adverse prognosis and fail to respond to endocrine therapy. We have identified a transcriptional enhancer in the human ER gene which is differentially active in ER-positive (ER+) and ER-negative (ER-) human breast cancer cell lines. Enhancer function was mapped to a 35-bp element located from -3778 to -3744 upstream of the major human ER mRNA start site, which we have termed ER-EH0 (for estrogen receptor enhancer). Gel retardation assays with ER+ and ER- cell lines identified multiple DNA-protein complexes which specifically form on this enhancer. One of these complexes could be supershifted by anti-Jun or anti-Fos antibodies, identifying it as an AP-1-containing complex. Methylation interference assays suggest binding of factors to both the AP-1 site and adjacent base pairs. Enhancer activity requires both the AP-1 site and these adjacent sequences. Mutations introduced into ER-EH0 and the recently described proximal promoter element ERF-1 in the context of the full-length promoter confirm ER-EH0 as the dominant cis-acting element involved in differential ER expression.