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Biomedical subjects

R G Carroll

Publications and source records attributed to R G Carroll.

At least 37 records · Page 2Linked to original sources
PubMed1997

Intrinsic resistance to T cell infection with HIV type 1 induced by CD28 costimulation.

When HIV-infected leukocytes are activated by the CD28 costimulatory receptor, HIV-1 is rapidly cleared from cultures, suggesting that costimulation can render T cells resistant to HIV-1 infection. In this study we tested the hypothesis that enhanced secretion of cytokines or chemokines could account for CD28-induced antiviral effects. In an acute infection system, resistance to infection with macrophage-tropic strains of HIV-1 was shown to be comprised of both soluble and cell-associated components. Induction of HIV-1 resistance was specific for CD28 costimulation, in that a variety of other accessory receptors, such as CD2, CD4, CD5, and MHC class I, failed to confer the antiviral resistance. The soluble component was secreted by both CD4 and CD8 T cells, was not unique to CD28 costimulation, and could be neutralized by removal of C-C chemokines (RANTES (regulated upon activation, normal T cell expressed and secreted) and macrophage inflammatory protein-1alpha and -1beta) from the culture supernatants of costimulated CD4 T cells. In contrast, CD28 stimulation of CD4 cells resulted in the specific induction of a pronounced intrinsic resistance to HIV-1 infection by macrophage tropic isolates of HIV-1.

CD28 Antigens↗
PubMed1997

Differential regulation of HIV-1 fusion cofactor expression by CD28 costimulation of CD4+ T cells.

Activation of CD4(+) T lymphocytes from human immunodeficiency virus-type 1 (HIV-1)-infected donors with immobilized antibodies to CD3 and CD28 induces a virus-resistant state. This effect is specific for macrophage-tropic HIV-1. Transcripts encoding CXCR4/Fusin, the fusion cofactor used by T cell line-tropic isolates, were abundant in CD3/CD28-stimulated cells, but transcripts encoding CCR5, the fusion cofactor used by macrophage-tropic viruses, were not detectable. Thus, CD3/CD28 costimulation induces an HIV-1-resistant phenotype similar to that seen in some highly exposed and HIV-uninfected individuals.

Antibodies, Monoclonal↗
PubMed1997

Incorporating active learning into a traditional curriculum.

During the past three academic years, "self-learning exercises" (SLEs) have been incorporated into the Medical Physiology course for first-year students at the Morehouse School of Medicine. Roughly 20-30% of the material covered in the course is presented to the students in the form of these exercises, instead of in lectures. The exercises are intended to help the students develop skills in active learning and problem solving. Formal analysis of student performances on multiple-choice exam questions showed that the SLEs did not significantly impair learning evaluated by this traditional means. Student feedback was strongly negative the first year and prompted a number of revisions in the format of the SLEs, which seem to have made them more palatable, without negating their emphasis on active learning and application of material.

Adult↗
PubMed1997

Gamma probe guided sentinel node biopsy in breast cancer.

Axillary lymph node status is the most important pathological determinant of prognosis in early breast cancer. Determination of axillary status is crucial in clinical decision-making. It is currently accepted that the total axillary lymphadenectomy is the most reliable staging procedure. However, routine axillary dissection does not benefit a majority of early breast cancer patients who are node-negative, and the patients sustain the potential morbidity and the economic cost of this procedure. There is substantial evidence that there is an orderly progression of breast cancer metastases in a lymphatic basin, sentinel node being the first node to receive lymphatic drainage from the tumor site. Sentinel lymph node biopsy may prove to be the optimal sampling technique for staging of breast cancer patients. A large multicenter trial to study the clinical validity of sentinel lymph node biopsy in breast cancer is underway. This paper addresses the rationale for sentinel lymph node biopsy and discusses the technical issues with regard to anatomy and physiology of breast lymphatics.

Axilla↗
PubMed1996

Antiviral effect and ex vivo CD4+ T cell proliferation in HIV-positive patients as a result of CD28 costimulation.

Because stimulation of CD4+ lymphocytes leads to activation of human immunodeficiency virus-type 1 (HIV-1) replication, viral spread, and cell death, adoptive CD4+ T cell therapy has not been possible. When antigen and CD28 receptors on cultured T cells were stimulated by monoclonal antibodies (mAbs) to CD3 and CD28 that had been immobilized, there was an increase in the number of polyclonal CD4+ T cells from HIV-infected donors. Activated cells predominantly secreted cytokines associated with T helper cell type 1 function. The HIV-1 viral load declined in the absence of antiretroviral agents. Moreover, CD28 stimulation of CD4+ T cells from uninfected donors rendered these cells highly resistant to HIV-1 infection. Immobilization of CD28 mAb was crucial to the development of HIV resistance, as cells stimulated with soluble CD28 mAb were highly susceptible to HIV infection. The CD28-mediated antiviral effect occurred early in the viral life cycle, before HIV-1 DNA integration. These data may facilitate immune reconstitution and gene therapy approaches in persons with HIV infection.

Antibodies, Monoclonal↗
PubMed1996

Professional development: a guide to the educator's portfolio.

The educator's portfolio provides a mechanism for identifying and evaluating faculty teaching activities. The educator's portfolio has separate areas for educational research, teaching encounters, and educational service. This article describes the components of a traditional educator's portfolio and relates them to the basic scientist's curriculum vitae. The article concludes with suggestions for implementing use of the educator's portfolio at the departmental and institutional level.

Education, Medical↗
PubMed1995

CT determination of tibial tubercle lateralization in patients presenting with anterior knee pain.

Anterior knee pain is commonly associated with patellofemoral malalignment. Both conventional radiographic measurements and CT measurements have been proposed to define and confirm the sometimes difficult clinical diagnosis of anterior knee pain secondary to patellofemoral malalignment. Using CT imaging with computerized technique to measure anatomic relationships, we evaluated patients (n = 50) with anterior knee pain for excessive lateralization of the tibial tubercle. The symptomatic knee of each patient was compared with their asymptomatic knee as well as with the knees of patients with other causes of anterior knee pain (n = 10) and with the knees of asymptomatic controls (n = 10). The symptomatic knee of patients with suspected patellofemoral malalignment demonstrated significantly greater lateralization of the tibial tubercle (12.2 +/- 0.5 mm) than did the asymptomatic knee (9.0 +/- 0.7 mm). The symptomatic knees of patients with patellofemoral malalignment also demonstrated significantly greater lateralization of the tibial tubercle than did the knees of patients with other causes of anterior knee pain (5.9 +/- 0.9 mm). When a control population was added to the analysis, the patients with symptomatic patellofemoral malalignment demonstrated significantly greater lateralization of the tibial tubercle than did the controls (6.4 +/- 0.4 mm). Using a critical value of 9 mm lateralization, the CT diagnosis of patellofemoral malalignment had a specificity of 95% and a sensitivity of 85%. We conclude that CT determination of tibial tubercle position assists the diagnosis of patellofemoral malalignment.

Female↗
PubMed1994

Use of technetium antigranulocyte monoclonal antibody Fab' fragments for the detection of osteomyelitis.

Accurate early diagnosis of osteomyelitis is critical for optimal clinical management. Conventional radiology (X-rays, CT) and nuclear medicine scans (bone, gallium, and technetium/indium white blood cell [WBC]) have limitations and drawbacks. The monoclonal antibody (MAb) ImmuRAID-MN3 (Immunomedics Inc., Morris Plains, NJ), a 99m-Tc Antigranulocyte Fab' fragment, recognizes a surface glycoprotein NCA-90/95 shared by granulocytes, carcino-embryonic antigen (CEA), and meconium antigen (MA). Intravenous injection of radiolabeled MAb enables in vivo labeling of human granulocytes and targets infected lesions in the bone and throughout the body. Technetium labeled Fab' fragments rapidly clear the blood pool and high-quality images can be obtained the same day, as early as 1 h postinjection. Results at our institution on 13 patients with clinically suspected osteomyelitis of infected long bones, prostheses, and diabetic foot ulcers were compared with the surgical/bacteriological verification of the presence or absence of infection. The MAb scan showed six true positives, six true negatives, and one false negative (very low grade infection). The procedure was safe, no clinical or laboratory adverse reactions were encountered. The MAb fragments are markedly less immunogenic than whole IgG, resulting in lower induction of human antimouse antibody (HAMA) titers. No HAMA to this MAb fragment has been detected in 24 patients (data from multiple institutions). Our preliminary results suggest that 99m-Tc ImmuRAID-MN3 is highly accurate for detection of osteomyelitis. This study is part of an ongoing multiinstitutional project sponsored by Immunomedics, Inc. to evaluate the efficacy and safety of this radiopharmaceutical.

Adult↗
PubMed1994

Prehospital blood pressures: inaccuracies caused by ambulance noise?

Blood pressure measurements in a moving ambulance can be difficult to obtain. Sirens, engine noise, and road noise can all interfere with the accurate detection of a patient's blood pressure. This study was undertaken to determine the influence of ambulance noise and vibration on auscultated blood pressures. A model was developed that used dynamic pressures to simulate systolic Korotkoff sounds. Forty-nine emergency personnel were asked to obtain blood pressures using the model in both a quiet environment and in a moving ambulance. A total of 485 blood pressure measurements were obtained. Systolic pressures were randomized to two settings: 76 mm Hg and 138 mm Hg. Stationary readings were compared with moving readings using analysis of variance for repeated measures. Systolic blood pressure measurements obtained in the quiet environment averaged 133 +/- 5 mm Hg at the high setting, and 45 +/- 6 mm Hg at the low setting. Systolic blood pressure measurements obtained in a moving ambulance averaged 86 +/- 7 mm Hg at the high setting, and 41 +/- 7 mm Hg at the low setting. The average differences between quiet and moving measurements were 47 mm Hg at the "high" setting (P < .01) and 4 mm Hg at the "low" setting (P > .01). At physiological levels, blood pressures obtained in moving ambulances differ significantly from those obtained in a quiet environment, which may be caused by road noise and ambulance motion.

Ambulances↗
PubMed1994

Environmental temperature variations cause degradations in epinephrine concentration and biological activity.

This study determined the biological consequence of temperature induced epinephrine degradation. Two different epinephrine preparations (1:1,000 and 1:10,000) were exposed to either cold (5 degrees C) or hot (70 degrees C) temperature. The exposure occurred for 8-hour periods each day in 4-, 8-, and 12-week intervals. Samples and identical controls were then chemically evaluated using high-pressure liquid chromatography (HPLC), and biological activity of samples showing chemical degradation was assessed in conscious rats. Epinephrine (1:10,000) underwent a significant degradation and a loss of concentration of the parent compound after 8 weeks of heat treatment. By 12 weeks, 64% of the epinephrine was degraded. A smaller (30%) but significant loss of cardiovascular potency was determined by blood pressure and heart rate responses in conscious rats. The degradation of epinephrine (1:1,000) was not statistically significant even after 12 weeks of heat exposure. No change was noted from control in either epinephrine concentration when exposed to cold temperatures. In conclusion, epinephrine (1:10,000) deteriorates in the presence of elevated temperature and should be protected from high temperatures when carried by EMS providers. The degradation products may possess biological activity.

Animals↗
PubMed1994

Adverse effect of helicopter flight on the ability to palpate carotid pulses.

STUDY OBJECTIVE: To determine if the air medical helicopter environment compromises the ability to palpate carotid pulses. DESIGN: Using a carotid pulse model, flight nurses were tested for their ability to palpate the simulated carotid pulse at normal (120/80 mm Hg) and low (80/60 mm Hg) blood pressures on the ground and during helicopter flight. SETTING: Palpation tests were performed during flight in an MBB BO-105 twin-turbine engine, single-rotor air medical helicopter; control palpation tests were performed on the ground. TYPE OF PARTICIPANTS: Ten flight nurses. MEASUREMENTS AND MAIN RESULTS: Tracings of pulsatile pressure from the carotid pulse model verified its ability to simulate a wide range of arterial pressures. Analyses of variance for repeated measures, including polynomial contrasts, were performed to compare the number of correct detections of the presence or absence of pulse pressures in flight with the number of correct detections in the two control conditions for both carotid pulse pressures. The mean in-flight number of correct detections was lower than both the preflight and postflight control tests, which were themselves nearly equal, at each simulated carotid pulse pressure. The quadratic terms for both the 120/80 mm Hg trial (F1,14 = 9.28; P = .0087) and the 80/60 mm Hg trial (F1,18 = 5.69; P = .0283) were statistically significant. CONCLUSION: Factors associated with transport of patients in an MBB BO-105 helicopter impair the ability of flight nurses to detect carotid pulses in a simulated physiologic model.

Aircraft↗
PubMed1994

Fluorescent monitoring of Jurkatt cell intracellular magnesium during metabolic poisoning.

Divalent cation movement characterizes the final common pathway of cellular death from ischemic or metabolic injury. The influx of calcium is an essential step in cellular death. We hypothesized that intracellular magnesium levels may change during the progression to cellular death. Verapamil-sensitive changes in free ionized intracellular Mg2+ ([Mg2+[i) and Ca2+ ([Ca2+]i) levels were estimated in transformed T-lymphocytes exposed to metabolic inhibitors. Separate experiments used a Mg(2+)-sensitive fluoroprobe, fura-2 (Ex 1,344, Ex 2,376, Em 500), and a Ca(2+)-sensitive fluoroprobe, fura-2 (Ex 1,340, Ex 2,380, Em 510). Chemical anoxia (sodium cyanide 1 mM, iodoacetic acid 10 mM) caused a gradual increase in [Ca2+]i (control 126 +/- 13 nM) to > 1 mM by 10 min. This increase in [Ca2+]i was not affected by verapamil treatment. In separate experiments, [Mg2+]i levels were monitored during chemical anoxia. The specificity of mag-fura for Mg2+ over Ca2+ was reflected in the absence of a response to the lymphocyte Ca2+ mobilizer OKT-3. Uncorrected control [Mg2+]i levels (.4 +/- .1 mM) were not affected by the combined cyanide-iodoacetate treatment. A small increase in mag-fura-2 fluorescence was noted, probably due to binding of Ca2+ to the fluoroprobe when [Ca2]i exceeded 1 mM. Elimination of Ca2+ from the extracellular buffer increased the resting estimate of intracellular [Mg2+] to 1.6 + .1 mM. These results indicate that 1) extracellular Ca2+ can interfere with the fluorescent determination of intracellular magnesium concentration, and 2) intracellular free Mg2+ concentrations do not change in this cell line during chemical anoxia.

Adenosine Triphosphate↗
PubMed1994

Evaluation of a summer enrichment physiology course for matriculating medical students.

A summer enrichment physiology course for matriculating medical students has met a number of short-term goals, including bringing the students to the level of average medical student performance by the end of the summer. The long-term benefit of the program was evaluated by constructing a prospective expectation for each member of the medical class. Physiology grades obtained by past medical students were regressed on their undergraduate grades and MCAT scores. This regression model was used in a prospective manner to predict a physiology course grade for the entering class. Six of the seven summer program participants achieved scores equal to or higher than their predicted scores. Additionally, the regression model identified prospectively four of the six medical students who scored below 70% for the medical physiology course. This study suggests that a summer enrichment program can benefit participants.

Education, Medical↗
PubMed1994

Centrally mediated reduction in cardiac output elicits the enhanced hypotensive effect of clonidine in conscious aortic barodenervated rats.

In a previous study, we showed that centrally mediated hypotensive responses are enhanced in aortic barodenervated (ABD) rats as compared with sham-operated (SO) rats. In the present study, we tested the hypothesis that the high basal total peripheral resistance (TPR) of ABD rats accounts for enhanced hypotensive responses to clonidine in this rat model. Aortic barodenervation resulted in acute increases in blood pressure (BP) and heart rate (HR) in anesthetized rats, associated with significant increases in plasma norepinephrine (NE) levels and TPR; cardiac index (CI) and stroke volume (SV) were not affected. After recovery from anesthesia, conscious ABD rats had significantly increased BP at 3 h after barodenervation; BP returned to SO levels by 48 h even though plasma NE levels and TPR remained significantly increased. On the other hand, CI and SV showed significant reductions, beginning at 3 h, and remained low throughout the postdenervation period (48 h); the reduction in CI offset the increase in TRP and may therefore account for the restoration of BP of ABD rats to normal levels. Beginning at similar baseline BP values, cumulative intracisternal (i.c.) doses of clonidine (0.02-2.5 micrograms) elicited greater decreases in BP and plasma NE levels in conscious ABD as compared with SO rats. These responses were centrally mediated because systemic administration of 0.12 micrograms clonidine, a dose that elicited near maximal hypotensive response after i.c. administration, affected neither BP nor plasma NE levels. Contrary to the hypothesis, the hypotensive effect of clonidine in ABD rats resulted exclusively from a reduction in CO (owing to reductions in both HR and SV) because TPR was not affected. These findings suggest that (a) in ABD rats, a reduction in CO offsets a sustained sympathetically mediated elevation in TPR and restores BP to normal levels; and (b) an enhanced hypotensive response to clonidine in ABD as compared with SO rats cannot be accounted for by a higher basal TRP but rather by elicitation of greater reductions in CO through a centrally mediated sympathoinhibitory action.

Animals↗
PubMed1994

Endurance exercise in mild hypertension: effects on blood pressure and associated metabolic and quality of life variables.

The effects of a ten week endurance exercise training programme on blood pressure and associated metabolic and quality of life variables were examined in 28 unmedicated mildly hypertensive men (21-54 years of age). At baseline, BP averaged 138.8/94.8 mmHg, body mass index averaged 27.9 and percentage body fat averaged 29%. The average reduction in BP of 11.4/9.8 mmHg (P = 0.0001) was accompanied by decreases in plasma renin activity of 1.82 ng/ml/h (P = 0.001) and in total plasma catecholamines of 77.9 pg/ml (P = 0.05). Percentage body fat decreased 1.3% (P = 0.02) and work capacity increased 1.2 METS (P = 0.002). There were no significant changes in body weight or plasma lipids, cortisol, insulin or urinary electrolyte excretion. Changes in SBP were correlated significantly with change in plasma renin activity (r = 0.38, P = 0.05). Favourable changes were also observed in mood (P = 0.04) and in one measure of type A behaviour (P = 0.04). None of the participants sustained an injury. We conclude that reduction of BP with endurance exercise training in these mildly hypertensive men was primarily associated with reduced plasma renin activity and did not adversely affect quality of life.

Adolescent↗
PubMed1993

Evaluation of vignette-type examination items for testing medical physiology.

Step 1 of the United States Medical Licensing Examination has now replaced the National Board of Medical Examiners part 1 examination as the initial step in medical licensure. The new examination format places an increased emphasis on clinical vignettes to test basic physiological concepts. Suggestions from a question-writing workshop were incorporated into cardiovascular items in a midcourse physiology examination. Item analysis indicated that the overall examination difficulty was not different from examinations administered in the preceding years. Within the examination, however, the vignette questions had significantly higher discrimination indexes than other question types. The slope of the difficulty-to-discrimination relationship was significantly higher in 1992 than in previous years. This means that questions of equivalent difficulty were more discriminating in 1992 than in previous years. Finally, this report suggests a method of identifying questions with both high discrimination and high difficulty index for the development of an (informal) test item bank. The clinical vignette question types are a valuable method of examining basic physiological principles.

Licensure, Medical↗