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Biomedical subjects

S Adler

Publications and source records attributed to S Adler.

At least 109 records · Page 6Linked to original sources
PubMed1995

The undergraduate medical curriculum: centralized versus departmentalized.

The authors describe the advantages and disadvantages of central governance of the undergraduate medical curriculum as contrasted with traditional departmental approaches, based upon their school's experience with a new centrally governed curriculum during the preceding four years. Central governance has more advantages, but also more costs, compared with traditional departmental approaches. Central governance does what it was intended to do: it provides rational and integrative mechanisms for ensuring a broad general education in medicine focusing on the doctor-patient relationship. It also provides an effective mechanism for dealing with "turf" and time issues in the curriculum while allowing for and encouraging changes and providing mechanisms for evaluating those changes. However, as the allocation of resources and rewards remains more departmentally than centrally based, a major challenge of central governance has been to help faculty resolve a "conflict of loyalty" (the sense of serving two masters) between school and department, particularly in the evaluation and reward of teaching. On balance, central governance provides a powerful means of introducing broad-based reforms into all elements of the undergraduate medical curriculum, but it requires ongoing collaboration with faculty and chairs to assist them in negotiating competing pressures and priorities as they strive to become excellent teachers.

Administrative Personnel↗
PubMed1995

Differential positive and negative transcriptional regulation by tamoxifen.

Tamoxifen, a nonsteroidal antiestrogen and breast cancer chemotherapeutic, exhibits both estrogen agonist and antagonist properties. Rat GC3 cells grown under estrogen-free conditions were analyzed for the expression of model luciferase reporter genes, either positively or negatively regulated by estrogens. Expression assays adding tamoxifen alone or in combination with 17 beta-estradiol were performed to determine agonist or antagonist activities. In rat GC3 cells, tamoxifen acts as an estrogen antagonist for gene activation, but as an agonist for repression. Regulation by tamoxifen is mediated by estrogen receptor (ER), not via nonreceptor tamoxifen effects. Evaluation of human ER shows that although the wild-type receptor behaves similarly to the rat receptor, the Gly400 to Val400 mutant receptor does not. Tamoxifen, an effective agonist for gene repression with rat and wild-type receptor, shows no agonist activity using this mutated Val400 receptor. Yet, 17 beta-estradiol and clomiphene, another mixed agonist/antagonist, are effective agonists for gene repression with all three receptors. In this model system, tamoxifen functions as antagonist or agonist, depending on whether the ER acts to activate or repress its gene target. In other systems regulated by estrogens, functional analyses of ER action might also serve to predict the agonist or antagonist activity of tamoxifen.

Animals↗
PubMed1995

Integrated case studies and medical decision making: a novel, computer-assisted bridge from the basic sciences to the clinics.

This article describes a novel course that was designed to bridge the gap between the basic science years and clinical experiences in medical school by using information science and computer technology as major components of problem-based learning (PBL) sessions. The course, Integrated Case Studies and Medical Decision Making, was first given to second-year students at the University of Pittsburgh School of Medicine in the spring of 1994. It consists of 13 PBL exercises, each of which explores a clinical case. The cases, including images and gated access to information, are housed on a computer. Using one of 16 networked terminals in specially designed small-group rooms, groups of nine students progress through the cases with a faculty facilitator. The responses of students and faculty to the initial year of the course were favorable. In comparison with traditional PBL sessions, enhanced quality of and access to images and accountability for accessing case information in sequential fashion were cited as major strengths of the course. Juxtaposition of basic science and clinical material and utility in reviewing for the United States Medical Licensing Examination were also cited as strengths. The diversity of the basic science material involved in completing the cases drew overwhelming enthusiasm from students and facilitators alike. In conclusion, the course successfully employs computer and information science technology, which will be of increasing importance to future physicians. The course also serves as an effective bridge to the clinical years of medical school and as a study adjunct for the USMLE.

Clinical Competence↗
PubMed1994

Multiple-sensor systems for physiologic cardiac pacing.

PURPOSE: To review the status of artificial sensors in cardiac pacemakers and the rationale for developing pacing systems that use multiple sensors. DATA SOURCES: Journal articles published between 1982 and 1993 indexed in MEDLINE using the keywords pacemakers, sensors, and rate-adaptive, as well as abstracts and articles in the authors' personal files. STUDY SELECTION: Articles describing clinical experience with or clinical evaluation of cardiac pacing systems using multiple artificial sensors. DATA SYNTHESIS: Artificial sensors were created to adjust pacing rate reliably in response to changes in levels of physical exertion for patients with sinoatrial disease in whom exercise heart rate response is inadequate (for example, chronotropic incompetence in sinoatrial disease). To achieve this, various artificial sensors were developed and many reports confirm improved exertional tolerance. More recently, sensors have assumed a greater role in cardiac pacemakers. For example, sensors are used to permit automatic adjustment of certain programmable pacemaker settings, such as the atrioventricular interval. In the future, they may also be used to maximize pacemaker longevity by automatically optimizing energy output (voltage, pulse width). No single sensor is ideal for all potential applications, and investigators have advocated using two or more sensors. Several pacemakers that use multiple sensors with different but complementary operating characteristics are already commercially available outside the United States. Although preliminary findings are encouraging, additional clinical experience with these pacemakers is needed to determine their ultimate role in clinical practice. CONCLUSION: Simultaneous use of multiple complementary artificial sensors may permit development of cardiac pacemakers that operate more physiologically yet require less specialized medical follow-up.

Clinical Trials as Topic↗
PubMed1994

T cell epitope analysis with peptides simultaneously synthesized on cellulose membranes: fine mapping of two DQ dependent epitopes.

Several MHC class II restricted, CD4+ human T cell clones from three donors were induced with soluble matrix protein of influenza virus. The epitopes recognized by these clones were mapped using a complete set of overlapping 15-mer peptides synthesized with the newly developed SPOT method which allows the simple simultaneous synthesis of numerous peptides on cellulose membranes. Fine analysis of two clones by truncation of the stimulatory peptide by single subsequent amino acids from either the NH2- or the COOH-terminus revealed the minimal stimulatory determinants of two DQ dependent T cell epitopes.

Amino Acid Sequence↗
PubMed1994

Chronotherapy with 5-fluorouracil and folinic acid in advanced colorectal carcinoma. Results of a chronopharmacologic phase I trial.

BACKGROUND: Chronotherapy with antineoplastic drugs is a rather new strategy of reducing cytotoxic side effects. Because the circadian timing of 5-fluorouracil (5-FU) was reported to result in a higher efficacy and lower toxicity, the authors conducted a chronopharmacologic Phase I trial with 5-FU and folinic acid (FA). METHODS: Eight patients with advanced colorectal cancer received 5-FU (initial dose of 500 mg/m2/day) and FA (20 mg/m2/day) as a continuous intravenous infusion over 5 consecutive days. Using a portable, ambulatory drug delivery system, 75% of the daily dose of 5-FU and FA were given from Oh00-7h00, and the remaining 25% from 7h00-24h00. Treatment courses were repeated after 28 days. Dose escalations of 250 mg/m2/day of 5-FU and 10 mg/m2/day of FA per course were performed in the absence of any toxicity greater than WHO (World Health Organization) grade 2. RESULTS: Dose-limiting toxicity WHO grade 3 was observed at a dose of 750 mg/m2/day of 5-FU and 30 mg/m2/day of FA in five, and 1000 mg/m2/day of 5-FU and 40 mg/m2/day of FA in two patients, respectively. One patient tolerated 1000 mg/m2/day of 5-FU and 40 mg/m2/day of FA, but the treatment was stopped before further dose escalation because of rapid disease progression. Mucositis was the dose-limiting toxicity in seven patients and diarrhea in two. Disease stabilization occurred in three patients and disease progression in five. Compared with conventional Phase I/II trials using a 5-day infusion regimen, the maximal tolerated dose of 5-FU and FA was slightly higher but significantly lower than in a chronotherapeutic trial that used a different, sinusoidal mode of drug application. CONCLUSION: Based on these results, the authors feel justified to caution that the circadian timing of 5-FU plus FA may not always allow the safe application of high dose levels. Future Phase I/II studies need to define whether specific drug delivery systems or schedules are necessary for chronotherapy with 5-FU and FA in patients with colorectal carcinoma.

Adult↗
PubMed1994

Positive inotropic effects of the beta 2-adrenoceptor agonist terbutaline in the human heart: effects of long-term beta 1-adrenoceptor antagonist treatment.

OBJECTIVES: This study was conducted to determine whether activation of cardiac beta 2-adrenoceptors increases contractility in humans and whether this is affected by long-term beta 1-adrenoceptor antagonist treatment. BACKGROUND: Coexistence of beta 1- and beta 2-adrenoceptors in the human heart is generally accepted. The functional importance of cardiac beta 2-adrenoceptors for increases in contractility in humans, however, has not been completely established. METHODS: We studied 1) the beta-adrenoceptor subtype mediating positive inotropic effects of the beta 2-adrenoceptor agonist terbutaline in vitro (on right atrial and left ventricular preparations from nonfailing human hearts) and increases in contractility (by measurement of systolic time intervals) in vivo in seven healthy male volunteers; and 2) in vivo whether long-term treatment of volunteers with the beta 1-adrenoceptor antagonist bisoprolol affects terbutaline-induced increases in contractility. RESULTS: In vitro terbutaline caused a concentration-dependent increase in atrial and ventricular adenylate cyclase activity and force of contraction. Terbutaline effects were antagonized only by the beta 2-adrenoceptor antagonist ICI 118,551, indicating that they were mediated by beta 2-adrenoceptor stimulation. In vivo intravenous infusions of terbutaline (dose range 25 to 300 ng/kg body weight per min for 15 min) dose dependently increased heart rate and shortened the pre-ejection period and heart rate-corrected electromechanical systole (QS2) time. These effects are mediated predominantly by beta 2-adrenoceptor stimulation because they were only marginally affected by the beta 1-adrenoceptor antagonist bisoprolol (1 x 10 mg orally), either given 2 h before infusion or long term for 3 weeks. CONCLUSIONS: Stimulation of cardiac beta 2-adrenoceptors in humans causes not only in vitro but also in vivo positive inotropic effects. Long-term beta 1-adrenoceptor antagonist treatment does not considerably affect beta 2-adrenoceptor-mediated in vivo increases in contractility. Thus, it may be possible to treat patients with chronic heart failure and long-term beta 1-adrenoceptor antagonist therapy with beta 2-adrenoceptor agonists if immediate inotropic support is needed.

Adenylyl Cyclases↗
PubMed1994

Perfusion imaging of the rat kidney with MR.

PURPOSE: To develop a technique for measurement of regional renal perfusion with magnetic resonance (MR) imaging. MATERIALS AND METHODS: Quantitative renal perfusion images in rats were obtained by measurement of the reduction in kidney MR image signal intensity after steady state magnetic labeling of arterial blood in the suprarenal aorta. Labeling was achieved with adiabatic fast passage inversion of arterial water. RESULTS: Cortical renal blood flow was 4.9 mL/g/min +/- 0.15 (12 rats), which correlated well with previous measurements obtained with other techniques. Serial perfusion images obtained every 5 minutes during intravenous infusion of either acetylcholine or angiotensin II showed that one increased and the other decreased renal blood flow, respectively, also correlating with previous measurements. CONCLUSION: Quantitative measurement of cortical renal blood flow can be obtained with proton MR imaging techniques, with use of endogenous arterial water as a tracer. This technique should be readily applicable to measurement of renal perfusion in humans.

Acetylcholine↗
PubMed1994

Brain buffering is restored in hyponatremic rats by correcting their plasma sodium concentration.

Previous studies from this laboratory showed that both acute and chronic hyponatremia impaired active brain buffering. These studies were performed to determine whether correcting the plasma sodium restored normal buffering in hyponatremic rats. Acute (1- and 2-day) and chronic (7- and 14-day) hyponatremia was induced in male Sprague-Dawley rats by constant desmopressin administration combined with a liquid diet. Plasma sodium was corrected by stopping desmopressin for 6 h, substituting solid chow, and allowing free access to water. Studies were performed 24 h later. Uncorrected hyponatremic rats who continued to receive desmopressin and liquid diet served as controls. Brain pH was determined by [31P]NMR in rats anesthetized with N2O and paralyzed with pancuronium. Brain buffering was determined by the response to CO2 loading. Resting brain pH was the same in corrected and uncorrected rats, but the two groups responded differently to CO2 loading. Thus, 55 min after ventilation with 20% CO2, corrected rat brain pH was 0.13 pH units higher than in uncorrected rats despite statistically similar changes in CO2 tension and arterial pH in both groups. Moreover, 15 min into recovery from CO2 exposure, brain pH in corrected rats overshot resting pH by 0.07, whereas no overshoot occurred in uncorrected rats. Buffering in corrected rats was identical to that shown previously in normonatremic rats. The complete restoration of late-phase buffering achieved by normalizing the plasma sodium of hyponatremic rats indicates that at least some portion of active hydrogen ion transport is sodium dependent in the brain.

Acute Disease↗
PubMed1994

Structure-function relationships associated with extracellular matrix alterations in diabetic glomerulopathy.

Proteinuria and progressive renal insufficiency are the primary manifestations of diabetic nephropathy. Accumulating evidence suggests that these clinical features can be linked, at least in part, to pathologic changes in the glomerular extracellular matrix. Most evidence suggests that glomerular basement membrane thickening and mesangial matrix expansion consist of at least three elements. These are (1) an accumulation of normal extracellular components; (2) an increase in the novel peptide chains of the normal components of Type IV collagen; and (3) an increase in matrix elements not normally expressed in the glomerulus. The pathogenetic features underlying these changes include increased synthesis and decreased degradation of matrix. Abnormal physico-chemical interactions among these matrix elements likely contribute to alterations in three-dimensional structure, leading to proteinuria and loss of glomerular basement membrane filtering surface area. Many of these changes may be explained in whole or in part by direct or secondary effects of hyperglycemia, as well as by hemodynamic changes.

Animals↗
PubMed1994

Integrin matrix receptors in renal injury.

Integrins play a major role in cell-matrix interactions. They alter cellular functions upon binding to matrix proteins or following cross linking and can in turn be regulated by other stimuli acting on the cell. In the kidney integrins may help regulate cellular proliferation and matrix turnover during renal injury, effects which could play an important role in the pathogenesis of glomerulosclerosis and the resultant loss of renal function. Alterations in cell adhesiveness may contribute to tubular epithelial cell sloughing and tubular obstruction in acute renal failure and may play a role in alterations of glomerular capillary wall permeability, leading to proteinuria. Adhesion molecules on GEC may be important targets of antibodies in several models of proteinuric renal disease and areas of GEC detachment from the GBM may be involved in the development of glomerulosclerosis. Since integrins are major links between the ECM and cells, better understanding of their function in the normal kidney and during injury is of importance to a better understanding of the pathogenesis of renal disease.

Animals↗
PubMed1993

Hepatitis C in the health care setting. II. Seroprevalence among hemodialysis staff and patients in suburban New York City.

BACKGROUND: Hepatitis C virus (HCV) is a newly identified blood-borne virus that may pose an occupational hazard for health care workers. Hemodialysis nurses could be anticipated to be at high risk for HCV infection because this group of health care workers frequently comes into contact with blood of a patient population with a seroprevalence rate of at least 10%. METHODS: To assess the risk of HCV infection for hemodialysis nurses, serum samples from all of the nurses (22/22, 100%) and patients (125/125, 100%) in one hemodialysis unit (unit A) and 85% (29/34) of nurses from a second unit (unit B), both units in suburban New York City, were tested for HCV antibodies. Samples with positive results of enzyme-linked immunosorbent assay underwent supplemental testing by a first-generation recombinant immunoblot assay. RESULTS: Twenty-four (19%) of the hemodialysis patients in unit A were HCV seropositive. Despite an average of 4.7 years spent working in hemodialysis unit A, none of the nurses tested seropositive for HCV antibody. In unit B, despite an average of 6.4 years working in the unit studied, only one nurse tested seropositive for HCV antibody. This nurse reported a long history of elevated liver function values and a negative HBV core antibody status that predated her hemodialysis nursing career. CONCLUSIONS: In contrast to the experience with hepatitis B virus infection, hemodialysis nurses appear to be at low risk for occupationally acquired HCV infection.

Adult↗
PubMed1993

Evaluation of platelet hyperfunction in hemodialysis patients receiving recombinant human erythropoietin.

There are data suggesting that recombinant human erythropoietin (rHuEPO) may induce thromboses in hemodialysis patients, possibly due to alterations in platelet function. In an earlier study, we found evidence of platelet hyperfunction in several patients 4 to 8 weeks following the start of rHuEPO therapy, which was begun shortly after hemodialysis was initiated. Studies were performed to examine the effects of rHuEPO on whole blood platelet aggregation and adenosine triphosphate (ATP) release independent of changes in hematocrit or the uremic state. Eight hemodialysis patients without and four with a history of vascular access clotting had platelet aggregation tests performed at baseline while receiving rHuEPO, off rHuEPO for 2 weeks, and 4 to 6 weeks after restarting the drug. While the plasma EPO level decreased significantly after the 2-week period off rHuEPO (P < 0.0001), the hematocrit did not change at any of the three time periods. Whole blood platelet aggregation in response to adenosine diphosphate (ADP), collagen, and ristocetin was not significantly altered on or off rHuEPO in either patient group. Platelet hyperfunction, determined by aggregation or ATP release either spontaneously or in response to low-dose ADP or ristocetin, was not seen in any patient. These data suggest that the increase in access clotting is not the result of platelet hyperfunction induced directly by rHuEPO.

Adenosine Diphosphate↗
PubMed1993

Macroscopic hematuria as a presenting manifestation of oliguric acute tubular necrosis.

Macroscopic hematuria associated with acute renal failure usually results from glomerulonephritis or structural abnormalities (stones, tumors, or infections). Acute tubular necrosis is rarely associated with macroscopic hematuria in the absence of other genitourinary abnormalities. We describe a patient who presented with macroscopic hematuria, in whom only acute tubular necrosis could be identified as a causative factor.

Adult↗
PubMed1993

Integrin receptors and function on cultured glomerular endothelial cells.

Integrin expression and function on a cloned line of rat glomerular endothelial cells (GEndoC) were studied in an effort to obtain a better understanding of the means by which these cells interact with components of the glomerular basement membrane. Cultured GEndoC adhered to fibronectin, laminin and types I and IV collagen and expressed alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha v beta 1 and alpha v beta 3 integrins. Synthetic RGDS peptides significantly decreased adhesion to fibronectin (53.1 +/- 4.7% of control). Antibody to rat beta 1 integrin strongly inhibited adhesion to laminin, fibronectin and types I and IV collagen (11.2, 19.0, 67.3 and 31.9% of control adhesion, respectively), while antibody to the rat alpha 1 integrin chain strongly inhibited adhesion to laminin (65.2% of control), but only mildly inhibited adhesion to type IV collagen (77.2% of control) and did not affect adhesion to type I collagen (97.8% of control). Affinity chromatography of GEndoC lysates on a column of immobilized type I collagen displayed predominantly binding of alpha 3 beta 1 integrin with trace amounts of alpha 1 beta 1 and alpha 2 beta 1, documenting the major role of alpha 3 beta 1 in GEndoC adhesion to collagen. Chromatography on the immobilized cell-binding fragment of fibronectin revealed the alpha 5 beta 1 integrin to be the major fibronectin receptor on these cells, but antibody to alpha v beta 3 integrin also documented a minor role for alpha v beta 1 or alpha v beta 3 in fibronectin adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Automated real-time analysis of intraoperative transesophageal echocardiograms.

BACKGROUND: Although transesophageal echocardiography (TEE) produces real-time images depicting left ventricular (LV) filling and ejection, the quantitative analysis of these images has been too time consuming to be of practical value in the operating room. Therefore, the authors investigated whether a new automated border detection system (ABD) could track the endocardial border continuously and compute the cross-sectional area of the LV cavity. METHODS: Using data from 25 patients who were monitored with TEE as part of their routine clinical care, the authors compared ABD estimates of LV end-diastolic area (EDA in square centimeters), end-systolic area (ESA in square centimeters), and fractional area change (FAC) with the laboratory measurements made independently by an expert. RESULTS: ABD slightly underestimated EDA (10.7 +/- 1.0 vs. 11.2 +/- 1.0 cm2) and slightly overestimated ESA (5.6 +/- 0.7 vs. 4.8 +/- 0.6 cm2, mean +/- standard error). However, when ABD tracking of the endocardial border was judged as "good" or "excellent" (84% of the patients at end diastole and 72% at end systole), the limits of agreement between ABD and the expert's findings were within the limits expected for two experts. By contrast, ABD significantly underestimated FAC (0.44 +/- 0.03 vs. 0.56 +/- 0.03) and the limits of agreement between ABD and the expert were more than twice as great as expected for experts, even when ABD performance was judged as "excellent." CONCLUSION: The authors conclude that, when ABD appears to be performing adequately, it underestimates LV FAC, but provides valid real-time estimates of LV EDA and ESA. Thus, it warrants further evaluation as a potentially powerful clinical and research tool.

Adult↗