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Biomedical subjects

S Tessler

Publications and source records attributed to S Tessler.

At least 37 records · Page 2Linked to original sources

Medical student initiatives to promote the education of generalist physicians.

Medical student organizations--including the American Medical Student Association (AMSA), the Association of American Medical Colleges's Organization of Student Representatives (AAMC-OSR), and the American Academy of Family Physicians' National Congress of Student Members (AAFP-NCSM)--are responding to the increased need for generalist physicians. Through a variety of initiatives drawing on each organization's unique strengths and capabilities, students are developing curricular and extracurricular initiatives to increase trainees' exposure to and knowledge about generalist medicine. These projects indicate that future physicians are interested in learning about generalist careers and in working with generalist mentors early in their medical training. Students are addressing these needs through community-based experiences, student interest groups, legislative activity, curricular reform, and research in generalist medicine.

Clinical Clerkship↗

Heparin modulates the interaction of VEGF165 with soluble and cell associated flk-1 receptors.

The 165-amino acid form of vascular endothelial growth factor (VEGF165) is a mitogen for vascular endothelial cells and a potent angiogenic factor. Expression of a chimeric receptor containing the extracellular domain of the flk-1 receptor fused to the transmembrane and intracellular domains of the human c-fms receptor in NIH-3T3 cells, resulted in the appearance of high affinity binding sites for 125I-VEGF165 on transfected cells. The binding of 125I-VEGF165 to the flk-1/fms chimeric receptor of the transfected cells as well as the VEGF165-induced autophosphorylation of the chimeric receptors were inhibited in the presence of low concentrations of heparin (1-10 micrograms/ml). In contrast, similar concentrations of heparin potentiated the binding of 125I-VEGF165 to the endogenous VEGF receptors of the transfected cells, indicating that to some extent, the effect of heparin on 125I-VEGF165 binding is receptor type-dependent. A soluble fusion protein containing the extracellular domain of flk-1 fused to alkaline phosphatase (flk-1/SEAP) was used to study the effects of heparin on the binding of 125I-VEGF165 to flk-1 in a cell-free environment. The fusion protein specifically inhibited VEGF165-induced proliferation of vascular endothelial cells, but bound 125I-VEGF165 inefficiently in the absence of heparin. Addition of low concentrations of heparin or heparan sulfate (0.1-1 microgram/ml) resulted in a strong potentiation of 125I-VEGF165 binding, whereas higher heparin or heparan sulfate concentrations inhibited the binding. The effect of heparin on the binding of 125I-VEGF165 to flk-1/SEAP could not be mimicked by desulfated heparin or by chondroitin sulfate. Both bFGF and aFGF inhibited the binding when low concentrations of heparin were added to the binding reaction. However, higher concentrations of heparin abolished the inhibition, indicating that the inhibition is probably caused by competition for available heparin. Taken as a whole, these results indicate that heparin-like molecules regulate the binding of VEGF165 to its receptors in complex ways which depend on the heparin binding properties of VEGF165, on the specific VEGF receptor type involved, and on the amount and composition of heparin-like molecules that are present on the cell surface of VEGF receptor containing cells.

3T3 Cells↗

Vascular endothelial growth factor and its receptors.

Vascular endothelial growth factor (VEGF) is a highly specific mitogen for vascular endothelial cells and an angiogenic factor that is structurally related to platelet derived growth factor (PDGF). It is also known as the vascular permeability factor (VPF) because it efficiently potentiates the permeabilization of blood vessels. Five types of VEGF mRNA encoding VEGF species which differ in their molecular mass and in their biological properties are transcribed from a single gene as a result of alternative splicing. VEGFs are produced and secreted by several normal cell types including smooth muscle, luteal and adrenal cortex cells. VEGFs are also produced by different tumorigenic cells, and appear to play a major role in tumour angiogenesis. Antibodies directed against VEGF can inhibit the growth of a variety of VEGF producing tumours. Of the various VEGF species, the best characterized is the 165 amino acid long form (VEGF165). VEGF165 is a heparin binding growth factor, and its interaction with VEGF receptors on the cell surface of vascular endothelial cells depends on the presence of heparin-like molecules. Several cell types which do not proliferate in response to VEGF such as bovine corneal endothelial cells, HeLa cells and human melanoma cells also express cell surface VEGF receptors, but the function of the VEGF receptors in these cells is unclear. Recently, the tyrosine-kinase receptors encoded by the flt and KDR/flk-1 genes were found to function as VEGF165 receptors.

Animals↗

Right-sided pneumothorax as a result of a left-sided chest tube.

Chest tubes are inserted for a variety of reasons, and a number of complications have been associated with their use. We report a case of traumatic hemopneumothorax in which the chest tube crossed the mediastinum into the contralateral lung causing a pneumothorax. Its position was not apparent on portable chest radiographs.

Adult↗

Basic fibroblast growth factor accumulates in the nuclei of various bFGF-producing cell types.

The intracellular localization of basic fibroblast growth factor (bFGF) was studied in BHK-21 cells transfected with an expression vector containing the complementary DNA (cDNA) of the human bFGF gene (pbFGF). The intracellular location of bFGF was determined using indirect immunofluorescence. The antibodies used were polyclonal antibodies directed against either recombinant human bFGF or recombinant Xenopus bFGF. The nuclei of transfected cells that produce bFGF, but not the nuclei of untransfected cells, were labeled strongly by the antibodies. The nuclear staining was totally abolished when anti-bFGF antibodies preadsorbed with bFGF were used. Several types of endothelial cells known to produce bFGF were also stained in their nuclei by the antibodies. Nuclear extracts prepared from transfected cells were found to contain bFGF as determined using heparin-sepharose affinity chromatography, followed by Western blot analysis of fractions, which stimulated the proliferation BHK-21 cells. The mitogenic activity associated with the nuclei was not destroyed when isolated cell nuclei were digested by trypsin. It is therefore likely that the nucleus associated bFGF is intranuclear. These findings suggest that some biological activities of bFGF may be mediated by nuclear bFGF binding proteins or by the direct binding of bFGF to DNA.

Adrenal Glands↗

Massive gastric distention in the intubated patient. A marker for a defective airway.

Tracheal intubation is a commonly performed procedure generally associated with a low complication rate. A clinical sign that could lead to early detection of complications could improve management of mechanically ventilated patients. We present two instances of potentially lethal complications that were heralded by the presence of massive gastric distention. This finding should alert physicians that an abnormal communication may exist between the endotracheal tube and the gastrointestinal tract.

Aged↗

Effect of sternotomy and coronary bypass surgery on postoperative pulmonary mechanics. Comparison of internal mammary and saphenous vein bypass grafts.

Coronary artery bypass grafting (CABG) is commonly performed via a median sternotomy with a reversed saphenous vein (SV) and/or an internal mammary artery (IMA) graft. Sternotomy and IMA harvesting may adversely affect postoperative respiratory function (PFTs) as disruption of the sternun may impair chest wall stability, and the decrease in intercostal muscle blood supply after removal of the IMA may reduce the force of respiration. We compared preoperative and six- to eight-week postoperative PFTs in patients undergoing CABG. The results were independent of age, sex, number of grafts, aortic cross clamp time, duration of bypass run, and postbypass fluid gradient. It was concluded that sternotomy caused a decrease in postoperative PFTs and that IMA harvesting may be accompanied by greater impairment in PFTs than when SV grafts alone were used.

Aged↗

A randomized, double-blind, placebo-controlled study of verapamil and metoprolol in treatment of multifocal atrial tachycardia.

PURPOSE: Multifocal atrial tachycardia is a difficult arrhythmia to treat. Patients not showing a response to the correction of predisposing conditions present a therapeutic dilemma. To assess the efficacy of two agents reported to be effective in this condition, verapamil, metoprolol, or placebo was given intravenously in a randomized, double-blind trial. PATIENTS AND METHODS: Thirteen patients meeting inclusionary criteria were enrolled. Therapeutic response was defined as conversion to sinus rhythm, a decline in the ventricular rate of 15 percent or more [corrected], or a ventricular rate of less than 100 beats/minute. Four male and nine female patients having a mean age (+/- SD) of 81.9 +/- 14.2 years were enrolled. Automated serum chemistries, complete blood cell count with differential, arterial blood gas values, and serum digoxin and theophylline levels were determined and a 12-lead electrocardiogram was obtained at the start of the trial. Following the completion of each phase of the study, a repeat physical examination was performed, and arterial blood gas values and an electrocardiogram were obtained. The trial was designed to run for two days. RESULTS: Two of 10 (20 percent), four of nine (44 percent), and eight of nine (89 percent) showed a response to placebo, verapamil, or metoprolol, respectively. Mean slowing of ventricular rate was 3.4, 7.3, and 24.5 percent for placebo, verapamil, and metoprolol, respectively (p less than 0.01 for metoprolol versus placebo). Five patients who showed a response to metoprolol had failed to have a response to verapamil. CONCLUSION: We conclude that metoprolol appears to be more effective than verapamil in treating multifocal atrial tachycardia. However, careful patient selection is necessary in its use.

Aged↗

Metoprolol in the treatment of multifocal atrial tachycardia.

Multifocal atrial tachycardia (MAT) is a difficult arrhythmia to treat. Pharmacologic treatment is generally disappointing, and successful conversion in a predictable manner is uncommon. To assess the efficacy of metoprolol, a relatively selective beta 1-adrenergic blocking agent, we administered this agent to 11 patients (aged 71.8 +/- 8.3 yr). All patients had serious pulmonary disease. Hypoxia, hypercarbia, acidosis, and electrolyte abnormalities were corrected before the study. Nine patients were receiving theophylline derivatives and six digoxin. Serum levels for both drugs were in the therapeutic range. Four patients had received verapamil without control of MAT. Mean atrial rate before administration of metoprolol was 142.3 +/- 17.2 beat/min and mean ventricular rate was 131.4 +/- 24.3 beat/min. One to 3 h after metoprolol (25 or 50 mg orally), all patients were restored to sinus rhythm, with a mean ventricular rate of 86.9 +/- 6.8 beat/min (p less than .01). Six patients had 3 to 6 premature atrial contractions per minute. No adverse effects were noted, and arterial blood gases before and after therapy were comparable. Five patients expired from their underlying disease and four were continued on metoprolol to maintain sinus rhythm. Metoprolol is effective in the acute and chronic treatment of MAT and may be given to patients with MAT and respiratory failure without serious adverse effects.

Aged↗

Metabolic acidosis not due to lactic acidosis in patients with severe acute asthma.

Asthmatics seeking emergency care for severe acute asthma may show metabolic acidosis. We sought to determine the frequency of metabolic acidosis in such patients and to assess the relative contributions of renal bicarbonate loss and lactic acid accumulation to this acidosis. Twenty-two asthmatics (21-71 yr; four males, and 18 females) who came consecutively to the emergency department with severe acute asthma were studied. Most patients reported that their asthmatic symptoms had begun to worsen greater than or equal to 2 days before the emergency department visit. Within several hours, simultaneous measurements of arterial blood gases, whole blood lactate, and serum electrolytes were made. Ten of 22 patients were found to have metabolic acidosis (base deficit greater than 2 mEq/L). All ten patients had nonanion gap acidosis, while nine of ten had whole blood lactate values in the normal range (0.33 to 2.55 mmol/L). In the one patient with an elevated whole blood lactate level, the concentration of lactate in excess of normal (0.45 mmol/L) could not account for the magnitude of the base deficit (-4.9 mEq/L). We conclude that a) nonanion gap metabolic acidosis is very common in asthmatics with acute severe asthma (prevalence 45% in our series), and b) the mechanism of the base deficit in these patients is excessive renal bicarbonate excretion. We believe that the latter occurs as a renal compensatory response to a preceding period of hypocapnia due to hyperventilation related to worsening asthma.

Acid-Base Equilibrium↗

Mouse sperm motility affected by factors in the T/t complex.

Motility characteristics of epididymal sperm from tw32/+ and T/+ males of several strains were compared to those of sperm from the congenic, wild, type mice. Epididymal sperm from C57BL/6-tw32/+ (B6-tw32/+) males showed a significant decline in vigorous motility and a significant increase in adhesivity to glass during 7.5 hours in vitro, while sperm from B6-+/+ males showed no changes in these characteristics. The apparent mean velocities of epididymal sperm were: B6tw32/+, 32 micro/sec; C3H-tw32/+, 60; B6XC3H hybrids (F2*-tw32/+), 44; and C3HXB6 hybrids (F2-tw32/+), 58. Each of these values was significantly lower than that of sperm from their congenic wild-type strains: B6- +/+, 115; C3H- +/+, 177; F1*-+/+, 168 and F1-+/+, 195 micro/sec. B6-T2J/+ sperm had velocities intermediate to the congenic +/+ and tw32/+ genotypes, whereas C3HT/+ sperm velocity was not significantly different from C3H- +/+. These differences in measured sperm velocity may not reflect real differences in swimming speed, but rather may indicate a difference in the shape of swimming trajectories. Erratic and convoluted swimming trajectories were observed for the majority of sperm from tw32/+ males of all genotypes. Differences in motility patterns of sperm from tw32/+ males could play a role in the abnormally high transmission of tw32 through the male.

Animals↗