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Biomedical subjects

M A Levitt

Publications and source records attributed to M A Levitt.

At least 73 records · Page 4Linked to original sources

Beneficial effects of prostaglandin E1 infusion in experimental traumatic shock.

The effects of prostaglandin E1 (PGE1) were studied in a standardized model of traumatic shock in rats. Pentobarbital anesthetized rats were subjected to standardized drum trauma of 525 revolutions in a Noble-Collip drum. These traumatized rats were characterized by a survival time of 108 +/- 19 min, a 12-fold increase in plasma cathepsin D activity, and a three-fold increase in plasma myocardial depressant factor (MDF) activity. PGE1 (1.2 micrograms/kg X min) significantly improved survival time during traumatic shock (191 +/- 29 vs. 108 +/- 19 min), drug vs. vehicle, respectively (p less than .03). In addition, PGE1 significantly attenuated plasma MDF activity during traumatic shock (58 +/- 10 vs. 27 +/- 7 U/ml), vehicle vs. drug, respectively (p less than .02). Plasma cathepsin D activity was also significantly retarded (12.1 +/- 1.8 vs. 1.70 +/- 1.50 U/ml), vehicle vs. drug, respectively (p less than .01). PGE1 appears to exert a membrane stabilizing effect, decreasing plasma cathepsin D and attenuating MDF production. PGE1 thus appears to have significant antishock activity.

Alprostadil↗

Efficacy of two leukotriene antagonists in rat traumatic shock.

The effects of CGP 33304 and CGP 35949 were studied in standardized model of traumatic shock. Both drugs are dual leukotriene receptor antagonists and phospholipase A2 inhibiting agents. Pentobarbital anesthetized rats (35 kg/mg) subjected to Noble-Collip drum trauma were characterized by a 128 +/- 16 min survival time and a 4-fold increase in plasma myocardial depressant factor (MDF) activity. CGP 33304 and CGP 35949 both significantly (p less than 0.01) attenuated the accumulation of MDF activity in the plasma (24 +/- 3 and 29 +/- 3 U/ml, respectively, vs. 57 +/- 5 U/ml in the trauma and vehicle group). A significant improval in survival time (p less than 0.05) was observed in the CGP 33304 treated group (182 +/- 23 min) and the CGP 35949 treated group (204 +/- 33 min). Both drugs exhibited significant anti-proteolytic activity in pancreatic homogenates. CGP 33304 and CGP 35949 appear to attenuate MDF production, probably secondary to their anti-proteolytic effect and the improved state of the splanchnic circulation. Both drugs also may prevent hypoxia secondary to leukotriene induced bronchoconstriction in shock states. CGP 33304 and CGP 35949 may, therefore, prove to be useful therapeutic agents in acute ischemic disorders including traumatic shock.

Animals↗

Isolation and partial characterization of endothelial cell extracellular complexes.

Human endothelial cells release components into the growth medium that stimulate cell-substratum adhesion. Several macromolecular components were isolated by ultracentrifugation of the endothelial cell conditioned medium. The components were heterogeneous, consisting of several sizes when examined by sedimentation velocity and gel filtration. When the extracellular components were evaluated by electron microscopy, structurally discrete particles were observed. The extracellular components and the complexes mediated cell-substratum adhesion to both human umbilical and arterial endothelial cells. The majority of the extracellular components that promote endothelial cell adhesion were pelleted by ultracentrifugation. Although the complexes contained fibronectin, antibodies to fibronectin did not inhibit cell adhesion to the complexes. Significant inhibition of endothelial cell adhesion was observed in the presence of heparin and heparan sulfate. The supernatant fraction following ultracentrifugation of the growth medium contained a component that suppressed endothelial cell adhesion to culture dishes coated with fibronectin, type I collagen, and endothelial cell complexes. SDS-polyacrylamide gel electrophoresis indicated that the complexes contained several components, and the majority of the large-molecular-weight components were pelleted by ultracentrifugation. The conditioned medium from human endothelial cells contains specific complexes that promote cell-substratum adhesion and components that suppress cell-substratum adhesion.

Antigens, Surface↗

Anti-shock properties of the prostacyclin analog, iloprost, in traumatic shock.

The effects of iloprost, a synthetic carbacyclin derivative of prostacyclin (PGI2) was studied in a standardized model of traumatic shock. Pentobarbital anesthetized rats (35 mg/kg) subjected to Noble-Collip drum trauma were characterized by a 84 +/- 10 minute survival time, a 16-fold increase in plasma cathepsin D activity, and a 5-fold increase in plasma myocardial depressant factor (MDF) activity. Iloprost significantly attenuated the accumulation of MDF activity in the plasma (69 +/- 14 vs. 20 +/- 6 U/ml) vehicle vs. drug (p less than 0.01), respectively, and significantly prolonged survival time to 243 +/- 36 minutes (p less than 0.01). Plasma cathepsin D activity was also significantly attenuated (12 +/- 1.8 vs. 6.2 +/- 2.1 U/ml), vehicle vs. drug, respectively (p less than 0.02). Iloprost exhibited significant anti-proteolytic activity in pancreatic homogenates. Iloprost appears to exert a membrane stabilizing effect decreasing plasma cathepsin D activity and attenuating MDF production, probably secondarily to its anti-proteolytic effect and its maintenance of the splanchnic circulation. Iloprost may therefore prove to be a useful therapeutic agent in acute ischemic disorders including traumatic shock.

Animals↗

Amitriptyline plasma protein binding: effect of plasma pH and relevance to clinical overdose.

Reversing ventricular ectopy with plasma alkalinization following acute tricyclic antidepressant overdose is a recognized mode of therapy. The mechanism responsible for this effect is unclear. Changes in plasma protein binding of free drug, effects of the sodium ion on the myocardium, and alterations of plasma concentrations of alpha-1-acid glycoprotein may all interact to alter toxicity of tricyclics in overdose. An in vitro investigation using equilibrium dialysis was designed to examine the effect of altering plasma pH on percentage of free amitriptyline at clinical overdose plasma concentrations. A 1973 report on this effect lacked adequate controls and was faulty in experimental protocol. The current investigation used plasma concentrations typically present in amitriptyline overdose, a sensitive gas liquid chromatographic assay to detect total and free drug, and adequate control of plasma pH. The results of two separate experiments demonstrated a significant decrease in percentage of free amitriptyline of 20% over a pH range of 7.0-7.4 (P less than 0.05) and 42% over a pH range of 7.4-7.8 (P less than 0.05). The rate of change in slope in both experiments was not significantly different (P less than 0.01) indicating similar effects of pH change on plasma protein binding of amitriptyline within the two groups.

Amitriptyline↗

Survey of undergraduate emergency medical education in the United States.

To determine the status of undergraduate education in emergency medicine, questionnaires were sent to 141 medical schools. Of the 135 schools responding, 15.2% require emergency medicine courses in the fourth year (mean, 164 hours); 11.9% require these courses (average, 84 hours) in the third year. Emergency medicine is offered in 21.8% of second-year and 37.9% of first-year curriculums. Training in cardiopulmonary resuscitation is offered in 96% of the schools responding, and certification is required in 53%. Training in advanced cardiac life support is offered in 73% of schools, with 23% requiring it for graduation. Training in advanced trauma life support is offered in 17.2% of schools. Osteopathic schools require more time for emergency medicine in the clinical years but less time in formal lectures. Schools with a residency program in emergency medicine more frequently offer emergency medicine in the preclinical years. This survey provides some basic data on the status of undergraduate emergency medicine education in medical school curriculums, and it encourages medical educators to review the undergraduate curriculum to ensure that students receive adequate exposure to the essentials of emergency medicine.

Curriculum↗

Should the emergency IVP be used more selectively in blunt renal trauma?

A retrospective study was performed to determine if the emergency intravenous pyelogram (IVP) is being overused in the evaluation of blunt renal trauma. Medical records of 105 blunt renal trauma patients undergoing IVPs for suspected blunt renal trauma were analyzed. Eighty-eight patients (83.8%) had normal IVPs, and 17 patients (16.2%) had abnormal IVPs. Three of the 105 patients (2.9%) required urologic surgical intervention. The medical records of these patients were examined in detail because it was believed that this patient population needed to be identified by emergency IVP. All three patients requiring urologic surgery had gross hematuria. All three patients had one or more associated injuries. Two of the three patients had flank tenderness and/or flank mass. The third patient was obtunded. From this study and information from the literature an algorithm has been constructed as a guideline for a prospective study. Following this guideline no patients in the study requiring urologic surgical intervention would have been missed. Of patients requiring an emergency IVP, 7.3% would have required urologic surgery. This would have resulted in a savings of $10,432 at our institution.

Emergencies↗

Bacterial adherence to human endothelial cells in vitro.

Differences in the ability of bacteria to adhere to normal valvular endothelium may account for the predominance of particular species as pathogens in acute endocarditis. An in vitro adherence assay was developed to simulate the host surface encountered in acute bacterial endocarditis by using confluent monolayers of human endothelial cells. Adherence of 32 gram-positive and -negative blood culture isolates to this surface was compared. All five Staphylococcus aureus strains tested were highly adherent to endothelial cells, as was one gram-negative strain (Serratia marcescens). The remaining gram-positive and -negative isolates, including four viridans streptococci, were relatively nonadherent. Transmission electron microscopy demonstrated attachment of Staphylococcus aureus and invagination of the underlying endothelial cell membrane at 1 h followed by engulfment of large numbers of bacteria after 3 h. The intracellular bacteria appeared to be contained within vacuoles. Preferential attachment of some strains of bacteria, in particular Staphylococcus aureus, to human endothelial cells occurred in vitro, suggesting that adherence is an important determinant of bacterial pathogenicity in acute endocarditis. Active uptake of bacteria by endothelial cells may help account for the virulence of Staphylococcus aureus in endovascular infections and for the ability of this organism to establish multiple metastatic foci of infection.

Adhesiveness↗

The effect of the extracellular matrix on the detachment of human endothelial cells.

Human umbilical vein endothelial cells can be serially passaged by supplementing medium with a partially purified growth factor. Cell-substratum detachment of early and late passage endothelial cells was examined using trypsin, collagenase, or homocysteine. Late-passage cells detached more rapidly than early passage cells under all conditions tested. The rate of detachment was dependent upon the specific agent used. Protease-mediated detachment was most rapid, occurring over minutes, in contrast to homocysteine-induced detachment, which occurred over hours. When detached cells were collected and replated in the absence of the detaching agent, these cells reattached, spread, and continued to proliferate. No significant difference was observed in the rate of adhesion of either early or late passage cells to a gelatin matrix. When early or late-passage endothelial cells were plated and grown to confluence on a matrix synthesized by the opposite cell type, the rate of protease-mediated cell detachment resembled the cell type from which the matrix was derived. The ease of endothelial cell detachment was determined by the origin of the extracellular matrix. Examination of the extracellular matrices from early and late passage cells revealed significant differences in the amounts of glycosaminoglycans and sulfated proteins present. These studies demonstrate the importance of the endothelial cell extracellular matrix in protease-mediated cell detachment. The rate of cell detachment was controlled by the extracellular matrices are not altered by the endothelial cells.

Cell Adhesion↗

Alternative forms of emergency care: the Arizona experience.

Federal, state, and county governments, along with the medical community, are continually attempting to find ways to curtail rising health care costs. Prepaid capitated health care systems have been devised and implemented in an attempt to control these costs. The Arizona Health Care Cost Containment System (AHCCCS) is an experimental system being tried in Arizona in an attempt to stabilize expenses within the Medicaid system.

Arizona↗

Acute post-traumatic diabetes insipidus: treatment with continuous intravenous vasopressin.

A young male presented within hours after closed head injury with hypotension, tachycardia, and polyuria. A diagnosis of post-traumatic diabetes insipidus was made. Although a rare entity, the rapid diagnosis of diabetes insipidus and early treatment with vasopressin may have been life-saving in this case. A detailed approach for treatment with continuous intravenous vasopressin may be the most accurate and efficient method of managing acute onset diabetes insipidus, especially in the hemodynamically compromised patient. This will allow for a controlled fluid management in order to achieve hemodynamic stability and prevent aggravation of cerebral edema.

Acute Disease↗

Evidence against insulin synthesis BY IM-9 lymphocytes.

Insulin concentrated from acid/ethanol extracts of IMg lymphocytes by the use of octadecylsilyl (ODS) silica cartridges averaged 0.13 ng/ml cell volume compared with the 0.12 ng insulin/ml cell culture medium. The insulin content of these cells appears to be less than 1% of previously reported values and probably could be accounted for by concentration of insulin from the incubation medium on cell receptors.

Cell Extracts↗

Enhanced neutral protease activity in proliferating rheumatoid synovial cells.

Proteolytic enzymes associated with rheumatoid synovial cells (RSC) have been implicated in the degradation of articular cartilage. Proteases have been measured in proliferating rheumatoid synovial cells (P-RSC), proliferating nonrheumatoid synovial cells (P-NSC), and their nonproliferating counterparts (NP-RSC and NP-NSC). The P-RSC and P-NSC exhibit enhanced total surface-associated plus secreted neutral protease activity, as compared with NP-RSC and NP-NSC. The P-RSC exhibited significantly higher protease activity in this category compared to P-NSC. The RSC also secreted higher levels of secreted proteases alone compared to NSC. The secreted protease activity alone was not related to the proliferative state of the cells. Extractable protease activity was measured in early-passaged and serially-passaged P-RSC, NP-RSC, P-NSC, and NP-NSC. Extractable cellular protease activity measured at pH ranges from 5.0 through 8.0 was not significantly different between P-RSC and NP-RSC or between P-NSC and NP-NSC. The RSC contained elevated extractable cellular protease activity measured at pH ranges from 5.0 through 8.0 compared to extracts from later-passaged cells. The neutral protease activity in the early-passaged RSC was also higher than that measured at pH 6.0 or 8.0. In synovial cells cellular protease activity was related to the proliferative state and the origin of the cells. The P-RSC exhibited the highest levels of surface associated plus secreted neutral protease activity. The RSC also possessed the highest levels of extractable protease activity compared to NSC.

Arthritis, Rheumatoid↗

Serial use of bedside CKMB/myoglobin device to detect acute myocardial infarction in emergency department chest pain patients.

A qualitative bedside device (Spectral Diagnostics, Toronto, Canada) for CKMB and myoglobin (MYOG) detection was evaluated in emergency department (ED) patients with chest pain to determine performance characteristics. At presentation (0 h) and at three hours (3 h), serum was analyzed in the ED with results considered positive if either 0-h or 3-h CKMB or MYOG bands were visible. The results were compared with the diagnosis of myocardial infarction (MI) per hospital discharge diagnosis (n = 132, 87%) or telephone follow-up (n = 19; 1 patient lost to follow-up). Of 151 study patients, 30 (20%) were diagnosed with MI; all were admitted to hospital. On electrocardiogram (EKG), 17 (57%) MI patients had ST-segment elevation. At 0-h, 26 of 30 (87%) MI patients were positive for CKMB/MYOG. By 3 h, 21 of 23 (91%) MI patients were positive for CKMB/MYOG; 7 MI patients were already admitted to hospital. Combining 0-h and 3-h results, the device sensitivity for MI was 93% (28/30) with specificity of 54%. Combining device results plus diagnostic EKG, sensitivity was found to be 100% (30/30). If the device result was positive, then the odds ratio for having an ischemic complication was 6.5. We conclude that the CKMB/MYOG device identified most MI patients at ED presentation and 3 h later. Combining device results with EKG detected all MI patients in the ED.

Adult↗