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Biomedical subjects

S Lemeshow

Publications and source records attributed to S Lemeshow.

At least 73 records · Page 4Linked to original sources

Role of membrane phospholipids in myocardial injury induced by ischemia and reperfusion.

Depletion of membrane phospholipids is known to be associated with myocardial ischemia, but its relationship to the injury involved with the reperfusion of ischemic myocardium is not known. The present study was designed to relate phospholipid degradation with reperfusion injury. The isolated in situ pig heart was subjected to 60 min of regional ischemia induced by occluding the left anterior descending (LAD) coronary artery and 60 min of global ischemia by hypothermic cardioplegic arrest followed by 60 min of reperfusion. The pigs were divided into two groups. In the treatment group, the heart was preperfused with mepacrine (0.05 mM), a known phospholipase inhibitor, for 15 min prior to LAD occlusion. In the control group, the total phospholipid content was not significantly decreased during LAD occlusion and arrest, but was reduced appreciably after reperfusion. Phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol followed a similar pattern. The lowering of these phospholipids during reperfusion was accompanied by enhancement of lysophosphatidylcholine. Mepacrine restored the normal levels of these phospholipids. During reperfusion, fatty acyl CoA synthetase, lysophospholipase, and lysophosphatidylcholine acyltransferase were depressed, whereas phospholipase A2 was enhanced. Mepacrine inhibited phospholipase A2, but had no effects on the other enzymes. Mepacrine also provided significant protection against reperfusion injury, as documented by the preservation of high-energy phosphate compounds and inhibition of the appearance of creatine kinase activity in the perfusate. These results suggest that membrane phospholipids play an important role in myocardial injury associated with ischemia and reperfusion, primarily because the deacylation-reacylation cycle of phospholipid biosynthesis becomes defective.

1-Acylglycerophosphocholine O-Acyltransferase↗

Effect of superoxide dismutase and catalase on myocardial energy metabolism during ischemia and reperfusion.

Survival of cardiac patients undergoing heart surgery depends critically upon the recovery of myocardial energy metabolism during reperfusion of ischemic myocardium. The present study compares various parameters of myocardial energy metabolism using an isolated in situ pig heart. The left anterior descending (LAD) coronary artery was occluded for 60 min, followed by 60 min of global hypothermic cardioplegic arrest and 60 min of reperfusion. Free radical scavengers [superoxide dismutase SOD and catalase] were used to protect the ischemic heart from reperfusion injury. In both control and SOD plus catalase-treated groups, ATP, creatine phosphate (CP), ATP/ADP ratio, energy charge and phosphorylation potential dropped significantly during ischemic insult. After reperfusion, CP, ATP/ADP ratio and phosphorylation potential improved significantly, but they were restored to control level only in treated animals. In either case, free energy of ATP hydrolysis (delta G) lowered only by 5% during ischemia, but recovered promptly upon reperfusion. SOD and catalase also improved coronary blood flow and reduced creatine kinase release compared to those of untreated animals, suggesting improved myocardial recovery upon reperfusion. Our results suggest that SOD and catalase significantly improve the myocardial recovery during reperfusion by enhancing rephosphorylation steps, and the value of delta G is more critical compared to those of ATP and CP for myocardial recovery.

Adenosine Triphosphate↗

Mepacrine, a phospholipase inhibitor. A potential tool for modifying myocardial reperfusion injury.

Cardioprotective effects of phospholipase inhibitor, mepacrine, on ischemic reperfused myocardium were investigated in the isolated in situ pig heart preparation, which was subjected to 120 minutes of regional ischemia, with the final 60 minutes having superimposed global cardioplegic arrest followed by 60 minutes of reperfusion. Mepacrine (0.05 mmol/L) was administered before ischemia into the perfusion circuit in 15 of 29 experiments. Significant depletion of myocardial phospholipids occurred in nontreated animals during 60 minutes of reperfusion. Mepacrine prevented the reperfusion-induced phospholipid degradation. Further, the level of high-energy phosphate compounds was higher during ischemia and reperfusion in the mepacrine-treated hearts. Left ventricular developed pressure, maximum rate of rise of left ventricular pressure, and left ventricular end-diastolic pressure were measured under isovolumic conditions to assess cardiac contractility and compliance. During incubation with mepacrine, before ischemia, left ventricular developed pressure and maximum rate of rise of left ventricular pressure decreased to 45% and 51% of baseline values, respectively. This initial decline was improved to 65% and 70% in mepacrine-treated animals during the early period of regional ischemia. In the nontreated control heart, a progressive decline in contractility was observed with ischemia such that no significant difference was apparent in the two groups. Reperfusion resulted in a further deterioration of global cardiac performance in both mepacrine-treated and control animals. Although pretreatment with mepacrine did not improve contractility, myocardial oxygen consumption, coronary flow, and cardiac compliance significantly improved. These results suggest that myocardial injury may develop during reperfusion after temporary ischemia. Mepacrine inhibits such injury by acting as a phospholipase inhibitor, but it also behaves as a negative inotropic agent in ischemic reperfused myocardium.

Animals↗

Enhanced bleeding with cefoxitin or moxalactam. Statistical analysis within a defined population of 1493 patients.

Most cases of beta-lactam-associated coagulopathy occur in patients with other risk factors. This study analyzed temporally related clinical bleeding events in 1493 patients who received one antibiotic for at least three days. Univariate and multivariate analyses controlled for condition variables (nutritional status, renal, hepatic, or hematologic dysfunction, intensive care unit stay) and treatment variables (use of antiplatelet agents, anticoagulants, vitamin K, antitumor chemotherapy or antiulcer therapy, steroids) that could have been associated with bleeding independently. Rates of bleeding ranged from 0% (chloramphenicol sodium succinate, vancomycin hydrochloride, erythromycin lactobionate) to 8.2% (cefoxitin) to 22.2% (moxalactam disodium). Multiple logistic regression analyses revealed that only moxalactam (odds ratio, 9.9) and cefoxitin (odds ratio, 2.1) exhibited significantly higher likelihoods of bleeding than other agents. This study statistically confirms increased risk of bleeding with moxalactam, heretofore reported only anecdotally. Cefoxitin may carry risks greater than previously believed.

Anti-Bacterial Agents↗

Metabolic enhancement of myocardial preservation during cardioplegic arrest.

An experimental study was undertaken to evaluate the relative efficacy of oxygenated versus unoxygenated cardioplegic solutions and to determine if the addition of certain metabolically active substrates to cardioplegic solutions had any effect on myocardial preservation. Sixty-one pigs were divided into seven groups of animals (5 to 15 animals per group). The impact of different cardioplegic vehicles, i.e., crystalloid versus the oxygen-carrying vehicles, blood and Fluosol-DA, on preservation of high-energy phosphates (adenosine triphosphate and creatine phosphate) was examined in the first three animal groups. The influence of Krebs cycle intermediates, i.e., glutamate, malate, succinate and fumarate, on adenosine triphosphate and creatine phosphate preservation was evaluated in the other four animal groups. All hearts underwent 120 minutes of hypothermic cardioplegic arrest at 15 degrees C followed by 60 minutes of normothermic reperfusion. Higher adenosine triphosphate and creatine phosphate levels were maintained during arrest when oxygenated solutions were used as the cardioplegic vehicle and when any of the four intermediates were added to the crystalloid cardioplegic solution, especially succinate and fumarate. During reperfusion, however, adenosine triphosphate levels were uniformly lower than control whereas creatine phosphate levels rose to either control levels or higher in all groups. No significant intergroup difference could be identified during reperfusion. These findings lead to the conclusion that the presence of either oxygen or certain Krebs cycle intermediates enhances the protective effect of hyperkalemic hypothermic cardioplegia on high-energy phosphates during the arrest period only. This enhancement is not maintained during the reperfusion period.

Adenosine Triphosphate↗

Cardiac performance during reperfusion improved by pretreatment with oxygen free-radical scavengers.

We studied the effects of oxygen free radicals on cardiac performance during reperfusion of ischemic myocardium. The pig heart, isolated in situ, was subjected to 60 minutes of regional ischemia at normothermia by occlusion of the left anterior descending coronary artery followed by 60 minutes of hypothermic cardioplegic arrest and 60 minutes of normothermic reperfusion. The oxygen free-radical scavengers, superoxide dismutase and catalase, were administered before occlusion of the left anterior descending coronary artery in the experimental group. The generation of free radicals in the untreated group, estimated by the measurement of malondialdehyde in the perfusate, was significant during reperfusion and was associated with a corresponding increase in creatine kinase. Superoxide dismutase and catalase significantly slowed the appearance of malondialdehyde and the release of creatine kinase during reperfusion. Superoxide dismutase and catalase did not alter coronary flow and myocardial oxygen extraction or consumption during occlusion of the left anterior descending coronary artery; however, coronary flow and oxygen consumption were significantly higher (p less than 0.05) during reperfusion in hearts treated with antioxidants. Left ventricular developed pressure and its maximum first derivative were measured under isovolumic conditions. In the untreated group, left ventricular developed pressure and its maximum first derivative declined to 61.1% and 57.1% of baseline values, respectively, after 60 minutes' occlusion of the left anterior descending, and to 45% of baseline values after 15 minutes of reperfusion. The decline in left ventricular developed pressure and its maximum first derivative during reperfusion was significantly (p less than 0.05) inhibited by superoxide dismutase and catalase, but left ventricular end-diastolic pressure was not significantly altered. These results implicate oxygen-derived free radicals in the injury resulting from reperfusion of ischemic myocardium and suggest that oxygen free-radical scavengers effectively protect against such injury.

Animals↗

Late postoperative tamponade following coronary artery bypass grafting in patients on antiplatelet therapy.

Myocardial revascularization was performed in 1,361 patients over a 66-month period (February, 1978 to August, 1983) without a single occurrence of late cardiac tamponade. During a subsequent 4-month-period, aspirin and dipyridamole were administered routinely to all coronary bypass patients. The incidence of late cardiac tamponade rose significantly (p less than 0.001) to 3 of 85 patients (3.5%). Routine perioperative administration of aspirin and dipyridamole to patients undergoing myocardial revascularization may be associated with an increased incidence of delayed cardiac tamponade.

Adult↗

A computer simulation of the EPI survey strategy.

A Monte Carlo simulation study was designed to evaluate the sample survey technique currently used by the Expanded Programme on Immunization (EPI) of the World Health Organization. Of particular interest was how the EPI strategy compared to a more traditional sampling strategy with respect to bias and variability of estimates. It was also of interest to investigate whether the estimates of population vaccination coverage were accurate to within 10 percentage points of the actual levels. It was found that within particular clusters, the EPI method was particularly sensitive to pocketing of vaccinated individuals, but the more traditional method gave more accurate and less variable results under a variety of conditions. However, the stated goal of the EPI, of being able to produce population estimates accurate to within 10 percentage points of the true levels in the population, was satisfied in the artificially created populations studied.

Child, Preschool↗

Applications of microcomputer spreadsheet packages as adjuncts to multiple logistic regression analysis.

This paper illustrates how a microcomputer spreadsheet package can be used by epidemiologists to facilitate the computation of multiple logistic regression (MLR) probabilities, as well as odds ratios and associated confidence intervals, given the coefficients of the MLR model. By formatting a spreadsheet, data entry is greatly simplified, and computations are accomplished without any arithmetic manipulations on the part of the user. This approach makes it feasible for clerical support staff to assist in the computation of seemingly complex expressions. The increasing availability of microcomputers in clinical and research settings suggests that numerous analytic applications are amenable to this approach, thereby decreasing reliance on mainframe computers and desk-top calculators.

Computers↗

A method for predicting survival and mortality of ICU patients using objectively derived weights.

Data at ICU admission and after 24 h in the ICU were collected on 755 patients, to derive multiple logistic regression models for predicting hospital mortality. The derived models contained relatively few and easily obtained variables. The weight associated with each variable was determined objectively. There were seven admission variables, none of which were treatment dependent, and seven 24-h variables reflecting treatments and patients' conditions in the ICU. Predicted outcomes using these two models were closely correlated with actual outcome. Theoretically, a predictive model would be useful to physicians for triage decisions as well as determining aggressiveness of care through discussions with families, determining utilization of ICU facilities, and objectively comparing different ICUs. This research represents an initial attempt to develop models that are not based on subjectively determined weights.

Adolescent↗

Does the type of venous drainage or cardioplegia affect postoperative conduction and atrial arrhythmias?

Five consecutive patient groups undergoing coronary bypass surgery were studied for postoperative conduction disturbances and atrial arrhythmias. Group I (50 patients) had blood cardioplegic solution (25 meq/liter potassium) and unsnared venae cavae, group II (156 patients) had low-volume crystalloid cardioplegic solution (25 meq/liter potassium) and unsnared venae cavae, group III (56 patients) was similar to group II except that a single cavoatrial venous cannula was used instead of two separate cannulas, group IV (218 patients) had high-volume crystalloid cardioplegic solution (25 meq/liter potassium) and snared venae cavae, and group V (37 patients) was the same as group IV except that the cardioplegic solution contained 10 meq/liter potassium after the first dose, which contained 25 meq/liter. All postoperative electrocardiograms were analyzed for conduction disturbances and atrial arrhythmias. The results showed a significantly lower incidence of conduction disturbances in group I (12%) as compared with groups II to IV. In addition, groups IV and V (high-volume crystalloid cardioplegic solution) had a significantly higher incidence of conduction disturbances than groups II and III (lower-volume crystalloid solution) (55.0% and 62.1% vs 26.2% and 35.1%, respectively). The majority of these disturbances were temporary. Group I also had the lowest incidence of postoperative atrial arrhythmias (3.8%). There was no significant difference between the groups receiving high- and low-volume crystalloid solution. It is concluded that blood cardioplegic solution affords the best protection against postoperative conduction disturbances and atrial arrhythmias. High-volume crystalloid cardioplegic solution affords the least protection against conduction disturbances but has no effect on atrial arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

Postinfarction angina: an expanding subset of patients undergoing coronary artery bypass.

An analysis of patients undergoing coronary artery bypass for unstable postinfarction angina (less than or equal to 30 days of infarct) during two time periods was undertaken: Group I, January, 1982, through December, 1982; Group II, September, 1983, through August, 1984. Clinical, angiographic, and operative data were coded, and statistical analysis was used to compare the two patient groups, evaluate operative results, and identify risk factors. The incidence of unstable postinfarction angina as an indication for bypass grafting increased significantly (p less than 0.01) from the first to the second time frame, 8.7% (24/276) to 18% (51/283). A greater proportion of Group II patients were operated upon within 7 days of infarct (37% versus 21%, p less than 0.01). All other variables examined were similar in the two patient groups. Analysis of the combined Group I and II patients (N = 75) indicates the following: The ratio of transmural to nontransmural infarction was 39%/61%, and 39% of patients had a previous infarction. Three-vessel disease was present in 76%, two-vessel in 21%, one-vessel in 3%, and left main disease in 20%. Left ventricular ejection fraction was greater than or equal to 40% in 27% of patients, less than 40% in 32%, and not obtained in 41%. Mean left ventricular end-diastolic pressure was 19.5 mm Hg. Intra-aortic balloon pumping was necessary preoperatively in 39%. The mean interval from infarction to revascularization was 12 days, and the mean number of grafts was 3.1 (range one to six). The overall in-hospital mortality was 8% (6/75). Statistical analysis demonstrated that decreased ejection fraction was associated with an increased risk of mortality. No other variables were correlated with mortality. Mean follow-up for the combined Group I and II patients is 13 months (range 4 to 32). Ninety percent of survivors remain in Canadian Heart Association Functional Class I and 6% in Class II. No late deaths have occurred. Patients with unstable postinfarction angina constitute an ever-increasing subset of the coronary bypass population of the 1980s. Operation can be performed with a satisfactory mortality and excellent long-term outlook compared to less acceptable published results with medical management alone. Preoperative left ventricular function constitutes the major indicator of operative risk.

Angina Pectoris↗

Cancer mortality among workers exposed to formaldehyde.

Proportionate mortality among workers exposed to formaldehyde was analyzed among employees of a large chemical plant in Western Massachusetts. Twenty-four such decedents, all males, were identified through union records, reports of former co-workers, and a systematic review of obituaries in local newspaper. Work histories were obtained from seniority lists. Race-age-sex-adjusted proportionate mortality ratios ( PMRs ) were significantly elevated for cancer of the colon based on United States, county, and county cancer mortality proportions (PMR = 702, 424, 333, p less than or equal to .05), as were PMRs for the category buccal and pharyngeal cancer (PMR = 870, 952, 833, p less than .05). This study provides evidence of formaldehyde's carcinogenicity. These findings are at variance with a previous report of the mortality experience of workers at the same plant from an earlier period.

Aged↗

Two-year outcome of adult intensive care patients.

Five hundred fifty-eight patients admitted to a general/medical surgical intensive care unit were studied 2 years after hospital discharge to determine whether they were still alive, were able to perform daily activities, and had returned to work. The overall 2-year survivorship (hospital and long-term) was 63.5%. Two-year survival was considerably lower for patients with certain condition or treatment characteristics than for others. This ranged from 14% 2-year survival for patients with 48 or more hours of coma to 82.2% for patients with no condition or treatment characteristics recorded. Once a patient was discharged alive, the 2-year cumulative survival of surgical ICU patients (84.6%) was significantly better than that of medical ICU patients (76.5%). Among ICU survivors responding to a follow-up survey, 85% were able to perform daily activities, but only 66% were working. Of the 44 patients experiencing a change in ability to perform daily activities at time of follow-up compared with pre-ICU admission, functional status of 34 (77%) improved, while 10 (23%) got worse. By comparison, of the 45 patients experiencing a change in working status, only 7 patients (16%) who did not work prior to ICU admission had returned to work, whereas the remaining 38 patients (84%) who worked prior to ICU admission were not working at time of follow-up study.

Activities of Daily Living↗

Lymphocytopenia in the surgical intensive care unit patient.

Total lymphocyte counts were monitored in 328 consecutive adult patients in the intensive care unit of a large community hospital. Lymphocytopenia was common with a severe reduction in circulating lymphocytes (less than 900/mm3) present in 37% of the patients and moderate reduction (900-1500/mm3) in 38% of the patients. Mortality was 30% and 13% in these two groups, respectively. Patients undergoing high-risk elective surgery frequently had moderate lymphocytopenia even when corticosteroids were not administered. Patients having two or more clinically evident infections with severe lymphocytopenia had a 59% mortality rate. Among patients who did not manifest any clinically detectable infection, mortality associated with those having severe lymphocyte reduction was significantly greater than those with normal lymphocyte counts or moderate depletion.

Adrenal Cortex Hormones↗