PubMed Health⌕ Search

Biomedical subjects

L Michael

Publications and source records attributed to L Michael.

At least 19 recordsLinked to original sources
PubMed2006

Estimation of the cost of Taenia solium cysticercosis in Eastern Cape Province, South Africa.

OBJECTIVES: To provide a comprehensive estimate of the societal costs of Taenia solium cysticercosis for the Eastern Cape Province (ECP), South Africa, as an objective measure of its impact in this endemic area. METHODS: Epidemiological data on the prevalence of epilepsy, proportion of epilepsy cases due to neurocysticercosis (NCC) and consequences of cysticercosis were gathered from published and unpublished sources. Economical data were mostly obtained from governmental sources. Three methods were used for estimating productivity losses. Monte Carlo sampling was used to represent the uncertainty of the estimates with 95% Credible Intervals (95% CI). The estimation is for 1 year using a societal approach. All costs are reported in 2004 US Dollars. RESULTS: Overall, there were an estimated 34 662 (95% CI: 17 167-54 068) NCC-associated cases of epilepsy in ECP in 2004. The overall monetary burden (in million of US Dollars) was estimated to vary from US Dollars 18.6 (95% CI: US Dollars 9.0-32.9) to US Dollars 34.2 (95% CI: US Dollars 12.8-70.0) depending on the method used to estimate productivity losses. The agricultural sector contributed an average of Dollars 5.0 million. The prevalence of epilepsy, proportion of productivity reduction and the proportion of epilepsy cases attributable to NCC had the largest impact on the overall estimates. CONCLUSION: This preliminary estimate suggests that T. solium cysticercosis results in considerable monetary costs to a region that is already economically constrained. Because this infection is preventable, these results could guide stakeholders in deciding where to invest scarce health and agricultural resources in their countries.

Agriculture↗
PubMed2005

Quantification of 2,4-D on solid-phase exposure sampling media by LC-MS-MS.

Three types of solid-phase chemical exposure sampling media: cellulose, polyurethane foam, and XAD-2, were analyzed for 2,4-dichlorophenoxyacetic acid (2,4-D) and the amine salts of 2,4-D. Individual samples were extracted into acidified methanol, and the extracts were analyzed via liquid chromatography-tandem mass spectrometry using electrospray ionization and a C(8) reversed-phase LC column. (13)C 2,4-D and a labeled benzoic acid (13)C or d5) were employed as the surrogate and internal standard, respectively. Over a three-year study of pesticide exposure among agricultural workers involving a high volume of analyses, values of average % recovery for (13)C 2,4-D on personal exposure samples ranged from 87 to 98 with a % relative standard deviation ranging from 7 to 12. The performance of the method compares favorably with that of the current National Institute for Occupational Safety and Health-recommended approach for the analysis of 2,4-D on these types of exposure sampling matrices.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2001

Matrix-dependent mechanism of neutrophil-mediated release and activation of matrix metalloproteinase 9 in myocardial ischemia/reperfusion.

BACKGROUND: A key component of reperfusion of myocardial infarction is an immediate inflammatory response, which enhances tissue repair. Matrix turnover is crucial to tissue repair, and matrix metalloproteinases (MMPs) are key enzymes involved in matrix degradation. The hypothesis tested is that one inflammation-based effector of tissue repair is the secretion and activation of MMP-9 by infiltrating neutrophils. METHODS AND RESULTS: Cardiac lymph and tissue were assayed for atent and active MMP-2 and MMP-9 by zymography and immunochemistry. Dual-labeling immunofluorescence determined the cellular source of MMP-9 protein. Isolated canine neutrophils were incubated with preischemic and postischemic cardiac lymph in the presence and absence of collagen-fibronectin pads, and the supernatants were assayed for latent and active MMP-9. MMP-9 increased during the first hours of reperfusion in both lymph supernatants and myocardial extracts, and this increase was of neutrophil origin. MMP-9 in the cardiac lymph remained latent but was activatable. In contrast, MMP-9 in the myocardium was in both latent and active forms. In situ zymography demonstrated that activated MMP-9 surrounded the infiltrated neutrophils. When postischemic cardiac lymph was incubated with neutrophils in vitro, MMP-9 secretion and activation occurred only in the presence of a collagen-fibronectin substrate; preischemic cardiac lymph did not induce significant secretion or activation. CONCLUSIONS: Infiltrating neutrophils are an early source of MMP-9 after reperfusion, and a portion of MMP-9 in the myocardium is active. Infiltrating neutrophils may localize MMP-9 activation by secreting MMP-9 and as a source of activating proteases.

Animals↗
PubMed2001

Erk MAP kinase regulates branching morphogenesis in the developing mouse kidney.

Branching morphogenesis of epithelium is a common and important feature of organogenesis; it is, for example, responsible for development of renal collecting ducts, lung airways, milk ducts of mammary glands and seminal ducts of the prostate. In each case, epithelial development is controlled by a variety of mesenchyme-derived molecules, both soluble (e.g. growth factors) and insoluble (e.g. extracellular matrix). Little is known about how these varied influences are integrated to produce a coherent morphogenetic response, but integration is likely to be achieved at least partly by cytoplasmic signal transduction networks. Work in other systems (Drosophila tracheae, MDCK models) suggests that the mitogen-activated protein (MAP) kinase pathway might be important to epithelial branching. We have investigated the role of the MAP kinase pathway in one of the best characterised mammalian examples of branching morphogenesis, the ureteric bud of the metanephric kidney. We find that Erk MAP kinase is normally active in ureteric bud, and that inhibiting Erk activation with the MAP kinase kinase inhibitor, PD98059, reversibly inhibits branching in a dose-dependent manner, while allowing tubule elongation to continue. When Erk activation is inhibited, ureteric bud tips show less cell proliferation than controls and they also produce fewer laminin-rich processes penetrating the mesenchyme and fail to show the strong concentration of apical actin filaments typical of controls; apoptosis and expression of Ret and Ros, are, however, normal. The activity of the Erk MAP kinase pathway is dependent on at least two known regulators of ureteric bud branching; the GDNF-Ret signalling system and sulphated glycosaminoglycans. MAP kinase is therefore essential for normal branching morphogenesis of the ureteric bud, and lies downstream of significant extracellular regulators of ureteric bud development.

Animals↗
PubMed2000

Frataxin activates mitochondrial energy conversion and oxidative phosphorylation.

Friedreich's ataxia (FA) is an autosomal recessive disease caused by decreased expression of the mitochondrial protein frataxin. The biological function of frataxin is unclear. The homologue of frataxin in yeast, YFH1, is required for cellular respiration and was suggested to regulate mitochondrial iron homeostasis. Patients suffering from FA exhibit decreased ATP production in skeletal muscle. We now demonstrate that overexpression of frataxin in mammalian cells causes a Ca(2+)-induced up-regulation of tricarboxylic acid cycle flux and respiration, which, in turn, leads to an increased mitochondrial membrane potential (delta psi(m)) and results in an elevated cellular ATP content. Thus, frataxin appears to be a key activator of mitochondrial energy conversion and oxidative phosphorylation.

3T3 Cells↗
PubMed1998

Linomide suppresses acute experimental autoimmune encephalomyelitis in Lewis rats by counter-acting the imbalance of pro-inflammatory versus anti-inflammatory cytokines.

Linomide (quinoline-3-carboxamide) is a synthetic immunomodulator that suppresses several experimental autoimmune diseases. Here we report the effects of Linomide on experimental autoimmune encephalomyelitis (EAE), a CD4+ T cell-mediated animal model of multiple sclerosis (MS). EAE induced in Lewis rats by inoculation with homogenized guinea pig spinal cord and Freund's complete adjuvant was strongly suppressed by Linomide administered daily subcutaneously from the day of inoculation. Linomide dose-dependently delayed the interval between immunization and onset of clinical EAE, and reduced severity of EAE symptoms. These clinical effects were associated with dose-dependent down-modulation of myelin antigens-induced T cell responses and by suppression of the proinflammatory cytokines IFN-gamma and TNF-alpha, and upregulation IL-4, IL-10 and TGF-beta as evaluated by in situ hybridization for mRNA expression in spleen mononuclear cells and spinal cord sections. These findings suggest that Linomide could be useful in certain T cell dependent autoimmune diseases.

Acute Disease↗
PubMed1998

Iatrogenic DNA damage induced in human spermatozoa during sperm preparation: protective significance of seminal plasma.

Before the advent of intracytoplasmic sperm injection (ICSI) semen preparation techniques focused on the need to sustain the fertilizing potential of the spermatozoa particularly by reducing oxidative stress. However, for severely oligozoospermic patients treated by ICSI, sperm preparation protocols are used which aim to maximize sperm recovery rather than sperm function. In this study we have examined the impact of different sperm preparation techniques on oxidative stress, sperm motion and DNA integrity. Reactive oxygen species (ROS) generation was monitored using luminol-dependent chemiluminescence, seminal antioxidant activity was assessed using a total reactive antioxidant potential (TRAP) assay while sperm motility and DNA damage were evaluated using computer assisted semen analysis and in-situ nick translation respectively. The results demonstrate a significant increase in the levels of ROS generated by samples prepared by swim-up from a washed pellet compared with spermatozoa isolated directly from seminal plasma. This oxidative stress was associated with a highly significant increase in the level of DNA damage sustained by the spermatozoa while the quality of sperm motility remained largely unchanged. These results suggest that if repeated centifugation protocols are to be used to prepare spermatozoa, strategies should be developed for minimizing collateral DNA damage.

Centrifugation, Density Gradient↗
PubMed1993

Developmental differences in canine cardiac surgical scars.

Sudden death and arrhythmias are significant problems in patients with various types of repaired congenital heart disease and have been associated with increasing time after and older age at surgery. Arrhythmias have been mapped clinically to areas of surgical scars in some patients, leading to the hypothesis that scar morphology changes with age. This study compared the morphology and histology of right ventriculotomy scars or right atriotomy scars in newborn (2 to 3 weeks), young (5 to 8 weeks), and older (> or = 6 months) dogs at postmortem examination 5 months postoperatively. Atriotomy lengths increased significantly compared with the initial incision in the newborn (6.0 mm +/- 0.1 to 15.2 mm +/- 5.8; p < 0.05) and young (6.8 mm +/- 0.9 to 19.6 mm +/- 4.8; p < 0.01) groups but were similar in the older group (35.5 mm +/- 11.7 to 27.0 mm +/- 2.5). Ventriculotomy scars grew 110 +/- 69% in the newborn group and 126 +/- 71% in the young group but shrank 31 +/- 6% of the original length in the older group (young vs older; p < 0.05). This increase in the atriotomy and ventriculotomy scars in the young group and the decrease in the older group resulted in scars of similar length; only those scars in the newborn group remained significantly shorter than scars in the older group (p < 0.05). Atriotomy and ventriculotomy scars in the older group had more bone or cartilage (p < 0.05) but less dystrophic calcification (p < 0.05) than those scars in the younger groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Regulation of intercellular adhesion molecule-1 (ICAM-1) in ischemic and reperfused canine myocardium.

Previous studies in vitro have shown an important role for intercellular adhesion molecule-1 (ICAM-1) in adherence interactions of canine neutrophils with canine jugular vein endothelial cells and in cytotoxicity of canine neutrophils for adult cardiac myocytes. To evaluate the regulation of ICAM-1 in myocardial inflammation and its role in the pathogenesis of myocardial ischemia and reperfusion, a series of in vivo and ex vivo studies were performed in canine animals. Systemic administration of LPS elicited ICAM-1 mRNA in several tissues, including myocardium, which demonstrated increasing ICAM-1 staining on intercalated discs of cardiac myocytes. In ischemia and reperfusion protocols: (a) ICAM-1 mRNA was found in ischemic segments within 1 h of reperfusion and in both ischemic and normally perfused segments by 24 h of reperfusion; (b) expression of ICAM-1 was detected in cardiac myocytes in the ischemic region by 6 h of reperfusion; increased expression was seen thereafter as a function of time; (c) post-ischemic (but not preischemic) cardiac lymph collected at intervals from 1 to 24 h after reperfusion elicited ICAM-1 mRNA, ICAM-1 expression, and ICAM-1-dependent neutrophil adhesion in canine jugular vein endothelial cells and in cardiac myocytes with peak cytokine activity seen by 1 h; (d) extravascular localization of neutrophils was detected in ischemic areas only, and was associated with endothelium bearing high levels of ICAM-1 within 1 h of reperfusion; infiltration increased thereafter in association with increasing levels of ICAM-1 mRNA in myocardial segments and increasing levels of ICAM-1 expression on cardiac myocytes. These findings provide the first direct evidence for inflammatory regulation of ICAM-1 in ischemic and reperfused canine myocardium. They support the hypothesis that ICAM-1 participates in neutrophil-mediated myocardial damage.

Animals↗
PubMed1993

Economic impact of cost-containment strategies in third party programmes in the US. Part II.

This is the second article in a 2-part series that examines the economic impact of several different strategies used to control costs in third party programmes. This article investigates 5 different methods: (a) formularies; (b) capitation; (c) drug utilisation review; (d) prior approval; and (e) drug product selection. The published literature indicates that use of formularies decreases drug expenditures, but these savings may be offset by expenditures in other areas of healthcare programmes. Capitation, though less well studied than other strategies, may show some effectiveness in reducing costs by increasing generic dispensing and promoting switching from prescription drug to over-the-counter. Drug utilisation review, as a systematic programme of claims data review, has been shown to yield positive economic return in a variety of areas, including both impersonal and face-to-face educational interventions with healthcare practitioners. Prior approval and drug product selection both result in savings when examined in isolation from other aspects of healthcare. Cost-shifting, administrative costs and costs incurred because of possible decreased access to care have yet to be fully accounted for.

Capitation Fee↗
PubMed1991

Inflammation in the course of early myocardial ischemia.

Experimental models of acute ischemic myocardial injury indicate that the inflammatory response after the ischemic event contributes to tissue damage. This is especially apparent with reperfusion of the ischemic tissue. In such models some therapeutic strategies designed to reduce neutrophil accumulation or function have resulted in apparently beneficial effects. Although such findings are encouraging, interventions into these pathological processes using specific molecular targets will require greater understanding of specific mechanisms. Current evidence indicates that potential sites of therapeutic intervention will be found in pathways leading to complement activation, generation of lipid-derived mediators, adhesion of neutrophils to endothelial cells and cardiac myocytes, and activation of neutrophil secretory processes releasing, for example, proteolytic enzymes and reactive oxygen. Understanding the dynamic interplay between the mediators, adhesion pathways, and secretory processes that results in myocardial damage will allow a rational approach to controlling the detrimental inflammatory consequences of ischemia and reperfusion.

Animals↗
PubMed1991

The Los Angeles TEAM Study: personal exposures, indoor-outdoor air concentrations, and breath concentrations of 25 volatile organic compounds.

The U.S. Environmental Protection Agency and the California Air Resources Board studied the exposures of 51 residents of Los Angeles, California, to 25 volatile organic chemicals (VOCs) in air and drinking water in 1987. A major goal of the study was to measure personal, indoor, and outdoor air concentrations, and breath concentrations of VOCs in persons living in households that had previously been measured in 1984. Other goals were to confirm the marked day-night and seasonal differences observed in 1984; to determine room-to-room variability within homes; to determine source emission rates by measuring air exchange rates in each home; and to extend the coverage of chemicals by employing additional sampling and analysis methods. A total of 51 homes were visited in February of 1987, and 43 of these were revisited in July of 1987. The results confirmed previous TEAM Study findings of higher personal and indoor air concentrations than outdoor concentrations of all prevalent chemicals (except carbon tetrachloride); higher personal, indoor, and outdoor air concentrations in winter than in summer; and (in winter only) higher outdoor concentrations at night than in the daytime. New findings included the following: (1) room-to-room variability of 12-hour average concentrations was very small, indicating that a single monitor may be adequate for estimating indoor concentrations over this time span; (2) "whole-house" source emission rates were relatively constant during both seasons, with higher rates for odorous chemicals such as p-dichlorobenzene and limonene (often used in room air fresheners) than for other classes of chemicals; (3) breath concentrations measured during morning and evening were similar for most participants, suggesting the suitability of breath measurements for estimating exposure in the home; (4) limited data obtained on two additional chemicals-toluene and methylene chloride-indicated that both were prevalent at fairly high concentrations and that indoor air concentrations exceeded outdoor concentrations by a factor of about three.

Adolescent↗
PubMed1989

The effects of hypoxemia on myocardial blood flow during exercise.

We evaluated the adequacy of regional and transmural blood flow during exercise and rapid pacing after 1 wk of hypoxemia. Seven mature mongrel dogs were made hypoxemic (mean O2 saturation = 72.4%) by anastomosis of left pulmonary artery to left atrial appendage. Catheters were placed in the left atrium, right atrium, pulmonary artery, and aorta. Atrial and ventricular pacing wires were placed. An aortic flow probe was placed to measure cardiac output. Ten nonshunted dogs, similarly instrumented, served as controls. Recovery time was approximately 1 wk. Cardiac output, mean aortic pressure, and oxygen saturation were measured at rest, with ventricular pacing, atrial pacing, and with treadmill exercise. Ventricular and atrial pace and exercise were at a heart rate of 200. Right ventricular free wall, left ventricular free wall, and septal blood flow were measured with radionuclide-labeled microspheres. Cardiac output, left atrial blood pressure, and aortic blood pressure were similar between the two groups of dogs in all testing states. Myocardial blood flow was significantly higher in the right and left ventricular free wall in the hypoxemic animals during resting and exercise testing states. Myocardial oxygen delivery was similar between the two groups of animals. Pacing resulted in an increase in myocardial blood flow in the control animals but not the hypoxemic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Acidosis-induced glucose intolerance is not prevented by adrenergic blockade.

The determinants of the altered glucoregulation in acidosis were investigated in anesthetized dogs. Because CO2 rapidly equilibrates and its effects are mediated by pH changes, CO2 inhalation was examined. Plasma acid-base composition, glucose, insulin, glucagon, and blood flows were evaluated before and after an intravenous glucose load (1.2 +/- 0.1 g/kg body wt) in normal and acidotic dogs with flow probes and catheters chronically implanted in the portal circulation. A simultaneous infusion of phentolamine (5 micrograms.kg-1.min-1), propranolol (3.5 micrograms.kg-1.min-1), both, or none was used. All acidemic dogs had lower hepatic extraction of insulin and greater hyperglycemia after the glucose challenge; thus the adrenergic system is not critical for these responses. Because arterial insulin levels were either normal (propranolol) or increased (all others) in acidosis, insulin resistance was likely. Insulin infusion (2 and 4 mU.kg-1.min-1) with euglycemic clamp and [3-3H]glucose documented that acidemia decreases peripheral glucose utilization and the insulin suppression of hepatic glucose production. Acidemia also enhances plasma glucagon levels, yet this effect plays a limited role in the observed hyperglycemia.

Acid-Base Equilibrium↗
PubMed1988

Endogenous opioids do not mediate HCl-induced myocardial dysfunction.

We evaluated the hypothesis that increased endogenous opioid activity mediates part or all of the left ventricular contractile and pump dysfunction previously demonstrated in HCl-induced metabolic acidemia. Eighteen Western newborn lambs were catheterized and instrumented; pacing wires were sutured to the right atrial appendage; a catheter mounted micromanometer pressure transducer was inserted into the left ventricle; and a 2.5 F thermistor was inserted into the distal abdominal aorta. The lambs were studied 3 days after surgery. Metabolic acidemia was produced with an infusion of 0.5 N HCl into the inferior vena cava. Inhibition of endogenous opioids was achieved with a bolus of 2 mg/kg of intravenous naloxone, which was demonstrated to inhibit morphine sulfate-induced myocardial dysfunction. The effects of opioid inhibition were contrasted with our previously published results after restoration of a normal arterial pH with intravenous sodium bicarbonate. In agreement with our previous study, we found that reducing the arterial pH from 7.41 +/- 0.01 to 6.97 +/- 0.04 was associated with a 45% reduction in cardiac output which resulted from a 50% reduction in stroke volume. These changes in turn were mediated by a 35% reduction in the maximal first derivative of left ventricular pressure and/or a 63% increase in systemic vascular resistance which we used to estimate contractility and afterload, respectively. Left ventricular end diastolic pressure increased during acidemia. Although opioid inhibition produced a consistent increase in the maximal first derivative of left ventricular pressure, this increase was relatively small and was not associated with a significant change in cardiac output, stroke volume, or systemic vascular resistance.

Acidosis↗
PubMed1988

Elevated coronary sinus pressure does not alter myocardial blood flow or left ventricular contractile function in mature sheep. Implications after the Fontan operation.

The hypothesis that elevation of coronary sinus pressure affects coronary blood flow and ventricular function was tested in this study of seven adult ewes placed under pentobarbital anesthesia. Coronary sinus pressure was elevated by partial balloon occlusion. Right atrial, left atrial, and aortic mean pressures and rate of rise of left ventricular pressure were measured. Coronary blood flow was determined with radioactive microspheres. Studies were performed at control and at moderate (15 to 20 mm Hg) and marked (30 to 35 mm Hg) elevation of coronary sinus mean pressures. Despite increase of coronary sinus pressure from a control value of 2 mm Hg +/- 1 to levels of 19 mm Hg +/- 1 and 34 mm Hg +/- 1, no significant changes were observed in right atrial, left atrial, or aortic mean pressure or rate of rise of left ventricular pressure. Both endocardial and epicardial blood flows were unaffected. The endocardial/epicardial flow ratio at moderate coronary sinus pressure elevation was significantly increased, which suggested local subendocardial vasodilation in the absence of changes in transmural perfusion. The findings suggest that isolated increase in coronary sinus pressure is not a major determinant of myocardial blood flow or ventricular performance in the normal ewe.

Animals↗
PubMed1987

Maturational changes in the pharmacological characteristics and actomyosin content of canine arterial and venous tissue.

The purpose of this study was to compare the pharmacological characteristics and actomyosin content of arterial and venous tissue at different times during development. Rings of arteries (femoral, renal, carotid, pulmonary) and veins (saphenous, pulmonary, jugular) were obtained from 1 wk, 1 month, and adult dogs, mounted at their optimal length for force development and the contractile response to potassium chloride and phenylephrine determined. The strain at optimal length was less at all ages in pulmonary artery and pulmonary and jugular veins than in other vessels. All vessels exhibited an increase in maximum contractile response with development but the increase was greater for phenylephrine. In general, the magnitude of the maximum response of the jugular and pulmonary veins and pulmonary artery was less than other vessels at all ages. The sensitivity (half maximum response) either increased or was unchanged in arteries with development, while in the veins it either decreased or was unchanged. The relaxant effects of verapamil and isoproterenol were determined on potassium chloride contracted vessels. Arterial tissue was minimally responsive to isoproterenol at all ages while venous tissue either increased its responsiveness (saphenous, pulmonary) with development or remained highly responsive (jugular). Verapamil, unlike isoproterenol, was an effective relaxant of all vessels. The actomyosin content (mg/mm) of femoral and renal arteries and saphenous and jugular veins increased with development but this increase was accompanied by a parallel increase in total protein so that the ratio (actomyosin/total protein) was unchanged. In jugular veins from adult dogs this ratio was smaller than in arterial tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Actomyosin↗