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Biomedical subjects

M E Ward

Publications and source records attributed to M E Ward.

At least 55 records · Page 3Linked to original sources
PubMed1997

Modulation of myogenic responsiveness by CO2 in rat diaphragmatic arterioles: role of the endothelium.

The effect of hypercapnia on the myogenic response was determined in arterioles (80- to 100-microm internal diameter) isolated from the diaphragms of rats killed by decapitation. All arterioles were exposed to step changes in intraluminal pressure over a range of 10-200 mmHg and had no flow through their lumen. In five separate groups of vessels (n = 7 per group), PCO2 of the superfusing buffer was adjusted to 40, 60, 80, 90, or 100 mmHg. In three further groups of vessels (n = 7 per group), the endothelium was removed by low-pressure air perfusion (2 ml at 20 mmHg) and PCO2 of the superfusing buffer was adjusted to 40, 80, or 100 mmHg. In endothelium-intact vessels, increasing PCO2 to 80 mmHg enhanced the myogenic response, as reflected by a negative slope of the pressure-diameter relationship (slope = -0.164 +/- 0.03 vs. 0.004 +/- 0.02 for vessels at PCO2 = 40 mmHg, P < 0.05). With a PCO2 of 100 mmHg, dilation accompanied increasing intraluminal pressure and the slope of the pressure-diameter curve was positive (0.154 +/- 0.03, P < 0.05 for difference from vessels at PCO2 = 40 mmHg). In deendothelialized vessels, the curve was shifted upward in a parallel manner during exposure to increased PCO2 levels. Moderate hypercapnia (PCO2 < 80 mmHg) elicits endothelium-dependent enhancement of myogenic tone. Severe hypercapnia (PCO2 > 80 mmHg) inhibits myogenic tone through a direct effect on vascular smooth muscle and through endothelium-dependent inhibitory mechanisms.

Acetylcholine↗
PubMed1997

Hyporeactivity of rat diaphragmatic arterioles after exposure to hypoxia in vivo. Role of the endothelium.

The effect of prior in vivo hypoxia on the in vitro responses to changes in transmural pressure, alpha-adrenoceptor activation, and depolarization with KCl were evaluated in first-order diaphragmatic arterioles. Rats (n = 14 per group) were exposed to normoxia (controls) or to hypoxia (inspired O2 concentration = 10%) for 12 or 48 h. The arteriolar pressure-diameter relationships were recorded over a pressure range from 10 to 200 mm Hg. In separate groups of arterioles (n = 12 per group), the diaphragmatic arteriolar responses to phenylephrine (10(-8) to 10(-5 M) or KCl (10 to 100 mM) were determined after exposure to either room air or hypoxia for 48 h. In half of the arterioles studied, the endothelium was removed. After 12 h of hypoxia, the pressure-diameter relationship was normal in endothelialized arterioles but was shifted upward in de-endothelialized vessels (p < 0.05). After 48 h of hypoxia, the constrictor response to increasing transmural pressure was severely suppressed in all arterioles. The intraluminal diameters during activation with phenylephrine and KCl were larger in arterioles from rats exposed to hypoxia (103 +/- 8 and 81 +/- 7 microns, respectively) than in control arterioles (41 +/- 5 and 54 +/- 6 microns, respectively; p < 0.05 for differences). During maximum phenylephrine- and KCl-induced constriction in de-endothelialized arterioles, diameters averaged 125 +/- 8 and 105 +/- 8 microns, respectively, for arterioles from hypoxic rats and 32 +/- 6 and 40 +/- 5 microns, respectively, for arterioles from control vessels. Exposure to hypoxia results in impairment of diaphragmatic arteriolar smooth muscle reactivity and reversal of the normal inhibitory influence of the endothelium on diaphragmatic arteriolar tone.

Animals↗
PubMed1997

Diethyl ether, a chemical asphyxiant used as a prelude to homicide: a report of three cases.

Homicides in which the victims are first subdued with a chemical asphyxiant rare unusual and quite rare. We report three cases in which victims were first overcome by ether containing compounds and then killed by other means of asphyxiation. The ether containing compounds used in these three cases were readily available commercial products. In two cases, the distinctive spectra of the volatile compounds in the decedents' blood, from the gas chromatograph and from the gas chromatograph/mass spectrometer, were compared with suspect ether containing products recovered during the scene investigations. In one case, an identical match was obtained. In the other case, the chromatographic spectra differed slightly from the compounds found at the scene, but the difference was explainable by metabolic breakdown of the compounds in vivo.

Adult↗
PubMed1997

Echocardiographic detection of pulmonary embolism in transit: implications for institution of thrombolytic therapy.

Right atrial or ventricular thrombi in patients with pulmonary embolism are emboli in transit and are a medical emergency because they are associated with a high mortality rate when treated conservatively with anticoagulation. The current standard therapy is less well accepted because of the risk of clot fragmentation and distal embolization. A case in which an unsuspected right ventricular thrombus was diagnosed by echocardiography is reported. This findings led to treatment with streptokinase (250,000 U, followed by 100,000 U/h for 24 h). Clinical improvement was rapidly obtained and the thrombus disappeared 10 h after the initial study. There was no complication. The case illustrates the utility of two-dimensional enchocardiography in the evaluation of patients with pulmonary embolic disease and the efficacy and safety of thrombolytic therapy in the treatment of pulmonary embolism in transit.

Echocardiography↗
PubMed1996

Intrapleural placement of a nasogastric tube: an unusual complication of nasotracheal intubation.

PURPOSE: Although rare, the misplacement of nasogastric tubes into the pleural space has been described. The prognosis of such injuries is improved by prompt recognition; therefore, it is important for physicians who practice nasogastric intubation to be aware of this potential complication, and to be familiar with an approach to early diagnosis. CLINICAL FEATURES: We present a case of perforation of the cervical oesophagus by a polyvinylchloride nasogastric tube, following a traumatic attempt at nasotracheal intubation. This resulted in passage of the nasogastric tube into the pleural space. CONCLUSIONS: Our experience with this case and a review of the relevant literature suggest that such trauma may predispose to malplacement of nasogastric tubes. Clinical signs, such as aspiration of fluid from a nasogastric tube, and auscultation of air insufflated into the stomach, are unreliable; however, the presence of subcutaneous air in the neck on chest radiograph, and the presence of cervical crepitance on physical examination, are valuable signs in the early diagnosis of perforation of the cervical oesophagus. Contrast oesophagography remains the diagnostic manoeuvre of choice in confirming the diagnosis, but early diagnosis will depend on a high index of suspicion and prompt viewing of chest x-rays. The management and the prognosis of such injuries depends on the level of the perforation, delays in diagnosis, and the presence of associated mediastinitis.

Aged↗
PubMed1996

Estimation of capitation expense for specialty services.

Sources of financial uncertainty under capitation plans include not knowing the game rules, using the wrong game rules, basing financial decisions on incomplete data, or even being clueless about the factors that will determine financial risk. Financial risks under managed care can involve price, utilization, selection, and partner risks. Risks can vary by contract type. Controlling risk requires adequate information. Methods to manage risk include the modeling of risk implications; reliance on the law of large numbers; and the use of risk-sharing arrangements, stop-loss insurance, traditional insurance techniques, and various specific contracting techniques.

Actuarial Analysis↗
PubMed1996

Effect of alpha-adrenoreceptor stimulation on the diaphragmatic oxygen delivery-consumption relationship.

PURPOSE: In the vascularly isolated canine hemidiaphragm, we tested the hypothesis that alpha-adrenoreceptor stimulation may influence diaphragmatic function and O2 extraction during reductions in O2 delivery (QO2di). METHODS: The diaphragm was perfused using a constant flow pump with blood diverted from the left femoral artery. QO2di was reduced in a stepwise fashion by progressive reductions in pump flow. The tension generated by the contracting diaphragm (3 Hz), the critical O2 delivery (QO2di,c) below which O2 consumption (VO2di) becomes dependent on O2 supply and the oxygen extraction ratio at this critical point (ERc) were assessed in two groups of animals. Phenylephrine (10(-5) mol/L) was infused into the phrenic artery in one group and saline was infused in another group. RESULTS: In the contracting diaphragm, VO2di was higher in the phenylephrine infused group than in the control group (5.2 +/- 0.5 vs 2.11 +/- 0.3 mL/min/100 g). QO2di,c and ERc were also higher in the phenylephrine group than in the control group (6.16 +/- 0.43 vs 3.1 +/- 0.5 mL/min/100 g and 0.87 +/- 0.035 vs 0.63 +/- 0.05, respectively). In the resting diaphragm, VO2di was not significantly different between the two groups and no critical oxygen delivery could be identified in either group. CONCLUSIONS: These results indicate that alpha-adrenoreceptor activation may increase the tension generated by the diaphragm as well as its oxygen consumption and oxygen extraction. Although this may be beneficial during moderate reductions in oxygen delivery, in more severe shock states, activation of these receptors by endogenous or exogenously administered catecholamines may hasten the development of delivery limitation of VO2di and compromise the ability to sustain ventilation.

Adrenergic alpha-Agonists↗
PubMed1996

Effect of acute respiratory acidosis on the limits of oxygen extraction during hemorrhage.

BACKGROUND: Hypercapnia can impair cells' capacity to maintain energy status anerobically and enhances the risk of hypoxic injury when oxygen availability is reduced. The ability to maintain tissue oxygenation is determined by both bulk blood flow and the efficiency of oxygen extraction. Bulk blood flow is maintained during hypercapnia through increased sympathetic activity. The effect of hypercapnia on oxygen extraction, however, is unknown. This study evaluates the effect of hypercapnia on cells' capacity to adapt to reductions in oxygen availability by increasing oxygen extraction. METHODS: In three groups of paralyzed, mechanically ventilated dogs that were anesthetized with alpha-chloralose, the concentration of carbon dioxide in the inhaled gas mixture was adjusted to achieve normocapnia, moderate hypercapnia (Paco2 = 72 +/- 3 [SE] mmHg) or severe hypercapnia (Paco2 = 118 +/- 4 [SE] mmHg). Stepwise hemorrhage was induced until each dog's blood pressure was destabilized. At each stage in the hemorrhage protocol, the oxygen delivery, oxygen consumption, and oxygen extraction ratios (ratio of arteriovenous oxygen content difference to arterial oxygen content) were determined. RESULTS: At the point of onset of delivery dependence of oxygen consumption, the oxygen delivery rate (critical oxygen delivery) was 7.8 +/- 1.5 (SE) ml.kg-1.min-1 and the oxygen extraction ratio (critical oxygen extraction ratio) was 0.72 +/- 0.04 (SE) in the normocapnic dogs. Moderate hypercapnia had no effect on these parameters. In the severely hypercapnic dogs, the critical values for oxygen delivery and extraction ratios were 12.5 +/- 1.8 (SE) ml.kg-1.min-1 and 0.54 +/- 0.035 (SE), respectively (P < 0.05 for differences from the normocapnic dogs). CONCLUSIONS: The results identify a previously unrecognized threat to tissue oxygenation and emphasize the importance of ensuring adequate oxygen delivery when adopting mechanical ventilatory strategies that permit respiratory acidosis to develop.

Acidosis, Respiratory↗
PubMed1996

The association of Chlamydia trachomatis/gonococcal infection and tubal factor infertility.

OBJECTIVE: To determine the association of past Chlamydia trachomatis and past Neisseria gonorrhoeae infection with tubal factor infertility. METHODS: A cross-sectional study was conducted. Cases consisted of 55 primary infertile women with laparoscopy confirmed tubal damage (group A) and their husbands, consecutively attending the Infertility Unit at Maharaj Nakorn Chiang Mai Hospital between 1990 and 1992; and 58 primary infertile women with laparoscopy confirmed normal tubes (group B) and their husbands, consecutively attending the same hospital over the same period. Controls consisted of 59 postpartum women (group C) and their husbands omitted to the same hospital over the same period as cases. Past chlamydial and gonococcal infections were assessed by measuring serum IgG antibodies by enzyme immunoassay (EIA). The EIA antigens consisted of purified elementary bodies of C. trachomatis serovar L1, or purified alpha pili of N. gonorrhoeae strain P9. RESULTS: The prevalence of positive IgG antibody to gonococcal pili in sera from group A was 29.1%, significantly higher than the prevalence of 5.2% in group B or 3.4% in group C (p = 0.000). The husbands of women in group A had a significantly higher prevalence of IgG antibody to gonococcal pili (36.4%) than the husbands of women in group B (8.6%) or group C (18.6%) (p = 0.002). There was no significant difference in positive IgA antibody between case and control groups. After controlling for age, group A showed significantly higher prevalences of past gonorrhea (OR = 32.4, 95% CI 4.3, 242.2) and past chlamydial infection (OR = 3.2, 95% CI 1.2, 8.5) than group C. The husbands of women in group A also had higher prevalences of both types of infection than the husbands of women in group C; the odds ratios for past gonorrhea or chlamydial infections were 2.8 (95% CI 1.1, 6.9) and 2.9 (95% CI 1.2, 7.1), respectively. Neither infertile women with normal tubes (group B) nor their husbands showed any difference when compared with controls. CONCLUSION: These results suggest that in this region of northern Thailand there is an association between past gonorrhea and past chlamydial infection and tubal factor infertility.

Adult↗
PubMed1996

Interaction between hypoxia and hypercapnia in regulating canine diaphragm arteriolar diameter.

In alpha-chloralose-anesthetized mongrel dogs, the microvascular responses to hypoxia and hypercapnia were studied in the vascularly isolated ex vivo left hemidiaphragm. The diaphragm was perfused with arterial blood diverted from the femoral artery by a pump. A series of membrane oxygenators was used to adjust the blood gas composition of the blood perfusing the diaphragm. Arteriolar diameters were measured by intravital microscopy during an infusion of sodium nitroprusside, moderate hypoxia (phrenic venous PO2 25 Torr), severe hypoxia (phrenic venous PO2 13 Torr), hypercapnia (phrenic venous PCO2 100 Torr), and a simultaneous presentation of hypoxia and hypercapnia. Recordings were made after 15 min under each condition when a steady state had been established for vessel diameter and flow. Pump speed was adjusted manually under each condition to ensure that the steady-state perfusion pressure was the same as that under the control condition. Moderate hypoxia generally resulted in dilation; however, vasoconstriction was seen in some arterioles. Severe hypoxia caused vasodilation that was inversely related to baseline vessel diameter and paralleled the response to sodium nitroprusside. Hypercapnia resulted in vasodilation of the diaphragmatic circulation at values of phrenic venous PCO2 > 80 Torr. The arteriolar response to hypercapnia was also inversely related to baseline vessel diameter. Hypoxia and hypercapnia in combination exerted an additive effect on arteriolar diameter but produced a greater than additive effect on blood flow. Both PO2 and PCO2 may contribute to the local regulation of diaphragmatic blood flow. The vasodilator effects of both hypoxia and hypercapnia are greater in smaller than in larger arterioles. The interaction between PO2 and PCO2 on arteriolar diameter is additive. An apparent synergistic effect on blood flow results from the power function relating diameter to flow.

Animals↗
PubMed1996

Effect of inhibition of nitric oxide synthesis on the diaphragmatic microvascular response to hypoxia.

The purpose of this study was to determine the effect of inhibition of nitric oxide (NO) release on the diaphragmatic microvascular responses to hypoxia. In alpha-chloralose-anesthetized mongrel dogs, the microcirculation of the vascularly isolated ex vivo left hemidiaphragm was studied by intravital microscopy. The diaphragm was pump perfused with blood diverted from the femoral artery through a series of membrane oxygenators. The responses to supramaximal concentrations of sodium nitroprusside, moderate hypoxia (phrenic venous PO2 27 Torr), and severe hypoxia (phrenic venous PO2 15 Torr) were recorded before and after an infusion of NG-nitro-L-arginine (L-NNA; 6 x 10(-4) M) into the phrenic circulation for 20 min. Under control conditions, diaphragmatic blood flow was 12.4 +/- 1.1 ml.min-1.100g-1. Diaphragmatic blood flows recorded during moderate and severe hypoxia were 15.6 +/- 1.2 and 24.3 +/- 1.5 ml.min-1. 100 g-1, respectively (P < 0.05 for both compared with control values). Treatment with L-NNA reduced diaphragmatic blood flow to 9.6 +/- 0.8 ml.min-1.100 g-1 under control conditions (P < 0.05) and caused arteriolar vasoconstriction to a degree that was dependent on vessel size (i.e., larger vessels constricted more than smaller vessels). L-NNA eliminated the increase in blood flow during moderate hypoxia and inhibited arteriolar dilation by an amount that was related to vessel size (i.e., dilation of larger vessels was inhibited more than that of smaller vessels). Inhibition of NO synthesis had no effect on the increase in diaphragmatic blood flow (23.6 +/- 1.9 ml.min-1.100 g-1; P > 0.05 compared with that during severe hypoxia before treatment with L-NNA) or arteriolar diameters during severe hypoxia. NO release plays a role in the diaphragmatic vascular response to hypoxia, but this role is limited to dilation of larger arterioles during hypoxia of moderate severity.

Animals↗
PubMed1996

The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis.

We have shown that viruses are associated with 80 to 85% of asthma exacerbations in school-age children in the community. We hypothesize that viral infections are also associated with severe attacks of asthma precipitating hospital admissions. To investigate this, we conducted a time-trend analysis, comparing the seasonal patterns of respiratory infections and hospital admissions for asthma in adults and children. During a 1-yr study in the Southampton area of the United Kingdom, 108 school-age children monitored upper and lower respiratory symptoms and took peak expiratory flow rate (PEFR) recordings. From children reporting a symptomatic episode or a decrease in PEFR, samples were taken for detection of viruses and atypical bacteria. A total of 232 respiratory viruses and four atypical bacteria were detected. The half-monthly rates of upper respiratory infection were compared with the half-monthly rates for hospital admissions for asthma (International Classification of Diseases [ICD] code 493) for the same time period for the hospitals serving the areas from which the cohort of schoolchildren was drawn. The relationships of upper respiratory infections and hospital admissions for asthma with school attendance were studied. Strong correlations were found between the seasonal patterns of upper respiratory infections and hospital admissions for asthma (r = 0.72; p < 0.0001). This relationship was stronger for pediatric (r = 0.68; p < 0.0001) than for adult admissions (r = 0.53; p < 0.01). Upper respiratory infections and admissions for asthma were more frequent during periods of school attendance (87% of pediatric and 84% of total admissions), than during school holiday periods (p < 0.001). These relationships remained significant when allowance was made for linear trend and seasonal variation using multiple regression analysis (p < 0.01). Not surprisingly, school attendance, because it is a major factor in respiratory virus transmission, was found to be a major confounding variable in children. This study demonstrates that upper respiratory viral infections are strongly associated in time with hospital admissions for asthma in children and adults. Rhinoviruses were the major pathogen implicated, and the majority of viral infections and asthma admissions occurred during school attendance.

Adolescent↗
PubMed1995

Extent and kinetics of genetic change in the omp1 gene of Chlamydia trachomatis in two villages with endemic trachoma.

Variants of Chlamydia trachomatis in two Gambian villages with hyperendemic trachoma were analyzed by omp1-based polymerase chain reaction and sequencing from conjunctival swabs. Samples collected over a 22-month period included a complete cross-sectional study of each village. Overall, 4 genovar A and 4 B variants were characterized by point mutations in the omp1 gene, resulting in changes in the inferred amino acid sequence. Two genovar A and 2 B variants accounted for 87% of the total ocular chlamydial infection in both villages. Although some flux in the prevalence of individual variants was observed overtime, their overall distribution remained remarkably stable. There was no evidence of major antigenic shift arising from recombination events at the omp1 locus as described for genital tract infection. These results indicate that omp1 variation in these two trachoma-hyperendemic communities is limited and unlikely to hamper development of trachoma vaccines based on the major outer membrane protein.

Amino Acid Sequence↗
PubMed1995

SCOTI--a new device for identification of tracheal intubation.

A new lightweight device for the detection of placement of a tracheal tube in the trachea or oesophagus is described. The device utilises a sonic technique detecting resonating frequencies in an open (trachea) or closed (oesophagus) structure. Evaluation of the device in a clinical environment is described and it has been shown to be capable of verifying the correct placement of the tracheal tube in the trachea in 98% of patients studied. Further evaluation of this intubating aid appears justified.

Adolescent↗
PubMed1995

The immunobiology and immunopathology of chlamydial infections.

Chlamydiae are obligate intracellular bacterial pathogens of eukaryotic cells responsible for a wide variety of important human and animal infections. In humans, chlamydial infections are generally localised to superficial epithelial or mucosal surfaces, are frequently asymptomatic and may persist for long periods of time if untreated, inducing little protective immunity. Nevertheless, neutralising antibodies of limited efficacy are produced against the main chlamydial outer envelope protein, while gamma interferon (IFN gamma) is chlamydiastatic and paradoxically may play a role both in chlamydial persistence and in protective immunity. Delayed hypersensitivity responses to chlamydiae caused by repeated or persistent infection are thought to be important in the development of the severe scarring sequelae characteristic of cicatricial trachoma and of chronic salpingitis. Chlamydial heat shock proteins bearing close homology with their human equivalents may be major targets for immunopathological responses and their expression is upregulated in IFN gamma induced persistent infection. C. pneumoniae, a common cause of acute respiratory infection in humans, may persist in coronary arteries and is strongly implicated as a risk factor in atherosclerosis and in acute myocardial infarction. This paper reviews the immunology and immunopathology of chlamydial infections in the context of the unique biology of this fascinating but challenging group of organisms.

Animals↗
PubMed1995

A peptide of Chlamydia trachomatis shown to be a primary T-cell epitope in vitro induces cell-mediated immunity in vivo.

Chlamydiae are a major cause of infertility and preventable blindness and there is currently no effective vaccine in humans or rodents against these organisms. We have previously shown that a peptide of 12 amino acids (termed TINKP) from a conserved region of the major outer membrane protein (MOMP) of Chlamydia trachomatis (C. trachomatis) is a primary T-cell epitope in humans. Here we showed that when dendritic cells (DC) from C3H or BALB/c mice were pulsed in vitro with the peptide they stimulated proliferation of syngeneic T cells in vitro indicating that the peptide is also a primary T-cell epitope in mice. Since the skin is a rich source of DC, we immunized mice from each strain with an intradermal injection of the peptide. Humoral and cell-mediated immunity to peptide, MOMP or whole elementary bodies (EB) of C. trachomatis (F/NI1/GU) were assessed. No antibody response to TINKP was observed. However, immunized mice showed recall responses to all three chlamydial antigens. T-cell-mediated immunity in the absence of antibody was induced by a single injection of the peptide intradermally. C. trachomatis isolated from the human genital tract causes salpingitis in mice. Preliminary studies in susceptible C3H mice indicated that intradermal injection of peptide conferred some protection against the development of salpingitis. Thus, a primary T-cell epitope identified by in vitro stimulation using DC can also initiate cell-mediated immunity in vivo and this approach may be useful in the development of vaccines.

Animals↗
PubMed1995

[Species-specific monoclonal antibodies against the major outer membrane protein (MOMP) of Chlamydia trachomatis].

The synthesized one quarter N-terminal MOMP of C. trachomatis was used for primary immunization of three male BALB/c mice (8 weeks of age), and the boost with C. trachomatis L1/440/Bu elementary bodies (EBs) was followed on day 14. Spleen cells from one mouse with good response of immunization were fused with murine myeloma NS-1 cells on day 24. The hybrid cell suspension was seeded into the wells of 96-well microtest plates which contained macrophage feeder layers. Anti-chlamydial antibodies in culture fluids were screened by ELISA with 1/4 MOMP & L1 EBs coated 96-well trays. Positive wells were cloned by limiting dilution. Four clones which secreted immunoglobulin G1 & G2a class were obtained after elimination of those clones that produced antibodies to C. psittaci strain EAE, C. pneumoniae strain ATCC VR1310 and uninfected BGMK cells. In micro-IF test, we found that the all four clones of MAbs reacted with our laboratory prepared L1, L2, A, B, C, E EBs, L2 tissue culture inclusions, as well as the EBs of all 15 standard serovars of C. trachomatis. The titers of their ascites were more than 1:12,800 in micro-IF test. It was shown that the four clones of MAbs reacted predominantly with 40,000 MOMP of C. trachomatis L1 in Western blot.

Animals↗