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Biomedical subjects

W R Clarke

Publications and source records attributed to W R Clarke.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effect of inhaled nitric oxide during group B streptococcal sepsis in piglets.

Group B streptococcus (GBS), a common gram-positive pathogen, causes similar pathophysiologic changes in newborn humans and animals. Infusion of GBS into neonatal animals produces pulmonary hypertension and ventilation/perfusion (Va/Q) mismatch in both early-phase (< 1 h) and late-phase (2 to 6 h) responses. Contrary to early phase, late phase causes pulmonary vascular injury. Nitric oxide (NO) is an inhaled vasodilator whose effect on pulmonary hypertension and Va/Q matching during early and late phases of GBS sepsis is unclear. We hypothesized that inhaled NO (150 ppm) would: (1) reverse early-phase GBS-induced pulmonary hypertension; (2) demonstrate less effectiveness in reversing late-phase GBS-induced pulmonary hypertension because of vascular injury; (3) improve late-phase GBS-induced Va/Q mismatching. Anesthetized, mechanically ventilated piglets (n = 10; 14 +/- 4 days of age) received a 240-min infusion of GBS (1.5 x 10(9) CFU/kg/h). Piglets received 30 min of NO (Study) or N2 (Control) at 30 and 210 min of GBS infusion. We found that inhaled NO selectively reversed early- and late-phase GBS-induced pulmonary hypertension and that NO was equally as effective in each phase. Inhaled NO did not reverse Va/Q mismatching during late-phase GBS. We conclude that 4 h of GBS sepsis does not injure neonatal pulmonary vascular smooth muscle sufficiently to impair its response to inhaled NO.

Administration, Inhalation↗
PubMed1993

Thyroxine and fetal blood coagulation: a fetal lamb study.

Glucocorticoids have been shown to accelerate the development of blood coagulation in the fetal lamb (Kisker, Robillard & Bohlken, 1983). The current studies examine the influence of high levels of triiodothyronine (T3) on the development of blood coagulation in the fetal lamb. Eight twin fetal lambs were studied during the last trimester of pregnancy (109-138 days gestation) using chronically placed arterial and venous catheters for infusion of T3 and withdrawal of blood samples. One fetus of each twin was infused intravenously with T3 at a constant rate of 0.6 micrograms T3/0.4 ml/h for 48 h. The other twin was infused with 5% dextrose at 0.4 ml/h for 48 h. Blood samples for measuring PT, PTT, TT, fibrinogen, factors II, V, VII, VIII, IX, X, XI and XII were obtained prior to and at the completion of the infusions. The results were analyzed for differences between the samples from paired control and T3 treated animals. Factor V significantly decreased in the T3 infused animals from 51.2% +/- 12.5% to 44.8% +/- 13.8% (P = 0.038). Factor VII also decreased in the treated animals 57.8% +/- 20% to 43.6% +/- 10.8%, but the changes were not statistically significant (P = 0.06). Factor XII significantly increased in the treated animals from 37% +/- 10.5% to 45% +/- 13.7% (P = 0.004). High levels of T3 in third trimester fetal lambs are accompanied by a moderate decrease in factor V and an increase in factor XII activity.

Animals↗
PubMed1992

A child with valproic acid-associated carnitine deficiency and carnitine-responsive cardiac dysfunction.

Valproic acid enhances renal losses of carnitine esters and leads to decreased plasma free carnitine concentrations in many patients receiving valproic acid therapy. However, decreased serum carnitine levels are of unclear pathologic significance, and most children manifest no symptoms of carnitine deficiency. We report a child with valproic acid-associated carnitine deficiency who had severe cardiac dysfunction develop that resolved with carnitine replacement therapy.

Carnitine↗
PubMed1991

Are leg electromyogram profiles symmetrical?

Electromyographic (EMG) patterns reflect function of the neuromuscular system. Abnormality of a given pattern may be established by comparison with that of the contralateral (presumably normal) limb if one ensures a difference beyond normal degrees of symmetry. We studied EMG patterns in six homologous knee muscles during freely selected, slow, and fast gaits in normal subjects. EMG signals were electronically conditioned to produce linear envelopes; envelopes from at least eight cycles from each subject at each speed were ensemble averaged. Grand ensemble averages for each muscle and speed were assembled from all subjects for right and left muscles. Transformed correlation coefficients (r') and variance ratios established the degree of similarity. All muscles exhibited a fair degree of symmetry (mean r' = 0.797-0.953), but we saw exceptions. On rare occasion, muscles repeatedly exhibited monophasic signals on one side and biphasic on the other. With increasing speed, signals generally became more repeatable, but we occasionally saw monophasic patterns becoming biphasic or vice versa. Considerable caution is essential before presuming any given pattern is abnormal. To ensure that a given pattern is abnormal one could establish that the pattern lies outside some statistical limits for normal population patterns controlled for speed and outside statistical limits for normal symmetry. Alternatively, one could determine the level of statistical differences in EMG patterns associated with distinct differences in level of functional performance between normal subjects and patients.

Adult↗
PubMed1991

Childhood predictors of high blood pressure.

Longitudinal studies in children have tracked blood pressure through childhood and from childhood into adult life. However, many children do not maintain their rank during these periods of observation. Several of the factors contributing to maintenance of rank order are reviewed, such as initial level of blood pressure, body size, sexual maturation, and family history of high blood pressure. Children with initially high level of blood pressure are more likely to become adults with high blood pressure, particularly if they are obese as children or become obese as young adults, and if they have a positive family history for hypertension.

Adolescent↗
PubMed1991

Amrinone reduces pulmonary vascular resistance elevated by U46619 in isolated perfused lungs.

The effects of amrinone on pulmonary vascular resistance (PVR) were studied in an isolated, perfused rabbit lung model where all the major determinants of PVR were controlled. In this preparation, the alveolar oxygen and carbon dioxide tensions, vascular pH and vascular oxygen and carbon dioxide tensions, and zonal conditions of the lung and phasic variations of pulmonary artery pressures could be precisely measured and controlled. Measurements of PVR were made by a complete determination of the pulmonary pressure-flow curve and determination of the PVR under identical flow conditions for all studies. This approach allowed a more precise determination of the primary effects of amrinone on normal and elevated PVR than has been previously possible. We found that amrinone in final concentrations of either 4 or 8 micrograms/ml had no effect on basal PVR and no effect on lung water weight to dry ratios. When PVR was elevated by the addition of the thromboxane A2 mimetic U46619, amrinone reduced the PVR by 27% at a final concentration of 4 micrograms/ml and by 74% at a final concentration of 8 micrograms/ml. We conclude that in the doses tested, amrinone has no effects on basal PVR but is able to reduce elevated PVR in a dose-dependent manner. These results are the first to demonstrate clearly that amrinone has the ability to reduce elevated pulmonary vascular tone through a direct mechanism and not through secondary effects on other determinants of PVR such as left atrial pressure (Pla), increased cardiac output with resultant vascular recruitment, or increases in mixed venous oxygen tension. The possible implications for the clinical use of amrinone in situations of elevated PVR are discussed.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

Factors affecting tracking of coronary heart disease risk factors in children. The Muscatine Study.

The public health implications of reducing or preventing the excess increase in blood pressure and the acquisition of obesity during childhood years are important. Many children with high blood pressure, particularly those who are initially obese or become obese as young adults and those with excess left ventricular mass for body size, become adults with high blood pressure. Although blood pressure and cholesterol have been shown to track during childhood and from childhood into the adult years, the use of repeated determinations along with measures of obesity and information concerning family history of diabetes and coronary heart disease can significantly add to the prediction of future elevated levels.

Adolescent↗
PubMed1991

Childhood predictors of future blood pressure.

Blood pressure in infants and children is much lower than that in adults. It is suspected that children whose blood pressures are greatest for their age or body size may be destined for future hypertension. However, it is apparent that some children with lower blood pressures are also destined for hypertension as adults. Children with a family history of hypertension demonstrate greater blood pressure and heart rate responses to mental challenge. These responses are enhanced when a high salt diet is consumed. Increased maximal exercise systolic blood pressure and increased left ventricular wall mass in childhood add significantly to the prediction of future high blood pressure. In addition, the acquisition of excess weight for height from childhood to young adult life adds to the prediction of future blood pressure elevations. Both children and adults who are obese have significantly higher blood pressures than those who are lean. Approximately 34% of the variability in body mass index is explained by genotype differences at a single recessive locus, 41% by genotype differences at polygenic loci, and 25% by nongenetic factors. Thus, the genetic influence of obesity may be an important factor responsible for elevated blood pressure in both children and adults.

Adult↗
PubMed1990

Use of cholesterol measurements in childhood for the prediction of adult hypercholesterolemia. The Muscatine Study.

This article describes the validity and utility of screening tests for total cholesterol levels in school-age children to predict those who, when adults, will have cholesterol levels that the National Cholesterol Education Program suggests need continuing surveillance and intervention. Two thousand three hundred sixty-seven children aged 8 to 18 years were examined on several occasions and were followed up to ages 20 to 30 years. Of children with cholesterol concentrations exceeding the 75th percentile on two occasions, 75% of girls and 56% of boys would not qualify for intervention as adults by the National Cholesterol Education Program criteria. Of children with cholesterol levels exceeding the 90th percentile on two occasions, 57% of girls and 30% of boys would not qualify for intervention as adults. Because the efficacy, safety, acceptability, and cost of treatment for high cholesterol concentrations in childhood is evolving, the need for universal screening of childhood cholesterol levels must be considered carefully in view of the number of children with high levels of cholesterol who, as adults, do not meet the criteria for intervention suggested by the National Cholesterol Education Program.

Adolescent↗
PubMed1990

The role of lung perfusate PO2 in the control of the pulmonary vascular resistance of exteriorized fetal lambs.

The isolated perfused lower left lung lobe of the exteriorized fetal lamb was used to define quantitatively the relationship between pulmonary perfusate oxygen tension and pulmonary vascular resistance (PVR) in the fetus at multiple oxygen tensions over the range from 8.3 to 433 mm Hg. This allowed variation of the perfusate PO2 over the range of partial pressures from less than 10 mm Hg to over 400 mm Hg while constant values of PCO2, temperature and perfusate flow were maintained. In all animals, calculated pulmonary vascular resistance varied in an inverse manner with the perfusate PO2. The relationship between PVR and perfusate oxygen tension is described by the equation: PVR = 7.67 - 1.54 (log PO2) R2 = 0.70. While others have shown that a single, large increase in blood oxygen tension will decrease the PVR in fetal lambs, these data present the first quantitative description of the role of oxygen tension in the modulation of fetal pulmonary vascular resistance as determined at multiple perfusate oxygen tensions over a fifty-fold range.

Animals↗
PubMed1990

A prospective study of the risk of an immediate adverse reaction to protamine sulfate during cardiopulmonary bypass surgery.

Protamine sulfate administration may cause life-threatening reactions. We prospectively examined the incidence of immediate adverse reaction after protamine in 243 patients who underwent cardiopulmonary bypass surgery. Twenty-six patients (10.7%) had reactions, and 1.6% had a precipitous drop in blood pressure immediately after protamine administration. Risk factors were previous exposure to protamine, diabetes, history of receiving protamine-containing insulin, and possibly vasectomy. However, neither a positive skin test nor a positive IgE ELISA for antiprotamine antibody predicted that a patient would have a reaction. C4a levels were increased in patients who had reactions as compared with age-, sex-, and cardiac disease-matched patients who did not have reactions, suggesting a role for complement in some reactions. Immediate adverse reactions to protamine are very common, and alternative therapies are urgently needed to eliminate the use of protamine.

Adult↗
PubMed1990

Low-dose almitrine bismesylate enhances hypoxic pulmonary vasoconstriction in closed-chest dogs.

The effect of almitrine bismesylate on the hypoxic pulmonary vasoconstrictor response was studied in six closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2; the left lung was ventilated either with 100% O2 ("hyperoxia") or with an hypoxic gas mixture ("hypoxia": end-tidal oxygen tension = 60.3 +/- 0.6 mm Hg). On two consecutive days, each dog received either almitrine (Vectarion, Servier Lab) or malic acid. Consecutive almitrine doses of 0.003, 0.03, 0.3, and 3.0 micrograms.kg-1.min-1, or the equivalent volumes of malic acid without almitrine, were administered intravenously as a constant peripheral infusion for 15 min. Percent blood flow to each lung was calculated based on a variation of the traditional shunt equation. The change in percent left lung blood flow (delta %QL-VA) increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. The change in arterial oxygen tension (delta PaO2) also increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. It is concluded that in dogs low-dose almitrine enhances hypoxic pulmonary vasoconstriction and that this enhancement is dose-related.

Almitrine↗
PubMed1990

Autoradiographic study of the attrition of migrating schistosomula in the skin of mice. II. Mice challenged with normal S. mansoni cercariae after immunization with highly irradiated cercariae.

The migratory pattern and attrition of 75Se-labelled S. mansoni challenge cercariae in CF1 mice immunized 0, 1, 3, or 5 times with 12kR- or 48kR-irradiated cercariae were investigated by compressed organ autoradiography. Mice were percutaneously inoculated with 500-1000 cercariae for each immunization and with a known count of approximately 90 cercariae at a different site for challenge. The skin, lungs, liver, other organs, and carcass were processed for autoradiography. Hepatic and mesenteric perfusions for worm collection were also sampled from day 19 through 34. In naive mice, 25% of challenge cercariae died in the skin. Skin attrition of challenge cercariae in mice immunized with 12kR-irradiated cercariae was 43% with 1 immunization, 54% with 3, and 58% with 5, whereas in mice immunized with 48kR-irradiated cercariae, skin attrition was 48% with 1, 63% with 3, and 76% with 5 immunizations. In all immunized mice, a high percentage of migrating schistosomula died in the skin within 24 hours of a challenge infection. Utilizing autoradiography, it was found that the silver foci created by single labelled worms were difficult to differentiate from those of paired worms. This study documents the induction of acquired resistance against a challenge infection in the skin by vaccination with highly irradiated cercariae, with the degree of attenuation of immunizing cercariae and the number of immunizations being closely related to the attrition rate in the skin. Finally, we discuss the contradictory views concerning the site of attrition of challenge cercariae.

Animals↗
PubMed1989

Predicting adult cholesterol levels from measurements in childhood and adolescence: the Muscatine Study.

2,446 subjects initially examined at ages eight to 18 years were reexamined as young adults at ages 20-25 years or 26-30 years. Measurements of cholesterol, height, weight, and triceps skinfold thickness were obtained during childhood. Lipids, lipoprotein fractions, family history as well as medication, alcohol, and tobacco use were determined during the adult examination. Elevated levels of cholesterol during childhood were associated with elevation in adult life. On average, of children found to have cholesterol levels greater than or equal to the 90th percentile for their age and gender, on a single measurement 43% remained above the 90th percentile, 62% remained above the 75th percentile, and 81% remained above the 50th percentile. Obesity acquired in adolescence and the young adult years, oral contraceptive use, and cigarette smoking had deleterious effects upon adult cholesterol levels and lipoprotein fractions.

Adolescent↗
PubMed1989

Childhood risk factors for high adult blood pressure: the Muscatine Study.

In adult populations, elevated blood pressure is related to the development of occlusive atherosclerosis, stroke, and renal disease. The significance of blood pressure levels in childhood, unless extremely elevated, has not been related to disease outcomes. In this study, the risk of high blood pressure in young adult life is evaluated based on the observations of blood pressure and other factors made during the school-aged years. Subjects, 2445 in number, were first observed at ages 7 through 18 years and again between 20 and 30 years. During childhood, measurements of blood pressure, height, and weight were made in alternate years. At adult ages, the same measurements were again made and a health questionnaire was administered. According to the data, adult blood pressure is correlated with childhood blood pressure, body size, and change in ponderosity from childhood to adult life. Adult ponderosity is related to childhood ponderosity, and those who are most obese as adults show the greatest increase in weight for height from their childhood years. These observations suggest that strategies to prevent the acquisition of excess ponderosity during adolescence may be useful in preventing adult hypertension.

Adolescent↗
PubMed1988

Left ventricular mass and exercise responses predict future blood pressure. The Muscatine Study.

Increased blood pressure and left ventricular mass are associated with increased morbidity and mortality in adults with coronary heart disease. To define the predictors of subsequent childhood blood pressure and left ventricular mass, serial echocardiograms and blood pressure responses during exercise were studied in 274 children aged 6 to 15 years, whose systolic blood pressures were in the high, middle, or low range. Persistence of rank order for left ventricular mass and blood pressure, at rest and during exercise, was maintained over a mean follow-up period of 3.4 years, with correlations ranging from 0.33 to 0.44. Subsequent systolic blood pressure was best predicted from initial resting and maximal exercise systolic blood pressures and left ventricular mass. Subsequent left ventricular mass was best predicted from initial left ventricular mass and maximal exercise diastolic blood pressure, but resting systolic blood pressure did not add to this latter prediction. Since left ventricular mass relates best to exercise blood pressure and not to resting blood pressure, left ventricular mass may provide an integrated view of the effects of blood pressure both at rest and during stress. We speculate that increased left ventricular mass in childhood may be an important predictor of subsequent hypertension and its consequences.

Adolescent↗