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Biomedical subjects

M J Morton

Publications and source records attributed to M J Morton.

At least 19 recordsLinked to original sources

Effects of estrogen and progestin on aortic size and compliance in postmenopausal women.

OBJECTIVE: Our purpose was to determine whether sex steroids alter aortic size and compliance in postmenopausal women. STUDY DESIGN: Twenty-six postmenopausal women were randomized to receive either conjugated estrogens 0.625 mg per day (group 1) or conjugated estrogens 0.625 mg per day and medroxyprogesterone 2.5 mg per day (group 2). Aortic cross-sectional area was measured by magnetic resonance imaging before and after 3 months of hormone therapy. RESULTS: Estradiol levels increased in both group 1 and group 2 (p < 0.0001). Ascending aortic cross-sectional area increased from 439 +/- 7 mm2 to 466 +/- 7 mm2 in group 1 (p < 0.008) but was unchanged in group 2. Within the range of aortic pressures studied, no change in aortic compliance could be detected. CONCLUSION: Estrogen therapy in postmenopausal women was associated with an increase in aortic size; but this effect was not detectable with the addition of progestin. The potential antagonistic effect of progestin on estrogen-induced aortic enlargement suggests that the favorable cardiovascular effects of postmenopausal estrogen therapy cannot be automatically extended to the combination estrogen-progestin.

Aorta, Thoracic

Right ventricular function in chronically anemic fetal lambs.

OBJECTIVE: Our purpose was to determine whether the increase in extravascular fluid in chronic fetal anemia occurs either because of heart failure or despite successful cardiac adaptation. STUDY DESIGN: Right ventricular function curves were obtained in five ovine fetuses at the start, midpoint, and end of 5 to 8 days of anemia induced by isovolemic daily hemorrhage. Least-squares fit of the ascending and plateau lines of stroke volume versus right atrial pressure were used to establish breakpoints (intersection of the ascending and plateau lines), which were compared by analysis of variance for repeated measures. Myocardial blood flow was measured by microspheres. RESULTS: Carotid arterial oxygen content was reduced from 7.0 +/- 0.3 to 2.1 +/- 0.1 ml/dl and the hematocrit from 29% +/- 1.8% to 13% +/- 0.6%. Breakpoint analysis of function curves showed that although right atrial pressure remained unchanged (3.4 +/- 0.7 and 3.6 +/- 0.6 mm Hg) stroke volume increased from 1.03 +/- 0.14 to 1.62 +/- 0.25 ml/kg. Both right and left ventricular coronary blood flow were increased, 1351 +/- 313 and 1166 +/- 264 ml/min per 100 gm. Excess fluid was present in abdomen and chest of most animals at autopsy. CONCLUSION: Tissue edema during severe anemia occurs despite normal right atrial pressure, increased stroke volume, and markedly increased coronary blood flow, markers of successful cardiac adaptation.

Anemia

Correlation of hematologic markers of inflammation and lung function: a comparison of asymptomatic smokers and nonsmokers.

Increased inflammation of the peripheral airways has been implicated as a cause of pulmonary function impairment. However, little information is available on the correlation between subclinical decrements of pulmonary function and inflammation in asymptomatic individuals. A relationship between markers of inflammation and lung function may be useful in predicting the early onset of lung function impairment. The purpose of this study was to investigate the correlation of hematologic markers of inflammation and spirometry in asymptomatic smokers and nonsmokers. The specific objectives of this study were twofold. The first objective was to quantify and compare the spirometric measures of lung function in smokers and nonsmokers having similar demographic and lifestyle characteristics. The second objective was to define the correlation between these spirometric measurements and hematologic markers of inflammation (white blood cells, monocytes, basophils, PGE1, IgG, and IgE). Systemic blood samples and spirometric measurements were obtained from 61 age-matched (33 +/- 9 years) healthy, asymptomatic smokers and nonsmokers, with similar self reported lifestyles (i.e., food, alcohol, vitamin consumption and exercise). Both male and female smokers self reported a higher coffee consumption (P < 0.05) compared to nonsmokers. Male smokers self-reported a trend toward current blue-collar versus white-collar occupation when compared with the nonsmokers. Body weight (77.6 +/- 16.6 kg) did not differ between the smokers and nonsmokers. The male nonsmokers were taller than the male smokers (P < 0.05). All subjects were asymptomatic and had clinically normal spirometry. Compared to male nonsmokers, the male smokers had lower FEF25-75% and FEF75-45% values (P < 0.05). No additional spirometric measurements, including FEV1/FVC, FEV1 and FVC were significantly different. The female smokers did not differ from the female nonsmokers (P < 0.05) in any of the spirometric endpoints measured. Thirteen statistically significant (P < 0.05) correlations involving inflammatory (white blood cells, monocytes, basophils, and PGE1) or immunologic endpoints (IgE) and spirometric measurements were observed in female smokers, female nonsmokers and male nonsmokers. No statistically significant correlations involving immunologic or inflammatory endpoints were observed in the male smokers. A better mechanistic understanding of the observed relationship between elevated hematologic inflammatory endpoints and reduced lung function may provide valuable insight into the clinical significance of these correlations.

Adult

Use of clozapine in a child with treatment-resistant schizophrenia.

BACKGROUND: Schizophrenia can be diagnosed in adults and requires treatment with antipsychotic medication. Clozapine is used effectively in adults with treatment-resistant schizophrenia but little is published on the use of clozapine in children. METHOD: Supported by parental consent and a second opinion, standardised observations were used to chart the progress of treatment with clozapine in a child in-patient detained under mental health legislation with severe drug-resistant schizophrenia and tardive dyskinesia. RESULTS: Sixteen months of clozapine treatment led to significant reduction of symptomatology with marked improvement in social functioning and diminished tardive dyskinesia. CONCLUSIONS: This case illustrates the successful use of clozapine in treatment-resistant childhood schizophrenia.

Antipsychotic Agents

The association between physical function and psychological problems in children with juvenile chronic arthritis.

Twenty-nine children with juvenile chronic arthritis, aged from 7 to 16 yr were studied using the Juvenile Arthritis Functional Assessment Report for Children and Parents questionnaires (JAFAR-C and JAFAR-P). The results showed that JAFAR-C and JAFAR-P were highly correlated (P < 0.001) with each other and also with a predicted JAFAR score (P < 0.05). The JAFAR score correlated with the arthritic joint count at the time of the study (P < 0.01), Steinbrocker classification (P < 0.001), pain score (P < 0.01) and stiffness score (P < 0.005). Evidence of psychological dysfunction was found in eight of the 29 children (27%). Six children (21%) scored 13 or more on the Rutter A(2) for parents and one patient scored more than nine on the Rutter B(2) for teachers. Only one child had a score on the Birleson self-rating scale that was high enough to suggest a likely diagnosis of depression. The median Lipsitt self-concept scale score was 86, that expected for a healthy population. There was no correlation between the psychological scores and any of the other functional measurements, although the numbers affected were small. There was no significant difference between type of arthritis at onset with regard to any of the scores obtained.

Activities of Daily Living

Effects of ductus arteriosus occlusion on pulmonary artery pressure during in utero ventilation in fetal sheep.

Seven fetal sheep were prepared to study the short-term effects of in utero ventilation and ductus arteriosus occlusion on pulmonary artery pressure and on fetal right ventricular function assessed using the right atrial pressure-right ventricular stroke volume relationship. Nine days post-surgery (140 days gestation), blood gas and haemodynamic values were obtained before and during in utero ventilation with 100% O2, and during ventilation with the ductus arteriosus occluded. Oxygen content increased significantly from 7.2 to 14.5 ml dl-1 with ventilation and remained elevated at 14.4 ml dl-1 with ventilation with the ductus arteriosus occluded. In utero ventilation produced a left to right atrial pressure gradient and depression of the right atrial pressure-right ventricular stroke volume relationship. Ductus arteriosus occlusion during in utero ventilation reduced the left to right atrial pressure gradient, and along with a decrease in pulmonary artery pressure, resulted in an upward shift of the right atrial pressure-right ventricular stroke volume relationship, but only to the preventilation level. This study indicates that the fetal right atrial pressure-right ventricular stroke volume relationship is significantly altered, both by changes in the left to right atrial pressure gradient and by changes in pulmonary artery pressure seen with in utero ventilation and subsequent ductus arteriosus occlusion.

Animals

Nitric oxide is an important determinant of coronary flow at rest and during hypoxemic stress in fetal lambs.

Fourteen fetal lambs were instrumented with atrial, coronary sinus, and arterial catheters and a proximal left circumflex coronary artery Doppler probe and were studied at a mean gestational age of 130 +/- 3 (SD) days, 7 +/- 2 days after surgery. Myocardial blood flow was assessed using 15-microns microspheres and Doppler flow velocities. In 11 fetuses, the maximal myocardial flow response to left atrial adenosine infusion was 802 +/- 215 ml.min-1 x 100 g-1, 3.5-fold greater than baseline flow. Acute fetal hypoxemia in six fetuses to an arterial PO2 of 8.8 +/- 0.8 mmHg and an arterial O2 content (CaO2) of 1.7 +/- 0.2 ml/dl was not associated with significant change in coronary perfusion pressure; yet left ventricular myocardial flow increased to 1,020 +/- 198 ml.min-1 x 100 g-1, a value significantly greater than that seen with adenosine (P < 0.05). Left atrial N omega-nitro-L-arginine (L-NNA), a competitive inhibitor of nitric oxide synthase (NOS), was infused at a dosage of approximately 1 mg.kg-1.min-1 for 60 min in 10 fetuses. Although L-NNA was associated with a significant increase in arterial pressure, left ventricular myocardial flow decreased (162 +/- 79 ml.min-1 x 100 g-1) as did myocardial O2 consumption (P < 0.05). Acute hypoxemia in five fetuses that received L-NNA was associated with significant further increases in systemic arterial pressure; however, left ventricular myocardial flow was only 771 +/- 237 ml.min-1 x 100 g-1, a value similar to that seen with adenosine and approximately 75% of that seen with acute hypoxemia alone. We conclude that nitric oxide plays an important role in the regulation of fetal myocardial flow during basal conditions as well as in the exuberant vasodilatory response associated with acute hypoxemic stress.

Adenosine

Bilateral internal mammary-to-pulmonary artery fistulas after a coronary operation.

A case of bilateral internal mammary artery-to-pulmonary artery fistulas presenting as recurrent angina late after revascularization is described. Objective evidence of ischemia was documented using stress electrocardiography and thallium-201 scintigraphy. The patient was managed conservatively to date with medical therapy. Fistula formation may complicate internal mammary artery bypass grafting and should be considered as a potential cause of recurrent angina.

Angina Pectoris

Psychiatric adjustment in end-stage renal disease: a follow up study of former paediatric patients.

Life-time psychiatric adjustment was studied in forty-five young adult survivors of a paediatric dialysis and transplantation programme and in a comparison group matched for age and sex. Renal patients reported more psychological problems in childhood and had lower self-esteem in adulthood, but adult lifetime psychiatric morbidity was comparable in both groups. There were differences in the pattern of psychiatric disorder with a trend for more depressive states in the renal group. Lower self-esteem was linked to early onset renal disease and to educational and social dysfunction. Results indicate relatively favourable adult adjustment of juvenile renal patients.

Adaptation, Psychological

Atrial myocardial blood flow during acute right ventricular pressure load and adenosine infusion in late gestation fetal sheep.

The purpose of this study was to investigate atrial myocardial blood flow in the fetus under conditions of acute right ventricular pressure load and adenosine infusion. Late gestation fetal sheep were instrumented for acute right ventricular pressure loading or adenosine infusion, and regional myocardial blood flow was measured at rest and under experimental conditions with radiolabeled microspheres and standard reference sample technique. Resting myocardial blood flow to the atria was less than half of ventricular flow per gram tissue. During the maximum tolerated pulmonary artery pressure load, right atrial peak systolic pressure rose significantly, and atrial blood flow increased 3-fold. The percentage of total myocardial blood flow received by the right atrium during maximal pressure loading increased from 4.3 +/- 1.4% to 5.9 +/- 1.6%, p < 0.05. Adenosine infusion was associated with a 4-fold increase in atrial myocardial blood flow and a 3-fold increase in ventricular and septal blood flow. The percentage of total myocardial blood flow to both atria also increased with adenosine infusion (right atrium, 3.8 +/- 0.4% to 5.4 +/- 1.3%, and left atrium, 4.2 +/- 0.8% to 6.9 +/- 2.0%, p < 0.05). We conclude the following: 1) at rest, fetal atrial myocardial blood flow is less than one half of ventricular myocardial blood flow per gram tissue; 2) fetal atrial blood flow increases more than ventricular blood flow with acute right ventricular pressure load or adenosine infusion; and 3) these data suggest that fetal atrial blood flow is regulated independently from ventricular blood flow and may be influenced by atrial work.

Adenosine

The changing pattern of children's dialysis and transplantation over 20 years.

The changing treatment and outcome for children with chronic renal failure (CRF) requiring renal replacement therapy (RRT) was assessed in children referred to the only paediatric unit in the North West Region of England between 1968 and 1988. There were 108 children. Referrals in consecutive 5-year time periods increased from 9 to 41 over the 20 years with the overall incidence of new referrals less than 15 years old reaching 8.5 per million childhood population in 1983-87, whilst the proportion of children under 5-years increased from 0% to 22%. The survival rate was better in those commencing RRT in the later years: 5-year survival 56% for the 1968-72 cohort vs 88% for 1978-82. The increasing number of referrals particularly among young children, coupled with improved survival rates have considerable implications when determining the provision of care for children with ESRD.

Adolescent

Indicator amount, temperature, and intrinsic cardiac output affect thermodilution cardiac output accuracy and reproducibility.

OBJECTIVE: To determine the accuracy and reproducibility of four thermodilution indicators (5-mL room temperature, 10-mL room temperature, 5-mL iced, and 10-mL iced injectates) at clinically relevant flow rates. DESIGN: Quasi-experimental study. SETTING: Animal research laboratory of a health sciences university. SUBJECTS: Six virgin western-breed ewes. INTERVENTIONS: Data were collected from six ewes that had ascending aorta electromagnetic flow probes and inferior vena cava occluders. Cardiac output was manipulated by inferior vena cava occlusion and isoproterenol infusion. Four thermodilution indicators were tested at high and low levels of cardiac output and compared with the electromagnetic flowmeter measurements of cardiac output. MEASUREMENTS AND MAIN RESULTS: The indicator amounts were determined from both injectate volume and temperature difference between the injectate and blood. Using 5-mL room temperature injectate as a reference, 10-mL room contained 2 x, 5-mL iced 2.1 x, and 10-mL iced 4.1 x the indicator amount of 5-mL room temperature injectate. Approximately 210 simultaneous thermodilution and electromagnetic flow measurements were made for each injectate over a flow range of 1.5 to 15.7 L/min. For the entire cardiac output range, systematic error was not present. However, the r2 value (.92) for the 10-mL iced injectate group was greater (p < .05) than that value (.79) for the 5-mL iced injectate group, while r2 values were .79 for the 10-mL room temperature group and .49 for the 5-mL room temperature group. At flow rates of < 4.7 L/min, r2 was not different among injectates, but reduced indicator amounts progressively overestimated output (p < .05), reaching 21% for the 5-mL room temperature group. At flow rates of > 7.7 L/min, the r2 value (.81) for the 10-mL iced group was greater (p < .05) than that value (.45) for the 5-mL iced group, while r2 values were .24 for the 10-mL room temperature group and .08 for the 5-mL room temperature group. Systematic error was not present. CONCLUSIONS: At low cardiac output levels, reduced indicator impairs accuracy but not reproducibility, a phenomenon that is perhaps related to indicator loss. At high cardiac output rates, reduced indicator impairs reproducibility. This phenomenon is probably related to low signal-to-noise ratio. Thermodilution indicator amounts should be tailored to the output range.

Animals

Psychosocial adjustment of adult survivors of a paediatric dialysis and transplant programme.

The social adjustment of 45 young adult renal patients who commenced treatment for end stage renal disease (ESRD) as children and of 48 age and sex matched controls were compared. Renal patients were less socially mature than controls. More lived with their parents, fewer had an intimate relationship outside the family, they had fewer school qualifications, and there was more unemployment among them. The majority, however, were in employment and the level of subjective stress and support derived from most of these areas was comparable in renal patients and in controls. Having a close relationship with a member of the opposite sex was the only domain in which renal patients reported more stress than controls. Early start of illness and current health problems were associated with poorer social outcome. A lifelong history of ESRD leads to suboptimal or delayed social functioning on conventional indicators. However this does not lead to increased overall distress in the patients about their social circumstances and quality of life does not appear to be substantially impaired.

Adaptation, Psychological

Phase-contrast cine MR angiography in chronic liver disease.

Thirty-one patients with portal venous hypertension underwent phase-contrast cine magnetic resonance (MR) angiography to validate the technique for assessment of main portal vein patency and blood flow direction. Correlative findings from Doppler ultrasonography, conventional angiography, and surgery were acquired in 30, 17, and 16 patients, respectively. Findings from MR angiography correlated well with those of the other methods for determining portal vein patency and flow direction. The main portal vein was patent in 29 patients and was thrombosed in two patients at MR angiography. With the use of a 40-mm slab projection acquisition that required 5 minutes, the splenic and superior mesenteric veins, as well as extensive varices (when present), were seen in the majority of cases. Phase-contrast cine MR angiography is an accurate method of rapidly assessing morphologic characteristics, patency, and flow direction of the portal venous system and thus is a useful method for evaluating the condition of patients with chronic liver disease.

Adult

Estrogen-induced left ventricular chamber enlargement in ewes.

We studied the chronic effect of administration of a single large intramuscular dose of 17 beta-estradiol on left ventricular chamber size and output in the ewe. Fourteen oophorectomized ewes were successfully instrumented and studied, with measurements made of left ventricular, aortic, right and left atrial pressures, left ventricular stroke volume, and left ventricular minor axis dimension. Unanesthetized ewes were studied before and 1, 2, and 3 wk after intramuscular administration of 0.6 mg/kg 17 beta-estradiol (7 ewes) or 1.5 ml sesame oil placebo (7 ewes). Left ventricular end-diastolic pressure-end-diastolic dimension (LVEDP-EDD) and left ventricular end-diastolic pressure-stroke volume (LVEDP-SV) relationships were quantified during graded inferior vena caval occlusion and volume infusion. Left ventricular end-diastolic diameter was larger after estrogen but not after placebo administration. The LVEDP-EDD relationship shifted progressively rightward, indicating left ventricular chamber enlargement in the estrogen group but was unchanged in the placebo group. The plateau limb of the LVEDP-SV relationship in the estrogen group shifted up from a mean stroke volume of 77.1-89.5 ml/beat and did not change in the placebo group. We conclude that administration of a single large intramuscular dose of 17 beta-estradiol resulted in left ventricular chamber enlargement and increased stroke volume in the ewe.

Animals

Prediction of repetition of parasuicide: with special reference to unemployment.

Economically active male parasuicides admitted to the Regional Poisoning Treatment Centre, Edinburgh in 1984 were divided into two groups--those with a previous history of parasuicide and those without. The two groups were compared on a number of psychosocial and clinical characteristics to examine which were related to repetition. A further analysis (of economically active male admissions in 1985 and 1986) tested the predictive value of these discriminating characteristics. By stratification of the population, the interaction of unemployment (a discriminator and a predictor of repetition) with certain other variables was examined. A final analysis examined the risk of repetition by duration of unemployment. Unemployment discriminated those with a past history of repetition from those with no past history and also predicted repetition within a calendar year of the initial episode. The 35-64 age group were particularly vulnerable to repetition if unemployed as were those in social classes I-III and those with a past psychiatric history (inpatient or outpatient). The relationship between unemployment and parasuicide was no longer significant when the population was stratified by presence or absence of personality disorder and history of previous parasuicide, suggesting that these might be confounding variables in the relationship. The particular vulnerability of the long-term unemployed (greater than one year) to repetition was confirmed.

Adolescent

Volumetric flow rates in the portal venous system: measurement with cine phase-contrast MR imaging.

OBJECTIVE: The purposes of this study were to (1) validate the accuracy of cine phase-contrast MR flow measurements within the portal vein, (2) develop a suitable protocol for using this method to measure volumetric flow rate in the portal venous system, and (3) use this protocol, with Doppler sonography as a reference, to measure portal venous flow in healthy volunteers and in patients with protal venous hypertension. SUBJECTS AND METHODS: Flow determinations were obtained in a model of fluid movement approximating blood-flow conditions in the portal venous system. A suitable protocol was based on consideration of the theoretical effects of (1) spatial resolution, (2) obliquity of the imaging plane to the direction of flow, and (3) signal-to-noise ratio of the signed quantitative velocity images (in three volunteers) on the accuracy and precision of flow measurements. This protocol was used to obtain cine phase-contrast MR images of the portal venous system in five volunteers and six patients. RESULTS: Values obtained with a flow phantom showed good accuracy of cine phase-contrast-measured vs actual volumetric flow rate (r = .995; p = .0001; MR rate = [0.94 x actual rate] + 65.6 ml/min; standard error of the y estimate = 67.3 ml/min). Velocity encoding and section thickness substantially influenced the signal-to-noise ratio of the velocity images, whereas flip angle and matrix size had only minimal effect. In volunteers and patients, portal volumetric flow rates determined by using MR images and Doppler sonography showed good correlation (r = .94; p = .0003). CONCLUSION: Our results indicate that cine phase-contrast MR imaging is a practical noninvasive method for measuring volumetric flow rates in the portal venous system.

Adult

Maximal myocardial blood flow is enhanced by chronic hypoxemia in late gestation fetal sheep.

The measurement of maximal myocardial blood flow gives information about the total cross-sectional area of the coronary resistance vessels. During a continuous left atrial infusion of adenosine (60 micrograms.kg-1.min-1), maximal myocardial blood flow was measured in 4 fetuses hypoxemic for a minimum of 5-8 days (pH = 7.33 +/- 0.01, arterial PCO2 = 49.8 +/- 4.2 Torr, arterial PO2 = 16.1 +/- 1.3 Torr, and arterial concentration of O2 = 5.3 +/- 1.2 ml/dl). These data were compared with an identically instrumented group of normoxemic fetuses (n = 7) following the same study protocol (pH = 7.38 +/- 0.02, arterial PCO2 = 43.1 +/- 3.8 Torr, arterial PO2 = 19.8 +/- 2.0 Torr, and arterial concentration of O2 = 7.9 +/- 1.0 ml/dl) (P < 0.05). At comparable arterial pressures, the maximal myocardial flow (ml.min-1.100 g tissue-1) for hypoxemic vs. normoxemic fetuses was 974 +/- 273 and 630 +/- 181 for the total myocardium, 986 +/- 367 and 602 +/- 192 for the left ventricular free wall, 1,025 +/- 346 and 614 +/- 178 for the septum, and 1,231 +/- 274 and 757 +/- 269 for the right ventricular free wall, respectively (P < 0.01). These data suggest that hypoxemia in the fetus can significantly alter the coronary vascular bed, which, if confirmed, would represent an important adaptation in the developing fetus.

Animals