Biomedical subjects

M J Morton

Publications and source records attributed to M J Morton.

At least 19 recordsLinked to original sources

PubMed1999

Myocardial blood flow and coronary reserve in chronically anemic fetal lambs.

Chronic fetal anemia produces large compensatory increases in coronary blood flow in the near-term fetal lamb. To determine if increased coronary flow in anemic fetuses is associated with decreased coronary flow reserve or, alternatively, an increase in coronary conductance, we measured maximal coronary artery conductance during adenosine infusion before and during anemia. Isovolemic hemorrhage over 7 days reduced hematocrit from 30.6 +/- 2. 7 to 15.8 +/- 2.4% (P < 0.02) and the oxygen content from 7.3 +/- 1. 4 to 2.6 +/- 0.4 ml/dl (P < 0.001). Coronary blood flow increased from control (202 +/- 60) to 664 +/- 208 ml. min(-1). 100 g(-1) with adenosine to 726 +/- 169 ml. min(-1). 100 g(-1) during anemia and to 1,162 +/- 250 ml. min(-1). 100 g(-1) (left ventricle) during anemia with adenosine infusion (all P < 0.001). Coronary conductance, determined during maximal vasodilation, was 18.2 +/- 7.7 before and 32.8 +/- 11.9 ml. min(-1). 100 g(-1). mmHg(-1) during anemia (P < 0. 001). Coronary reserve, the difference between resting and maximal myocardial blood flow interpolated at 40 mmHg, was unchanged in control and anemic fetuses (368 +/- 142 and 372 +/- 201 ml/min). Because hematocrit affects viscosity, anemic fetuses were transfused with blood to acutely increase the hematocrit back to control, and conductance was remeasured. Coronary blood flow decreased 57.3 +/- 18.9% but was still 42.6 +/- 18.9% greater than control. We conclude that in chronically anemic fetal sheep coronary conductance is increased and coronary reserve is maintained, and this is attributed in part to angiogenesis as well as changes in viscosity.

Anemia↗

PubMed1998

The sequential effects of estrogen administration and hypertension on cardiac function in ewes.

OBJECTIVE: Our objective was to study the effect of estrogen administration and moderate hypertension on left ventricular size, pump function, and contractility in chronically instrumented ewes. STUDY DESIGN: Ewes were either given 0.06 mg/kg 17beta-estradiol intramuscularly (n = 8) or were made hypertensive (n = 6) by inflation of an occluder around the aorta and were studied weekly. After 3 weeks each ewe received the opposite treatment. RESULTS: Estrogen administration caused an increase in left ventricular chamber size at a given pressure, fractional shortening (21.9% +/- 2.9% to 28.5% +/- 3.7%), and stroke volume (1.4 +/- 0.3 mL/kg to 1.6 +/- 0.3 mL/kg). Subsequent hypertension further increased left ventricular size at a given pressure but decreased fractional shortening (20.0% +/- 4.4%) and stroke volume (1.3 +/- 0.3 mL/kg). With hypertension first, there was no left ventricular enlargement, even with subsequent estrogen administration, and there were no changes in left ventricular pump function. End-systolic pressure and stress-dimension relationships did not change with either treatment. The end-systolic wall stress-fractional shortening relationship was likewise unchanged, suggesting that neither treatment changed contractility. CONCLUSIONS: The left ventricle previously exposed to hypertension does not remodel when exposed to estrogen, and cardiac pump function decreases when the estrogen enlarged heart is faced with moderate, subacute hypertension.

Animals↗

PubMed1998

Adenosine receptor mRNA levels during postnatal renal maturation in the rat.

Adenosine may affect the pattern of intrarenal blood flow during renal development. It provides an angiogenic stimulus for the growth of new blood vessels and may be involved in compensatory renal growth. It is therefore of interest to investigate the expression of adenosine receptor genes during postnatal renal development. In the present study this was carried out by measuring adenosine receptor mRNA levels in rats aged between 2 and 60 days. The order of abundance of adenosine receptor mRNA levels in 60-day-old rats was A2A > A2B > or = A1 > A3. A1 receptor mRNA levels showed only small changes with increasing age although, by contrast, A3 receptor mRNA increased markedly with age with levels at 60 days twenty-fold greater than at 2 days. A2A receptor mRNA levels declined during renal maturation with transcript numbers four- to fivefold that at 12-18 days compared with numbers at 60 days. By contrast to the A2A receptor, there were no significant changes in the renal levels of A2B receptor mRNA during kidney maturation. During postnatal renal maturation, the levels of mRNA for A2A and A3 adenosine receptor subtypes undergo marked changes which may be related to functional maturation, morphological development, or both.

Animals↗

PubMed1998

A repeatable method for determination of carboxyhemoglobin levels in smokers.

Fourteen male smokers participated in ten afternoon test sessions to determine the daily variation in expired breath carbon monoxide (CO), and whole blood percent carboxyhemoglobin (%COHb), hemoglobin and hematocrit levels. Each individual's test session was conducted at approximately the same time of day to estimate CO-related measures under relatively stable conditions. Subjects smoked ad libitum prior to testing. The 'usual brand' cigarette was smoked during the first measurement week (sessions 1-5 held on Monday through Friday) and a research cigarette prototype which primarily heats rather than burns tobacco (TOB-HT) was smoked by 12 of the 14 subjects for 3 weeks prior to and during the second measurement week (sessions 6-9 held on Tuesday through Friday). Following the last 'usual brand' measurement session, subjects completed 21 days of ad libitum smoking of the TOB-HT cigarette before starting sessions 6-9 to allow acclimation to the TOB-HT research cigarette. Following session 9, 11 of the 14 subjects continued to smoke the TOB-HT cigarette for an additional 3 weeks and then participated in an additional test session (session 10). The data indicate that daily measurements of afternoon %COHb and expired breath CO values for an individual are reproducible when using this protocol. Carboxyhemoglobin and expired breath CO levels were elevated by 24.4 and 30.6%, respectively, after switching to the TOB-HT cigarette. This increase was not due to an increase in the number of cigarettes consumed since the subjects smoked an average of 21 cigarettes prior to the measurement session when smoking either their 'usual brand' or the TOB-HT cigarette.

Adult↗

PubMed1997

QSAR treatment of multiple toxicities: the mutagenicity and cytotoxicity of quinolines.

A series of 15 quinoline congeners were assayed for mutagenicity and cytotoxicity in the Ames test using strain TA100 bacteria. Statistical analysis of the data allowed simultaneous determination of the mutagenicity and cytotoxicity of each quinoline. These data were used to develop three quantitative structure-activity relationships (QSAR). In all three QSAR, the strength of the relationship between hydrophobicity (as measured by log P) and biological activity was similar as h was near 1 in all three cases. For the mutagenicity of these quinolines, both hydrophobic and steric interactions appear to be important. In contrast, the cytotoxicity is mainly affected by increasing hydrophobicity and by the addition of electron withdrawing substituents to the quinoline ring. Comparison to other QSAR from our laboratory and others lends support to these findings. Both simultaneous consideration of different biological activities and the comparison of newly developed QSAR with previous data for the purpose of lateral validation should be encouraged in future QSAR studies.

Models, Statistical↗

PubMed1997

Alteration of ascending thoracic aorta compliance after treatment with menotropin.

OBJECTIVE: Our purpose was to determine whether aortic size and compliance are altered by an exogenously induced rise in estrogen. STUDY DESIGN: Magnetic resonance imaging was used to determine the aortic cross-sectional area/aortic pressure relationship in nine premenopausal women before and after menotropin therapy. Simultaneous electrocardiograms, carotid pulse tracings, phonocardiograms, and brachial artery pressures were obtained before each magnetic resonance imaging acquisition. Ascending thoracic aorta cross-sectional area was obtained every 32 msec and aligned with brachial artery pressures extrapolated from the carotid pulse tracing, allowing construction of the ascending thoracic aorta cross-sectional area/aortic pressure relationships. Aortic cross-sectional area was normalized to body surface area, and the shifts in the position for the ascending thoracic aorta cross-sectional area/aortic pressure relationship were determined with use of analysis of covariance. RESULTS: Heart rate and aortic pressure were unchanged before and after menotropin treatment. Initial estradiol levels were < 20 pg/ml. After menotropin treatment (7.4 +/- 1.0 days) estradiol levels rose to 905 +/- 371 pg/ml (p < 0.0001). Ascending thoracic aorta cross-sectional area/body surface area was not significantly increased, adjusted y mean of 389 +/- 7 mm2/m2 before and 403 +/- 7 mm2/m2 after menotropin treatment (p < 0.24). The slope of the ascending aorta cross-sectional area/aortic pressure relationship, an index of aortic compliance, increased from 1.4 +/- 0.6 mm2/m2/mm Hg before to 1.7 +/- 0.6 mm2/m2/mm Hg after menotropin treatment (p < 0.001). CONCLUSION: In premenopausal women a short-term rise in estrogen induced by menotropin treatment is associated with an increase in aortic compliance. Aorta size is not significantly increased within this time frame.

Adult↗

PubMed1997

Renal adenosine A1 receptor binding characteristics and mRNA levels during the development of acute renal failure in the rat.

1. The binding characteristics and mRNA levels for renal adenosine A1 receptors were investigated in normal rats and rats with acute renal failure (ARF) induced by either glycerol or HgCl2. 2. Saturation isotherms determined from the binding of [3H]-1,3-dipropyl-8-cyclopentylxanthine ([3H]-DPCPX), a selective adenosine A1 antagonist, to renal membranes of untreated rats gave values of 0.62 nM for the equilibrium dissociation constant (Kd) and 19.9 fmol mg-1 protein for the density of binding sites (Bmax). No saturable binding was observed with [3H]-2-(p-(carboxylethyl)-phenylethylamino)-5'-N-ethylcar box amido adenosine ([3H]-CGS 21680), a selective adenosine A2a agonist. 3. By contrast to time-matched controls, renal membranes obtained from rats 16 and 48 h following the induction of ARF with glycerol, showed statistically significant increases (2-4 fold) in both Bmax and Kd for the binding of [3H]-DPCPX. No significant changes in the binding characteristics of [3H]-DPCPX were noted with membranes from rats 48 h following the production of ARF with HgCl2. 4. Adenosine A1 receptor mRNA levels were significantly elevated 0.5, 16 and 48 h following induction of ARF with glycerol, whilst no change was noted in mRNA levels for beta-actin at the same time points. No statistically significant changes in adenosine A1 receptor or beta-actin mRNA levels were noted 48 h after the induction of ARF with HgCl2. 5. This study indicates that glycerol-induced ARF in the rat is associated with an increase in renal adenosine A1 receptor density which appears to result from increased transcription of the gene for this receptor. An increase in adenosine A1 receptor density in renal resistance vessels may explain, at least in part, the enhanced renal vasoconstrictor response to adenosine in glycerol-induced ARF that was noted in a previous study.

Acute Kidney Injury↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1994

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↗

PubMed1994

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↗

PubMed1994

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↗

PubMed1994

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↗