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Biomedical subjects

G Davison

Publications and source records attributed to G Davison.

18 recordsLinked to original sources

Osteopontin expression is increased in the heritable cardiomyopathy of Syrian hamsters.

BACKGROUND: Osteopontin, a noncollagenous matrix protein, is transiently expressed in the heart after experimental cardiac injury, but its expression in states of continuing cardiac remodeling is unknown. We evaluated osteopontin expression in the heritable cardiomyopathy of the Syrian hamster. METHODS AND RESULTS: Hamster hearts were obtained for RNA isolation and analysis and in situ hybridization from two groups: normal control animals (n = 4) and untreated cardiomyopathic hamsters (n = 5). Osteopontin mRNA was 12-fold greater in cardiomyopathic hearts compared with normal controls (1.76 +/- 0.31 versus 0.14 +/- 0.04 arbitrary units normalized to GAPDH, mean +/- SEM, P < .05). In situ hybridization was used to define the origin of osteopontin in the heart. Osteopontin mRNA above background levels was not detected in sections from noncardiomyopathic hamster hearts but was readily detected in sections from cardiomyopathic hamsters, in which it originated in cells morphologically consistent with tissue macrophages. CONCLUSIONS: In the hamster, osteopontin is expressed in heritably cardiomyopathic hearts under conditions of chronic injury and repair, and the source of ostopontin message appears to be issue macrophage-like cells in foci of inflammation. This model could be used to evaluate the biological role of osteopontin in myocardial inflammation and remodeling.

Animals

Ultrasonic tissue characterization of end-stage dilated cardiomyopathy.

The clinical use of angiotensin-converting enzyme (ACE) inhibitors now represents the standard of care for the treatment of chronic congestive heart failure. We utilized ultrasonic tissue characterization to define potentially salutary effects of treatment with ACE inhibitors on the material properties of the heart and its potential influence on cardiac remodeling at the cellular level. Ten 1-month-old cardiomyopathic (CM) Syrian hamsters were treated with captopril (2 g/L water ad libitum), and 10 CM and 5 normal hamsters were maintained untreated for 9 months. Hearts were excised, and backscattered radio-frequency data were acquired from 1200 independent sites from each specimen with a high-resolution 50-MHz acoustic microscope for calculation of integrated backscatter. Treatment with captopril elicited relative decreases in left ventricular (LV) wet weight, LV calcium concentration and integrated backscatter (IB) in treated as compared with untreated cardiomyopathic hearts without affecting LV collagen concentration. The IB from hearts of treated cardiomyopathic hamsters was significantly less in both grossly normal regions of myocardium (P < 0.02) and scar tissue regions (P = 0.0005) as compared with IB from hearts of untreated hamsters. The reduced integrated backscatter from hearts of treated cardiomyopathic hamsters indicates direct alterations in the material properties of cardiomyopathic hearts after captopril therapy. The lower IB from scar tissue in the treated animals was associated with decreased scar tissue calcification, which represents a novel therapeutic effect of captopril. This is the first report that delineates direct effects of ACE inhibitors on the material properties of both scar tissue and grossly normal myocardium at the cellular level in experimental dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors

Cellular mechanisms of captopril-induced matrix remodeling in Syrian hamster cardiomyopathy.

BACKGROUND: Although angiotensin-converting enzyme (ACE) inhibitors have become a mainstay of treatment for chronic congestive heart failure (CHF), it is not known whether the cardiac remodeling effects are a secondary phenomenon, resulting from ACE inhibitors' hemodynamic actions of afterload reduction, or occur through an independent mechanism. METHODS AND RESULTS: We used ultrasonic tissue characterization to define potentially salutary effects of treatment with ACE inhibitors on the material properties of the heart and its potential influence on cardiac remodeling at the cellular level. Ten 1-month-old, cardiomyopathic (CM) Syrian hamsters and 6 normal (NL) hamsters were treated with captopril (2 g/L water ad libitum), and 10 CM hamsters and 10 NL hamsters were maintained untreated for 3 months. Hearts were excised, and backscattered radiofrequency data were acquired from 1200 independent sites from each specimen with a high-resolution 50-MHz acoustic microscope for calculation of integrated backscatter (IB). Treatment with captopril reduced left ventricular mass, calcium concentration, and IB in CM hearts without affecting myofiber size or collagen concentration. The IB from grossly normal regions of myocardium in NL hamsters, treated CM hamsters, and untreated CM hamsters was not significantly different. The IB from the microscopic regions of scar tissue in treated CM hamsters was significantly less (P = .0004) than that from scar tissue in untreated CM hamsters. CONCLUSIONS: The reduced IB from treated scar tissue components reflects specific alterations in the material properties (elastic stiffness, density) of fibrous regions in CM hearts induced by captopril. This is the first report that defines specific cellular effects of ACE inhibitors on the material properties of isolated components of cardiac tissue in experimental cardiomyopathy. These alterations in material properties of scar tissue components represent a potential mechanism for the salutary actions of ACE inhibitors in heart failure.

Animals

Post transfusion septicaemia 1980-1989: importance of donor arm cleansing.

AIMS: To determine the prevalence of Pseudomonas fluorescens on the arms of blood donors, and to elucidate one possible cause for its predominance (60% of cases during 1980-89) in exogenous post transfusion septicaemia (PTS). METHODS: Skin swabs were taken from the arms of 782 blood donors and cultured on to heated blood agar. After incubation, Oxidase reagent and the Gram stain were used to select non-fermentative Gram negative rods, which were then subcultured and identified using the Analytical Profile System (API) 20 NE system. RESULTS: Non-fermentative Gram negative rods were found on the arms of 11.7% of donors, Pseudomonas spp on 1.0%, and Ps fluorescens on the arms of 0.3% of donors. CONCLUSIONS: This evidence emphasises the absolute requirement for efficient skin cleansing of blood donors' arms to minimise the risk of exogenous PTS.

Bacteremia

Relaxation therapy lowers blood pressure more effectively in hypertensives with raised plasma norepinephrine and blunts pressor response to anger.

The effects of relaxation therapy on blood pressure and neural responses to "social stress"-anger instigation were determined in 30 male patients with mild primary hypertension. "Social stress"-anger induced increases in systolic and diastolic blood pressures (both p less than 0.01) and plasma norepinephrine (p less than 0.05) before therapy. Diastolic blood pressure before and during anger challenge were related to simultaneous plasma norepinephrine (r = 0.56, p less than 0.01 and r = 0.39, p less than 0.05). Relaxation reduced resting diastolic blood pressure (p less than 0.01), the reduction of blood pressure was related to baseline plasma norepinephrine (p less than 0.05). The pressor response of systolic blood pressure to anger challenge (p less than 0.02) was blunted by relaxation therapy. These findings suggested that noradrenergic control of blood pressure was amplified during stress and relaxation therapy was effective in lowering blood pressure and neutralizing the response to "social stress" anger instigation.

Adult

Behavioral vs beta-blocker therapy in patients with primary hypertension: effects on blood pressure, left ventricular function and mass, and the pressor surge of social stress anger.

We compared the relative effects of relaxation therapy, conventional hygienic techniques, and a beta-receptor blocker, atenolol, on control of arterial pressure, left ventricular mass, and diastolic function in patients with mild primary hypertension. Furthermore, we related these effects to baseline neural tone and its changes and assessed the efficacy of relaxation or the pressor surge of "social stress" anger. In group I left ventricular mass index was related to both systolic and diastolic blood pressure (r = 0.46; p less than 0.05). Plasma norepinephrine was related to age (r = 0.33; p less than 0.01). Slope was inversely related to both plasma norepinephrine (r = -0.29; p less than 0.05) and age (r = -0.31; p less than 0.05). Relaxation therapy reduced both supine systolic and diastolic blood pressures, 4.5% and 7.6%, respectively, but did not affect plasma norepinephrine. Hygienic informational therapy reduced plasma norepinephrine by 18%, (p less than 0.05) and did not change blood pressure. Blood pressure responders to nondrug therapy (i.e., diastolic blood pressure reduction of 7% or more) had a 7% reduction of left ventricular mass index (p less than 0.02). On the other hand, atenolol reduced systolic and diastolic blood pressure by 10% and 15%, respectively, (p less than 0.01) and improved left ventricular function by 17% (p less than 0.05) without a significant change in left ventricular mass index. Finally, relaxation therapy but not hygienic therapy reduced systolic blood pressures 4% and 6%, respectively (p less than 0.01), both before and during social stress anger.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Nonsurgical management of unruptured tubal pregnancy with intra-amniotic methotrexate: preliminary report of two cases.

Two cases of unruptured tubal pregnancy were managed conservatively by the aspiration and injection of 50 mg methotrexate into the amniotic sac with the use of a vaginal ultrasound transducer under local anesthesia. Both women experienced no pain or side effects and went home within 12 hours. Spontaneous menstruation began in both cases within 6 weeks of the procedure.

Adult

Primary hypertension: left ventricular mass and function, sympathetic nervous system activity, and therapy.

Left ventricular (LV) mass is a predictor of morbidity in patients with hypertension. To elucidate the mechanisms of left ventricular hypertrophy (LVH) in primary hypertension, we examined the relationships of LV mass, arterial blood pressure, and plasma norepinephrine--as a marker of sympathetic nervous system tone--in three populations of patients with mild or moderate hypertension. We found linking of neural tone with (a) arterial blood pressure in mild and moderate hypertension, (b) LV mass in moderate hypertension, and (c) diastolic function in mild hypertension, suggesting that neural tone is a factor in both the pathogenesis and the sequelae of hypertension. Additionally, elevated norepinephrine level may reflect subtle loss of diastolic function before hypertrophy is manifest. Both nondrug and drug therapy may regress LV mass after blood pressure reduction with disparate effects on neural tone.

Adult

Neurohumoral mechanisms and left ventricular hypertrophy: effects of hygienic therapy.

To determine the effects of hygienic (non-drug) therapy on blood pressure (BP) control and its relationship to sympathetic tone and left ventricular mass (LVM) in primary hypertension, plasma norepinephrine (NE) and renin activity (PRA), LVM, and nutritional and behavioral status were assessed in 76 borderline to mild hypertensives. Pretherapy plasma NE was related to diastolic blood pressure (DBP) and PRA (r = 0.24, P less than .05 and r = 0.37, P less than .01, respectively). Plasma NE of high renin patients (221 +/- 52) (mean +/- SD) was greater than that of normal renin patients (159 +/- 61, ng/l, P less than .01). LVM was related to systolic blood pressure (SBP) (P less than .001), DBP (P less than .01) and urinary sodium (P less than .05), and inversely related to PRA (P less than .01). Septal wall thickness was related to hostility (r = 0.42, P less than .05). After seven weeks of hygienic therapy, DBP was reduced by 6 mmHg (P less than .01). The change in SBP was related to baseline plasma NE (P less than .05) and inversely related to LVM (P less than .05). These results suggest that raised sympathetic tone may be a pathogenic factor in primary hypertension and that hygienic therapy lowers BP more effectively in patients with raised sympathetic tone and low LVM.

Adult

The ghost artifact.

A ghost artifact is produced when refraction of an ultrasound beam occurs in one part of a scanning plane. Image duplication or even triplication may result. This may lead to error of diagnosis and measurement. Ghost artifacts are commonly seen in transverse echograms of pelvic organs because the rectus muscle interposed between the transducer and the area of interest is acting as a lens and refracts the ultrasound beam. Three illustrative case reports are presented.

Adult

Antenatal diagnosis of homozygous beta thalassaemia in Mediterraneans in Australia.

Facilities for the antenatal diagnosis of homozygous beta thalassaemia have recently become available in Australia and in this paper, data from a series of 18 pregnancies examined at The Royal Women's Hospital, Melbourne, are analysed. Fetal blood was collected by fetoscopy and adequate samples were obtained in 16 cases (89%). In 5 pregnancies, fetal blood was shown to have a marked reduction in beta globin production (beta/alpha synthesis less than 0.030) and these pregnancies were terminated. Two pregnancies (11%) were lost in the immediate post-fetoscopy period and in a third pregnancy, neonatal death followed premature labour at 26 weeks' gestation. Seven babies were delivered normally at 36-40 weeks' gestation and cord blood studies excluded homozygous thalassaemia in all cases. The remaining pregnancy has yet to be delivered.

Australia

Prenatal diagnosis of the Meckel syndrome.

Prenatal diagnosis of the Meckel syndrome was made at 20 weeks of gestation from the findings of a biparietal diameter smaller than expected for gestational age, a grossly raised amniotic fluid alphafetoprotein level and a rapid growth of foetal macrophages after 20 hours culture. Termination at 23 weeks of gestation resulted in a male foetus with an occipital encephalocele, microcephaly, polydactyly, and bilateral polycystic kidneys. This case report emphasies the importance for genetic counselling of delineating the Meckel syndrome from the multifactorial cases of neural tube defects, and also illustrates, at least in some cases, that the syndrome can be diagnosed in utero.

Abnormalities, Multiple

The dynamic uterus revealed by time-lapse echography.

The dynamic aspects of the uterus have hitherto gone unrecognized by ultrasonographers. The inherent contractility of the uterus produces dynamic artifacts on static echograms that may lead to serious misdiagnoses. Four cases are presented which illustrated these dynamic changes. Time-lapse echography is proposed as a method of assessing uterine dynamics and improving diagnostic accuracy.

Female

Predictors of left atrial thrombus in mitral valve disease.

OBJECTIVE: To determine the risk factors for left atrial thrombus (LAT) and the prevalence of thrombi in cases of mitral valve disease whose severity was judged to necessitate surgical intervention. DESIGN: Hospital record review of all operative cases from 1982 to 1985. SETTING: A community serving a referral population encompassing 1.5 million people. Only two hospitals in the geographic area performed cardiac surgery, and both hospitals' records were reviewed. PATIENTS: All 372 patients who underwent either mitral valve replacement or open mitral commissurotomy. MAIN RESULTS: Twenty-six patients (7%) were noted to have LAT at surgery. Five preselected factors were significantly (p less than 0.05) associated with LAT in univariate analysis: female gender, prior history of embolism, prior anticoagulant therapy, mitral stenosis (MS), and atrial fibrillation (AF). In logistic regression analysis, only MS and AF remained as significant independent predictors of LAT. Mitral stenosis patients in sinus rhythm had a relatively low [2.4 +/- 3.3% (observed +/- 95% confidence interval)] likelihood of having an LAT. Likewise, mitral regurgitation patients in sinus rhythm (n = 139) had an extremely low (0.7 +/- 1.4%) prevalence of LAT. In contrast, MS patients in AF (n = 122) had a prevalence of LAT of 18.0 +/- 6.8%. CONCLUSIONS: These findings indicate that, overall, LAT in mitral valve disease may be less common than previous studies have suggested. In addition, mitral valve disease patients who remain in sinus rhythm appear to have a low risk of harboring an LAT. Conversely, MS patients, especially those in AF, appear to be at high risk of harboring an LAT. These results may be helpful in formulating strategies for the use of prophylactic anticoagulation in categories of patients with clinically severe mitral valve disease, or perhaps in estimating the likelihood of a cardiac source of embolism in mitral valve disease patients with suspected cerebral or peripheral emboli.

Confidence Intervals

Reducing unnecessary coronary care unit admissions: a comparison of three decision aids.

OBJECTIVE: To determine whether published decision rules for ischemic heart disease have practical value in reducing unnecessary admissions to coronary care units. DESIGN: Prospective cohort study. SETTING: A community hospital emergency room. PATIENTS: 235 consecutive patients presenting to an emergency room with a chief complaint of chest pain. MEASUREMENTS: Clinical information, including observations needed to use previously published decision aids, was collected on special forms at the time of the emergency room visit. Follow-up information was obtained from the medical records of patients who were admitted and by telephone interviews with patients who were discharged. The authors compared the residents' actual decisions with the predictions of the decision aids regarding their ability to predict complications (that is, to identify patients who needed admission or intensive care). MAIN RESULTS AND CONCLUSIONS: None of the decision aids could reduce unnecessary admissions without seriously increasing the rate of inappropriate discharges. However, within the clinically relevant subgroup of patients for whom the decision to admit or discharge was not obvious on clinical grounds (those without complications on presentation whom the residents chose not to discharge), the decision aids examined, used in combination to verify the need for admission, might have safely averted some unnecessary admissions.

Clinical Protocols