Doppler color-flow echocardiographic recognition of left ventricular pseudoaneurysm.
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Biomedical subjects
Publications and source records attributed to R Hall.
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The metabolism of 17 beta-estradiol in both estrogen receptor positive and negative human breast cancer cell lines has been compared. Initial experiments in which confluent cells were exposed to 1 nM [3H]17 beta-estradiol for 24 h, revealed that the main metabolites formed by estrogen receptor positive MCF-7 and ZR-75-1 cells were 17 beta-estradiol-3-sulfate (together with lesser amounts of estrone sulfate) and estrone. In estrogen receptor negative cell lines, production of estrogen sulfates was either significantly lower (MDA-MB-231 cells) than receptor positive cells, or failed to be produced at all (MDA-MB-330 cells). In both these receptor negative cell lines, production of estrone was significantly higher than in receptor positive cells. Accumulation of estrogen sulfates resulted from attainment of a steady state between synthesis catalysed by estrogen sulfotransferase and degradation catalysed by estrogen sulfatase. The former was present in the cytosol and showed a very high affinity for 17 beta-estradiol and estrone (low nM range). Complex initial velocity versus estrogen substrate curves were obtained with enzyme purified 106-fold by affinity chromatography. Such curves were consistent with a rate equation of degree 3 or 4 and suggest the presence of cooperatively linked dependent binding sites.
The regulation of bile acid synthesis was studied in rabbits after interruption of the enterohepatic circulation by choledochoureteral anastomosis. Total daily bile acid output was 772 +/- 130 (SD) mumol/24 h, of which greater than 95% was glycocholic acid. Administration of deoxycholic or cholic acid or their conjugates (300-800 mumol) or gall-bladder bile failed to down-regulate endogenous bile acid synthesis. In contrast, chenodeoxycholic acid administration did down-regulate bile acid synthesis, but this effect was related to the formation and excretion of lithocholic acid. This observation was confirmed by the finding that i.v. infusion of 10-20 mumol of either lithocholic acid or 3 beta-hydroxy-5-cholenoic acid significantly reduced cholic acid synthesis. Thus monohydroxy bile acids, derived from either hepatic or intestinal sources, participate in the down-regulation of bile acid synthesis.
In order to investigate the mechanisms by which arginine and L-dopa cause GH release in humans we measured the GH response to GHRH 1-44 (200 micrograms i.v.), arginine (30 g i.v. over 30 min) and L-dopa (500 mg orally) administered alone and 120 minutes following pretreatment with GHRH 1-44 (200 micrograms i.v.) in normal male subjects. Prior GHRH administration abolished the GH response to subsequent GHRH. Arginine infusion induced a rise in GH levels maximal at 45 min. Following GHRH pretreatment the GH response to arginine was enhanced, with peak values of 19.3 +/- 6.4 vs 53.3 +/- 16.5 mU/l (mean +/- SEM) respectively (P less than 0.02). L-dopa alone induced a rise in GH levels maximal at 90 min (17.6 +/- 7.4 mU/l, mean +/- SEM) but this rise was abolished by pretreatment with GHRH.
A modification of the single optotype Sheridan Gardiner test for pre-school children has been used to measure visual crowding. A significant 'crowding effect' has been found in children between the ages of 3 and 6 years with a general decrease in the effect over the pre-school years. The 'crowding' in 5-7 year olds is not significantly greater than that found in adults. No significant difference has been found in the extent of crowding using the test at 3 m rather than the normal 6 m viewing distance, although in general the test has been found to be practically easier with better co-operation at 3 m for the younger children. For these reasons, this particular test at 3 m would seem to be well suited to acuity testing in pre-school children, when an acuity equivalent to Snellen values is required.
Vibrio cholerae O1 A-B- vaccine strain JBK 70 and A-B+ CVD 101 prepared by recombinant DNA techniques from pathogenic EI Tor Inaba N16961 and classical Ogawa 395, respectively, were fed to 38 volunteers in single doses of 10(4) to 10(10). Although severe diarrhea did not occur in any vaccine, more than one-half developed mild diarrhea. These attenuated strains colonized well and elicited prominent vibriocidal and antitoxic (CVD 101) antibody responses. Recipients of a single dose of JBK 70 were significantly protected when challenged with 10(6) wild-type N16961. Diarrhea occurred in 7 of 8 controls but in only 1 of 10 vaccines (P less than 0.003, 89% vaccine efficacy), demonstrating the potency of immune mechanisms that do not involve cholera antitoxin. Further derivatives were prepared to explore the pathogenesis of the residual diarrhea, considering that either intestinal colonization by the vaccine itself or accessory toxins might be responsible. CVD 102, an auxotrophic mutant of CVD 101, did not cause diarrhea but colonized poorly and elicited feeble immune responses. Derivatives of JBK 70 and CVD 101 (CVD 104 and 105) deleted of genes encoding the EI Tor hemolysin still caused mild diarrhea. Genetically engineered strains can be colonizing, highly immunogenic, and protective single-dose oral vaccines, but they must be further attenuated before they can be considered for use as public health tools.
Among steps to improve immunisation rates in Clwyd an advisory service was introduced for children with immunisation problems. We report on setting up the service and the first two years of running it; during this time 191 children attended. Influencing parental and professional attitudes through education, counselling, and the demonstration of good practice is emphasised.
Following the discovery and biochemical characterization of natural somatostatin its action profile has been thoroughly investigated. Although the name somatostatin was coined in virtue of its growth hormone release-inhibiting properties, a number of central and peripheral endocrine and paracrine actions have been ascribed to this peptide. Its inhibitory effect on a series of pituitary and gastrointestinal hormones has characterized somatostatin as a classical brain-gut hormone. Circulating and tissue levels of somatostatin and its possible physiological role are analyzed and clinical implications are drawn.
Serum prostatic acid phosphatase and prostate-specific antigen have been measured in a group of 106 cases of newly diagnosed prostate cancer. The serum levels of the tumour markers have been correlated with the clinical and ultrasound staging of the prostate cancer at diagnosis. All patients were managed by a deferred treatment policy. Patients without detectable metastases at presentation have been assessed after a period of 2 years to determine if the level of serum tumour markers at diagnosis could predict subsequent disease progression. The study has demonstrated that a combination of immunologically measured acid phosphatase and prostate-specific antigen is the best method of assessing the prognosis of an individual prostate cancer at the time of presentation.
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Single or infrequent observations in patients or animals with autoimmune thyroid disease (AITD) have failed to elucidate the exact sequence of pathogenetic events leading to thyroid cell destruction. A detailed serial morphological and functional study of experimental AITD (EAITD) in the female AUG rat was therefore undertaken. Following induction of EAITD with thyroglobulin (Tg) in adjuvant antibodies to Tg were detectable one week after the initial immunization, at which stage Ia positive vascular endothelium was observed within the thyroid. This was followed by large numbers of Ia positive dendritic-like cells. With time, in almost all the animals whose titre of Tg antibody rose above a critical level, lymphocytic infiltration was observed consisting mainly of Ia positive B cell aggregates with fewer scattered T cells. This was associated with raised levels of serum TSH and concomitant focal follicular hyperplasia and necrosis. Expression of Ia was mainly restricted to the outer epithelial wall of follicular thyrocytes in direct contact with invading lymphoid cells, although occasional staining on the internal apical membrane was observed as a late event in the destructive process. The Ia expression on thyroid epithelial cells was only observed in areas of thyroid lymphoid infiltration. The immune infiltration of the thyroid in the AUG rat appears to be very similar to that observed in Hashimoto's thyroiditis, with the exception that Ia was not regularly observed on the apical surfaces of thyrocytes. Whether or not the diminished or absent epithelial Ia expression contributes to the spontaneous recovery of the disease observed in this model remains to be resolved.
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The present study evaluated the treatment and generalization effects of implementing a peer social initiation intervention with four severely withdrawn maltreated preschool children. Positive social response and initiation data were collected across the treatment (a playroom) and the natural classroom setting. A reversal design superimposed on a multiple baseline was used to evaluate the effectiveness. The results indicated increases in positive social responses and initiations across treatment and generalization settings. Follow-up data for two children indicated time and setting-time generalization effects. Teacher reports validated treatment gains.
The effects of hypothyroidism in utero, and continuing into postnatal life, on the central turnover of catecholamines, noradrenaline and dopamine were studied in rats. Rats were rendered hypothyroid in utero by treating pregnant females with methimazole in the drinking water. In two groups goitrogen treatment continued for 3 or 10 weeks postnatally. Methimazole treatment in utero did not produce significant changes in noradrenaline, dopamine or tyrosine content in either the hypothalamus or striatum. Three weeks' postnatal treatment reduced tyrosine specific radioactivity in the anterior hypothalamus and dopamine specific radioactivity in the striatum. Ten weeks' treatment increased dopamine content and reduced noradrenaline synthesis in the mediobasal hypothalamus and a reduction in tyrosine content in the anterior hypothalamus. These data suggest that hypothyroidism restricted to intrauterine life does not produce permanent changes in adult catecholamine neuronal function. Long term hypothyroidism produced localized changes, suggesting a specific rather than general effect.
Cholinergic receptor blockade has been shown to abolish GH secretion in a variety of physiological and pharmacological situations in normal subjects. We have investigated the effect of pirenzepine on nocturnal GH secretion in young adult patients with Type I insulin-dependent diabetes mellitus. Five patients (three male, two female; aged 20-27 years) were studied in a randomized order on two days separated by at least 1 week. All patients showed episodes of slow wave sleep on each occasion and this was followed by peaks of GH release when placebo alone was administered (range of GH peaks 6-115 mU/l). In contrast, cholinergic muscarinic receptor blockade with pirenzepine (100 mg orally at 2200 and 2400 h) completely abolished nocturnal GH release in each individual without altering the occurrence of slow wave sleep itself. Mean plasma glucose levels at each sampling time between each study did not differ significantly. The ability to abolish nocturnal GH secretion may be important in the field of diabetes, since excess GH secretion is implicated in several acute metabolic and chronic microvascular complications of the disease.
The syndrome of inappropriate TSH secretion is described in a euthyroid girl and her father. Based on nuclear T3 binding studies in fibroblasts, generalized tissue resistance was associated with a lower binding affinity for T3 in nuclear extracts suggestive of a structurally abnormal receptor for T3. Early recognition of the syndrome and observation of the short-term response to thyroid medication prevented unnecessary trials of antithyroid medication and later radical ablative thyroid treatment.
A retrospective study was undertaken to assess the influence of known ischaemic heart disease on the operative and the long-term survival of patients undergoing elective repair of an abdominal aortic aneurysm. One hundred and seventy-one patients underwent elective surgery between June 1977 and December 1983. The patients were divided on routine clinical grounds into cardiac and noncardiac groups. Ninety-five patients had a history of heart disease and/or an abnormal resting pre-operative ECG. Seventy-six patients had no history of heart disease and a normal pre-operative resting ECG. Two of the seven operative deaths were due to myocardial infarction with one each from the cardiac and noncardiac groups. Eight patients suffered an acute myocardial infarction with five from the cardiac and three from the noncardiac group and this was not significantly different. The overall survival of 95% at 1 year and 76% at 5 years closely follows the age/sex matched Australian population. The survival at 1 year in the cardiac group was 97% and 95% in the noncardiac group. The 5 year survival was 72% and 79% respectively. During follow-up to December 1984, 11 patients died from ischaemic heart disease with six from the cardiac and five from the noncardiac group. No significant difference was found between the two groups in the incidence of myocardial infarction or the short- and long-term survival. This study does not support a more aggressive approach to coronary artery disease in the pre-operative management of patients with abdominal aortic aneurysm.