Biomedical subjects
Publications and source records attributed to D A Robertson.
A 63 year old white woman presented with abdominal discomfort, anorexia, and weight loss. Investigations showed hepatocellular carcinoma with pulmonary metastases. The primary and secondary tumours resolved without specific treatment.
A 30 year old bodybuilder who had been taking anabolic steroids for 18 months presented with bleeding oesophageal varices. Serious liver disease secondary to anabolic steroids including peliosis hepatis, nodular hyperplasia and malignant change is well recognized. We report what is, to our knowledge, the first case of bleeding oesophageal varices associated with the use of anabolic steroids.
For cows on d 137 (n = 6), 180 (n = 8), 226 (n = 9) and 250 (n = 5) of gestation (Exp. 1), concentrations of insulin and glucose were two- to three-fold less (P less than .01) in fetal venous plasma than in uterine arterial plasma. Concentrations of growth hormone, conversely, were 10- to 20-fold greater (P less than .01) in fetal venous than in uterine arterial plasma. Concentrations of insulin and glucose in maternal and fetal plasmas and concentrations of growth hormone in maternal plasma did not vary with stage of gestation. Concentrations of growth hormone in fetal venous plasma, however, were greater on d 226 and 250 than on d 137 and 180. For cows (n = 6) on d 198 of gestation (Exp. 2), concentrations of insulin and glucose in maternal and fetal plasmas and of growth hormone in maternal plasma remained relatively constant in samples collected every 30 min for 3 h. In contrast, growth hormone concentrations in fetal venous plasma were highly variable and appeared to be episodic, with pulses of 10 to 60 ng/ml in amplitude. No significant correlations were found among concentrations of insulin, glucose and growth hormone in fetal venous plasma. When samples were collected every 15 min for 4 h from cows (n = 5) on d 198 of gestation (Exp. 3), episodes of growth hormone in fetal venous plasma were irregular in amplitude and frequency.(ABSTRACT TRUNCATED AT 250 WORDS)
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Patterns of oesophageal motility were recorded in 17 healthy volunteers and 12 patients with the irritable bowel syndrome. Recordings were taken at rest and under stress by hyperventilation, a dichotic hearing challenge and a cold pressor test. In healthy volunteers the dichotic hearing challenge was associated with a significant increase in the mean amplitude of oesophageal peristalsis from 69.9 mmHg to 82.4 mmHg (p less than 0.01) and in the percentage of simultaneous waves from 9.7% to 24.5% (p less than 0.01). The cold pressor test increased the peristaltic amplitude from 69.9 mmHg to 87.1 mmHg (p less than 0.001) and the percentage of simultaneous waves from 9.7% to 34.4% (p less than 0.01). Both manoeuvres were associated with increases in pulse and blood pressure. In patients with irritable bowel syndrome, the resting mean oesophageal peristaltic amplitude was higher than that seen in normal volunteers (95.9 mmHg v 69.9 mmHg p less than 0.05). Changes in oesophageal motility during stress were similar in these patients to those seen in normal subjects although the changes were not significant. This study refutes the hypothesis that symptoms of irritable bowel syndrome and their association with stress are attributable to increased sensitivity of oesophageal motility to disruption by stressful stimuli.
The Eysenck Personality Inventory and Hospital Anxiety and Depression scale were administered to 80 patients undergoing medical treatment for long standing inflammatory bowel disease: 22 patients were studied before the diagnosis was established and 40 patients with diabetes mellitus served as controls. High neuroticism and introversion scores were more prevalent in the patients with inflammatory bowel disease than controls (p less than 0.05) and these characteristics were as prominent in patients before diagnosis as in established cases. Introversion scores increased with the duration of disease (r = 0.51). Depression was uncommon, occurring only in patients with active chronic disease. Patients believed there was a close link between personality, stress and disease activity. Fifty six of the patients recognised factors that initiated the disease and in 42 this was thought to be a stressful life event or a 'nervous personality'.
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A patient with partial lipodystrophy, fatty liver and cirrhosis, and autoimmune thyroid disease is described. Treatment with thyroxine led to partial improvement in the hepatic abnormality.
Respiratory disease and subclinical pulmonary abnormalities are recognised complications of both coeliac disease (CD) and inflammatory bowel disease (IBD) but the pathogenesis of the lung disease remains uncertain. We have studied lung function, including permeability measured by clearance of inhaled technetium-99m diethylene triamine pentaacetic acid in 25 patients with IBD, 18 patients with CD on a gluten-free diet, and in 20 normal controls, all without respiratory symptoms. In IBD there was evidence of obstruction to airflow (mean forced expiratory volume in 1 s/forced vital capacity equals 75.8%, control 81%; p less than 0.05) but no change in pulmonary permeability (half-time clearance equals 70.3 vs. 69.2 min). In CD airflow was not significantly different from control (forced expiratory volume in 1 s/forced vital capacity equals 80%) but there was an increase in pulmonary permeability (half-time clearance equals 48.9 min; p less than 0.01). These findings suggest that the mechanisms of lung disease in CD differs from that in IBD and supports the hypothesis of a common mucosal defect in lung and small intestine in CD allowing increased permeability.
Ten normotensive subjects had their omnivore diet supplemented with increasing doses of linoleic acid in the form of safflower seed oil in order to examine the effects of this polyunsaturated fat upon leucocyte sodium transport. Increasing the dose ingested to the limits of tolerance produced a significant decrease in ouabain resistant sodium efflux (P less than 0.05) but no significant change in total or ouabain-sensitive sodium extrusion. Intraleucocytic sodium content was correlated with erythrocyte membrane oleic acid % (r = 0.368, P less than 0.05); leucocyte ouabain resistant flux was correlated with oleic acid % (r = 0.453, P less than 0.01) and linoleic acid % (r = -0.319, P less than 0.05). No such associations were observed with ouabain sensitive sodium extrusion. No changes in body weight or urinary electrolyte excretion were observed. It is concluded that, at physiological concentrations, membrane linoleic acid content influences transmembrane sodium fluxes but not through modulation of sodium pump activity. Furthermore, the beneficial effect of this dietary manoeuvre, observed previously with small increments of safflower seed oil, was not seen in this experiment so the hypotensive activity of this manipulation must be regarded as limited.
Glucosamine-6-sulfatase is a lysosomal enzyme which degrades glycosaminoglycans and is deficient in mucopolysaccharidosis type IIID. Human liver contains two major active forms of glucosamine-6-sulfatase, form A which has a single 78 kDa polypeptide and form B which has two polypeptides of 48 kDa and 32 kDa. A 1761 base pair cDNA clone encoding the complete 48 kDa polypeptide of form B was isolated. Form A is shown to be processed to form B with the 48 kDa polypeptide C-terminal to the 32 kDa polypeptide, and it is shown that C-terminal processing is limited to a region of thirty amino acids. The glucosamine-6-sulfatase sequence reveals homology with steroid sulfatase, a microsomal enzyme.
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Glucosamine-6-sulphatase (G6S), a lysosomal enzyme found in all cells, is involved in the catabolism of heparin, heparan sulphate, and keratan sulphate. Deficiency of G6S results in the accumulation of undegraded substrate and the lysosomal storage disorder mucopolysaccharidosis type IIID (Sanfilippo D syndrome). Regional mapping by in situ hybridization of a 3H-labelled human G6S cDNA probe to human metaphase chromosomes indicated that the G6S gene is localized to chromosome 12 at q14. The localization of the G6S gene to chromosome 12 was confirmed using the G6S cDNA clone in Southern blot hybridization analysis of DNA from human x mouse hybrid cell lines.
This case report describes the technique of balloon catheter dilatation of an ileocolic anastomotic stricture in a patient with Crohn's disease. The technique has an established role in the management of oesophageal strictures, and recently has been adapted by both radiologists and endoscopists in the management of gastric surgical stenosis. Isolated reports of its use in the colon are now emerging. Balloon catheter dilatation may be of value in selected patients with gastrointestinal strictures.
The evidence that hyperinsulinaemia represents an independent risk factor for cardiovascular disease is tantalizing but the hypothesis cannot be said to be proven. The inconsistencies arising from the major prospective studies require that further work be done. Hyperinsulinaemia may not carry the same implications in all subjects and its interactions with other risk factors and with blood glucose are not well described. Possible further research has been discussed and outlined at a recent meeting (Colwell, 1985). The suggestions include delineating the action of growth factors and insulin in defined serum-free tissue culture, and the use of more sophisticated culture models, such as smooth muscle covered by vascular endothelium. The choice of human or primate tissue is desirable because of the species specificity of the atherosclerotic lesions. Prospective trials of modifying peripheral insulin levels in treated diabetic patients are probably still impracticable. The case for attempting to achieve normoglycaemia in diabetes to avoid microvascular complications is strong, and current insulin treatment regimens accept peripheral hyperinsulinaemia as a consequence of achieving portal insulin concentrations sufficient to suppress hepatic glucose output. It is hard to envisage a trial to examine reduced peripheral insulin concentrations which would not give unacceptably poor blood glucose control. Current studies of different methods and degrees of control of blood glucose might be used to provide some indication of whether such a trial could ever be justified. The Diabetes Control and Complication Trial (DCCT) is a prospective multicentre study of intensive versus conventional insulin treatment in insulin-dependent diabetic patients in the USA, and the UK Prospective Study of therapies of maturity onset diabetes (UKPS) is following patients not satisfactorily controlled on diet, randomized to different treatment modalities. These may produce some evidence within the next few years, on insulin concentrations and complications (Tattersall and Scott, 1987). Should any of this change current management of non-insulin-dependent diabetes? Despite claims of enthusiasts, special treatment regimens with intensive exercise, a particular oral agent or the addition of sulphonylureas to insulin therapy are either not generally applicable or have little theoretical basis (Martin, 1986). Current 'good practice' in Europe as put forth in a consensus document (Alberti and Gries, 1988), recognizes the need to address risk factors other than diabetes in the management of the non-insulin-dependent diabetic patient.(ABSTRACT TRUNCATED AT 400 WORDS)
Platelet-activating factor (PAF) is an autacoid whose cardiovascular actions include a potent negative inotropic effect. The mechanism of this decrease in myocardial contractility is still at issue, as both a decrease and an increase in trans-sarcolemmal Ca++ influx have been reported. Because changes in intracellular sodium activity (aiNa) are known to influence myocardial contractility, we investigated whether PAF affects aiNa. Thus, we have measured contractile responses to PAF (1 nM-1 microM) in isolated guinea pig right ventricular papillary muscles paced at constant rate, and recorded transmembrane action potential and aiNa with conventional and sodium-selective microelectrodes, respectively. Our findings suggest that PAF does not affect slow inward Ca++ current, because PAF neither affected nor prevented histamine-induced restoration of contractile responses in K+-depolarized papillary muscles. On the other hand, we found the negative inotropic effect of PAF to be associated with a shortening of the action potential duration and with a decrease in aiNa. The specific PAF antagonist compound CV-3988 inhibited all three electro-mechanical responses. Our findings imply that the decrease in contractile force caused by PAF may depend on the reduction in aiNa; as aiNa falls, intracellular Ca++ may be lost via the Na+/Ca++ exchange and contractility decreases. The shortening of the action potential duration by PAF may reflect a decrease in Na+ influx and the consequent reduction in aiNa.
A non-operative method of palliation in malignant obstructive jaundice was used in 14 patients in whom a biliary stent could not be placed endoscopically. A guide wire was manipulated through the obstructing lesion through the percutaneous transhepatic route and retrieved through an endoscope. The stent was then fed through the endoscope over the guide wire and across the biliary stricture. There were no early complications, and worth-while palliation was obtained in most cases. The success rate for placing an endoscopic stent increased in this unit from 69 to 97% with the introduction of this technique.
A radiolabelled 50-base oligonucleotide complementary with the measles virus gene encoding the nucleocapsid was used as a probe to identify persistent measles virus genome in the lymphocytes from patients with autoimmune chronic active hepatitis (AICAH). Positive hybrids were found in 12 of 18 patients, and correlated strongly with high antibody titres to measles. Among the 45 controls, positive hybrids were found in 1 patient with measles, 1 of 3 patients with systemic lupus erythematosus, and 2 of 4 patients with cryptogenic cirrhosis. Persistence of part of the measles virus genome in AICAH may have important implications in the pathogenesis of the liver disease, and possibly in other disorders such as systemic lupus erythematosus, multiple sclerosis, and Paget's disease where an abnormal immune response to measles has been observed.