Biomedical subjects
Publications and source records attributed to G Roberts.
We report on fetal hydrops presenting at 18 weeks of gestation and diagnosed as beta-glucuronidase deficiency. The parents were first cousins and there were 2 previous similar fetal deaths. beta-Glucuronidase was absent in cultured fetal fibroblasts and lymphoblasts but was normal in the tested relatives. The activities of other lysosomal enzymes were normal.
Triple-phase bone scintigraphy was used to evaluate tissue viability in the forelimb of a dog after gunshot injury. This technique was reliable, noninvasive, and easily performed. It was used to complement radiography by providing functional, rather than structural, assessment of tissues on the basis of regional vascular patterns. In this dog, vascular impairment caused by trauma appeared as photopenic or "cold" spots during immediate (vascular), soft tissue and bone phases of the scintigraphic study. On the basis of gross morphologic and scintigraphic findings, forelimb amputation was performed.
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"The philosophy of Community Care has resulted in the closure of several mental hospitals in this country. The ethos of the Worcester Development Project saw the closure of St Wulstan's and Powick Hospitals, and their replacement by a community-based service. This paper briefly describes the outcome of a three-year retrospective study completed in 1988 following the closure of both hospitals. The findings provide a comparison of the two hospitals, including details of the destination of all the patients. It is suggested that the term 'hospital replacement' might be preferable to 'hospital closure'." "The Worcester Development Project began in 1968 when the Department of Health and Social Security brought together the Worcester and Kidderminster Hospital Management Committee and the County Council in a co-ordinated joint planning venture. Powick Hospital was chosen as the location for testing the hypothesis that closing a mental hospital and replacing it with general hospital psychiatric units, supported by a variety of community facilities, would provide a more economical and better service. This paper describes the outcome of this unique opportunity to study the problems involved in closing a mental hospital and its replacement with other facilities."
Although delusion remains one of the basic problems in psychopathology, attempts to understand its pathogenesis have been dominated by unsubstantiated speculation. Previous psychodynamic formulations have recently given way to increasing interest in measurement, and testing of models derived from cognitive psychology. However, the formation, elaboration, and persistence of delusional beliefs may be an expression of the convergence of numerous causal influences, each exerting an effect at a different stage in the evolution of the belief. This review takes a structured overview of the literature, placing the numerous part theories and scant experimental findings within a general model of delusional development. It argues for a return to systematic research on symptoms rather than complex diagnostic formulations to facilitate better understanding of the development of delusional disorders and stimulate further interest in therapeutic intervention.
The effects of Mg2+, K+ and ATP on a H-ATPase activity from a native plasmalemma fraction of oat roots were explored at 20 degrees C and pH 6.5. In the presence of 3 mM ATP and no K+, H-ATPase activity vs. [Mg2+] approached a monotonic activation but it became biphasic, with a decline above 3 mM Mg2+, in the presence of 20 mM K+. Mg2+ inhibition occurred also in K-free solutions when [ATP] was lowered to 0.05 mM. Also, an apparent monotonic H-ATPase activation by [K+] at 3.0 mM ATP was transformed in biphasic (inhibition by high [K+]) when [ATP] was reduced to 0.05 mM. The best fits of the ATP stimulation curves of hydrolysis satisfied the sum of two Michaelian functions where that with higher affinity had lower Vmx. Taking into consideration all conditions of activity assay, the high-affinity component (1) had a Km about 11-16 microM and a Vmx around 0.14-0.28 mumol Pi/mg per min whereas that with lower affinity (2) had a Km of 220-540 microM and a Vmx of 0.5-1.0 mumol Pi/mg per min. Km2 was markedly affected by the [K+] and [Mg2+]; at optimal concentrations of these cations (1 mM Mg2+ and 10 mM K+) it had a value of 235 +/- 24 microM which was increased to 540 +/- 35 microM at 20 mM [Mg2+] and 60 mM [K+]. In addition, Vmx1 was reduced to about a half when the concentrations of Mg2+ and K+ were increased to inhibitory levels. These results could be explained by the existence of two different enzymes or one enzyme with two ATP sites. In the second case, we could not tell at this stage if both are catalytic or one is regulatory.
Surprisingly inappropriately high levels of plasma atrial natriuretic factor (ANF) in subjects with Bartter's syndrome are lowered by indomethacin therapy. Indomethacin in normal man causes sodium retention. One might therefore expect plasma ANF to increase in subjects taking indomethacin as a secondary phenomenon. On the other hand a decrease of plasma ANF in normal man similar to that reported in Bartter's subjects may explain the sodium retention caused by the drug in normals. We have studied plasma ANF before and during a two litre, four hour normal saline infusion in eight healthy male subjects both before and following five days of oral indomethacin. Plasma ANF basally was 4.2 +/- 0.9 pmol/l (mean +/- SEM) on no drug and 5.2 +/- 0.6 pmol/l on indomethacin (NS). It increased in response to saline in both studies (7.8 +/- 1.5 pmol/l after two litres of saline on control day; 10.6 +/- 1.5 pmol/l on the drug at the equivalent time, both p less than 0.05 vs basal value). Overall response to saline as assessed by the area under the curve above the basal value of hourly measurements, was not different in the two studies. Basal serum aldosterone and plasma renin activity were reduced by indomethacin. Urinary sodium excretion was not different between groups during the 12 hours before, four hours during and eight hours after the infusion. We have shown that indomethacin does not alter basal or saline stimulated plasma ANF in normal man, a finding in contrast to that reported in subjects with Bartter's syndrome. The sodium retention caused by indomethacin in normal man is not therefore due to a decrease of plasma ANF.
In chemonucleolysis, accuracy of injection can be in doubt if the patient fails to respond. Discography preceding chemonucleolysis is associated with increased neurologic complications. Biplane fluoroscopy may fail to provide a clear picture on many occasions. The serum keratan sulphate levels were estimated in patients undergoing chemonucleolysis to ascertain if this could be used as a biochemical indicator to confirm accurate needle placement and to predict outcome. Serum keratan sulphate levels rose significantly following chemonucleolysis during the first 3 days (P less than 0.01). The rise was not significantly different, however, in patients who had improvement in their leg pain from those who did not improve (P = 0.35). Serum keratan sulphate level estimation before chemonucleolysis and at 24 or 48 hours following the procedure can be used to confirm accuracy of needle placement, but the rise in keratan sulphate is not predictive of the clinical outcome of the procedure.
Hypertension is linked to the development of nephropathy in Type 1 diabetes. Total exchangeable sodium is elevated in patients with Type 1 diabetes in good metabolic control, and correlates with blood pressure. Atrial natriuretic factor has been shown to have effects on sodium and blood pressure homeostasis in man. Basal and NaCl-stimulated plasma atrial natriuretic factor was therefore studied in 33 patients with Type 1 diabetes. Seventeen had no evidence of nephropathy, 11 had incipient nephropathy (albumin excretion rate 20-199 micrograms min-1) and five had overt nephropathy. Seventeen age- and sex-matched normal control subjects were also studied. Subjects fasted from 2200 h, rose at 0745 h and remained ambulant until 0945 h. After 15 min supine, 2 l 0.15 mmol l-1 NaCl was infused over 4 h. Basal erect (0945 h) plasma atrial natriuretic factor was 4.2 +/- 0.5, 3.5 +/- 0.4, 2.5 +/- 0.2, and 2.5 +/- 0.3 pmol l-1 in the control, non-nephropathic, incipient-nephropathic, and overt nephropathic diabetic groups, respectively (all NS). Levels in all groups increased in response to NaCl infusion, and the responses were not different between groups. Urinary sodium excretion for 12 h before NaCl infusion was not different between groups, but during the 12 h after the start of the infusion was significantly (p less than 0.05) less in the Type 1 diabetic group without nephropathy than in the control group. These results suggest that atrial natriuretic factor does not play a major role in the development of changes in sodium balance which are associated with Type 1 diabetes and nephropathy.
The pathogenesis of hypertension associated with Cushing's syndrome is incompletely understood. We have studied basal and saline-stimulated levels of plasma atrial natriuretic hormone in 10 subjects with active Cushing's syndrome (8 F: 2 M), aged 43 +/- 4 years (mean +/- SEM). Ten age- and sex-matched normal control subjects were also studied. Subjects fasted from 22.00 h, rose at 07.45 h, and remained ambulant until 09.45 h when blood was taken for plasma ANH, plasma renin activity and serum aldosterone. Subjects then rested supine until 10.00 h when blood was again taken, and blood pressure recorded. Then, while subjects remained supine, 21 of 0.9% NaCl were infused between 10.00 and 14.00 h. Blood was taken hourly. Basal plasma ANH was 8.0 +/- 0.9 pmol/l in Cushing's subjects and 6.9 +/- 2.5 pmol/l in controls. Levels increased in response to saline in both groups, and became significantly higher in the group of patients with Cushing's syndrome (14.00 h level 21.3 +/- 3.9 vs 10.4 +/- 1.9 pmol/l; p less than 0.05). Serum aldosterone and plasma renin activity were not different between groups. Mean blood pressure was higher in patients (114 +/- 4 vs 91 +/- 7 mmHg; p less than 0.05). Urinary sodium excretion was not different between groups before saline, but during the four hours of saline was higher in Cushing's subjects (133 +/- 12 vs 67 +/- 11 mmols; N = 6; p less than 0.05). Our results suggest that during salt loading the exaggerated natriuresis seen in the Cushing's group may have been caused by ANH.
The immunomodulator ditiocarb sodium (sodium diethyldithiocarbamate, DTC, CAS 148-18-5) is finding increasing use in treating AIDS-patients. Using a macro broth dilution method the minimal inhibitory concentrations and minimal fungicidal concentrations of DTC were studied for 76 fungal strains (54 species) and a broad spectrum of direct antifungal activity was found. All 6 Candida albicans strains tested were inhibited by 1.2 micrograms DTC/ml, a concentration achievable by i.v. administration of DTC in doses as presently used for immunomodulation. All strains of Cryptococcus were inhibited by DTC in concentrations of 2.5 micrograms/ml. In combination with amphotericin B, DTC showed a synergistic mode of action for 6 out of 7 Cryptococcus neoformans strains (checkerboard technique). As far as the direct antifungal activity of DTC was tested (11 strains, 5 species), the combination with amphotericin B or flucytosine showed no antagonistic mode of action. The augmentation of host defences by the immunomodulating agent DTC could become an adjunct to conventional therapy in immunocompromised patients with systemic fungal infections.
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Subjects with Type 2 diabetes have been reported to have elevated total exchangeable sodium when compared with normal subjects. Sodium retention may contribute to the development of hypertension in these subjects. Atrial natriuretic factor may play a role in sodium and blood pressure homeostasis in Type 2 diabetes. We have studied plasma atrial natriuretic factor in 17 subjects with Type 2 diabetes (9M:8F; aged 49 +/- 2 years) (mean +/- SE) and in 17 age- (49 +/- 2 years) and sex-matched controls. Mean fasting blood sugar was 8.3 +/- 0.6 mmol l-1 in the diabetic subjects. After fasting from 2200h, subjects remained upright from 0745h until 0945h when blood was taken for plasma atrial natriuretic factor, plasma renin activity and serum aldosterone. Two litres of 0.15 mmol l-1 NaCl was infused intravenously between 1000h and 1400h while the subjects remained supine. Blood was taken hourly. At 0945h plasma atrial natriuretic factor was 3.8 +/- 0.4 pmol l-1 in diabetic subjects and 6.1 +/- 1.6 pmol l-1 in controls (NS), at 1000h after 15 mins supine 3.5 +/- 0.3 and 7.9 +/- 2.3 pmol l-1 respectively (p < 0.05) and increased to 9.4 +/- 1.5 and 9.4 +/- 1.2 pmol l-1 in diabetic subjects and controls at 1400h (NS; both p < 0.01 vs basal values). Serum aldosterone, plasma renin activity, blood pressure and urinary sodium output for 12h before, 4h during and 8h after the NaCl infusion were not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Two reference laboratories (CDC, Atlanta, and Institute of Hygiene, Vienna) were evaluated for their ability to diagnose echinococcosis from single serum-specimens by serological assays. Out of 18 specimens, both laboratories correctly identified the 12 sera from patients with echinococcosis. Each laboratory was able to give the species diagnosis for 11 of 12 cases. The CDC abstained from giving a final species-diagnosis for a serum from a patient with alveolar echinococcosis, the Institute of Hygiene similarly, for a case of cystic echinococcosis. Our findings reveal the considerable potential of today's serological methods for primary diagnosis of infections with Echinococcus granulosus and Echinococcus multilocularis.
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The frequency of different types of lysosomal storage diseases in 125 referred cases, collected over three years, was compared to the occurrence elsewhere. The data suggest that mucopolysaccharidosis (MPS) type IVA (Morquio disease), multiple sulphatase deficiency, Niemann-Pick disease type B, GM2 gangliosidosis type '0' (Sandhoff disease), and ceroid lipofuscinosis (Jansky-Bielschowsky and Batten-Spielmeyer-Vogt syndromes) are encountered frequently in Saudi Arabia, as compared to other storage diseases. In contrast, some other diseases such as the adult variant of Gaucher's disease were not observed. Half of the GM2 gangliosidosis type '0' cases originated from one large tribe in the country. Other conditions did not show tribal predilection. The ceroid lipofuscinosis cases in Saudi Arabia originated from four large families. Consanguineous marriages taking place within tribal boundaries probably account for the pattern observed.
A monoclonal antibody detecting amniotrophoblastic antigen 5T4 has shown reactivity against various neoplastic cell lines and tumour specimens but with a relatively restricted normal tissue expression. This antibody has been investigated as a potential indicator of premalignant changes identified as cervical intra-epithelial neoplasia and malignant cervical lesions using immunohistochemistry on frozen tissue biopsies. The basal cells of normal cervical stratified epithelium exhibited faint staining, but a general increase in intensity and extent of specific labeling of this tissue was seen from the first premalignant stage through to carcinoma. In most cases, this was in accordance with the distribution of dysplastic cells, and was accompanied by increased specific staining of the stromal tissue. All invasive squamous carcinomas of the cervix were 5T4 antigen positive. Common inflammatory non-malignant diseases did show a certain degree of epithelial and stromal reactivity. These results, showing 5T4 reactivity with neoplastic and pre-neoplastic lesions, may provide a quantitative basis for its potential use as a tumour marker in the immunochemical detection on immunoassay of cervical cancer.