Biomedical subjects
Publications and source records attributed to J Stephenson.
A case of a 12-year-old boy with tuberous sclerosis who developed life-threatening hematuria is presented. An angiomyolipoma of the lower two thirds of the left kidney resulted in a tumor hemorrhage that was successfully treated by partial nephrectomy.
The neuropeptide galanin inhibits glucose-stimulated insulin release in dogs and rodents and has been proposed as having a role in the control of insulin release in humans. The effect of infused galanin on intravenous glucose tolerance in humans was investigated by giving an intravenous glucose tolerance test (0.5 g glucose/kg body wt) alone and with infusions of synthetic porcine galanin at high-dose levels (80 and 160 pmol.kg-1.min-1) to seven healthy male volunteers. The results showed no effect of galanin infusion on plasma glucose or serum insulin, although a rise in serum growth hormone even in the face of the intravenous glucose load confirmed the potent growth hormone-stimulating effect of galanin. These results suggest that caution should be exercised in extrapolating a physiological role for galanin in humans from the results of animal studies.
Thirty-four patients with essential hypertension were allocated, in a controlled trial, to a treatment diet of high fibre, low fat and low sodium composition, or to a control diet by the hospital dietitian. Clinical observations were made by a separate 'blinded' nursing sister. After three months treatment, the modified diet-treated group showed a significant reduction in mean systolic (169.4 +/- 23.4 to 150.6 +/- 16.1 mmHg) and diastolic blood pressure (101.5 +/- 7.3 to 89.4 +/- 6.8 mmHg), accompanied by significant reductions in urinary sodium excretion (140.4 +/- 34.6 to 93.7 +/- 44 mmol/day) and weight (73.1 +/- 10 to 71.2 +/- 8.4 kg). The changes in control were; systolic 171.2 +/- 14.1 to 162.1 +/- 19.5 mmHg and diastolic pressure 97.2 +/- 10.8 to 91.7 +/- 9.7 mmHg. The mean differences in reductions between treated and control were 8.8 mmHg Systolic (95% confidence intervals: -2.6 to 21.2 mmHg) and 7.0 mmHg diastolic blood pressure (95% confidence intervals: 0.4 to 14.4 mmHg). The number of patients with normal blood pressure in the diet treated group at three months was double that in the control (eleven versus five). No relationships were shown between blood pressure changes and those of weight or urinary sodium excretion during the trial. The findings in this study are broadly in agreement with similar ones in essential hypertension and suggest that this form of dietary regimen has a clinically worthwhile hypotensive effect and this should be readily achievable in routine clinical practice.
At the inception of a general practice well child clinic, a checklist card was introduced into the clinic notes to summarize specific and relative contraindications to immunizations. This card was used by the practice nurses as they ran the immunization procedures during the clinic. A failure on the checklist led to a consultation with the clinic doctor who decided whether to proceed with the immunization. Of 155 immunizations given during the six-month period, only 23 (15%) failed the checklist and required the child to be assessed by the clinic doctor. Of these, nine (39%) were for simple upper respiratory tract infection. All the children were deemed fit to receive immunization. Only one child was found to have a specific contraindication to pertussis. The checklist cards allowed the smooth operation of the immunization procedures by practice nurses who were able to check comprehensively whether there were any contraindications and whether immunizations were being inappropriately refused.
The alkaloid derivative 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene)-beta-D-glucopyranoside (etoposide, VP-16) is believed to exert cytotoxicity by causing double-stranded DNA breaks through interruption of the breaking-resealing reaction of topoisomerase II (topo II). Thus it was conceivable that cells could become resistant to VP-16 by a decrease in topo II enzyme level, since this would lead to fewer DNA breaks. As well, given the structure of VP-16, it was also possible that a pleiotropic mechanism of resistance could decrease sensitivity to this drug. To study these possibilities, a series of VP-16-resistant human KB cell lines was established by stepwise selection. The concentrations of VP-16 required to inhibit cell proliferation by 50% in the parent line and KB/1c, KB/7d, KB/20a, and KB/40a lines were, respectively, 0.16, 4.7, 24, 31, and 47 microM. These cell lines expressed cross-resistance to 4'-(9-acridinylamino)methanesulfon-m-anisidide, doxorubicin, vincristine, and methotrexate, although the pattern of relative drug sensitivity was quite different from that of pleiotropic resistant cell lines reported elsewhere. The resistance to vincristine and methotrexate did not increase above the level of the KB/1c cells, and resistance to VP-16, doxorubicin, and especially vincristine was unstable in VP-16-resistant cells cultured in the absence of drug. Although the drug resistance marker Mr 180,000 glycoprotein could not be detected in any of our cell lines, cellular accumulation of [3H]VP-16 was reduced 50-75% in the resistant lines compared with parent KB. With increasing VP-16 resistance, the level of topo II protein, detected by antibody staining, decreased at each step of selection, concomitant with a general decrease in topo II unknotting activity. Sensitivity of the topo II unknotting assay to inhibition by VP-16 was the same for the parent and all resistant cell lines. The level of topo I activity and enzyme increased slightly in the resistant cells. Thus, these cell lines are resistant to VP-16 by virtue of at least two mechanisms: (a) reduced levels of topo II, which confers cross-resistance to other compounds which are topo II-dependent cytotoxic agents; and (b) reduced accumulation of drug, which is likely also responsible for vincristine and methotrexate resistance. However, the possible existence of other mechanisms of resistance cannot be ruled out.
Previous reports have documented that cyclosporin A (CsA) can inhibit the production of interferon-gamma (HuIFN-gamma) and interleukin-2 (IL-2). In this report we have extended these earlier findings and have demonstrated that the defect in the production of HuIFN-gamma persists even after the CsA is removed and is associated with altered synthesis of other lymphokines, mainly a cytotoxin and leukocyte migration inhibition factor. In the presence of recombinant exogenous IL-2, the effect of CsA on the synthesis of HuIFN-gamma can be reversed depending on the concentrations of both the IL-2 and CsA. In addition, the presence of the calcium ionophore A23187 partially reverses the inhibitory effect of CsA by synergistically enhancing the synthesis of HuIFN-gamma.
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Thrombocytopenia in cirrhotic patients is usually attributed to splenic pooling whereas in idiopathic thrombocytopenic purpura it is related to platelet bound immunoglobulin (PA-IgG). Since primary biliary cirrhosis (PBC) is an autoimmune disorder we have undertaken a prospective study to assess the frequency and possible relationship of PA-IgG to thrombocytopenia in this condition. Sixty-two primary biliary cirrhosis patients (28 precirrhotic; 34 cirrhotic) were studied. Twenty-five patients (40%) had raised PA-IgG of whom 18 had cirrhosis. There was a significant inverse correlation between platelet count and PA-IgG (p less than 0.001) and between platelet count and spleen size (p less than 0.001). Thrombocytopenia (platelets less than 100 X 10(9)/l) was found in nine patients (15%); all nine had raised PA-IgG and eight were cirrhotic with an enlarged spleen. Two cirrhotic patients with persistent thrombocytopenia and bleeding episodes were treated with prednisolone and showed a useful therapeutic response. These results suggest that immune mediated platelet destruction and splenic pooling of platelets may both play a part in the thrombocytopenia observed in primary biliary cirrhosis.
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Three experiments are reported which examined the temporal stability of cardiac reactions to a video game of the 'space invaders' genre. Experiment 1 also addressed the matter of inter-task consistency; in addition to the video game, subjects were presented with an unsignalled reaction time task and led to believe that relatively quick reactions attracted financial reward, while slower ones brought either a burst of loud noise or withdrawal of money previously earned. Forty-two male subjects were tested on both tasks on two occasions, a week apart. Of the two tasks, the video game elicited the greater reactivity. In addition, individual variations in reactivity showed striking temporal stability for both tasks. However, inter-task consistency was much less marked; in fact, a significant inter-task correlation was obtained only on the first occasion of testing. It is probable that limited consistency here was in some measure due to the ineffectiveness of our reaction time task in eliciting substantial reactivity. Finally, reactivity was independent of baseline heart rate level. In experiment 2, three extreme high and three extreme low cardiac reactors were selected from an initial sample of 23 male subjects, on the basis of reactivity during an initial session with the video game, and subsequently studied during four further sessions. Once more, impressive stability of heart rate reactivity was apparent over sessions. In experiment 3, we examined the reliability of individual variations in cardiac reactivity in women and the issue of whether temporal stability is constrained by menstrual cycle effects. Twenty-four females were tested on the video game both preovulatory and postovulatory, with half being tested first during the preovulatory phase and half being tested first during the postovulatory phase. Again, the most striking finding was the marked stability of individual variations in cardiac reactivity over both time and menstrual cycle phase.
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One hundred and sixty-three asymptomatic people with thyroid antibodies or raised serum thyrotrophin (TSH) concentrations, or both, and 209 age-matched and sex-matched controls without either marker of thyroid disorder were followed up for four years to determine the natural history of autoimmune thyroiditis. Mildly raised TSH concentrations alone and the presence of thyroid antibodies alone did not significantly increase the risk of developing overt hypothyroidism during the four years compared with the controls. Overt hypothyroidism developed at the rate of 5% a year in women who initially had both raised TSH concentrations and thyroid antibodies. Prophylactic treatment with thyroxine may be justified in women found to have both markers of impending thyroid failure. The cost effectiveness of screening the adult population remains to be evaluated.
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The investigation of methods of treatment known to be effective in controlling nocturnal enuresis may yield information on the pathophysiology of the condition. An attempt has been made to mimic the known alpha-adrenolytic action of imipramine by treating a group of 14 enuretic school-children with a competitive alpha-adrenoceptor blocking substance, indoramin. Treatment in the doses used had no significant effect on night-wetting frequency.
A survey in a general practice in the North-East of England in 1963 detected thyroglobulin antibodies in 16.2% of women and 4.3% of men. High titres of antibodies were found in 4.6% of women and 1.6% of men. Forty six subjects with thyroglobulin antibodies (from an original total of fifty-two) were studied in 1972 and forty of these were studied further in 1975. These subjects were compared with a group of age- and sex-matched controls from the original survey. Three of the subjects had developed overt hypothyroidism by 1975 and a raised serum thyroid-stimulating hormone (TSH) concentration was found more frequently in euthyroid subjects peviously found to be antibody positive. There was a striking difference in the antibody studies in that only 26% of the previously antibody positive subjects had thyroglobulin antibodies in 1972 and 30% in 1975. A raised serum TSH concentration was found to correlate with cytoplasmic a-tibodies and particularly with the combination of cytoplasmic and thyroglobulin antibodies.
Tissue auto-antibodies were investigated in fifty-one patients (twenty-five female, twenty-six male) receiving practolol for ischaemic heart disease or dysrhythmias and compared with those found in 204 patients (fifty-eight female, 146 male) with ischaemic heart disease who did not receive practolol. Antinuclear factor (ANF) was found in 24% female and 16% male patients receiving practolol, but only in 5% of female and 4% of male patients who were not taking practolol. Thyroid cytoplasmic antibody (TCA) was detected in 16% female and 20% of male patients receiving practolol, compared to 10% of females and 6% of males in the control group. The incidence of ANF and TCA was significantly higher (P less than 0-05) in patients receiving practolol compared to the control group. The occurrence of gastric parietal cell antibody (PCA) and smooth muscle antibody (SMA) was not associated with practolol therapy (odds ratio of 2-4 and 1-9 respectively). The incidence of skin and eye complications was found to be 10% and the female to male ratio of this complication was 4 : 1. The correlation between autoantibody production and oculo-cutaneous complications could not be established in such a small group but three of the patients with the complications were found to have PCA, although PCA was found not to be associated with practolol therapy. Four of the five patients with the complications did not have circulating ANF.
The isolation of meningococci from the vagina is unusual. This report concerns a young woman who presented with vaginal bleeding and subsequently developed a febrile illness which responded to oral ampicillin. The main clinical features included vomiting and drowsiness followed by a rash and arthritis. Neisseria meningitidis group B was isolated from cultures of a vaginal swab and blood. A brief literature review of genital infections with meningococci is given.