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Biomedical subjects

C W Havard

Publications and source records attributed to C W Havard.

At least 55 records · Page 3Linked to original sources

Plasma pyridostigmine levels in myasthenia gravis.

Plasma concentrations of pyridostigmine were measured after oral administration in 16 patients with myasthenia gravis. The levels varied greatly among both well- and poorly controlled patients, but were usually higher in the latter group. Absorption of the drug appears to be erratic; its clearance from the plasma is slow and its metabolism could involve an enterohepatic circulation. Drugs such as methylcellulose may prevent absorption. Three poorly controlled patients were studied on a high-dose alternate-day steroid regimen, and a marked decrease in pyridostigmine bioavailability on the same dose of drug was observed in all three. No such changes were demonstrated in a volunteer group taking a lower dose of steroids.

Biological Availability↗

Setting up a drip.

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Catheterization↗

Sputum and blood concentrations of cefuroxime in lower respiratory tract infection.

A detailed pharmacokinetic study of cefuroxime has been carried out. Levels of cefuroxime were determined in the blood, sputum, saliva, and urine of 23 patients receiving parenteral cefuroxime eight hourly for chest infections. Profiles were obtained after the first dose and on the final (fifth) day of treatment. Antibiotic levels in the sputum reached 0.8 mg/l within one hour of the first injection, and were maintained close to this value for six hours. There was a build-up by the fifth day, mean cefuroxime concentrations at this time reaching 1.8 mg/l. This concentration was maintained for a prolonged period. Salivary concentrations were detectable but low (maximum mean value was 0.6 mg/l). Concentrations of antibiotic were significantly higher in the serum than those observed after the same doses in volunteers. In the patients there was no build-up in serum levels between the first and fifth days. The data obtained explain the clinical efficacy of cefuroxime in the treatment of lower respiratory infections, and suggest that a 12-hour schedule may be feasible.

Bronchitis↗

Clinical study of cefuroxime in the treatment of lower respiratory tract infections.

Twenty-three hospital in-patients with severe lower respiratory tract infections were treated with cefuroxime sodium. The drug was given intramuscularly in a dose of either 750 mg or 1000 mg at 8-hourly intervals for 5 days. Of the 21 patients who could be assessed, the response to treatment was highly satisfactory and there were no treatment failures. Eight patients had failed to respond to a course of oral antibiotics before being seen. Most of the patients were elderly and all were very ill. The sputum became mucoid in all but 1 patient. There was no change in tests of liver or renal function. Cefuroxime appears to be an effective and well-tolerated drug for the treatment of patients with severe chest infections.

Adult↗

Biochemical and haematological changes induced by tienilic acid combined with propranolol in essential hypertension.

Sixteen patients with moderate essential hypertension completed a double-blind crossover trial with four treatment periods each of 6 weeks. They received in random order: placebo; tienilic acid 250 mg/day; propranolol 80 mg twice daily; and tienilic acid 250 mg/day combined with propranolol 80 mg twice daily. Average blood-pressure in the lying position was 22.6/13.1 kPa (169/98 mm Hg) on placebo; 21.0/12.5 (157/94) on tienilic aicd; 21.2/12.0 (159/90) on propranolol, and 18.9/11.5 (142/86) on tienilic acid combined with propranolol. The effects of tienilic acid and propranolol on blood-pressure were additive and there were no statistically significant interactions. Tienilic acid significantly reduced serum-urate from 0.33 to 0.18 mmol/l and induced hypokalaemia which was corrected by propranolol. Basophil count and haemoglobin were lower after tienilic acid treatment than they had been at the start of the study.

Adult↗

Successful treatment of exophthalmos and pretibial myxoedema with plasmapheresis.

A patient with Graves's disease with acute progressive exophthalmos and pretibial myxoedema was treated twice with plasmapheresis. Two weeks after the first treatment the symptoms recurred, but 20 weeks after the second treatment the exophthalmos was much improved and the pretibial myxoedema had disappeared. Analysis of sequential serum IgG concentrations and the thyroid-stimulating immunoglobulin index suggested that the two conditions were caused by specific IgGs. The results suggest that plasmapheresis has a useful place in the treatment of acute and rapidly progressive ophthalmopathy and pretibial myxoedema in patients with Graves's disease.

Acute Disease↗

The effect of metoprolol on plasma lipids.

Fifteen hypertensive patients entered a single-blind study to examine the effects of metoprolol (100 mg twice daily) on fasting plasma lipids. In 12 patients who completed the study, non-esterified fatty acid concentrations fell, but cholesterol and triglyceride levels were unchanged after 12 weeks' treatment. These results conflict with earlier reports of the effect of metoprolol on plasma triglyceride concentrations.

Adult↗

Humoral immunity before and after thymectomy in myasthenia gravis.

Humoral immunity was studied in 10 patients with myasthenia gravis before thymectomy, in 15 different patients over 10 years after thymectomy, and in normal controls. Antibody titers to acetylcholine receptor were significantly (p less than 0.01) lower in the post-thymectomy group. However, other antibody titers to common viruses, and to Escherichia coli, and isohemagglutinins showed no significant change. Levels of IgM and IgE (with atopic subjects excluded) decreased following thymectomy (p less than 0.05). Autoantibodies persisted, apart from those directed against the acetylcholine receptor. The absence of any significant changes in humoral immunity after thymectomy for myasthenia gravis suggests that there is no generalized loss of helper T-cell function.

Adult↗

The immunological effects of thymectomy in myasthenia gravis.

Thymus-derived (T) lymphocytes in the peripheral blood and cellular immune function have been studied in ten patients with myasthenia gravis and in fifteen different myasthenic patients more than 10 years after thymectomy. The results were compared with those of a normal control population. The non-thymectomized myasthenic patients had normal T lymphocyte concentrations measured by rosetting with native sheep red cells. These patients also showed normal sensitization and recall of delayed hypersensitivity, phytohaemagglutinin (PHA) induced lymphocyte transformation and antibody-assisted (K cell) cytotoxicity; however, PHA-induced cytotoxicity was markedly reduced (P less than 0.001). The thymectomized group exhibited a lower mean percentage and absolute number of E-rosette-forming cells, which returned toward normal after in vitro treatment with thymosin. PHA-induced lymphocyte cytotoxicity, however, was normal in the patients who had undergone thymectomy, as were lymphocyte transformation, antibody-assisted cytotoxicity and sensitization to dinitrochlorobenzene (DNCB); there was a decrease in recall of established delayed hypersensitivity. Adult thymectomy in man, therefore, produces a partial and dissociated decrease in T cell responses and it is unlikely that the beneficial effect of this operation in myasthenia gravis is related to immunosuppression.

Adolescent↗

Propranolol and tienilic acid in essential hypertension.

Sixteen patients with moderately severe essential hypertension completed a double-blind crossover trial with four treatment periods each lasting for six weeks. They received in random order, placebo; tienilic acid 250 mg/day; propranolol 80 mg b.d.; and tienilic acid 250 mg/day and propranolol 80 mg b.d. in combination. Mean blood pressure in the lying position was 169/98 mmHg on placebo, 157/94 mmHg on tienilic acid, 159/90 mmHg on propranolol and 142/86 mmHg on the combination of tienilic acid and propranolol. The effects of tienilic acid and propranolol on blood pressure were additive and there was no evidence of any interaction. The onset of the hypotensive effect of tienilic acid was gradual while the effect of propranolol was maximal within 2 weeks of the start of treatment. Tienilic acid produced a significant reduction in serum urate from 0.33 mmol/l to 0.18 mmol/l. The combination of tienilic acid and propranolol in the doses used in the trial was effective and acceptable in the reduction of raised blood pressure.

Adult↗

Comparison of effects on cerebral blood flow of rapid reduction in systemic arterial pressure by diazoxide and labetalol in hypertensive patients: preliminary findings.

1 Diazoxide 300 mg and labetalol 150 mg were each injected intravenously on separate occasions into five patients with essentail hypertension. The reduction in BP caused by labetalol was slightly greater than that produced by diazoxide. 2 In contrast the reduction in cerebral blood flow (CBF) by labetalol was not statistically significant, whereas diazoxide gave a greater and statistically significant reduction in CBF. 3 These observations suggest that labetalol may have an advantage over diazoxide for the rapid reduction in BP.

Blood Pressure↗

A comparison of slow release oxprenolol with conventional oxprenolol in the treatment of hypertension.

Sixteen patients with uncomplicated hypertension were studied in a double-blind within-patient trial comparing slow release oxprenolol (SRO) with conventional oxprenolol (CO). The anti-hypertensive effect of SRO once daily was greater than that of CO once daily, although this did not reach statistical significance. CO once daily was less effective than CObd and this difference was statistically significant for lying diastolic blood pressure. After exercise testing 26 hours post-dose, blood pressure and pulse rate were marginally lower on SRO than on CO, but this difference was not significant. Blood pressure readings 24 h post-dose were lower following morning dosing than following evening dosing, although pulse rates showed the opposite trend.

Adult↗

Intravenous labetalol in hypertensive patients given by fast and slow injection.

1 Labetalol reduces blood pressure when given by fast or slow intravenous injection. 2 The extent of the reduction in arterial pressure is independent of the rate of injection but the rate of fall of blood pressure can be controlled by varying the rate of injection. There is little effect on heart rate. 3 These observations suggest that labetalol possesses important advantages over other vasodilator hypotensive drugs in current use.

Adult↗