Biomedical subjects
Publications and source records attributed to C W Havard.
A 41 year old woman with severe emaciation due to longstanding anorexia nervosa presented with recurrent hypoglycaemia. During an episode of hypoglycaemia, serum insulin and C peptide were undetectable and plasma beta hydroxybutyrate, free fatty acids and lactate were inappropriately low. Response to intravenous glucagon was poor. Muscle enzymes were grossly elevated until she gained weight. Hypoglycaemia was abolished by weight gain.
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Twenty-seven patients with myasthenia gravis have been treated with azathioprine in conjunction with pyridostigmine and prednisolone for a total of 138 patient years. Side effects necessitated discontinuation of treatment in only four patients. Treatment with azathioprine was associated with marked clinical improvement in all the remaining 23 patients, resulting in reduction in the dose of pyridostigmine and prednisolone. The number of hospital admissions as well as the number of episodes of respiratory failure were markedly reduced.
Myasthenia gravis is an autoimmune disorder in which neuromuscular transmission is impaired by autoantibodies to the acetylcholine receptor (AChR). There are 3 varieties of generalised myasthenia with differing genetic susceptibilities. There is also a purely ocular form in which the weakness is confined to the extraocular muscles, and a neonatal variety which occurs in 20% of babies born to myasthenic mothers due to transplacental passage of the acetylcholine receptor antibody. Another variety of myasthenia occurs several months after treatment with D-penicillamine. The role of the thymus is suggested by abnormal histology in patients with myasthenia and by the beneficial effects of thymectomy in more than two-thirds of patients. Thymectomy is indicated in most patients unless the symptoms are minimal or the weakness is confined to the extraocular muscles. Most patients require treatment with anticholinesterase drugs to prolong the action of acetylcholine at the muscle end-plate. Overdosage of these drugs can provoke a cholinergic weakness. Remissions can be achieved with corticosteroids in 80% of patients. Immunosuppression with azathioprine is used mainly in patients who do not respond to thymectomy or in those patients who are considered unsuitable for operation. Plasma exchange can cause a rapid but temporary improvement in myasthenia, and has no long term place in its treatment.
A 42-year-old man suffered a head injury in a road traffic accident and subsequently developed anosmia and isolated adrenocorticotropic hormone (ACTH) deficiency. There was no other evidence of pituitary dysfunction. No previous case of isolated ACTH deficiency following head injury has been reported.
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A 52 year old man with myasthenia gravis and normal liver function was treated with neostigmine, prednisolone and azathioprine. Three years after starting azathioprine he developed clinical evidence of portal hypertension. A liver biopsy showed nodular regenerative hyperplasia (NRH). The development of NRH following azathioprine treatment in a patient with myasthenia gravis strengthens the case for a causal role of azathioprine in producing NRH and portal hypertension.
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A twelve-week parallel study was conducted to compare the efficacy and safety of nicardipine plus propranolol with that of propranolol alone in 67 patients with mild to moderate essential hypertension. Efficacy data was analysed for 50 patients. The regimens used were 90 mg X day-1 of nicardipine and 120 mg X day-1 of propranolol. Both treatments significantly reduced supine and standing systolic and diastolic blood pressure from baseline values at all visits. At all visits, concomitant administration of nicardipine and propranolol produced a greater reduction in systolic and diastolic pressures than did propranolol alone, although the difference between treatments did not always reach statistical significance. Few adverse events were reported, and none was clinically important. We conclude that nicardipine taken concomitantly with propranolol is more effective than propranolol alone in treating patients with hypertension and that the combined regimen is well tolerated.
Platelet function and thromboxane A2 release were measured in 71 patients admitted to a coronary care unit with a provisional diagnosis of acute myocardial infarction (AMI). All measurements were carried out within twenty-four hours of admission. Of these, 35 patients had the diagnosis of AMI confirmed. The remainder (n = 36), who did not have AMI (NMI), were divided into two groups: those (n = 18) with an unequivocal history of previous vascular disease and those without vascular disease (n = 18). Platelet aggregation and thromboxane A2 (TXA2) release were significantly increased in the AMI group when compared with those in the NMI without vascular disease group or a healthy control group with similar age and sex distribution. Aggregation and TXA2 release in the NMI patients with vascular disease were greater than those in controls and did not differ significantly from those in the AMI group. Patients in the AMI or NMI with vascular disease groups who were taking beta-blockers or calcium channel antagonists at the time of admission showed significantly less platelet aggregation than those who were not taking these drugs. Heparin, added in vitro at therapeutic concentrations, induced significantly more aggregation in patients in the AMI and NMI with vascular disease groups than in the NMI without vascular disease group. We conclude that: platelets obtained from patients with AMI are hyperaggregable and release more TXA2; platelets from patients with significant vascular disease are hyperaggregable, even in the absence of AMI, although they are not as hyperaggregable as those from AMI; treatment with nifedipine and beta-blockers protects these patients from platelet hyperaggregability; heparin induces significant aggregation of platelets from patients with AMI and NMI with vascular disease. These observations are of importance in considering the pathogenesis and treatment of AMI and ischemic heart disease.
Seven young male volunteers received a single oral dose of Oruvail (ketoprofen 200 mg capsule) on two occasions, immediately after either a light/lean or a heavy/fatty meal at breakfast time. Administration of ketoprofen immediately following the heavy meal slightly, but significantly, delayed the absorption of the drug, as evidenced by mean (+/- S.D.)Tmax values of 6.7 (+/- 1.0) and 9.0 (+/- 1.4) hours respectively. Changing the type of meal had no statistically significant effect on the maximum plasma level, apparent plasma elimination half-life (t 1/2 h), area under the plasma level versus time curve, total plasma clearance, and urinary recovery of total ketoprofen, indicating that the bioavailability (and the systemic level) of ketoprofen was not affected by meal composition.