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.

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.

Myasthenia gravis. Pathogenesis and current concepts in management.

Myasthenia gravis is a disorder of autoimmunity in which neuromuscular transmission is impaired by autoantibodies to the acetylcholine receptor (AChR). There is evidence for more than one form of the disorder with differing genetic susceptibilities. The aetiology is unknown, but thymic involvement is suggested by abnormal histology and by the beneficial response of the disorder to thymectomy in more than two-thirds of patients. Thymectomy is indicated in most patients unless the symptoms are minimal or are confined to the extraocular muscles alone, or the patient is elderly. Thymectomy alone results in remission in about one-third of patients, but, in addition, most patients require symptomatic anticholinesterase drugs to prolong the action of acetylcholine at the muscle end-plate. Over-dosage of these drugs can also cause weakness. Immunosuppression with corticosteroids or azathioprine may also improve myasthenia; at present, these drugs are used mainly in patients who do not respond to thymectomy or in those patients considered unsuitable for operation. Plasma exchange can cause a rapid, though temporary, involvement in myasthenia, but it probably has no long term place in its treatment. Future therapy will probably involve specific immunotherapy, such as anti-idiotype antibodies.

New treatment approaches to myasthenia gravis.

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.

Diminished creatinine clearance in anorexia nervosa: reversal with weight gain.

To assess whether patients with anorexia nervosa have abnormalities in creatinine clearance, we measured plasma creatinine concentration, urinary creatinine excretion, and creatinine clearance in 10 patients with anorexia nervosa before and during treatment. Urinary creatinine excretion and creatinine clearance were diminished in all patients. Nine patients had significant decreases in their plasma creatinine and creatinine clearance was increased even when corrected for body weight and body surface area respectively. The patient who did not show these changes in plasma creatinine concentration and creatinine clearance had gained only 4% in body weight. Body weight and corrected creatinine clearance were significantly correlated, as were percentage increases in body weight and creatinine clearance. Thus anorexia nervosa is associated with a reversible decrease in creatinine clearance. Increase in body weight appears to be cardinal to the recovery of renal function in these patients.

Xipamid, a potent new diuretic.

The effects of xipamid and frusemide were comapred in 9 oedematous patients. Xipamid was found to be equipotent with frusemide in doses of 40 mg. and 80 mg., with respect to its effect on sodium and water excretion. The time course of action of xipamid was observed to be more prolonged than that of frusemide. It is concluded that xipamid is a potent and safe diuretic.

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.

Anosmia and isolated ACTH deficiency following a road traffic accident. Case report.

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.

Platelet function in patients admitted with a diagnosis of myocardial infarction.

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.