SUMMARY Mitral valve prolapse was sought clinically and with phonocardiography and M mode and sector echocardiography in 15 women aged 22-57 years with joint hypermobility syndrome. The type III:III + I collagen ratio was measured in skin biopsy specimens and was found to be raised in seven of 10 patients sampled. Thirteen patients had increased aortic wall compliance measured by the continuous wave Doppler ultrasound technique. Ten (67%) patients had mitral valve prolapse shown by auscultatory signs or echocardiography or both-a prevalence at least three times greater than that in the general adult population.It is concluded that if the abnormality of collagen biosynthesis found in skin biopsy samples in these patients is also present in their mitral valve tissue this may predispose them to prolapse of the valve.The primary mitral valve prolapse syndrome is one of the commonest cardiac abnormalities, being present in 4-21% of the adult population.' 2 Most of those affected are symptom free and have a good prognosis,3 but sudden death,45 infective endocarditis,6 spontaneous chordal rupture, and progressive mitral regurgitation7 are rare complications and make this an important condition to recognise. The subject has been well reviewed.28-12The synonymous term, floppy mitral valve syndrome, emphasises the well established structural abnormality of the valve leaflets, although the molecular basis for this defect remains unclear. The main structural abnormality of the valve leaflets in primary mitral valve prolapse consists of myxomatous degeneration and disruption of the pars fibrosa and there is dilatation of the mitral annulus.2The association of mitral valve prolapse with certain inherited diseases (secondary mitral valve prolapse) including the Marfan syndrome,'3 the Ehlers-Danlos syndrome,'4 and osteogenesis imperfecta,'5 lends support to the hypothesis that mitral valve prolapse may be due to abnormalities in the Requests for reprints to Dr Clive E Handler, Department of Cardiology, Guy's Hospital, London SEI 9RT.Accepted for publication 22 July 1985 production or structure of collagen. Such changes have been shown to occur in these conditions.'6The hypermobility syndrome is a sex influenced usually dominantly inherited disorder of collagen production characterised by non-inflammatory joint pain associated with generalised joint laxity.17Mitral valve prolapse is present in about a third of cases,' 819 providing further evidence that a systemic abnormality of collagen may be associated with mitral valve prolapse. There is, at present, little information on this connection. One study of the family of a patient with type IV Ehlers-Danlos syndrome has shown a consistent association of mitral valve prolapse and abnormally low type III collagen production.20 A more recent study, however, has shown an increased proportion of type III collagen in floppy mitral valve tissue compared with normal controls.21The purpose of this study, therefore, was to assess the frequency of mitral valve prolapse among a group of patie...

We have studied the effect of nitrous oxide on cerebral haemodynamics in 24 healthy male volunteers. Hemispherical cerebral blood flow (CBF) was measured using the xenon-133 inhalation technique, blood flow velocities in the right middle cerebral artery were calculated using transcranial Doppler ultrasound and the pulsatility index (PI)--the inverse of which is theoretically proportional to flow in the vessel under investigation--was derived from analysis of the spectrally analysed velocity pulse wave form obtained from the middle cerebral artery. Each variable was measured with the subject inhaling 100% oxygen (1st baseline), 30% nitrous oxide in oxygen, 100% oxygen (2nd baseline) and 60% nitrous oxide in oxygen. CBF was significantly greater with 30% (0.01 > P > 0.001) and 60% nitrous oxide (P < 0.001) compared with baseline, although the difference between 30% and 60% nitrous oxide was not significant. Changes in 1/PI correlated closely with those in hemispherical CBF. Blood flow velocities increased significantly with 30% (P < 0.001) and 60% nitrous oxide (0.005 > P > 0.001), the difference between 30% and 60% nitrous oxide also being significant (0.005 > P > 0.001). We observed a plateau in the change in CBF caused by nitrous oxide and suggest that this may be explained by activation of intact autoregulative mechanisms in healthy human brain.

Seventy-five consecutive patients with subarachnoid haemorrhage (SAH) were entered into a randomized, double-blind, placebo-controlled trial prior to angiography in order to determine the effect of early intervention with nimodipine on blood pressure (BP), cerebral blood flow (CBF), and clinical outcome. Of these patients, 50 fulfilled the criteria for the final analysis (i.e. SAH due to cerebral aneurysm and receiving 21 days of treatment). There was no difference between the BP recordings of the two treatment groups, but mean CBF decreased slightly in the nimodipine group over the 21-day treatment period. At three months, one patient on nimodipine and six patients receiving placebo had died (P = 0.049, Fisher's exact test), but no significant difference was observed between the two groups, when the 'intent to treat' group of 75 patients was considered. We conclude that nimodipine does not increase CBF or alter BP following SAH, but an improved clinical outcome is evident at three months for patients with SAH due to cerebral aneurysm who had been treated with nimodipine. There were no side-effects due to nimodipine.

We enrolled 75 consecutive patients admitted with subarachnoid hemorrhages in a randomized, double-blind, placebo-controlled trial to determine the effect of early intervention with nimodipine on outcome and cerebral blood flow. The cardioprotective effect of nimodipine was assessed by measuring the electrocardiographic changes over the first 3 days of drug treatment. There was a mild lowering of the mean cerebral blood flow in the nimodipine-treated group over the 21-day period. Analysis of the continuous electrocardiographic traces showed no difference between the nimodipine and placebo groups in the frequency or type of abnormality detected. At 3 months, 4 of the 38 patients receiving nimodipine had died, compared with 10 of the 37 placebo-receiving patients. Of the 50 eligible patients who had a proven cerebral aneurysm, 1 patient (4%) on nimodipine died compared with 6 (24%) receiving placebo (0.01 less than P less than 0.05, chi 2 test; approximate 95% confidence interval for mortality difference, 0.4% to 39.6%). We conclude that nimodipine does not increase the cerebral blood flow or protect the heart after a subarachnoid hemorrhage. There were no side effects from nimodipine. The trend toward improved outcome should be verified in a larger series of patients.

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