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promoted as a fairly inexpensive holiday

destination for the UK

traveller. We wish to emphasise that, for the short-term traveller to East Africa (overseas stay of 3 weeks or less), mefloquine 250 mg weekly is the preferred choice for prophylaxis against the highly prevalent resistant P falciparum in that area. once

Regional Department of Infectious Tropical Medicine, Monsall Hospital, Diseases and

Manchester M10 8WR, UK

A.

J. BARNES

E. E. B. E.

L. C. ONG M. DUNBAR K. MANDAL G. L. WILKINS

weeks. Symptomatic orthostatic hypotension was not seen in any patient and the drop in orthostatic systolic blood pressure did not differ among placebo, lovastatin, and pravastatin groups (2-4 [SD 75] vs 25 [11.4] vs 3-7 [9-1] mm Hg at 1 min and 2-9 [8.5] vs 3-4 [10-6] vs 2-1 [9-2] mm Hg at 3 min). Changes in diastolic blood pressure were less pronounced. Thus, in this controlled study, lovastatin and pravastatin did not cause orthostatic hypotension. UMDNJ-Robert Wood Johnson Medical School New Brunswick, New Jersey 08903, USA 1. French J, White H. Transient Lancet 1989; ii. 807-08.

Phillips-Howard PA, Bradley DJ, Blaze M, Hurn M. Malaria in Britain: 1977-86. Br Med J 1988; 296: 245-48. 2. British National Formulary, no 22, September, 1991: 225. 3. Report of meetings convened by the Malaria Reference Laboratory and the Ross Institute. Prophylaxis against malaria for travellers from the United Kingdom. Br Med J 1989; 299: 1087-89. 1.

Late Plasmodium ovale malaria SIR,-Dr Facer and Dr Rouse (Oct 5, p 896) report a case of spontaneous splenic rupture due to Plasmodium ovale malaria. We agree that visitors to malaria-endemic regions should be given advice on protection against mosquito bites and on malaria prophylaxis. However, chemoprophylaxis does not prevent infection with P ovale, although it can prevent the disease. After a mosquito bite, sporozoites are quickly taken up by the liver, resulting in exoerythrocytic schizogony with, eventually formation of hypnozoites. Sporozoites and hyponozoites are not sensitive to chemoprophylaxis.Hypnozoites can survive a long time in the liver and can give rise to malaria attacks long after chemoprophylaxis has been stopped. Of the 59 cases of P ovale infection we treated between Jan 1, 1987, and Nov 1, 1991, 48 had reliable travel data recorded on file. 40/48 patients (83 %) became ill more than one month after they had left the malarious region, and 23 of these reported that they had appropriate chemoprophylaxis regularly. Of the 8 early infections, 4 were seen in Europeans and 4 in Africans travelling to Belgium. No patient had taken chemoprophylaxis. 2 of the 8 presented with splenomegaly: 1 of them had a mixed infection with P falciparum. Disease severity was not different between early and late cases. The early death in the case reported by Facer and Rouse would have been avoided with chloroquine prophylaxis, but it should be realised that late P ovale malaria attacks are possible, not

JOHN B. KOSTIS ALAN C. WILSON

symptomatic hypotension in patients on

simvastatin.

Right ventricular conduction disturbance after balloon valvuloplasty in congenital pulmonary valve stenosis SIR,-Percutaneous balloon valvuloplasty (PBV) is accepted as effective and safe non-surgical treatment for congenital pulmonary valve stenosis. Transient extrasystoles or bradycardia are common during balloon valvuloplasty.1,2 However, conduction disturbances have rarely been described. We have noted that right ventricular conduction disturbance was frequently detected after PBV in breastfed infants and young children with severe pulmonary valve stenosis. We report electrocardiographic (ECG) changes an

associated with this disturbance after PBV in 4 such breastfed babies (group 1) and 4 young children (group 2) (pressure gradient > 80 mm Hg, and right left ventricular pressure). These patients were among 23 who have undergone PBV in our hospital during the past two years. Breastfed infants were aged 1-4 months (mean 2-9), and young children 2-5 years (mean 3-3). After PBV, pressure gradients between right ventricule and pulmonary artery decreased from 99 (7-3) mm Hg to 39 (11 -5) mm Hg in group 1 and from 99 (6-8) mm Hg to 27 (6-2) mm Hg in group 2. Mean ratio of balloon size to diameter of pulmonary valve annulus was 1-25 (0-09) in group 1 and 1-4 (01) in group 2. The balloon was inflated by hand and was filled with diluted (30%) contrast medium. The inflation/deflation cycle took less than 12 s in group 1 and 10 s in group 2. Amplitude of the R wave in V1 was

withstanding correct chemoprophylaxis.

Institute for Tropical Medicine, B-2000 Antwerp, Belgium

E. VAN DEN ENDEN ALFONS VAN GOMPEL JEF VAN DEN ENDE TONY VERVOORT

1 Desjardins RE, Doberstyn EB, Wernsdorfer WA. The treatment and prophylaxis of malaria. In: Wernsdorfer WH, McGregor I, eds. Malaria: Principles and practice of malariology, vol 1. Edinburgh: Churchill Livingstone, 1988: 827-64.

Lack of

hypotension with lovastatin and pravastatin

SIR,—After French and White’sl report of transient symptomatic hypotension in patients on simvastatin, we added measurement of blood pressure in the sitting and standing positions to a randomised, placebo-controlled, double-blind, crossover study of pravastatin and lovastatin. 17 men took part; they were aged 36-65 years (mean 57, SD 7) and had type II hypercholesterolaemia defmed as low-density lipoprotein (LDL) cholesterol greater than 165 mg/dl after 6 weeks of a low fat ( < 30%), low cholesterol ( < 300 mg/day) diet and triglyceride less than 350 mg/dl. 9 patients were on aspirin, 3 on diuretics, 6 on converting enzyme inhibitors, 3 on calcium antagonists, 2 on digitalis, 1 on a &bgr;-blocker, and 2 on

dipyridamole. Blood pressure was measured with random zero sphygmomanometry in the sitting position and after 1 and 3 minutes standing by nurses certified in the use of the technique. Striking decreases of LDL cholesterol (by 28-30%) compared with placebo were

noted after lovastatin 40 mg and pravastatin 40 mg daily for 6

QRS frontal axis (upper) and QRS time (lower) after percutaneous balloon valvuloplasty (PBV) in 8 infants and young children. -

E-1 - breastfed babtes, --0-- young children.

1340

substantially higher after PBV in 3 patients in group 1 and 3 in 2, and the grade of right axis deviation (RAD) increased transiently in all 8 patients after PBV (figure). These changes in QRS amplitude and QRS axis improved within seven days of PBV. Before PBV, QRS duration was within 0-08 s in all cases, but after the procedure it was substantially prolonged in 3 patients in group 1, and remained within 0 08 s throughout the clinical course in all patients in group 2 (figure). The prolonged QRS duration in group 1 improved slightly and this persisted for more than six months after PBV. QRS wave patterns in right precordial leads developed from notched R to a right bundle branch block pattern in 3 patients in group 1 and in 3 in group 2. This pattern persisted for more than six months after PBV in 5 of these 6 patients. None showed prolonged QTc after PBV.3 These changes on standard ECGs were not detected in patients with mild or moderate pulmonary valve stenosis or in school-aged children. During PBV, right ventricular pressure was strikingly increased during inflation of the balloon. Furthermore, the right ventricular

workers should provide details about their assay and express their results on an absolute scale. Moreover, they referred to the use of statistical tests but did not provide any data or p values, ranges, or standard deviation; nor did they indicate Bonferroni correction. Finally, in the figure, we do not understand why the osteocalcin concentrations obtained at day 0 are different for the two curves. We agree with Teelucksingh et al that the clinical relevance of the most recent findings should be established by long-term prospective studies in asthmatic patients with biochemical bone remodelling indices in parallel with bone densitometry

group

measurements.

Departments of Rheumatology and Nuclear Medicine, Free University of Brussels, ANNE PERETZ Hôpital Saint Pierre, PIERRE P. BOURDOUX B-100 Brussels, Belgium A, Praet JP, Bosson D, Rozenberg S, Bourdoux P. Serum osteocalcin m the of corticosteroid-induced osteoporosis. Effect of long and short term corticosteroid treatment. J Rheumatol 1989; 16: 363-67 2. Hodsman AB, Toogood JH, Jennings B, Fraher LJ, Baskerville JC. Differential effects of inhaled budesonide and oral prednisolone on serum osteocalcin. J Clin Endocrinol Metab 1991; 72: 530-40. 3. Jennings B, Andersson KE, Johansson SA. Assessment of systemic effects of inhaled glucocorticosteroids: comparison of the effects of inhaled budesonide and oral 1. Peretz

assessment

outflow tract was stenotic in breastfed infants and young children with severe pulmonary valve stenosis. Therefore the changes in QRS duration and QRS wave pattern reported here may indicate that the transient but striking increase of right ventricular pressure or physical stimulation of the inflated balloon further damage the right ventricular myocardium, especially the right ventricular conduction system and outflow tract, which have already been damaged by pressure overload due to pulmonary valve stenosis. Division of Paediatrics, Children’s Research Hospital, Kyoto Prefectural University of Medicine,

Kyoto 602, Japan 1. Kveselis

prednisolone on adrenal function and markers of bone turnover Eur J Clin Pharmacol 1991; 40: 77-82. 4. Pouw EM, Prummel MF, Oosting H, Roos CM, Endert E. Beclomethasone inhalation decreases serum osteocalcin concentrations. Br Med J 1991; 302: 627-28. 5. Ali NJ, Morrison D, Capewell S, Ward MJ Beclomethasone and osteocalcin. Br Med J 1991; 302: 1080. 6. Delmas PD, Christiansen C, Mann KG, Price PA. Bone gla protein (osteocalcin) assay strandardization report. J Bone Miner Res 1990; 5: 5-11.

KENJI HAMAOKA KOHICHI SAKATA ZENSHIRO ONOUCHI

Epi demic pneumocystis pneumonia in

DA, Rocchini AP, Snider AR, et al. Results of balloon valvuloplasty in the of congenital valvular pulmonary stenosis in children. Am J Cardiol

children before the AIDS

treatment

1985; 56: 527-32. 2. Tynan M, Baker EJ, Rohmer J,

et al. Percutanous balloon pulmonary valvuloplasty. J 1985, 53: 520-24. Stanger P. Transient prolongation of the QTc interval after balloon valvuloplasty and angioplasty in children. Am J Cardiol 1986; 58: 1233-35.

Br Heart 3. Martin GR,

Inhaled corticosteroids, bone formation, and osteocalcin SIR,--On the basis of changes in serum osteocalcin concentrations, Dr Teelucksingh and colleagues (July 6, p 60) claim that inhaled beclomethasone, even at low doses (400 Ilg per day), reduces bone formation in adults. Nowadays, osteocalcin is usually regarded as a good marker of bone formation, being especially sensitive to the inhibitory effects of corticosteroids.l The effects of inhaled corticosteroids (budesonide or beclomethasone) on bone metabolism have received much attention. Most workers have reported no change in osteocalcin concentrations for doses of budesonide lower than 800 ag per day, contrasting with the inhibitory effects (decrease in osteocalcin concentrations) at doses higher than 800 and up to 3200 Ilg per day.2,3 For beclomethasone, an inhibitory effect has been reported by Pouw et al4 and Ali et als at doses of 2000 ug per day. We investigated in a placebo-controlled trial the effects of beclomethasone 1000 ug daily (the usual inhaled dose) given twice a day for one week. Ten healthy volunteers took part. In contrast with Teelucksingh and colleagues’ results, neither serum osteocalcin (Incstar radioimmunoassay; reference range 2 2-6-2 jjg/1; interassay coefficient of variability 9’ 1 %) nor other indices of bone metabolism (serum alkaline phosphatase and immunoreactive parathyroid hormone, calciuria, hydroxyprolinuria) showed substantial changes during the study period. Teelucksingh and colleagues’ results are questionable. Osteocalcin was measured by an in-house radioimmunoassay without indication of the antibody used in the assay or of their reference range; they used plasma but did not mention sampling conditions. It has recently been emphasised that such information is essential for correct interpretation of published reports.’ Teelucksingh et al showed a maximum decrease of about 3 ug/1 in osteocalcin concentrations. In our hands, with the Incstar assay, this would lead to osteocalcin concentrations similar to those achieved by the daily administration of 60 mg of prednisolone.’ These

SIF

era

reports of clusters of Pneumocystis carinii in pneumoiiid (PCP) HIV-seronegative adults without prediposing disease!,2 are unusual in the clinical setting of the past 30 years. Before the AIDS epidemic, PCP in adults was almost exclusively restricted to the immunocompromised. Epidemic PCP in children in former years seems to have been overlooked even though these outbreaks happened within the memory of some physicians still in "wo

recent

practice. Epidemic "interstitial cell pneumonia" in children occurred in Europe in the late 1930s and during the 1940s and 1950s. It was first noted in German speaking countries. Ammich described 11cases among premature babies coming to necropsy in Berlin in 1938,3and in 1942 a report from the same hospital showed that the interstitial pneumonia frequently followed blood transfusions and noted that 4 .4 of the Icases described by Amrnich had received transfusions." These outbreaks are often attributed to prematurity and malnutrition in war-torn zones. This seems unlikely, however. Gormsen, reviewing 350 cases reported by 1950,5 noted that these outbreaks of pneumonia occurred in waves, often in the same clinics and rooms, suggesting that the disease was contagious or that it was a

reaction of premature infants

to some treatment

used in central

Europe where German was a common language in higher education. Especially striking are the large number of cases reported from German-speaking Switzerland (707 between 1941 and 1949) but not one from the French-speaking part.6 This may simply reflect lack of awareness: the French-speaking doctors may not have been familiar with the reports published in German. Most cases reported in the early 1950s-from Hamburg and Cologne, for example, and the Czech city of Olomouc. In 1957 Ahvenainen’ estimated that more than 2000 cases had been published and felt that the disease might have become so commonplace in some areas that cases were no longer reported. He suggested that the disease first arose in a fairly small area of central Europe and then slowly spread from country to country. P carinii was first described as the agent causing interstitial plasma cell pneumonia by the Czech investigator J. Vanek in 1951. were

He noted that the organisms can be seen in photomicrographs in Ammich’s paper of 1938. In the United States, where this disease was unknown, Vanek’s report was treated with scepticism until 1957, when an extensive review was published by GajdusekIn this

Right ventricular conduction disturbance after balloon valvuloplasty in congenital pulmonary valve stenosis.

1339 promoted as a fairly inexpensive holiday destination for the UK traveller. We wish to emphasise that, for the short-term traveller to East Afr...
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