1468
Treatment of
high-altitude pulmonary oedema
SiR,—High-altitude pulmonary oedema (HAPO) is life threatening with appreciable morbidity and mortality in climbers who ascend to over 4000 m,’ although pharmacological intervention benefit. We describe a case of HAPO at 6550 m, which treated with nifedipine. During an expedition to Mount Putha Hiunchuli, Nepal, a 26-year-old woman ascended with two other climbers from 5700 to 6550 m over 10 h in a technically straightforward climb. 6 h later she developed symptoms of acute mountain sickness (AMS)--namely headache, exertional dyspnoea, and dizziness. 2 h later her condition deteriorated (central cyanosis, dyspnoea at rest, tachypnoea, orthopnoea, cough productive of frothy sputum, and ataxia). One of us (G.W.K.) found coarse pulmonary crackles throughout both lung fields. Nifedipine 20 mg was administered orally and glyceryl trinitrate given sublingually, which promptly resolved her symptoms and signs (AMS score, which had been 9 when nifedipine was given, was 2 at 7 h and 1 at 16 h). She remained at this altitude for 16 h because of bad weather, taking nifedipine 20 mg 8 hourly, and was able to return to base unaided 36 h after the start of illness. The two other climbers who had taken nifedipine 20 mg 8 hourly from the start of the ascent had no symptoms of HAPO, and were able to continue the climb. Nifedipine significantly reduces indirectly measured pulmonary artery pressure and AMS score.3 When given prophylactically to climbers ascending to over 4000 m nifedipine may prevent HAPO or lessen its severity.4 Our case illustrates two extra features: efficacy at very high altitude (6250 m) in the absence of other prophylaxis (eg, acetazolamide5) and rapid reversal. The mechanism of action of nifedipine is presumed to be related to reversal of hypoxia-induced pulmonary hypertension. What part sublingual nitrate has is uncertain. Nitrates can acutely reduce pulmonary artery pressure and it remains to be answered whether nitrates have similar effects to nifedipine in HAPO and if so, whether they are synergistic or better than currently used drugs in prevention and treatment.
has
some
was
Department of Medicine and Gardiner Institute, Western Infirmary, Glasgow G11 6NT, UK
Therapeutics, ANDREW JAMIESON
Dungavel, Auchterarder Road,
Dunning
GARY W. KERR
1. Hackett PH, Rennie D, Levine HD. The incidence, importance, and prophylaxis of acute mountain sickness. Lancet 1976; ii: 1249-55. 2. Coote J. Pharmacological control of altitude sickness. TIPS 1991; 12: 450-55. 3. Oelz O, Maggiorini M, Ritter M, et al. Nifedipine for high altitude pulmonary oedema. Lancet 1989; ii: 1241-44. 4. Bartsch P, Maggiorini M, Ritter M, Noti C, Vock P, Oelz O. Prevention of high-altitude pulmonary edema by nifedipine. N Engl J Med 1991; 325: 1284-89. 5. Oelz O. A case of high-altitude pulmonary edema treated with nifedipine. JAMA 1987; 257: 780.
Mesalazine versus olsalazine for prophylaxis of ulcerative colitis relapse SIR,-Dr Courtney and colleagues (May 23, p 1279) in their study of 12-month relapse rates in ulcerative colitis after prophylactic treatment with either mesalazine or olsalazine show a much lower rate (24-5%) with olsalazine than with mesalazine (46%). Although this is the only study comparing these two treatments directly, other studies comparing one or other of these drugs with sulphasalazine give good reason to suspect that the difference found by Courtney and colleagues may be due to chance or some methodological flaw. In reviewing the various studies, like Courtney et al, we have used (where sufficient information is provided) an intention-to-treat analysis in which patients withdrawn after randomisation are classed as treatment failures. Three trials have compared mesalazine and sulphasalazine. Dew et all showed a 16-week relapse rate of 26-5% for mesalazine and 18-2% for sulphasalazine (chi-square test, p 0-42). They later reported2 a 6-month relapse rate of 21-9% with mesalazine and 20 0% with sulphasalazine (p = 0-87). Finally Riley et al3 recorded a 40% 48-week relapse rate with mesalazine =
and a 46% relapse rate with sulphasalazine (p = 0-54). Thus none of the individual studies shows a significant difference between mesalazine and sulphasalazine. In addition, the Mantel-Haenszel chi-square obtained by pooling all these studies (meta-analysis) is 0-02 (p = 0-89). Three trials have also compared olsalazine and sulphasalazine. Ireland et al4 showed a 6-month relapse rate of 39% with olsalazine and 23-2% with sulphsalazine (p= 0-029), a significantly better result for sulphasalazine. Rijk et all noted a 48-week relapse rate of 60-9% with olsalazine and 47-8% with sulphasalazine, (p=037), Lastly, Kiilerich et al6 obtained a 12-month relapse rate of 54% with olsalazine and 48-2% with sulphasalazine (p=0’45). The metaanalysis Mantel-Haenszel chi-square is 4-90 (p=0-027)-a statistically significant difference in favour of sulphasalazine. Thus, relapse rates with mesalazine do not differ significantly from those with sulphasalazine, and one trial and the meta-analysis showed significant differences in favour of sulphasalazine when compared with olsalazine. The apparently large difference between olsalazine and mesalazine obtained in the Courtney study is inconsistent with these results. The relapse rates for each treatment vary considerably from study to study, probably reflecting selection criteria and assessment methods used: relapse rates with sulphasalazine were 1821-1182%6; with mesalazine 21-9-40%; and with olsalazine 394-60,9%5. The relapse rate for mesalazine in the Courtney study is above the upper range in other studies, whereas that for olsalazine is below the lower range. Therefore, there is a strong suggestion that the patient groups were not comparable in that study. Perhaps the explanation may be in the definition of remission-"Remission was defmed as absence of symptoms or the presence of only mild stable symptoms of colitis". The latter part of this definition is a possible source of difficulty, in that it is subjective and indicates some disease activity. Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK
Royal
Charing
Cross
Hospital
C. O. RECORD
Medical School,
K. MACRAE
London
1. Dew MJ, Hughes P, Harries AD, Williams G, Evans BK, Rhodes J. Maintenance of remission in ulcerative colitis with oral preparation of 5-aminosalicylic add. BMJ 1982; 285: 1012. 2. Dew MJ, Harries AD, Evans N, Evans BK, Rhodes J. Manitenance of remission in ulcerative colitis with 5-aminosalicylic add in high does by mouth. BMJ 1983; 287: 23-24. 3. Riley SA, Mani V, Goodman MJ, Herd ME, Dutt S, Turnberg LA. Comparison of delayed-release 5-aminosalicylic add (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis. Gastroenterology 1988; 94: 1383-89. 4. Ireland A, Mason CH, Jewell DP. Controlled trial comparing olsalazine and sulphasalazine for the maintenance treatment of ulcerative colitis. Gut 1988; 29: 835-57. 5. Rijk MCM, Van Lier HJJ, Van Tongeren JHM. Relapse-preventing effect and safety of sulfasalazine and olsalazine in patients with ulcerative colitis in remission: a prospective, double-blind, randomized multicenter study. Am J Gastroenterol
1992; 87: 348-42. 6. Kiilerich S, Ladefoged K, Rannem T, Ranlov PJ, the Danish Olsalazine Study Group. Prophylactic effects of olsalazine v sulphasalazine during 12 months maintenance treatment of ulcerative colitis. Gut 1992; 33: 252-55.
False-positive cases in detection of testosterone doping SiR,—Oftebro reported a 23-year-old male athlete who had been testosterone doping on the basis of a testosterone/ epitestosterone (T/E) ratio in urine of about 9. The definition of a accused of
positive doping case depends on the administration of testosterone or the use of any other manipulation that increases this ratio to above 6.2 The endocrinological investigation of this patient led to the conclusion that the high T/E ratio was due to a naturally reduced excretion of epitestosterone, and not testosterone misuse or a testosterone-secreting tumour. We have seen three similar cases. First, a 19-year-old male cyclist who denied using testosterone was referred to our laboratory to clarify the reason of his positive doping test. Basal serum concentrations of testosterone, androstenedione, dehydroepiandrosterone, sex-hormone-binding globulin, luteinising and follicle-stimulating hormones, oestradiol, and cortisol were normal. Adrenocorticotropic hormone and human chorionic gonadotropin tests were also normal. We found a urinary T/E ratio of 6-7, corresponding to testosterone and
Treatment of
high-altitude pulmonary oedema
SiR,—High-altitude pulmonary oedema (HAPO) is life threatening with appreciable morbidity and mortality in climbers who ascend to over 4000 m,’ although pharmacological intervention benefit. We describe a case of HAPO at 6550 m, which treated with nifedipine. During an expedition to Mount Putha Hiunchuli, Nepal, a 26-year-old woman ascended with two other climbers from 5700 to 6550 m over 10 h in a technically straightforward climb. 6 h later she developed symptoms of acute mountain sickness (AMS)--namely headache, exertional dyspnoea, and dizziness. 2 h later her condition deteriorated (central cyanosis, dyspnoea at rest, tachypnoea, orthopnoea, cough productive of frothy sputum, and ataxia). One of us (G.W.K.) found coarse pulmonary crackles throughout both lung fields. Nifedipine 20 mg was administered orally and glyceryl trinitrate given sublingually, which promptly resolved her symptoms and signs (AMS score, which had been 9 when nifedipine was given, was 2 at 7 h and 1 at 16 h). She remained at this altitude for 16 h because of bad weather, taking nifedipine 20 mg 8 hourly, and was able to return to base unaided 36 h after the start of illness. The two other climbers who had taken nifedipine 20 mg 8 hourly from the start of the ascent had no symptoms of HAPO, and were able to continue the climb. Nifedipine significantly reduces indirectly measured pulmonary artery pressure and AMS score.3 When given prophylactically to climbers ascending to over 4000 m nifedipine may prevent HAPO or lessen its severity.4 Our case illustrates two extra features: efficacy at very high altitude (6250 m) in the absence of other prophylaxis (eg, acetazolamide5) and rapid reversal. The mechanism of action of nifedipine is presumed to be related to reversal of hypoxia-induced pulmonary hypertension. What part sublingual nitrate has is uncertain. Nitrates can acutely reduce pulmonary artery pressure and it remains to be answered whether nitrates have similar effects to nifedipine in HAPO and if so, whether they are synergistic or better than currently used drugs in prevention and treatment.
has
some
was
Department of Medicine and Gardiner Institute, Western Infirmary, Glasgow G11 6NT, UK
Therapeutics, ANDREW JAMIESON
Dungavel, Auchterarder Road,
Dunning
GARY W. KERR
1. Hackett PH, Rennie D, Levine HD. The incidence, importance, and prophylaxis of acute mountain sickness. Lancet 1976; ii: 1249-55. 2. Coote J. Pharmacological control of altitude sickness. TIPS 1991; 12: 450-55. 3. Oelz O, Maggiorini M, Ritter M, et al. Nifedipine for high altitude pulmonary oedema. Lancet 1989; ii: 1241-44. 4. Bartsch P, Maggiorini M, Ritter M, Noti C, Vock P, Oelz O. Prevention of high-altitude pulmonary edema by nifedipine. N Engl J Med 1991; 325: 1284-89. 5. Oelz O. A case of high-altitude pulmonary edema treated with nifedipine. JAMA 1987; 257: 780.
Mesalazine versus olsalazine for prophylaxis of ulcerative colitis relapse SIR,-Dr Courtney and colleagues (May 23, p 1279) in their study of 12-month relapse rates in ulcerative colitis after prophylactic treatment with either mesalazine or olsalazine show a much lower rate (24-5%) with olsalazine than with mesalazine (46%). Although this is the only study comparing these two treatments directly, other studies comparing one or other of these drugs with sulphasalazine give good reason to suspect that the difference found by Courtney and colleagues may be due to chance or some methodological flaw. In reviewing the various studies, like Courtney et al, we have used (where sufficient information is provided) an intention-to-treat analysis in which patients withdrawn after randomisation are classed as treatment failures. Three trials have compared mesalazine and sulphasalazine. Dew et all showed a 16-week relapse rate of 26-5% for mesalazine and 18-2% for sulphasalazine (chi-square test, p 0-42). They later reported2 a 6-month relapse rate of 21-9% with mesalazine and 20 0% with sulphasalazine (p = 0-87). Finally Riley et al3 recorded a 40% 48-week relapse rate with mesalazine =
and a 46% relapse rate with sulphasalazine (p = 0-54). Thus none of the individual studies shows a significant difference between mesalazine and sulphasalazine. In addition, the Mantel-Haenszel chi-square obtained by pooling all these studies (meta-analysis) is 0-02 (p = 0-89). Three trials have also compared olsalazine and sulphasalazine. Ireland et al4 showed a 6-month relapse rate of 39% with olsalazine and 23-2% with sulphsalazine (p= 0-029), a significantly better result for sulphasalazine. Rijk et all noted a 48-week relapse rate of 60-9% with olsalazine and 47-8% with sulphasalazine, (p=037), Lastly, Kiilerich et al6 obtained a 12-month relapse rate of 54% with olsalazine and 48-2% with sulphasalazine (p=0’45). The metaanalysis Mantel-Haenszel chi-square is 4-90 (p=0-027)-a statistically significant difference in favour of sulphasalazine. Thus, relapse rates with mesalazine do not differ significantly from those with sulphasalazine, and one trial and the meta-analysis showed significant differences in favour of sulphasalazine when compared with olsalazine. The apparently large difference between olsalazine and mesalazine obtained in the Courtney study is inconsistent with these results. The relapse rates for each treatment vary considerably from study to study, probably reflecting selection criteria and assessment methods used: relapse rates with sulphasalazine were 1821-1182%6; with mesalazine 21-9-40%; and with olsalazine 394-60,9%5. The relapse rate for mesalazine in the Courtney study is above the upper range in other studies, whereas that for olsalazine is below the lower range. Therefore, there is a strong suggestion that the patient groups were not comparable in that study. Perhaps the explanation may be in the definition of remission-"Remission was defmed as absence of symptoms or the presence of only mild stable symptoms of colitis". The latter part of this definition is a possible source of difficulty, in that it is subjective and indicates some disease activity. Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK
Royal
Charing
Cross
Hospital
C. O. RECORD
Medical School,
K. MACRAE
London
1. Dew MJ, Hughes P, Harries AD, Williams G, Evans BK, Rhodes J. Maintenance of remission in ulcerative colitis with oral preparation of 5-aminosalicylic add. BMJ 1982; 285: 1012. 2. Dew MJ, Harries AD, Evans N, Evans BK, Rhodes J. Manitenance of remission in ulcerative colitis with 5-aminosalicylic add in high does by mouth. BMJ 1983; 287: 23-24. 3. Riley SA, Mani V, Goodman MJ, Herd ME, Dutt S, Turnberg LA. Comparison of delayed-release 5-aminosalicylic add (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis. Gastroenterology 1988; 94: 1383-89. 4. Ireland A, Mason CH, Jewell DP. Controlled trial comparing olsalazine and sulphasalazine for the maintenance treatment of ulcerative colitis. Gut 1988; 29: 835-57. 5. Rijk MCM, Van Lier HJJ, Van Tongeren JHM. Relapse-preventing effect and safety of sulfasalazine and olsalazine in patients with ulcerative colitis in remission: a prospective, double-blind, randomized multicenter study. Am J Gastroenterol
1992; 87: 348-42. 6. Kiilerich S, Ladefoged K, Rannem T, Ranlov PJ, the Danish Olsalazine Study Group. Prophylactic effects of olsalazine v sulphasalazine during 12 months maintenance treatment of ulcerative colitis. Gut 1992; 33: 252-55.
False-positive cases in detection of testosterone doping SiR,—Oftebro reported a 23-year-old male athlete who had been testosterone doping on the basis of a testosterone/ epitestosterone (T/E) ratio in urine of about 9. The definition of a accused of
positive doping case depends on the administration of testosterone or the use of any other manipulation that increases this ratio to above 6.2 The endocrinological investigation of this patient led to the conclusion that the high T/E ratio was due to a naturally reduced excretion of epitestosterone, and not testosterone misuse or a testosterone-secreting tumour. We have seen three similar cases. First, a 19-year-old male cyclist who denied using testosterone was referred to our laboratory to clarify the reason of his positive doping test. Basal serum concentrations of testosterone, androstenedione, dehydroepiandrosterone, sex-hormone-binding globulin, luteinising and follicle-stimulating hormones, oestradiol, and cortisol were normal. Adrenocorticotropic hormone and human chorionic gonadotropin tests were also normal. We found a urinary T/E ratio of 6-7, corresponding to testosterone and
