478

think that such success rates could not be achieved elsewhere. no reason to

1. Wroblewski BM. 15-21 year results of the Charnley low friction arthroplasty. Clin Orthop 1986; 211: 30-35. 2. Rand JA, Ilstrup DM. Survivorship analysis of total knee arthroplasty. J Bone Joint Surg 1991; 73A: 397-409. 3. Tew M, Waugh W. Estimating the survival time of knee replacements. J Bone Joint Surg 1982; 64B: 579-82. 4. Grimer RJ, Karpinski MR, Edwards AN. The long term results of Stanmore total knee replacements. J Bone Joint Surg 1984; 66B: 55-62. 5. Insall JN, Ranawat CS, Aglietti P, Shine J. A comparison of four models of total knee replacement prostheses. J Bone Joint Surg 1976; 58A: 754-65. 6. Ranawat CS, Boachie-Adjei O. Survivorship analysis and results of total condylar knee arthroplasty. Clin Orthop 1988; 226: 6-13. 7. Vince KG, Insall JN, Kelly MA. The total condylar prosthesis. J Bone Joint Surg 1989; 71B: 793-97. 8. Wright J, Ewald FC, Walker PS, et al. Total knee arthroplasty with the kinematic prosthesis. J Bone Joint Surg 1990; 72A: 1003-09. 9. Stulberg BN, Insall JN, Williams GW, Ghelm B. Deep vein thrombosis following total knee replacement. J Bone Joint Surg 1984; 66A:

194-201. 10. Wilson MG, Kelly K, Thornhill TS. Infection as a complication of total knee replacement arthroplasty. Risk factors and treatment in 67 cases. J Bone Joint Surg 1990; 72A: 878-83. 11. Rand JA, Bryans RS. The outcome of failed knee arthrodesis following total knee arthroplasty. Clin Orthop 1986; 205: 86-92. 12. Broughton NS, Mewman JH, Bailey RAJ. Unicompartmental replacement and high tibial osteotomy for osteoarthritis of the knee. J Bone Joint Surg 1996; 68B: 447-52. 13. Marmor L. Unicompartmental knee arthroplasty. Clin Orthop 1988; 226: 14-20. 14. Ranawat CS, Padgett DE, Ohashi Y. Total knee arthroplasty for patients younger than 55 years. Clin Orthop 1989; 248: 27-33. 15. Knutson KA, Lindstarnd A, Lidgren L. Survival of knee arthroplasties. J Bone Joint Surg 1986; 68B: 795-803.

dexamethasone for chemotherapy-induced emesis

Ondansetron

vs

days when patients refused cancer chemotherapy because of the severity of drug-induced nausea and vomiting should now be over. The importance of 5-hydroxytryptamine3 (5-HT3) receptor mechanisms in the pathogenesis of nausea with highly emetic regimens containing cisplatin is well recognised,l and partly stemmed from the work of Gralla et aP with high-dose metoclopramide, a drug with some 5-HT3 receptor antagonist activity. New 5- HT antagonists are a real advance because they do not cause the unpleasant extrapyramidal effects that sometimes limit metoclopramide treatment. Nevertheless, metoclopramide, even at very high doses, is not universally effective, and it was unreasonable to assume that specific 5-HT33 antagonists would be very different in this respect. Combinations of high-dose metoclopramide and other agents, including benzodiazepines and corticosteroids, have been widely used to enhance antiemetic potential.3 The

The mechanism of action of these additional therapies is less certain than that of 5-HT3antagonists, but clinical efficacy makes basic scientific considerations a secondary issue. The report in this issue (p 487) by Smith et al is therefore interesting and reassuring. These researchers show that the combination of the 5-HT3 antagonist ondansetron with dexamethasone is, as has been suggested,4more

effective than ondansetron alone in patients receiving highly emetic "high-dose" cisplatin in the POMB treatment schedule (vincristine, methotrexate, bleomycin, and cisplatin with folinic acid rescue). Thus, in the 24-48 h period following cisplatin, 30% of patients receiving ondansetron had a complete or major response (two or fewer episodes of vomiting) compared with 78 % (p 0-001) for the combination. These response rates to ondansetron alone are lower than those of earlier studies, in which the drug was more effective than high-dose metoclopramide, especially during the first 8 h of chemotherapy.s Nevertheless, the message is that, for highly emetic chemotherapeutic regimens, the combination of ondansetron and dexamethasone is effective for the great majority of patients. New drugs usually have another irnplication-cost. Ondansetron (the only 5-HT3 antagonist marketed in the UK) has an impressive price tag. Although use of this agent in patients receiving cisplatin is clearly justified, what about its role with less emetic chemotherapeutic regimens? Readers should bear this in mind when they evaluate another study reported in this issue-by Jones et al on p 483. These researchers examined the efficacy of ondansetron and dexamethasone in patients receiving less emetic treatment than that of Smith et al, usually an =

anthracycline and/or cyclophosphamide and/or etoposide. Such patients are more representative of the bulk of those who receive chemotherapy. Ondansetron (4 mg) or dexamethasone (8 mg) was given by intravenous injection before chemotherapy and was followed by oral therapy, 6-hourly for 5 days with 4 mg doses of ondansetron, or a reducing dose of dexamethasone. As might be expected with a less emetic regimen, complete or substantial control of acute emesis was good, (major control in 80%), but no difference was detected between the two treatments. For late nausea (days 2-5), dexamethasone seemed to be more effective (88 vs 73% response, p 0-003) but this difference was not present when the number of vomiting episodes was considered. Fewer patients had more than five emetic episodes on dexamethasone than with ondansetron (17 vs 36%). The cost-inspired policy adopted in some centres of giving ondansetron to patients receiving less emetic treatment only if they are refractory to other therapies therefore seems vindicated by the results of Jones et al. The cost of dexamethasone as used by these workers is 3.45 for 5 days vs C135.50 for ondansetron. Questions for the future include: the optimum dose of dexamethasone; whether it needs to be given intravenously (a route which may contribute to some of its adverse reactions); how the steroid is exerting its effect; and the role of dexamethasone, alone or in combination with other, cheaper drugs, including and standard antiemetics. benzodiazepines Ondansetron can reasonably be reserved as a secondline therapy in all but the most emetic cancer =

chemotherapy regimens.

479

1. Editorial. 5-HT3 receptor antagonists: a new class of antiemetics. Lancet 1987; i: 1470-71. 2. Gralla RJ, Hri LM, Pisko SE. Antiemetic efficacy of high-dose metoclopramide: randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. N Engl J Med 1981; 305: 905-09. 3. Triozzi PL, Laszlo J. Optimum management of nausea and vomiting in cancer chemotherapy. Drugs 1989; 34: 136-49. 4. Cunningham D, Turner A, Hawthorn J, Rosin RD. Ondansetron with and without dexamethasone to treat chemotherapy-induced emesis. Lancet 1989; i: 1323. 5. Marty M. Ondansetron in the prophylaxis of acute cisplatin-induced nausea and vomiting. Eur J Cancer Clin Oncol 1989; 25 (suppl 1): 541-45.

Injected corticosteroids refractory asthma

in

Most patients with asthma have mild symptoms that are usually controlled by a combination of inhaled &bgr;2 agonist and low-dose inhaled corticosteroid.1 When symptoms are more severe, other agents may be added to or substituted for baseline treatment;l.2 examples include sodium, cromoglycate, nedocromil

methylxanthines, anticholinergic bronchodilators, high-dose inhaled steroids, and oral steroids. Oral corticosteroids are reserved mainly for deteriorating asthma or for acute life-threatening exacerbations. However, a few patients require continuous oral corticosteroid treatment because of chronic severe asthma. This condition may become life threatening and is almost always associated with considerable morbidity-eg, frequent hospital admissions and respiratory failure requiring mechanical ventilation. The chronicity of the asthma may additionally lead to long-term complications of corticosteroid treatment. Concern over the chronic administration of oral corticosteroids in patients with refractory asthma has led to the introduction of other treatments including and methotrexate,33 gold,44 troleandomycin,S intramuscular triamcinolone.. The use of high-dose intramuscular triamcinolone was lately supported by a placebo-controlled, doubleblind, cross-over study in twelve patients with chronic severe asthma, in which the effects of this drug in a dose of 360 mg given over 3 days were compared with prednisone 15 mg daily over 3 months.8 All the patients had progressive worsening of their asthma documented over 1-7 years. They required prednisone 5-20 mg daily while receiving inhaled corticosteroids and other standard treatment. The severity of their asthma can be gauged from the fact that eleven of the patients had sixty hospital admissions over the preceding year; five of these episodes required mechanical ventilation. At the time of entry to the study there were clear side-effects of corticosteroid treatment; nine had the facies of Cushing’s syndrome; three were hypertensive; two had diet-controlled diabetes; and one was very obese. Intramuscular triamcinolone improved lung function, with the peak flow reaching an average of 91-5% of predicted compared with 75 % while the patients were receiving prednisone. There were no visits to the emergency room and no hospital admissions during

the triamcinolone period of treatment vs twenty-one emergency visits and ten hospital admissions with two episodes of ventilatory failure during the prednisone period. Other benefits of triamcinolone were that total corticosteroid treatment during the period of triamcinolone treatment was reduced, although there

tendency to more steroid-related side-effects after treatment with triamcinolone. The researchers concluded that high-dose intramuscular triamcinolone was more effective than low-dose prednisone in patients with severe chronic life-threatening asthma, but were cautious about recommending such treatment other than in patients with this type of asthma. At the time of reporting, in the 13 months since the study began only four patients had required repeated injections of triamcinolone, and in the remaining eight patients corticosteroids were needed only infrequently for acute exacerbations; no patient required daily maintenance doses of oral steroids. These results suggest that triamcinolone may have advantages in refractory asthma in patients with chronic severe symptoms who require chronic oral corticosteroids. Studies are now needed to show longer term benefits with respect to asthma and to the corticosteroid-induced side-effects, and to define the lowest dose of triamcinolone that will achieve lasting symptomatic relief. was a

Higgins BG, Tattersfield AE. Modern management of asthma. Hosp Update 1989 (May): 341-18. 2. British Thoracic Society, Research Unit of the Royal College of Physicians of London, Kings Fund Centre, National Asthma 1.

Guidelines for the management of asthma in adults. I-chronic persistent asthma. Br Med J 1990; 301: 651-53. 3. Mullarkey MF, Blumenstein BA, Andrade WP, Bailey GA, Olason I, Wetzel CE. Methotrexate in the treatment of corticosteroid-dependent asthma: a double-blind crossover study. N Engl J Med 1988; 31: 603-07. 4. Muranaka M, Miyamoto T, Shida T, et al. Gold salt in the treatment of bronchial asthma—a double-blind study. Ann Allergy 1978; 40: 132-37. 5. Wald JA, Friedman BF, Farr RS. An improved protocol for the use of troleandomycin (TAO) in the treatment of steroid-requiring asthma. J Allergy Clin Immunol 1986; 78: 36-43. 6. Peake MD, Cayton RM, Howard P. Triamcinolone in corticosteroidresistant asthma. Br J Dis Chest 1979; 73: 39-44. 7. Willey RF, Fergusson RJ, Godden DJ, Crompton GK, Grant IWB. Comparison of oral prednisolone and intramuscular depot triamcinolone in patients with severe chronic asthma. Thorax 1984; 39: 340-44. 8. Ogirala RGO, Aldrich TK, Prezant DJ, Sinnett MJ, Enden JB, Williams MH. High-dose intramuscular triamcinolone in severe, chronic, life-threatening asthma. N Engl J Med 1991; 324: 585-89.

Campaign.

Testing for carpal tunnel syndrome Although median nerve compression within the carpal tunnel is usually easy to diagnose clinically, many patients are subjected to electrophysiological investigation before operation. The need for electrodiagnosis has been questioned and less painful provocative tests have been suggested; there are potential pitfalls with such an approach. Typically, the patients present with pain, paraesthesiae, and numbness of the median-nerveinnervated fingers on awakening. Pain may radiate up