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and natural killer cells in acute human lesions presumed to be viral in origin. Membrane lesions in myocardial cells were displayed in endomyocardial biopsy specimens by ultrastructural methods and consisted of 15-20 nm pores that are typical of perforin action. These pores can be distinguished from the 10 nm lesions induced in cellular targets by the membrane attack complex of complement, a distinct but structurally homologous agent of humoral immune lysis. Many questions remain unanswered about the specific signals responsible for recruitment and activation of different effector cells at sites of inflammation, and about the relative contribution of different granule products to target cell lysis. The cellular mechanisms for target recognition4 and precisely controlled local degranulation are worthy of intense studys as is the polarised process of destruction of the target cell without suicidal injury to effector leucocytes.6 Above all, will it be possible to limit destruction of vital cells, as in the myocardium, without compromising the ability of the immune system to eradicate an intracellular infectious agent? The results of Young et al serve to remind physicians that a mononuclear cell infiltrate brings with it a two-edged sword.

lymphocytes myocarditis

1. Young

J Ding-E. Killing of target cells by lymphocytes: a mechanistic Am Physiol Soc 1989; 69: 250-313. 2. Young LHY, Klavinskis LS, Oldstone MBA, et al. In vivo expression of perforin by CD8+ lymphocytes during an acute viral infection. J Exp Med 1989; 169: 2159-71. 3. Muller C, Kagi D, Aebischer T, et al. Detection of perforin and granzyme A mRNA in infiltrating cells during infection of mice with lymphocytic choriomeningitis virus. Eur J Immunol 1989; 19: 1253-59. 4. Townsend A, Bodmer H. Antigen recognition by class I-restricted T lymphocytes. Annu Rev Immunol 1989; 7: 601-24. 5. Kupfer A, Singer SJ. Cell biology of cytotoxic and helper T-cell view.

functions. Annu Rev Immunol 1989; 7: 309-37. 6. Persechini PM, Young J Ding-E, Almers W. Membrane channel formation by the lymphocyte pore-forming protein: comparison between susceptible and resistant target cells. J Cell Biol 1990; 110: 2109-16.

better tolerated than others. Moreover, availability of so many drugs, mere control of hypertension is not enough. Clinicians must not only strive to minimise drug-specific adverse events but also to assess the possible impact of treatment on a patient’s quality of life. Croog and colleagues4 conducted one of the first large studies to assess quality of life; this work was supported by Squibb. Men with mild to moderate hypertension were

although

some are

with the

recruited into a double-blind randomised trial for 6 months to determine the effects of captopril, methyldopa, or propranolol on their quality of life as assessed by interviews throughout the study. Blood pressure control was similar with all three drugs, although some patients needed additional diuretics. Fewer patients withdrew from therapy with captopril because of adverse events. Patients receiving captopril scored better on measures of general wellbeing and had fewer side-effects and better measures of life satisfaction than those receiving methyldopa. Captopril also scored better than propranolol in measures of wellbeing. The subsequent marketing campaign alerted physicians to examine their prescribing practices but also initiated the controversy about the validity of what was measured. The difficulty is how to make a formal objective assessment of the subjective feelings and needs of an individual and obtain results with scientific credibility. Although captopril appeared best in the study by Croog et al4 the trial did not examine, for example, whether patients were troubled by cough, which is now known to affect 15 % of those who take this drug. The tests were confined to patients’ subjective responses, which may not be enough. Jachuck et al5 asked physicians, patients taking antihypertensive drugs, and patients’ relatives or close companions about quality of life.5 In their overall assessment of each patient’s condition, 100% of physicians thought the patient was improved, 48 % of patients thought that they had improved, but 98% of relatives or companions believed that the patients’ quality of life was worse during

therapy. DOING BETTER, FEELING WORSE

hypertension has undergone a remarkable transformation in the past twenty years; prescribers now have a vast number of drugs from which to choose. However, although much time has been spent on defining groups of patients suited to various classes of drug, none of the resulting classifications is satisfactory. If official guidelines are followed, drug treatment should be offered to anyone with a diastolic pressure consistently greater than 100 mg Hg.l In the UK, for example, use of this criterion would net 10-15% of the adult population, and with the Treatment for

emphasis on detection and prevention, more patients than ever are going to be found. The potential market for antihypertensive agents is enormous and pharmaceutical companies know it. One difficulty about treating high blood pressure is that most patients have no symptoms-therapy may cause side-effects in people who previously felt well. In trials of antihypertensive therapy, adverse reactions to drugs have resulted in withdrawal rates of 16-33%.’ Practitioners are often struck by the lower frequency of side-effects when an agent is used for antianginal rather than antihypertensive therapy, but the patient with angina knows when something is working. No antihypertensive drug is without side-effects,

To refine the objective estimates of quality of life, Bulpitt and Fletcher> have now produced a questionnaire for use in short-term trials (less than 1 year) of antihypertensive treatment.6 The questionnaire covers symptomatic (physical) wellbeing, psychological wellbeing with the symptom rating test/ and perception of the effects of antihypertensive treatment on lifestyle. There are 46 questions, most of which require yes/no responses. This approach must represent the most comprehensive attempt so far to obtain useful information about antihypertensive therapy by means of a standardised repeatable format. However, the feelings of relatives are not assessed. The test has been applied in three comparisons of drug treatments7-9 and the results suggest that propranolol causes a deterioration in symptomatic wellbeing and possibly increases depression, whereas nifedipine may adversely affect self-reported cognitive function. In another study, verapamil was compared with nifedipine with regard to effects on quality of life by use of this questionnaire. 10 There was a significant increase in reporting of side-effects with nifedipine, and measures of psychiatric morbidity tended to improve on verapamil and deteriorate on nifedipine. Only the change in cognitive function was significant between the drugs, being worse on nifedipine. Notwithstanding these results, many patients will be satisfied with P-blockers or nifedipine, and the possibility of a modest improvement in cognitive function

1038

by a change to verapamil might be offset by the increased risk of constipation. So, do assessments of quality of life help prescribers? Bulpitt and Fletcher’s questionnaire provides interesting information about important aspects of drug treatment and may highlight previously unsuspected adverse effects. It will provide a standardised protocol for future studies and may reveal small differences between drugs. The relevance of such trial assessments to the individual needs of patients or prescribing practices is uncertain. They will not replace the close personal monitoring that all patients should receive when they are expected to embark on a treatment regimen for life. JD, Ramsay LE, Coope JR, et al. Treating mild hypertension. Report of the British Hypertension Society Working Party. Br Med J

1. Swales

1989; 298: 694-98.

Working Party on Mild to Moderate Hypertension. Adverse reactions to bendrofluazide and propranolol for the treatment of mild hypertension. Lancet 1981; ii: 539-43. 3. Curb JD, Borhani NO, Blaszkowski TP, Zimbaldi N, Fotiu S, Williams W. Long-term surveillance for adverse effects of antihypertensive 2. MRC

drugs. JAMA 1985; 253: 3263-68. Croog SH, Levine S, Testa M, et al. The effects of antihypertensive therapy on the quality of life. N Engl J Med 1986; 314: 1657-64. 5. Jachuck SJ, Brierley H, Jachuck S, Willcox PM. The effect of hypotensive drugs on the quality of life. J Coll Gen Pract 1982; 32: 4.

103-05.

6. Bulpitt CJ, Fletcher AE. The measurement of quality of life in hypertensive patients: a practical approach. Br J Clin Pharmacol 1990; 30: 353-64. 7. Fletcher AE, Chester PC, Hawkins CMA, Latham AN, Pike LA, Bulpitt

CJ. The effects of verapamil and propranolol on quality of life in hypertension. J Hum Hypertens 1989; 3: 125-30. 8. Fletcher AE, Bulpitt CJ. Quality of life during antihypertensive treatment: results from a randomised double-blind trial of pinacidil and nifedipine. J Hypertens 1989; 7 (suppl 6): 364 (abstr). 9. Fletcher AE, Bulpitt CJ, Hawkins CM, et al. Quality of life on anti-hypertensive therapy: a randomised double-blind controlled trial of captopril and atenolol. J Hypertens 1990; 8: 463-66. 10. Palmer A, Fletcher A, Hamilton G, Muriss S, Bulpitt C. A comparison of verapamil and nifedipine on quality of life. Br J Clin Pharmacol 1990; 30: 365-70.

GLOBAL SCALE OF AVOIDABLE BLINDNESS As many as 35 million of the world’s population are blind. A quarter of a million undernourished children are blinded each year by xerophthalmia in Asia alone. Onchocerciasis affects about 28 million people, blinding nearly half of all adults in some endemic parts of Africa. 6-9 million people are blind as a result of trachoma, while another 80 million need treatment.A disproportionate number of blind people live in developing countries, with little hope of recovering their sight, yet blindness due to all these diseases is potentially avoidable, by either prevention or cure. The scale of the figures is difficult to grasp, and their implications almost impossible to imagine. For logistical and geographical reasons reliable epidemiological data are not easy to collect, and most studies have been cross-sectional descriptions of the prevalence of disease in populations. Such a survey,2 from rural Kenya, reports a prevalence of blindness of 1-7%, with a five-fold increase in risk in successive 20-year age cohorts. These results show that blindness is about eight times commoner in rural Kenya than in the USA. Whilst prevalence surveys indicate the "backlog" of existing untreated cases, an estimate of incidence, or the rate that new cases arise, is needed for health care resource planning. Minassian and Mehra33 estimate from a longitudinal survey that 3-8 million people are blinded by cataract in India each year. Since 1-2 million

operations are carried out in India annually, the backlog must be increasing substantially. cataract

Cataract is the main cause of blindness worldwide; the for the greater incidence of cataract in tropical and developing countries is not entirely clear. Ultraviolet radiation is cataractogenic, but the role of sunlight in cataractogenesis in developing countries is not established. There is some evidence that recurrent episodes of dehydration, such as occur in severe diarrhoeal disease, can cause irreversible changes in lens protein, and may cumulatively lead to cataract.4 In round (and conservative) figures, the cataract backlog is about 10 million, and growing quickly. There are probably not enough eye surgeons in the whole world to treat more than a fraction of these people. Moreover, a surgical team needs transport, instruments, and drugs, as well as the infrastructure to identify, select, and prepare patients and to arrange postoperative care. Periodic tours by visiting eye surgeons have brought benefit to countless thousands of individuals, but on a global scale are scarcely more than symbolic. Occasional jet-borne highprofile, high-technology visits are at best irrelevant. However, cataract can be cured surgically by use of technology appropriate to mobile teams or eye camps. It is not essential for the operators to have medical, surgical, or ophthalmic qualifications; in Africa, surgical field programmes are run effectively by ophthalmic assistants. Prevention, where it is possible, must be a better option. Hygiene, nutrition, and sanitation are implicated in the pathogenesis of trachoma and nutritional blindness, which occur mainly in communities with marginal infant nutrition and inadequate water suplies. Carefully targeted proteincalorie and vitamin supplements, and antimicrobial therapy, can greatly reduce the incidence of blindness due to trachoma and xerophthalmia in individuals and communities at risk, but ultimately the solution to these disorders is political and economic rather than medical or surgical. As yet there is not such a well-defined place for prevention in reducing blindness due to cataract. According to the diarrhoea-dehydration theory, during episodes of dehydration, increased serum levels of isocyanate, in equilibrium with urea, lead to lens opacification by altering lens protein binding. If so, cataract may unexpectedly prove to be amenable to improvements in basic public health measures-water supply, nutrition, and sanitationalongside xerophthalmia and trachoma. For now, curative resources are inadequate, on such a scale that millions become blind worldwide, at great cost to their families, their communities, and their countries in care and lost production. The cumulative increase in unnecessary misery can be reversed only with help from the developed world, which should contribute sufficient resources, equipment, and training for surgery in the field to match the needs. In the longer term industrialised countries can help by continuing the research into cause and prevention of blindness. reason

1. IAPB. World blindness and its prevention; vol 3. Oxford: Oxford University Press, 1988. 2. Whitfield R, Schwab L, Ross-Degnan D, Steinkuller P, Swartwood J.

Blindness and eye disease in Kenya: ocular status survey results from the Kenya Rural Blindness Prevention Project. Br J Ophthalmol 1990; 74: 333-40. 3. Minassian DC, Mehra V. 3·8 million blinded by cataract each year: projections from the first epidemiological study of incidence of cataract blindness in India. Br J Ophthalmol 1990; 74: 341-43. 4. Minassian DC, Mehra V, Jones BR. Dehydrational crises from severe diarrhoea or heatstroke and risk of cataract. Lancet 1984; i: 751-53.

Doing better, feeling worse.

1037 and natural killer cells in acute human lesions presumed to be viral in origin. Membrane lesions in myocardial cells were displayed in endomyoca...
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