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signs of mental impairment. His Katz score was 6 his MMSE score was 29. and (minimum) In case 1, timely rehabilitation prevented progressive disability and the patient is now functioning almost independently. In case 3, readjustment of medication reversed a disability that was about to become chronic. In the other two cases, there was a subacute disabling disorder; after treatment for this disorder both patients now function independently. showed

no

Department of Geriatric Medicine, Dijkzigt University Hospital, Erasmus University, 3015 GD Rotterdam, Netherlands

TISCHA J. M. VAN DER CAMMEN C. J. VERSCHOOR

S, Ford AB, Moskowitz RW, et al. Studies of illness in the aged: the index of ADL; standardized measure of biological and psychosocial function. JAMA 1963;

1. Katz

185: 94.

SIR,-As your Aug 10 editorial hints, there is a pressing need for ways of assessing success or failure in the management of incurable or chronic disease. We can evaluate different interventions in acute myocardial infarction or acute leukaemia because short-term mortality is a reasonable outcome to study. However, even when a difference in survival

be shown, the story does not end there. Does thrombolytic therapy salvage lives disabled by angina or heart failure? Does chemotherapy prolong life at the expense of nausea, alopecia, and falsely-raised expectations? The assessment of complex interventions such as rehabilitation programmes, psychiatric management, or the siting and organisation of long-term care institutions for the elderly is even more difficult. We must try to assess quality of life in a wide range of circumstances and those who decry such attempts deny what we do from day to day under the name of "clinical judgment" and ignore the benefits that would accrue from being able to evaluate properly new treatments or service innovations. Those who argue that it is unethical to allocate resources on the basis of perceived need and existing service patterns, rather than proven benefits, would be unanswerable if can

convincing quality-of-life measures were available; unfortunately, they are not.1 The first step in trying to measure something is to define it, so that you can then establish some entity that is quantifiable-but there is no adequate definition of quality of life. Furthermore, many factors influence quality of life besides ill-health, such as relationships, employment, interests, and wealth, on which health care can at best have only an indirect influence. An alternative approach exists. The World Health Organisation’s International Classification of Impairments, Disabilities and Handicaps (ICIDH)2 provides a new taxonomy for evaluating the consequences of chronic disease. An impairment is an abnormality of structure or function of a limb or organ (eg, weakness, pain, shortness of breath). A disability is the inability to perform a task or activity, such as walking, dressing, or maintaining continence. A handicap is the disadvantage resulting from ill-health that an individual has compared with others of his or her age, sex, and background. It seems to be handicap that concerns patients most,3,4 so handicap is a suitable outcome measure for assessing interventions in chronic disease. Moreover, handicap is well defined, and its reduction is the goal of management in chronic disease. By restricting the definition of quality of life to healthrelated disadvantage, the effects of health-care interventions will not be diluted by non-health-related influences. Unfortunately, measures of handicap have so far been rudimentary. 5,6 The ICIDH remains one of the best-kept secrets of modern medicine, yet its concepts provide the key to rational management of chronic diseased Attempts to measure handicap give the best chance of developing a valid quality outcome measure for research into disability and the management of chronic disease. Department of Health Care of the Elderly, Medical Colleges of Royal London and St Bartholomew’s Hospitals,

Royal London Hospital, London E1 4DG, UK 1. Rosser R. From health indicators to

2. World Health

Organisation. International classification of impairments, disabilities and handicaps. Geneva: WHO, 1980. 3. Bury MR. The ICIDH: a review of research and prospects. Int Disabil Stud 1987; 9: 118-28. 4. Williams GH. Disablement and the social context of daily activity. Int Disabil Stud 1987; 9: 97-102. 5. Herbert R, Carrier R, Bilodeau A. The functional autonomy measurement system (SMAF): description and validation of an instrument for the measurement of

handicaps. Age Ageing 1988; 17: 293-302. 6. Affleck JW, Aitken RCB, Hunter JAA, McGuire RJ, Roy CW. Rehabilitation status: a measure of medicosocial dysfunction. Lancet 1988; i: 230-33. 7. Ebrahim S. Measurement of impairment, disability and handicap. In: Hopkins A, Costain D, eds. Measuring the outcomes of medical care. London: Royal College of Physicians of London, 1990: 27-41.

An African Index Medicus SIR,-At the third biennial congress of the Association for Health Information and Libraries in Africa (AHILA-3) which took place in Harare, Zimbabwe, a small event occurred that could have far-reaching implications in the way health and medical information is accessed in African countries and elsewhere. Bibliographical records from the World Health Organisation (WHO) office of health literature and information sevices, the Malawi Ministry of Health library and documentation centre, and the University of Nairobi medical library were successfully merged into one database with ’CDS/ISIS’ software and the WHO ’WHOBIS’ format. The result was an African Index Medicus. At the Sixth International Congress on Medical Librarianship (New Delhi, 1990) the African librarians had agreed to try and work on locally created databases that would be compatible with the WHOBIS format so that records could be exchanged or compiled into a single database. The records produced at the AHILA-3 3 were an that Index Congress successfully merged, proving African Medicus is possible. The database could be published on CD-ROM disk, like MEDLINE. The participants of the AHILA-3 congress approved a recommendation to use CDS/ISIS software (a database management package distributed free to developing countries by UNESCO) and the WHOBIS format (distributed free by WHO) as the medium for exchange of computerised database records. The WHO regional office for Africa or the University of Zimbabwe medical library will be the places of collection and dissemination of database records from individual institutions. They will compile the individual institutional records to form the African Index Medicus (a similar project is successfully being done in the Americas). Because there are conversion programs from CDS/ISIS to other database management programs such as ’dBase’ or ’Cardbox’ previous records on other software packages do not have to be redone. Individual institutions therefore have some flexibility to make their database as locally relevant as possible but still exchangeable. For libraries and documentation centres not already using a software package, the WHOBIS format can be installed and used directly as the database. The African Index Medicus will help to improve the way health and medical research is conducted in African countries. Although much research is being done in these countries, very little is indexed in standard bibliographies. Many researchers publish in nonAfrican journals because they fear no one will otherwise notice their work. The African Index Medicus will make available much health and medical information previously unrecorded and probably overlooked. If African workers know that their work can be published locally but still be available to an international audience, they may keep local medical journals going and support the local publishing industry. This may forestall suggestions by some countries to prohibit the publication of research elsewhere. Ministry of Health, PO Box 30377, Capital City, Lilongwe 3, Malawi

MARC LIPPMAN

Management of chronic renal failure ROWAN HARWOOD SHAH EBRAHIM

quality adjusted life years: technical and ethical issues. In: Hopkins A, Costain D, eds. Measuring the outcomes of medical care. London: Royal College of Physicians of London, 1990: 1-17.

SIR,-Professor Klahr (Aug 17, p 423) is generous when he says that creatinine clearance reflects renal function as long as the glomerular filtration rate (GFR) exceeds 20 ml/min. The reflection can be very dim indeed. Shemesh et all showed creatinine clearances ranging from 90 to 220 ml/min in patients with inulin

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clearances of 130 ml/min, and creatinine clearances ranging from 50 to 165 ml/min in those with inulin clearances of 70 ml/min; by contrast, there was very close agreement between the clearance values for 99mTc-diethylenetriamine pentaacetic acid (DTPA) and inulin. They suggested that by combining the routine plasma creatinine-based monitoring of glomerular disease with occasional measurements of DTPA clearance appropriate changes in therapy were more likely to be made. Because serum creatinine concentration is easy to measure, it will remain the most widely used index of renal function in clinical practiced However, care must be taken to avoid being misled.3 Samples should be taken at least 10 h after the last meat-containing meal because of creatinine absorption. Values measured by the widely-used Jaffe method may be spuriously high in ketosis and in patients taking cefoxitin or cephalothin (but not other cephalosporins), and may be raised by inhibition of the tubular secretion of creatinine in patients receiving salicylate, cotrimoxazole, trimethroprim, or cimetidine. Department of Chemical Pathology, University Hospital, Leeds LS9 7TF, UK

St James’s

R. B. PAYNE

1. Shemesh O, Goldbetz H, Kriss JP, Myers BD. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int 1985; 28: 830-38. 2. Levy AS. Measurement of renal function in chronic renal disease. Kidney Int 1990; 38: 167-84. 3. Payne RB. Creatinine clearance: a redundant clinical investigation. Ann Clin Biochem 1986; 23: 243-50. 4. Jacobsen FK, Christensen CK, Mogensen CE, Heilskov NSC. Evaluation of kidney function after meals. Lancet 1980; i: 319.

Genomic imprinting in an Angelman and Prader-Willi translocation family SIR,-Attention has lately focused on the syndromes of Angelman (AS) and Prader-Willi (PWS) as outstanding clinical examples of genomic imprinting, in which an apparently identical chromosomal mutation is associated with a differential phenotype, depending on parental origin.1 These two mental deficiency syndromes have different, and in some ways opposite, phenotypes, showing specific facial dysmorphisms. AS is further characterised by a stiff jerky gait, inappropriate laughter, and absent speech, while children with PWS have muscular hypotonia, overeating, obesity,

hypogonadism,

short stature, and small hands and feet. Yet both

syndromes are characterised by an apparently identical mutationa deletion within the proximal region of the long arm of chromosome 15 but with the difference that in AS the abnormal chromosome 15 is inherited from the mother, whereas in PWS it

from the father. An important aspect of these events is the unipotential disomy of chromosome 15. Some children with AS have two (apparently normal) chromosomes 15 from their father and none from their mother, while exactly the opposite is true for some PWS children who have inherited both their chromosomes 15 from their mother but lack a chromosome 15 from their father. Almost all cases of AS and PWS are sporadic, occurring de novo in patients from different families. This makes it difficult to exclude the possibility that some factor other than the 15q deletion dictates the AS/PWS phenotype. Familial structural rearrangements, such as inversions and translocations, are rare, and so far all familial AS cases have had cytogenetically normal chromosomes. By genomic imprinting we would expect to fmd translocation and inversion families with both AS and PWS children, dependent on transmitting parental sex. We now report such a translocation family. The index child with classic AS has a maternally derived comes

unbalanced translocation, leading to a deletion 15pter- > ql3 and a duplication 22pter- > ql 1. Another branch of this family has two children with PWS, having the same unbalanced translocation, but of paternal derivation.’ The family tree is shown in fig 1. The affected children III:1, and 11:9 and 11 show classic symptoms of AS and PWS, respectively, with no indication of any deviation of phenotype, as might be expected from the duplication 22pter- > qll, which they share in common with the relevant deletion 15pter- > ql3. The most likely explanation for this lack of phenotypic effect of the duplication may be its heterochromatic nature, being comprised mainly of repeated DNA sequences of the chromosome 22 centromere, the 22 short arm, and the nucleolar organiser. The unbalanced 15;22 translocation in the index children with AS and PWS (III:land 11:11) was overlooked at first and classified as the typical 15q11- > 13 deletion. It was only detected by the

application of more specialised cytogenetic techniques (distamycinDAPI and fluorescence in-situ hybridisation) (fig 2). Also, the biological relation between the PWS and AS children has only come to light after intensive and specific inquiries. It would now appear important both to obtain detailed pedigree information and to reinvestigate other cases of apparent sporadic PWS and AS cases cytogenetically with fluorescence in-situ hybridisation. It is essential to note that the translocation is not detectable by standard molecular analysis with chromosome 15 probes. To our knowledge this family represents the first clear-cut example in man of genomic imprinting. This result has important clinical implications for genetic counselling. The carrier females 11:2 and 11:6 are at high risk of having children with AS, while their brothers II:3, II:5, II:8, and II: 12 have a high risk of having PWS children. The reason why a 15ql 1- > ql3 deletion should give rise

Fig 1-Family tree showing segregation of balanced translocation t(15;22)(q13;q11). Translocation identified by G-bandng, distamycin-DAPI, and fluorescence in-situ hybridisation with genomic library for chromosome 15 (pBs1 5) and D1 5Z1 pericentromeric probe. 1:1, 1:3, and 11:1 have normal karyotypes. 1.2, 11:2, 11.3, 11.5, 11:6, 11:8, and H 12are phenotypically normal carriers of the balanced translocation; index child with AS 111:1 and two children with PWS 11.9 and 11:11 share same unbalanced and duplication 22pter- > q11. Pregnancies 111:2 and 111:3 terminated due translocation leading to deletion 15q11> 13 to antenatal diagnosis of same unbalanced karyotype, and other unbalanced translocation with duplication 15q11 - > 13 and deletion 22pter->q11, respectively. Children 11:7 and 11:10 died m the neonatal period.

Management of chronic renal failure.

637 signs of mental impairment. His Katz score was 6 his MMSE score was 29. and (minimum) In case 1, timely rehabilitation prevented progressive disa...
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