- Email: [email protected]
BALDNESS AND MINOXIDIL ADVERTISING
442 AUDIT AND NECROPSY
SIR,-Audit is a prominent feature of several recent proposals on postgraduate training and clinical practice in the UK. The Government’s white-paper on the National Health Service encourages it. In 1988 a Royal College of Physicians working-party stated that a post for training might not be approved "if adequate clinical review meetings are not held", and the National Confidential Enquiry into Perioperative Deaths (NCEPOD) has instigated the formal audit of deaths within 30 days of surgery. The low necropsy rate in the UK invalidates any form of clinical audit where death is possible outcome.
Clinical diagnoses, often made with confidence, are frequently verified at necropsy. 1,2 Patients die from treatable conditions because of diagnostic errors revealed only at necropsy. In one survey, covering a period during which the necropsy rate had been increased to 65%, 42% of causes of death were unconfirmed and 15% of errors were conceded to be significant by the requesting clinicians.3 Such errors will usually remain undiscovered unless a necropsy is asked for. Undoubtedly, the necropsy rate for deaths in UK hospitals has fallen from over 60% to 25% or less in the past thirty years.4 The rate is especially low for deaths in geriatric units.s Elderly patients are assumed to have irreversible disease processes which are themselves a function of senility. Yet one necropsy study in patients over 65 revealed that in 31 % of cases a potentially treatable contributory factor to death had not been diagnosed during life.’7
not
Low necropsy rates may be attributable to a variety of factors-the pressures of more immediate clinical commitments; the view that imaging, biopsy, and biochemical techniques applied during life render necropsy superfluous; the reluctance of relatives to give consent because the deceased has "suffered enough"; the low priority given to necropsies by pathologists burdened with a heavy biopsy and cytology workload; the reluctance of some clinicians to have diagnostic errors revealed; the fear of litigation for diagnostic errors; and the lack of interest that results if pathologists do not communicate their findings rapidly and clearly to the clinicians who ask for a necropsy. In the USA, the importance of necropsy has been drawn to the public’s attention through the columns of the New York Times (cited by Hill and Anderson8). The Joint Commission on Accreditation of Health Organisations has recommended the use of necropsies for quality assurance. A senior administrator of the Health Care Financing Administraton has expressed concern about the falling necropsy rate. The reliability of death certificate data, unverified by necropsy, has also been questioned in the USA because of the implications for national health policy. In the UK, there should be greater professional, managerial, and public awareness of the importance of necropsy as the "ultimate audit" of clinical outcome. The task of seeking consent from relatives should not be left to the most inexperienced, and often exhausted, member of the clinical team. Adequate funding should be provided for the maintenance of a necropsy rate of at least 75% for deaths in hospital. The importance of the necropsy must be sustained in the new training programmes and examinations in histopathology for membership of the Royal College of Pathologists. Necropsy data should be collected systematically to provide a reliable demographic database of morbidity and
mortality. All hospitals, NHS and private, should be obliged to audit and report internally their necropsy rates and the rates attributable to individual consultants. Staffing levels should be increased where necessary so that necropsies are done thoroughly and the results communicated rapidly to the clinician. The Royal Colleges should monitor necropsy rates and the procedures for disseminating information from them, accreditation for training being conditional on an adequate local necropsy rate that permits valid audit of diagnoses and treatments. Department of Pathology, University of Sheffield Medical School, Sheffield S10 2RX
J. C. E. UNDERWOOD D. W. K. COTTON T. J. STEPHENSON
F, Vecchiet F, Barbierato D, Melato A, Manconi R. Inaccuracy of death certificate diagnoses in malignancy an analysis of 1405 autopsied cases. Hum Pathol 1982; 13: 1036-38. Stevanovic G, Tucakovic G, Dotlic R, Kanjish V. Correlation of clinical diagnoses with autopsy findings. Hum Pathol 1986, 17: 1225-30. Cameron HM, McGoogan E, Watson H. Necropsy as a yardstick for clinical diagnoses. Br MedJ 1980; 281: 985-88. Cameron HM. Future of the hospital autopsy. BrJ Hosp Med 1988; 40: 335 Kohn RR. Causes of death in very old people. JAMA 1982; 247: 2793-97. Editorial. Death in old age. Lancet 1982, ii: 477. Puxty JA, Horan MA, Fox RA. Necropsies in the elderly. Lancet 1983; i: 1262-64 Hill RB, Anderson RE Is a valid quality assurance program possible without the autopsy? Hum Pathol 1988; 19: 1125-26.
1 Gobbato
2. 3. 4. 5.
6. 7. 8.
MEDICAL RESEARCH FUNDING
SIR,-A Lancet editorial of Oct 29 on funding for medical research in the UK (Wellcome Steps into the Breach Once More) accused the Medical Research Council of being "lacklustre clearly unable to inspire any important changes in official policy". The MRC’s "modest stillness and humility" (Henry V) should not have misled you; we can "disguise fair nature with hard-favour’d rage" and have long argued the case for an increase in public funding (as have many others) with conviction and with force. The extra allocation of 14-5 million over 3 years for AIDS research, additional to our grant-in-aid, is one recent (1987) example of successful persuasion. It is rewarding to be able to report that the allocation of the science vote for 1989-90 (announced on Feb 7 by the Secretary of State for Education Science) provides the MRC with an additional C20 4 million. The Council can now look forward, over the next three years, to an overall grant-in-aid averaging some ;C180 million annually. Can we now expect to see another lead article from you-perhaps under the heading "say not the struggle naught availeth" (A. H. Clough)? ...
Medical Research 20 Park Crescent,
Council,
D. A.
London WIN 4AL
REES,
Secretary
BROTHER-TO-SISTER TRANSMISSION OF MEASLES AFTER MMR IMMUNISATION
SIR,-Dr Millson (Feb 4, p 271) claims that the timing of a measles-like illness in two siblings indicates "the probable transmission" of measles from the live attenuated Schwartz strain contained in measles-mumps-rubella (MMR) vaccine. He suggests that caution should be exercised when vaccinating normal children with immunocompromised siblings and complains that the Department of Health publication Immunisation Against Infectious Disease offers no specific advice on this problem. Extensive testing and experience with measles vaccine and MMR vaccine has not shown evidence of vaccine virus transmission to susceptible contacts. It would be wrong to modify current advice that "children with post vaccination symptoms are not infectious" on the basis of a clinical report unsubstantiated by laboratory evidence. Furthermore, Immunisation Against Infectious Disease (page 3) contains specific advice about immunocompromised children. "Siblings and close contacts of such children must be immunised against measles. Oral poliomyelitis vaccine (OPV) should not be given to these children, their siblings or other household contacts; inactivated poliomyelitis vaccine (IPV) should be used in its place. There is no risk of virus transmission following measles, mumps or rubella vaccines." Department of Child Health, University of Aberdeen, Aberdeen AB9 2ZD
A. G. M. CAMPBELL, Chairman-elect, Joint Committee on
Vaccination and Immunisation
BALDNESS AND MINOXIDIL ADVERTISING
SIR,-In my local pharmacy recently I was regaled by a promotional wall-video which pointed out that male-pattern alopecia is bad for the image and is hereditary. It showed a miserable and worried-looking bald father and an equally worried young son who was anxiously examining his hair in the mirror. The message to the son was that something could now be done to prevent this awful fate, if only preventive measures were taken early enough. The firm
443 which produced this advert was Upjohn, and the pharmacist said that if people asked him about preventive measures to be taken he recommended that they should see their general practitioner to discuss treatment with topical minoxidil (’Regaine’), which is available only on private prescription. Doctors often see young men with male-pattern alopecia who are very anxious about their hair loss, and few of them can afford to buy topical minoxidil long term. I have seen several young men who have been so depressed that they asked for systemic anti-androgen therapy and have said that they are willing to lose their libido so long as they do not lose their hair. On talking to these patients I fmd that their worries are largely stimulated by the advertisements that they see, m which baldness is uniformly portrayed in a very negative way. Not once have I seen an advertisement that points out that in our sexist capitalist society the richest and most powerful people, statistically speaking, are likely to be going bald, and that men with testosterone deficiency do not lose their hair. One expects cosmetics salesmen to prey on human weaknesses but I was saddened to see a reputable pharmaceutical firm seeking to increase anxiety about a physiological event in order to increase their profits. Department of Dermatology, Bnstol Royal Infirmary, Bnstol BS2 8HW
J.
L. BURTON
they did not feel ill enough to leave work. We stress that is it not only food handlers who should abstain from work but also all health care workers, however mild their illness. IAN BUTCHER GOURA KUDESIA JOHN GORDON J. MILLER
Department of Microbiology, Gartnavel General Hospital; and Regional Virus Laboratory, Ruchill Hospital, Glasgow
Xp21 DNA PROBE IN DIAGNOSIS OF MUSCULAR DYSTROPHY AND SPINAL MUSCULAR ATROPHY StR,—Ten years ago/ J. Peam and one of us (P. H.) reported in The Lancet some cases of apparent spinal muscular atrophy (SMA), which mimicked Becker muscular dystrophy both clinically and on the basis of myopathic features on muscle biopsy. We have had the opportunity to reassess the diagnosis of two affected brothers in that series (cases 4 and 5). They come from a large X-linked pedigree in which a deletion of exons from the Duchenne/Becker muscular dystrophy gene at Xp21 has been consistently found in the affected males, recognised by the Cf23a DNA marker. These brothers are members of the family2 where the clinical severity varied between members, who all shared the same DNA deletion. We have as yet been unable to reinvestigate the other three cases of "SMA", but it is possible that they also have Xp21 (Duchenne/Becker) muscular
dystrophy. SMALL ROUND STRUCTURED VIRUSES AND THEIR SPREAD
SIR-DR Palmer (Nov 26, p 1247) raises the important issue of environmental contamination in the spread of infection by Norwalk-like viruses. Our experience in a large outbreak of gastroenteritis with small round structured viruses supports this view. Over 21 days at a district hospital in Glasgow, there were 86 cases of gastroenteritis-53 in patients and 33 in staff. Diarrhoea alone was the most common symptom (54%), followed by diarrhoea and vomiting (38%), and vomiting alone (8%). Most of the cases were from three units (medical, orthopaedic, and geriatric) and nine wards were affected. Small round structured viruses were detected in 7 of 19 stools examined by electron microscopy, positive cases being detected from all three units. All bacteriological investigations were negative. The wards were of similar design, with a wide central corridor linking three sections with rooms of one or four beds; swing doors separate each ward. The outbreak started on a medical ward when a patient had an explosive attack of diarrhoea resulting in gross soiling of clothing, bed, and surroundings. Two other patients in the same four-bed room subsequently had diarrhoea, as did a nurse and domestic assistant who had helped to clean up. 9 days after the first case, 8 cases appeared on an orthopaedic ward which is six floors away from the medical ward. The only contact was a physiotherapist who worked over the weekend despite having diarrhoea and vomiting. The explosive nature of diarrhoea resulted in gross faecal contamination of the bed area and many patients were confined to bed. Dissemination of droplets would form an important route of spread, via environmental contamination or inhalation (the virus gaining entry to the gastrointestinal tract through the nasopharynx). This inhalation route needs to be investigated further. In the Glasgow outbreak there was strong epidemiological evidence for such a route of spread, which would have been facilitated by the open design of the wards. A history of direct contact could not be elicited from several people, staff and patients, who subsequently became ill. The outbreak lasted for 3 weeks with a peak on the tenth day. Containment procedures including disinfection, rigorous handwashing, and restriction of movement of patients and staff failed to halt the spread of infection. The orthopaedic ward was closed to admissions for one week, which brought the epidemic to a halt. The short duration of the illness and its self-limiting nature makes it difficult to persuade people to adhere strictly to isolation procedures. Many of the staff continued to work despite being sick;
Besides correcting the misdiagnosis in the original report, we highlight this application of DNA technology in diagnosis. Wood et aP previously reported two females diagnosed as having KugelbergWelander syndrome who were shown to be manifesting carriers of a muscular dystrophy with a deletion recognised by the Xp21 marker XJ I - 1. We also cast doubt upon the existence of an X-linked type of SMA characterised by adolescent-onset proximal muscle weakness with large calves and raised serum creatine kinase activity. Such cases should probably be regarded as Becker dystrophy, until proven otherwise. Electrophysiological and biopsy findings of an apparently mixed myopathic/neurogenic nature can occur in Becker dystrophy, as in some of Becker’s original patients.’ Dr Lunt and colleagues (Jan 7, p 46) use DNA probes to diagnose Xp21 dystrophy in some cases initially diagnosed as SMA, but Lunt et al do not dispute the existence of SMA. The occurrence of the X-linked, bulbospinal form of SMA is not in question. Now that dystrophin can be measured in muscle tissue, the correct diagnosis of Xp21 dystrophy will be reached more easily. The clinical importance of the correct diagnosis is that the proband and family can receive appropriate genetic counselling. It is especially important to consider whether females with "atypical SMA" or with "limb-girdle dystrophy" may be manifesting carriers of Xp21 dystrophy, due to an unfavourable pattern of X inactivation, because they will have a very high chance of producing sons with Duchenne dystrophy. We have come across such a case. The correct diagnosis was made only after the birth of the affected son.
Department of Human Genetics, University of Newcastle upon Tyne; Nuffield Department of Medicine, John Radcliffe Hospital, Oxford; and Regional Neurological Centre, Newcastle General Hospital
A. CLARKE* K. E. DAVIES D. GARDNER-MEDWIN
J. BURN P. HUDGSON
Present address Institute of Medical Genetics, University CF4 4XW. *
Hospital of Wales, Cardiff
1. Peam J, Hudgson P. Anterior-horn cell degeneration and gross calf hypertrophy with
adolescent onset: a new spinal muscular atrophy syndrome. Lancet 1978; i: 1059-61 2. Forrest SM, Cross GS, Speer A, Gardner-Medwin D, Bum J, Davies KE. Preferential deletion of exons in Duchenne and Becker muscular dystrophies. Nature 1987; 329: 638-40. 3. Wood S, Shukin RJ, McGillivray BC, Ray PN, Worton RG. A grandpatemally derived de novo deletion within Xp21 initially presenting in carrier females diagnosed as Kugelberg-Welander syndrome. Am J Med Genet 1988; 29: 419-23. 4. Goebel HH, Prange H, Gullotta F, Kiefer H, Jones MZ. Becker’s X-linked muscular dystrophy: histological, enzyme-histochemical and ultrastructural studies of two cases, originally reported by Becker. Acta Neuropathol (Berl) 1979; 46: 69-77.
SIR,-Audit is a prominent feature of several recent proposals on postgraduate training and clinical practice in the UK. The Government’s white-paper on the National Health Service encourages it. In 1988 a Royal College of Physicians working-party stated that a post for training might not be approved "if adequate clinical review meetings are not held", and the National Confidential Enquiry into Perioperative Deaths (NCEPOD) has instigated the formal audit of deaths within 30 days of surgery. The low necropsy rate in the UK invalidates any form of clinical audit where death is possible outcome.
Clinical diagnoses, often made with confidence, are frequently verified at necropsy. 1,2 Patients die from treatable conditions because of diagnostic errors revealed only at necropsy. In one survey, covering a period during which the necropsy rate had been increased to 65%, 42% of causes of death were unconfirmed and 15% of errors were conceded to be significant by the requesting clinicians.3 Such errors will usually remain undiscovered unless a necropsy is asked for. Undoubtedly, the necropsy rate for deaths in UK hospitals has fallen from over 60% to 25% or less in the past thirty years.4 The rate is especially low for deaths in geriatric units.s Elderly patients are assumed to have irreversible disease processes which are themselves a function of senility. Yet one necropsy study in patients over 65 revealed that in 31 % of cases a potentially treatable contributory factor to death had not been diagnosed during life.’7
not
Low necropsy rates may be attributable to a variety of factors-the pressures of more immediate clinical commitments; the view that imaging, biopsy, and biochemical techniques applied during life render necropsy superfluous; the reluctance of relatives to give consent because the deceased has "suffered enough"; the low priority given to necropsies by pathologists burdened with a heavy biopsy and cytology workload; the reluctance of some clinicians to have diagnostic errors revealed; the fear of litigation for diagnostic errors; and the lack of interest that results if pathologists do not communicate their findings rapidly and clearly to the clinicians who ask for a necropsy. In the USA, the importance of necropsy has been drawn to the public’s attention through the columns of the New York Times (cited by Hill and Anderson8). The Joint Commission on Accreditation of Health Organisations has recommended the use of necropsies for quality assurance. A senior administrator of the Health Care Financing Administraton has expressed concern about the falling necropsy rate. The reliability of death certificate data, unverified by necropsy, has also been questioned in the USA because of the implications for national health policy. In the UK, there should be greater professional, managerial, and public awareness of the importance of necropsy as the "ultimate audit" of clinical outcome. The task of seeking consent from relatives should not be left to the most inexperienced, and often exhausted, member of the clinical team. Adequate funding should be provided for the maintenance of a necropsy rate of at least 75% for deaths in hospital. The importance of the necropsy must be sustained in the new training programmes and examinations in histopathology for membership of the Royal College of Pathologists. Necropsy data should be collected systematically to provide a reliable demographic database of morbidity and
mortality. All hospitals, NHS and private, should be obliged to audit and report internally their necropsy rates and the rates attributable to individual consultants. Staffing levels should be increased where necessary so that necropsies are done thoroughly and the results communicated rapidly to the clinician. The Royal Colleges should monitor necropsy rates and the procedures for disseminating information from them, accreditation for training being conditional on an adequate local necropsy rate that permits valid audit of diagnoses and treatments. Department of Pathology, University of Sheffield Medical School, Sheffield S10 2RX
J. C. E. UNDERWOOD D. W. K. COTTON T. J. STEPHENSON
F, Vecchiet F, Barbierato D, Melato A, Manconi R. Inaccuracy of death certificate diagnoses in malignancy an analysis of 1405 autopsied cases. Hum Pathol 1982; 13: 1036-38. Stevanovic G, Tucakovic G, Dotlic R, Kanjish V. Correlation of clinical diagnoses with autopsy findings. Hum Pathol 1986, 17: 1225-30. Cameron HM, McGoogan E, Watson H. Necropsy as a yardstick for clinical diagnoses. Br MedJ 1980; 281: 985-88. Cameron HM. Future of the hospital autopsy. BrJ Hosp Med 1988; 40: 335 Kohn RR. Causes of death in very old people. JAMA 1982; 247: 2793-97. Editorial. Death in old age. Lancet 1982, ii: 477. Puxty JA, Horan MA, Fox RA. Necropsies in the elderly. Lancet 1983; i: 1262-64 Hill RB, Anderson RE Is a valid quality assurance program possible without the autopsy? Hum Pathol 1988; 19: 1125-26.
1 Gobbato
2. 3. 4. 5.
6. 7. 8.
MEDICAL RESEARCH FUNDING
SIR,-A Lancet editorial of Oct 29 on funding for medical research in the UK (Wellcome Steps into the Breach Once More) accused the Medical Research Council of being "lacklustre clearly unable to inspire any important changes in official policy". The MRC’s "modest stillness and humility" (Henry V) should not have misled you; we can "disguise fair nature with hard-favour’d rage" and have long argued the case for an increase in public funding (as have many others) with conviction and with force. The extra allocation of 14-5 million over 3 years for AIDS research, additional to our grant-in-aid, is one recent (1987) example of successful persuasion. It is rewarding to be able to report that the allocation of the science vote for 1989-90 (announced on Feb 7 by the Secretary of State for Education Science) provides the MRC with an additional C20 4 million. The Council can now look forward, over the next three years, to an overall grant-in-aid averaging some ;C180 million annually. Can we now expect to see another lead article from you-perhaps under the heading "say not the struggle naught availeth" (A. H. Clough)? ...
Medical Research 20 Park Crescent,
Council,
D. A.
London WIN 4AL
REES,
Secretary
BROTHER-TO-SISTER TRANSMISSION OF MEASLES AFTER MMR IMMUNISATION
SIR,-Dr Millson (Feb 4, p 271) claims that the timing of a measles-like illness in two siblings indicates "the probable transmission" of measles from the live attenuated Schwartz strain contained in measles-mumps-rubella (MMR) vaccine. He suggests that caution should be exercised when vaccinating normal children with immunocompromised siblings and complains that the Department of Health publication Immunisation Against Infectious Disease offers no specific advice on this problem. Extensive testing and experience with measles vaccine and MMR vaccine has not shown evidence of vaccine virus transmission to susceptible contacts. It would be wrong to modify current advice that "children with post vaccination symptoms are not infectious" on the basis of a clinical report unsubstantiated by laboratory evidence. Furthermore, Immunisation Against Infectious Disease (page 3) contains specific advice about immunocompromised children. "Siblings and close contacts of such children must be immunised against measles. Oral poliomyelitis vaccine (OPV) should not be given to these children, their siblings or other household contacts; inactivated poliomyelitis vaccine (IPV) should be used in its place. There is no risk of virus transmission following measles, mumps or rubella vaccines." Department of Child Health, University of Aberdeen, Aberdeen AB9 2ZD
A. G. M. CAMPBELL, Chairman-elect, Joint Committee on
Vaccination and Immunisation
BALDNESS AND MINOXIDIL ADVERTISING
SIR,-In my local pharmacy recently I was regaled by a promotional wall-video which pointed out that male-pattern alopecia is bad for the image and is hereditary. It showed a miserable and worried-looking bald father and an equally worried young son who was anxiously examining his hair in the mirror. The message to the son was that something could now be done to prevent this awful fate, if only preventive measures were taken early enough. The firm
443 which produced this advert was Upjohn, and the pharmacist said that if people asked him about preventive measures to be taken he recommended that they should see their general practitioner to discuss treatment with topical minoxidil (’Regaine’), which is available only on private prescription. Doctors often see young men with male-pattern alopecia who are very anxious about their hair loss, and few of them can afford to buy topical minoxidil long term. I have seen several young men who have been so depressed that they asked for systemic anti-androgen therapy and have said that they are willing to lose their libido so long as they do not lose their hair. On talking to these patients I fmd that their worries are largely stimulated by the advertisements that they see, m which baldness is uniformly portrayed in a very negative way. Not once have I seen an advertisement that points out that in our sexist capitalist society the richest and most powerful people, statistically speaking, are likely to be going bald, and that men with testosterone deficiency do not lose their hair. One expects cosmetics salesmen to prey on human weaknesses but I was saddened to see a reputable pharmaceutical firm seeking to increase anxiety about a physiological event in order to increase their profits. Department of Dermatology, Bnstol Royal Infirmary, Bnstol BS2 8HW
J.
L. BURTON
they did not feel ill enough to leave work. We stress that is it not only food handlers who should abstain from work but also all health care workers, however mild their illness. IAN BUTCHER GOURA KUDESIA JOHN GORDON J. MILLER
Department of Microbiology, Gartnavel General Hospital; and Regional Virus Laboratory, Ruchill Hospital, Glasgow
Xp21 DNA PROBE IN DIAGNOSIS OF MUSCULAR DYSTROPHY AND SPINAL MUSCULAR ATROPHY StR,—Ten years ago/ J. Peam and one of us (P. H.) reported in The Lancet some cases of apparent spinal muscular atrophy (SMA), which mimicked Becker muscular dystrophy both clinically and on the basis of myopathic features on muscle biopsy. We have had the opportunity to reassess the diagnosis of two affected brothers in that series (cases 4 and 5). They come from a large X-linked pedigree in which a deletion of exons from the Duchenne/Becker muscular dystrophy gene at Xp21 has been consistently found in the affected males, recognised by the Cf23a DNA marker. These brothers are members of the family2 where the clinical severity varied between members, who all shared the same DNA deletion. We have as yet been unable to reinvestigate the other three cases of "SMA", but it is possible that they also have Xp21 (Duchenne/Becker) muscular
dystrophy. SMALL ROUND STRUCTURED VIRUSES AND THEIR SPREAD
SIR-DR Palmer (Nov 26, p 1247) raises the important issue of environmental contamination in the spread of infection by Norwalk-like viruses. Our experience in a large outbreak of gastroenteritis with small round structured viruses supports this view. Over 21 days at a district hospital in Glasgow, there were 86 cases of gastroenteritis-53 in patients and 33 in staff. Diarrhoea alone was the most common symptom (54%), followed by diarrhoea and vomiting (38%), and vomiting alone (8%). Most of the cases were from three units (medical, orthopaedic, and geriatric) and nine wards were affected. Small round structured viruses were detected in 7 of 19 stools examined by electron microscopy, positive cases being detected from all three units. All bacteriological investigations were negative. The wards were of similar design, with a wide central corridor linking three sections with rooms of one or four beds; swing doors separate each ward. The outbreak started on a medical ward when a patient had an explosive attack of diarrhoea resulting in gross soiling of clothing, bed, and surroundings. Two other patients in the same four-bed room subsequently had diarrhoea, as did a nurse and domestic assistant who had helped to clean up. 9 days after the first case, 8 cases appeared on an orthopaedic ward which is six floors away from the medical ward. The only contact was a physiotherapist who worked over the weekend despite having diarrhoea and vomiting. The explosive nature of diarrhoea resulted in gross faecal contamination of the bed area and many patients were confined to bed. Dissemination of droplets would form an important route of spread, via environmental contamination or inhalation (the virus gaining entry to the gastrointestinal tract through the nasopharynx). This inhalation route needs to be investigated further. In the Glasgow outbreak there was strong epidemiological evidence for such a route of spread, which would have been facilitated by the open design of the wards. A history of direct contact could not be elicited from several people, staff and patients, who subsequently became ill. The outbreak lasted for 3 weeks with a peak on the tenth day. Containment procedures including disinfection, rigorous handwashing, and restriction of movement of patients and staff failed to halt the spread of infection. The orthopaedic ward was closed to admissions for one week, which brought the epidemic to a halt. The short duration of the illness and its self-limiting nature makes it difficult to persuade people to adhere strictly to isolation procedures. Many of the staff continued to work despite being sick;
Besides correcting the misdiagnosis in the original report, we highlight this application of DNA technology in diagnosis. Wood et aP previously reported two females diagnosed as having KugelbergWelander syndrome who were shown to be manifesting carriers of a muscular dystrophy with a deletion recognised by the Xp21 marker XJ I - 1. We also cast doubt upon the existence of an X-linked type of SMA characterised by adolescent-onset proximal muscle weakness with large calves and raised serum creatine kinase activity. Such cases should probably be regarded as Becker dystrophy, until proven otherwise. Electrophysiological and biopsy findings of an apparently mixed myopathic/neurogenic nature can occur in Becker dystrophy, as in some of Becker’s original patients.’ Dr Lunt and colleagues (Jan 7, p 46) use DNA probes to diagnose Xp21 dystrophy in some cases initially diagnosed as SMA, but Lunt et al do not dispute the existence of SMA. The occurrence of the X-linked, bulbospinal form of SMA is not in question. Now that dystrophin can be measured in muscle tissue, the correct diagnosis of Xp21 dystrophy will be reached more easily. The clinical importance of the correct diagnosis is that the proband and family can receive appropriate genetic counselling. It is especially important to consider whether females with "atypical SMA" or with "limb-girdle dystrophy" may be manifesting carriers of Xp21 dystrophy, due to an unfavourable pattern of X inactivation, because they will have a very high chance of producing sons with Duchenne dystrophy. We have come across such a case. The correct diagnosis was made only after the birth of the affected son.
Department of Human Genetics, University of Newcastle upon Tyne; Nuffield Department of Medicine, John Radcliffe Hospital, Oxford; and Regional Neurological Centre, Newcastle General Hospital
A. CLARKE* K. E. DAVIES D. GARDNER-MEDWIN
J. BURN P. HUDGSON
Present address Institute of Medical Genetics, University CF4 4XW. *
Hospital of Wales, Cardiff
1. Peam J, Hudgson P. Anterior-horn cell degeneration and gross calf hypertrophy with
adolescent onset: a new spinal muscular atrophy syndrome. Lancet 1978; i: 1059-61 2. Forrest SM, Cross GS, Speer A, Gardner-Medwin D, Bum J, Davies KE. Preferential deletion of exons in Duchenne and Becker muscular dystrophies. Nature 1987; 329: 638-40. 3. Wood S, Shukin RJ, McGillivray BC, Ray PN, Worton RG. A grandpatemally derived de novo deletion within Xp21 initially presenting in carrier females diagnosed as Kugelberg-Welander syndrome. Am J Med Genet 1988; 29: 419-23. 4. Goebel HH, Prange H, Gullotta F, Kiefer H, Jones MZ. Becker’s X-linked muscular dystrophy: histological, enzyme-histochemical and ultrastructural studies of two cases, originally reported by Becker. Acta Neuropathol (Berl) 1979; 46: 69-77.