Ischaemic colitis due to mitochondrial cytopathy

equipment,

resources

need

to

be made available

to

support

collaborative studies involving the sports councils and the various

sports

and

leisure

regulatory

and

safety

organisations. *Harry Campbell, Sally O’Driscoll Department of Public Health Medicine,

Fife Health Board, Cupar, Fife KY15 5UP, UK

1 Campbell H, O’Driscoll S. Leisure and water accidents in Scotland. Presented at the Scottish Needs Assessment Programme, Scottish Forum for Public Health Medicine, Glasgow, 1994. 2 Department of Trade and Industry. Home and leisure accident research: 1991. London: Data Consumer Safety Unit, DTI, 1993. 3 Scottish Office Home and Health Department. Scotland’s health a challenge to us all. London: HM Stationery Office, 1992. 4 Garraway WM, MacLeod DAD, Sharp JCM. Rugby injuries: the need for case registers. BMJ 1991; 303: 1082-03.

SIR-Garraway and Macleod raise two important questions relevant to injury prevention. First, why do players aged 20-24 have a significantly greater injury risk than those aged 16-19: the former are twice as likely to experience an injury episode as the latter? Before it can be established whether this observation is spurious or real, we need to know whether these teenage players (16-19 years) were less likely to report injuries than their older counterparts, or whether they were involved in "colts rugby", in which the risk of injuries may not be as great as other senior rugby games. Second, tackling was identified as the most important risk factor for causing injuries, accounting for almost half of all injury episodes in matches. What proportion of these injuries can be attributed to foul play, faulty technique, or a combination of both? It is noteworthy that 30% of all rugby injuries in 1978 occurred as a result of foul play.’ Further identification of causative factors giving rise to tackling injuries is therefore an important task. We believe that video recordings will be potentially very helpful because matches to be examined in detail. The use of video recordings has already been shown to help in diagnosis of patients with movement disordersand epilepsy.3 Rugby injuries are an important source of morbidity in young players. The challenge here is to identify those risk factors that can be readily eliminated, thereby making the game safer while retaining the inherent flow and character of the sport.

they allow

*Su Vui Lo, Peter Donnelly, Sharon South

Glamorgan

Health

Hopkins, Darren Shickle

Authority, Cathays Park, Cardiff CF1 3NW, UK

1 Davies JE, Gibson T. Injuries in Rugby Union football. BMJ 1978; ii: 1759-61. 2 De Leon D, Moskowitz CB, Stewart C. Proposed guidelines for videotaping individuals with movement disorders. J Neurosci Nurs

1991, 23: 191-93. 3

Sheth RD, Bodensteiner JB. Effective utilisation of home-video recordings for the evaluation of paroxysmal events in paediatrics. Clin Paediatr 1994; 33: 578-82.

Ischaemic colitis due to mitochondrial

cytopathy SiR-Mitochondrial cytopathies disorders encompass associated with identified mitochondrial DNA (mtDNA) defects. This is illustrated by mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).’ The common MELAS mutation (A3243G) can be identified in variable phenotypes, such as maternally inherited diabetes mellitus with deafness.2 Gastrointestinal manifestations are rare in mitochondrial cytopathies. We report a case of ischaemic colitis associated with the A3243G mutation and a new mtDNA polymorphism.

most

Figure: Detection of MELAS mutation and sequence variant of 16 S- RNA gene A: Region between nucleotides 3171 and 3420 was amplified by PCR with y[32P] ATP-labelled oligonucleotides, restricted with Apaxl, and subjected to gel electrophoresis. N=normal band; M-mutant band; hd=heteroduplex. Percentages of mutant DNA, measured with a phosphoimager, are shown in PBL=peripheral blood leucocytes. B: Single-stranded conformation analysis of MELAS mutation and T3197C polymorphism was performed as in A, and subjected to nondenaturing gel electrophoresis. Lane 1 shows pattern obtained from a typical patient heteroplasmic for A3243G MELAS mutation, and lanes 2, 3, and 5, patterns of normal individuals. Presence of A3243G mutation in presence of T3197C polymorphism produces an abnormal pattern from patient’s muscle DNA.

A 49-year-old woman had a history of maternally inherited uncomplicated diabetes mellitus since 1985. Progressive hearing loss was noted from 1992. She had complained of exercise-induced painful weakness of the girdle area and low limbs since 1993. Clinical examination showed short stature (152 cm), bilateral sensorineural hearing loss, girdle weakness, and generalised hyporeflexia. Serum lactate (2-67 mmol/L, normal 1-1-9 mmol/L) and pyruvate (193 jjbmol/L), normal 45-69 jjbmol/L) were increased at rest; serum lactate rose to 8-98 mmol/L (normal <5 mmol/L) after exercise. Electromyography was suggestive of myopathy. A muscle biopsy specimen indicated a lipid Electron storage myopathy. microscopy revealed mitochondria containing inclusion bodies and abnormal cristae. Mitochondrial DNA was isolated from blood and muscle, and the A3243G MELAS mutation detected. 189

with ubidecarenone (50 to 300 mg per day), riboflavine (100 mg per day), and allopurinol (150 mg per day) resulted in clinical improvement. In February, 1994, she presented with sudden abdominal pain and haematochezia. Colonscopy showed ulcerations at the splenic flexure. Histological examination was compatible with ischaemic colitis. PCR of mtDNA from intestinal wall specimens revealed the highest proportion of mutant DNA at the splenic flexure. In addition to the A3243G mutation, a new variant from the published mtDNA sequence was detected (T3197C) (figure). The biochemical changes in muscle tissue from patients with mtDNA mutations are consistent with the hypothesis that overall mitochondrial protein synthesis is impaired, leading to defects of respiratory chain complexes containing mtDNA-encoded subunits. We speculate that the higher fraction of abnormal mitochondria at the splenic flexure reached the critical level for impaired energy metabolism, resulting in ischaemia. It is possible that the sequence variant of the 16S RNA gene modifies the expression of the A3243G mutation. The new association of ischaemic colitis and the MELAS mutation indicates that mitochondrial cytopathies should be considered when unexplained ischaemic colitis is associated with maternally inherited diabetes.

Therapy

*Jürg Hess, Pierre Burkhard, Michael Morris, Myers, Antoine Hadengue

Maria Lalioti,

Peter

Divisions of *Gastroenterology and Medical Genetics, and Department of Geneva University Hospital, 1211 Geneva 11, Switzerland

1 2

3

Neurology,

Trischler H-J, Medori R. Mitochondrial DNA alterations as a source of human disorders. Neurology 1993; 43: 280-88. Kadowaki T, Kadowaki H, Mori Y, et al. A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. N Engl J Med 1994; 330: 962-68. Di Mauro S, Moraes C. Mitochondrial encephalomyopathies. Arch Neurol 1993; 50: 1197-208.

Prevention of nosocomial transmission of hepatitis C virus SiR-Allander and colleagues (March 11, p 603) describe a nosocomial outbreak of hepatitis C in patients in a haematology ward in a Swedish hospital, in which the route of transmission was obscure. We have investigated a small nosocomial outbreak of hepatitis C in a neighbouring Swedish hospital with similar hygienic standards and routines. The outbreak involved three people participating in a research project. One patient contracted an acute hepatitis C infection (patient A) with raised aminotransferase, RIBApositivity, and HCV-RNA positivity, and another had symptomless seroconversion (patient B). Both patients were seronegative before entering the research project, seroconverted during the course of the project, which lasted for several months, and had no other risk factors. As the probable source of infection we identified a third patient (patient C) who was retrospectively diagnosed as having a chronic hepatitis C infection with repeatedly raised aminotransferases, and who was RIBA-positive and HCVRNA positive in a frozen serum sample taken before entering the research project. The temporal relation and the absence of other risk factors for patients A and B suggest that hepatitis C virus was transmitted from patient C to patients A and B. This hypothesis was further supported by virological analysis. Thus, analysis of HCV-RNA from patients A and C (viraemic samples were not available from patient B) showed that they shared the same genotype, 2b. Phylogenetic analyses of the sequences obtained from the 190

NS5 region, were in accord with patients A and C being infected with closely related HCV strains. The research project, which examined the effect of proton-pump inhibitors, included repeated blood sampling from an intravenous catheter during 24 h. Patients B and C were in the same study group and were on several occasions together in one room during the entire experiment; patient A joined the study group on two occasions. An investigation on possible routes of transmission during the experiments revealed two routines that were not in accordance with standards published and recommended in the hospital. First, the syringes for flushing the intravenous catheter were not discarded after each flushing but, rather, were marked with the person’s name and used repeatedly at intervals, which greatly increased the risk of a mix-up. Second, nurses did not change gloves between subjects unless there were visible blood stains on them, but disinfected their gloves with an alcohol-based disinfectant. Both these faulty routines have the potential to cause bloodto-blood transmission between patients. Either routine could have been the cause of transmission in this outbreak, but the mixing of syringes for flushing, with its potential to transfer a high virus load, is the more likely cause. This outbreak shows that nursing and procedure routines have to be continuously supervised, even in hospitals with well-educated staff and high standards. It is of vital importance that medical personnel who handle blood samples or material contaminated with blood strictly adhere to hygienic methods, which are carefully worked out to prevent transmission of blood-borne viruses. Our findings are in line with Heptonstall and Mortimer’s commentary (March 11, p 599), that it is probably not necessary to look for ways of transmission for HCV other than those already established, and that it is possible that failure of hygienic routines was a cause of the outbreak described by Allander and colleagues. *Robert Schvarcz, Bertil Anders Sönnerborg

Nyström,

Antti Oksanen,

Departments of *Infectious Diseases, Clinical Microbiology, Gastroenterology and Hepatology, and Virology, Huddinge University Hospital, S-14186 Huddinge, Sweden

Are focal white matter lesions in patients with inflammatory bowel disease linked to multiple sclerosis? SiR-Geissler and colleagues (April 8, p 897) report an excess of focal white matter lesions in brain magnetic resonance images (MRI) in patients with inflammatory bowel disease. They suggest that symptomless lesions are ischaemic in origin, proposing vasculitis and atherosclerosis as possible causes. Inflammatory demyelinating lesions also need to be considered, as shown by our case. A 29-year-old woman with an 8-year history of Crohn’s disease, confirmed by biopsy and barium enema, whose disease was quiescent at the time of neurological presentation, developed bilateral visual loss, slurred speech, clumsy right hand, and unsteady gait. Visual acuities were finger counting on the right and 6/60 on the left, with large central scotomas, and the patient was judged to have bilateral optic neuritis. Blood tests, including erythrocyte sedimentation rate, were normal, apart from weakly positive c-antineurotrophil cytoplasmic antibodies. Visual-evoked responses were abnormal, being absent on the right and of small amplitude on the left. MRI scans showed three whitematter lesions, one in the right superior cerebellar peduncle, one deep in the left cerebral hemisphere, and one in the