- Email: [email protected]
LOCAL ANAESTHESIA FOR CATARACT SURGERY
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aplasia has not previously been reported after arthropod sting or bite; rhabdomyolysis may be caused by the venom of Hymenoptera2-4 or other arthropods, and it has been associated with acute renal failure after the bite of a centipede.5 Hymenoptera venom could have a facultative and occasionally cytopenic effect on bone marrow in an individual. Rhabdomyolysis is more difficult to explain; it seems unlikely to be caused by a single
sting.44 Department of Forensic Toxicology, University of Genoa, 16132 Genoa, Italy
F. TORREGIANI C. LA CAVERA
1. Torregiani F, La Cavera C Il Latrodectismo od avvelenamento da morso di Malmignatta (Latrodectus tredecimguttatus) m Italia. Minerva Med (m press). 2. Bousquet J, Huchard G, Michel F-B. Toxic reactions induced by hymenoptera venom. Ann Allergy 1984; 52: 371. 3 García Martin F, Martín Escobar E, Fernández Rodríguez A, Orte L, Quereda C, Ortuño J. Fracaso renal agudo asociado a rabdomiólisis no traumática por picaduras múltiples de abejas. Med Clin 1984; 83: 87. 4 Shilkin KB, Chen BTM, Khoo OT. Rhabdomyolysis caused by hornet venom. Br Med J 1972; i: 156. 5. Logan JL, Ogden DA Rhabdomyolysis and acute renal failure following the bite of the giant desert centipede Scolopendra heros. West J Med 1985; 142: 549.
SEX DIFFERENCE IN D7S8 MARKER ALLELE DISTRIBUTION IN ADULT CYSTIC FIBROSIS PATIENTS
SiR,—The clinical course of cystic fibrosis (CF) is variable and may depend on both genetic and environmental factors. Attempts to correlate clinical phenotypes with the distribution of alleles of markers closely linked to CF have given conflicting results-Dr Auvinet and colleagues (Jan 21, p 161) could not confirm all the findings of Momet et al.’ We have tried to relate survival rates of patients with CF to marker genotypes and found a sex difference for the MspI-RFLP detected by probe pj3 11 (D7S8), which presents the two alleles 4-2 kb (1) and 1kb (2).2 In a group of 147 German CF families, 18 patients (8 male) were older than 18 years at the time of DNA analysis, well above the present average life expectancy. The joint allele frequencies in this group did not differ from those observed in all patients. However, all six patients typing 1-1 were males; thus all female patients carried at least one allele 2. Three females but no male typed 2-2. These differences were significant (Fisher’s exact test, p < 0-003). Since allele 1 occurs on most CF chromosomes,3our fmding may indicate that a factor associated with D7S8 confers a modifying effect restricted to female patients. No such effects could be detected for the closely linked CF markers, KM19 and XV2c (D7S23). Institute of Human Genetics, Universitatsklinikum Charlottenburg, D-1000 Berlin 19, West Germany
JÖRG SCHMIDTKE
Institute of Human Genetics, University of Gottingen, Gottingen, West Germany
MICHAEL KRAWCZAK
1 Momet E, Simon-Bouy B, Serre JL, et al. Genetic differences between cystic fibrosis with and without meconium ileus. Lancet 1988; i: 376-78. 2 Bartels I, Grzeschik K-H, Cooper DN, Schmidtke J. Regional assignment of six cloned DNA sequences on human chromosome 7 Am J Hum Genet 1986; 38:
280-07 3. Schmidtke
J, Krawczak M, Schwartz M,
associations
et al. Linkage relationships and allelic of the cystic fibrosis locus and four marker loci. Hum Genet 1987, 76:
337-43.
LOCAL ANAESTHESIA FOR CATARACT SURGERY
SiR,—Dr Rassam and Dr Thomas (Jan 14, p 110) describe a favourable response to local anaesthesia (LA) for cataract surgery. We have completed a study in which we compared the hormonal and metabolic responses to cataract surgery under LA or general anaesthesia (GA). Eighteen elderly patients who had no metabolic or endocrine abnormalities were allocated randomly to receive GA or LA. No patient received premedication. The patients were anaesthetised either with a retrobulbar and facial block administered by one ophthalmic surgeon or with a thiopentone, vecuronium, and nitrous
oxygen, and enflurane technique. Blood samples were collected before, during, and after the operation. In the GA group plasma cortisol increased from 348 nmol/1 before induction of anaesthesia to a peak of 749 nmol/1 (p <0 01) after 1 h of recovery. In the LA group, however, plasma cortisol did not change significantly from the preinduction value of 320 nmol/1. Thus there was a significant difference between the groups both Blood glucose intraoperatively and postoperatively (p < 001). increased non-significantly in the GA group (4-7 to 52 mmol/1); there was no significant alteration in the LA group from the preinduction value of 4 4 mmol/1. The small glycaemic response in the GA patients was sufficient to result in a significant difference between the groups at the completion of the operation and after 30 min of recovery (p < 0-05). The operative time was significantly less in the GA group (25 min vs 30 min, p < 0-05), but the overall theatre times were similar (47 min, GA; 49 min, LA). This extra time in the GA patients was due to the need to reverse neuromuscular blockade and to establish spontaneous respiration on completion of the operation. Our results suggest that although cataract surgery is a minor procedure, as assessed by changes in circulating cortisol and glucose, these responses can be prevented by use of LA. Our results and the data of Rassam and Thomas suggest that the use of LA in cataract surgery should be extended.
oxide,
Department of Anaesthetics and Ophthalmic Surgery, Edgware General Hospital, Middlesex
Departments of Medicine and Anaesthetics, Royal Postgraduate Medical School, London W12 0HS
J. P. BARKER P. N. ROBINSON G. C. VAFIDIS G. R. HART G. M. HALL
IDENTICAL MITOCHONDRIAL DNA DELETION IN BLOOD AND MUSCLE
SIR,-Several patients with mitochondrial encephalomyopathy have been found to harbour large deletions in a proportion of mitochondrial DNA (mtDNA) in skeletal musclels and liver.s Blood mtDNA deletion has been demonstrated only in a single case of pancytopenia and lactate acidosis.6 All mtDNA deletions reported to date have been detected by Southern blot analysis. Using the polymerase chain reaction (PCR),’ we have been able to demonstrate an identical 4-3 kb mtDNA deletion in the skeletal muscle and peripheral blood of a 52-year-old woman with chronic progressive external ophthalmoplegia. She has a 30 year history of this condition, mild proximal limb girdle weakness, facial diplegia, and electromyographic findings consistent with a diffuse myopathy. Oxygen electrode polarography showed a defect in complex IV of the mitochondrial electron transport Numerous chain. characteristic "ragged red fibres" were revealed by muscle biopsy. Southern blotting demonstrated a dimorphic population of mtDNAs in skeletal muscle, mostly 12kb in size (consistent with a 4-3 kb deletion), while the peripheral blood showed only a single population of normal mtDNA. However, PCR amplification of the region surrounding the deletion demonstrated an identical deletion in both blood and muscle. Skeletal muscle contained a higher proportion of deleted mtDNA and generated a stronger single band at 375 base pairs than did blood. Restriction endonuclease digestion of the PCR-amplified deleted mtDNAs from blood and muscle showed an identical 43 kb deletion, extending from about 9400 to 13 700, and thus encompassing part of the genes that encode cytochrome oxidase III, NADH dehydrogenase subunits 3,4L, 4, and part of 5, and several transfer RNAs. This is the first demonstration of the same mtDNA deletion in two different tissues of a living patient, which indicates that the mutation occurred before divergence of the haematopoietic and myogenic cell lines either early in embryonic development or in a maternal predecessor. Different proportions of normal and deleted mtDNA species in two tissues may reflect either random mitotic segregation during development or, more likely, different selection pressures against the mutant species in the more rapidly proliferating haematopoietic cells than in skeletal muscle. The PCR
aplasia has not previously been reported after arthropod sting or bite; rhabdomyolysis may be caused by the venom of Hymenoptera2-4 or other arthropods, and it has been associated with acute renal failure after the bite of a centipede.5 Hymenoptera venom could have a facultative and occasionally cytopenic effect on bone marrow in an individual. Rhabdomyolysis is more difficult to explain; it seems unlikely to be caused by a single
sting.44 Department of Forensic Toxicology, University of Genoa, 16132 Genoa, Italy
F. TORREGIANI C. LA CAVERA
1. Torregiani F, La Cavera C Il Latrodectismo od avvelenamento da morso di Malmignatta (Latrodectus tredecimguttatus) m Italia. Minerva Med (m press). 2. Bousquet J, Huchard G, Michel F-B. Toxic reactions induced by hymenoptera venom. Ann Allergy 1984; 52: 371. 3 García Martin F, Martín Escobar E, Fernández Rodríguez A, Orte L, Quereda C, Ortuño J. Fracaso renal agudo asociado a rabdomiólisis no traumática por picaduras múltiples de abejas. Med Clin 1984; 83: 87. 4 Shilkin KB, Chen BTM, Khoo OT. Rhabdomyolysis caused by hornet venom. Br Med J 1972; i: 156. 5. Logan JL, Ogden DA Rhabdomyolysis and acute renal failure following the bite of the giant desert centipede Scolopendra heros. West J Med 1985; 142: 549.
SEX DIFFERENCE IN D7S8 MARKER ALLELE DISTRIBUTION IN ADULT CYSTIC FIBROSIS PATIENTS
SiR,—The clinical course of cystic fibrosis (CF) is variable and may depend on both genetic and environmental factors. Attempts to correlate clinical phenotypes with the distribution of alleles of markers closely linked to CF have given conflicting results-Dr Auvinet and colleagues (Jan 21, p 161) could not confirm all the findings of Momet et al.’ We have tried to relate survival rates of patients with CF to marker genotypes and found a sex difference for the MspI-RFLP detected by probe pj3 11 (D7S8), which presents the two alleles 4-2 kb (1) and 1kb (2).2 In a group of 147 German CF families, 18 patients (8 male) were older than 18 years at the time of DNA analysis, well above the present average life expectancy. The joint allele frequencies in this group did not differ from those observed in all patients. However, all six patients typing 1-1 were males; thus all female patients carried at least one allele 2. Three females but no male typed 2-2. These differences were significant (Fisher’s exact test, p < 0-003). Since allele 1 occurs on most CF chromosomes,3our fmding may indicate that a factor associated with D7S8 confers a modifying effect restricted to female patients. No such effects could be detected for the closely linked CF markers, KM19 and XV2c (D7S23). Institute of Human Genetics, Universitatsklinikum Charlottenburg, D-1000 Berlin 19, West Germany
JÖRG SCHMIDTKE
Institute of Human Genetics, University of Gottingen, Gottingen, West Germany
MICHAEL KRAWCZAK
1 Momet E, Simon-Bouy B, Serre JL, et al. Genetic differences between cystic fibrosis with and without meconium ileus. Lancet 1988; i: 376-78. 2 Bartels I, Grzeschik K-H, Cooper DN, Schmidtke J. Regional assignment of six cloned DNA sequences on human chromosome 7 Am J Hum Genet 1986; 38:
280-07 3. Schmidtke
J, Krawczak M, Schwartz M,
associations
et al. Linkage relationships and allelic of the cystic fibrosis locus and four marker loci. Hum Genet 1987, 76:
337-43.
LOCAL ANAESTHESIA FOR CATARACT SURGERY
SiR,—Dr Rassam and Dr Thomas (Jan 14, p 110) describe a favourable response to local anaesthesia (LA) for cataract surgery. We have completed a study in which we compared the hormonal and metabolic responses to cataract surgery under LA or general anaesthesia (GA). Eighteen elderly patients who had no metabolic or endocrine abnormalities were allocated randomly to receive GA or LA. No patient received premedication. The patients were anaesthetised either with a retrobulbar and facial block administered by one ophthalmic surgeon or with a thiopentone, vecuronium, and nitrous
oxygen, and enflurane technique. Blood samples were collected before, during, and after the operation. In the GA group plasma cortisol increased from 348 nmol/1 before induction of anaesthesia to a peak of 749 nmol/1 (p <0 01) after 1 h of recovery. In the LA group, however, plasma cortisol did not change significantly from the preinduction value of 320 nmol/1. Thus there was a significant difference between the groups both Blood glucose intraoperatively and postoperatively (p < 001). increased non-significantly in the GA group (4-7 to 52 mmol/1); there was no significant alteration in the LA group from the preinduction value of 4 4 mmol/1. The small glycaemic response in the GA patients was sufficient to result in a significant difference between the groups at the completion of the operation and after 30 min of recovery (p < 0-05). The operative time was significantly less in the GA group (25 min vs 30 min, p < 0-05), but the overall theatre times were similar (47 min, GA; 49 min, LA). This extra time in the GA patients was due to the need to reverse neuromuscular blockade and to establish spontaneous respiration on completion of the operation. Our results suggest that although cataract surgery is a minor procedure, as assessed by changes in circulating cortisol and glucose, these responses can be prevented by use of LA. Our results and the data of Rassam and Thomas suggest that the use of LA in cataract surgery should be extended.
oxide,
Department of Anaesthetics and Ophthalmic Surgery, Edgware General Hospital, Middlesex
Departments of Medicine and Anaesthetics, Royal Postgraduate Medical School, London W12 0HS
J. P. BARKER P. N. ROBINSON G. C. VAFIDIS G. R. HART G. M. HALL
IDENTICAL MITOCHONDRIAL DNA DELETION IN BLOOD AND MUSCLE
SIR,-Several patients with mitochondrial encephalomyopathy have been found to harbour large deletions in a proportion of mitochondrial DNA (mtDNA) in skeletal musclels and liver.s Blood mtDNA deletion has been demonstrated only in a single case of pancytopenia and lactate acidosis.6 All mtDNA deletions reported to date have been detected by Southern blot analysis. Using the polymerase chain reaction (PCR),’ we have been able to demonstrate an identical 4-3 kb mtDNA deletion in the skeletal muscle and peripheral blood of a 52-year-old woman with chronic progressive external ophthalmoplegia. She has a 30 year history of this condition, mild proximal limb girdle weakness, facial diplegia, and electromyographic findings consistent with a diffuse myopathy. Oxygen electrode polarography showed a defect in complex IV of the mitochondrial electron transport Numerous chain. characteristic "ragged red fibres" were revealed by muscle biopsy. Southern blotting demonstrated a dimorphic population of mtDNAs in skeletal muscle, mostly 12kb in size (consistent with a 4-3 kb deletion), while the peripheral blood showed only a single population of normal mtDNA. However, PCR amplification of the region surrounding the deletion demonstrated an identical deletion in both blood and muscle. Skeletal muscle contained a higher proportion of deleted mtDNA and generated a stronger single band at 375 base pairs than did blood. Restriction endonuclease digestion of the PCR-amplified deleted mtDNAs from blood and muscle showed an identical 43 kb deletion, extending from about 9400 to 13 700, and thus encompassing part of the genes that encode cytochrome oxidase III, NADH dehydrogenase subunits 3,4L, 4, and part of 5, and several transfer RNAs. This is the first demonstration of the same mtDNA deletion in two different tissues of a living patient, which indicates that the mutation occurred before divergence of the haematopoietic and myogenic cell lines either early in embryonic development or in a maternal predecessor. Different proportions of normal and deleted mtDNA species in two tissues may reflect either random mitotic segregation during development or, more likely, different selection pressures against the mutant species in the more rapidly proliferating haematopoietic cells than in skeletal muscle. The PCR