882
Koenig M, Beggs AH, Moyer M, et al. The molecular basis for Duchenne versus Becker muscular dystrophy, correlation of severity with type of deletion Am J Hum
4
(a) Normal
Genet 1989; 45: 498-506
Nicholson LV, Johnson MA, et al. Very mild muscular dystrophy associated with the deletion of 46% of dystrophin. Nature 1990; 343: 180-82. 6. Hoffman EP, Beggs AH, Koenig M, Kunkel LM, Angelini C. Cross-reactive protein in Duchenne muscle Lancet 1989; ii: 1211-12. 7 Nguyen thi Man, Cartwright AJ, Morris GE, Love DR, Bloomfield JR, Davies KE Monoclonal antibodies against defined regions of the muscular dystrophy protein. dystrophin FEBS Lett 1990; 262: 237-40 5.
England SB,
Acute compartment syndrome secondary to
theophylline poisoning SIR,-Mr Lloyd and his colleagues (Aug 4, p 312) describe an acute compartment syndrome and renal failure in a patient severely
(b) Duchenne
with theophylline. Both these features are recognised sequelae of rhabdomyolysis," which developed in their panent and which we have also noted in theophylline poisoning. Acute compartment syndrome should be anticipated in any case of severe rhabdomyolysis.’,’The major precipitating factor in Lloyd and colleagues’ patient was probably repeated seizures, exacerbated by hypokalaemia and hypotension; limb compression may also have played a part.’ These complications are generally related to the severity of theophylline intoxication and it is therefore appropriate to administer large doses of activated charcoal both to prevent theophylline absorption (which may be prolonged if a slow-release preparation has been taken as in this patient) and to increase elimination. The secondary rise in the plasma theophylline concentration that Lloyd et al note suggests that charcoal therapy may have been stopped prematurely. It is also important to attempt to reduce the likelihood of the development of rhabdomyolysis and its sequelae. Our practice is to ventilate prophylactically all patients who have repeated convulsions despite the use of intravenous diazepam and the
poisoned
Fig 2-lmmunofluorescent detection of the C-terminal region of dystrophin in the membranes of normal, but not Duchenne, muscle fibres.
lmmunostaining of frozen
muscle
section
described,’ with monoclonal antibody shown
m
was performed fig 1 b. (Reduced
as
to
x75)
correction of
purified and used to immunise mice for monoclonal antibody preparation.7 The monoclonal antibodies clearly fell into two classes immunoblots: two stained dystrophin in normal muscle extracts and cross-reacted in dystrophic muscle with a lower abundance protein of the same size as dystrophin (400 kD), as described for polyclonal antisera6 (fig la) and seventeen were dystrophin-specific and stained nothing in dystrophic muscle (fig lb). Six of the fifteen dystrophin-specific antibodies also gave strong staining of dystrophin on frozen sections from normal, but not Duchenne, muscle (fig 2), enabling the use of these antibodies for both
electrolyte and acid-base disturbances. If these fail, as Lloyd and colleagues indicate, compartment pressure monitoring is an important diagnostic tool. measures
on
diagnostic techniques. Polyclonal antisera against the N-terminal of dystrophin show a similar cross-reaction, possibly with the same proteinand it seems likely that this problem will also be resolved in the same way. Monoclonal antibodies against the central rod region are already available.’
West Midlands Poisons Unit, Dudley Road Hospital, Birmingham B18 7QH. UK
Research Division, N E Wales Institute, Deeside, Clwyd CH5 4BR. UK
NGUYEN THI MAN G. E. MORRIS
Department of Anatomy and Embryology, Academisch-Medisch Centrum, University of Amsterdam, Amsterdam, Netherlands, and Department of Human Genetics, Sylvius Laboratories,
University of Leiden
I. B. GINJAAR A. F. M. MOORMAN G.-J. B. VAN OMMEN
J. A. VALE
HM, Cowan RA Rhabdomyolysis and acute renal failure after theophylline overdose. Lancet 1985, i: 932-33. Briner V, Colombi A, Brunner W, Truniger B. Die akute rhabdomyolyse Schweiz Med Wochenschr 1986; 116: 198-208 Ward MM. Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern
1. Macdonald JB, Jones 2
3
Med 1988; 148: 1553-57. 4. Owen CA, Mubarak SJ, Hargens AR, Rutherford L, Geretto LP, Akeson WH Intramuscular pressures with limb compression, clarification of the pathogenesis of the drug-induced muscle-compartment syndrome. N Engl J Med 1979; 300: 1169-72. 5. Koppel C. Clinical features, pathogenesis and management of drug-induced rhabdomyolysis. Med Toxicol Adverse Drug Exper 1989; 4: 108-26
We thank the Muscular Dystrophy Group of Great Britain and Northern Ireland and the Prinses Beatrix Fund for financial support, Tim Helliwell (Department of Pathology, Royal Liverpool Hospital) for human muscle sections, and Marleen van Paassen for preparing recombinant plasmids.
J. M. ELLIS
M. F. RYAN
Diagnosis of phaeochromocytoma StR,—Your May 19 editorial
phaeochromocytoma states that who entered the Mayo Clinic between 1928 and 1977 were diagnosed only at necropsy". That is incorrect. The referenced article was a review of a 50-year post-mortem series and included only those patients who died at the Mayo Clinic and in whom a full necropsy was done. About 400 cases have been operated on from 1950 through 1989. While it is true that phaeochromocytoma may not be considered when the presentation is unusual, the vast majority of cases are readily diagnosed during "85% of patients with this
on
tumour
life.’ EP, Fischbeck KH, Brown RH, et al. Characterization of dystrophm m muscle-biopsy specimens from patients with Duchenne’s or Becker’s muscular dystrophy. N Engl J Med 1988; 318: 1363-68. 2. Hurko O, Hoffman EP, McKee L, Johns DR, Kunkel LM Dystrophin analysis in clonal myoblasts denved from a Duchenne muscular dystrophy carrier. Am J Hum Genet 1989; 44: 820-26 3. Koenig M, Monaco AP, Kunkel LM. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 1988, 53: 219-26. 1 Hoffman
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
1.
Sheps SG, Jiang N-S,
S. G. SHEPS
Klee GG, Van Heerden JA. Recent developments in the diagnosis and treatment of pheochromocytoma Mayo Clin Proc 1990, 65: 88-95
Koenig M, Beggs AH, Moyer M, et al. The molecular basis for Duchenne versus Becker muscular dystrophy, correlation of severity with type of deletion Am J Hum
4
(a) Normal
Genet 1989; 45: 498-506
Nicholson LV, Johnson MA, et al. Very mild muscular dystrophy associated with the deletion of 46% of dystrophin. Nature 1990; 343: 180-82. 6. Hoffman EP, Beggs AH, Koenig M, Kunkel LM, Angelini C. Cross-reactive protein in Duchenne muscle Lancet 1989; ii: 1211-12. 7 Nguyen thi Man, Cartwright AJ, Morris GE, Love DR, Bloomfield JR, Davies KE Monoclonal antibodies against defined regions of the muscular dystrophy protein. dystrophin FEBS Lett 1990; 262: 237-40 5.
England SB,
Acute compartment syndrome secondary to
theophylline poisoning SIR,-Mr Lloyd and his colleagues (Aug 4, p 312) describe an acute compartment syndrome and renal failure in a patient severely
(b) Duchenne
with theophylline. Both these features are recognised sequelae of rhabdomyolysis," which developed in their panent and which we have also noted in theophylline poisoning. Acute compartment syndrome should be anticipated in any case of severe rhabdomyolysis.’,’The major precipitating factor in Lloyd and colleagues’ patient was probably repeated seizures, exacerbated by hypokalaemia and hypotension; limb compression may also have played a part.’ These complications are generally related to the severity of theophylline intoxication and it is therefore appropriate to administer large doses of activated charcoal both to prevent theophylline absorption (which may be prolonged if a slow-release preparation has been taken as in this patient) and to increase elimination. The secondary rise in the plasma theophylline concentration that Lloyd et al note suggests that charcoal therapy may have been stopped prematurely. It is also important to attempt to reduce the likelihood of the development of rhabdomyolysis and its sequelae. Our practice is to ventilate prophylactically all patients who have repeated convulsions despite the use of intravenous diazepam and the
poisoned
Fig 2-lmmunofluorescent detection of the C-terminal region of dystrophin in the membranes of normal, but not Duchenne, muscle fibres.
lmmunostaining of frozen
muscle
section
described,’ with monoclonal antibody shown
m
was performed fig 1 b. (Reduced
as
to
x75)
correction of
purified and used to immunise mice for monoclonal antibody preparation.7 The monoclonal antibodies clearly fell into two classes immunoblots: two stained dystrophin in normal muscle extracts and cross-reacted in dystrophic muscle with a lower abundance protein of the same size as dystrophin (400 kD), as described for polyclonal antisera6 (fig la) and seventeen were dystrophin-specific and stained nothing in dystrophic muscle (fig lb). Six of the fifteen dystrophin-specific antibodies also gave strong staining of dystrophin on frozen sections from normal, but not Duchenne, muscle (fig 2), enabling the use of these antibodies for both
electrolyte and acid-base disturbances. If these fail, as Lloyd and colleagues indicate, compartment pressure monitoring is an important diagnostic tool. measures
on
diagnostic techniques. Polyclonal antisera against the N-terminal of dystrophin show a similar cross-reaction, possibly with the same proteinand it seems likely that this problem will also be resolved in the same way. Monoclonal antibodies against the central rod region are already available.’
West Midlands Poisons Unit, Dudley Road Hospital, Birmingham B18 7QH. UK
Research Division, N E Wales Institute, Deeside, Clwyd CH5 4BR. UK
NGUYEN THI MAN G. E. MORRIS
Department of Anatomy and Embryology, Academisch-Medisch Centrum, University of Amsterdam, Amsterdam, Netherlands, and Department of Human Genetics, Sylvius Laboratories,
University of Leiden
I. B. GINJAAR A. F. M. MOORMAN G.-J. B. VAN OMMEN
J. A. VALE
HM, Cowan RA Rhabdomyolysis and acute renal failure after theophylline overdose. Lancet 1985, i: 932-33. Briner V, Colombi A, Brunner W, Truniger B. Die akute rhabdomyolyse Schweiz Med Wochenschr 1986; 116: 198-208 Ward MM. Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern
1. Macdonald JB, Jones 2
3
Med 1988; 148: 1553-57. 4. Owen CA, Mubarak SJ, Hargens AR, Rutherford L, Geretto LP, Akeson WH Intramuscular pressures with limb compression, clarification of the pathogenesis of the drug-induced muscle-compartment syndrome. N Engl J Med 1979; 300: 1169-72. 5. Koppel C. Clinical features, pathogenesis and management of drug-induced rhabdomyolysis. Med Toxicol Adverse Drug Exper 1989; 4: 108-26
We thank the Muscular Dystrophy Group of Great Britain and Northern Ireland and the Prinses Beatrix Fund for financial support, Tim Helliwell (Department of Pathology, Royal Liverpool Hospital) for human muscle sections, and Marleen van Paassen for preparing recombinant plasmids.
J. M. ELLIS
M. F. RYAN
Diagnosis of phaeochromocytoma StR,—Your May 19 editorial
phaeochromocytoma states that who entered the Mayo Clinic between 1928 and 1977 were diagnosed only at necropsy". That is incorrect. The referenced article was a review of a 50-year post-mortem series and included only those patients who died at the Mayo Clinic and in whom a full necropsy was done. About 400 cases have been operated on from 1950 through 1989. While it is true that phaeochromocytoma may not be considered when the presentation is unusual, the vast majority of cases are readily diagnosed during "85% of patients with this
on
tumour
life.’ EP, Fischbeck KH, Brown RH, et al. Characterization of dystrophm m muscle-biopsy specimens from patients with Duchenne’s or Becker’s muscular dystrophy. N Engl J Med 1988; 318: 1363-68. 2. Hurko O, Hoffman EP, McKee L, Johns DR, Kunkel LM Dystrophin analysis in clonal myoblasts denved from a Duchenne muscular dystrophy carrier. Am J Hum Genet 1989; 44: 820-26 3. Koenig M, Monaco AP, Kunkel LM. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 1988, 53: 219-26. 1 Hoffman
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
1.
Sheps SG, Jiang N-S,
S. G. SHEPS
Klee GG, Van Heerden JA. Recent developments in the diagnosis and treatment of pheochromocytoma Mayo Clin Proc 1990, 65: 88-95
