- Email: [email protected]
MUSCLE G6PD DEFICIENCY
212 expect such as shortness-of-breath and wheezing, also complained of other non-specific side-effects such as lethargy. All these symptoms improved when the patients were placed on an antihypertensive agent that does not lower cardiac output. Over the past year all newly diagnosed patients and patients on review have had respiratory function measured. If the fraction of measured vital capacity to predicted vital capacity was below 0-75, then treatment choice was limited or changed to a drug or drugs which are thought not to lower cardiac output. Subsequent audit of both new and previously treated patients whose treatment had been changed showed that the incidence of reported side-effects was 1-33 per patient in the group of 51 so far questioned. Of these, 32 patients had a measured to predicted vital capacity of less than 0-75 and 19 were over 0-75. The side-effect frequency in the two groups was 11 and 1-6, respectively. The improvement in well-being of these patients with this method of treatment choice has been encouraging. Health Centre, Eastcliffe Road, Par PL24 2AJ
F. D. SKERRETT M. J. WALDRON
CIPROFLOXACIN FOR CHOLANGITIS
SIR,-Dr Houwen and colleagues (June 13, p 1367) report 3 cases of cholangitis in children treated successfully with ciprofloxacin. These patients had undergone portoenterostomy because of biliary atresia. We have also successfully treated an older patient who had
cholangitis. patient is a 74-year-old uraemic woman with adult polycystic kidney disease. Since October, 1983, she has been treated uneventfully with haemodialysis. From November, 1986, to February, 1987, she had three episodes of septicaemia caused by Escherichia coli. According to bacterial susceptibility, the patient was treated with ampicillin, cephalothin, streptomycin, and gentamicin. The clinial response was satisfactory, but after each antibiotic the patient had severe idiosyncratic reactions. Only treatment with chloramphenicol was tolerated, but withdrawal was followed by spiking temperature. The upper right abdominal quadrant was tender, and kidney infection was suspected. On March 6, both kidneys were removed. Examination of the removed kidneys showed no signs of inflammation. Three new serious episodes of septicaemia occurred between March 25 and April 12. E coli with the same susceptibility pattern as found in the previously isolated strains was cultivated. Computerised tomography of the abdomen and an indium-labelled granulocyte scintigram were normal. Ultrasound revealed several 2-3 mm gallstones. Thus the gallbladder was suspected of harbouring E coli which caused recurrent cholangitis. By this time there was doubt whether the patient would survive cholecystectomy. From April 16, she has been treated with ciprofloxacin, 250 mg twice daily. No febrile episodes have occurred
recurrent
The
since.
Despite absence of definite positive signs, we think that this patient has recurrent cholangitis. We agree with Dr Houwen and colleagues that ciprofloxacin has a place in the treatment of this condition. Two questions emerge: how long is it necessary to continue the treatment, and when resistance to evolve? First University Clinic of Internal Medicine, Aarhus Kommunehospital, 8000 Aarhus, Denmark
can
one
expect bacterial
If these findings are important in the aetiology of idiopathic PD, would expect to find a lower incidence or less severe form among people of darker races compared with those who are fair-skinned, because dermal melanin might compete with neuromelanin in binding neurotoxins. Melanin in the skin of dark-skinned people presents many potential sites to which neurotoxins could bind. As the pigment is normally transferred to keratinocytes, which are shed with a turnover time of about a month,s neurotoxins bound to neuromelanin would be naturally removed. Several epidemiological studies have found a lower incidence of PD in black people. For example, in a study in 1972 of inpatiems,6 the mean annual incidence per 100 000 males was 28 for white vs 46 for black people, while in females it was 22-9 vs 4-3. It was suggested that melanin may help prevent PD. In Sardinia, among people of mixed southern European and northern African descent, the prevalence of PD was about one half that reported for people of northern European descent,7 Similarly, the prevalence of PD among Ashkenazic Jews in Israel was estimated at over five times the prevalence for the darker-skinned Sephardic Jews8 Schwenberg et al9 found no difference in the incidence of PD between black and white people when all cases were considered; however, the incidence was lower in black people when only "definite" cases were considered. The general finding of a decreased prevalence of PD in darker-skinned compared with lighter-skinned groups is consistent with the view that some cases of PD are caused by a toxin that can bind to either neuromelanin or dermal melanin. Indeed the finding of a difference in racial prevalence in some geographical areas but not in others may imply that a toxin is present in some areas but not in others. Whilst more clinical studies are needed, we wonder whether suntanning, whatever its deleterious effects in the skin as regards ageing or malignant changes, might be of benefit in preventing PD by decreasing the effect of neurotoxins on cells in the substantia one
nigra. Section of Molecular Neurobiology and Department of Neurology, Yale University School of Medicine, New Haven, 06510 Connecticut, USA
SR, Chiueh CC, Markey SP, et al. A primate model of parkinsonism: Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 1983; 80: 4546-50. 2. Langston JW, Fomo LS, Rebert CS, Irwin I Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey. Brain Res 1984; 292: 390-94. 3. Lyden A, Bondesson U, Larsson BS, et al. Melanin affinity of 1-methyl-4-phenyl1,2,5,6-tetrahydropyridine, an inducer of chronic parkinsonism in humans. Acta Pharmacol Toxicol 1983; 53: 429-32. 4. D’Amato RJ, Alexander GM, Schwartzman RJ, et al. Evidence for neuromelanin involvement in MPTP-induced neurotoxicity. Nature 1987; 327: 324-26 5. Wolff K. Melanocyte-keratinocyte interactions in vivo: The fate of melanosomes Yale J Biol Med 1973; 46: 384-96. 6. Kessler II. Epidemiologic studies of Parkinson’s disease II: A hospital-based survey Am J Epidemiol 1972; 95: 308-18. 7. Rosati G, Granieri E, Pinna L, et al. The risk of Parkinson’s disease in Mediterranean people. Neurology 1980; 30: 250-55. 8. Melamed E, Bitton B, Kidron D. Parkinson’s disease in Israelis: Relationship to ethnic origin supports etiologic importance of genetic factors. Neurology 1987; 37 (suppl 1. Bums
1): 121. 9.
Schoenberg BS, Anderson DW, Haerer AF. Prevalence of Parkinson’s disease in the biracial population of Copiah County, Mississippi. Neurology 1985; 35: 841-45
LISELOTTE LONKA ROBERT SMITH PEDERSEN
COLOUR, MPTP, AND PARKINSON’S DISEASE SIR,-Exposure to methylphenyltetrahydropyridine (MPTP) in man and monkeys leads to a syndrome resembling idiopathic Parkinson’s disease (PD).l,2 Melanin from several sources can bind SKIN
MPTP and its toxic derivative MPP +. Neuromelanin isolated from cells from the substantia nigra of monkeys can also bind MPP + .3 It was suggested that idiopathic PD may result from the binding of an environmental toxin to neuromelanin. Subsequent gradual release of the toxin over a long time may lead to destruction of the pigmented neurons. In support of this hypothesis, chloroquine, which competes with MPP + for binding sites on neuromelanin, protects monkeys from the neurotoxic effects of MPTP.4
MICHAEL R. LERNER ROBERT S. GOLDMAN
MUSCLE G6PD DEFICIENCY
SiR,—The deficiency of glucose-6-phosphate dehydrogenase (G6PD) is the most thoroughly studied, red blood cell (RBC) enzymopathy. The defect is widely distributed geographically and has been reported in over 160 variants affecting more than 100 million people.’ Muscle involvement and/or myoglobinuria have never been investigated in these patients. However, myalgia, fatigue, and hypostenia are common clinical symptoms. We report a defect of muscle G6PD in a 30-year-old pentathlon-trained athlete, who lost consciousness and lapsed into a coma with myoglobinuria the end of a 12-km run. The patient was transported to the emergency room in coma with sweating, hypotension, tachycardia, and raised temperature, but with preserved renal function. Hypoglycaemia (31 mg/dl) was immediately corrected without improvement in condition. BUN.
near
213
electrolytes, and proteins
were
normal.
Reticulocytosis
and mild
normochromic anaemia, decreased haptoglobin (41 mg/dl), and haemolysis were observed. Blood gas analysis showed metabolic acidosis. The patient had jaundice with increases in total (20-6 mg/dl) and direct bilirubin (9-22 mg/dl) (1 mg/dl= 17-1 umol/1). AST was 5080 and ALT 5650 IU/I; creatine kinase was 41 x 106 and LDH 4800 IU/1. Haemoglobin and myoglobin were present in the urine. The day after admission the patient recovered consciousness and denied any previous drug consumption. Diffuse, multifocal, infectious, or metabolic causes for coma were excluded. Our patient reported a previous similar episode but the urine had not been examined for myoglobinuria. Family history showed two brothers with pigmenturia after unspecified drug ingestion and a third brother who died at age 7 after ingestion of Viciafaba beans. When examined by us, the patient had a normal electromyography and was neurologically normal. Ischaemic exercise in the forearm was followed by a normal rise of venous lactate. Serum carnitine was also normal. A muscle biopsy done three months later was normal on light and electron microscopy, but a histochemical stain for G6PD was negative. Muscle carnitine and carnitine palmityl transferase were normal. All glycolytic and mitochondrial enzymes in a muscle homogenate were also normal. The G6PD activity was 0-9% in RBC and 0% in the muscle homogenate, compared with controls. Residual activity was present in leucocytes (20%) and in platelets (50%). Characterisation of the mutant enzyme classified this deficiency as a Mediterranean variant.2 Cellulose acetate electrophoresis of G6PD in the patient’s tissues showed no detectable band of activity in RBC and muscle homogenates. G6PD activity in the patient’s myotubes and fibroblasts was 18-8% and 18.3% of controls, respectively. The residual enzyme showed a single electrophoretic band migrating like normal muscle G6PD. The possible causes of myoglobinuria in our patient during "oxidative stress" induced by metabolic acidosis and hypoglycaemia could be lack of NADPH, which is necessary to stabilise the membranes, and impaired conversion of pentose into hexose, reducing the supply of energy.3 The frequency of this enzyme defect and the potentially lethal consequences of muscle involvement with myoglobinuria suggest the usefulness of further investigation in cases such as ours. N. BRESOLIN L. BET M. MOGGIO G. MEOLA Institute of Clinical Neurology, G. COMI Centro Dino Ferrari, A. GILARDI University of Milan, G. SCARLATO 20122 Milan, Italy 1. Travis SF. Red cell
enzymopathies in the newborn:
enzymes. Ann Clin Lab Sci 1982; 12: 163-77 2 Luzzatto L, Battistuzzi G. Glucose-6-phosphate 3
Plasma ANP and RAP in Shaded
1985; 4: 217-323. Rowland LP Myoglobinuria 1984. J Can Sci Neural 1984; 11: 1-13.
PHYSIOLOGICAL RELEASE OF ATRIAL
NATRIURETIC PEPTIDE IN HEART TRANSPLANT RECIPIENT
SIR,-Atrial natriuretic peptide (ANP) is present in the plasma of transplant recipients,’ but it is not known whether a denervated human heart will release ANP physiologically in cardiac
response to altered atrial pressure. We have studied a 35-year-old patient three days after she had received a heart transplant from a live donor who had primary lung pathology. A fraction of the right atrium of the recipient remained in situ. A transplant biopsy on the day of study did not reveal evidence of rejection. Peripheral venous ANP (normal mean [SD] 40 [16] pmol/1, n = 30) was measured by radioimmunoassay during a twenty-four hour period when severe plasma-volume depletion was corrected by administration of colloid and saline. A high right atrial pressure (RAP) was required to maintain an adequate cardiac output in this heart, which showed electrocardiographic evidence of right ventricular hypertrophy. Plasma ANP increased from an
a
patient after cardiac transplantation.
normal ranges.
initial value of 9-6 pmol/1 (29-7 pg/ml) to a peak of 45-0 pmol/1 during the period of fluid repletion, when RAP rose from 10 to 27 cm H2O (figure). There was a positive correlation between ANP level and RAP (r = 0-87, p = 0-02). Our results agree with animal studies in which physically and pharmacologically denervated atria released immunoreactive and biologically active natriuretic factors when atrial pressures were increased.2,3Although it is not possible to exclude a contribution to our patient’s measured plasma ANP by the small remnant of her right atrium, we conclude that when large changes of atrial pressure
(and therefore atrial stretch) occur, intact cardiac innervation is not necessary for the physiological release of ANP. Academic Unit of Endocrinology and Diabetes,
A. S. WOOLF P. J. A. MOULT M. SUTTERS M. A. MANSELL
Whittington Hospital, London N19 5NF; and St Peter’s Hospitals and Institute of Urology,
London 1.
Singer DRJ, Buckley MG, MacGreggor GA, Khaghani A, Banner NR, Yacoub MH. Raised concentrations of plasma atrial natriuretic peptides in cardiac transplant recipients. Br Med J 1986; 292: 1391-92. 2. Dietz JR. Release of natriuretic factor from rat heart-lung preparation by atrial distension. Am J Physiol 1984; 247: R1093-96. 3. Ledsome JR, Wilson N, Coumeya CA, Rankin AJ. Release of atrial natriuretic peptide by atrial distension. Can J Physiol Pharmacol 1985; 63: 739-42.
Inherited deficiencies of red cell
dehydrogenase. Adv Hum Genet
area =
AZTREONAM IN CAPD PERITONITIS
SIR,-Dr Neville and colleagues (June 6, p 1320)
state
that they
planning to use aztreonam, a monobactam with no known toxicity in patients with renal failure,l to treat gram-negative peritonitis. We have completed a multicentre open study of aztreonam in CAPD peritonitis. are
Since
January, 1985, in
our
four
CAPD programmes,
intraperitoneal aztreonam (500 mg/1 in the first exchange after recognition of a cloudy effluent, and 250 mg/1 in the next bags) with intraperitoneal cloxacillin or, more frequently, vancomycin was used to treat peritonitis. Treatment with aztreonam alone was continued in 31 episodes of gram-negative infection among 26 patients. These episodes represent 20% of all peritonitis recorded during the 30 months of the study. Microorganisms isolated were: Escherichia coli 8, Pseudomonas sp 8, Acinetobacter sp 6, Klebsiella sp 5, and other gram-negative 7. In 3 episodes, two organisms were cultured. The microbiological response was cure in 24 episodes, cure with relapse in 2, cure with superinfection in 2, and failure in 3 (with resistance to aztreonam in 2). Clinically we observed 26 cures, 1 part response, and 4 failures. No side-effects due to aztreonam were noted. In addition, we compared the 31 gram-negative peritonitis episodes treated with aztreonam to 35 episodes observed during 1983 and 1984 (historical controls), treated mainly with
F. D. SKERRETT M. J. WALDRON
CIPROFLOXACIN FOR CHOLANGITIS
SIR,-Dr Houwen and colleagues (June 13, p 1367) report 3 cases of cholangitis in children treated successfully with ciprofloxacin. These patients had undergone portoenterostomy because of biliary atresia. We have also successfully treated an older patient who had
cholangitis. patient is a 74-year-old uraemic woman with adult polycystic kidney disease. Since October, 1983, she has been treated uneventfully with haemodialysis. From November, 1986, to February, 1987, she had three episodes of septicaemia caused by Escherichia coli. According to bacterial susceptibility, the patient was treated with ampicillin, cephalothin, streptomycin, and gentamicin. The clinial response was satisfactory, but after each antibiotic the patient had severe idiosyncratic reactions. Only treatment with chloramphenicol was tolerated, but withdrawal was followed by spiking temperature. The upper right abdominal quadrant was tender, and kidney infection was suspected. On March 6, both kidneys were removed. Examination of the removed kidneys showed no signs of inflammation. Three new serious episodes of septicaemia occurred between March 25 and April 12. E coli with the same susceptibility pattern as found in the previously isolated strains was cultivated. Computerised tomography of the abdomen and an indium-labelled granulocyte scintigram were normal. Ultrasound revealed several 2-3 mm gallstones. Thus the gallbladder was suspected of harbouring E coli which caused recurrent cholangitis. By this time there was doubt whether the patient would survive cholecystectomy. From April 16, she has been treated with ciprofloxacin, 250 mg twice daily. No febrile episodes have occurred
recurrent
The
since.
Despite absence of definite positive signs, we think that this patient has recurrent cholangitis. We agree with Dr Houwen and colleagues that ciprofloxacin has a place in the treatment of this condition. Two questions emerge: how long is it necessary to continue the treatment, and when resistance to evolve? First University Clinic of Internal Medicine, Aarhus Kommunehospital, 8000 Aarhus, Denmark
can
one
expect bacterial
If these findings are important in the aetiology of idiopathic PD, would expect to find a lower incidence or less severe form among people of darker races compared with those who are fair-skinned, because dermal melanin might compete with neuromelanin in binding neurotoxins. Melanin in the skin of dark-skinned people presents many potential sites to which neurotoxins could bind. As the pigment is normally transferred to keratinocytes, which are shed with a turnover time of about a month,s neurotoxins bound to neuromelanin would be naturally removed. Several epidemiological studies have found a lower incidence of PD in black people. For example, in a study in 1972 of inpatiems,6 the mean annual incidence per 100 000 males was 28 for white vs 46 for black people, while in females it was 22-9 vs 4-3. It was suggested that melanin may help prevent PD. In Sardinia, among people of mixed southern European and northern African descent, the prevalence of PD was about one half that reported for people of northern European descent,7 Similarly, the prevalence of PD among Ashkenazic Jews in Israel was estimated at over five times the prevalence for the darker-skinned Sephardic Jews8 Schwenberg et al9 found no difference in the incidence of PD between black and white people when all cases were considered; however, the incidence was lower in black people when only "definite" cases were considered. The general finding of a decreased prevalence of PD in darker-skinned compared with lighter-skinned groups is consistent with the view that some cases of PD are caused by a toxin that can bind to either neuromelanin or dermal melanin. Indeed the finding of a difference in racial prevalence in some geographical areas but not in others may imply that a toxin is present in some areas but not in others. Whilst more clinical studies are needed, we wonder whether suntanning, whatever its deleterious effects in the skin as regards ageing or malignant changes, might be of benefit in preventing PD by decreasing the effect of neurotoxins on cells in the substantia one
nigra. Section of Molecular Neurobiology and Department of Neurology, Yale University School of Medicine, New Haven, 06510 Connecticut, USA
SR, Chiueh CC, Markey SP, et al. A primate model of parkinsonism: Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 1983; 80: 4546-50. 2. Langston JW, Fomo LS, Rebert CS, Irwin I Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey. Brain Res 1984; 292: 390-94. 3. Lyden A, Bondesson U, Larsson BS, et al. Melanin affinity of 1-methyl-4-phenyl1,2,5,6-tetrahydropyridine, an inducer of chronic parkinsonism in humans. Acta Pharmacol Toxicol 1983; 53: 429-32. 4. D’Amato RJ, Alexander GM, Schwartzman RJ, et al. Evidence for neuromelanin involvement in MPTP-induced neurotoxicity. Nature 1987; 327: 324-26 5. Wolff K. Melanocyte-keratinocyte interactions in vivo: The fate of melanosomes Yale J Biol Med 1973; 46: 384-96. 6. Kessler II. Epidemiologic studies of Parkinson’s disease II: A hospital-based survey Am J Epidemiol 1972; 95: 308-18. 7. Rosati G, Granieri E, Pinna L, et al. The risk of Parkinson’s disease in Mediterranean people. Neurology 1980; 30: 250-55. 8. Melamed E, Bitton B, Kidron D. Parkinson’s disease in Israelis: Relationship to ethnic origin supports etiologic importance of genetic factors. Neurology 1987; 37 (suppl 1. Bums
1): 121. 9.
Schoenberg BS, Anderson DW, Haerer AF. Prevalence of Parkinson’s disease in the biracial population of Copiah County, Mississippi. Neurology 1985; 35: 841-45
LISELOTTE LONKA ROBERT SMITH PEDERSEN
COLOUR, MPTP, AND PARKINSON’S DISEASE SIR,-Exposure to methylphenyltetrahydropyridine (MPTP) in man and monkeys leads to a syndrome resembling idiopathic Parkinson’s disease (PD).l,2 Melanin from several sources can bind SKIN
MPTP and its toxic derivative MPP +. Neuromelanin isolated from cells from the substantia nigra of monkeys can also bind MPP + .3 It was suggested that idiopathic PD may result from the binding of an environmental toxin to neuromelanin. Subsequent gradual release of the toxin over a long time may lead to destruction of the pigmented neurons. In support of this hypothesis, chloroquine, which competes with MPP + for binding sites on neuromelanin, protects monkeys from the neurotoxic effects of MPTP.4
MICHAEL R. LERNER ROBERT S. GOLDMAN
MUSCLE G6PD DEFICIENCY
SiR,—The deficiency of glucose-6-phosphate dehydrogenase (G6PD) is the most thoroughly studied, red blood cell (RBC) enzymopathy. The defect is widely distributed geographically and has been reported in over 160 variants affecting more than 100 million people.’ Muscle involvement and/or myoglobinuria have never been investigated in these patients. However, myalgia, fatigue, and hypostenia are common clinical symptoms. We report a defect of muscle G6PD in a 30-year-old pentathlon-trained athlete, who lost consciousness and lapsed into a coma with myoglobinuria the end of a 12-km run. The patient was transported to the emergency room in coma with sweating, hypotension, tachycardia, and raised temperature, but with preserved renal function. Hypoglycaemia (31 mg/dl) was immediately corrected without improvement in condition. BUN.
near
213
electrolytes, and proteins
were
normal.
Reticulocytosis
and mild
normochromic anaemia, decreased haptoglobin (41 mg/dl), and haemolysis were observed. Blood gas analysis showed metabolic acidosis. The patient had jaundice with increases in total (20-6 mg/dl) and direct bilirubin (9-22 mg/dl) (1 mg/dl= 17-1 umol/1). AST was 5080 and ALT 5650 IU/I; creatine kinase was 41 x 106 and LDH 4800 IU/1. Haemoglobin and myoglobin were present in the urine. The day after admission the patient recovered consciousness and denied any previous drug consumption. Diffuse, multifocal, infectious, or metabolic causes for coma were excluded. Our patient reported a previous similar episode but the urine had not been examined for myoglobinuria. Family history showed two brothers with pigmenturia after unspecified drug ingestion and a third brother who died at age 7 after ingestion of Viciafaba beans. When examined by us, the patient had a normal electromyography and was neurologically normal. Ischaemic exercise in the forearm was followed by a normal rise of venous lactate. Serum carnitine was also normal. A muscle biopsy done three months later was normal on light and electron microscopy, but a histochemical stain for G6PD was negative. Muscle carnitine and carnitine palmityl transferase were normal. All glycolytic and mitochondrial enzymes in a muscle homogenate were also normal. The G6PD activity was 0-9% in RBC and 0% in the muscle homogenate, compared with controls. Residual activity was present in leucocytes (20%) and in platelets (50%). Characterisation of the mutant enzyme classified this deficiency as a Mediterranean variant.2 Cellulose acetate electrophoresis of G6PD in the patient’s tissues showed no detectable band of activity in RBC and muscle homogenates. G6PD activity in the patient’s myotubes and fibroblasts was 18-8% and 18.3% of controls, respectively. The residual enzyme showed a single electrophoretic band migrating like normal muscle G6PD. The possible causes of myoglobinuria in our patient during "oxidative stress" induced by metabolic acidosis and hypoglycaemia could be lack of NADPH, which is necessary to stabilise the membranes, and impaired conversion of pentose into hexose, reducing the supply of energy.3 The frequency of this enzyme defect and the potentially lethal consequences of muscle involvement with myoglobinuria suggest the usefulness of further investigation in cases such as ours. N. BRESOLIN L. BET M. MOGGIO G. MEOLA Institute of Clinical Neurology, G. COMI Centro Dino Ferrari, A. GILARDI University of Milan, G. SCARLATO 20122 Milan, Italy 1. Travis SF. Red cell
enzymopathies in the newborn:
enzymes. Ann Clin Lab Sci 1982; 12: 163-77 2 Luzzatto L, Battistuzzi G. Glucose-6-phosphate 3
Plasma ANP and RAP in Shaded
1985; 4: 217-323. Rowland LP Myoglobinuria 1984. J Can Sci Neural 1984; 11: 1-13.
PHYSIOLOGICAL RELEASE OF ATRIAL
NATRIURETIC PEPTIDE IN HEART TRANSPLANT RECIPIENT
SIR,-Atrial natriuretic peptide (ANP) is present in the plasma of transplant recipients,’ but it is not known whether a denervated human heart will release ANP physiologically in cardiac
response to altered atrial pressure. We have studied a 35-year-old patient three days after she had received a heart transplant from a live donor who had primary lung pathology. A fraction of the right atrium of the recipient remained in situ. A transplant biopsy on the day of study did not reveal evidence of rejection. Peripheral venous ANP (normal mean [SD] 40 [16] pmol/1, n = 30) was measured by radioimmunoassay during a twenty-four hour period when severe plasma-volume depletion was corrected by administration of colloid and saline. A high right atrial pressure (RAP) was required to maintain an adequate cardiac output in this heart, which showed electrocardiographic evidence of right ventricular hypertrophy. Plasma ANP increased from an
a
patient after cardiac transplantation.
normal ranges.
initial value of 9-6 pmol/1 (29-7 pg/ml) to a peak of 45-0 pmol/1 during the period of fluid repletion, when RAP rose from 10 to 27 cm H2O (figure). There was a positive correlation between ANP level and RAP (r = 0-87, p = 0-02). Our results agree with animal studies in which physically and pharmacologically denervated atria released immunoreactive and biologically active natriuretic factors when atrial pressures were increased.2,3Although it is not possible to exclude a contribution to our patient’s measured plasma ANP by the small remnant of her right atrium, we conclude that when large changes of atrial pressure
(and therefore atrial stretch) occur, intact cardiac innervation is not necessary for the physiological release of ANP. Academic Unit of Endocrinology and Diabetes,
A. S. WOOLF P. J. A. MOULT M. SUTTERS M. A. MANSELL
Whittington Hospital, London N19 5NF; and St Peter’s Hospitals and Institute of Urology,
London 1.
Singer DRJ, Buckley MG, MacGreggor GA, Khaghani A, Banner NR, Yacoub MH. Raised concentrations of plasma atrial natriuretic peptides in cardiac transplant recipients. Br Med J 1986; 292: 1391-92. 2. Dietz JR. Release of natriuretic factor from rat heart-lung preparation by atrial distension. Am J Physiol 1984; 247: R1093-96. 3. Ledsome JR, Wilson N, Coumeya CA, Rankin AJ. Release of atrial natriuretic peptide by atrial distension. Can J Physiol Pharmacol 1985; 63: 739-42.
Inherited deficiencies of red cell
dehydrogenase. Adv Hum Genet
area =
AZTREONAM IN CAPD PERITONITIS
SIR,-Dr Neville and colleagues (June 6, p 1320)
state
that they
planning to use aztreonam, a monobactam with no known toxicity in patients with renal failure,l to treat gram-negative peritonitis. We have completed a multicentre open study of aztreonam in CAPD peritonitis. are
Since
January, 1985, in
our
four
CAPD programmes,
intraperitoneal aztreonam (500 mg/1 in the first exchange after recognition of a cloudy effluent, and 250 mg/1 in the next bags) with intraperitoneal cloxacillin or, more frequently, vancomycin was used to treat peritonitis. Treatment with aztreonam alone was continued in 31 episodes of gram-negative infection among 26 patients. These episodes represent 20% of all peritonitis recorded during the 30 months of the study. Microorganisms isolated were: Escherichia coli 8, Pseudomonas sp 8, Acinetobacter sp 6, Klebsiella sp 5, and other gram-negative 7. In 3 episodes, two organisms were cultured. The microbiological response was cure in 24 episodes, cure with relapse in 2, cure with superinfection in 2, and failure in 3 (with resistance to aztreonam in 2). Clinically we observed 26 cures, 1 part response, and 4 failures. No side-effects due to aztreonam were noted. In addition, we compared the 31 gram-negative peritonitis episodes treated with aztreonam to 35 episodes observed during 1983 and 1984 (historical controls), treated mainly with