935 oL,-A.T. TYPES
OF PATIENTS WITH RHEUMATOID ARTHRITIS
We suggest that the false-negative alpha-fetoprotein concentrations in plasma and liquor were caused by an anatomical block between the third and fourth ventricle which prevented significant quantities of c.s.F. circulating into the amniotic fluid and maternal tissues. B. V. LEWIS Divisions of Obstetrics & Gynæcology and Pathology,
J. ENGLAND
Watford General Hospital, Watford, Hens WD1 8HB
Although the PiZ allele was found in Swiss blood-donors a frequency similar to that in other middle European populations,5 there was no MZ phenotype in our patients (see table). The frequencies of the MS and MM1 phenotypes were
R. CHADWICK
with
those in other European and North American White populations.6’ These results therefore do not support an association of the MZ phenotype of o-A.T. with rheumatoid arthritis. The serum concentration of ot-A.T. was higher in patients (3-16+1.12 mg/ml) than in healthy blood donors (2.20±0.21 S.D. mg/ml).8 (Two serum pools from Dr M. K. Fagerhol and Dr J. Pierce used by some laboratories as 100% standards had (XCA.T. concentrations of 2-23 mg/ml and 2.15 mg/ml respectively.) o-A.T. in female patients (3-37±1-01 mg/ml) was higher than in males (3.05±0.88 mg/ml) but not significantly so (e>01). A rise of lX1-A.T. in rheumatoid arthritis, which has been previously reported,9 confirms the view that o-A.T. is an acute-phase reactant protein which increases in concentration in response to an inflammatory stimulus.
close
to
Rheumatologische Universitätsklinik, Basle, Switzerland
D. BRACKERTZ
Temple University School of Medicine, Philadelphia, Pennsylvania 19140, U.S.A.
F. KUEPPERS
DIABETES MELLITUS IN PATIENTS ON LITHIUM
SiR,—The following two cases suggest a possible association between lithium therapy and acute-onset diabetes mellitus. Case1 This 52-year-old woman with manic-depressive psychosis had been put on lithium therapy in June 1967, and routine urine tests had always been negative for sugar and ketones. She was admitted in an hypomanic state in February, 1976, but her condition deteriorated rapidly. Serum-lithium was 2-4 mmol/1 and plasma-glucose 7.3 mmol/l. The initial diagnosis was lithium toxicity and bronchopneumonia. Within 24 h she was comatose and decerebrate but an E.E.G. and carotid angiogram were normal. 5 days after admission she had frank hyperglycsemia and dehydration (plasma-glucose 21.3 mmol/1). Despite electrolyte replacement, insulin, and antibiotics she died. Necropsy revealed: massive pulmonary embolism, pulmonary oedema, bronchopneumonia, ileofemoral thrombosis, and cholelithiasis. The pituitary was large and cystic but histologically normal. There was no comment on the macroscopic or microscopic appearance of the pancreas. Case 2
FALSE-NEGATIVE SCREEN FOR NEURAL TUBE DEFECT IN SPINA BIFIDA WITH STENOSIS OF THE AQUEDUCT OF SYLVIUS
SIR,-We describe here a patient aged 25 who delivered an anencephalic stillborn female infant in her first pregnancy in 1975. After 17 weeks of her second pregnancy, a blood sample taken and transabdominal amniocentesis done. 12 ml clear liquor was collected without difficulty. The serum alpha-fetoprotein concentration, by radioimmunoassay,was 64 ng/ml (1.2 median) and the amniotic fluid alpha-fetoprotein, by Laurell electrophoresis, was 18 g/ml (2.0 median). Both values were normal for our laboratory, which participates in a national quality-control scheme. The fetal karyotype (Dr. M. d’A Crawfurd) was 46XY with no detectable abnormality. Ultrasonography at 28 weeks confirmed maturity and showed no fetal abnormality. At 37 weeks, X-ray confirmed a breech presentation with an abnormality highly suggestive of a lumbar meningomyelocele. Labour was induced at term and after 8 h a stillborn 3210 g male infant with a meningomyelocele and hydrocephalus was delivered. Necropsy (Prof. C. V. Harrison) confirmed that incomplete fusion of the sacral bones had produced a large open spina bifida. The lateral ventricles and third ventricle were grossly distended with cerebrospinal fluid (c.s.F.) but the fourth ventricle was normal. There was stenosis of the aqueduct of Sylvius with very little c.s.F. around a spinal cord which was macroscopically normal. was
5.
Kauffmann, J. C., Grob,
P.
-
J., Hany, A. Schweiz. med. Wschr. 1971, 101,
1473. 6. 7. 8.
This 39-year-old woman had a history of hospital admissions for depressive psychosis. Routine testing of urine and fasting blood-sugar had been normal. In March, 1976, polydipsia and polyuria were noted, and at first, attributed to lithium. She was depressed and apathetic and hypothyroidism was suspected. The serum-lithium the previous month had been only 0.4 mmol/1 so the dose was increased from 800 to 1200 mg daily. The following day her general practitioner, noting her drowsiness and polydipsia, discontinued the lithium. 24 h later the patient was comatose and febrile and was admitted to hospital dehydrated and hyperventilating. She had glycosuria, ketonuria, and a plasmaglucose of 107 mmol/l. She was treated with intramuscular insulin and intravenous, fluids but ventricular fibrillation.developed and she died. Serum-lithium was 0.95 mmol/1. Thyroid function checked at the lithium clinic indicated a serum-thyroxine of 0-61 nmol/1, and her serum-lithium had been 0.35 mmol/l. Necropsy was refused. Publications on lithium and carbohydrate metabolism are confusing. Lithium has been described as having insulin-like1 and insulin-antagonist effects,2.3 and it has been claimed that diabetes mellitus may be a late complication of manic-depressive psychosis.’1 Shopsin and Gershonhave described a middle-aged woman who had weight gain and fatigue after she had been on lithium for more than one year. Diabetes mellitus developed but remitted spontaneously. Van der Velde, and Gordon’ reported a patient with polyuria, thirst, fatigue, and profuse perspiration interpreted as lithium toxicity until a glucose-tolerance test
Kueppers, F., Black, L. F. Am. Rev. resp. Dis. 1974, 110, 176. Kueppers. F. Am. J. hum. Genet. 1976, 28, 370. Kueppers, F., Dickson, E. R., Summerskill, W. H. J. Mayo Clin. Proc. 1976, 51, 286. 9. Miesch, F., Bieth, J., Metais, P. Clin. chim. Acta, 1971, 31, 231.
1. B’an der Velde, C. D., Gordon, M. W. Archs gen. Psychiat. 1969, 21, 478. 2. Shopsin, B., Stern, S., Gershon, S. ibid. 1972, 26, 566. 3. Heninger, G. R, Mueller, P. S. ibid. 1970, 23, 310. 4. Shopsin, B., Gershon, S. in Lithium: Its Role in Psychiatric Research and Treatment edited by S. Gershon, and B. Shopsin); p. 128. New York, 1973
OF PATIENTS WITH RHEUMATOID ARTHRITIS
We suggest that the false-negative alpha-fetoprotein concentrations in plasma and liquor were caused by an anatomical block between the third and fourth ventricle which prevented significant quantities of c.s.F. circulating into the amniotic fluid and maternal tissues. B. V. LEWIS Divisions of Obstetrics & Gynæcology and Pathology,
J. ENGLAND
Watford General Hospital, Watford, Hens WD1 8HB
Although the PiZ allele was found in Swiss blood-donors a frequency similar to that in other middle European populations,5 there was no MZ phenotype in our patients (see table). The frequencies of the MS and MM1 phenotypes were
R. CHADWICK
with
those in other European and North American White populations.6’ These results therefore do not support an association of the MZ phenotype of o-A.T. with rheumatoid arthritis. The serum concentration of ot-A.T. was higher in patients (3-16+1.12 mg/ml) than in healthy blood donors (2.20±0.21 S.D. mg/ml).8 (Two serum pools from Dr M. K. Fagerhol and Dr J. Pierce used by some laboratories as 100% standards had (XCA.T. concentrations of 2-23 mg/ml and 2.15 mg/ml respectively.) o-A.T. in female patients (3-37±1-01 mg/ml) was higher than in males (3.05±0.88 mg/ml) but not significantly so (e>01). A rise of lX1-A.T. in rheumatoid arthritis, which has been previously reported,9 confirms the view that o-A.T. is an acute-phase reactant protein which increases in concentration in response to an inflammatory stimulus.
close
to
Rheumatologische Universitätsklinik, Basle, Switzerland
D. BRACKERTZ
Temple University School of Medicine, Philadelphia, Pennsylvania 19140, U.S.A.
F. KUEPPERS
DIABETES MELLITUS IN PATIENTS ON LITHIUM
SiR,—The following two cases suggest a possible association between lithium therapy and acute-onset diabetes mellitus. Case1 This 52-year-old woman with manic-depressive psychosis had been put on lithium therapy in June 1967, and routine urine tests had always been negative for sugar and ketones. She was admitted in an hypomanic state in February, 1976, but her condition deteriorated rapidly. Serum-lithium was 2-4 mmol/1 and plasma-glucose 7.3 mmol/l. The initial diagnosis was lithium toxicity and bronchopneumonia. Within 24 h she was comatose and decerebrate but an E.E.G. and carotid angiogram were normal. 5 days after admission she had frank hyperglycsemia and dehydration (plasma-glucose 21.3 mmol/1). Despite electrolyte replacement, insulin, and antibiotics she died. Necropsy revealed: massive pulmonary embolism, pulmonary oedema, bronchopneumonia, ileofemoral thrombosis, and cholelithiasis. The pituitary was large and cystic but histologically normal. There was no comment on the macroscopic or microscopic appearance of the pancreas. Case 2
FALSE-NEGATIVE SCREEN FOR NEURAL TUBE DEFECT IN SPINA BIFIDA WITH STENOSIS OF THE AQUEDUCT OF SYLVIUS
SIR,-We describe here a patient aged 25 who delivered an anencephalic stillborn female infant in her first pregnancy in 1975. After 17 weeks of her second pregnancy, a blood sample taken and transabdominal amniocentesis done. 12 ml clear liquor was collected without difficulty. The serum alpha-fetoprotein concentration, by radioimmunoassay,was 64 ng/ml (1.2 median) and the amniotic fluid alpha-fetoprotein, by Laurell electrophoresis, was 18 g/ml (2.0 median). Both values were normal for our laboratory, which participates in a national quality-control scheme. The fetal karyotype (Dr. M. d’A Crawfurd) was 46XY with no detectable abnormality. Ultrasonography at 28 weeks confirmed maturity and showed no fetal abnormality. At 37 weeks, X-ray confirmed a breech presentation with an abnormality highly suggestive of a lumbar meningomyelocele. Labour was induced at term and after 8 h a stillborn 3210 g male infant with a meningomyelocele and hydrocephalus was delivered. Necropsy (Prof. C. V. Harrison) confirmed that incomplete fusion of the sacral bones had produced a large open spina bifida. The lateral ventricles and third ventricle were grossly distended with cerebrospinal fluid (c.s.F.) but the fourth ventricle was normal. There was stenosis of the aqueduct of Sylvius with very little c.s.F. around a spinal cord which was macroscopically normal. was
5.
Kauffmann, J. C., Grob,
P.
-
J., Hany, A. Schweiz. med. Wschr. 1971, 101,
1473. 6. 7. 8.
This 39-year-old woman had a history of hospital admissions for depressive psychosis. Routine testing of urine and fasting blood-sugar had been normal. In March, 1976, polydipsia and polyuria were noted, and at first, attributed to lithium. She was depressed and apathetic and hypothyroidism was suspected. The serum-lithium the previous month had been only 0.4 mmol/1 so the dose was increased from 800 to 1200 mg daily. The following day her general practitioner, noting her drowsiness and polydipsia, discontinued the lithium. 24 h later the patient was comatose and febrile and was admitted to hospital dehydrated and hyperventilating. She had glycosuria, ketonuria, and a plasmaglucose of 107 mmol/l. She was treated with intramuscular insulin and intravenous, fluids but ventricular fibrillation.developed and she died. Serum-lithium was 0.95 mmol/1. Thyroid function checked at the lithium clinic indicated a serum-thyroxine of 0-61 nmol/1, and her serum-lithium had been 0.35 mmol/l. Necropsy was refused. Publications on lithium and carbohydrate metabolism are confusing. Lithium has been described as having insulin-like1 and insulin-antagonist effects,2.3 and it has been claimed that diabetes mellitus may be a late complication of manic-depressive psychosis.’1 Shopsin and Gershonhave described a middle-aged woman who had weight gain and fatigue after she had been on lithium for more than one year. Diabetes mellitus developed but remitted spontaneously. Van der Velde, and Gordon’ reported a patient with polyuria, thirst, fatigue, and profuse perspiration interpreted as lithium toxicity until a glucose-tolerance test
Kueppers, F., Black, L. F. Am. Rev. resp. Dis. 1974, 110, 176. Kueppers. F. Am. J. hum. Genet. 1976, 28, 370. Kueppers, F., Dickson, E. R., Summerskill, W. H. J. Mayo Clin. Proc. 1976, 51, 286. 9. Miesch, F., Bieth, J., Metais, P. Clin. chim. Acta, 1971, 31, 231.
1. B’an der Velde, C. D., Gordon, M. W. Archs gen. Psychiat. 1969, 21, 478. 2. Shopsin, B., Stern, S., Gershon, S. ibid. 1972, 26, 566. 3. Heninger, G. R, Mueller, P. S. ibid. 1970, 23, 310. 4. Shopsin, B., Gershon, S. in Lithium: Its Role in Psychiatric Research and Treatment edited by S. Gershon, and B. Shopsin); p. 128. New York, 1973
