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CAPILLARY BASEMENT MEMBRANE THICKNESS IN MONOZYGOTIC TWINS
650 caused obvious deleterious effects.4 We feel that it should be given in the severe case, until better alternatives are available.. The use of ribavirin5 and protection by immunisation with a closely related arenavirus,6 both in the experimental stage, hold out hope for the future.
Wusasa
Hospital, DAVID
Zaria, Nigeria
J. GRUNDY*
National
(U.K.) Reference Laboratory for Anticoagulant Reagents and Control, Withington Hospital,
Special Pathogens Reference Laboratory, E. T. W. BOWEN P.H.L.S. Centre for Applied Microbiology and Research, G. LLOYD Porton Down, Salisbury, Wiltshire *Present address: Stoke Mandeville
amniotic fluid in normal pregnancy parallels the increase in prostacyclin in peripheral blood in normal pregnancy reported by Lewis et al. The much lower values for PGI2-like activity in the amniotic fluid from the pre-eclamptic patients complements the data of Dr Remuzzi and colleagues (Aug. 9, p. 310) who recorded a significant depression of PGI2 production in umbilical and placental vessels in such patients. A clinical trial of prostacyclin in the treatment of pre-eclampsia seems warranted.
Manchester M20 8LR
ANNA BODZENTA JEAN M. THOMSON L. POLLER
Hospital, Aylesbury.
LOW 1,25-DIHYDROXYVITAMIN D IN HEPARIN-INDUCED OSTEOPENIA
CAPILLARY BASEMENT MEMBRANE THICKNESS IN MONOZYGOTIC TWINS
SIR,-Dr Barbosa and his colleagues (Aug. 16, p. 330) seem to misdataon muscle capillary basement membrane (CBM) thickness in the monozygotic non-diabetic twins of insulindependent diabetic (IDD) patients. Contrary to their assertion, we construe our
did
not
claim that "muscle CBM thickness can serve as a marker of
prediabetes", a suggestion made by others in the literature. 2,3 Of the thirteen pairs of monozygotic twins discordant for IDD, reported by the 1979 annual meeting of the American Diabetes Associathe 7 non-diabetic twins with evidence of CBM thickness were unaffected with diabetes after discordance intervals as long as 32, 19, 18, 15, 15, 13, and 9 years. This would imply, unlike Barbosa’s misleading interpretation of our data, that the thick CBM did not confer a greater susceptibility to diabetes in these unaffected twins, despite long follow-ups after the onset of diabetes in the affected twin. The only conclusion to be drawn from our studies is that the thick CBM, per se, does not indicate a true pre-diabetic state. A major reason for the discrepancy between the results of CBM thickness in the report by Barbosa et al. and in our series may be that they have studied a small number of discordant twin-sets (five pairs). The detailed results of CBM within our larger series of eighteen pairs of monozygotic twins will be published elsewhere.
us at
tion,l
E. P. Joslin Research
Laboratory, Department of Medicine, Harvard Medical School, Boston, Massachusetts, U.S.A.
OM P. GANDA
J. STUART SOELDNER
SIR,-Generalised skeletal demineralisation has been reported often enough in patients on long-term high-dose heparin for a cause-and-effect relation between heparin therapy and osteopenia to be established.2-4 The pathogenesis of this complication of heparin treatment is unclear. We have studied vitamin D metabolism in a 22-year-old pregnant woman who acquired severe osteopenia while being treated with heparin for thrombosis. Subcutaneous heparin injections were started 8 weeks before term, in doses up to 15 000 units three times daily, and continued for 4 weeks after delivery of a healthy infant, at 5000 units three times daily. The baby was breast fed. The history suggested an average calcium intake during pregnancy and lactation. 1 week post parturn the patient had increasing lower back pain; heparin treatment was stopped when X-rays disclosed gross thoracolumbar spinal osteoporosis with compression fractures. Serum calcium concentrations were 2-36-2-56 mmol/1 (9-44-10-24 mg/dl), phosphate concentrations 1-37-1-62 mmol/1 (425-5-02 mg/dl), and alkaline phosphate 220 units/1 (normal <279 units/1). Urinary excretion of calcium and phosphate were normal, and routine estimates of renal and hepatic function were unremarkable. Urinary excretion of cortisol and 17-ketogenic steroids were normal. Osteodensitometry showed an abnormally low value of 0-90 g/cm (normal 1-3-2. Heparin treatment was discontinued, and she was given calcium supplements. During a regimen of physiotherapy her lower back pain abated slowly over a period of 3 weeks. The
serum
concentrations of vitamin D metabolites and uri-
cyclic AMP are summarised in the table. The concentration of 25-hydroxyvitamin D (OHD) and 24,25-(OH2D were normal, indicating an adequate vitamin D intake and exposure nary
PROSTACYCLIN ACTIVITY IN AMNIOTIC FLUID IN PRE-ECLAMPSIA
SIR,-We have studied the prostacyclin-like activity (PGI2) of amniotic fluid by its inhibition of platelet aggregation. In five consecutive patients with pre-eclamptic toxaemia, amniotic-fluid PGI2-like activity was 2-4±1-03 (mean±SD) ng/ml whereas it was 8-8±1-2 ng/ml in fifteen uncomplicated The prostacyclin-like activity pregnancies (p<0.001).
in
4. Keane E, Gilles HM. Lassa fever m Panguma Hospital, Sierre Leone, 1973-6. Br Med J 1977; i: 1399. 5. Stephen EL, Jahrling PB. Experimental Lassa fever virus infection successfully treated with ribavirin. Lancet 1979; 1: 268. 6. Kiley MP, Lange JV, Johnson KM. Protection of rhesus monkeys from Lassa virus by immunisation with closely related areanavirus. Lancet, 1979; ii: 738. 1.
2
3.
Ganda OP, Williamson JR, Soeldner JS, Gleason R, Kilo C, Kaldany A, Garovoy, MR, Carpenter CB. Muscle capillary basement membrane width and HLA typing in monozygotic twins. Diabetes 1979; 28: 396. Siperstein MD, Unger RH, Madison LL. Studies of muscle capillary basement membranes in normal subjects, diabetic, and prediabetic subjects. J Clin Invest 1968; 47: 1973-99. Raskin P, Marks JF, Burns H, Plumer ME, Siperstein MD. Capillary basement membrane width in diabetic children. Am J Med 1975; 58: 365-72.
levels of 1,25-(OH)2D, which is the the physiological active vitamin D metabolite, were well below normal on two separate determinations. The first sample was taken when the patient was on heparin therapy and the second 1 week after treatment had been stopped. 4 weeks later the serum concentration of 1,25-(OH)2D had increased to the lower limit of normal for healthy adults. The serum concentration of 1,25-(OH)2D is normally higher in late pregnancy and during lactation than it is in non-pregnant women.5 The finding of normal urinary cyclic AMP excretion indicated normal parathyroid function
to sun. most
However, the
potent and
serum
probably
1. Lewis
PJ, Boylan P, Friedman LA, Hensby CN, Downing T. Prostacyclin in pregnancy. Br Med J 1980; 280: 1581-82. 2. Avioli LV. Heparin-induced osteopenia: an appraisal. Adv Exp Med Biol 1975; 52: 375-87. 3. Sackler JP, Lin L. 548-50. 4. Wise PH, Hall AJ.
Heparin-induced osteoporosis. Br J Heparin-induced osteopenia
Radiol
1973; 46:
in pregnancy. Br Med
J
1980; 281: 110-11. 5. Kumar R, Cohen WR, Silva P, Epstein FH. Elevated 1,25-dihydroxy-vitamin D levels in normal human pregnancy and lactation. J Clin Invest
1979; 63: 342-44.
Wusasa
Hospital, DAVID
Zaria, Nigeria
J. GRUNDY*
National
(U.K.) Reference Laboratory for Anticoagulant Reagents and Control, Withington Hospital,
Special Pathogens Reference Laboratory, E. T. W. BOWEN P.H.L.S. Centre for Applied Microbiology and Research, G. LLOYD Porton Down, Salisbury, Wiltshire *Present address: Stoke Mandeville
amniotic fluid in normal pregnancy parallels the increase in prostacyclin in peripheral blood in normal pregnancy reported by Lewis et al. The much lower values for PGI2-like activity in the amniotic fluid from the pre-eclamptic patients complements the data of Dr Remuzzi and colleagues (Aug. 9, p. 310) who recorded a significant depression of PGI2 production in umbilical and placental vessels in such patients. A clinical trial of prostacyclin in the treatment of pre-eclampsia seems warranted.
Manchester M20 8LR
ANNA BODZENTA JEAN M. THOMSON L. POLLER
Hospital, Aylesbury.
LOW 1,25-DIHYDROXYVITAMIN D IN HEPARIN-INDUCED OSTEOPENIA
CAPILLARY BASEMENT MEMBRANE THICKNESS IN MONOZYGOTIC TWINS
SIR,-Dr Barbosa and his colleagues (Aug. 16, p. 330) seem to misdataon muscle capillary basement membrane (CBM) thickness in the monozygotic non-diabetic twins of insulindependent diabetic (IDD) patients. Contrary to their assertion, we construe our
did
not
claim that "muscle CBM thickness can serve as a marker of
prediabetes", a suggestion made by others in the literature. 2,3 Of the thirteen pairs of monozygotic twins discordant for IDD, reported by the 1979 annual meeting of the American Diabetes Associathe 7 non-diabetic twins with evidence of CBM thickness were unaffected with diabetes after discordance intervals as long as 32, 19, 18, 15, 15, 13, and 9 years. This would imply, unlike Barbosa’s misleading interpretation of our data, that the thick CBM did not confer a greater susceptibility to diabetes in these unaffected twins, despite long follow-ups after the onset of diabetes in the affected twin. The only conclusion to be drawn from our studies is that the thick CBM, per se, does not indicate a true pre-diabetic state. A major reason for the discrepancy between the results of CBM thickness in the report by Barbosa et al. and in our series may be that they have studied a small number of discordant twin-sets (five pairs). The detailed results of CBM within our larger series of eighteen pairs of monozygotic twins will be published elsewhere.
us at
tion,l
E. P. Joslin Research
Laboratory, Department of Medicine, Harvard Medical School, Boston, Massachusetts, U.S.A.
OM P. GANDA
J. STUART SOELDNER
SIR,-Generalised skeletal demineralisation has been reported often enough in patients on long-term high-dose heparin for a cause-and-effect relation between heparin therapy and osteopenia to be established.2-4 The pathogenesis of this complication of heparin treatment is unclear. We have studied vitamin D metabolism in a 22-year-old pregnant woman who acquired severe osteopenia while being treated with heparin for thrombosis. Subcutaneous heparin injections were started 8 weeks before term, in doses up to 15 000 units three times daily, and continued for 4 weeks after delivery of a healthy infant, at 5000 units three times daily. The baby was breast fed. The history suggested an average calcium intake during pregnancy and lactation. 1 week post parturn the patient had increasing lower back pain; heparin treatment was stopped when X-rays disclosed gross thoracolumbar spinal osteoporosis with compression fractures. Serum calcium concentrations were 2-36-2-56 mmol/1 (9-44-10-24 mg/dl), phosphate concentrations 1-37-1-62 mmol/1 (425-5-02 mg/dl), and alkaline phosphate 220 units/1 (normal <279 units/1). Urinary excretion of calcium and phosphate were normal, and routine estimates of renal and hepatic function were unremarkable. Urinary excretion of cortisol and 17-ketogenic steroids were normal. Osteodensitometry showed an abnormally low value of 0-90 g/cm (normal 1-3-2. Heparin treatment was discontinued, and she was given calcium supplements. During a regimen of physiotherapy her lower back pain abated slowly over a period of 3 weeks. The
serum
concentrations of vitamin D metabolites and uri-
cyclic AMP are summarised in the table. The concentration of 25-hydroxyvitamin D (OHD) and 24,25-(OH2D were normal, indicating an adequate vitamin D intake and exposure nary
PROSTACYCLIN ACTIVITY IN AMNIOTIC FLUID IN PRE-ECLAMPSIA
SIR,-We have studied the prostacyclin-like activity (PGI2) of amniotic fluid by its inhibition of platelet aggregation. In five consecutive patients with pre-eclamptic toxaemia, amniotic-fluid PGI2-like activity was 2-4±1-03 (mean±SD) ng/ml whereas it was 8-8±1-2 ng/ml in fifteen uncomplicated The prostacyclin-like activity pregnancies (p<0.001).
in
4. Keane E, Gilles HM. Lassa fever m Panguma Hospital, Sierre Leone, 1973-6. Br Med J 1977; i: 1399. 5. Stephen EL, Jahrling PB. Experimental Lassa fever virus infection successfully treated with ribavirin. Lancet 1979; 1: 268. 6. Kiley MP, Lange JV, Johnson KM. Protection of rhesus monkeys from Lassa virus by immunisation with closely related areanavirus. Lancet, 1979; ii: 738. 1.
2
3.
Ganda OP, Williamson JR, Soeldner JS, Gleason R, Kilo C, Kaldany A, Garovoy, MR, Carpenter CB. Muscle capillary basement membrane width and HLA typing in monozygotic twins. Diabetes 1979; 28: 396. Siperstein MD, Unger RH, Madison LL. Studies of muscle capillary basement membranes in normal subjects, diabetic, and prediabetic subjects. J Clin Invest 1968; 47: 1973-99. Raskin P, Marks JF, Burns H, Plumer ME, Siperstein MD. Capillary basement membrane width in diabetic children. Am J Med 1975; 58: 365-72.
levels of 1,25-(OH)2D, which is the the physiological active vitamin D metabolite, were well below normal on two separate determinations. The first sample was taken when the patient was on heparin therapy and the second 1 week after treatment had been stopped. 4 weeks later the serum concentration of 1,25-(OH)2D had increased to the lower limit of normal for healthy adults. The serum concentration of 1,25-(OH)2D is normally higher in late pregnancy and during lactation than it is in non-pregnant women.5 The finding of normal urinary cyclic AMP excretion indicated normal parathyroid function
to sun. most
However, the
potent and
serum
probably
1. Lewis
PJ, Boylan P, Friedman LA, Hensby CN, Downing T. Prostacyclin in pregnancy. Br Med J 1980; 280: 1581-82. 2. Avioli LV. Heparin-induced osteopenia: an appraisal. Adv Exp Med Biol 1975; 52: 375-87. 3. Sackler JP, Lin L. 548-50. 4. Wise PH, Hall AJ.
Heparin-induced osteoporosis. Br J Heparin-induced osteopenia
Radiol
1973; 46:
in pregnancy. Br Med
J
1980; 281: 110-11. 5. Kumar R, Cohen WR, Silva P, Epstein FH. Elevated 1,25-dihydroxy-vitamin D levels in normal human pregnancy and lactation. J Clin Invest
1979; 63: 342-44.