1358
Perhaps those studying immunopathogenetic mechanisms of and C.D. could test our hypothesis that antibodies to bird gut cross-react with the patient’s gut and thereby provoke simultaneous c.D. The patient’s serum would have to be tested against autologous and heterologous human gut-biopsy specimens by indirect immunofluorescent and immunodiffusion techniques. B.F.L.
DAVID T. PURTILO ALEX BONICA JAMES P. S. YANG
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, U.S.A.
VITAMIN K AND THE NEWBORN your timely editorial (April 8, p. 755) controvitamin K and the newborn is likely to continue. The basis for disagreement is really the criteria for diagnosis of vitamin-K deficiency. Some workers, such as van Doorm, Muller, and Henkerl require demonstration of abnormal prothrombin in order to differentiate vitamin-K deficiency from failure of synthesis of factors n, vu, rx, and x. A compound designated as P.I.V.K.A.-II (protein induced by vitamin-K absence analogous to factor n) or descarboxyprothrombin has been unequivocally demonstrated in human and bovine plasma after the administration of coumarin compounds.2-’ As I pointed out earlier6 there are clear differences between the effects of coumarin drugs and those of vitamin-K deficiency. In such circumstances it is not unlikely that there would also be differences in the effects of venom from Echis carinatus or of staphylocoagulase, and even in the results of crossed immunoelectrophoresis. Testing of cord blood and of samples obtained more than 72 h postnatally is not ideal for demonstration of vitamin-K deficiency. In either period most babies will not show a clear-cut deficiency. The possibility that other reasons may be responsible for failure to demonstrate abnormal prothrombin in newborns cannot be excluded. Regardless of the explanation, it seems premature to equate such abnormal prothrombin with vitamin-K deficiency. We have differentiated deficiency from failure of synthesis of clotting factors by the corrective effect of the vitamin on characteristic coagulation defects.’-9 These have included deficiences of factors 11, vn, ix, and x and non-specific tests such as the one-stage prothrombin, the plasma recalcification, and the partial thromboplastin time, as well as the thromboplastic activity of serum. In many of our studies we selected sub-
SIR,-Despite
versy
jects by screening one-stage prothrombin-times in groups of ten to twenty babies 6-24 h after birth. Only those with less than 40% activity were investigated further. As the table shows, microgram doses of vitamin K produced a marked improvement in 4 h. Controls which failed to receive vitamin K never showed any significant correction in that short period of time. These results have been obtained with striking consistency. Babies with true hasmorrhagic disease of the newborn’O," have very severe alterations of coagulation following the abovementioned pattern. In these cases the bleeding tendency and the results of hxmostatic tests are also rapidly improved by administration of the vitamin. Such spectacular effects, both
clinically and in laboratory tests, seem wholly convincing. By contrast, failure of synthesis is not modified by vitamin-K administration.
on
1. VanDoorm, J. M., Muller, A. D., Henker, H. C. Lancet, 1977, ii, 852. 2. Henker, H. C., Vehkam, J. J., Hensen, A., Loeliger, E. A. Nature, 1965, 200, 589. 3. Ganrot, P. O., Nilehn, J. E. Scand. clin. Lab. Invest. 1967, 22, 23. 4. Stemflo, J., Ganrot, P. O. J. biol. Chem. 1972, 247, 8160. 5. Stemflo, J., and others Proc. nat.Acad.Sci. U.S.A. 1974, 71, 2730. 6. Abalh, A. J. Lancet, 1977, ii, 559. 7. Aballi, A. J. South Med. J. 1965, 58, 48. 8. Aballi, A. J., Lopez-Banus, V., deLamerens, S., Rozengvaigs, S. Amr. J. Dis.
Child. 1957, 94, 504. 9. Aballi, A. J., deLamerens, S. Pediat. Clin. N. EFFECT IN
4h
School of Medicine, Health Sciences Center, State University of New York at Stony Brook, New York, U.S.A.
NON-CŒLIAC GLUTEN SENSITIVITY?
SIR,-Further to the letter on food allergy by Professor Dickerson and colleagues (April 8, p. 773) we would like to report the case of a 43-year-old woman who presented in January, 1974, with a 4-month history of loose motions, three times a day with no blood or mucus. The diarrhoea was accompanied initially by periumbilical colic, which recurred intermittently, and abdominal distension, but she had not lost weight and had retained her appetite. She had been taking tetracycline for 6 years for acne conglobata; she smoked 15 cigarettes a day but drank very little. She had no pets and had not been abroad. Examination was unremarkable apart from the acne. Investigations, which included examination of fxces for ova, cysts, parasites, and occult blood, X-rays (barium meal, small-bowel meal, barium enema), sigmoidoscopy, and jejunal biopsy, were all normal except for a hiatus hernia. She did not improve when tetracycline was withdrawn or when antidiarrhoeal agents or tranquillisers were tried. Her symptoms continued for 2 years. However, when a gluten-free diet was tried the diarrhoea stopped within 4 days and the patient felt very much better. Jejunal biopsy was repeated after 6-week gluten challenge (accompanied by recurrence of diarrhoea) but was normal in every way including normal intraepithelial lymphocytecounts. Resumption of the gluten-free diet was followed by a rapid disappearance of all her symptoms. We consider it very likely that this woman’s symptoms were due to gluten sensitivity. Her recovery is unlikely to be a placebo response because other treatments had failed; moreover,
10.
Aballi,
A.
Child. Am.
1962, 9, 785.
ARTURO J. ABALLI
11.
J., Lopez-Banus, V., deLamerens, S., Rozengvaigs, 1959, 97, 524.
S.
Amr. J. Dis.
Aballi, A. J. Ped. Ann. 1974, 3, 35.
OF DIFFERENT DOSES OF VITAMIN K ON CERTAIN COAGULATION TESTS OF
182
NORMAL BABIES
Figures are means adjusted to nearest unit. B=before; A=after; *Link-Shapiro method. tNon-activated P.T.T.. tThromboplastin generation experimental cases were selected by microprothrombin times; only those with moderate or severe alterations were studied.
All
test.
Perhaps those studying immunopathogenetic mechanisms of and C.D. could test our hypothesis that antibodies to bird gut cross-react with the patient’s gut and thereby provoke simultaneous c.D. The patient’s serum would have to be tested against autologous and heterologous human gut-biopsy specimens by indirect immunofluorescent and immunodiffusion techniques. B.F.L.
DAVID T. PURTILO ALEX BONICA JAMES P. S. YANG
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, U.S.A.
VITAMIN K AND THE NEWBORN your timely editorial (April 8, p. 755) controvitamin K and the newborn is likely to continue. The basis for disagreement is really the criteria for diagnosis of vitamin-K deficiency. Some workers, such as van Doorm, Muller, and Henkerl require demonstration of abnormal prothrombin in order to differentiate vitamin-K deficiency from failure of synthesis of factors n, vu, rx, and x. A compound designated as P.I.V.K.A.-II (protein induced by vitamin-K absence analogous to factor n) or descarboxyprothrombin has been unequivocally demonstrated in human and bovine plasma after the administration of coumarin compounds.2-’ As I pointed out earlier6 there are clear differences between the effects of coumarin drugs and those of vitamin-K deficiency. In such circumstances it is not unlikely that there would also be differences in the effects of venom from Echis carinatus or of staphylocoagulase, and even in the results of crossed immunoelectrophoresis. Testing of cord blood and of samples obtained more than 72 h postnatally is not ideal for demonstration of vitamin-K deficiency. In either period most babies will not show a clear-cut deficiency. The possibility that other reasons may be responsible for failure to demonstrate abnormal prothrombin in newborns cannot be excluded. Regardless of the explanation, it seems premature to equate such abnormal prothrombin with vitamin-K deficiency. We have differentiated deficiency from failure of synthesis of clotting factors by the corrective effect of the vitamin on characteristic coagulation defects.’-9 These have included deficiences of factors 11, vn, ix, and x and non-specific tests such as the one-stage prothrombin, the plasma recalcification, and the partial thromboplastin time, as well as the thromboplastic activity of serum. In many of our studies we selected sub-
SIR,-Despite
versy
jects by screening one-stage prothrombin-times in groups of ten to twenty babies 6-24 h after birth. Only those with less than 40% activity were investigated further. As the table shows, microgram doses of vitamin K produced a marked improvement in 4 h. Controls which failed to receive vitamin K never showed any significant correction in that short period of time. These results have been obtained with striking consistency. Babies with true hasmorrhagic disease of the newborn’O," have very severe alterations of coagulation following the abovementioned pattern. In these cases the bleeding tendency and the results of hxmostatic tests are also rapidly improved by administration of the vitamin. Such spectacular effects, both
clinically and in laboratory tests, seem wholly convincing. By contrast, failure of synthesis is not modified by vitamin-K administration.
on
1. VanDoorm, J. M., Muller, A. D., Henker, H. C. Lancet, 1977, ii, 852. 2. Henker, H. C., Vehkam, J. J., Hensen, A., Loeliger, E. A. Nature, 1965, 200, 589. 3. Ganrot, P. O., Nilehn, J. E. Scand. clin. Lab. Invest. 1967, 22, 23. 4. Stemflo, J., Ganrot, P. O. J. biol. Chem. 1972, 247, 8160. 5. Stemflo, J., and others Proc. nat.Acad.Sci. U.S.A. 1974, 71, 2730. 6. Abalh, A. J. Lancet, 1977, ii, 559. 7. Aballi, A. J. South Med. J. 1965, 58, 48. 8. Aballi, A. J., Lopez-Banus, V., deLamerens, S., Rozengvaigs, S. Amr. J. Dis.
Child. 1957, 94, 504. 9. Aballi, A. J., deLamerens, S. Pediat. Clin. N. EFFECT IN
4h
School of Medicine, Health Sciences Center, State University of New York at Stony Brook, New York, U.S.A.
NON-CŒLIAC GLUTEN SENSITIVITY?
SIR,-Further to the letter on food allergy by Professor Dickerson and colleagues (April 8, p. 773) we would like to report the case of a 43-year-old woman who presented in January, 1974, with a 4-month history of loose motions, three times a day with no blood or mucus. The diarrhoea was accompanied initially by periumbilical colic, which recurred intermittently, and abdominal distension, but she had not lost weight and had retained her appetite. She had been taking tetracycline for 6 years for acne conglobata; she smoked 15 cigarettes a day but drank very little. She had no pets and had not been abroad. Examination was unremarkable apart from the acne. Investigations, which included examination of fxces for ova, cysts, parasites, and occult blood, X-rays (barium meal, small-bowel meal, barium enema), sigmoidoscopy, and jejunal biopsy, were all normal except for a hiatus hernia. She did not improve when tetracycline was withdrawn or when antidiarrhoeal agents or tranquillisers were tried. Her symptoms continued for 2 years. However, when a gluten-free diet was tried the diarrhoea stopped within 4 days and the patient felt very much better. Jejunal biopsy was repeated after 6-week gluten challenge (accompanied by recurrence of diarrhoea) but was normal in every way including normal intraepithelial lymphocytecounts. Resumption of the gluten-free diet was followed by a rapid disappearance of all her symptoms. We consider it very likely that this woman’s symptoms were due to gluten sensitivity. Her recovery is unlikely to be a placebo response because other treatments had failed; moreover,
10.
Aballi,
A.
Child. Am.
1962, 9, 785.
ARTURO J. ABALLI
11.
J., Lopez-Banus, V., deLamerens, S., Rozengvaigs, 1959, 97, 524.
S.
Amr. J. Dis.
Aballi, A. J. Ped. Ann. 1974, 3, 35.
OF DIFFERENT DOSES OF VITAMIN K ON CERTAIN COAGULATION TESTS OF
182
NORMAL BABIES
Figures are means adjusted to nearest unit. B=before; A=after; *Link-Shapiro method. tNon-activated P.T.T.. tThromboplastin generation experimental cases were selected by microprothrombin times; only those with moderate or severe alterations were studied.
All
test.
