- Email: [email protected]
LEUKAEMIA AND THE PRADER-WILLI SYNDROME
46 The evidence on the effect of alcohol on peptic ulceration is limited and generally relates to ulcer healing rather than recurrence. Roberts et all concluded that above-average alcohol consumption was associated with resistance to ulcer healing in response to ranitidine. This association had previously been demonstrated by Hasanzfor cimetidine. Okada et al3 similarly reported that consumption of over 60 g of alcohol per day might directly damage the gastric mucosa and thus decrease healing. In contrast, Sonnenberg et al4 showed that moderate alcohol intake might favour ulcer healing. The explanation for this could lie in the fact that small amounts of dilute ethanol completely protect rat stomach against the mucosal necrosis produced other toxins such as 0’ 6 mol/1 hydrochloric acid or pure ethanol. Small amounts of alcohol may induce mucosal prostaglandin (PG) production. The PGs could exert a cytoprotective action on the stomach. Thus, if alcohol has similar effects on ulcer relapse and ulcer healing, then differences in alcohol consumption between the two groups in Gough’s study become more significant. 170 patients on ranitidine and 145 patients on cimetidine consumed moderate amounts of alcohol (<56’8 8 ml daily)-ie, there were 25 more patients in the ranitidine group who might have been less likely to relapse. Also, there were 15 patients on ranitidine and 21 patients on cimetidine who consumed large amounts of alcohol (>56 - 8 ml daily). Thus, there were 6 more patients in the cimetidine subgroup who were more likely to relapse. Thus if the protective/exacerbatory role for alcohol is correct, the trial was biased in favour of ranitidine to the extent of 31 patients. Reanalysis of the data to take into account alcohol intake might help clarify both the association between alcohol consumption and the recurrence of peptic ulcers and the conclusions of the trial itself.
by
Department of Pharmacy, Royal Liverpool Hospital, Liverpool L7 8XP
J. P. HAMPSON J. C. SMITH
Mersey Regional Health Authority
C. PROUDLOVE
ANTIBODIES TO HEPATITIS A AND B VIRUS ANTIGENS IN Rho(D) IMMUNE GLOBULIN
SIR,-Rho(D) immune globulin (RhIG) is administered to Rhnegative mothers within 72 h of delivery of an Rh-positive infant, and in certain other related obstetric situations. This IgG product is manufactured from a pool of plasma from donors who have been immunised to stimulate production of anti-Rho(D), so it is not representative of immune serum globulin (ISG) preparations. Indeed, the pre-immunisation antibodies of these donors might differ from those of other plasma donors if the immunisation programme attracted donors from socioeconomic groups with greater exposure to hepatitis viruses. We tested 55 lots of RhIG for antibodies to the antigens of hepatitis A and B viruses (HAV, HBV) to determine whether their prevalences were similar to those reported in ISG, and whether the use of RhIG might confuse the interpretation of any diagnostic test for hepatitis that might be done on the mother’s serum post partum. The material consisted of all RhIG lots released by the US Food and Drug Administration in 1980; the 55 lots had been made by four manufacturers (37, 4, 5, 9). RhIG and dilutions of RhIG (according to the manufacturer’s instructions for each hepatitis test) were tested by Abbott radioimmunoassays for anti-HBs, anti-HBc, antiHBe and anti-HAV. For each antibody evaluated, all tests were done at one time using test kits from a single production lot. IgM antibodies were not tested because RhIG is composed almost entirely of IgG. All 55 lots contained anti-HBs, anti-HBc, anti-HBe, and antiHAV at similar endpoint dilution titres (table). The only distinguishing feature among the four manufacturers was the antiHBs titre which was 1: 100 in all 4 lots made by one manufacturer, in 5/37 made by another, and in 2/5 in a third. HEPATITIS ANTIBODIES IN
Rho(D) IMMUNE GLOBULIN
DM, Wilson JA, Ratcliffe GE, et al. Clinical trial ofranitidine m the treatment of peptic ulcer. Br] Clin Pract 1982, 36: 9-12 2 Hasan M, Sircus W Chmcal study of the features associated with failure and success of cimetidine in the treatment ofpeptic ulcer Gut 1980; 21: A463 3 Okada M, Yao T, Fuchigami T, Imamvra K, Omae T. Factors influencing the healing rate of gastric ulcer 10 hospitalised subjects. Gut 1984; 25: 881-85 4 Sonnenberg A, Muller-Lissner SA, Vogel E, et al. Predictors of duodenal ulcer healing and relapse. Gastroenterology 1981; 81: 1061-67. 5. Robert A. Cytoprotection by prostaglandins. Gastroenterology 1979; 77: 761-67. 1 Roberts
LEUKAEMIA AND THE PRADER-WILLI SYNDROME
SIR,-I have recently become aware of a boy with the Prader-Willi syndrome in whom acute myeloblastic leukaemia (AML) developed 61/2 years of age. Both diagnoses were made at the Massachusetts General Hospital. His family moved to Kentucky, where he was followed up by the haematology/oncology and endocrinology services of the University of Kentucky. He has since returned to the Boston area and is lost to follow-up. A recent issue of The Gathered Vzeu; a regular newsletter of the Prader-Willi Syndrome Association, noted that leukaemia had developed in two young women (aged 22 and 29 years) with the Prader-Willi syndrome. One had acute myeloid leukaemia and the other chronic myeloid leukaemia. As a scientific adviser to the Prader-Willi Syndrome Association, I was made aware of the details of these cases. Neither woman had any known exposure to radiation, drugs, or toxic chemicals. Both were resident in the same group home, and their leukaemias developed within a month of each other. I do not know whether karyotyping has been done. Three instances of leukaemia in patients with the Prader-Willi syndrome do not necessarily imply an increased risk of leukaemia in this relatively uncommon disorder, but they do indicate a need for vigilance. The presence ofa deletion of the long arm of chromosome 15 (del [ 15] [q 1 ]) in approximately half the cases of the Prader-Willi syndrome is of interest with regard to the known association of various types of leukaemias and chromosome abnormalities.
at
Department
of Pediatrics.
Division of Genetics and
The antibody profile of RhIG seems almost the same as that of ISG. The endpoint dilution titres of anti-HAV and anti-HBs in these lots of RhIG were identical to those found in 106 lots of ISG manufactured in 19771 and in 76 lots of ISG manufactured in 1979.2 Although the protein concentration of RhIG (14±4-0%) can be slightly lower than that of ISG (16 - 5±1 -5%), this difference would not have significantly affected the titres detected because of the large intervals between the dilutions. The titres of anti-HBc and anti-HBe in globulin preparations such as ISG have not been
previously reported.
Administration of a 1 ml dose of RhIG could be expected in some result in borderline detectable anti-HAV or anti-HBs in the mother’s blood for periods of a few weeks, based on the average 3 22-day half-life of ISG given intramuscularly to normal individuals3 and the 17-day half-life reported for the catabolism of anti-HBs given as intravenous ISG to normal individuals.4The results of hepatitis diagnostic tests may therefore be difficult to interpret for serum samples obtained during this period. cases to
We thank L. Stevan for technical Center for Drugs and Biologics, Food and Drug Administration, Rockville, Maryland 20857, USA
1. Smallwood
3
Dysmorphology,
University of Kentucky, Lexington, Kentucky 40536, USA
4
BRYAN D. HALL
EDWARD TABOR LINDA A. SMALLWOOD ROBERT J. GERETY
LA, Tabor E, Finlayson JS, Gerety RJ. Antibodies to hepatitis A virus in globulin J Med Virol 1981; 7: 21-27. Gerety RJ, Smallwood LA, Tabor E. Hepatitis B immune globulin and immune serum globulin. N Engl J Med 1980, 303: 529. Morell A, Schurch B, Ryser D, Hofer F, Skvaril F, Barandun S. In vivo behaviour of gamma globulin preparations. Vox Sang 1980, 38: 272-83 Shibata Y, Baba M, Kuniyuki M. Studies on the retention of passively transferred antibodies in man. Vox Sang 1982; 43: 205-11 immune serum
2
assistance.
by
Department of Pharmacy, Royal Liverpool Hospital, Liverpool L7 8XP
J. P. HAMPSON J. C. SMITH
Mersey Regional Health Authority
C. PROUDLOVE
ANTIBODIES TO HEPATITIS A AND B VIRUS ANTIGENS IN Rho(D) IMMUNE GLOBULIN
SIR,-Rho(D) immune globulin (RhIG) is administered to Rhnegative mothers within 72 h of delivery of an Rh-positive infant, and in certain other related obstetric situations. This IgG product is manufactured from a pool of plasma from donors who have been immunised to stimulate production of anti-Rho(D), so it is not representative of immune serum globulin (ISG) preparations. Indeed, the pre-immunisation antibodies of these donors might differ from those of other plasma donors if the immunisation programme attracted donors from socioeconomic groups with greater exposure to hepatitis viruses. We tested 55 lots of RhIG for antibodies to the antigens of hepatitis A and B viruses (HAV, HBV) to determine whether their prevalences were similar to those reported in ISG, and whether the use of RhIG might confuse the interpretation of any diagnostic test for hepatitis that might be done on the mother’s serum post partum. The material consisted of all RhIG lots released by the US Food and Drug Administration in 1980; the 55 lots had been made by four manufacturers (37, 4, 5, 9). RhIG and dilutions of RhIG (according to the manufacturer’s instructions for each hepatitis test) were tested by Abbott radioimmunoassays for anti-HBs, anti-HBc, antiHBe and anti-HAV. For each antibody evaluated, all tests were done at one time using test kits from a single production lot. IgM antibodies were not tested because RhIG is composed almost entirely of IgG. All 55 lots contained anti-HBs, anti-HBc, anti-HBe, and antiHAV at similar endpoint dilution titres (table). The only distinguishing feature among the four manufacturers was the antiHBs titre which was 1: 100 in all 4 lots made by one manufacturer, in 5/37 made by another, and in 2/5 in a third. HEPATITIS ANTIBODIES IN
Rho(D) IMMUNE GLOBULIN
DM, Wilson JA, Ratcliffe GE, et al. Clinical trial ofranitidine m the treatment of peptic ulcer. Br] Clin Pract 1982, 36: 9-12 2 Hasan M, Sircus W Chmcal study of the features associated with failure and success of cimetidine in the treatment ofpeptic ulcer Gut 1980; 21: A463 3 Okada M, Yao T, Fuchigami T, Imamvra K, Omae T. Factors influencing the healing rate of gastric ulcer 10 hospitalised subjects. Gut 1984; 25: 881-85 4 Sonnenberg A, Muller-Lissner SA, Vogel E, et al. Predictors of duodenal ulcer healing and relapse. Gastroenterology 1981; 81: 1061-67. 5. Robert A. Cytoprotection by prostaglandins. Gastroenterology 1979; 77: 761-67. 1 Roberts
LEUKAEMIA AND THE PRADER-WILLI SYNDROME
SIR,-I have recently become aware of a boy with the Prader-Willi syndrome in whom acute myeloblastic leukaemia (AML) developed 61/2 years of age. Both diagnoses were made at the Massachusetts General Hospital. His family moved to Kentucky, where he was followed up by the haematology/oncology and endocrinology services of the University of Kentucky. He has since returned to the Boston area and is lost to follow-up. A recent issue of The Gathered Vzeu; a regular newsletter of the Prader-Willi Syndrome Association, noted that leukaemia had developed in two young women (aged 22 and 29 years) with the Prader-Willi syndrome. One had acute myeloid leukaemia and the other chronic myeloid leukaemia. As a scientific adviser to the Prader-Willi Syndrome Association, I was made aware of the details of these cases. Neither woman had any known exposure to radiation, drugs, or toxic chemicals. Both were resident in the same group home, and their leukaemias developed within a month of each other. I do not know whether karyotyping has been done. Three instances of leukaemia in patients with the Prader-Willi syndrome do not necessarily imply an increased risk of leukaemia in this relatively uncommon disorder, but they do indicate a need for vigilance. The presence ofa deletion of the long arm of chromosome 15 (del [ 15] [q 1 ]) in approximately half the cases of the Prader-Willi syndrome is of interest with regard to the known association of various types of leukaemias and chromosome abnormalities.
at
Department
of Pediatrics.
Division of Genetics and
The antibody profile of RhIG seems almost the same as that of ISG. The endpoint dilution titres of anti-HAV and anti-HBs in these lots of RhIG were identical to those found in 106 lots of ISG manufactured in 19771 and in 76 lots of ISG manufactured in 1979.2 Although the protein concentration of RhIG (14±4-0%) can be slightly lower than that of ISG (16 - 5±1 -5%), this difference would not have significantly affected the titres detected because of the large intervals between the dilutions. The titres of anti-HBc and anti-HBe in globulin preparations such as ISG have not been
previously reported.
Administration of a 1 ml dose of RhIG could be expected in some result in borderline detectable anti-HAV or anti-HBs in the mother’s blood for periods of a few weeks, based on the average 3 22-day half-life of ISG given intramuscularly to normal individuals3 and the 17-day half-life reported for the catabolism of anti-HBs given as intravenous ISG to normal individuals.4The results of hepatitis diagnostic tests may therefore be difficult to interpret for serum samples obtained during this period. cases to
We thank L. Stevan for technical Center for Drugs and Biologics, Food and Drug Administration, Rockville, Maryland 20857, USA
1. Smallwood
3
Dysmorphology,
University of Kentucky, Lexington, Kentucky 40536, USA
4
BRYAN D. HALL
EDWARD TABOR LINDA A. SMALLWOOD ROBERT J. GERETY
LA, Tabor E, Finlayson JS, Gerety RJ. Antibodies to hepatitis A virus in globulin J Med Virol 1981; 7: 21-27. Gerety RJ, Smallwood LA, Tabor E. Hepatitis B immune globulin and immune serum globulin. N Engl J Med 1980, 303: 529. Morell A, Schurch B, Ryser D, Hofer F, Skvaril F, Barandun S. In vivo behaviour of gamma globulin preparations. Vox Sang 1980, 38: 272-83 Shibata Y, Baba M, Kuniyuki M. Studies on the retention of passively transferred antibodies in man. Vox Sang 1982; 43: 205-11 immune serum
2
assistance.