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VERTICAL TRANSMISSION OF HEPATITIS-B SURFACE ANTIGEN
1211 VERTICAL TRANSMISSION OF HEPATITIS-B SURFACE ANTIGEN first report, in December, 1974,’ several similar studies have been published from different parts of the world. In particular, the recent work of Stevens et a1. in Taiwan has shown that about 40% of infants born to symptom-free carrier mothers developed antigenaemia in the 1st year of life. From France, Dupuy3 has described cases of severe viral hepatitis type B 2-3 months after birth in 3 infants whose mothers were reported to be chronic carriers of the antigen. Our results seem to indicate a different situation in the West Midlands of England. We have tried to follow the fate, during early months and years of life, of infants born to mothers who are chronic carriers. To detect these, blood samples from women attending antenatal clinics throughout the Birmingham Region are being screened by the Regional Transfusion Centre in Birmingham by counter-electrophoresis (C.E.P.). The Region contains a population of over 5 million, with about 70 000 births per year. All positive sera are referred to the Regional Virus Laboratory for confirmation by reversed passive haemagglutination (R.P.H.) (’Hepatest’, Wellcome Laboratories). In addition to the above tests, all cord blood and follow-up blood samples from the infants are being tested by solid-phase
SIR,-Since
our
radioimmunoassay (R.LA.) (’Ausria tut-125’, Abbott Laboratories). When the sample is sufficient, immune electron-microscopy (i.E.M.) is carried out on cord-blood samples after an initial concentration by ultracentrifugationatechnique also used to examine samples of breast milk by I.E.M. and before testing samples of breast milk by R.I.A. HBsAb is routinely tested for by a haemagglutination-inhibition test using the hepatest reagents. Some follow-up sera are also being tested for antibody by solid-phase radioimmune-assay (’Ausab’, Abbott Laboratories). Since the survey started, we have received blood samples ,
from 75 infants. From these deliveries we have received 58 samples of cord blood of which 33 (57%) have been positive by R.LA. 7 out of 14 samples examined by LE.M. were positive. Breast-milk samples were concentrated in the same manner for testing by R.I.A. and I.E.M. 15 out of 27 (56%) were found positive; 13 samples were also tested by I.E.M.; antigen particles were found in 4; these were also positive by R.I.A. The R.I.A. test used (ausria 11-125) detects only the hepatitis-B surface antigen, which cannot be equated with the "virus" of hepatitis B, on good grounds presumed to be the Dane particle. We have already reported the presence of Dane particles in cord blood, and have now found them in 2 samples of cord blood and in 1 sample of breast milk. Summarised below are the results of follow-up studies on 39 infants: .
Those born with positive cord blood (14)-5 were still positive at about 6 weeks. Much less antigen was present then than that found in the cord blood. Later samples from these infants have been negative. 7 other infants had become negative on follow-up, 1 as early as 2 days after birth. One child, positive at birth, was antigen-negative at 7 weeks, positive at 4 months, but is now negative 8 months after birth. Another child, who was not tested regularly, was found positive at 10 months. Negative cord blood (8)-Only 1 infant, negative at birth, has been positive on follow-up (at 4 days). We have not had a further specimen from him. All others negative at birth (7) were negative a month later. Infants not tested at birth (17)-A number of infants have been foltowed up whose cord Mood was not tested, tested; 13 were negative on follow-up (from 3 days to 8 months). 4 infants were positive a few weeks after birth at a level similar to that in the infants born with positive cord blood. One of these became negative at 5 months and is still negative after 8 months. Another infant, the child of Chinese parents, had
lowedupwhosecord blood
1. Boxall, E. H., Davies, H. Lancet, 1974, ii, 1513. 2. Stevens, C. E., Palmer Beasley, R., Tsui, J., Lee, W. New
Engl. J. Med. 1975, 292, 771. 3. Dupuy, J. M., Frommel, D., Alagille, D. Lancet, 1975, i, 1912. 4. Linnemann, C. C., Goldberg, S. ibid. 1974, ii, 155. 5. Beasley, R. P., Stevens, C. E., Shiao, I-S., Meng, H-C. ibid. Oct. 18, 1975, p. 740. 6. Krugman, S. ibid. Nov. 8,
1975, p. 916.
at 4 and 8 months become strongly positive for hepatitis-B with titres by R.P.H. of 1/2000 and 1/8000 respectively.
antigen
The ausab R.I.A. test for antibody was used to test sera from of the infants (4) from whom samples had been obtained when they were older than 3 months. Antibody was detected in the 10-month sample from 1 child. This child was born with HBsAg present in the cord blood and still had detectable levels of antigen in his blood after 6 weeks. At 6 and 10 months there was no antigen present as measured by R.I.A. (ausria n). None of the babies, including the baby of Chinese parents, whose liver-function tests are normal, has developed jaundice or hepatitis in the past year. Results so far suggest that babies born to mothers who are carriers of hepatitis-B antigen may not be seriously at risk. Most of the babies in our study have become negative for hepatitis-B antigen. This is a continuing investigation, and further work may cause us to change our present views on the prognosis of these infants. However, in the view of recent correspondencel 6 we thought it may be helpful to present the findings which we have obtained to date. Regional Virus Laboratory, ELIZABETH BOXALL East Birmingham Hospital, T. H. FLEWETT Birmingham B9 5ST. some
IS A VILLOUS ADENOMA OF THE RECTUM AN ENDOCRINE TUMOUR?
SiR,—Vitlous adenomas of the rectum can be either asymptomatic or accompanied by fresh bleeding per rectum or additional symptoms specific to villous adenomas. These include a remarkable amount of mucus passed per rectum, often unassociated with bowel movements and occasionally severe enough to lead to hypoproteinaemia and hypokalsemia. Rarely, profuse watery diarrhoea may cause hypovolaemia. In 1958, Verner and Morrison’ described 2 patients who died from severe watery diarrhoea and were found to have a pancreatic non-beta-cell tumour.’ In a subsequent series, the main features of this syndrome were defined as watery diarrhoea, hypokalaemia, and achlorhydria or hypochlorhydria (W.D.H.A. syndrome). Because of the severity of the diarrhoea, the term "pancreatic cholera" has also been used. In 24 patients with the W.D.H.A. syndrome, the vasoactive intestinal peptide (v.i.p.) plasma-levels were greater than 200 pg/ml. All these patients were found at laparotomy to have a pancreatic tumour or ganglioneuroblastoma and, in those in whom the tumours were available for study, v.i.p. was found in large amounts.2 The known properties of v.i.p. accord well with the clinical features of this syndrome. A
79-year-old
woman
presented with
a
10-year history
of watery
diarrhoea, intermittently associated with fresh rectal bleeding. An incomplete excision of the villous adenoma, confirmed histologically, had been performed a year before admission. This partially relieved the symptoms, but they gradually recurred. General and abdominal examination was normal, and on rectal examination a large adenomatous tumour was palpable on the anterior wall of the rectum 7 cm from the anal margin. Haemoglobin was 8.5 g/dl, white-cell count 7800 mm3, mean corpuscular volume 88 flm3,mean corpuscular haemoglobin content 33.1%, sodium 132 mmoles/l, potassium 2.8 mmoles/1, chloride 100 mmoles/l, urea 7.5 mmoles/1. Microscopical examination of a biopsy specimen confirmed the presence of a villous papilloma.
As the clinical syndrome suggested a v.i.p.-secreting tumour, was taken for hormonal measurements. The v.i.p. level was 28 pg/ml (normal <50 pg/ml). Immunohistochemical studies of a biopsy specimen with antibodies to gastrin, sccretin.
blood
glucagon, v.i.p., gastric inhibitory polypeptide, motilin, and somatostatin demonstrated only a few scattered enteroglucagon and v.i.p. cells in the tumour, which were insufficient to account for the clinical symptoms. Thus it seems that villous adenomata of the rectum, which produce a syndrome reminis1. Verner, J. V., Morrison, A. B. Am. J. Med. 1958, 2. Bloom, S. R. Gut, 1975, 16, 399.
25, 374.
SIR,-Since
our
radioimmunoassay (R.LA.) (’Ausria tut-125’, Abbott Laboratories). When the sample is sufficient, immune electron-microscopy (i.E.M.) is carried out on cord-blood samples after an initial concentration by ultracentrifugationatechnique also used to examine samples of breast milk by I.E.M. and before testing samples of breast milk by R.I.A. HBsAb is routinely tested for by a haemagglutination-inhibition test using the hepatest reagents. Some follow-up sera are also being tested for antibody by solid-phase radioimmune-assay (’Ausab’, Abbott Laboratories). Since the survey started, we have received blood samples ,
from 75 infants. From these deliveries we have received 58 samples of cord blood of which 33 (57%) have been positive by R.LA. 7 out of 14 samples examined by LE.M. were positive. Breast-milk samples were concentrated in the same manner for testing by R.I.A. and I.E.M. 15 out of 27 (56%) were found positive; 13 samples were also tested by I.E.M.; antigen particles were found in 4; these were also positive by R.I.A. The R.I.A. test used (ausria 11-125) detects only the hepatitis-B surface antigen, which cannot be equated with the "virus" of hepatitis B, on good grounds presumed to be the Dane particle. We have already reported the presence of Dane particles in cord blood, and have now found them in 2 samples of cord blood and in 1 sample of breast milk. Summarised below are the results of follow-up studies on 39 infants: .
Those born with positive cord blood (14)-5 were still positive at about 6 weeks. Much less antigen was present then than that found in the cord blood. Later samples from these infants have been negative. 7 other infants had become negative on follow-up, 1 as early as 2 days after birth. One child, positive at birth, was antigen-negative at 7 weeks, positive at 4 months, but is now negative 8 months after birth. Another child, who was not tested regularly, was found positive at 10 months. Negative cord blood (8)-Only 1 infant, negative at birth, has been positive on follow-up (at 4 days). We have not had a further specimen from him. All others negative at birth (7) were negative a month later. Infants not tested at birth (17)-A number of infants have been foltowed up whose cord Mood was not tested, tested; 13 were negative on follow-up (from 3 days to 8 months). 4 infants were positive a few weeks after birth at a level similar to that in the infants born with positive cord blood. One of these became negative at 5 months and is still negative after 8 months. Another infant, the child of Chinese parents, had
lowedupwhosecord blood
1. Boxall, E. H., Davies, H. Lancet, 1974, ii, 1513. 2. Stevens, C. E., Palmer Beasley, R., Tsui, J., Lee, W. New
Engl. J. Med. 1975, 292, 771. 3. Dupuy, J. M., Frommel, D., Alagille, D. Lancet, 1975, i, 1912. 4. Linnemann, C. C., Goldberg, S. ibid. 1974, ii, 155. 5. Beasley, R. P., Stevens, C. E., Shiao, I-S., Meng, H-C. ibid. Oct. 18, 1975, p. 740. 6. Krugman, S. ibid. Nov. 8,
1975, p. 916.
at 4 and 8 months become strongly positive for hepatitis-B with titres by R.P.H. of 1/2000 and 1/8000 respectively.
antigen
The ausab R.I.A. test for antibody was used to test sera from of the infants (4) from whom samples had been obtained when they were older than 3 months. Antibody was detected in the 10-month sample from 1 child. This child was born with HBsAg present in the cord blood and still had detectable levels of antigen in his blood after 6 weeks. At 6 and 10 months there was no antigen present as measured by R.I.A. (ausria n). None of the babies, including the baby of Chinese parents, whose liver-function tests are normal, has developed jaundice or hepatitis in the past year. Results so far suggest that babies born to mothers who are carriers of hepatitis-B antigen may not be seriously at risk. Most of the babies in our study have become negative for hepatitis-B antigen. This is a continuing investigation, and further work may cause us to change our present views on the prognosis of these infants. However, in the view of recent correspondencel 6 we thought it may be helpful to present the findings which we have obtained to date. Regional Virus Laboratory, ELIZABETH BOXALL East Birmingham Hospital, T. H. FLEWETT Birmingham B9 5ST. some
IS A VILLOUS ADENOMA OF THE RECTUM AN ENDOCRINE TUMOUR?
SiR,—Vitlous adenomas of the rectum can be either asymptomatic or accompanied by fresh bleeding per rectum or additional symptoms specific to villous adenomas. These include a remarkable amount of mucus passed per rectum, often unassociated with bowel movements and occasionally severe enough to lead to hypoproteinaemia and hypokalsemia. Rarely, profuse watery diarrhoea may cause hypovolaemia. In 1958, Verner and Morrison’ described 2 patients who died from severe watery diarrhoea and were found to have a pancreatic non-beta-cell tumour.’ In a subsequent series, the main features of this syndrome were defined as watery diarrhoea, hypokalaemia, and achlorhydria or hypochlorhydria (W.D.H.A. syndrome). Because of the severity of the diarrhoea, the term "pancreatic cholera" has also been used. In 24 patients with the W.D.H.A. syndrome, the vasoactive intestinal peptide (v.i.p.) plasma-levels were greater than 200 pg/ml. All these patients were found at laparotomy to have a pancreatic tumour or ganglioneuroblastoma and, in those in whom the tumours were available for study, v.i.p. was found in large amounts.2 The known properties of v.i.p. accord well with the clinical features of this syndrome. A
79-year-old
woman
presented with
a
10-year history
of watery
diarrhoea, intermittently associated with fresh rectal bleeding. An incomplete excision of the villous adenoma, confirmed histologically, had been performed a year before admission. This partially relieved the symptoms, but they gradually recurred. General and abdominal examination was normal, and on rectal examination a large adenomatous tumour was palpable on the anterior wall of the rectum 7 cm from the anal margin. Haemoglobin was 8.5 g/dl, white-cell count 7800 mm3, mean corpuscular volume 88 flm3,mean corpuscular haemoglobin content 33.1%, sodium 132 mmoles/l, potassium 2.8 mmoles/1, chloride 100 mmoles/l, urea 7.5 mmoles/1. Microscopical examination of a biopsy specimen confirmed the presence of a villous papilloma.
As the clinical syndrome suggested a v.i.p.-secreting tumour, was taken for hormonal measurements. The v.i.p. level was 28 pg/ml (normal <50 pg/ml). Immunohistochemical studies of a biopsy specimen with antibodies to gastrin, sccretin.
blood
glucagon, v.i.p., gastric inhibitory polypeptide, motilin, and somatostatin demonstrated only a few scattered enteroglucagon and v.i.p. cells in the tumour, which were insufficient to account for the clinical symptoms. Thus it seems that villous adenomata of the rectum, which produce a syndrome reminis1. Verner, J. V., Morrison, A. B. Am. J. Med. 1958, 2. Bloom, S. R. Gut, 1975, 16, 399.
25, 374.