801
suppressed for variable periods of time. Concern has been raised that oversuppression of PTH may lead to low bone tumover.s Our findings suggest that calcitriol can be given intermittently for brief periods when PTH is above a threshold concentration. Division of Paediatric
Nephrology,
Ruperto Carola University, 6900 Heidelberg 1, Germany
GÜNTER KLAUS OTTO MEHLS JÖRG HINDERER
Division of Nephrology, Ruperto Carola University,
EBERHARD RITZ
Heidelberg
1.Brumbaugh PF, Huges MR, Haussler MR. Cytoplasmatic and nuclear binding components for 1-alpha-dihydroxyvitamin D3 in chick parathyroid glands. Proc Natl Acad Sci (USA) 1975; 72: 4871-75. 2. Naveh-Many T, Silver J. Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat. J Clin Invest 1990; 86: 1313-19. 3. Szabo A, Merke J, Beier E, Mall G, Ritz E. 1,25(OH)2 vitamin D3 inhibits parathyroid cell proliferation in experimental uremia. Kidney Int 1989; 35:1049-56. 4. Blind E, Schmidt-Gayk H, Scharla S, Flentje D, Fischer S, Göhring U, Hitzler W. Two-site assay of intact parathyroid hormone in the investigation of primary hyperparathyroidism and other disorders of calcium metabolism compared with a midregion assay. J Clin Endocrinol Metab 1988; 67: 353-60. 5. Baker LRI, Abrams SML, Roe CJ, et al. 1,25(OH)2D3 administration in moderate renal failure: a prospective double-blind trial. Kidney Int 1989; 35: 661-69.
Haemorrhagic shock, encephalopathy,
and
sudden infant death SIR,-Dr Trounce and his associates (Jan 26, p 202) suggest that the haemorrhagic shock and encephalopathy syndrome should be regarded as one of the causes of sudden infant death. I agree, but am amazed that, despite the plethora of publications concerning this syndrome, no one has pursued the obvious similarity to toxic-shock syndrome after influenza-like illnesses.’ In the past few years, I have seen four infants with encephalopathy, fever, shock, diarrhoea, disseminated intravascular coagulation, and renal and hepatic dysfunction, who presented in the winter months after a viral cough. Two patients survived with severe brain damage. Staphylococcus aureus was found in the trachea of three of the infants, in whom it was looked for; and in one child the organism had produced toxic-shock syndrome toxin-1and the patient had an antibody titre of 512 against this toxin. I suggest that toxic-shock syndrome as a cause of haemorrhagic shock and encephalopathy syndrome was dismissed in the UK without adequate data. Division of Pediatric Nephrology, Marshfield Clinic, Marshfield, WI 54449, USA
EDWARD B. BLAU
KL, Osterholm MT, Hedberg CW, et al. Toxic shock syndrome. A newly recognised complication of influenza and influenza-like illness. JAMA 1987;
1. MacDonald
257: 105-58.
neutralisation test, 2 weeks after the third dose. 10 of them were still antibody positive 1 year after vaccination. In view of the antigenic difference between viruses of the Apodemus and rat type of HFRS,2 it is thought that a monovalent vaccine may not be as effective as one that prevents both types of HFRS.2 Bivalent vaccine was prepared with GHKC adapted Hantaan virus JR strain3and Seoul virus, L99 strain.l Virus titres before inactivation were 6’67-7-17 and 7-33-7-67 log TCID/ml, respectively, and antigenic titres were 256-512. Trials were done in 206 volunteers as for the monovalent vaccine. Minor side-effects were observed in 5 vaccinees. Blood was collected before immunisation and 56 days after the first dose. The seroconversion rate by immunofluorescent antibody test (IFAT) was 93-2% (192/206), and neutralising antibody was present in all 15 randomly sampled vaccinees on challenge with L virus and in all but 1 on challenge with JR virus. Specific and non-specific T-cell transformation indices were increased, by 96% and 48%,
respectively. These results suggest that the inactivated GHKC vaccine against HFRS is safe, and induces antibody responses (especially neutralising antibody) and cellular immunity. We also found that cellular immunity can be elicited by an inactivated vaccine against HFRS and that it can be detected. Institute of Virology, Chinese Academy of Preventive Medicine, Beijing 100052, China
G. SONG C. S. HANG
Changchun Institute of Biological Products, Ministry of Public Health, Changchun
Y. C. HUANG F. Y. Hou
1. Liu PQ, Liao HX, Fu JL, et al. Isolation of epidemic hemorrhagic fever viruses from Rattus losea and R confucianus and their antigenic identification. Bull Jiangxi Med Coll 1984; 3: 1-5 (in Chinese). 2. Song G, Hang CS, Liao HX, Fu JL. Antigenic comparison of virus strains of mild and classical types of epidemic haemorrhagic fever isolated in China and adaptation of these to cultures of normal cells. Lancet 1984; i: 677-78. 3. Han HZ, Hou FY, et al. A discovery of rabbit infection in the EHF endemic area of Yanbian of Jilin Province and isolation of EHF viruses from rabbits. ChinJ Publ Health 1990; 9: 73-76.
Mode of death in Duchenne muscular
dystrophy SIR,-Major advances in the molecular understanding of Duchenne muscular dystrophy (DMD) have not made the psychosocial management of this disease any less important. DMD causes death, usually in the teens or early twenties, and our impression is that throughout their child’s illness parents are fearful of the death itself. Our muscle clinic has contact with most patients with DMD in Northern Ireland. We collected information on deaths between 1983 and 1989 among all boys with DMD known to us, using hospital notes, and talking to doctors and parents. The 11 boys who died were aged 9-21:
Preliminary trials of inactivated vaccine against haemorrhagic fever with renal syndrome SIR,-Haemorrhagic fever with renal syndrome (HFRS) is a public health problem in China, there being no effective treatment of prevention and control strategies. A safe and effective vaccine is urgently needed. We have been developing an inactivated golden hamster kidney cell culture (GHKC) vaccine against HFRS and report here preliminary trials in volunteers. The monovalent vaccine was produced with Seoul virus L99 serious
strainl inactivated with 0-025% formalin. The virus titre before inactivation was 7-0 log TCID50/ml and the antigenic titre of the vaccine was 512 by ELISA. 12 volunteers were immunised intramuscularly with three doses on days 0, 7, and 28, 1 ml being injected each time. General and local reactions were carefully monitored for 3 days after each inoculation, and blood was taken on days 0, 28, and 42, and 6 and 12 months after the first dose. No untoward reactions were observed, and all 12 vaccinees (10 received three doses, and 2 received two doses) showed seroconversion for neutralising antibodies, as judged by an enzyme focus reduction
All the boys with chest infection died in hospital. 1 of 2 sudden deaths happened during venepuncture on a patient admitted with abdominal pain; the other boy died in his father’s arms while watching television. 3 of the boys with chest infections died unexpectedly; 2 had been improving and all appeared in little distress when last seen by the nurses, yet were found dead shortly afterwards. Only 2 were in acute distress at the time of death-the 1 with abdominal pain and a boy who had become obsessed with his death and had pain for which no physical cause could be found (he
802
died under psychiatric
supervision, requiring morphine for increasing pain). Parents of 4 boys were not present at the time of death, and only in these parents were there concerns about the death. Reassurance that death had been peaceful relieved two set of parents but the other two were inconsolable. The parents of the boy who died during venepuncture were outside the room at the time and their grief was compounded by their son’s distress. 1 boy was admitted with a chest infection and his parents had been told that he was in no danger; he died that night and his parents have been consumed with guilt because they did not visit him. Death in DMD is usually peaceful, and parents should be told this early in their son’s illness and have this message reiterated later. The causes of death (chest infection, respiratory failure, and "sudden") are similar to those in other series.1 However death was often unexpected in boys with chest infection, so perhaps chest infections should be regarded as potentially life-threatening so that parents can arrange to visit and clear up any unfinished business with their sons.2 Doctors and nurses looking after these boys on the ward should know that death in DMD is often unpredictable. Long-term ventilation is now a treatment option, with the advent of techniques such as positive-pressure ventilation by nasal mask.3 This was not available for most of our study period, but it might have been appropriate for only 1 of the 11 boys who died. Muscle Clinic, Belfast City Hospital, Belfast BT9 7AB, UK
VICTOR PATTERSON OONAGH MORRISON ELAINE HICKS
Treatment of HBV reactivation after withdrawal of immunosuppression SIR,-Reactivation of chronic hepatitis B virus (HBV) infection by corticosteroids or chemotherapy is a well-recognised complication in patients with chronic HBV infection. Severe and sometimes fulminant hepatitis may develop after withdrawal of drugs and is associated with high mortality.1-3 Orthotopic liver transplantation has been suggested as the optimum treatment for fulminant patients.’ We report a patient with chronic HBV infection in whom severe hepatitis was reversed after treatment withdrawal by early reintroduction of corticosteroids. A 54-year-old Greek man, seropositive for HBsAg since 1975, noticed diffuse purpura on his lower limbs in April, 1989, and had a platelet count of 6 x 109/1. He was seropositive for platelet antibodies and a diagnosis of idiopathic thrombocytopenic purpura was made. His platelet count increased to 125 x 109/1 after four weeks of corticosteroid treatment (prednisolone 75 mg/day). He was seropositive for anti-HBe, negative for IgM anti-HBc, and his serum aspartate aminotransferase (AST) was 57 IU/1 before treatment. When prednisolone was reduced to 15 mg/day over three weeks, he became tired and his AST rose, first to 243 IU/1 and then to
669
IU/1 when he was transferred to our unit a week later.
On
Biochemical, serological, and histological results. Serum AST, W———W, ULN, upper limitof normal for serum AST; liver biopsy, units of serum HBV DNA, pg/40 pl serum.
Bx’
6400, HBV DNA fell
to 9 pg/40 µl serum, and he remained for both seronegative IgM anti-HBc and antibody to HDV. Repeat liver biopsy showed moderate chronic active hepatitis with severe bridging fibrosis. Reactivation of chronic HBV infection has been reported to occur 10-90 days after withdrawal of corticosteroids or chemotherapy.1-4 Reactivation of HBV replication during treatment followed by restoration of the immune system after withdrawal of the drug(s) is thought to be the cause of hepatocyte damage.1-3 The evidence for reactivation in our patient included the high serum HBsAg titre, positive serum HBV DNA, and reappearance of IgM anti-HBc. The reintroduction of corticosteroids in the early phase of this reactivation prevented both progressive clinical deterioration and the potential need for orthotopic liver transplantation.
JOHNSON Y. N. LAU Institute of Liver Studies,
King’s College Hospital, London SE5 9RS, UK
GEORGE L. A. BIRD ALEXANDER E. S. GIMSON GRAEME J. M. ALEXANDER ROGER WILLIAMS
1. Lau
JYN, Lai CL, Lin HJ, et al Fatal reactivation of chronic hepatitis B virus infection following chemotherapy withdrawal in lymphoma patients. Q J Med 1989, 73:
911-17. 2. Bird GLA, Smith
H, Portmann B, Alexander GJM, Williams R. Acute liver decompensation on withdrawal of cytotoxic chemotherapy and immunosuppressive therapy in hepatitis B carriers. QJ Med 1989; 73: 895-902. 3. Editorial. Chemotherapy and hepatitis B. Lancet 1989; ii 1136-37. 4. Cherqui D, Girardin MFS, Haioun C, et al. Liver transplantation for fulminant hepatitis following chemotherapy for malignant lymphoma. Lancet 1990; 335: 1400
arrival, his serum HBsAg titre was greater than 51 200, serum HBV DNA 79 pg/40µl serum, and serum IgM anti-HBc weakly positive, indicative of a reactivation of the HBV replication (although he remained seropositive for anti-HBe). There was no serological evidence of hepatitis D virus (HDV) and human immunodeficiency virus. His platelet count was 183 x 109/1 and his prothrombin time (INR) was 1-3. Liver biopsy showed severe acute-on-chronic hepatitis with extensive bridging necrosis. Extensive immunohistochemical staining for HBsAg was found but lack of nucleocapsid antigen suggested immune clearance of HBV-infected cells. In view of the rapid deterioration in liver biochemistry and the aggressive histology, corticosteroids were reintroduced (prednisolone 40 mg/day). Over the next week, there was clinical improvement and his serum AST fell to 250 IU/1. He remained seropositive for HBV DNA (71 pg/40 µl serum) but seronegative for IgM anti-HBc with falling serum HBsAg titre. There was further improvement in clinical and laboratory features over the next six months (figure). One year later, he was well and working normally. Corticosteroid dose had been reduced to 7.5 mg/day. His serum AST was 57 IU/1 and platelet count was 205 x 109/1. His serum HBsAg titre fell to
Reduced arylsulphatase A activity in children with severe mental retardation SIR,-Lysosomal enzyme arylsulphatase A (ASA) activity may 50-60% of control values in the presence of for a mutant allele. One such mutant is responsible heterozygosity for metachromatic leucodystrophy, an autosomal recessive neurological disorder; another is the pseudodeficiency allele mainly detected in healthy individuals. However, low activity in leucocytes from patients with neurological and/or mental disturbances other than metachromatic leucodystrophy have been reported, and we wondered how often reduced ASA activity might be found in individuals with such disorders but no specific diagnosis, or a diagnosis but no known aetiology. We have tested a sample of 19 children with severe mental retardation of unknown aetiology drawn from 90 severely retarded children identified in an epidemiological study in Bologna of the prevalence and distribution of severe mental retardation among children aged 6-13 years.’ We found 4 individuals (21 %) with reduced ASA activities (33-59% of control values). The expected prevalence, on the basis be reduced
to
suppressed for variable periods of time. Concern has been raised that oversuppression of PTH may lead to low bone tumover.s Our findings suggest that calcitriol can be given intermittently for brief periods when PTH is above a threshold concentration. Division of Paediatric
Nephrology,
Ruperto Carola University, 6900 Heidelberg 1, Germany
GÜNTER KLAUS OTTO MEHLS JÖRG HINDERER
Division of Nephrology, Ruperto Carola University,
EBERHARD RITZ
Heidelberg
1.Brumbaugh PF, Huges MR, Haussler MR. Cytoplasmatic and nuclear binding components for 1-alpha-dihydroxyvitamin D3 in chick parathyroid glands. Proc Natl Acad Sci (USA) 1975; 72: 4871-75. 2. Naveh-Many T, Silver J. Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat. J Clin Invest 1990; 86: 1313-19. 3. Szabo A, Merke J, Beier E, Mall G, Ritz E. 1,25(OH)2 vitamin D3 inhibits parathyroid cell proliferation in experimental uremia. Kidney Int 1989; 35:1049-56. 4. Blind E, Schmidt-Gayk H, Scharla S, Flentje D, Fischer S, Göhring U, Hitzler W. Two-site assay of intact parathyroid hormone in the investigation of primary hyperparathyroidism and other disorders of calcium metabolism compared with a midregion assay. J Clin Endocrinol Metab 1988; 67: 353-60. 5. Baker LRI, Abrams SML, Roe CJ, et al. 1,25(OH)2D3 administration in moderate renal failure: a prospective double-blind trial. Kidney Int 1989; 35: 661-69.
Haemorrhagic shock, encephalopathy,
and
sudden infant death SIR,-Dr Trounce and his associates (Jan 26, p 202) suggest that the haemorrhagic shock and encephalopathy syndrome should be regarded as one of the causes of sudden infant death. I agree, but am amazed that, despite the plethora of publications concerning this syndrome, no one has pursued the obvious similarity to toxic-shock syndrome after influenza-like illnesses.’ In the past few years, I have seen four infants with encephalopathy, fever, shock, diarrhoea, disseminated intravascular coagulation, and renal and hepatic dysfunction, who presented in the winter months after a viral cough. Two patients survived with severe brain damage. Staphylococcus aureus was found in the trachea of three of the infants, in whom it was looked for; and in one child the organism had produced toxic-shock syndrome toxin-1and the patient had an antibody titre of 512 against this toxin. I suggest that toxic-shock syndrome as a cause of haemorrhagic shock and encephalopathy syndrome was dismissed in the UK without adequate data. Division of Pediatric Nephrology, Marshfield Clinic, Marshfield, WI 54449, USA
EDWARD B. BLAU
KL, Osterholm MT, Hedberg CW, et al. Toxic shock syndrome. A newly recognised complication of influenza and influenza-like illness. JAMA 1987;
1. MacDonald
257: 105-58.
neutralisation test, 2 weeks after the third dose. 10 of them were still antibody positive 1 year after vaccination. In view of the antigenic difference between viruses of the Apodemus and rat type of HFRS,2 it is thought that a monovalent vaccine may not be as effective as one that prevents both types of HFRS.2 Bivalent vaccine was prepared with GHKC adapted Hantaan virus JR strain3and Seoul virus, L99 strain.l Virus titres before inactivation were 6’67-7-17 and 7-33-7-67 log TCID/ml, respectively, and antigenic titres were 256-512. Trials were done in 206 volunteers as for the monovalent vaccine. Minor side-effects were observed in 5 vaccinees. Blood was collected before immunisation and 56 days after the first dose. The seroconversion rate by immunofluorescent antibody test (IFAT) was 93-2% (192/206), and neutralising antibody was present in all 15 randomly sampled vaccinees on challenge with L virus and in all but 1 on challenge with JR virus. Specific and non-specific T-cell transformation indices were increased, by 96% and 48%,
respectively. These results suggest that the inactivated GHKC vaccine against HFRS is safe, and induces antibody responses (especially neutralising antibody) and cellular immunity. We also found that cellular immunity can be elicited by an inactivated vaccine against HFRS and that it can be detected. Institute of Virology, Chinese Academy of Preventive Medicine, Beijing 100052, China
G. SONG C. S. HANG
Changchun Institute of Biological Products, Ministry of Public Health, Changchun
Y. C. HUANG F. Y. Hou
1. Liu PQ, Liao HX, Fu JL, et al. Isolation of epidemic hemorrhagic fever viruses from Rattus losea and R confucianus and their antigenic identification. Bull Jiangxi Med Coll 1984; 3: 1-5 (in Chinese). 2. Song G, Hang CS, Liao HX, Fu JL. Antigenic comparison of virus strains of mild and classical types of epidemic haemorrhagic fever isolated in China and adaptation of these to cultures of normal cells. Lancet 1984; i: 677-78. 3. Han HZ, Hou FY, et al. A discovery of rabbit infection in the EHF endemic area of Yanbian of Jilin Province and isolation of EHF viruses from rabbits. ChinJ Publ Health 1990; 9: 73-76.
Mode of death in Duchenne muscular
dystrophy SIR,-Major advances in the molecular understanding of Duchenne muscular dystrophy (DMD) have not made the psychosocial management of this disease any less important. DMD causes death, usually in the teens or early twenties, and our impression is that throughout their child’s illness parents are fearful of the death itself. Our muscle clinic has contact with most patients with DMD in Northern Ireland. We collected information on deaths between 1983 and 1989 among all boys with DMD known to us, using hospital notes, and talking to doctors and parents. The 11 boys who died were aged 9-21:
Preliminary trials of inactivated vaccine against haemorrhagic fever with renal syndrome SIR,-Haemorrhagic fever with renal syndrome (HFRS) is a public health problem in China, there being no effective treatment of prevention and control strategies. A safe and effective vaccine is urgently needed. We have been developing an inactivated golden hamster kidney cell culture (GHKC) vaccine against HFRS and report here preliminary trials in volunteers. The monovalent vaccine was produced with Seoul virus L99 serious
strainl inactivated with 0-025% formalin. The virus titre before inactivation was 7-0 log TCID50/ml and the antigenic titre of the vaccine was 512 by ELISA. 12 volunteers were immunised intramuscularly with three doses on days 0, 7, and 28, 1 ml being injected each time. General and local reactions were carefully monitored for 3 days after each inoculation, and blood was taken on days 0, 28, and 42, and 6 and 12 months after the first dose. No untoward reactions were observed, and all 12 vaccinees (10 received three doses, and 2 received two doses) showed seroconversion for neutralising antibodies, as judged by an enzyme focus reduction
All the boys with chest infection died in hospital. 1 of 2 sudden deaths happened during venepuncture on a patient admitted with abdominal pain; the other boy died in his father’s arms while watching television. 3 of the boys with chest infections died unexpectedly; 2 had been improving and all appeared in little distress when last seen by the nurses, yet were found dead shortly afterwards. Only 2 were in acute distress at the time of death-the 1 with abdominal pain and a boy who had become obsessed with his death and had pain for which no physical cause could be found (he
802
died under psychiatric
supervision, requiring morphine for increasing pain). Parents of 4 boys were not present at the time of death, and only in these parents were there concerns about the death. Reassurance that death had been peaceful relieved two set of parents but the other two were inconsolable. The parents of the boy who died during venepuncture were outside the room at the time and their grief was compounded by their son’s distress. 1 boy was admitted with a chest infection and his parents had been told that he was in no danger; he died that night and his parents have been consumed with guilt because they did not visit him. Death in DMD is usually peaceful, and parents should be told this early in their son’s illness and have this message reiterated later. The causes of death (chest infection, respiratory failure, and "sudden") are similar to those in other series.1 However death was often unexpected in boys with chest infection, so perhaps chest infections should be regarded as potentially life-threatening so that parents can arrange to visit and clear up any unfinished business with their sons.2 Doctors and nurses looking after these boys on the ward should know that death in DMD is often unpredictable. Long-term ventilation is now a treatment option, with the advent of techniques such as positive-pressure ventilation by nasal mask.3 This was not available for most of our study period, but it might have been appropriate for only 1 of the 11 boys who died. Muscle Clinic, Belfast City Hospital, Belfast BT9 7AB, UK
VICTOR PATTERSON OONAGH MORRISON ELAINE HICKS
Treatment of HBV reactivation after withdrawal of immunosuppression SIR,-Reactivation of chronic hepatitis B virus (HBV) infection by corticosteroids or chemotherapy is a well-recognised complication in patients with chronic HBV infection. Severe and sometimes fulminant hepatitis may develop after withdrawal of drugs and is associated with high mortality.1-3 Orthotopic liver transplantation has been suggested as the optimum treatment for fulminant patients.’ We report a patient with chronic HBV infection in whom severe hepatitis was reversed after treatment withdrawal by early reintroduction of corticosteroids. A 54-year-old Greek man, seropositive for HBsAg since 1975, noticed diffuse purpura on his lower limbs in April, 1989, and had a platelet count of 6 x 109/1. He was seropositive for platelet antibodies and a diagnosis of idiopathic thrombocytopenic purpura was made. His platelet count increased to 125 x 109/1 after four weeks of corticosteroid treatment (prednisolone 75 mg/day). He was seropositive for anti-HBe, negative for IgM anti-HBc, and his serum aspartate aminotransferase (AST) was 57 IU/1 before treatment. When prednisolone was reduced to 15 mg/day over three weeks, he became tired and his AST rose, first to 243 IU/1 and then to
669
IU/1 when he was transferred to our unit a week later.
On
Biochemical, serological, and histological results. Serum AST, W———W, ULN, upper limitof normal for serum AST; liver biopsy, units of serum HBV DNA, pg/40 pl serum.
Bx’
6400, HBV DNA fell
to 9 pg/40 µl serum, and he remained for both seronegative IgM anti-HBc and antibody to HDV. Repeat liver biopsy showed moderate chronic active hepatitis with severe bridging fibrosis. Reactivation of chronic HBV infection has been reported to occur 10-90 days after withdrawal of corticosteroids or chemotherapy.1-4 Reactivation of HBV replication during treatment followed by restoration of the immune system after withdrawal of the drug(s) is thought to be the cause of hepatocyte damage.1-3 The evidence for reactivation in our patient included the high serum HBsAg titre, positive serum HBV DNA, and reappearance of IgM anti-HBc. The reintroduction of corticosteroids in the early phase of this reactivation prevented both progressive clinical deterioration and the potential need for orthotopic liver transplantation.
JOHNSON Y. N. LAU Institute of Liver Studies,
King’s College Hospital, London SE5 9RS, UK
GEORGE L. A. BIRD ALEXANDER E. S. GIMSON GRAEME J. M. ALEXANDER ROGER WILLIAMS
1. Lau
JYN, Lai CL, Lin HJ, et al Fatal reactivation of chronic hepatitis B virus infection following chemotherapy withdrawal in lymphoma patients. Q J Med 1989, 73:
911-17. 2. Bird GLA, Smith
H, Portmann B, Alexander GJM, Williams R. Acute liver decompensation on withdrawal of cytotoxic chemotherapy and immunosuppressive therapy in hepatitis B carriers. QJ Med 1989; 73: 895-902. 3. Editorial. Chemotherapy and hepatitis B. Lancet 1989; ii 1136-37. 4. Cherqui D, Girardin MFS, Haioun C, et al. Liver transplantation for fulminant hepatitis following chemotherapy for malignant lymphoma. Lancet 1990; 335: 1400
arrival, his serum HBsAg titre was greater than 51 200, serum HBV DNA 79 pg/40µl serum, and serum IgM anti-HBc weakly positive, indicative of a reactivation of the HBV replication (although he remained seropositive for anti-HBe). There was no serological evidence of hepatitis D virus (HDV) and human immunodeficiency virus. His platelet count was 183 x 109/1 and his prothrombin time (INR) was 1-3. Liver biopsy showed severe acute-on-chronic hepatitis with extensive bridging necrosis. Extensive immunohistochemical staining for HBsAg was found but lack of nucleocapsid antigen suggested immune clearance of HBV-infected cells. In view of the rapid deterioration in liver biochemistry and the aggressive histology, corticosteroids were reintroduced (prednisolone 40 mg/day). Over the next week, there was clinical improvement and his serum AST fell to 250 IU/1. He remained seropositive for HBV DNA (71 pg/40 µl serum) but seronegative for IgM anti-HBc with falling serum HBsAg titre. There was further improvement in clinical and laboratory features over the next six months (figure). One year later, he was well and working normally. Corticosteroid dose had been reduced to 7.5 mg/day. His serum AST was 57 IU/1 and platelet count was 205 x 109/1. His serum HBsAg titre fell to
Reduced arylsulphatase A activity in children with severe mental retardation SIR,-Lysosomal enzyme arylsulphatase A (ASA) activity may 50-60% of control values in the presence of for a mutant allele. One such mutant is responsible heterozygosity for metachromatic leucodystrophy, an autosomal recessive neurological disorder; another is the pseudodeficiency allele mainly detected in healthy individuals. However, low activity in leucocytes from patients with neurological and/or mental disturbances other than metachromatic leucodystrophy have been reported, and we wondered how often reduced ASA activity might be found in individuals with such disorders but no specific diagnosis, or a diagnosis but no known aetiology. We have tested a sample of 19 children with severe mental retardation of unknown aetiology drawn from 90 severely retarded children identified in an epidemiological study in Bologna of the prevalence and distribution of severe mental retardation among children aged 6-13 years.’ We found 4 individuals (21 %) with reduced ASA activities (33-59% of control values). The expected prevalence, on the basis be reduced
to
