- Email: [email protected]
Cerebral abscess associated with dental procedure in hereditary haemorrhagic telangiectasia
508
respect to 28-day mortality, no patient with maximum response to hydrocortisone and short-term vasopressor therapy died, whereas 4 in the other group did so. Our data support the hypothesis of relative adrenocortical insufficiency in septic shock, which contributes, in part, to circulatory collapse. Low cortisol (ie, < 30 )ig/dl) may be indicative of cortisol deficiency in early septic shock.2 Response to corticotropin, however, did not denote cortisol deficiency. The role of cortisol replacement in the modulation of the immune response remains to be elucidated.3 Intensive Care Unit, Institute of Anaesthesiology, Klinikum Grosshadern, University of Munich, 8000 Munchen 70, Germany
JOSEF BRIEGEL HELMUTH FORST HILDEGARD HELLINGER MATHIAS HALLER
P, Pruzanski W, Stefanski E, et al. Concordance of endogenous cortisol and phospholipase A2 levels in gram-negative septic shock: a prospective study. J Lab
1. Vadas
Clin Med 1988; 111: 584-90. 2. Catalano RD, Parameswaran V, Ramachandran J, Trunkey DD. Mechanisms of adrenocortical depression during Escherichia coli shock. Arch Surg 1984; 119: 145-50. 3. Hermus ARMM, Sweep CGJ. Cytokines and the hypothalamic-pituitary-adrenal axis. J Steroid Biochem Molec Biol 1990; 37: 867-71.
Postcoital
contraception
SIR,-Dr Silvestre and colleagues (July 6, p 39) from Roussel criticise several recent studies about postcoital contraception and cast some doubt on its efficacy, especially when combined oestrogen-progestagen preparations (CEP) were used. They suggest that a prospective controlled assessment of postcoital contraception with either high-dose oestrogen or CEP is needed, together with studies of emergency insertion of an intrauterine device or late luteal administration of an antiprogesterone. We published such a study in 1985.1 We evaluated Yuzpe’s CEP method and Haspels’ high-dose ethinyloestradiol method. Our prospective double-blind randomised study confirmed the efficacy of both regimens. Van Santen and Haspels were also the first to use mifepristone as an emergency postcoital contraceptive.2 A pregnancy rate of 1-6% was observed. This method provides a good interceptive technique when the time for use of postcoital steroids or for a postcoital intrauterine device has lapsed. It is not a good method to be used every month3 because 600 mg mifepristone in the first cycle may disturb the next cycle and postpone ovulation. Subsequent administration of mifepristone may then be incorrectly timed. University of Utrecht, 3584 CX Utrecht, the Netherlands
ARY A. HASPELS
MR, Haspels AA. A comparison of high-dose oestrogen versus low-dose ethinyl estradiol-norgestrel combination in post-coital interception: a study in 493
1. Van Santen
women. Fertil Steril 1985; 43: 206. 2. Van Santen MR, Haspels AA. Post-coital luteal contragestion by an Contraception 1987; 35: 423. 3. Van Santen MR, Haspels AA. Failure of mifepristone as a monthly Contraception 1987; 35: 433.
antiprogestin. contragestive.
Cerebral abscess associated with dental procedure in hereditary haemorrhagic
telangiectasia SIR,-Brain abscess has been associated with the pulmonary arteriovenous fistulae often seen in patients with hereditary haemorrhagic telangiectasia (HIT)1 but not previously reported to follow dental procedures. A 45-year-old woman presented with a right occipital brain abscess manifested by headache and left homonymous hemianopsia 3 weeks after a dental procedure. Computed tomography (CT) indicated two small lesions in the right lung base consistent with arteriovenous malformations. Magnetic resonance imaging (MRI) revealed a right occipital lesion with a gadolinium-enhancing wall (figure). Aspiration yielded purulent material which grew Bacteroides sp, a microaerophilic streptococcus, and Fusobacterium sp sensitive to penicillin and chloramphenicol. The patient
MRI
Upper
on
scans
of brain.
presentation.
Lower after treatment with intravenous antibiotics and needle aspiration of abscess
responded to intravenous chloramphenicol and repeated aspiration. An MRI scan 4 months after treatment showed resolution of the lesion (figure). A 65-year-old man presented in January, 1991, with right frontal and left frontoparietal brain lesions manifested by broken, nonfluent speech, impaired short-term memory, and right-arm weakness. He had right mandibular pain and X-rays revealed osteomyelitis in the area where a tooth had been extracted 2 months previously. (He had a history of frequent epistaxis, haematemesis, passage of bloody stools, and melaena from telangiectasias in the stomach and small bowel and therapeutic endoscopy and intensive care had often been required. The frequency of his bleeding had been diminished considerably by danazol 200 mg three times daily.) He was treated with intravenous metronidazole, ceftriaxone, and penicillin and neurosurgical drainage. Biopsy findings were consistent with cerebritis but no frankly purulent material was obtained and cultures were negative. His postoperative course was complicated by reaccumulation of multiple areas of brain abscess requiring aspiration. Gram-positive cocci were identified. Since the operation the expressive aphasia and right facial droop have improved. In HHT, an autosomal dominant disease characterised by telangiectasias and arteriovenous malformations, the salient feature is recurrent mucous membrane haemorrhage. Although clinical manifestations of pulmonary arteriovenous malformations are usually present by the third or fourth decades, half the patients may
509
be symptom-free despite radiographic evidence of pulmonary arteriovenous fistulas.2,3 15-25% of individuals with HHT have pulmonary arteriovenous malfonnations.1,4 Neurological complications have been reported in 8-12% of patients with HHT but in as many as 41 % of those who have pulmonary arteriovenous malformationsBrain abscesses are thought to occur in 5-6% of HHT patients with pulmonary arteriovenous malformations, and 1% of all patients with HHT might be expected to have brain abscess.6 The sources of the septic microemboli that lead to such brain abscesses include osteomyelitis, sinusitis, and submandibular abscess but we can find no previous report of brain abscess associated with dental procedures. Our two patients had had dental procedures 3 and 8 weeks before presentation and those may have been the source of the abscess. The pathogens most frequently isolated from brain abscesses in patients with HHT have been oral floraas in our patients. Prevention of recurrent brain abscess has been aimed at elimination of pulmonary fistulae by surgery or embolisation.7.7 However, in the series reported by Press and Ramsey6 resection was feasible in only 11 of 31 patients, and balloon embolisation, though less risky than surgery, may be ineffective. Our experience in these two patients leads us to consider non-invasive prophylaxis. Both patients had a tooth abscess, and symptoms developed shortly after dental manipulation. The dental abscess and ensuing procedure may well have caused the brain abscess. By analogy with bacteraemia associated with dental procedures as a cause of infective endocarditis, it seems justifiable to ask for clinical trials of antibiotic prophylaxis in patients with HHT undergoing dental and/or invasive procedures associated with infection. Presented in part at regional meeting of American College of Physicians (Washington, DC, September, 1990). We thank Dr Michael J. Sheridan, Dr Lawrence Eron, Dr James N. Cooper, and Dr Robert J. Jacobson for their encouragement and help.
Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA; and Division of Gastroenterology, Department of Medicine, National Naval Medical Center, Bethesda, Maryland
EMILE R. MOHLER BRIAN MONAHAN MICHAEL DON CANTY DAVID A. FLOCKHART
Diagnosis of liver disease was confirmed in all patients by histological examination of liver biopsies. 10 of 22 patients (45%) were HCV-RNA positive with Japanese-type primers. Subsequently, negative sera were tested with the 5’-non-coding region primer, a sequence showing more than 99 % homology with HCV genomes isolated from Japanese and Western patients.s This sequence is regarded as a universal HCV primer. The analysis detected 9 additional patients (41%) who’ were positive for HCV-RNA (Japanese-type negative). 3 patients (14%) who were c-100 ELISA and c-100 RIBA positive proved negative for Japanese-type RNA and 5’-non-coding sequences. No false positives were found. By matching the histopathological diagnosis with the viral type, we found that 9 of 10 patients positive for HCV-RNA Japanese type (mean [SD] age, 59 [12] years) had chronic active hepatitis with cirrhosis. 6 of these were treated with a-2a-interferon-6 MU thrice weekly for one month and thereafter 3 MU thrice weekly for nine months-without apparent benefit. In the remaining 3 patients, treatment was not given because of the presence of portal hypertension. 1 patient who presented with chronic active hepatitis without cirrhosis had a late response to interferon therapy. Among 9 patients (age 47 [13] years) who were positive for 5’-non-coding sequences and negative for Japanese-type HCV-RNA, 6 (66%) showed chronic persistent hepatitis and 3 (33%) had chronic active hepatitis without cirrhosis. 3 subjects were not treated because of their long-standing normal aminotransferase values. The remaining 6 patients were treated with a-2a-interferon (same protocol as before) with prompt nomialisation of serum aminotransferase
activities. Our results show that at least two HCV clones were present in our Italian population, and that detection of Japanese-type HCV-RNA in serum seems to be associated with the presence of more serious liver disease and with a poor response to interferon therapy. The use of different primers for HCV-RNA detection may provide valuable information about both disease outlook and expected response to
therapy.
Institute of
Dyer NH. Cerebral abscess m hereditary hemorrhagic telangiectasia: report of two cases in a family. Neurol J Neurosurg Psychiatry 1967; 30: 563-67. 2. Perry WH. Clinical spectrum of hereditary hemorrhagic telangiectasia (Osler-WeberRendu disease). Am J Med 1987; 82: 989-97. 3. Dines DE, Arms RA, Bernatz PE, Gomes MR. Pulmonary arteriovenous fistulas. Mayo Clin Proc 1974, 49: 460-65. 4. Hodgson CH, Burchell HB, Good A, Clagett OT. Hereditary hemorrhagic telangiectasia and pulmonary arteriovenous fistula. N Engl J Med 1959; 261: 1.
625-36. 5. Roman G, Fischer
M, Perl DP, Poser CM. Neurologic manifestations of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber): report of 2 cases and review of
the literature. Ann Neurol 1978; 4: 130-44. 6. Press OW, Ramsey PG. Central nervous system infections associated with hereditary hemorrhagic telangiectasia. Am J Med 1984; 77: 86-77. 7. Terry PB, White RI, Barth KH, Kaufman SL, Mithchell SE. Pulmonary arteriovenous malformations: physiologic observations and results of the therapeutic balloon embolization. N Engl J Med 1983; 308: 1197-200.
Severity of liver disease with different hepatitis C viral clones SIR,-Although knowledge about hepatitis C virus (HCV) is growing rapidly, no clear relation has yet been established between HCV replication and either severity of liver disease or response to antiviral therapy. Detection of serum HCV RNA should yield important information on the biology of this virus, but the titre of circulating virus is low.2 In addition, HCV has a high nucleotide sequence heterogeneity, which is usually a feature of singlestranded RNA viruses. The isolation by the polymerase chain reaction (PCR) of a "Japanese-type" HCV clone3 that has a rather low level of nucleotide homology (77%) with Chiron’s published sequence prompted us to examine the correlation between different HCV clones and clinical aspects of the disease. 34 serum samples from Italian patients with different stages of liver disease were blindly tested for detection of HCV-RNA by PCR.4 22 were HCV c-100 ELISA and c-100 RIBA positive.
Pathology, University School of Medicin 34149 Trieste, Italy
First Department of Internal Medicine, Kanazawa University,
Kanazawa, Japan
GABRIELE POZZATO MICHÈLE MORETTI FRANCESCO FRANZIN LORY SAVERIA CROCÈ CLAUDIO TIRIBELLI TAKENCHI MASAYU SHUICHI KANEKO MASASHI UNOURA KENICHI KOBAYASHI
1. Van der Poel CL, Cuypers HTM, Reesink HW, et al. Confirmation of hepatitis C virus infection by new four-antigen recombinant immunoblot assay. Lancet 1991; 337: 317-19. 2. Weimer AJ, Kuo G, Bradley DW, et al. Detection of hepatitis C viral sequences in non-A, non-B hepatitis. Lancet 1990; 335: 1-3. 3. Kato N, Ohkoshi S, Shimotohno K. Japanese isolates of the non-A, non-B hepatitis viral genome show sequence variations from the original isolate in the U.S.A. Proc Jpn Acad 1989; 65: 219-23. 4. Kaneko S, Feinstone SM, Miller RH. Rapid and sensitive method for the detection of serum hepatitis B virus DNA using polymease chain reaction technique. J Clin Microbiol 1989; 27: 1930-33. 5. Han JK, Shymala V, Richman KM, et al. Characterization of the terminal regions of hepatitis-C viral RNA: identification of conserved sequences in the 5’-untranslated region and poly (A) tails at the 3’ end. Proc Natl Acad Sci USA 1991; 88: 1711-15.
Propranolol in the prevention of ascites SIR,-Dr Perez-Ayuso and colleagues (June 15, p 1433) report a propranolol on rebleeding rates from severe portal hypertensive gastropathy and show that the frequency of encephalopathy was similar in both the treated and control groups (27% propranolol, 21% control). However, ascites developed in 53% of patients receiving placebo and in 23% of those taking propranolol (p < 0 05) during a mean follow-up of 21 months. In a previous randomised controlled trial of propranolol in the primary prevention of bleeding in patients with cirrhosis, we found similar results.1 Ascites, hepatic encephalopathy, and Child-Pugh scores were recorded at entry into the study and during follow-up. During a mean follow-up of 14 months among 230 patients, we observed beneficial effect of
respect to 28-day mortality, no patient with maximum response to hydrocortisone and short-term vasopressor therapy died, whereas 4 in the other group did so. Our data support the hypothesis of relative adrenocortical insufficiency in septic shock, which contributes, in part, to circulatory collapse. Low cortisol (ie, < 30 )ig/dl) may be indicative of cortisol deficiency in early septic shock.2 Response to corticotropin, however, did not denote cortisol deficiency. The role of cortisol replacement in the modulation of the immune response remains to be elucidated.3 Intensive Care Unit, Institute of Anaesthesiology, Klinikum Grosshadern, University of Munich, 8000 Munchen 70, Germany
JOSEF BRIEGEL HELMUTH FORST HILDEGARD HELLINGER MATHIAS HALLER
P, Pruzanski W, Stefanski E, et al. Concordance of endogenous cortisol and phospholipase A2 levels in gram-negative septic shock: a prospective study. J Lab
1. Vadas
Clin Med 1988; 111: 584-90. 2. Catalano RD, Parameswaran V, Ramachandran J, Trunkey DD. Mechanisms of adrenocortical depression during Escherichia coli shock. Arch Surg 1984; 119: 145-50. 3. Hermus ARMM, Sweep CGJ. Cytokines and the hypothalamic-pituitary-adrenal axis. J Steroid Biochem Molec Biol 1990; 37: 867-71.
Postcoital
contraception
SIR,-Dr Silvestre and colleagues (July 6, p 39) from Roussel criticise several recent studies about postcoital contraception and cast some doubt on its efficacy, especially when combined oestrogen-progestagen preparations (CEP) were used. They suggest that a prospective controlled assessment of postcoital contraception with either high-dose oestrogen or CEP is needed, together with studies of emergency insertion of an intrauterine device or late luteal administration of an antiprogesterone. We published such a study in 1985.1 We evaluated Yuzpe’s CEP method and Haspels’ high-dose ethinyloestradiol method. Our prospective double-blind randomised study confirmed the efficacy of both regimens. Van Santen and Haspels were also the first to use mifepristone as an emergency postcoital contraceptive.2 A pregnancy rate of 1-6% was observed. This method provides a good interceptive technique when the time for use of postcoital steroids or for a postcoital intrauterine device has lapsed. It is not a good method to be used every month3 because 600 mg mifepristone in the first cycle may disturb the next cycle and postpone ovulation. Subsequent administration of mifepristone may then be incorrectly timed. University of Utrecht, 3584 CX Utrecht, the Netherlands
ARY A. HASPELS
MR, Haspels AA. A comparison of high-dose oestrogen versus low-dose ethinyl estradiol-norgestrel combination in post-coital interception: a study in 493
1. Van Santen
women. Fertil Steril 1985; 43: 206. 2. Van Santen MR, Haspels AA. Post-coital luteal contragestion by an Contraception 1987; 35: 423. 3. Van Santen MR, Haspels AA. Failure of mifepristone as a monthly Contraception 1987; 35: 433.
antiprogestin. contragestive.
Cerebral abscess associated with dental procedure in hereditary haemorrhagic
telangiectasia SIR,-Brain abscess has been associated with the pulmonary arteriovenous fistulae often seen in patients with hereditary haemorrhagic telangiectasia (HIT)1 but not previously reported to follow dental procedures. A 45-year-old woman presented with a right occipital brain abscess manifested by headache and left homonymous hemianopsia 3 weeks after a dental procedure. Computed tomography (CT) indicated two small lesions in the right lung base consistent with arteriovenous malformations. Magnetic resonance imaging (MRI) revealed a right occipital lesion with a gadolinium-enhancing wall (figure). Aspiration yielded purulent material which grew Bacteroides sp, a microaerophilic streptococcus, and Fusobacterium sp sensitive to penicillin and chloramphenicol. The patient
MRI
Upper
on
scans
of brain.
presentation.
Lower after treatment with intravenous antibiotics and needle aspiration of abscess
responded to intravenous chloramphenicol and repeated aspiration. An MRI scan 4 months after treatment showed resolution of the lesion (figure). A 65-year-old man presented in January, 1991, with right frontal and left frontoparietal brain lesions manifested by broken, nonfluent speech, impaired short-term memory, and right-arm weakness. He had right mandibular pain and X-rays revealed osteomyelitis in the area where a tooth had been extracted 2 months previously. (He had a history of frequent epistaxis, haematemesis, passage of bloody stools, and melaena from telangiectasias in the stomach and small bowel and therapeutic endoscopy and intensive care had often been required. The frequency of his bleeding had been diminished considerably by danazol 200 mg three times daily.) He was treated with intravenous metronidazole, ceftriaxone, and penicillin and neurosurgical drainage. Biopsy findings were consistent with cerebritis but no frankly purulent material was obtained and cultures were negative. His postoperative course was complicated by reaccumulation of multiple areas of brain abscess requiring aspiration. Gram-positive cocci were identified. Since the operation the expressive aphasia and right facial droop have improved. In HHT, an autosomal dominant disease characterised by telangiectasias and arteriovenous malformations, the salient feature is recurrent mucous membrane haemorrhage. Although clinical manifestations of pulmonary arteriovenous malformations are usually present by the third or fourth decades, half the patients may
509
be symptom-free despite radiographic evidence of pulmonary arteriovenous fistulas.2,3 15-25% of individuals with HHT have pulmonary arteriovenous malfonnations.1,4 Neurological complications have been reported in 8-12% of patients with HHT but in as many as 41 % of those who have pulmonary arteriovenous malformationsBrain abscesses are thought to occur in 5-6% of HHT patients with pulmonary arteriovenous malformations, and 1% of all patients with HHT might be expected to have brain abscess.6 The sources of the septic microemboli that lead to such brain abscesses include osteomyelitis, sinusitis, and submandibular abscess but we can find no previous report of brain abscess associated with dental procedures. Our two patients had had dental procedures 3 and 8 weeks before presentation and those may have been the source of the abscess. The pathogens most frequently isolated from brain abscesses in patients with HHT have been oral floraas in our patients. Prevention of recurrent brain abscess has been aimed at elimination of pulmonary fistulae by surgery or embolisation.7.7 However, in the series reported by Press and Ramsey6 resection was feasible in only 11 of 31 patients, and balloon embolisation, though less risky than surgery, may be ineffective. Our experience in these two patients leads us to consider non-invasive prophylaxis. Both patients had a tooth abscess, and symptoms developed shortly after dental manipulation. The dental abscess and ensuing procedure may well have caused the brain abscess. By analogy with bacteraemia associated with dental procedures as a cause of infective endocarditis, it seems justifiable to ask for clinical trials of antibiotic prophylaxis in patients with HHT undergoing dental and/or invasive procedures associated with infection. Presented in part at regional meeting of American College of Physicians (Washington, DC, September, 1990). We thank Dr Michael J. Sheridan, Dr Lawrence Eron, Dr James N. Cooper, and Dr Robert J. Jacobson for their encouragement and help.
Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA; and Division of Gastroenterology, Department of Medicine, National Naval Medical Center, Bethesda, Maryland
EMILE R. MOHLER BRIAN MONAHAN MICHAEL DON CANTY DAVID A. FLOCKHART
Diagnosis of liver disease was confirmed in all patients by histological examination of liver biopsies. 10 of 22 patients (45%) were HCV-RNA positive with Japanese-type primers. Subsequently, negative sera were tested with the 5’-non-coding region primer, a sequence showing more than 99 % homology with HCV genomes isolated from Japanese and Western patients.s This sequence is regarded as a universal HCV primer. The analysis detected 9 additional patients (41%) who’ were positive for HCV-RNA (Japanese-type negative). 3 patients (14%) who were c-100 ELISA and c-100 RIBA positive proved negative for Japanese-type RNA and 5’-non-coding sequences. No false positives were found. By matching the histopathological diagnosis with the viral type, we found that 9 of 10 patients positive for HCV-RNA Japanese type (mean [SD] age, 59 [12] years) had chronic active hepatitis with cirrhosis. 6 of these were treated with a-2a-interferon-6 MU thrice weekly for one month and thereafter 3 MU thrice weekly for nine months-without apparent benefit. In the remaining 3 patients, treatment was not given because of the presence of portal hypertension. 1 patient who presented with chronic active hepatitis without cirrhosis had a late response to interferon therapy. Among 9 patients (age 47 [13] years) who were positive for 5’-non-coding sequences and negative for Japanese-type HCV-RNA, 6 (66%) showed chronic persistent hepatitis and 3 (33%) had chronic active hepatitis without cirrhosis. 3 subjects were not treated because of their long-standing normal aminotransferase values. The remaining 6 patients were treated with a-2a-interferon (same protocol as before) with prompt nomialisation of serum aminotransferase
activities. Our results show that at least two HCV clones were present in our Italian population, and that detection of Japanese-type HCV-RNA in serum seems to be associated with the presence of more serious liver disease and with a poor response to interferon therapy. The use of different primers for HCV-RNA detection may provide valuable information about both disease outlook and expected response to
therapy.
Institute of
Dyer NH. Cerebral abscess m hereditary hemorrhagic telangiectasia: report of two cases in a family. Neurol J Neurosurg Psychiatry 1967; 30: 563-67. 2. Perry WH. Clinical spectrum of hereditary hemorrhagic telangiectasia (Osler-WeberRendu disease). Am J Med 1987; 82: 989-97. 3. Dines DE, Arms RA, Bernatz PE, Gomes MR. Pulmonary arteriovenous fistulas. Mayo Clin Proc 1974, 49: 460-65. 4. Hodgson CH, Burchell HB, Good A, Clagett OT. Hereditary hemorrhagic telangiectasia and pulmonary arteriovenous fistula. N Engl J Med 1959; 261: 1.
625-36. 5. Roman G, Fischer
M, Perl DP, Poser CM. Neurologic manifestations of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber): report of 2 cases and review of
the literature. Ann Neurol 1978; 4: 130-44. 6. Press OW, Ramsey PG. Central nervous system infections associated with hereditary hemorrhagic telangiectasia. Am J Med 1984; 77: 86-77. 7. Terry PB, White RI, Barth KH, Kaufman SL, Mithchell SE. Pulmonary arteriovenous malformations: physiologic observations and results of the therapeutic balloon embolization. N Engl J Med 1983; 308: 1197-200.
Severity of liver disease with different hepatitis C viral clones SIR,-Although knowledge about hepatitis C virus (HCV) is growing rapidly, no clear relation has yet been established between HCV replication and either severity of liver disease or response to antiviral therapy. Detection of serum HCV RNA should yield important information on the biology of this virus, but the titre of circulating virus is low.2 In addition, HCV has a high nucleotide sequence heterogeneity, which is usually a feature of singlestranded RNA viruses. The isolation by the polymerase chain reaction (PCR) of a "Japanese-type" HCV clone3 that has a rather low level of nucleotide homology (77%) with Chiron’s published sequence prompted us to examine the correlation between different HCV clones and clinical aspects of the disease. 34 serum samples from Italian patients with different stages of liver disease were blindly tested for detection of HCV-RNA by PCR.4 22 were HCV c-100 ELISA and c-100 RIBA positive.
Pathology, University School of Medicin 34149 Trieste, Italy
First Department of Internal Medicine, Kanazawa University,
Kanazawa, Japan
GABRIELE POZZATO MICHÈLE MORETTI FRANCESCO FRANZIN LORY SAVERIA CROCÈ CLAUDIO TIRIBELLI TAKENCHI MASAYU SHUICHI KANEKO MASASHI UNOURA KENICHI KOBAYASHI
1. Van der Poel CL, Cuypers HTM, Reesink HW, et al. Confirmation of hepatitis C virus infection by new four-antigen recombinant immunoblot assay. Lancet 1991; 337: 317-19. 2. Weimer AJ, Kuo G, Bradley DW, et al. Detection of hepatitis C viral sequences in non-A, non-B hepatitis. Lancet 1990; 335: 1-3. 3. Kato N, Ohkoshi S, Shimotohno K. Japanese isolates of the non-A, non-B hepatitis viral genome show sequence variations from the original isolate in the U.S.A. Proc Jpn Acad 1989; 65: 219-23. 4. Kaneko S, Feinstone SM, Miller RH. Rapid and sensitive method for the detection of serum hepatitis B virus DNA using polymease chain reaction technique. J Clin Microbiol 1989; 27: 1930-33. 5. Han JK, Shymala V, Richman KM, et al. Characterization of the terminal regions of hepatitis-C viral RNA: identification of conserved sequences in the 5’-untranslated region and poly (A) tails at the 3’ end. Proc Natl Acad Sci USA 1991; 88: 1711-15.
Propranolol in the prevention of ascites SIR,-Dr Perez-Ayuso and colleagues (June 15, p 1433) report a propranolol on rebleeding rates from severe portal hypertensive gastropathy and show that the frequency of encephalopathy was similar in both the treated and control groups (27% propranolol, 21% control). However, ascites developed in 53% of patients receiving placebo and in 23% of those taking propranolol (p < 0 05) during a mean follow-up of 21 months. In a previous randomised controlled trial of propranolol in the primary prevention of bleeding in patients with cirrhosis, we found similar results.1 Ascites, hepatic encephalopathy, and Child-Pugh scores were recorded at entry into the study and during follow-up. During a mean follow-up of 14 months among 230 patients, we observed beneficial effect of