501
readmitted for virus infection and for diarrhoea and vomiting, respectively. A third patient had neurological symptoms, and multiple sclerosis was diagnosed. The length of stay of these
patients was: Mean
length of stay in days (range) 2-4 (1-t) Vaginal Abdominal 2.8 (1--6) Thus the length of stay of these patients was little more than that claimed for LAVH patients, and the readmission rate does not Operation
Transbronchial biopsy showing the structure of vegetable fibre with polarising filters (haematoxylin and eosin,
X135). showed signs of peripheral neuropathy, but no serious neurological deficiencies. Chest radiography showed multiple spotted pulmonary infiltrations on the right upper and middle lobes.
Immunological, bacteriological, and serological tests were negative. Bronchoscopy was done, because he improved only slightly on antibiotics. Cytochemical and histological examination showed no signs of infection, vasculitis, or malignant disease, and bacteriological tests remained negative. Improvement of pulmonary infiltrations was obtained with intensive parenteral antibiotics, and the Cimino shunt was done. The patient insisted on diuretic treatment with ethacrynic acid and frusemide to delay haemodialysis. In January, 1991, he was readmitted because of progressive peripheral and pulmonary oedema, and haemodialysis was begun. Multiple pulmonary infiltrations in the right upper lobe were again found, which differed from previous findings in size and localisation. All serological indices remained negative; bronchoscopy was repeated, and control biopsies showed vegetable fibre with necrosis (figure). The patient then reported intensive abuse of snuff during the past months. After he stopped this, his radiographs improved rapidly. His lungs remained stable until August, 1991, when he died because of a heart attack after dialysis. Since snuffing is still common in central Europe, we think that this practice should be considered more often in aspiration pneumonia, especially in patients with reduced systemic or pulmonary defence mechanisms. F. HOPPICHLER M. LECHLEITNER P. KÖNIG
J. R. PATSCH Departments of Internal Medicine, Pathology, and Neurology, University Hospital Innsbruck, A-6020 Innsbruck, Austria
H. BRAUNSTEINER M. TÖTSCH G. LUEF
1. Balow JE. Nephrology forum: renal vasculitis. Kidney Int 1985, 27: 954-64. 2. Savage COS, Winearls CG, Jones S, Marshall PD. Prospective study of radiommunoassay for antibodies against neutrophil cytoplasm in the diagnosis of systemic vasculitis. Lancet 1987; ii: 1389-93 3. Goldblum SE, Reed WP. Host defenses and immunologic alterations associated with chronic hemodialysis. Ann Intern Med 1980; 93: 597-613.
Laparoscopically assisted vaginal hysterectomy SIR,-Your correspondents Dr Magos (Oct 26, p 1091), Mr Scrimgeour (Dec 7, p 1465), and Dr Fernandez (Jan 11, p 123) remark upon the advantages of laparoscopically assisted vaginal hysterectomy (LAVH) over traditional methods and draw attention to the shortened stay in hospital and therefore reduced costs. It has been my practice for over 25 years to encourage patients to go home early after operation, because I thought this to be in the interests of the
patient, and not for economical expediency. I have been prompted therefore to review my last 50 patients who had
hysterectomy. These patients were consecutive and unselected and the indication in all was symptoms related to uterine function and disease. Indications for abdominal hysterectomy were: pain (n = 5), uterine size (6), ovarian cyst (3), carcinoma (2), endometriosis (1), poor descent (1), and patient’s request (1). 2 patients were
No of patients 31 19
indicate that any patients were discharged prematurely. A major advantage in the orthodox method is the much shorter operating time and this factor alone should outweigh the advantages put forward for LAVH. Some of the abdominal hysterectomies (those in which pain was the indication for the abdominal route) could have been done vaginally if laparoscopy had been done before starting surgery, but the small difference in length of hospital stay would indicate that this was hardly worth while. St John’s
Hospital,
Chelmsford, Essex CM2 9BG, UK
G. L. S. RANKIN
Foscarnet for CMV retinitis SiR,—Your Dec 14 editorial was a thoughtful discussion of the foscamet-ganciclovir cytomegalovirus (CMV) retinitis trial in patients with AIDS. The trial was prematurely terminated despite efficacy for induction and maintenance therapy of CMV retinitis because of an apparent 4-month survival advantage in foscamettreated patients. This finding resulted in the distribution of a clinical alert from the US National Eye Instituted Your editorial offers several hypotheses to explain the observed survival advantage and discusses the confounding variable of possible differences in antiretroviral therapy between the two groups. Much more discussion of these key issues will probably take place when results of the trial are published. Two additional points deserve attention. The survival benefit found with foscamet was seen in a subgroup of patients with a predicted creatinine clearance (CrCI) of 1or more ml/min per kg. For patients with a predicted creatinine clearance of less than 1 ’2 ml/min per kg, a survival benefit was seen in ganciclovir treated patients. This modest 25% decrease in renal function is commonly seen in clinical practice, including in patients with AIDS. In addition, therapy with foscamet is substantially more expensive than treatment with ganciclovir. At my institution an induction course of 2-3 weeks with foscamet costs US$1694-2541 and maintenance therapy costs US$21900 per year. A similar induction course with ganciclovir costs US$840-1260 and maintenance therapy is US$10 950 per year. These cost figures include only acquisition cost and pharmacy expendables, and do not take into account labour or other expenses. Until more information is available, it would seem prudent to choose foscamet for the initial treatment of CMV retinitis only when the patient has relatively preserved renal function and would most likely benefit with prolonged survival. Patients with renal dysfunction should be treated with ganciclovir because of enhanced survival, in the context of a large cost differential between the two drugs. Department of Medicine, Hahnemann University, Philadelphia, Pennsylvania 19102, USA 1.
CRAIG A. WOOD
Kupfer C, Jabs D. Clinical alert to physicians and others who treat patients with AIDS. Bethesda: National Eye Institute, National Institutes of Health, October 17, 1991.
Need for second-generation anti-HCV testing in haemophilia SIR,-Dr Wan Chan and colleagues (Nov 30, p 1391) report the existence of more than one strain of hepatitis C virus (HCV). We have retested samples with two second-generation enzyme assays (Abbott, Innogenetics) from 35 patients with haemophilia who had already been tested by a first-generation assay (Ortho). All 14 samples originally positive for anti-HCV reacted positive with both
502
CLIN I CAL AND LABORATORY FINDINGS ON 8 SAMPLES FROM ANTI-C-100 NEGATIVE HAEMO PHI LIACS
CPH= chronic persistent hepatitis, CAH= chronic active hepatitis; NANBH =non -A, non-B hepatitis; NHT FVI I I= non -heat-treated factor Vlll *indeterminate RI BA and I nnogenetics LIA. P=posrtme, N= negative, I= indeterminate.
second-generation
assays;
however, 8 (38%) of the 21 first-
generation anti-HCV negative samples were positive on retesting. Confirmatory tests (Ortho recombinant immunoblot [RIBA], Innogenetics [line immunoassay, LIA]) on these 8 samples showed 3 to be indeterminate and 5 positive with the RIBA and 1 to be indeterminate and 7 positive with the LIA, 1 specimen being indeterminate in both tests (table). All 8 samples did not react with 5-1-1, C-100 (RIBA) and 7 did not react with NS4 (LIA) and so would be classified as HCV type 2 and 3 infections by Wan Chan et al. All samples reacted with core antigen bands in both tests. 4 of these patients had clinical or biopsy-proven chronic liver disease and 7 had received non-heat-treated factor VIII. Our results confirm the need to retest all patients with haemophilia with a second-generation test so that the prevalence and clinical relevance of this infection can be studied more accurately in this group.
We thank Dr E. 0. Caul (Bristol Public Health Laboratory Service) for anti-HCV confirmatory work. M.
JEAN GOODRICK
South Western Regional Transfusion Centre, Bristol BS10 5ND, UK
NICOLA A. B. ANDERSON IAN D. FRASER ANDREW ROUSE
G. KUDESIA S. CHAPMAN
Department of Public Health Medicine, Bristol and District Health Authority
Regional Haemophilia Centre, Royal Hallamshire Hospital, Sheffield
M. MAKRIS F. E. PRESTON
Department of Public Health Medicine,
SIR,-Dr MacLennan and colleagues (Jan 11, p 131) report a 46% frequency of intravenous drug use (IVDU) in their
both Ortho
19772 but 9 donors in our survey failed to exclude themselves on that criterion. Furthermore, there is a growing body of opinion that suggests that there should be no time limit on exclusion for those with a history of parenteral drug misuse, and our findings support that view. That 15 people were donating blood, having passed through the routine self-exclusion process, suggests that current procedures are inadequate or not properly enforced and that other high-risk blood donors might be being accepted also. The policy of self-exclusion needs to be re-evaluated and should extend to include anyone who has ever misused parenteral drugs.
Public Health Laboratory, Northern General Hospital, Sheffield S5 7AU, UK
History of previous drug misuse in HCV-positive blood donors
m
VIRGINIA PEARSON
Exeter
Department of Health. Guidelines for the blood transfusion services in the United Kingdom. London: Department of Health, 1989. 2. Department of Health Central Office of Information. AIDS leaflet (NBTS 1181B). June, 1990. 1.
Overexpression of p53 gene in head-and-neck cancer, linked with heavy smoking and drinking
preliminary investigation of the hepatitis C virus (HCV) seropositive donors in north London. In the south-west region of England in the first two months of testing, 31 936 donations were screened for antibodies to HCV (UBI-ELISA), confirmatory testing by radioimmunoblot assay (RIBA-2) being done at the Public Health Laboratory Service’s Bristol Laboratory. Donors whose samples were confirmed positive (25) or indeterminate positive (10) were contacted by letter and a counselling interview was arranged. The interviews were done in confidence. The carefully prepared questionnaire included the question "Have you ever injected substances under your skin or in a vein?". If the answer was "yes", the donor was then asked how long ago that was and
strong association between both p53 mutations and overexpression has been demonstrated in smoking-related lung cancers.4,5 We have investigated p53 expression in head-and-neck squamous cell carcinomas immunohistochemically, using the PAb 420 and 1801 antibodies.6 Since the normal p53 protein has a half-life of only 6-20
whether a shared needle had been used. Of the first 26 donors interviewed 8 were indeterminate positive (4 males) and 18 were confirmed positive (14 males). 15 of the 26 admitted to parenteral drug misuse (58%), 14 of these being confmmed positive by RIBA-2 (12 males); 1 female was indeterminate positive, with antibodies to C-22 on RIBA 2. All 15 had shared needles. 9 of the 15 (60%) admitted IVDU within the
may be inferred that detection of the p53 protein is synonymous with mutation, since the mutant form has a half-life of up to 6-8 h. We have found a correlation between smoking history and positive p53 staining. Six out of seven non-smokers with head-and-neck cancer did not express p53 whereas 29 of 37 heavy smokers had increased p53 expression.6 We have now investigated the relation between p53 expression and a history of smoking and
14 years. These findings are disturbing. The foundation of the UK national policy for ensuring safety of blood supplies has been self-exclusion of donors in high-risk groups/ However, specific questioning about IVDU has been limited to that advised in a leaflet prepared for donors by the Department of Health; the current version (June, 1990) excludes those who have injected drugs since
drinking. 48 patients with squamous cell carcinoma of the head and neck were classified as non-smoker, moderate smoker ( < 20 cigarettes per day), or heavy smoker and as non-drinker, moderate drinker
previous
SiR,—Mutations in the p53 gene are proving to be one of the genetic changes in human cancer.1,2 Normal levels of p53 act as tumour suppressor genes, but mutations in the p53 gene commonest
can convert
it into
a
dominant and no
longer suppressive gene.3 A
min, it
( < 21 units per week), or heavy drinker. No correlation was found between p53 expression and any clinicopathological features. We used weighted logistic regression analysis to look for a relation
readmitted for virus infection and for diarrhoea and vomiting, respectively. A third patient had neurological symptoms, and multiple sclerosis was diagnosed. The length of stay of these
patients was: Mean
length of stay in days (range) 2-4 (1-t) Vaginal Abdominal 2.8 (1--6) Thus the length of stay of these patients was little more than that claimed for LAVH patients, and the readmission rate does not Operation
Transbronchial biopsy showing the structure of vegetable fibre with polarising filters (haematoxylin and eosin,
X135). showed signs of peripheral neuropathy, but no serious neurological deficiencies. Chest radiography showed multiple spotted pulmonary infiltrations on the right upper and middle lobes.
Immunological, bacteriological, and serological tests were negative. Bronchoscopy was done, because he improved only slightly on antibiotics. Cytochemical and histological examination showed no signs of infection, vasculitis, or malignant disease, and bacteriological tests remained negative. Improvement of pulmonary infiltrations was obtained with intensive parenteral antibiotics, and the Cimino shunt was done. The patient insisted on diuretic treatment with ethacrynic acid and frusemide to delay haemodialysis. In January, 1991, he was readmitted because of progressive peripheral and pulmonary oedema, and haemodialysis was begun. Multiple pulmonary infiltrations in the right upper lobe were again found, which differed from previous findings in size and localisation. All serological indices remained negative; bronchoscopy was repeated, and control biopsies showed vegetable fibre with necrosis (figure). The patient then reported intensive abuse of snuff during the past months. After he stopped this, his radiographs improved rapidly. His lungs remained stable until August, 1991, when he died because of a heart attack after dialysis. Since snuffing is still common in central Europe, we think that this practice should be considered more often in aspiration pneumonia, especially in patients with reduced systemic or pulmonary defence mechanisms. F. HOPPICHLER M. LECHLEITNER P. KÖNIG
J. R. PATSCH Departments of Internal Medicine, Pathology, and Neurology, University Hospital Innsbruck, A-6020 Innsbruck, Austria
H. BRAUNSTEINER M. TÖTSCH G. LUEF
1. Balow JE. Nephrology forum: renal vasculitis. Kidney Int 1985, 27: 954-64. 2. Savage COS, Winearls CG, Jones S, Marshall PD. Prospective study of radiommunoassay for antibodies against neutrophil cytoplasm in the diagnosis of systemic vasculitis. Lancet 1987; ii: 1389-93 3. Goldblum SE, Reed WP. Host defenses and immunologic alterations associated with chronic hemodialysis. Ann Intern Med 1980; 93: 597-613.
Laparoscopically assisted vaginal hysterectomy SIR,-Your correspondents Dr Magos (Oct 26, p 1091), Mr Scrimgeour (Dec 7, p 1465), and Dr Fernandez (Jan 11, p 123) remark upon the advantages of laparoscopically assisted vaginal hysterectomy (LAVH) over traditional methods and draw attention to the shortened stay in hospital and therefore reduced costs. It has been my practice for over 25 years to encourage patients to go home early after operation, because I thought this to be in the interests of the
patient, and not for economical expediency. I have been prompted therefore to review my last 50 patients who had
hysterectomy. These patients were consecutive and unselected and the indication in all was symptoms related to uterine function and disease. Indications for abdominal hysterectomy were: pain (n = 5), uterine size (6), ovarian cyst (3), carcinoma (2), endometriosis (1), poor descent (1), and patient’s request (1). 2 patients were
No of patients 31 19
indicate that any patients were discharged prematurely. A major advantage in the orthodox method is the much shorter operating time and this factor alone should outweigh the advantages put forward for LAVH. Some of the abdominal hysterectomies (those in which pain was the indication for the abdominal route) could have been done vaginally if laparoscopy had been done before starting surgery, but the small difference in length of hospital stay would indicate that this was hardly worth while. St John’s
Hospital,
Chelmsford, Essex CM2 9BG, UK
G. L. S. RANKIN
Foscarnet for CMV retinitis SiR,—Your Dec 14 editorial was a thoughtful discussion of the foscamet-ganciclovir cytomegalovirus (CMV) retinitis trial in patients with AIDS. The trial was prematurely terminated despite efficacy for induction and maintenance therapy of CMV retinitis because of an apparent 4-month survival advantage in foscamettreated patients. This finding resulted in the distribution of a clinical alert from the US National Eye Instituted Your editorial offers several hypotheses to explain the observed survival advantage and discusses the confounding variable of possible differences in antiretroviral therapy between the two groups. Much more discussion of these key issues will probably take place when results of the trial are published. Two additional points deserve attention. The survival benefit found with foscamet was seen in a subgroup of patients with a predicted creatinine clearance (CrCI) of 1or more ml/min per kg. For patients with a predicted creatinine clearance of less than 1 ’2 ml/min per kg, a survival benefit was seen in ganciclovir treated patients. This modest 25% decrease in renal function is commonly seen in clinical practice, including in patients with AIDS. In addition, therapy with foscamet is substantially more expensive than treatment with ganciclovir. At my institution an induction course of 2-3 weeks with foscamet costs US$1694-2541 and maintenance therapy costs US$21900 per year. A similar induction course with ganciclovir costs US$840-1260 and maintenance therapy is US$10 950 per year. These cost figures include only acquisition cost and pharmacy expendables, and do not take into account labour or other expenses. Until more information is available, it would seem prudent to choose foscamet for the initial treatment of CMV retinitis only when the patient has relatively preserved renal function and would most likely benefit with prolonged survival. Patients with renal dysfunction should be treated with ganciclovir because of enhanced survival, in the context of a large cost differential between the two drugs. Department of Medicine, Hahnemann University, Philadelphia, Pennsylvania 19102, USA 1.
CRAIG A. WOOD
Kupfer C, Jabs D. Clinical alert to physicians and others who treat patients with AIDS. Bethesda: National Eye Institute, National Institutes of Health, October 17, 1991.
Need for second-generation anti-HCV testing in haemophilia SIR,-Dr Wan Chan and colleagues (Nov 30, p 1391) report the existence of more than one strain of hepatitis C virus (HCV). We have retested samples with two second-generation enzyme assays (Abbott, Innogenetics) from 35 patients with haemophilia who had already been tested by a first-generation assay (Ortho). All 14 samples originally positive for anti-HCV reacted positive with both
502
CLIN I CAL AND LABORATORY FINDINGS ON 8 SAMPLES FROM ANTI-C-100 NEGATIVE HAEMO PHI LIACS
CPH= chronic persistent hepatitis, CAH= chronic active hepatitis; NANBH =non -A, non-B hepatitis; NHT FVI I I= non -heat-treated factor Vlll *indeterminate RI BA and I nnogenetics LIA. P=posrtme, N= negative, I= indeterminate.
second-generation
assays;
however, 8 (38%) of the 21 first-
generation anti-HCV negative samples were positive on retesting. Confirmatory tests (Ortho recombinant immunoblot [RIBA], Innogenetics [line immunoassay, LIA]) on these 8 samples showed 3 to be indeterminate and 5 positive with the RIBA and 1 to be indeterminate and 7 positive with the LIA, 1 specimen being indeterminate in both tests (table). All 8 samples did not react with 5-1-1, C-100 (RIBA) and 7 did not react with NS4 (LIA) and so would be classified as HCV type 2 and 3 infections by Wan Chan et al. All samples reacted with core antigen bands in both tests. 4 of these patients had clinical or biopsy-proven chronic liver disease and 7 had received non-heat-treated factor VIII. Our results confirm the need to retest all patients with haemophilia with a second-generation test so that the prevalence and clinical relevance of this infection can be studied more accurately in this group.
We thank Dr E. 0. Caul (Bristol Public Health Laboratory Service) for anti-HCV confirmatory work. M.
JEAN GOODRICK
South Western Regional Transfusion Centre, Bristol BS10 5ND, UK
NICOLA A. B. ANDERSON IAN D. FRASER ANDREW ROUSE
G. KUDESIA S. CHAPMAN
Department of Public Health Medicine, Bristol and District Health Authority
Regional Haemophilia Centre, Royal Hallamshire Hospital, Sheffield
M. MAKRIS F. E. PRESTON
Department of Public Health Medicine,
SIR,-Dr MacLennan and colleagues (Jan 11, p 131) report a 46% frequency of intravenous drug use (IVDU) in their
both Ortho
19772 but 9 donors in our survey failed to exclude themselves on that criterion. Furthermore, there is a growing body of opinion that suggests that there should be no time limit on exclusion for those with a history of parenteral drug misuse, and our findings support that view. That 15 people were donating blood, having passed through the routine self-exclusion process, suggests that current procedures are inadequate or not properly enforced and that other high-risk blood donors might be being accepted also. The policy of self-exclusion needs to be re-evaluated and should extend to include anyone who has ever misused parenteral drugs.
Public Health Laboratory, Northern General Hospital, Sheffield S5 7AU, UK
History of previous drug misuse in HCV-positive blood donors
m
VIRGINIA PEARSON
Exeter
Department of Health. Guidelines for the blood transfusion services in the United Kingdom. London: Department of Health, 1989. 2. Department of Health Central Office of Information. AIDS leaflet (NBTS 1181B). June, 1990. 1.
Overexpression of p53 gene in head-and-neck cancer, linked with heavy smoking and drinking
preliminary investigation of the hepatitis C virus (HCV) seropositive donors in north London. In the south-west region of England in the first two months of testing, 31 936 donations were screened for antibodies to HCV (UBI-ELISA), confirmatory testing by radioimmunoblot assay (RIBA-2) being done at the Public Health Laboratory Service’s Bristol Laboratory. Donors whose samples were confirmed positive (25) or indeterminate positive (10) were contacted by letter and a counselling interview was arranged. The interviews were done in confidence. The carefully prepared questionnaire included the question "Have you ever injected substances under your skin or in a vein?". If the answer was "yes", the donor was then asked how long ago that was and
strong association between both p53 mutations and overexpression has been demonstrated in smoking-related lung cancers.4,5 We have investigated p53 expression in head-and-neck squamous cell carcinomas immunohistochemically, using the PAb 420 and 1801 antibodies.6 Since the normal p53 protein has a half-life of only 6-20
whether a shared needle had been used. Of the first 26 donors interviewed 8 were indeterminate positive (4 males) and 18 were confirmed positive (14 males). 15 of the 26 admitted to parenteral drug misuse (58%), 14 of these being confmmed positive by RIBA-2 (12 males); 1 female was indeterminate positive, with antibodies to C-22 on RIBA 2. All 15 had shared needles. 9 of the 15 (60%) admitted IVDU within the
may be inferred that detection of the p53 protein is synonymous with mutation, since the mutant form has a half-life of up to 6-8 h. We have found a correlation between smoking history and positive p53 staining. Six out of seven non-smokers with head-and-neck cancer did not express p53 whereas 29 of 37 heavy smokers had increased p53 expression.6 We have now investigated the relation between p53 expression and a history of smoking and
14 years. These findings are disturbing. The foundation of the UK national policy for ensuring safety of blood supplies has been self-exclusion of donors in high-risk groups/ However, specific questioning about IVDU has been limited to that advised in a leaflet prepared for donors by the Department of Health; the current version (June, 1990) excludes those who have injected drugs since
drinking. 48 patients with squamous cell carcinoma of the head and neck were classified as non-smoker, moderate smoker ( < 20 cigarettes per day), or heavy smoker and as non-drinker, moderate drinker
previous
SiR,—Mutations in the p53 gene are proving to be one of the genetic changes in human cancer.1,2 Normal levels of p53 act as tumour suppressor genes, but mutations in the p53 gene commonest
can convert
it into
a
dominant and no
longer suppressive gene.3 A
min, it
( < 21 units per week), or heavy drinker. No correlation was found between p53 expression and any clinicopathological features. We used weighted logistic regression analysis to look for a relation
