1039
EFFECT OF NITRIC OXIDE (NO, 10 ppm) DURING HAND VENTILATION
anti-HCV was a recombinant enzyme-linked immunosorbent assay (ELISA), and positive tests were confirmed by recombinant immunoblot assay (RIBA) (both Ortho, 2nd generation). HCVRNA was detected by polymerase chain reaction with a pair of primers at the 5’ non-coding region. All the patients seroconverted to anti-HCV during the first month post-transplantation. At the end of the sixth month, all patients were no longer reactive for anti-HCV. Throughout follow-up no patients had biochemical or clinical signs of HCV infection. HCV-RNA was not detectable in the final sample of serum of the 8 patients followed-up for a year. To assess the potential hazards of IVIG administered for prophylaxis, different lots of three different brands were tested for anti-HCV reactivity and HCV-RNA. All different lots of IVIG were positive for anti-HCV (ELISA and RIBA) but HCV-RNA was
I
I
I
I
PCV 28 cm HzO of mspiratory pressure with 8 cm HzO of PEEP, I/E ratio 1/1, respiratory rate 32/m!n FIOz’ 0 7 throughout 75 mm of study Hand ventilation to maintain end-tidal CO;, at 40 kPa
condition, we studied the effect of withdrawing the nitric oxide during a period of hand ventilation (table). Cardiac output was measured by thermodilution and oxyhaemoglobin concentration by laboratory co-oximetry. Falke’s group have described the successful use of inhaled nitric oxide in the management of 10 patients with ARDS.l Others, including ourselves, now use nitric oxide to improve arterial oxygenation and lower pulmonary artery pressure in patients with severe acute lung injury.2 Nevertheless, there is no evidence that nitric oxide on its own improves outcome in this condition and there is potential toxicity. Although our results suggest that nitric oxide may enable physiotherapy to be done in some patients who desaturate to dangerously low levels when otherwise handventilated, we emphasise that it is imperative to measure accurately the concentration of nitric oxide at all times.
negative.
These findings suggest that anti-HCV seroconversion was caused by the passive transfer of anti-HCV contained in IVIG. The absence of transmission of HCV is probably due to viral inactivation during fractionation and manufacture. Anti-HCV-positive IVIG prepared with standard methods can be safely given for prophylaxis of infections in heart-transplant recipients. There may be a therapeutically active effect against the virus by anti-HCV contained in these perparations.
Academic Department of Cardiac Surgery, Clinical Microbiology Laboratory, and Department of Gastroenterology,
Ospedale Molinette, 10126 Turin, Italy
ENRICO DONEGANI MICHELE DI SUMMA MARCO BOBBIO VALERIA GHISETTI GIOVANNA MARCHIARO MARIO RIZZETTO FERRUCCIO BONINO
1. Horst H-A, Schmitz N, Glinike C, et al. Seroconversion for hepatitis C virus antibody in bone marrow recipients treated with immune globulin. N Engl J Med 1991; 325:
132-33.
Quinti I, Paganelli R, Scala E, et al. Hepatitis C virus antibodies in gammaglobulin. Lancet 1990; 336: 1377. 3. Finlayson JS, Tankersley DL. Anti-HCV screening and plasma fractionation: the case against. Lancet 1990; 335: 1274-75. 4. Schiff P, Kemp A. Safety of IVIG made from HCV-antibody-screened plasma. 2.
Department of Intensive Care, Guy’s Hospital, London SE1 9RT, UK
ROBERT GROVER IAN MURDOCH MARK SMITHIES IMOGEN MITCHELL DAVID BIHARI
1. Rossaint R, Falke K, Keitel M, et al. Inhaled nitric oxide in severe ARDS. Proceedings of 9th National Congress, Italian Society of Intensive Therapy, Milan, 1992: 109-10. 2. Grover R, Bihari D. Acute pulmonary hypertension in the critically ill. Resp Med (in
press). 3. Foubert L, Fleming B, Latimer R, et al. 1992; 339: 1615-16.
Safety guidelines for use of nitric oxide. Lancet
Safety of anti-HCV-reactive immunoglobulin in heart transplant patients SIR,-Preparations of intravenous immunoglobulin (IVIG) used for prophylaxis of infections are frequently reactive for antibody to hepatitis C virus (HCV).1 It has been argued 3,1 that such antibody may be important in the prevention of HCV transmission and should not be omitted from source plasma pools until demonstration that the safety of IVIG is not compromised. Others’ have suggested that, since anti-HCV is a marker of infectivity, all anti-HCV-positive donors should be excluded from fractionation pools. The aim of our study was to verify the safety of IVIG used for prophylaxis in heart transplant patients, who are at particular risk of infectious diseases. 27 patients, transplanted between April, 1990, and December, 1991 (mean age 47-3), were screened for anti-HCV seroconversion from the day of transplantation. The follow-up for 18 patients was at least 1 year, whereas for the other 9 it ranged from 6 to 12 months. Before heart transplantation all patients were negative for antiHCV. The immunosuppresive protocol was: cyclosporin from the 2nd day post-transplantation, azathioprine, steroids, and antithymocyte globulin. Patients were treated with IVIG 200 mg/kg per day (Immuno, Sandoz, Sclavo) on days 1-3 and 14-16. Blood samples were obtained during months 1, 3-6, 9, 12, and 24, and tested for anti-HCV. The final serum samples of 8 patients of 18 who completed 1 year offollow-up were tested for HCV-RNA. The
Lancet 1991; 338: 1076. 5. Habibi B, Garretta M. Screening for hepatitis C virus fractionation. Lancet 1990; 335: 855-56.
antibody in plasma for
Atheroembolism in HIV-positive individuals SIR,-Dr Tabib and colleagues’ report (Sept 19, p 730) of a possible association between coronary atherosclerosis and HIV infection in 8 young men, prompts us to report briefly on 4 cases of atheroembolism of the legs seen in our two hospitals between 1987 and 1991. The table shows the main features of the patients. All 4 patients were men at various stages of HIV infection. The diagnosis of distal embolism to the leg arteries-not so common an event in the course of arteriosclerosis obliterans-was clinically obvious in all patients. That the source of emboli was an ulcerated atherosclerotic plaque was certain in 2 patients with histological proof (1 and 2, in whom severe ischaemia needed arterial surgery to avoid further emboli), almost certain in patient 3 with an irregular popliteal plaque at angiography, and probably so in patient 4 with a heterogeneous highly stenotic plaque of the lower superficial femoral artery on duplex scanning. In the 2 patients with histological examinations, the features of the culprit lesions were: in patient 1, several large ulcerated plaques of the lower abdominal aorta with thrombosis and moderate mononuclear infiltration of media and adventitia (surrounding vasa vasorum); and in patient 2, ulcerated plaque of popliteal artery with calcification, a rich network of new vessels, and foam cells in the media. These observations in 4 fairly young men suggest that there is a link between HIV infection and the occurrence of complicated atherosclerosis with ulceration, thrombosis, and distal embolism. Plaque ulceration is a key event in the evolution of atherosclerosis, provoking acute ischaemic symptoms and contributing to the progression of lesions.’ The mechanisms of ulceration remain incompletely understood; haemodynamicz and inflammatory33 influences may contribute to plaque rupture. Immunological disturbances4 and viral infection5 are both suspected to play a part in
1040
PATIENTS’ DETAILS
CDC= Centers for Disease Control, CMV=cytomegalovirus ND=notdone +=positive, --negative.
development of atherosclerosis, and offer clues for understanding a possible association between HIV infection and aggravated atherosclerosis. Aortic tissue from patient 1 has been examined histologically without detection of obvious signs of continuing viral infection (especially by cytomegalovirus). We would be glad to provide samples frozen in nitrogen to interested investigators (apply to L. C.). Such tissues could be useful to explore further the inflammatory components6 of atherosclerosis. the
of Vascular Medicine,
Department and Pathological Anatomy Laboratory, Hôpital Broussais, 75674 Paris, France, and Department of Vascular Hôpital Saint-Joseph, Paris
Surgery,
LOÏC CAPRON YONG-UN KIM CLAUDE LAURIAN PATRICK BRUNEVAL JEAN-NOEL FIESSINGER
1. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of
2.
3.
4. 5.
6.
coronary artery disease and the acute coronary syndromes. N Engl J Med 1992; 326: 242-50, 310-18. Richardson PD, Davies MJ, Born GVR. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet 1989; ii: 941-44. Henney AM, Wakeley PR, Davies MJ, et al. Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization. Proc Natl Acad Sci USA 1991; 88: 8154-58. Libby P, Hansson G. Involvement of the immune system m human atherogenesis: current knowledge and unanswered questions. Lab Invest 1991; 64: 5-15. Hajjar DP. Viral pathogenesis of atherosclerosis: impact of molecular mimicry and viral genes. Am J Pathol 1991; 139: 1195-211. Capron L. Mécanismes inflammatoires de l’athérosclérose inférences pathogéniques et étiologiques. Arch Mal Coeur (in press).
Topical trifluridine for mucocutaneous acyclovir-resistant herpes simplex II in AIDS patient SiR,—Acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infections are increasingly frequent in patients with advanced HIV disease. 1-3 Treatment requires intravenous foscamet/,3 preferably via a central venous catheter. Foscamet has several potentially serious side-effects, including renal impairment, granulocytopenia, and metabolic disturbances. Acyclovir-resistant mucocutaneous HSV infection has been successfully treated with topical trifluridine in patients with AIDS in the USA. We describe similar success in the UK. A 28-year-old man attending our unit with AIDS had a 2 year history of recurrent perianal HSV II infection that responded to standard oral acyclovir. In March, 1992, he developed persistent perianal ulceration unresponsive to acyclovir. He was profoundly immunosuppressed (CD4 20 x 10/1). Acyclovir-resistant HSV II was isolated on cell culture (PHLS, Leeds). Foscamet 40 mg/kg three times daily was started and re-epithelialisation of the ulcerated lesions occurred within 2 weeks. He had a second episode of acyclovir-resistant HSV II infection in May, 1992, again successfully treated with foscamet. In August, 1992, he again had perianal ulceration from which acyclovir-resistant HSV II was isolated. On this occasion topical trifluridine 1 % ophthalmic solution was applied twice daily, with a dressing soaked in solution, for 3 weeks. Within 10 days his pain had improved. By 14 days the ulcer was smaller and at 3 weeks had fully re-epithelialised. Although trifluridine ophthalmic solution is not licensed for use in the UK, it has been used in the treatment of herpes keratitis in the USA since the early 1970s.5 The drug is a pyrimidine nucleoside (5-trifluoromethyl-2’-deoxyuridine), structurally related to idoxuridine. Its mechanism of action seems to be by thymidine
during viral DNA replication and inhibition of thymidylate synthetase.1 Strains of acyclovir-resistant HSV are highly sensitive in vitro to this agent? Although an allergic contact dermatitis from trifluridine in eyedrops has been reported,8 topical treatment is well tolerated. Patients may experience a mild burning sensation after application. substitution
Department of Genitourinary Medicine, Leeds General Infirmary, Leeds LS1 3EX, UK, Pharmacy Department, Leeds General Infirmary, and Public Health Laboratory Services, Leeds LS1 7TR 1.
M. MURPHY A. MORLEY R. P. EGLIN E. MONTEIRO
Elrich KS, Mills J, Chatis P, et al Acyclovir-resistant herpes simplex virus infection in patients with the acquired immunodeficiency syndrome. N Engl J Med 1989; 320: 293-96.
2. Charts
PA, Miller CH, Schrager LE, et al. Successful treatment with foscamet of an acyclovir-resistant mucocutaneous infection with herpes simplex virus infection in a patient with acquired immunodeficiency syndrome. N Engl J Med 1989; 320: 297-300.
3. Safrin
S, Assaykeen T, Follansbee S, et al. Foscarnet therapy for acyclovir-resistant herpes simplex virus infection in 26 patients, preliminary data. J Infect Dis 1990; 161: 1078-84. 4 Kessler H, Weaver D, Benson C, et al. ACTG 172 treatment of acyclovir-resistant (ACV-R) mucocutaneous herpes simplex virus (HSV) infection in patients with AIDS: open label pilot study of topical trifluridine (TFT). 8th international conference on AIDS, Amsterdam, Holland. July 19-24, 1992: abstr WeB 1056. 5. Wellmgs PC, Awdry PN, Bors FH, et al. Clinical evaluation of trifluorothymidine in the treatment of herpes simplex corneal ulcers. Am J Ophthalmol 1972; 73: 932-42. 6. Heidleberger C, Parsons DG, Remy DC. Synthesis of 5-trimethyluracil and 5-trifluoromethyl-2’ deoxyuridine. J Am Chem Soc 1962; 84: 3597-98 7. Pottage J, Kessler H, Kapell K, Benson C. Acyclovir resistant (ACV-R) herpes simplex. susceptibility to alternative antiviral agents. 8th international conference on AIDS, Amsterdam, Holland. July 19-24, 1992: abstr PoB 3238 8. Millan-Parrilla F, de la Cuadra J. Allergic contact dermatitis from trifluridine in eyedrops. Contact Dermatitis 1990; 22: 289. mucocutaneous
Acceptability of screening for HIV seroprevalence in women with cervical pathology SiR,—There are many reports of an increased prevalence of cervical intraepithelial neoplasia (CIN) in women infected with HIV compared with well-matched controls.’,’ Women attending colposcopy clinics may represent a group with a high HIV seroprevalence rate. This was highlighted by Maiman et aP who reported a seroprevalence rate in a New York colposcopy clinic three times greater than that in the local sexually transmitted diseases clinic and five times higher than that in the antenatal clinic in the same area. This fmding not only has implications for staff in these clinics but also raises the question of whether HIV testing should be offered to women attending colposcopy clinics. We evaluated the acceptability of offering routine HIV antibody testing in the colposcopy clinics of a local teaching hospital. All women between the ages of 18 and 50 who were attending the clinic for management of an abnormal cervical smear were asked to participate. The investigator completed a short risk-analysis questionnaire with each patient. Pretest HIV counselling was given to all patients and HIV testing was offered. All patients were given follow-up appointments for post-test counselling with the same interviewer. 100 consecutive women took part. 60 accepted HIV testing. All results were HIV antibody negative. The groups who accepted and those who declined were similar (table). In the 40 who declined a test, the reasons given were: scared of positive result (16), not at risk (7), already had negative test (4), does not like blood test (3), just
EFFECT OF NITRIC OXIDE (NO, 10 ppm) DURING HAND VENTILATION
anti-HCV was a recombinant enzyme-linked immunosorbent assay (ELISA), and positive tests were confirmed by recombinant immunoblot assay (RIBA) (both Ortho, 2nd generation). HCVRNA was detected by polymerase chain reaction with a pair of primers at the 5’ non-coding region. All the patients seroconverted to anti-HCV during the first month post-transplantation. At the end of the sixth month, all patients were no longer reactive for anti-HCV. Throughout follow-up no patients had biochemical or clinical signs of HCV infection. HCV-RNA was not detectable in the final sample of serum of the 8 patients followed-up for a year. To assess the potential hazards of IVIG administered for prophylaxis, different lots of three different brands were tested for anti-HCV reactivity and HCV-RNA. All different lots of IVIG were positive for anti-HCV (ELISA and RIBA) but HCV-RNA was
I
I
I
I
PCV 28 cm HzO of mspiratory pressure with 8 cm HzO of PEEP, I/E ratio 1/1, respiratory rate 32/m!n FIOz’ 0 7 throughout 75 mm of study Hand ventilation to maintain end-tidal CO;, at 40 kPa
condition, we studied the effect of withdrawing the nitric oxide during a period of hand ventilation (table). Cardiac output was measured by thermodilution and oxyhaemoglobin concentration by laboratory co-oximetry. Falke’s group have described the successful use of inhaled nitric oxide in the management of 10 patients with ARDS.l Others, including ourselves, now use nitric oxide to improve arterial oxygenation and lower pulmonary artery pressure in patients with severe acute lung injury.2 Nevertheless, there is no evidence that nitric oxide on its own improves outcome in this condition and there is potential toxicity. Although our results suggest that nitric oxide may enable physiotherapy to be done in some patients who desaturate to dangerously low levels when otherwise handventilated, we emphasise that it is imperative to measure accurately the concentration of nitric oxide at all times.
negative.
These findings suggest that anti-HCV seroconversion was caused by the passive transfer of anti-HCV contained in IVIG. The absence of transmission of HCV is probably due to viral inactivation during fractionation and manufacture. Anti-HCV-positive IVIG prepared with standard methods can be safely given for prophylaxis of infections in heart-transplant recipients. There may be a therapeutically active effect against the virus by anti-HCV contained in these perparations.
Academic Department of Cardiac Surgery, Clinical Microbiology Laboratory, and Department of Gastroenterology,
Ospedale Molinette, 10126 Turin, Italy
ENRICO DONEGANI MICHELE DI SUMMA MARCO BOBBIO VALERIA GHISETTI GIOVANNA MARCHIARO MARIO RIZZETTO FERRUCCIO BONINO
1. Horst H-A, Schmitz N, Glinike C, et al. Seroconversion for hepatitis C virus antibody in bone marrow recipients treated with immune globulin. N Engl J Med 1991; 325:
132-33.
Quinti I, Paganelli R, Scala E, et al. Hepatitis C virus antibodies in gammaglobulin. Lancet 1990; 336: 1377. 3. Finlayson JS, Tankersley DL. Anti-HCV screening and plasma fractionation: the case against. Lancet 1990; 335: 1274-75. 4. Schiff P, Kemp A. Safety of IVIG made from HCV-antibody-screened plasma. 2.
Department of Intensive Care, Guy’s Hospital, London SE1 9RT, UK
ROBERT GROVER IAN MURDOCH MARK SMITHIES IMOGEN MITCHELL DAVID BIHARI
1. Rossaint R, Falke K, Keitel M, et al. Inhaled nitric oxide in severe ARDS. Proceedings of 9th National Congress, Italian Society of Intensive Therapy, Milan, 1992: 109-10. 2. Grover R, Bihari D. Acute pulmonary hypertension in the critically ill. Resp Med (in
press). 3. Foubert L, Fleming B, Latimer R, et al. 1992; 339: 1615-16.
Safety guidelines for use of nitric oxide. Lancet
Safety of anti-HCV-reactive immunoglobulin in heart transplant patients SIR,-Preparations of intravenous immunoglobulin (IVIG) used for prophylaxis of infections are frequently reactive for antibody to hepatitis C virus (HCV).1 It has been argued 3,1 that such antibody may be important in the prevention of HCV transmission and should not be omitted from source plasma pools until demonstration that the safety of IVIG is not compromised. Others’ have suggested that, since anti-HCV is a marker of infectivity, all anti-HCV-positive donors should be excluded from fractionation pools. The aim of our study was to verify the safety of IVIG used for prophylaxis in heart transplant patients, who are at particular risk of infectious diseases. 27 patients, transplanted between April, 1990, and December, 1991 (mean age 47-3), were screened for anti-HCV seroconversion from the day of transplantation. The follow-up for 18 patients was at least 1 year, whereas for the other 9 it ranged from 6 to 12 months. Before heart transplantation all patients were negative for antiHCV. The immunosuppresive protocol was: cyclosporin from the 2nd day post-transplantation, azathioprine, steroids, and antithymocyte globulin. Patients were treated with IVIG 200 mg/kg per day (Immuno, Sandoz, Sclavo) on days 1-3 and 14-16. Blood samples were obtained during months 1, 3-6, 9, 12, and 24, and tested for anti-HCV. The final serum samples of 8 patients of 18 who completed 1 year offollow-up were tested for HCV-RNA. The
Lancet 1991; 338: 1076. 5. Habibi B, Garretta M. Screening for hepatitis C virus fractionation. Lancet 1990; 335: 855-56.
antibody in plasma for
Atheroembolism in HIV-positive individuals SIR,-Dr Tabib and colleagues’ report (Sept 19, p 730) of a possible association between coronary atherosclerosis and HIV infection in 8 young men, prompts us to report briefly on 4 cases of atheroembolism of the legs seen in our two hospitals between 1987 and 1991. The table shows the main features of the patients. All 4 patients were men at various stages of HIV infection. The diagnosis of distal embolism to the leg arteries-not so common an event in the course of arteriosclerosis obliterans-was clinically obvious in all patients. That the source of emboli was an ulcerated atherosclerotic plaque was certain in 2 patients with histological proof (1 and 2, in whom severe ischaemia needed arterial surgery to avoid further emboli), almost certain in patient 3 with an irregular popliteal plaque at angiography, and probably so in patient 4 with a heterogeneous highly stenotic plaque of the lower superficial femoral artery on duplex scanning. In the 2 patients with histological examinations, the features of the culprit lesions were: in patient 1, several large ulcerated plaques of the lower abdominal aorta with thrombosis and moderate mononuclear infiltration of media and adventitia (surrounding vasa vasorum); and in patient 2, ulcerated plaque of popliteal artery with calcification, a rich network of new vessels, and foam cells in the media. These observations in 4 fairly young men suggest that there is a link between HIV infection and the occurrence of complicated atherosclerosis with ulceration, thrombosis, and distal embolism. Plaque ulceration is a key event in the evolution of atherosclerosis, provoking acute ischaemic symptoms and contributing to the progression of lesions.’ The mechanisms of ulceration remain incompletely understood; haemodynamicz and inflammatory33 influences may contribute to plaque rupture. Immunological disturbances4 and viral infection5 are both suspected to play a part in
1040
PATIENTS’ DETAILS
CDC= Centers for Disease Control, CMV=cytomegalovirus ND=notdone +=positive, --negative.
development of atherosclerosis, and offer clues for understanding a possible association between HIV infection and aggravated atherosclerosis. Aortic tissue from patient 1 has been examined histologically without detection of obvious signs of continuing viral infection (especially by cytomegalovirus). We would be glad to provide samples frozen in nitrogen to interested investigators (apply to L. C.). Such tissues could be useful to explore further the inflammatory components6 of atherosclerosis. the
of Vascular Medicine,
Department and Pathological Anatomy Laboratory, Hôpital Broussais, 75674 Paris, France, and Department of Vascular Hôpital Saint-Joseph, Paris
Surgery,
LOÏC CAPRON YONG-UN KIM CLAUDE LAURIAN PATRICK BRUNEVAL JEAN-NOEL FIESSINGER
1. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of
2.
3.
4. 5.
6.
coronary artery disease and the acute coronary syndromes. N Engl J Med 1992; 326: 242-50, 310-18. Richardson PD, Davies MJ, Born GVR. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet 1989; ii: 941-44. Henney AM, Wakeley PR, Davies MJ, et al. Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization. Proc Natl Acad Sci USA 1991; 88: 8154-58. Libby P, Hansson G. Involvement of the immune system m human atherogenesis: current knowledge and unanswered questions. Lab Invest 1991; 64: 5-15. Hajjar DP. Viral pathogenesis of atherosclerosis: impact of molecular mimicry and viral genes. Am J Pathol 1991; 139: 1195-211. Capron L. Mécanismes inflammatoires de l’athérosclérose inférences pathogéniques et étiologiques. Arch Mal Coeur (in press).
Topical trifluridine for mucocutaneous acyclovir-resistant herpes simplex II in AIDS patient SiR,—Acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infections are increasingly frequent in patients with advanced HIV disease. 1-3 Treatment requires intravenous foscamet/,3 preferably via a central venous catheter. Foscamet has several potentially serious side-effects, including renal impairment, granulocytopenia, and metabolic disturbances. Acyclovir-resistant mucocutaneous HSV infection has been successfully treated with topical trifluridine in patients with AIDS in the USA. We describe similar success in the UK. A 28-year-old man attending our unit with AIDS had a 2 year history of recurrent perianal HSV II infection that responded to standard oral acyclovir. In March, 1992, he developed persistent perianal ulceration unresponsive to acyclovir. He was profoundly immunosuppressed (CD4 20 x 10/1). Acyclovir-resistant HSV II was isolated on cell culture (PHLS, Leeds). Foscamet 40 mg/kg three times daily was started and re-epithelialisation of the ulcerated lesions occurred within 2 weeks. He had a second episode of acyclovir-resistant HSV II infection in May, 1992, again successfully treated with foscamet. In August, 1992, he again had perianal ulceration from which acyclovir-resistant HSV II was isolated. On this occasion topical trifluridine 1 % ophthalmic solution was applied twice daily, with a dressing soaked in solution, for 3 weeks. Within 10 days his pain had improved. By 14 days the ulcer was smaller and at 3 weeks had fully re-epithelialised. Although trifluridine ophthalmic solution is not licensed for use in the UK, it has been used in the treatment of herpes keratitis in the USA since the early 1970s.5 The drug is a pyrimidine nucleoside (5-trifluoromethyl-2’-deoxyuridine), structurally related to idoxuridine. Its mechanism of action seems to be by thymidine
during viral DNA replication and inhibition of thymidylate synthetase.1 Strains of acyclovir-resistant HSV are highly sensitive in vitro to this agent? Although an allergic contact dermatitis from trifluridine in eyedrops has been reported,8 topical treatment is well tolerated. Patients may experience a mild burning sensation after application. substitution
Department of Genitourinary Medicine, Leeds General Infirmary, Leeds LS1 3EX, UK, Pharmacy Department, Leeds General Infirmary, and Public Health Laboratory Services, Leeds LS1 7TR 1.
M. MURPHY A. MORLEY R. P. EGLIN E. MONTEIRO
Elrich KS, Mills J, Chatis P, et al Acyclovir-resistant herpes simplex virus infection in patients with the acquired immunodeficiency syndrome. N Engl J Med 1989; 320: 293-96.
2. Charts
PA, Miller CH, Schrager LE, et al. Successful treatment with foscamet of an acyclovir-resistant mucocutaneous infection with herpes simplex virus infection in a patient with acquired immunodeficiency syndrome. N Engl J Med 1989; 320: 297-300.
3. Safrin
S, Assaykeen T, Follansbee S, et al. Foscarnet therapy for acyclovir-resistant herpes simplex virus infection in 26 patients, preliminary data. J Infect Dis 1990; 161: 1078-84. 4 Kessler H, Weaver D, Benson C, et al. ACTG 172 treatment of acyclovir-resistant (ACV-R) mucocutaneous herpes simplex virus (HSV) infection in patients with AIDS: open label pilot study of topical trifluridine (TFT). 8th international conference on AIDS, Amsterdam, Holland. July 19-24, 1992: abstr WeB 1056. 5. Wellmgs PC, Awdry PN, Bors FH, et al. Clinical evaluation of trifluorothymidine in the treatment of herpes simplex corneal ulcers. Am J Ophthalmol 1972; 73: 932-42. 6. Heidleberger C, Parsons DG, Remy DC. Synthesis of 5-trimethyluracil and 5-trifluoromethyl-2’ deoxyuridine. J Am Chem Soc 1962; 84: 3597-98 7. Pottage J, Kessler H, Kapell K, Benson C. Acyclovir resistant (ACV-R) herpes simplex. susceptibility to alternative antiviral agents. 8th international conference on AIDS, Amsterdam, Holland. July 19-24, 1992: abstr PoB 3238 8. Millan-Parrilla F, de la Cuadra J. Allergic contact dermatitis from trifluridine in eyedrops. Contact Dermatitis 1990; 22: 289. mucocutaneous
Acceptability of screening for HIV seroprevalence in women with cervical pathology SiR,—There are many reports of an increased prevalence of cervical intraepithelial neoplasia (CIN) in women infected with HIV compared with well-matched controls.’,’ Women attending colposcopy clinics may represent a group with a high HIV seroprevalence rate. This was highlighted by Maiman et aP who reported a seroprevalence rate in a New York colposcopy clinic three times greater than that in the local sexually transmitted diseases clinic and five times higher than that in the antenatal clinic in the same area. This fmding not only has implications for staff in these clinics but also raises the question of whether HIV testing should be offered to women attending colposcopy clinics. We evaluated the acceptability of offering routine HIV antibody testing in the colposcopy clinics of a local teaching hospital. All women between the ages of 18 and 50 who were attending the clinic for management of an abnormal cervical smear were asked to participate. The investigator completed a short risk-analysis questionnaire with each patient. Pretest HIV counselling was given to all patients and HIV testing was offered. All patients were given follow-up appointments for post-test counselling with the same interviewer. 100 consecutive women took part. 60 accepted HIV testing. All results were HIV antibody negative. The groups who accepted and those who declined were similar (table). In the 40 who declined a test, the reasons given were: scared of positive result (16), not at risk (7), already had negative test (4), does not like blood test (3), just
