1613
We have more recently completed a study on the effects of the oral NSAID, tiaprofenic acid (as ’Surgam SA’), and now report results which we believe have a bearing on the current debate about chondoprotection. 12 adult Merino wethers were subjected to unilateral medial meniscectomy. All animals were housed in similar pens but 12 weeks postmeniscectomy half of the group (randomly selected) were given tiaprofenic acid daily (20 mg/kg orally). Joint synovial fluid was aspirated one week before drug treatment and on weeks 15, 20, and 24 after surgery. Animals were killed on week 26. The amounts of cartilage proteoglycan fragments in synovial fluid were measured with an ELISA for keratan sulphate epitopes9 in both drug and non-drug treated animals. Histological, biochemical, and metabolic studies on the cartilage, bone, and synovium were also undertaken and these will be reported elsewhere. We found that cartilage proteoglycan metabolism was not suppressed in the drug-treated group. Non-drug treated animals showed a progressive increase in the release of proteoglycan epitopes into joint fluid during the experimental period (figure). Tiaprofenic acid given half-way through the study failed to suppress the release of this marker in the first two months of treatment, but by the third month a statistically significant reduction in the quantity of proteoglycan fragments in synovial fluid was observed suggesting a reduction in proteoglycan catabolism. Our findings indicate that tiaprofenic acid may have a chondoprotective effect in vivo. Furthermore, the route and dose schedule in our experiments were shown by analysis of drug blood concentrations (20 fig/mi) to be similar to that achieved in man.
dysfunction.
Raymond Purves Research Laboratories, University of Sydney, Royal North Shore Hospital of Sydney, St Leonards, New South Wales 2065, Australia School of Veterinary Studies, Murdoch University,
Murdoch, Western Australia 6150
PETER GHOSH CHRISTINE HOLBERT RICHARD READ SARAH ARMSTRONG DIANNA WILSON
1. Ghosh P Chondoprotective drugs and osteoarthritis. Ann Rheum Dis 1990; 49: 338-39. 2. Ghosh P, Brooks P. Chondoprotection: exploring the concept. J Rheumatol 1991; 18: 161-66. 3. Buckland-Wright JC, Macfarlane DG, Lynch JA, Clark B. Quantitative microfocal radiographic assessment of progression in osteoarthritis of the hand. Arthritis Rheum 1990; 33: 57-65. 4. Karvonen RL, Negendank WG, Fraser SM, et al. Articular cartilage defects of the knee: correlation between magnetic resonance imaging and gross pathology. Ann Rheum Dis 1990; 49: 672-75. 5. Shinmei M, Inamori Y, Yoshiwara Y, et al. Molecular markers of joint disease: significance of the level of type II c-propeptide chondroitin sulphate and TIMP in joint fluid. Trans Orthop Res Soc 1991; 16: 230. 6. Ghosh P, Burkhardt D, Read R, Bellenger C. Recent advances in animal models for evaluating chondoprotective drugs. J Rheumatol 1991; 18 (suppl 27). 143-46. 7. Hannan N, Ghosh P, Bellenger C, Taylor TKF. The systemic administration of glycosaminoglycan polysulphate (Arteparon) provides partial protection of articular cartilage from damage produced by meniscectomy. J Orthop Res 1987; 5: 47-59. 8. Ghosh P, Sutherland JM, Taylor TKF, et al. The effects of postoperative joint immobilisation on articular cartilage degeneration following meniscectomy. J Surg Res 1983; 35: 461-73. 9. Kongtawelert P, Ghosh P. A new sandwich ELISA method for the determination of keratan sulphate peptides in biological fluids employing a monoclonal antibody and labelled avidin biotin technique. Clin Chim Acta 1990; 195: 17-26.
Fenoterol and its bromide SIR,-There have been three papers in the past 18 months from New Zealand suggesting that fenoterol prescriptions are associated with increased risk of death, especially in patients with severe asthma.1-3 Another paper suggests that regular use of fenoterol is associated with worsening asthma.4 These reports indicate that, at least in New Zealand, regular use of fenoterol may make asthma worse. We do need to know if this is a class effect, applicable to all
beta-agonists, or whether it is specific to fenoterol. Fenoterol is the only beta-agonist drug that is formulated as a bromide. Eosinophils frequently use bromide rather than chloride to generate a halogenating oxidant with characteristics similar to those of hypobromous acid.s Hypobromous acid is an oxidant
capable of destroying a wide range of cells.5,6 It disrupts oc2-macroglobulin function7 which is important because
ocz-macroglobulin
function may be
one
of the main mechanisms
whereby cationic proteins released from eosinophils are inactivated. The normal bromide concentration in the blood can be as low as 10 I1g/l. This amount is thought to be sufficient to produce oxidants that damage the heart.6 Bands of fibrous tissue were found in the hearts of some young asthmatics who died from asthma who had not had infusions of catecholamines.8 The concentration of bromide delivered by a ’Berotec’ (fenoterol) metered dose aerosol is 20 000 times that in the blood, and this high concentration of bromide in the airways may increase the potential for tissue damage by
hypobromous oxidants from eosinophils. Experiments are in progress to find out if fenoterol increases the oxidant properties of eosinophils from asthmatic patients. If it does, that may be one explanation for the apparent harmful effects of fenoterol which would not apply to the other &bgr;2-specific agonists. Furthermore, it may be a mechanism whereby damage from oxidants occurs both in the lungs and in the heart. Department of Medicine, University of Sydney, Sydney, NSW 2006, Australia, and Institute of Respiratory Medicine, Royal Price Alfred Hospital, Sydney
W. F. GREEN
1. Crane J, Pearce N, Flatt A, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-83: case-control study. Lancet 1989; i: 917-22. 2. Pearce N, Grainger J, Atkinson M, et al. Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81. Thorax 1990; 45: 170-75. 3. Grainger J, Woodman K, Pearce N, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-7: a further case-control study. Thorax 1991; 46: 105-11. 4. Sears MR, Taylor DR, Print CG, et al. Regular inhaled beta-agonist treatment in bronchial asthma. Lancet 1990; 336: 1391-96. 5. Weiss SJ, Test ST, Eckmann CM, et al. Brominating oxidants generated by human eosinophils. Science 1986; 234: 200-02. 6. Slungaard A, Mahoney JR Jnr. Bromide-dependent toxicity of eosinophil peroxidase for endothelium and isolated working rat hearts: a model for eosinophilic 7.
endocarditis. J Exp Med 1991; 173: 117-26. Reddy VY, Pizzo SV, Weiss SJ. Functional inactivation and structural disruption of human alpha 2 macroglobulin by neutrophils and eosinophils. J Biol Chem 1989;
264: 13801-09. 8. Schoen FJ. Cardiac pathology in asthma. J
Allergy Clin Immunol 1987; 80:
419-23.
Photodynamic therapy in patient with xeroderma pigmentosum SIR,-Xeroderma pigmentosum (XP), a heritable disease with increased sensitivity to cellular injury by ultraviolet radiation (UVR) and certain DNA-damaging chemicals associated with abnormal DNA repair, is characterised by the development of multiple skin tumours.’ It could be an advantage to use photodynamic therapy (PDT)2,3 if many tumours are present because a large number of them can be managed in short treatment sessions.4 We report our experience of topical PDT with endogenous porphyrin, a novel therapy described by Kennedy et al.5 A 47-year-old woman with XP of complementation group C was admitted for a skin tumour on the back of her left hand, a sharply demarcated, slightly elevated, scaly, hyperkeratotic plaque 1 -55 cm in diameter. Punch biopsy indicated superficial squamous cell carcinoma. An oil-in-water emulsion containing 40% 5aminolaevulinic acid (ALA) was applied under occlusive dressing to the tumour and adjacent skin for 4 h before exposure to 90 J /em2 of visible light from a Leica slide projector equipped with a 250 W lamp with a Schott RG 570 long-wave-pass colour glass filter. We observed an abnormally delayed peak erythema and oedema of the exposed area 72 h after therapy (normal 8-24 h); the induced erythema persisted for more than 2 weeks (normal 2-4 days), and the reaction on adjacent skin was unusually strong, with blistering. However, healing of the carcinoma could be observed within 4 weeks; the erythema on the adjacent skin resolved gradually, leaving residual pigmentation. 6 months later there was no clinical sign of tumour recurrence.
delayed peak in, but persistent, erythema with striking acute damage in XP is well known after exposure to UVR.1,6 However, in this patient UVR treatment was not used and exposure to natural UVR can also be excluded because the patient was in A skin
1614
hospital and did not go outside during or after the PDT. The unusually strong reaction in adjacent skin could, to some extent, at least be a result of enhanced penetration of ALA through the damaged skin of XP because ALA in aqueous solution passes readily through abnormal, but not through normal, keratin.5 The mechanism of the delayed but persistent reaction to PDT remains unclear, just as the abnormal UVR-induced erythema production is not understood in XP. It cannot be explained by the DNA-repair defect in XP cells because the main target of PDT is cell membranes rather than DNARepair does not seem to be a significant factor when PDT is applied to XP cells; cell inactivation by PDT in vitro was found to be equally effective in DNA-repair efficient and deficient cells.’ In this case topical PDT was successful; the delayed, but enhanced phototoxic reaction of adjacent normal skin to PDT suggests that care should be exercised when considering systemic PDT in XP. PDT with haematoporphyrin derivative or ’Photofrin II’ in XP could be associated with unexpectedly strong and much more persistent photosensitivity than that seen normally. Department of Dermatology, University of Graz, A-8036 Graz, Austria
PETER WOLF HELMUT KERL
significantly
lower in group A than in groups B and C combined
(p < 0’001), whereas no significant difference was observed between group B and group C: DU relapses in group:
ABC
22/39 (6 %)
3/30 (10%))
33/75 (44 % )
The results of this study confirm that long-term eradication of H pylori prevents ulcer recurrence, whereas clearance in the immediate post-treatment period without long-term eradication does not.
physicians who took part in this trial: G. Minoli Hospital, Como); A. Prada and P. G. Mandelli (Regional Hospital, Rho); U. Comin and A. M. Fertitta (C. Cantu’ Hospital, Abbiategrasso); F. Turpini, L. Villani (University of Pavia); L. Piazzi and V. Colombetti (Regional Hospital, Bolzano); S. Gullini and L. Cavazzini (S Anna Hospital, Ferrara); M. Curzio and M. Comaggia (Multizonal Hospital, Varese); S. Brunati and R. Negri (Fomaroli Hospital, Magenta); and P. Bodini and G. Bertoli (Regional Hospital, Cremona). We thank the following and V. Terruzzi (Valduce
Department of Human Pathology, University of Pavia, 27100 Pavia, Italy,
R. FIOCCA E. SOLCIA
and Policlinico S Matteo, Pavia Gist-Brocades Farma, Cologno Mon.
B. SANTORO
1. Kraemer KH. Xeroderma 2.
3. 4. 5.
6.
7.
pigmentosum. In: Demis DJ, ed. Clinical dermatology. Philadelphia: Lippincott, 1990; 4, unit 19-7: 1-33. Dougherty TJ. Photosensitizers therapy and detection of malignant tumors. Photochem Photobiol 1987; 45: 879-89. Manyak MJ, Russo A, Smith PD, Glatstein E. Photodynamic therapy J Clin Oncol 1988; 6: 380-91. Robinson PJ, Carruth JAS, Fairris GM. Photodynamic therapy: a better treatment for widespread Bowen’s disease. Br J Dermatol 1988; 119: 59-61. Kennedy JC, Pottier RH, Pross DC. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photochem Photobiol B Biol 1990; 6: 143-48. Kondo S, Mamada A, Miyamoto C, Keong CH, Satoh Y, Fujiwara Y. Late onset of skin cancers in 2 xeroderma pigmentosum group F siblings and a review of 30 Japanese xeroderma pigmentosum patients in groups D, E and F. Photodermatology 1989; 6: 89-95. Gomer CJ, Rucker N, Murphree AL Differential cell photosensitivity following porphyrin photodynamic therapy. Cancer Res 1988; 48: 4539-42.
Duodenal ulcer relapse after eradication of Helicobacter pylori SIR,-Evidence has been accumulating suggesting a close connection between duodenal ulcer (DU) and Helicobacter pylori infection of the stomach. Three studies1-3 have shown that H pylori status after treatment may predict DU recurrence: the frequency of ulcer relapse ranged from 79% to 89% in Hpylori positive and from 0 to 27% in H pylori negative cases of healed DU. In a multicentre, prospective study we evaluated recurrences in 144 patients with H pylori positive DU, healed after antibacterial and/or anti-secretory drug therapy and followed up for six months. After the first endoscopy, with two antral and two corpus biopsies, 167 males and 94 females were enrolled on the basis of both a positive urease test and histologically detected H pylori. They were randomly assigned to four treatment groups: (1) colloidal bismuth subcitrate (’DeNol’; two tablets twice daily for 6 weeks; (2) colloidal bismuth (as above) plus amoxycillin 1 g twice daily for 10 days; (3) ranitidine 300 mg at night for 6 weeks; or (4) ranitidine (as above) plus amoxycillin 1 g twice daily for 10 days. 244 patients completed treatment and were re-examined 6 weeks later by endoscopy with multiple biopsies. Ulcers had healed in 89 of 97 H pylori cleared patients and in 117 of the 147 patients who still had H pylori (p 0-01). No maintenance therapy was given and 144 of the 206 initially healed patients were re-examined six months later. Relapse rates were 44% (16/36) in patients treated with bismuth alone, 28% (11/39) in those on bismuth plus amoxycillin; 53% (20/38) in patients allocated to ranitidine alone; and 35% (11/31) in those on ranitidine plus amoxycillin. We also calculated relapse rates another way, by categorising patients as: (A) Hpylori "cleared/eradicated" (free of H pylori at 6 weeks and at 6 months); (B) "cleared/not eradicated" (free at 6 weeks but positive at 6 months); and (C) "not cleared/not eradicated" (H pylori colonisation at 6 weeks and at 6 months). The DU relapse rate was =
1.
Coghlan JG, Gilligan D, Humphries H, et al. Campylobacter pylori and recurrence of duodenal ulcers. a 12-month follow-up study. Lancet 1987; ii: 1109-11. 2. Marshall BJ, Goodwin CS, Warren JR, et al. Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. Lancet 1988; ii 1437-41. 3. Rauws EAJ, Tytgat GNJ. Cure of duodenal ulcer associated with eradication of Helicobacter pylori. Lancet 1990; 335: 1233-35.
Imported heterosexual HIV infection in London SIR,-In the UK the main source of information on numbers of heterosexuals with HIV infection is the Communicable Disease Surveillance Centre (CDSC), which collates data from physicians looking after AID S patients and from laboratories that test for HIV antibody. CDSC lists heterosexuals by exposure category. Injecting drug users (ID Us) and their sexual contacts make up the largest group but there is no breakdown into UK nationals and those from abroad. After haemophiliacs, the largest category is "other partner abroad". Although the CDSC states that this figure "includes persons from, or who have lived in, WHO transmission pattern II countries", the wording implies that most of this category are residents of the UK. A CDSC paper on travel, heterosexual intercourse, and HIV-1 infection! concentrates on the need for identification of these travellers and their health education. People with HIV infection are seen at St Thomas’ Hospital in the drug dependency unit, the haemophilia centre, or in a dedicated outpatient HIV unit attached to the department of genitourinary medicine. Out of 548 HIV-antibody-positive patients who have attended the outpatient HIV unit up to May, 1991, we have identified and reviewed the case-notes of 113 heterosexuals. 17 (15%) had had an AID S-defining illness; 8 were IDUs (all foreign), 8 were Africans, and 1 was a foreign contact of an IDU. The 113 patients consisted of 52 IDUs, 13 contacts of IDUs, 39 other partner abroad (34 Africans), 2 contacts of bisexual men, 2 recipients of blood transfusion in Africa, 1 contact of an African living in the UK, 1 haemophiliac, 1 contact of a blood transfusion patient in the UK, and 2 patients for whom risk factors have not yet been established: Risk factor
High-risk partner Other partner abroad Other partner UK Under investigation
Injecting drug use Blood factor Blood transfer
20 of the 52 IDUs ten other countries,
were
No 16 39 1 2 52 1 2
bom in the UK. The others
including Italy (13) and Eire (6). 5
°
came from of 13 contacts
We have more recently completed a study on the effects of the oral NSAID, tiaprofenic acid (as ’Surgam SA’), and now report results which we believe have a bearing on the current debate about chondoprotection. 12 adult Merino wethers were subjected to unilateral medial meniscectomy. All animals were housed in similar pens but 12 weeks postmeniscectomy half of the group (randomly selected) were given tiaprofenic acid daily (20 mg/kg orally). Joint synovial fluid was aspirated one week before drug treatment and on weeks 15, 20, and 24 after surgery. Animals were killed on week 26. The amounts of cartilage proteoglycan fragments in synovial fluid were measured with an ELISA for keratan sulphate epitopes9 in both drug and non-drug treated animals. Histological, biochemical, and metabolic studies on the cartilage, bone, and synovium were also undertaken and these will be reported elsewhere. We found that cartilage proteoglycan metabolism was not suppressed in the drug-treated group. Non-drug treated animals showed a progressive increase in the release of proteoglycan epitopes into joint fluid during the experimental period (figure). Tiaprofenic acid given half-way through the study failed to suppress the release of this marker in the first two months of treatment, but by the third month a statistically significant reduction in the quantity of proteoglycan fragments in synovial fluid was observed suggesting a reduction in proteoglycan catabolism. Our findings indicate that tiaprofenic acid may have a chondoprotective effect in vivo. Furthermore, the route and dose schedule in our experiments were shown by analysis of drug blood concentrations (20 fig/mi) to be similar to that achieved in man.
dysfunction.
Raymond Purves Research Laboratories, University of Sydney, Royal North Shore Hospital of Sydney, St Leonards, New South Wales 2065, Australia School of Veterinary Studies, Murdoch University,
Murdoch, Western Australia 6150
PETER GHOSH CHRISTINE HOLBERT RICHARD READ SARAH ARMSTRONG DIANNA WILSON
1. Ghosh P Chondoprotective drugs and osteoarthritis. Ann Rheum Dis 1990; 49: 338-39. 2. Ghosh P, Brooks P. Chondoprotection: exploring the concept. J Rheumatol 1991; 18: 161-66. 3. Buckland-Wright JC, Macfarlane DG, Lynch JA, Clark B. Quantitative microfocal radiographic assessment of progression in osteoarthritis of the hand. Arthritis Rheum 1990; 33: 57-65. 4. Karvonen RL, Negendank WG, Fraser SM, et al. Articular cartilage defects of the knee: correlation between magnetic resonance imaging and gross pathology. Ann Rheum Dis 1990; 49: 672-75. 5. Shinmei M, Inamori Y, Yoshiwara Y, et al. Molecular markers of joint disease: significance of the level of type II c-propeptide chondroitin sulphate and TIMP in joint fluid. Trans Orthop Res Soc 1991; 16: 230. 6. Ghosh P, Burkhardt D, Read R, Bellenger C. Recent advances in animal models for evaluating chondoprotective drugs. J Rheumatol 1991; 18 (suppl 27). 143-46. 7. Hannan N, Ghosh P, Bellenger C, Taylor TKF. The systemic administration of glycosaminoglycan polysulphate (Arteparon) provides partial protection of articular cartilage from damage produced by meniscectomy. J Orthop Res 1987; 5: 47-59. 8. Ghosh P, Sutherland JM, Taylor TKF, et al. The effects of postoperative joint immobilisation on articular cartilage degeneration following meniscectomy. J Surg Res 1983; 35: 461-73. 9. Kongtawelert P, Ghosh P. A new sandwich ELISA method for the determination of keratan sulphate peptides in biological fluids employing a monoclonal antibody and labelled avidin biotin technique. Clin Chim Acta 1990; 195: 17-26.
Fenoterol and its bromide SIR,-There have been three papers in the past 18 months from New Zealand suggesting that fenoterol prescriptions are associated with increased risk of death, especially in patients with severe asthma.1-3 Another paper suggests that regular use of fenoterol is associated with worsening asthma.4 These reports indicate that, at least in New Zealand, regular use of fenoterol may make asthma worse. We do need to know if this is a class effect, applicable to all
beta-agonists, or whether it is specific to fenoterol. Fenoterol is the only beta-agonist drug that is formulated as a bromide. Eosinophils frequently use bromide rather than chloride to generate a halogenating oxidant with characteristics similar to those of hypobromous acid.s Hypobromous acid is an oxidant
capable of destroying a wide range of cells.5,6 It disrupts oc2-macroglobulin function7 which is important because
ocz-macroglobulin
function may be
one
of the main mechanisms
whereby cationic proteins released from eosinophils are inactivated. The normal bromide concentration in the blood can be as low as 10 I1g/l. This amount is thought to be sufficient to produce oxidants that damage the heart.6 Bands of fibrous tissue were found in the hearts of some young asthmatics who died from asthma who had not had infusions of catecholamines.8 The concentration of bromide delivered by a ’Berotec’ (fenoterol) metered dose aerosol is 20 000 times that in the blood, and this high concentration of bromide in the airways may increase the potential for tissue damage by
hypobromous oxidants from eosinophils. Experiments are in progress to find out if fenoterol increases the oxidant properties of eosinophils from asthmatic patients. If it does, that may be one explanation for the apparent harmful effects of fenoterol which would not apply to the other &bgr;2-specific agonists. Furthermore, it may be a mechanism whereby damage from oxidants occurs both in the lungs and in the heart. Department of Medicine, University of Sydney, Sydney, NSW 2006, Australia, and Institute of Respiratory Medicine, Royal Price Alfred Hospital, Sydney
W. F. GREEN
1. Crane J, Pearce N, Flatt A, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-83: case-control study. Lancet 1989; i: 917-22. 2. Pearce N, Grainger J, Atkinson M, et al. Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81. Thorax 1990; 45: 170-75. 3. Grainger J, Woodman K, Pearce N, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-7: a further case-control study. Thorax 1991; 46: 105-11. 4. Sears MR, Taylor DR, Print CG, et al. Regular inhaled beta-agonist treatment in bronchial asthma. Lancet 1990; 336: 1391-96. 5. Weiss SJ, Test ST, Eckmann CM, et al. Brominating oxidants generated by human eosinophils. Science 1986; 234: 200-02. 6. Slungaard A, Mahoney JR Jnr. Bromide-dependent toxicity of eosinophil peroxidase for endothelium and isolated working rat hearts: a model for eosinophilic 7.
endocarditis. J Exp Med 1991; 173: 117-26. Reddy VY, Pizzo SV, Weiss SJ. Functional inactivation and structural disruption of human alpha 2 macroglobulin by neutrophils and eosinophils. J Biol Chem 1989;
264: 13801-09. 8. Schoen FJ. Cardiac pathology in asthma. J
Allergy Clin Immunol 1987; 80:
419-23.
Photodynamic therapy in patient with xeroderma pigmentosum SIR,-Xeroderma pigmentosum (XP), a heritable disease with increased sensitivity to cellular injury by ultraviolet radiation (UVR) and certain DNA-damaging chemicals associated with abnormal DNA repair, is characterised by the development of multiple skin tumours.’ It could be an advantage to use photodynamic therapy (PDT)2,3 if many tumours are present because a large number of them can be managed in short treatment sessions.4 We report our experience of topical PDT with endogenous porphyrin, a novel therapy described by Kennedy et al.5 A 47-year-old woman with XP of complementation group C was admitted for a skin tumour on the back of her left hand, a sharply demarcated, slightly elevated, scaly, hyperkeratotic plaque 1 -55 cm in diameter. Punch biopsy indicated superficial squamous cell carcinoma. An oil-in-water emulsion containing 40% 5aminolaevulinic acid (ALA) was applied under occlusive dressing to the tumour and adjacent skin for 4 h before exposure to 90 J /em2 of visible light from a Leica slide projector equipped with a 250 W lamp with a Schott RG 570 long-wave-pass colour glass filter. We observed an abnormally delayed peak erythema and oedema of the exposed area 72 h after therapy (normal 8-24 h); the induced erythema persisted for more than 2 weeks (normal 2-4 days), and the reaction on adjacent skin was unusually strong, with blistering. However, healing of the carcinoma could be observed within 4 weeks; the erythema on the adjacent skin resolved gradually, leaving residual pigmentation. 6 months later there was no clinical sign of tumour recurrence.
delayed peak in, but persistent, erythema with striking acute damage in XP is well known after exposure to UVR.1,6 However, in this patient UVR treatment was not used and exposure to natural UVR can also be excluded because the patient was in A skin
1614
hospital and did not go outside during or after the PDT. The unusually strong reaction in adjacent skin could, to some extent, at least be a result of enhanced penetration of ALA through the damaged skin of XP because ALA in aqueous solution passes readily through abnormal, but not through normal, keratin.5 The mechanism of the delayed but persistent reaction to PDT remains unclear, just as the abnormal UVR-induced erythema production is not understood in XP. It cannot be explained by the DNA-repair defect in XP cells because the main target of PDT is cell membranes rather than DNARepair does not seem to be a significant factor when PDT is applied to XP cells; cell inactivation by PDT in vitro was found to be equally effective in DNA-repair efficient and deficient cells.’ In this case topical PDT was successful; the delayed, but enhanced phototoxic reaction of adjacent normal skin to PDT suggests that care should be exercised when considering systemic PDT in XP. PDT with haematoporphyrin derivative or ’Photofrin II’ in XP could be associated with unexpectedly strong and much more persistent photosensitivity than that seen normally. Department of Dermatology, University of Graz, A-8036 Graz, Austria
PETER WOLF HELMUT KERL
significantly
lower in group A than in groups B and C combined
(p < 0’001), whereas no significant difference was observed between group B and group C: DU relapses in group:
ABC
22/39 (6 %)
3/30 (10%))
33/75 (44 % )
The results of this study confirm that long-term eradication of H pylori prevents ulcer recurrence, whereas clearance in the immediate post-treatment period without long-term eradication does not.
physicians who took part in this trial: G. Minoli Hospital, Como); A. Prada and P. G. Mandelli (Regional Hospital, Rho); U. Comin and A. M. Fertitta (C. Cantu’ Hospital, Abbiategrasso); F. Turpini, L. Villani (University of Pavia); L. Piazzi and V. Colombetti (Regional Hospital, Bolzano); S. Gullini and L. Cavazzini (S Anna Hospital, Ferrara); M. Curzio and M. Comaggia (Multizonal Hospital, Varese); S. Brunati and R. Negri (Fomaroli Hospital, Magenta); and P. Bodini and G. Bertoli (Regional Hospital, Cremona). We thank the following and V. Terruzzi (Valduce
Department of Human Pathology, University of Pavia, 27100 Pavia, Italy,
R. FIOCCA E. SOLCIA
and Policlinico S Matteo, Pavia Gist-Brocades Farma, Cologno Mon.
B. SANTORO
1. Kraemer KH. Xeroderma 2.
3. 4. 5.
6.
7.
pigmentosum. In: Demis DJ, ed. Clinical dermatology. Philadelphia: Lippincott, 1990; 4, unit 19-7: 1-33. Dougherty TJ. Photosensitizers therapy and detection of malignant tumors. Photochem Photobiol 1987; 45: 879-89. Manyak MJ, Russo A, Smith PD, Glatstein E. Photodynamic therapy J Clin Oncol 1988; 6: 380-91. Robinson PJ, Carruth JAS, Fairris GM. Photodynamic therapy: a better treatment for widespread Bowen’s disease. Br J Dermatol 1988; 119: 59-61. Kennedy JC, Pottier RH, Pross DC. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photochem Photobiol B Biol 1990; 6: 143-48. Kondo S, Mamada A, Miyamoto C, Keong CH, Satoh Y, Fujiwara Y. Late onset of skin cancers in 2 xeroderma pigmentosum group F siblings and a review of 30 Japanese xeroderma pigmentosum patients in groups D, E and F. Photodermatology 1989; 6: 89-95. Gomer CJ, Rucker N, Murphree AL Differential cell photosensitivity following porphyrin photodynamic therapy. Cancer Res 1988; 48: 4539-42.
Duodenal ulcer relapse after eradication of Helicobacter pylori SIR,-Evidence has been accumulating suggesting a close connection between duodenal ulcer (DU) and Helicobacter pylori infection of the stomach. Three studies1-3 have shown that H pylori status after treatment may predict DU recurrence: the frequency of ulcer relapse ranged from 79% to 89% in Hpylori positive and from 0 to 27% in H pylori negative cases of healed DU. In a multicentre, prospective study we evaluated recurrences in 144 patients with H pylori positive DU, healed after antibacterial and/or anti-secretory drug therapy and followed up for six months. After the first endoscopy, with two antral and two corpus biopsies, 167 males and 94 females were enrolled on the basis of both a positive urease test and histologically detected H pylori. They were randomly assigned to four treatment groups: (1) colloidal bismuth subcitrate (’DeNol’; two tablets twice daily for 6 weeks; (2) colloidal bismuth (as above) plus amoxycillin 1 g twice daily for 10 days; (3) ranitidine 300 mg at night for 6 weeks; or (4) ranitidine (as above) plus amoxycillin 1 g twice daily for 10 days. 244 patients completed treatment and were re-examined 6 weeks later by endoscopy with multiple biopsies. Ulcers had healed in 89 of 97 H pylori cleared patients and in 117 of the 147 patients who still had H pylori (p 0-01). No maintenance therapy was given and 144 of the 206 initially healed patients were re-examined six months later. Relapse rates were 44% (16/36) in patients treated with bismuth alone, 28% (11/39) in those on bismuth plus amoxycillin; 53% (20/38) in patients allocated to ranitidine alone; and 35% (11/31) in those on ranitidine plus amoxycillin. We also calculated relapse rates another way, by categorising patients as: (A) Hpylori "cleared/eradicated" (free of H pylori at 6 weeks and at 6 months); (B) "cleared/not eradicated" (free at 6 weeks but positive at 6 months); and (C) "not cleared/not eradicated" (H pylori colonisation at 6 weeks and at 6 months). The DU relapse rate was =
1.
Coghlan JG, Gilligan D, Humphries H, et al. Campylobacter pylori and recurrence of duodenal ulcers. a 12-month follow-up study. Lancet 1987; ii: 1109-11. 2. Marshall BJ, Goodwin CS, Warren JR, et al. Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. Lancet 1988; ii 1437-41. 3. Rauws EAJ, Tytgat GNJ. Cure of duodenal ulcer associated with eradication of Helicobacter pylori. Lancet 1990; 335: 1233-35.
Imported heterosexual HIV infection in London SIR,-In the UK the main source of information on numbers of heterosexuals with HIV infection is the Communicable Disease Surveillance Centre (CDSC), which collates data from physicians looking after AID S patients and from laboratories that test for HIV antibody. CDSC lists heterosexuals by exposure category. Injecting drug users (ID Us) and their sexual contacts make up the largest group but there is no breakdown into UK nationals and those from abroad. After haemophiliacs, the largest category is "other partner abroad". Although the CDSC states that this figure "includes persons from, or who have lived in, WHO transmission pattern II countries", the wording implies that most of this category are residents of the UK. A CDSC paper on travel, heterosexual intercourse, and HIV-1 infection! concentrates on the need for identification of these travellers and their health education. People with HIV infection are seen at St Thomas’ Hospital in the drug dependency unit, the haemophilia centre, or in a dedicated outpatient HIV unit attached to the department of genitourinary medicine. Out of 548 HIV-antibody-positive patients who have attended the outpatient HIV unit up to May, 1991, we have identified and reviewed the case-notes of 113 heterosexuals. 17 (15%) had had an AID S-defining illness; 8 were IDUs (all foreign), 8 were Africans, and 1 was a foreign contact of an IDU. The 113 patients consisted of 52 IDUs, 13 contacts of IDUs, 39 other partner abroad (34 Africans), 2 contacts of bisexual men, 2 recipients of blood transfusion in Africa, 1 contact of an African living in the UK, 1 haemophiliac, 1 contact of a blood transfusion patient in the UK, and 2 patients for whom risk factors have not yet been established: Risk factor
High-risk partner Other partner abroad Other partner UK Under investigation
Injecting drug use Blood factor Blood transfer
20 of the 52 IDUs ten other countries,
were
No 16 39 1 2 52 1 2
bom in the UK. The others
including Italy (13) and Eire (6). 5
°
came from of 13 contacts
