cardiac failure or hypertrophy) could adequately because of the sample size.
Participating centres were: Bergamo (C. Malinvemi, G. Mecca); Brescia (P. Berra, P. Feller, S. Mombelloni); Cinisello (F. Vallino, M. Saruggia, M. Mezzadri, G. F. Comolatti); Chiari e Rovato (V. Coppola, S. De Marinis, G. Torti); Desio (G. Bonforte, G. Cairo, A. SalvlOni); Lecco (R. Costanzo, A. Piloni, R. Ponti, F. Locatelli); Magenta (F. Bissoli, V. Oldani, M. Tusa); Ospedale Maggiore, Milano (G. Ambroso, S. Casati, R. Mangiarotti, C. Pini); Milano "L Sacco" (G. Barbiano di Belgiojoso, S. Bertoli, S. Corallo, M. Mutinelli); Milano "S Paolo" (G. Como, M. Garbin, M. Goventu, R. Silenzio); Monza (P. Mariani, R. Schiavina, M. R. Vigan6); Vizzolo Predabissi (C. Grassi, N. Malcovati, E. Orazi); Voghera (C. Barbieri, P. Bernini, P. Gandolfi, C. Pasotti). REFERENCES
1. Gruppo emodialisi e patologie cardiovascolari. Multicentre, crosssectional study of ventricular arrhythmias in chronically haemodialysed patients. Lancet 1988; ii: 305-09. 2. Brunner FP, Broyer M, Brynger H, et al. Registry report. Survival on renal replacement therapy: data from the EDTA Registry. Nephrol Dial Transplant 1988; 2: 109-22. 3. Degoulet P, Legrain M, Reach I, et al. Mortality risk factors in patients treated by chronic hemodialysis. Report of the ’Diaphane’ collaborative study. Nephron 1982; 31: 103-10. 4. Brynger H, Brunner FP, Chantler C, et al. Combined report on regular dialysis and transplant in Europe, X, 1979. In: Robinson BHB, ed. Proceedings of the 7th Congress of the European Dialysis and Transplant Association. London: Pitman, 1980: 36-38. 5. Bradley JR, Evans DB, Calne RY. Long term survival in haemodialysis patients. Lancet 1987; i: 295-96. 6. Kjellstrand CM, Hylander B, Collins AC. Mortality on dialysis: on the influence of early start, patient characteristics, and transplantation and acceptance rate. Am J Kidney Dis 1990; 15: 483-90. 7. Burton PR, Walls J. Selection-adjusted comparison of life-expectancy of patients on continuous ambulatory peritoneal dialysis, haemodialysis, and renal transplantation. Lancet 1987; i: 1115-18. 8. Gokal R, Jakubowsky C, King J, et al. Outcome in patients on continuous ambulatory peritoneal dialysis and haemodialysis: 4-year analysis of a prospective multicentre study. Lancet 1987; ii: 1105-09. ADDRESSES: Renal and Dialysis Division, Ospedale San Gerardo, Monza (S. Sforzini, MD, B Redaelli, MD); Istituto di Ricerche Farmacologiche Mario Negri, Milan (R Latini, MD); Division of Cardiology, Ospedale San Gerardo, Monza (A. Vincenti, MD); and Renal and Dialysis Division, Ospedali Riuniti, Bergamo, Italy (G Mingardi, MD). Correspondence to Dr Sergio Sforzini, Divisione di Nefrologia e Dialisi, Ospedale S Gerardo, Via
Solferino 16, Monza, Milan, Italy
Control of scarring in adult wounds by neutralising antibody to transforming
growth factor &bgr;
Adult wounds heal with scar-tissue formation, whereas fetal wounds heal without scarring and with a lesser inflammatory and cytokine response. We injected the margins of healing dermal wounds in adult rats with neutralising antibody (NA) to transforming growth factor-&bgr; (TGF-&bgr;). All control wounds (irrelevant antibody, or TGF-&bgr;, or no injection) healed with scarring, whereas the NAtreated wounds healed without scar-tissue formation; NA-treated wounds had fewer macrophages and blood vessels, lower collagen and fibronectin contents, but identical tensile strength and more normal dermal architecture than the other wounds. Early manipulation of the concentrations of selected cytokines may be a new approach to the control of Scarring.
Scar-tissue formation and subsequent contraction after trauma, surgery, or thermal injury often result in defective
growth, functional impairment,
appearance. The evolution and control of scarring are poorly understood. Fetal wounds heal without scarring and with a lesser inflammatory and cytokine response.1,2 Of the many cytokines that have been implicated in wound healing, transforming growth factor (3 (TGF-(3) affects all phases of the healing process, including the inflammatory response and extracellular matrix accumulation.3°4 TGF- 0 also induces scarring in fetal wounds5 and has been implicated in the pathogenesis of glomerulonephritis.6 Cytokines can be applied to wounds to accelerate the healing process. Despite the possibility that lowering of cytokine concentrations might inhibit wound healing, we experimentally reduced the concentration of TGF- 0 within the adult healing wound by means of neutralising antibodies (NA) to this cytokine in an attempt to reduce scarring. Adult male Sprague-Dawley rats (200-250 g) were anaesthetised with halothane, nitrous oxide, and oxygen inhalation. Four incisions, 10 mm in length and to the depth of the panniculus carnosus, were made on the dorsal skin equidistant from the midline and adjacent to the four limbs. The wounds were left unsutured to heal by secondary intention to produce the greatest amount of granulation tissue and scarring. In each animal, one wound (control) was unmanipulated, one (sham control) was injected with an irrelevant antibody (rabbit IgG), one (positive control) was injected with 10 ng per injection of TGF-1 (BDP 3, British Biotechnology, Oxford), and one was injected with 50 ug NA to TGF-P (10 Ilg antibody neutralises 0.25 ng TGF-1,2; BDA1, British Biotechnology, Oxford). Injections of 100 ul in phosphatebuffered saline were introduced into each wound daily on days 0-2. The fluid was infiltrated along the length of each wound margin through a single entry point 0-5 cm distal to the caudal end of the wound. At least 8 animals were killed by chloroform overdose on each of days 7, 14, 28, 42, 70, and 168 after wounding. The wounds were for bisected histology/immunocytochemistryl and tensiometry or biochemical analysis. For each staining procedure, at least 8 sections from randomly chosen positions throughout each wound were analysed. For tensiometry, one or more dumb-bell-shaped strips were cut perpendicular to the long axis of each wound with a template, 0-3 cm wide at the centre (wound) and 3-0 cm long. The wound and surrounding normal skin were microdissected free from the underlying muscle and fat. The strips were cut from identical sites in all the wounds. Each strip was immediately extended to failure at 20 mm/min in an RDP Howden tensile testing instrument with a 500 N load cell. The thickness of the wound was measured with a micrometer. All strips ruptured at the site of the healing wound. For biochemical analysis, individual wounds or normal skin samples were carefully microdissected free from the underlying fat and muscle, rapidly frozen, and lyophilised. The dried samples were weighed and the hydroxyproline content measured. We calculated the amount of collagen by assuming that it contains 13-6% hydroxyproline. COLLAGEN CONTENT AND TENSILE STRENGTH OF WOUNDS AT VARIOUS TIMES AFTER WOUNDING
*p < 0 05 for difference from