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Australia focuses on Mycobacterium ulcerans
SCIENCE AND MEDICINE
Genetic basis for idiopathic scoliosis brought a step nearer of Sciences, Novosibirsk, Russia). here is genetic susceptibility Several candidate genes in adolescent idiohave been eliminated, pathic scoliosis, conincluding the major cluded geneticscollagen genes and workshop participants the fibrillin genes assoat the tenth Philip ciated with Marfan and Zorab symposium on Beale’s syndromes in scoliosis aetiology which scoliosis develops (Oxford, UK; March secondarily. Other 30–April 1). genes are still being The overall picture of studied. adolescent idiopathic Researchers in scoliosis is of a complex Boston, MA, USA, disease trait with incomand Oxford, UK, are plete penetrance (it can now doing a genomeskip generations) and wide search with variable expression (disrandom markers in ease severity varies Fitting the phenotype? scoliosis families. The within families). In chair of the genetics group, Andrew some rare pedigrees, however, the Carr (Nuffield Orthopaedic Centre, condition is genetically dominant. Oxford, UK), called for international Some research has suggested that cooperation to avoid the pitfalls a major gene effect is present, associated with ascertainment of explained Tatiana Axenovich and twins and large families with several colleagues (Russian Academy Science Photo Library
T
affected generations needed for these studies. These genetic studies rely on accurate identification of individuals with a true idiopathic phenotype. A workshop, chaired by Ian Stokes, (University of Vermont, Burlington, VA, USA), examined this thorny issue. The basic proposed standard definition of the phenotype (to be available soon on the Internet at http://www.ndos.ox.ac.uk/pzs) is a minimum lateral curvature of the spine of 10º, some vertebral rotation at the apex of the curve, and no central-nervous-system involvement. Use of this classification by research nurses in family ascertainment should ensure that geneticists study families with idiopathic disease, rather than scoliosis of neuromuscular, congenital, syndromal, or degenerative origins. Stephanie Clark
Australia focuses on Mycobacterium ulcerans new focus of Buruli ulcer around Melbourne, Australia, was reported at a meeting held in the city (April 1–3) to commemorate the 50th anniversary of the isolation, also in Australia, of the causative agent, Mycobacterium ulcerans. Between 1992 and 1997, 46 cases of M ulcerans occurred, said Paul Johnson (Monash, Melbourne) the largest cluster (28 cases) being in Cowes, Phillip Island. In 1992 an embankment was built on the island across a swamp, preventing natural drainage, and over the next 2 years M ulcerans cases occurred mainly among people living near the swamp or a nearby golf course. PCR analysis revealed M ulcerans DNA in swamp-
A
water samples and ground water from the swamp, which was being used to irrigate the golf course. Many infected patients remembered being cut or scratched by sharp vegetation at the skin site where the Buruli ulcer developed. It seems likely that infecting bacteria had been inoculated from vegetation covered with biofilms deposited by the contaminated water. M ulcerans toxin is thought to cause the extensive necrosis but poor inflammatory response associated with Buruli ulcer. New work on the toxin was reported by groups from the US National Institutes of Health Rocky Mountain laboratory (MT, USA) and Imperial College, London, UK. In vitro, a toxin “filtrate” from
M ulcerans depressed cytokine secretion from T lymphocytes and macrophages and made the latter cells resistant to some interleukins. The filtrate did not kill immune cells, but arrested the cell cycle. The term immunosuppressive factor may thus be more accurate than toxin. Analysis of the semipurified factor showed it to be a low molecular weight lipid, possibly from the cell wall. A full description of the factor’s structure and synthesis may suggest new ways to treat Buruli ulcer—currently, the lesions can be controlled only by surgery and, in the case of extensive disease, by amputation. David Wright
Hit diabetes hard and early for best long-term results
S
ome people in the early stages of type I diabetes retain residual islet function. A new study from the DCCT (Diabetes Control and Complications Trial) research group has found that intensive therapy for these patients prolongs their ability to produce endogenous insulin and lowers their risk of diabetic complications. The study examined 855 trial participants who had been diagnosed with type I diabetes for 1–5 years. 303 “responders” had some resid-
1184
ual insulin secretion. 138 of these people were assigned to intensive therapy—three or more insulin injections daily or continuous subcutaneous insulin infusion—as were 274 non-responders. The remaining responders received conventional therapy—one or two insulin injections daily. Patients were followed for up to 6 years to monitor -cell function and diabetic complications. Responders treated intensively had greater endogenous insulin secretion during the first 5
years than those given conventional therapy. The risk of severe hypoglycaemia with seizure or coma was reduced by 65% and the risk of retinopathy progression by 50% in intensively treated responders compared with non-responders (Ann Intern Med 1998; 128: 517–23). The researchers estimate that islet function was extended for at least 2 years in responders who were treated intensively. Hannah Wunsch
THE LANCET • Vol 351 • April 18, 1998
Genetic basis for idiopathic scoliosis brought a step nearer of Sciences, Novosibirsk, Russia). here is genetic susceptibility Several candidate genes in adolescent idiohave been eliminated, pathic scoliosis, conincluding the major cluded geneticscollagen genes and workshop participants the fibrillin genes assoat the tenth Philip ciated with Marfan and Zorab symposium on Beale’s syndromes in scoliosis aetiology which scoliosis develops (Oxford, UK; March secondarily. Other 30–April 1). genes are still being The overall picture of studied. adolescent idiopathic Researchers in scoliosis is of a complex Boston, MA, USA, disease trait with incomand Oxford, UK, are plete penetrance (it can now doing a genomeskip generations) and wide search with variable expression (disrandom markers in ease severity varies Fitting the phenotype? scoliosis families. The within families). In chair of the genetics group, Andrew some rare pedigrees, however, the Carr (Nuffield Orthopaedic Centre, condition is genetically dominant. Oxford, UK), called for international Some research has suggested that cooperation to avoid the pitfalls a major gene effect is present, associated with ascertainment of explained Tatiana Axenovich and twins and large families with several colleagues (Russian Academy Science Photo Library
T
affected generations needed for these studies. These genetic studies rely on accurate identification of individuals with a true idiopathic phenotype. A workshop, chaired by Ian Stokes, (University of Vermont, Burlington, VA, USA), examined this thorny issue. The basic proposed standard definition of the phenotype (to be available soon on the Internet at http://www.ndos.ox.ac.uk/pzs) is a minimum lateral curvature of the spine of 10º, some vertebral rotation at the apex of the curve, and no central-nervous-system involvement. Use of this classification by research nurses in family ascertainment should ensure that geneticists study families with idiopathic disease, rather than scoliosis of neuromuscular, congenital, syndromal, or degenerative origins. Stephanie Clark
Australia focuses on Mycobacterium ulcerans new focus of Buruli ulcer around Melbourne, Australia, was reported at a meeting held in the city (April 1–3) to commemorate the 50th anniversary of the isolation, also in Australia, of the causative agent, Mycobacterium ulcerans. Between 1992 and 1997, 46 cases of M ulcerans occurred, said Paul Johnson (Monash, Melbourne) the largest cluster (28 cases) being in Cowes, Phillip Island. In 1992 an embankment was built on the island across a swamp, preventing natural drainage, and over the next 2 years M ulcerans cases occurred mainly among people living near the swamp or a nearby golf course. PCR analysis revealed M ulcerans DNA in swamp-
A
water samples and ground water from the swamp, which was being used to irrigate the golf course. Many infected patients remembered being cut or scratched by sharp vegetation at the skin site where the Buruli ulcer developed. It seems likely that infecting bacteria had been inoculated from vegetation covered with biofilms deposited by the contaminated water. M ulcerans toxin is thought to cause the extensive necrosis but poor inflammatory response associated with Buruli ulcer. New work on the toxin was reported by groups from the US National Institutes of Health Rocky Mountain laboratory (MT, USA) and Imperial College, London, UK. In vitro, a toxin “filtrate” from
M ulcerans depressed cytokine secretion from T lymphocytes and macrophages and made the latter cells resistant to some interleukins. The filtrate did not kill immune cells, but arrested the cell cycle. The term immunosuppressive factor may thus be more accurate than toxin. Analysis of the semipurified factor showed it to be a low molecular weight lipid, possibly from the cell wall. A full description of the factor’s structure and synthesis may suggest new ways to treat Buruli ulcer—currently, the lesions can be controlled only by surgery and, in the case of extensive disease, by amputation. David Wright
Hit diabetes hard and early for best long-term results
S
ome people in the early stages of type I diabetes retain residual islet function. A new study from the DCCT (Diabetes Control and Complications Trial) research group has found that intensive therapy for these patients prolongs their ability to produce endogenous insulin and lowers their risk of diabetic complications. The study examined 855 trial participants who had been diagnosed with type I diabetes for 1–5 years. 303 “responders” had some resid-
1184
ual insulin secretion. 138 of these people were assigned to intensive therapy—three or more insulin injections daily or continuous subcutaneous insulin infusion—as were 274 non-responders. The remaining responders received conventional therapy—one or two insulin injections daily. Patients were followed for up to 6 years to monitor -cell function and diabetic complications. Responders treated intensively had greater endogenous insulin secretion during the first 5
years than those given conventional therapy. The risk of severe hypoglycaemia with seizure or coma was reduced by 65% and the risk of retinopathy progression by 50% in intensively treated responders compared with non-responders (Ann Intern Med 1998; 128: 517–23). The researchers estimate that islet function was extended for at least 2 years in responders who were treated intensively. Hannah Wunsch
THE LANCET • Vol 351 • April 18, 1998