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HRT has little effect on stroke risk
SCIENCE AND MEDICINE
HRT has little effect on stroke risk
News in brief
researchers, since hormone replaceormone replacement therapy ment therapy had no overall protecwith conjugated equine oestrotive effect and actually caused a jump gen and progestin neither increases in heart attack risk during the first nor decreases the risk of stroke in year of treatment. post-menopausal women, The new paper looking according to a new US Rights were at stroke incidence study (Circulation 2001; not granted to among the HERS partici103: 638–42). The include this pants reports that after an researchers looked at the image in average follow-up of 4·1 incidence of stroke years, 149 of the 2763 among women participatelectronic women had one or more ing in Heart and media. Please strokes. More women in Estrogen–progestin refer to the the hormone treatment Replacement Study printed journal. group had strokes (82) (HERS). than in the placebo group HERS was a secondary (67) but the difference coronary heart disease HRT may not help was not statistically sigprevention trial in which nificant, with the relative hazard for all women who participated had having a stroke associated with horknown coronary artery disease mone therapy being 1·23 (95% CI (JAMA 1998; 280: 605–13). 0·89–1·70). The study also found no Observational studies had suggested increased risk for transient ischaemic that hormone replacement therapy, attacks associated with hormone use. which is thought to have strong Lead author Joel Simon of the protective effect on blood vessels, University of California, San would reduce the risk of heart attacks Francisco (San Francisco, California) in this group. In the study, 2763 said the results should be reassuring postmenopausal women were to women on oestrogen–progestin randomised to take either 0·625 mg therapy but cautioned that the results of conjugated oestrogen plus 2·5 mg may not apply to women who have of medroxyprogesterone or placebo. no history of heart disease or to It was the first randomised trial women taking only oestrogen. looking at the effect of hormone replacement therapy on heart disease risk. The results surprised Michael McCarthy
Inhaled insulin is safe for type 2 diabetes Last week, a Fast Track paper in The Lancet (Feb 3, p 331) demonstrated the potential use of inhaled insulin therapy in patients with type 1 diabetes mellitus. This week, a study is published by the same research group describing the benefits of inhaled insulin for patients with type 2 diabetes. The researchers showed that pulmonary delivery of insulin for 3 months was well tolerated in 26 patients and significantly improved glycaemic control (Ann Intern Med 2001; 134: 203–07).
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H
Doctors are a safe bet for motor insurance Physicians have one of the safest records behind the wheel, according to research by Bell Direct. 20% of UK doctors have had a car accident, 3% fewer than the national average and 9% fewer than the clergy, one of the highest risk occupations studied. In addition, only 13% of doctors have a driving conviction, compared with the national average of 16%. However, while the clergy may be accident prone when travelling around the parish, only 10% of vicars and priests have a motoring conviction.
Suppression of an src kinase may protect the brain after stroke
A
study published this month suggests that pp60, one of a family of signalling molecules known as src kinases, may be a new therapeutic target to prevent cerebral ischaemia after stroke. Mice treated with PP1, an inhibitor of pp60, up to 6 h after an induced stroke showed less vascular permeability, reduced oedema, improved cerebral perfusion, and decreased infarct volume 24 h later. David Cheresh (Scripps Research Institute, La Jolla, CA, USA) and co-workers showed that mice lacking pp60 are resistant to the vascular permeability that occurs in stroke in response to the release of vascular endothelial growth factor (VEGF). pp60-deficient mice showed decreased infarct sizes after induced stroke compared with control mice. Wild-type mice injected with PP1 15 min after the induction of cerebral ischaemia showed decreased infarct volumes. The effect was
THE LANCET • Vol 357 • February 10, 2001
dose-specific and a reduction of 70% was achieved at 1·5 g/kg. Treatment with PP1 given 6 h after stroke induction was less effective, with a 40% decrease in infarct volume observed at the same dose. In another experiment, mice were injected with PP1 15 min after stroke and monitored by MRI. Cerebral ischaemia occurred in treated and control mice after 1 h, but after 24 h PP1-treated mice showed significantly enhanced cerebral perfusion. Treated mice also showed a significant improvement in cerebral function after 24 h, with fewer neurological signs (Nat Med 2001; 7: 222–27). Cheresh hopes that src kinase inhibitors will move forward quickly to clinical trials. “We are currently in discussion with companies that have highly selective src inhibitors; these will be tested over the next 12–18 months in more than one stroke model”, he reports. Karl Plate (University of
Erlangen-Nürnberg, Germany) finds this approach “highly interesting” but warns that src kinase inhibitors “may not be easily transferable to the clinic because the target molecules are involved in many signal-transduction pathways”. VEGF is important for the formation and function of new blood vessels and disturbing this process may lead to severe side-effects, he says. “Some src inhibitors may turn out to be quite toxic and it will be important to thoroughly investigate their side effects before they are considered for use in patients.” Nevertheless, Cheresh anticipates an approach to the FDA in the next 2 years to apply for permission to begin phase I clinical testing. “At least one src inhibitor is about to begin clinical trials for late-stage cancer patients; this should hasten our attempts to move this compound ahead for stroke”, he says. Kathryn Senior
449
For personal use only. Reproduce with permission from The Lancet Publishing Group.
HRT has little effect on stroke risk
News in brief
researchers, since hormone replaceormone replacement therapy ment therapy had no overall protecwith conjugated equine oestrotive effect and actually caused a jump gen and progestin neither increases in heart attack risk during the first nor decreases the risk of stroke in year of treatment. post-menopausal women, The new paper looking according to a new US Rights were at stroke incidence study (Circulation 2001; not granted to among the HERS partici103: 638–42). The include this pants reports that after an researchers looked at the image in average follow-up of 4·1 incidence of stroke years, 149 of the 2763 among women participatelectronic women had one or more ing in Heart and media. Please strokes. More women in Estrogen–progestin refer to the the hormone treatment Replacement Study printed journal. group had strokes (82) (HERS). than in the placebo group HERS was a secondary (67) but the difference coronary heart disease HRT may not help was not statistically sigprevention trial in which nificant, with the relative hazard for all women who participated had having a stroke associated with horknown coronary artery disease mone therapy being 1·23 (95% CI (JAMA 1998; 280: 605–13). 0·89–1·70). The study also found no Observational studies had suggested increased risk for transient ischaemic that hormone replacement therapy, attacks associated with hormone use. which is thought to have strong Lead author Joel Simon of the protective effect on blood vessels, University of California, San would reduce the risk of heart attacks Francisco (San Francisco, California) in this group. In the study, 2763 said the results should be reassuring postmenopausal women were to women on oestrogen–progestin randomised to take either 0·625 mg therapy but cautioned that the results of conjugated oestrogen plus 2·5 mg may not apply to women who have of medroxyprogesterone or placebo. no history of heart disease or to It was the first randomised trial women taking only oestrogen. looking at the effect of hormone replacement therapy on heart disease risk. The results surprised Michael McCarthy
Inhaled insulin is safe for type 2 diabetes Last week, a Fast Track paper in The Lancet (Feb 3, p 331) demonstrated the potential use of inhaled insulin therapy in patients with type 1 diabetes mellitus. This week, a study is published by the same research group describing the benefits of inhaled insulin for patients with type 2 diabetes. The researchers showed that pulmonary delivery of insulin for 3 months was well tolerated in 26 patients and significantly improved glycaemic control (Ann Intern Med 2001; 134: 203–07).
Science Photo Library
H
Doctors are a safe bet for motor insurance Physicians have one of the safest records behind the wheel, according to research by Bell Direct. 20% of UK doctors have had a car accident, 3% fewer than the national average and 9% fewer than the clergy, one of the highest risk occupations studied. In addition, only 13% of doctors have a driving conviction, compared with the national average of 16%. However, while the clergy may be accident prone when travelling around the parish, only 10% of vicars and priests have a motoring conviction.
Suppression of an src kinase may protect the brain after stroke
A
study published this month suggests that pp60, one of a family of signalling molecules known as src kinases, may be a new therapeutic target to prevent cerebral ischaemia after stroke. Mice treated with PP1, an inhibitor of pp60, up to 6 h after an induced stroke showed less vascular permeability, reduced oedema, improved cerebral perfusion, and decreased infarct volume 24 h later. David Cheresh (Scripps Research Institute, La Jolla, CA, USA) and co-workers showed that mice lacking pp60 are resistant to the vascular permeability that occurs in stroke in response to the release of vascular endothelial growth factor (VEGF). pp60-deficient mice showed decreased infarct sizes after induced stroke compared with control mice. Wild-type mice injected with PP1 15 min after the induction of cerebral ischaemia showed decreased infarct volumes. The effect was
THE LANCET • Vol 357 • February 10, 2001
dose-specific and a reduction of 70% was achieved at 1·5 g/kg. Treatment with PP1 given 6 h after stroke induction was less effective, with a 40% decrease in infarct volume observed at the same dose. In another experiment, mice were injected with PP1 15 min after stroke and monitored by MRI. Cerebral ischaemia occurred in treated and control mice after 1 h, but after 24 h PP1-treated mice showed significantly enhanced cerebral perfusion. Treated mice also showed a significant improvement in cerebral function after 24 h, with fewer neurological signs (Nat Med 2001; 7: 222–27). Cheresh hopes that src kinase inhibitors will move forward quickly to clinical trials. “We are currently in discussion with companies that have highly selective src inhibitors; these will be tested over the next 12–18 months in more than one stroke model”, he reports. Karl Plate (University of
Erlangen-Nürnberg, Germany) finds this approach “highly interesting” but warns that src kinase inhibitors “may not be easily transferable to the clinic because the target molecules are involved in many signal-transduction pathways”. VEGF is important for the formation and function of new blood vessels and disturbing this process may lead to severe side-effects, he says. “Some src inhibitors may turn out to be quite toxic and it will be important to thoroughly investigate their side effects before they are considered for use in patients.” Nevertheless, Cheresh anticipates an approach to the FDA in the next 2 years to apply for permission to begin phase I clinical testing. “At least one src inhibitor is about to begin clinical trials for late-stage cancer patients; this should hasten our attempts to move this compound ahead for stroke”, he says. Kathryn Senior
449
For personal use only. Reproduce with permission from The Lancet Publishing Group.