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Who dies where in the USA
THE LANCET
SCIENCE AND MEDICINE
More pieces of the cancer puzzle are assembled t the American Association for Cancer Research meeting in San Diego (CA, USA; April 12–16), Richard Klausner (director of the US National Cancer Institute) described his agency’s approach to cancer diagnostics as a process of identifying the pieces and then assembling the puzzle. Parts of the puzzle that may be closer to interlocking after the San Diego meeting are apoptosis, DNA methylation, and angiogenesis. Regulation of apoptosis was discussed by Stanley Korsmeyer (Washington University School of Medicine, St Louis, MO, USA). The cell is an “autonomous rheostat of programmed cell death”, he said, with cell death regulated by both antiapoptotic (Bcl-2) and proapoptotic (Bax) members of the Bcl-2 family. Both proteins are upstream of “executioner” proteases (caspases), and both are multifunctional—one of their functions may be the formation of ion-selective channels. Ralph Weichselbaum (University of Chicago Center of Radiation Biology, IL, USA) discussed the role of membrane lipids and kinases in apoptosis induced by radiation.When protein kinase C is selectively inhibited by chelerythrine, ceramide production is increased through sphingomyelinase induction. This results in increased apoptosis of irradiated tumour cells in vitro and radiosensitisation of tumours in animal models. The darker side of chemotherapyinduced apoptosis was presented
A
by John Hickman (University of Liverpool, UK) who suggested that hierarchies of gene expression determine thresholds for apoptosis and these are different in different cells. The antiapoptotic molecule Bcl-2 is absent in the cells of the small intestine, he said, but present in colonic stem cells, making these cell types susceptible and resistant, respectively, to apoptosis. Thus, chemotherapy for colon cancer may result in unwanted collateral damage. Steve Baylin (Johns Hopkins Comprehensive Cancer Center, Baltimore, MD, USA) discussed the imbalance of DNA methylation in cancer and its consequences. Bulk DNA in tumour cells is hypomethylated, but CpG islands in gene promoters are hypermethylated. The methylation-density-dependent transcriptional silencing that results from this can inactivate tumour suppressor genes. This seems to be the case for p16INK4A, the second most frequently altered gene in tumours. Angiogenesis is a hot target for anticancer-drug development. Some enzymes involved in the process are matrix metalloproteases (MMPs). In animal models, inhibition of MMPs decreases both the number and size of metastases (Lynn Matrisian, Vanderbilt University, TN, USA). Several MMP inhibitors—eg, AG 3340 and batimastat—are now being developed for clinical use. More direct angiogenesis inhibitors, such as TNP 470, are also in clinical trials. Nafsika Georgopapadakou
Who dies where in the USA Heart disease in white males Age-adjusted death rate per 100 000 population 253·8 – 328·6 236·8 – 253·7 215·2 – 236·7 199·9 – 215·1 179·5 – 199·8 166·7 – 179·4 112·4 – 166·6 Source: Atlas of United States mortality http://www.cdc.gov/nchswww/nchshome.htm
he US Centers for Disease Control and Prevention’s National Center for Health Statistics has published an atlas of the leading causes of death by race and sex for
T
1226
small geographical areas throughout the USA. One finding (figure) is that death rates for heart disease are now higher in southeastern states than in northeastern states.
News in brief Too many hysterectomies in UK 53% of UK general practitioners believe that hysterectomies should be used only as a last resort in menorrhagia, says a survey published by the Task Force to Improve the Management of Menorrhagia (April 21). Nevertheless about 14% of UK women will have a hysterectomy before the age of 65 to solve this problem. The survey’s authors suggest that one reason for the high hysterectomy rate is that ineffective medicines are often prescribed for menorrhagia. Panic disorder worldwide Panic disorder is diagnosed at relatively constant rates around the world (Arch Psychiatr 1997; 54: 305–09). Prevalence rates of the condition, as defined by DSM-III, were gathered from surveys in the USA, Canada, France, Lebanon, Germany, Italy, Taiwan, Korea and New Zealand. The rates were remarkably consistent, ranging from 1·4 cases per 100 survey respondents in Edmonton, Canada, to 2·9 per 100 in Florence, Italy. Taiwan had an exceptionally low rate (0·4 per 100). The disorder was more common in women, and rates of agoraphobia and major depression were higher among panic patients in all nations. HIV-1-infected blood in UK Three UK patients have been infected with HIV-1 from a single blood donation. This is only the second such case out of over 30 million UK blood donations since HIV screening was introduced in 1985. The donor was in the “window period” before antibodies to HIV-1 develop, when infection cannot be detected by screening tests. The National Blood Authority was alerted in late March, 1997, after a transfusion recipient was found to be HIV-1 positive. Two other recipients were then traced. Midwives versus doctors A survey carried out in Washington, USA, reveals that low-risk women are less likely to receive obstetric interventions when cared for by certified nurse-midwives than when cared for by obstetrician-gynaecologists or family physicians. Caesarean section rates were 8·8%, 13·6%, and 15·1% for nurse-midwives, obstetricians, and family physicians, respectively.
Vol 349 • April 26, 1997
SCIENCE AND MEDICINE
More pieces of the cancer puzzle are assembled t the American Association for Cancer Research meeting in San Diego (CA, USA; April 12–16), Richard Klausner (director of the US National Cancer Institute) described his agency’s approach to cancer diagnostics as a process of identifying the pieces and then assembling the puzzle. Parts of the puzzle that may be closer to interlocking after the San Diego meeting are apoptosis, DNA methylation, and angiogenesis. Regulation of apoptosis was discussed by Stanley Korsmeyer (Washington University School of Medicine, St Louis, MO, USA). The cell is an “autonomous rheostat of programmed cell death”, he said, with cell death regulated by both antiapoptotic (Bcl-2) and proapoptotic (Bax) members of the Bcl-2 family. Both proteins are upstream of “executioner” proteases (caspases), and both are multifunctional—one of their functions may be the formation of ion-selective channels. Ralph Weichselbaum (University of Chicago Center of Radiation Biology, IL, USA) discussed the role of membrane lipids and kinases in apoptosis induced by radiation.When protein kinase C is selectively inhibited by chelerythrine, ceramide production is increased through sphingomyelinase induction. This results in increased apoptosis of irradiated tumour cells in vitro and radiosensitisation of tumours in animal models. The darker side of chemotherapyinduced apoptosis was presented
A
by John Hickman (University of Liverpool, UK) who suggested that hierarchies of gene expression determine thresholds for apoptosis and these are different in different cells. The antiapoptotic molecule Bcl-2 is absent in the cells of the small intestine, he said, but present in colonic stem cells, making these cell types susceptible and resistant, respectively, to apoptosis. Thus, chemotherapy for colon cancer may result in unwanted collateral damage. Steve Baylin (Johns Hopkins Comprehensive Cancer Center, Baltimore, MD, USA) discussed the imbalance of DNA methylation in cancer and its consequences. Bulk DNA in tumour cells is hypomethylated, but CpG islands in gene promoters are hypermethylated. The methylation-density-dependent transcriptional silencing that results from this can inactivate tumour suppressor genes. This seems to be the case for p16INK4A, the second most frequently altered gene in tumours. Angiogenesis is a hot target for anticancer-drug development. Some enzymes involved in the process are matrix metalloproteases (MMPs). In animal models, inhibition of MMPs decreases both the number and size of metastases (Lynn Matrisian, Vanderbilt University, TN, USA). Several MMP inhibitors—eg, AG 3340 and batimastat—are now being developed for clinical use. More direct angiogenesis inhibitors, such as TNP 470, are also in clinical trials. Nafsika Georgopapadakou
Who dies where in the USA Heart disease in white males Age-adjusted death rate per 100 000 population 253·8 – 328·6 236·8 – 253·7 215·2 – 236·7 199·9 – 215·1 179·5 – 199·8 166·7 – 179·4 112·4 – 166·6 Source: Atlas of United States mortality http://www.cdc.gov/nchswww/nchshome.htm
he US Centers for Disease Control and Prevention’s National Center for Health Statistics has published an atlas of the leading causes of death by race and sex for
T
1226
small geographical areas throughout the USA. One finding (figure) is that death rates for heart disease are now higher in southeastern states than in northeastern states.
News in brief Too many hysterectomies in UK 53% of UK general practitioners believe that hysterectomies should be used only as a last resort in menorrhagia, says a survey published by the Task Force to Improve the Management of Menorrhagia (April 21). Nevertheless about 14% of UK women will have a hysterectomy before the age of 65 to solve this problem. The survey’s authors suggest that one reason for the high hysterectomy rate is that ineffective medicines are often prescribed for menorrhagia. Panic disorder worldwide Panic disorder is diagnosed at relatively constant rates around the world (Arch Psychiatr 1997; 54: 305–09). Prevalence rates of the condition, as defined by DSM-III, were gathered from surveys in the USA, Canada, France, Lebanon, Germany, Italy, Taiwan, Korea and New Zealand. The rates were remarkably consistent, ranging from 1·4 cases per 100 survey respondents in Edmonton, Canada, to 2·9 per 100 in Florence, Italy. Taiwan had an exceptionally low rate (0·4 per 100). The disorder was more common in women, and rates of agoraphobia and major depression were higher among panic patients in all nations. HIV-1-infected blood in UK Three UK patients have been infected with HIV-1 from a single blood donation. This is only the second such case out of over 30 million UK blood donations since HIV screening was introduced in 1985. The donor was in the “window period” before antibodies to HIV-1 develop, when infection cannot be detected by screening tests. The National Blood Authority was alerted in late March, 1997, after a transfusion recipient was found to be HIV-1 positive. Two other recipients were then traced. Midwives versus doctors A survey carried out in Washington, USA, reveals that low-risk women are less likely to receive obstetric interventions when cared for by certified nurse-midwives than when cared for by obstetrician-gynaecologists or family physicians. Caesarean section rates were 8·8%, 13·6%, and 15·1% for nurse-midwives, obstetricians, and family physicians, respectively.
Vol 349 • April 26, 1997