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Brain injuries at birth linked to early psychiatric diseases
THE LANCET
SCIENCE AND MEDICINE
Breast cancer treatments take a step towards oral chemotherapy ment of oral therapy. Smith’s team is testing a combination of 5-ethynyluracil and 5-fluorouracil (5-FU). Clinical responses and low toxicity have already been found. Smith noted that “infusional chemotherapy has high activity in the treatment of breast cancer and oral 5-FU derivatives are the next step”. He predicted that infusional pumps may start to be phased out “within a year”. Michael Steel (St Andrews University, UK) dampened enthusiasm for moves Do women want to know about gene mutations? towards population Several studies have asked women with a family history screening for mutaof breast cancer whether they would have a genetic tions in BRCA1 test for BRCA1 and BRCA2 mutations. The latest of and BRCA2. With these (Psychosom Med 1997; 59: 459–66) reports that the exception of among 74 US women with one or more first-degree defined groups relative with breast cancer, 46% planned to seek such as the genetic testing immediately, 35% would get a test in Ashkenazi Jews, he the future, and 19% did not want the test. Women only said, there is no want the test, say the researchers, if they believe the point in mass advantages of knowing their mutation status outweighs screening because the disadvantages. Jane Bradbury a negative result cannot give women
hase-II trials on oral chemotherapy for breast cancer have at last started, said Ian Smith (Royal Marsden Hospital, London, UK), one of the speakers at the 5th Nottingham International Breast Cancer Conference (Sept 17–19). Oral chemotherapy might be more acceptable to patients than continuous pump infusion, but the unpredictable bioavailability and short biological half-life of many anticancer drugs has slowed develop-
P
Brain injuries at birth linked to early psychiatric diseases
A
prospective study of low birthweight babies suggests that those with white-matter brain injury are at increased risk of psychiatric disease in childhood . About 20% of a cohort of 564 low birthweight babies treated in the neonatal intensive-care units of three US hospitals had cranial abnormalities when screened by ultrasonography within 1 week of birth. When assessed 6 years later, 22% of the cohort had at least one psychiatric disease, most commonly attention deficit hyperactivity disorder (15·6%) but also tic disorders and separation anxiety (Arch Gen Psych 1997; 54: 847–56). Multivariate analysis indicated that haemorrhage into the germinal matrix, which occurs in up to 40% of very low birthweight infants, did not increase the risk of psychiatric disease. However, ischaemic injury to white matter, found in 5–10% of such babies, was associated with a four-fold increase in the risk of having at least one psychiatric disease. Jane Dawson
936
the all clear. Until all the BRCA genes are mapped and mutations in the genes fully understood, true population screening will not be viable, he concluded. Diagnosis and early treatment of breast cancer has improved greatly in the UK and other European countries, but the late consequences do not seem to be so well managed, said Hugh Bishop, a surgeon at the George Eliot Hospital, Nuneaton, UK. For instance, women who develop bone metastases do not always receive the best care— only 27% of patients with spinal metastases in whom surgical treatment would have been appropriate have decompression or stabilisation procedures. Bishop believes there is an urgent need for a multidisciplinary approach to metastatic bone disease and has produced a set of draft guidelines in which diagnosis, staging, and treatment are discussed. M-C McMenemy, Stephanie Clark
Apply neuroprotectants rapidly for best results he prompt initiation of treatment with neuroprotectants could alter the clinical outcome of ischaemic stroke, said delegates at the World Congress of Neurology in Buenos Aires, Argentina (Sept 14–19). James Grotta (University of Texas, USA) explained how neuroprotective agents are mainly designed to save potentially viable but ischaemically threatened brain tissue—the so called “ischaemic penumbra”. This is composed of neurones in which the reduced blood supply is insufficient to maintain normal metabolic and functional activity. According to Grotta, permanent neural damage occurs first in the infarct core. Later, waves of depolarisations spread into the peri-infarct tissue and adversely affect penumbral tissue survival. Grotta acknowledged that neuroprotection is not a new concept. Work has been done on a number of agents, he said, but in many cases has been abandoned, either because of unacceptable side-effects or lack of benefits. A new type of neuroprotective agent (lubeluzole) has now been developed that works by decreasing extracellular glutamate and blocking the glutamate-activated nitric oxide pathway. As with all
T
neuroprotection, the effectiveness of lubeluzole depends on how soon drug therapy is initiated after the onset of acute stroke, said Grotta. In on-going clinical trials, he noted, the compound has been given within 6 hours of stroke. Werner Hacke (Heidelberg University, Germany) has used positron-emission tomography to establish the duration of the therapeutic window after ischaemic stroke. His results revealed that some ischaemic tissues in the penumbra of the infarct are still potentially viable more than 6 hours after the onset of acute stroke. In order to maximise the effective use of neuroprotective agents, treatment strategies for early intervention in stroke need to be reconsidered. These, according to Thomas Brott of the University of Cincinnati, OH, USA, include improving public and media awareness and informing everyone concerned about steps to take after a stroke. This target group, he said, should include people at risk of stroke and their families, as well as paramedics and ambulance staff. Brott also identified a need to organise acute stroke care in special units. Peter Kandela
Vol 350 • September 27, 1997
SCIENCE AND MEDICINE
Breast cancer treatments take a step towards oral chemotherapy ment of oral therapy. Smith’s team is testing a combination of 5-ethynyluracil and 5-fluorouracil (5-FU). Clinical responses and low toxicity have already been found. Smith noted that “infusional chemotherapy has high activity in the treatment of breast cancer and oral 5-FU derivatives are the next step”. He predicted that infusional pumps may start to be phased out “within a year”. Michael Steel (St Andrews University, UK) dampened enthusiasm for moves Do women want to know about gene mutations? towards population Several studies have asked women with a family history screening for mutaof breast cancer whether they would have a genetic tions in BRCA1 test for BRCA1 and BRCA2 mutations. The latest of and BRCA2. With these (Psychosom Med 1997; 59: 459–66) reports that the exception of among 74 US women with one or more first-degree defined groups relative with breast cancer, 46% planned to seek such as the genetic testing immediately, 35% would get a test in Ashkenazi Jews, he the future, and 19% did not want the test. Women only said, there is no want the test, say the researchers, if they believe the point in mass advantages of knowing their mutation status outweighs screening because the disadvantages. Jane Bradbury a negative result cannot give women
hase-II trials on oral chemotherapy for breast cancer have at last started, said Ian Smith (Royal Marsden Hospital, London, UK), one of the speakers at the 5th Nottingham International Breast Cancer Conference (Sept 17–19). Oral chemotherapy might be more acceptable to patients than continuous pump infusion, but the unpredictable bioavailability and short biological half-life of many anticancer drugs has slowed develop-
P
Brain injuries at birth linked to early psychiatric diseases
A
prospective study of low birthweight babies suggests that those with white-matter brain injury are at increased risk of psychiatric disease in childhood . About 20% of a cohort of 564 low birthweight babies treated in the neonatal intensive-care units of three US hospitals had cranial abnormalities when screened by ultrasonography within 1 week of birth. When assessed 6 years later, 22% of the cohort had at least one psychiatric disease, most commonly attention deficit hyperactivity disorder (15·6%) but also tic disorders and separation anxiety (Arch Gen Psych 1997; 54: 847–56). Multivariate analysis indicated that haemorrhage into the germinal matrix, which occurs in up to 40% of very low birthweight infants, did not increase the risk of psychiatric disease. However, ischaemic injury to white matter, found in 5–10% of such babies, was associated with a four-fold increase in the risk of having at least one psychiatric disease. Jane Dawson
936
the all clear. Until all the BRCA genes are mapped and mutations in the genes fully understood, true population screening will not be viable, he concluded. Diagnosis and early treatment of breast cancer has improved greatly in the UK and other European countries, but the late consequences do not seem to be so well managed, said Hugh Bishop, a surgeon at the George Eliot Hospital, Nuneaton, UK. For instance, women who develop bone metastases do not always receive the best care— only 27% of patients with spinal metastases in whom surgical treatment would have been appropriate have decompression or stabilisation procedures. Bishop believes there is an urgent need for a multidisciplinary approach to metastatic bone disease and has produced a set of draft guidelines in which diagnosis, staging, and treatment are discussed. M-C McMenemy, Stephanie Clark
Apply neuroprotectants rapidly for best results he prompt initiation of treatment with neuroprotectants could alter the clinical outcome of ischaemic stroke, said delegates at the World Congress of Neurology in Buenos Aires, Argentina (Sept 14–19). James Grotta (University of Texas, USA) explained how neuroprotective agents are mainly designed to save potentially viable but ischaemically threatened brain tissue—the so called “ischaemic penumbra”. This is composed of neurones in which the reduced blood supply is insufficient to maintain normal metabolic and functional activity. According to Grotta, permanent neural damage occurs first in the infarct core. Later, waves of depolarisations spread into the peri-infarct tissue and adversely affect penumbral tissue survival. Grotta acknowledged that neuroprotection is not a new concept. Work has been done on a number of agents, he said, but in many cases has been abandoned, either because of unacceptable side-effects or lack of benefits. A new type of neuroprotective agent (lubeluzole) has now been developed that works by decreasing extracellular glutamate and blocking the glutamate-activated nitric oxide pathway. As with all
T
neuroprotection, the effectiveness of lubeluzole depends on how soon drug therapy is initiated after the onset of acute stroke, said Grotta. In on-going clinical trials, he noted, the compound has been given within 6 hours of stroke. Werner Hacke (Heidelberg University, Germany) has used positron-emission tomography to establish the duration of the therapeutic window after ischaemic stroke. His results revealed that some ischaemic tissues in the penumbra of the infarct are still potentially viable more than 6 hours after the onset of acute stroke. In order to maximise the effective use of neuroprotective agents, treatment strategies for early intervention in stroke need to be reconsidered. These, according to Thomas Brott of the University of Cincinnati, OH, USA, include improving public and media awareness and informing everyone concerned about steps to take after a stroke. This target group, he said, should include people at risk of stroke and their families, as well as paramedics and ambulance staff. Brott also identified a need to organise acute stroke care in special units. Peter Kandela
Vol 350 • September 27, 1997