- Email: [email protected]
"Poor old lady"
1087
and Powles’ ("Tamoxifen is likely to be the safest, the most effective, and the only realistic option... "). The risks cited by both sides are mostly those occurring shortly after the start of treatment (hepatic failure, thromboembolism, and ocular toxicity). The occurence of hepatic carcinoma in two women taking tamoxifen 40 mg/day for 2 years5 is noted but given little weight. Because large doses of tamoxifen give rats liver cancer after a short period (and smaller doses over a longer period), will small doses of tamoxifen taken for a long time give human beings cancer? For prophylactic treatment a "long time" may be 20 years or more. The urgency of settling this question (or at least according the risks of liver cancer due weight) is heightened by knowing that tamoxifen is a chemical relative of known carcinogens (eg, diethylstilboestrol), and that the liver may need to be exposed to carcinogens (eg, aflatoxins) over many years before cancer develops.
John Bignall
Central Province
(most-year-round transmission); and Kakuma/ Turkana (seasonal transmission). Much of the local population in these regions practise subsistence farning, and poverty and chloroquine resistance are endemic. AMREF aims to provide 30% bed-net coverage to at-risk groups and will organise 20 workshops for 5000 participants in each project
Ortum/Lokichoggio,
A malaria education programme will be introduced into at least 30% of primary schools. 40 non-electric sewing machines will be bought and distributed, together with 25 000 kg of net material and 1000 litres of insecticide. area.
Richard Horton 1. Alonso PL, Lindsay nets on
SW, Armstrong JRM, et al. The effect of insecticide-treated bed mortality of Gambian children. Lancet 1991; 337: 1499-502.
Depression treatment guidelines
1. Williams
GM, Iatropoulos MJ, Djordjevic MV, Kaltenberg OP. The triphenylethylene drug tamoxifen is a strong liver carcinogen in the rat. Carcinogenesis 1993; 14: 315-17. 2. Nayfield SG, Karp SE, Ford LG, et al. Potential role of tamoxifen in prevention of breast cancer. J Natl Cancer Inst 1991; 83: 1450-59. 3. Fugh-Berman A, Epstein S. Tamoxifen: disease prevention or disease substitution? Lancet 1992; 340: 1143-45. 4. Powles TJ. The case for clinical trials of tamoxifen for prevention of breast cancer. Lancet 1992; 340:1145-47. 5. Fornander T, Rutqvist LE, Cedermark B, et al. Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet 1989; i: 117-19.
Fusion vaccines for
lymphoma
The first vaccine to prevent B-cell lymphoma in mice by generating antibodies to a tumour-specific immunoglobulin and amplifying this response by means of a cytokine fused to the antigen is reported in this week’s Nature.1 Two difficulties face researchers working on tumour-cell vaccines: identifying a suitable tumour-specific antigen and ensuring its immunogenicity. Malignant B cells have surface immunoglobulin molecules that possess variable regions (idiotypes) which are candidate antigens but weak immunogens. Combination with an adjuvant both protects animals from further tumour-cell challenge and helps to cure animals of their cancer. Tao and Levy have fused granulocyte-macrophage colony-stimulating factor (GM-CSF), which enhances antigen presentation, with a tumourderived idiotype to produce a strong immunogen that protects against an otherwise fatal inoculation of tumour cells. Mice immunised with the idiotype alone or with a simple mixture of the idiotype and murine GM-CSF died between day 16 and day 23. In mice vaccinated with the fusion protein, there was a 40-60% long-term survival (greater than 120 days after challenge) depending on the dose of vaccine given. Recognition of the importance of local cytokine effects in regulating the immune response is likely to provide a strong since potentially toxic stimulus to vaccine research, immunoadjuvants can be avoided. For human cancer, the search for widely expressed but specific tumour-associated antigens should proceed with the knowledge that there are likely to be effective means of translating the antigen into an effective vaccine. Richard Horton 1. Tao
M-H, Levy Idiotype/granulocyte-macrophage colony-stimulating factor protein as a vaccine for B-cell lymphoma. Nature 1993; 362: 755-58. R.
fusion
Malaria prevention in Kenya Glaxo has donated 380000 to the African Medical and Foundation (AMREF) for malaria prevention programmes in Kenya. The funding extends over three years and will enable AMREF to pursue its twin goals of community education about malaria and provision of insecticide-impregnated bed nets to those at risk. Insecticide-treated bed nets are able to reduce overall mortality and mortality attributable to malaria by two-thirds among children under 5 years of age;’ malaria kills 1 in 20 children in this age-group. AMREF has targeted four areas (combined population of 1-75 million) for particular attention—Kololini, Kilifi district, and Migori, South Nyanza (all-year round transmission); Sagana,
Research
The US Agency for Health Care Policy and Research (AHCPR) panel has issued guidelines1 on the treatment of depression for primary-care doctors and has urged them to be more aggressive in their diagnosis and treatment of the disease. The panel said that less than a third of the 11 million Americans with depression are being properly diagnosed and treated, and that the disorder should be considered a medical disease which in most cases can be successfully treated. The recommendations, however, immediately drew fire from social workers, psychologists, and other mental health professionals who charged that the new guidelines reflected a bias favouring medication over psychotherapy. "It encourages relatively extensive treatment for depression in primary care settings without either consultation by or referral to a mental health professional", said Russ Newman of the American Psychological Association. The panel concluded that over 50% of depressed patients who begin treatment with antidepressant medication "experience a marked improvement or complete remission of their depressive symptoms", and that patients treated with medication alone responded more quickly than those treated with psychotherapy alone. It recommended medication
as
the initial
treatment
for
patients with the more severe or chronic symptoms, a history of recurrent episodes of depression, a family history of depression, and those with melancholic symptoms; psychotherapy alone when the depression was less severe, less chronic or recurrent, and less disabling; and a combination of medication and psychotherapy for more severe and complex cases and the patients who do not respond to either alone. The panel also concluded that light therapy was effective in mild to moderate seasonal depression, and that electroconvulsive therapy should be reserved for patients with severe depression that has not responded to other treatment. Michael
McCarthy
1. Depression Guideline Panel. Depression m Primary Care, vol 1, Diagnosis and Detection (AHCPR publication 93-0550), and vol 2, Treatment of Major Depression (AHCPR publication 93-0551). Clinical Practice Guideline, no 5. Rockville, Maryland: US Department of Health and Human Services, Agency of Health Care Policy and Research.
"Poor old
lady"
Most clinicians would accept that old age alone is no reason to withhold effective treatment. How many, though, would advise an 87-year-old with aortic valve stenosis and extensive coronary artery disease to undergo aortic valve replacement and coronary bypass surgery? The patient had the operations and did well. The case report is accompanied by a risk/benefit! analysis balancing an average life expectancy (5-6 years) for a US female of 87 with other factors, and concludes "... surgery wins out substantially over leaving the ’poor old lady’ alone". Substitute "total hip replacement" for the cardiac operations and this conclusion would not be so surprising: attitudes to treatments need to keep up with advances in their efficacy and availability. John JB, Salem DN, Pauker SG. "You’re 971-73.
1. Wong
never too
old". N Engl
Bignall
J Med 1993; 328:
and Powles’ ("Tamoxifen is likely to be the safest, the most effective, and the only realistic option... "). The risks cited by both sides are mostly those occurring shortly after the start of treatment (hepatic failure, thromboembolism, and ocular toxicity). The occurence of hepatic carcinoma in two women taking tamoxifen 40 mg/day for 2 years5 is noted but given little weight. Because large doses of tamoxifen give rats liver cancer after a short period (and smaller doses over a longer period), will small doses of tamoxifen taken for a long time give human beings cancer? For prophylactic treatment a "long time" may be 20 years or more. The urgency of settling this question (or at least according the risks of liver cancer due weight) is heightened by knowing that tamoxifen is a chemical relative of known carcinogens (eg, diethylstilboestrol), and that the liver may need to be exposed to carcinogens (eg, aflatoxins) over many years before cancer develops.
John Bignall
Central Province
(most-year-round transmission); and Kakuma/ Turkana (seasonal transmission). Much of the local population in these regions practise subsistence farning, and poverty and chloroquine resistance are endemic. AMREF aims to provide 30% bed-net coverage to at-risk groups and will organise 20 workshops for 5000 participants in each project
Ortum/Lokichoggio,
A malaria education programme will be introduced into at least 30% of primary schools. 40 non-electric sewing machines will be bought and distributed, together with 25 000 kg of net material and 1000 litres of insecticide. area.
Richard Horton 1. Alonso PL, Lindsay nets on
SW, Armstrong JRM, et al. The effect of insecticide-treated bed mortality of Gambian children. Lancet 1991; 337: 1499-502.
Depression treatment guidelines
1. Williams
GM, Iatropoulos MJ, Djordjevic MV, Kaltenberg OP. The triphenylethylene drug tamoxifen is a strong liver carcinogen in the rat. Carcinogenesis 1993; 14: 315-17. 2. Nayfield SG, Karp SE, Ford LG, et al. Potential role of tamoxifen in prevention of breast cancer. J Natl Cancer Inst 1991; 83: 1450-59. 3. Fugh-Berman A, Epstein S. Tamoxifen: disease prevention or disease substitution? Lancet 1992; 340: 1143-45. 4. Powles TJ. The case for clinical trials of tamoxifen for prevention of breast cancer. Lancet 1992; 340:1145-47. 5. Fornander T, Rutqvist LE, Cedermark B, et al. Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet 1989; i: 117-19.
Fusion vaccines for
lymphoma
The first vaccine to prevent B-cell lymphoma in mice by generating antibodies to a tumour-specific immunoglobulin and amplifying this response by means of a cytokine fused to the antigen is reported in this week’s Nature.1 Two difficulties face researchers working on tumour-cell vaccines: identifying a suitable tumour-specific antigen and ensuring its immunogenicity. Malignant B cells have surface immunoglobulin molecules that possess variable regions (idiotypes) which are candidate antigens but weak immunogens. Combination with an adjuvant both protects animals from further tumour-cell challenge and helps to cure animals of their cancer. Tao and Levy have fused granulocyte-macrophage colony-stimulating factor (GM-CSF), which enhances antigen presentation, with a tumourderived idiotype to produce a strong immunogen that protects against an otherwise fatal inoculation of tumour cells. Mice immunised with the idiotype alone or with a simple mixture of the idiotype and murine GM-CSF died between day 16 and day 23. In mice vaccinated with the fusion protein, there was a 40-60% long-term survival (greater than 120 days after challenge) depending on the dose of vaccine given. Recognition of the importance of local cytokine effects in regulating the immune response is likely to provide a strong since potentially toxic stimulus to vaccine research, immunoadjuvants can be avoided. For human cancer, the search for widely expressed but specific tumour-associated antigens should proceed with the knowledge that there are likely to be effective means of translating the antigen into an effective vaccine. Richard Horton 1. Tao
M-H, Levy Idiotype/granulocyte-macrophage colony-stimulating factor protein as a vaccine for B-cell lymphoma. Nature 1993; 362: 755-58. R.
fusion
Malaria prevention in Kenya Glaxo has donated 380000 to the African Medical and Foundation (AMREF) for malaria prevention programmes in Kenya. The funding extends over three years and will enable AMREF to pursue its twin goals of community education about malaria and provision of insecticide-impregnated bed nets to those at risk. Insecticide-treated bed nets are able to reduce overall mortality and mortality attributable to malaria by two-thirds among children under 5 years of age;’ malaria kills 1 in 20 children in this age-group. AMREF has targeted four areas (combined population of 1-75 million) for particular attention—Kololini, Kilifi district, and Migori, South Nyanza (all-year round transmission); Sagana,
Research
The US Agency for Health Care Policy and Research (AHCPR) panel has issued guidelines1 on the treatment of depression for primary-care doctors and has urged them to be more aggressive in their diagnosis and treatment of the disease. The panel said that less than a third of the 11 million Americans with depression are being properly diagnosed and treated, and that the disorder should be considered a medical disease which in most cases can be successfully treated. The recommendations, however, immediately drew fire from social workers, psychologists, and other mental health professionals who charged that the new guidelines reflected a bias favouring medication over psychotherapy. "It encourages relatively extensive treatment for depression in primary care settings without either consultation by or referral to a mental health professional", said Russ Newman of the American Psychological Association. The panel concluded that over 50% of depressed patients who begin treatment with antidepressant medication "experience a marked improvement or complete remission of their depressive symptoms", and that patients treated with medication alone responded more quickly than those treated with psychotherapy alone. It recommended medication
as
the initial
treatment
for
patients with the more severe or chronic symptoms, a history of recurrent episodes of depression, a family history of depression, and those with melancholic symptoms; psychotherapy alone when the depression was less severe, less chronic or recurrent, and less disabling; and a combination of medication and psychotherapy for more severe and complex cases and the patients who do not respond to either alone. The panel also concluded that light therapy was effective in mild to moderate seasonal depression, and that electroconvulsive therapy should be reserved for patients with severe depression that has not responded to other treatment. Michael
McCarthy
1. Depression Guideline Panel. Depression m Primary Care, vol 1, Diagnosis and Detection (AHCPR publication 93-0550), and vol 2, Treatment of Major Depression (AHCPR publication 93-0551). Clinical Practice Guideline, no 5. Rockville, Maryland: US Department of Health and Human Services, Agency of Health Care Policy and Research.
"Poor old
lady"
Most clinicians would accept that old age alone is no reason to withhold effective treatment. How many, though, would advise an 87-year-old with aortic valve stenosis and extensive coronary artery disease to undergo aortic valve replacement and coronary bypass surgery? The patient had the operations and did well. The case report is accompanied by a risk/benefit! analysis balancing an average life expectancy (5-6 years) for a US female of 87 with other factors, and concludes "... surgery wins out substantially over leaving the ’poor old lady’ alone". Substitute "total hip replacement" for the cardiac operations and this conclusion would not be so surprising: attitudes to treatments need to keep up with advances in their efficacy and availability. John JB, Salem DN, Pauker SG. "You’re 971-73.
1. Wong
never too
old". N Engl
Bignall
J Med 1993; 328: