Losing the "war against cancer": a need for public policy reforms.
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Biomedical subjects
Publications and source records attributed to I D Bross.
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The two steps necessary for the clinical expression of a mutagenic disease, genetic damage and viability, are countervailing forces and therefore the dosage response curve for mutagens must have a maximum. To illustrate that science is common sense reduced to calculation, a new mathematical derivation of this result and supporting data are given. This example also shows that the term "context-free" is a snare and a delusion. When statistical methods are used in a scientific context where their assumptions are known to fail and where there is a reasonable presumption of intent to deceive, they are fraudulent. Estimation of low-level mutagenic risks by linear extrapolation from high-dose data is one example of such a method that is widely used by Executive Branch agencies. Other examples are given of fraudulent statistical methods that are currently used in biomedical research done by or for U.S. government agencies. In the long run, it is argued, the surest way to eradicate such fraud is for biostatisticians to do their own science.
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A recently developed model of the human granulpoietic system had been used to analyze the toxic effects of 5-fluorouracil administered to cancer patients. From this analysis there appeared to be a relationship between the level of the early leukopenic depression and the rate at which the drug kills cells in the marrow. In particular, it may be possible to estimate this kill rate from the extent of the maximal depression in the white blood count during the second or third week after treatment begins. This estimate may be useful when planning modifications in treatment in order to prevent the onset of hematologic crises.
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Most exposure to low-level ionizing radiation, both diagnostic x-rays and nuclear radiation, occur in the range between 100 milirads and 10 rads--the "one rad range". In the past, the estimates of hazards in this range have been obtained by linear extrapolation from data on persons who were exposed to much higher dosages, generally in the centirad range used in radiotherapy of non-malignant disease. This article presents the first dosage response curve for the one rad range ever to be developed directly from data on men exposed to ordinary diagnostic radiation. The findings are based on approximately 220 men with non-lymphatic leukemia and more than 270 random-sample controls from the Tri-State Survey. The new findings suggest that the estimates previously obtained by extrapolation from high dosage levels to low dose levels underestimate the actual hazards by an order of magnitude. The new dosage response curves indicate that linear extrapolation fails because it disregards the subgroups in the general population that are particularly vulnerable to x-ray. There are immediate implications concerning the use of medical x-rays in screening or for routine purposes. The past risk-benefit calculations are based on extrapolative estimates and require drastic revision. Uses of x-ray which were previously marginal are now clearly counterindicated.
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This paper analyses the distribution of metastases at every site of the human body in acute lymphoblastic, chronic lymphocytic, acute myeblastic and chronic myelocytic leukemias in patients that come to autopsy. It appeared that the 4 types of leukemia had a similar seeding frequency of the skin, breast, trachea, diaphragm and all other muscles. The highest incidence of metastases was found in the lymphatic system (i.e. all lymph-nodes and spleen). Acute lymphoblastic leukemia showed an excess of metastases in the major blood vessels, pleura, large intestines, extrahepatic biliary tract, ureters, prostate, cervix uteri, central nervous system, thymus, ovaries and pituitary. The excess of metastases at specific sites did not cluster either in topographical areas or in anatomical systems, with the exception of metastases in the central nervous and endocrine systems (acute lymphoblastic leukemia). Chronic lymphocytic leukemia showed an excess of metastases in all lymph nodes, kidney, adrenals and heart. A lymphatic route of dissemination, as opposed to a blood-borne spread of malignant cells, was hypothesised to account for the excess of metastases in the above mentioned organs in patients affected with chronic lymphocytic leukemia. Soil specificity with the degree of anaplasia of leukemic cells may account for the higher than expected occurrence of metastases in a given organ, for a specific leukemia. This remark holds true particularly for acute lymphoblastic leukemia.
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