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Biomedical subjects

D Robson

Publications and source records attributed to D Robson.

At least 55 records · Page 3Linked to original sources

Radiation dose and breast cancer risk in patients treated for cancer of the cervix.

The relationship between breast cancer and radiation treatment for cervical cancer was evaluated in an international study of 953 women who subsequently developed breast cancer and 1,806 matched controls. Radiation doses to the breast (average 0.31 Gy) and ovaries (average 32 Gy) were reconstructed for exposed subjects on the basis of their original radiotherapy records. Overall, 88% of the breast cancer cases and 89% of the controls received radiation treatment [relative risk (RR) = 0.88; 95% confidence interval (CI) = 0.7-1.2]. Among women with intact ovaries (561 cases, 1,037 controls), radiotherapy was linked to a significant 35% reduction in breast cancer risk, attributable in all likelihood to the cessation of ovarian function. Ovarian doses of 6 Gy were sufficient to reduce breast cancer risk but larger doses did not reduce risk further. This saturation-type response is probably due to the killing of a critical number of ovarian cells. Cervical cancer patients without ovaries (145 cases, 284 controls) were analyzed separately because such women are at especially low natural risk for breast cancer development. In theory, any effect of low-dose breast exposure, received incidentally during treatment for cervical cancer, should be more readily detectable. Among women without ovaries, there was a slight increase in breast cancer risk (RR = 1.07; 95% CI = 0.6-2.0), and a suggestion of a dose response with the RR being 1.0, 0.7, 1.5 and 3.1 for breast doses of 0, 0.01-0.24, 0.25-0.49 and 0.50+ Gy, respectively. However, this trend of increasing RR was not statistically significant. If low-dose radiation increases the risk of breast cancer among women over age 40 years, it appears that the risk is much lower than would be predicted from studies of younger women exposed to higher doses.

Adult↗

Is ingestion of milk-associated bacteria by premature infants fed raw human milk controlled by routine bacteriologic screening?

Expressed human milk is often used to feed premature infants. Raw milk contains bacteria which may be a source of infection. Milk banks have developed screening programs which combine periodic quantitative milk cultures with arbitrary rules specifying limits of bacterial concentration. It is unknown whether such programs succeed in preventing infants from being fed milk containing bacteria. At the Health Sciences Centre (Winnipeg, Manitoba, Canada), milk is screened once weekly. When a woman's milk is found to have excess bacteria, it is discarded only if she is an unrelated donor (as opposed to an infant's mother). To assess the effectiveness of this screening program, we determined the frequency at which infants fed raw human milk were exposed to milk-associated bacteria and compared the bacterial contents of donor and maternal milk. From February 1986 to April 1987, all human milk fed to 98 premature infants during the first 2 weeks of feeding (n = 10,128 feeds) was cultured quantitatively. Among study infants, 100% were exposed at least once to coagulase-negative staphylococci, 41% were exposed to Staphylococcus aureus, and 64% were exposed to gram-negative bacilli. The proportions of feeds containing bacteria and the quantities (log10 CFU [mean +/- standard deviation]) ingested per positive feed were: 39% and 5.9 +/- 0.5 for coagulase-negative staphylococci; 2.4% and 5.1 +/- 1.0 for S. aureus; and 5.2% and 4.8 +/- 1.1 for gram-negative bacilli. There were no adverse events attributable to ingestion of milk-associated bacteria. Milk coagulase-negative staphylococcal isolates were multiply antibiotic susceptible, whereas infant isolates were antibiotic resistant. Donor milk was significantly less likely than maternal milk to contain coagulase-negative staphylococcal species in any quantity (40 versus 93% of samples, respectively [P < 0.001]) or in concentrations exceeding 10(8) CFU/liter (3 versus 27% of samples, respectively [P < 0.0001]). There was no difference between milk from either source in terms of S. aureus or gram-negative bacterial content (4 to 6%). These results suggest that the Health Sciences Centre screening program is effective in limiting the number of harmless coagulase-negative staphylococcal species but has no impact on the quantity of potentially pathogenic bacteria ingested by premature infants. Implications for screening donor milk are discussed.

Bacteria↗

Radiation dose and second cancer risk in patients treated for cancer of the cervix.

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.

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Influence of nonbiologic implants on laminectomy membrane formation in dogs.

The effects of various surgical implants, spinal cord hypothermia, and glucocorticoid administration on formation of the laminectomy membrane were evaluated in 32 preconditioned chondrodystrophoid dogs. Modified dorsal laminectomies and full-length durotomies, from T12 to L1, were performed on all dogs. Dogs were allotted to 2 groups. Group-1 dogs (n = 20) were further allocated to 4 subgroups (a, b, c, and d) consisting of 5 dogs each. Group-1a dogs received no implant, group-1b dogs had absorbable gelatin sponges implanted, group-1c dogs had absorbable gelatin films implanted, and group-1d dogs had absorbable gelatin sponges and absorbable gelatin films implanted. Daily neurologic examinations permitted correlation of neurologic dysfunction with secondary spinal cord compression in those dogs in which it developed. The influence of these implants on laminectomy membrane formation and dural healing was assessed by gross and microscopic evaluation of transverse sections of the vertebrae and spinal cord after euthanasia of one member of each subgroup at 1, 2, 4, 8, and 16 weeks after surgery. Group-2 dogs (n = 12) were further allotted to 3 subgroups (a, b, and c) consisting of 4 dogs each. One dog in each group-2 subgroup underwent the same surgical procedures described for the group-1 subgroups (ie, 4 procedures/group-2 subgroup). The additional effects of 3 conventional supportive techniques (selective regional spinal cord hypothermia, glucocorticoid administration, or spinal cord hypothermia and glucocorticoid administration) on laminectomy membrane formation and on immediate postoperative recovery were examined in groups 2a, 2b, and 2c, respectively. Neurologic examinations were performed daily until this time. All dogs in group 2 were euthanatized 1 week after surgery for gross and microscopic examination of transverse sections of the vertebrae and spinal cord. Qualitative histopathologic effects of the different implants and supportive techniques on formation of the laminectomy membrane were determined. Statistical analysis of the degrees of secondary spinal cord compression was performed in group-1 dogs by measuring and comparing ratios of the vertical to the horizontal diameters of the transverse spinal cord sections from locations within (T12 to L1) and out of (T11, T11-12, L1-2, and L2) the region of surgical intervention. The vertical/horizontal diameter ratios measured from transverse sections from T11 to L2 in size-matched, untreated control dogs formed the standards for a mean roundness index of the spinal cord in the various anatomic locations of the vertebral column.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Radiation dose and leukemia risk in patients treated for cancer of the cervix.

To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical cancer and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.

Adult↗

A preliminary double-blind study of intravenous nitroglycerin in acute myocardial infarction.

A preliminary double-blind, placebo-controlled study of the effects of a 48-h intravenous infusion of nitroglycerin (NG) in 140 patients with acute myocardial infarction has been carried out. The patients were randomised to placebo or active treatment within 12 h of the onset of symptoms. Those patients treated with nitroglycerin showed a significant reduction on both days in systolic blood pressure, haemoglobin concentration, and packed cell volume. There was also a significant reduction in diamorphine usage in the first 24 h. There was a higher incidence (non-significant) of dysrhythmia in the placebo group despite an increased usage of antidysrhythmic therapy. The mortality rate in the placebo group was 13%, and 7.8% in the active treatment group, but this difference was not significant. At the 3-month follow-up, 83% of treated patients as opposed to 60% of placebo group were able to resume normal or near-normal activities. Preliminary findings suggest that intravenous NG may be useful treatment for patients with acute myocardial infarction and a larger-scale trial is warranted.

Adult↗