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Biomedical subjects

D Robb

Publications and source records attributed to D Robb.

At least 19 recordsLinked to original sources

Typing for major histocompatibility complex class II antigens in thyroid tissue blocks: association of Hashimoto's thyroiditis with HLA-DQA0301 and DQB0201 alleles.

This study was undertaken 1) to find out whether we can type major histocompatibility class II antigens from the paraffin-embedded series of thyroid tissue, and 2) to investigate whether HLA-DQ genes are involved in conferring a risk of Hashimoto's thyroiditis. To this end we used the polymerase chain reaction to amplify DNA from paraffin-embedded thyroid tissue blocks of histologically proven Hashimoto's disease. We used 46 specimens for HLA-DQA and 32 for DQB typing. The alleles were identified by sequence-specific oligonucleotide hybridizations. Fifty controls from the same geographic region were also typed using peripheral leukocyte DNA. HLA-DQA0301 (in linkage disequilibrium with DR4) was significantly increased (58.7% vs. 32% in controls; chi 2 = 6.73; P less than 0.01) in patients compared to controls. DQB0201 (in linkage disequilibrium with DR3) was also increased in the patient group (66% vs. 36% in controls; chi 2 = 6.63; P less than 0.01). Although DQA0301/DQB0201 heterozygotes (18.8%) were increased in patients compared to controls (6%), the difference was not significant. However, 81% of the patients (26 of 32) were DQA0301 and/or DQB0201 positive compared to 48% of controls (chi 2 5.98; P less than 0.05). We conclude that it is feasible to type HLA antigens from tissue blocks and that susceptibility to Hashimoto's disease is probably mediated through two pathways: DQA0301/DR4 and DQB0201/DR3.

Alleles

A profile of Alexandra.

In this article publications on the demography and environmental and health status of Alexandra Township are reviewed and a demographic survey carried out in 1990 is reported. The demographic data presented in the article describe the age, sex and ethnic profile of the population. It also describes the health and disease status, provides some vital statistics, describes the health services and discusses the implications for the development of appropriate health care strategies. Approximately 19% of the population live in informal dwellings or shelters, 14% in the newly upgraded areas and 67% in old Alexandra. Mean household occupancy was 4.04 with a male/female (m/f) ratio of 0.86. It was 3.08 in informal dwellings (m/f = 1.11), 4.30 in the newly upgraded areas (m/f = 0.74) and 4.28 for Old Alex (m/f = 0.82). Old Alex had the highest proportion of inhabitants aged over 60 years. On average females have been resident in Alexandra for 16.8 years and males for 14.9 years.

Adolescent

Costs of primary health care at the Alexandra Health Centre.

This study provides a detailed analysis of costs and expenditure patterns at a primary health care centre serving an impoverished community of about 200,000 people. Data were collected on costs and utilisation of services at the Alexandra Health Centre and University Clinic (AHC) for the financial year ending March 1990. Capital and running costs were kept separate. The sources of data collection were statistics routinely collected in the different sections of the clinic, the accounting records, staff duty rosters and a prospective study done to collect information to apportion drug costs and to calculate the cost of a prescription. The audited operating expenditure at AHC for the 1990 financial year was R3.9 million, or R4,45 million with donations (mainly drugs and staff). Sixty-three per cent of total costs went on staff, 16% on drugs and supplies, 9% on buildings, furniture and transport, 3% on laboratory services, 2% on security and 8% on other items. The outpatients department accounted for 57% of expenditure, the 24-hour unit 37% and the outreach section 6%. Looked at another way, 66% went on curative services, 32% on preventive and promotive (including 13% on maternity costs) services, and 2% on rehabilitation services. The average cost per visit to each of 14 services is presented. The cost of a visit to casualty is R38.85, to the antenatal clinic R18.65 and to the child health outreach programme for immunisation R6.67. The component costs of each visit are analysed. The major cost component of a consultation is usually clinical staff, and detailed staff allocations for each section are given.(ABSTRACT TRUNCATED AT 250 WORDS)

Budgets

Developing a health information system for a primary health care centre in Alexandra, Johannesburg.

The development of a health information system, which went through 6 overlapping phases, appropriate for a primary health care centre at the Alexandra Health Centre and University Clinic (AHC) is reviewed. The three essential concepts were data, information and indicators. The system at the AHC moved from unused data to unused information and to operational indicators. It also moved from a concern with data and information to one concerned with communication of information. The way a health information system evolves is, to a large extent, a reflection of the information needed by the group that is planning the system. In the AHC information needs were initially felt by senior management and attempts to involve other staff failed because of lack of timely feedback and a lack of management skills at all levels. In the process of trying to involve people and of getting to the correct type and amount of information, it became obvious that a health information system is complex and involves data as the major outputs, with people being the common thread of the system.

Community Health Centers

High rates of ras codon 61 mutation in thyroid tumors in an iodide-deficient area.

Using polymerase chain reaction and sequence-specific oligonucleotide hybridization, the frequency of three ras oncogene mutations (N-ras, Ha-ras, and K-ras) in thyroid tumors (25 adenomas, 16 follicular carcinomas, and 22 papillary carcinomas) was investigated in both iodide-deficient and iodide-sufficient areas. The ras oncogene mutation rate was significantly higher in the iodide-deficient area, being 85 versus 17% in the adenomas, and 50 versus 10% in the follicular carcinomas. No mutations were found in papillary carcinomas. The most common mutation site was Ha-ras codon 61 with Gln----Arg substitution. Two ras mutations at codon 61 (Gln----Lys in N-ras and Gln----Arg in Ha-ras) were found in a microfollicular adenoma specimen from Eastern Hungary. We conclude that dietary iodine may modulate ras oncogene mutations, and that in the iodide-deficient area, ras oncogene activation may play a more important role in the initiation and/or maintenance of follicular tumors. Additional factors are, however, necessary to initiate carcinogenesis.

Adenocarcinoma

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

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.

Female

Fetal glycaemic control and neonatal complications in diabetic pregnancy.

To examine the relationship between fetal glycaemic control and macrosomia or neonatal hypoglycaemia, we measured umbilical cord glycosylated haemoglobin (GHb) by affinity chromatography in 44 diabetic and 40 normal pregnancies. Levels of GHb in cord blood were not significantly different between these two groups, suggesting good maternal glycaemic control was achieved in the diabetic patients. Moreover in the diabetic pregnancies, cord GHb levels did not differ in infants who were macrosomic or developed hypoglycaemia by comparison with those infants who showed neither phenomenon. We conclude that overall fetal glycaemic control in the 4-6 week period prior to delivery does not appear to influence these common neonatal complications of diabetic pregnancy.

Adult

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

Medical education.

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Education, Medical

The catecholase activity of Neurospora tyrosinase.

A highly purified preparation of tyrosinase from Neurospora crassa was isolated with a view to elucidating its mechanism of action. Both the resting and functioning molecular weights of the enzyme were determined as 33000 plus or minus 2000 and kinetic data in conjunction with binding studies indicated the presence of only one site within the enzyme for binding phenolic substrates. Kinetic constants for several 0-diphenols and for the inhibitors cyanide and benzoic acid were determined and the kinetics are consistent with a mechanism in which either the substrates are bound in a random order or the diphenol binds first. The enzyme forms an oxygenated complex and a complex with hydrogen peroxide and both are detectable spectroscopically

Benzoates