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Biomedical subjects

D B Thomas

Publications and source records attributed to D B Thomas.

At least 91 records · Page 5Linked to original sources
PubMed1993

Histologic types and hormone receptors in breast cancer in men: a population-based study in 282 United States men.

Histologic slides from 282 incident cases of breast cancer in men, that were identified in 10 population-based cancer registries in the United States, were reviewed by a single pathologist. Breast cancer more often presented in the noninvasive stage in men (10.8 percent of all cases) than would be expected among women. All noninvasive carcinomas were of the ductal type. Of invasive carcinomas, compared with women, men had smaller proportions of lobular and mucinous types and larger proportions of ductal and papillary types and Paget's disease. No case of tubular or medullary carcinoma was seen. The breast in men is composed only of ducts and normally contains no lobules, and the histologic types of breast carcinomas that predominate in men are likely of ductal origin. Estrogen and progesterone receptors were present in 86.7 percent and 76.3 percent of invasive carcinomas, respectively, which are higher proportions than would be expected among women. Also, unlike findings in women, receptor content was not associated with patient age at diagnosis.

Age Factors↗
PubMed1993

Tamm Horsfall protein binds to a single class of carbohydrate specific receptors on human neutrophils.

Several studies have implicated urinary Tamm Horsfall protein (THP) in the aetiology of tubulointerstitial inflammation. Previous research has demonstrated that particulate THP will initiate inflammatory activation of human polymorphonuclear leukocytes (PMN) through a trypsin sensitive mechanism. The present study describes the binding of 125I-monomeric THP to human PMN at 4 degrees C and demonstrates that radiolabeled THP binds to PMN in a saturable, reversible and time dependent manner. The addition of 400 to 600 ng 125I-THP/2 x 10(6) PMN was sufficient to achieve saturable binding. Scatchard analysis of binding data yielded linear plots suggesting a single class of receptors with a mean density of 26218/cell and a dissociation constant (KD) of 4.2 x 10(-9) M. Binding reached steady state by 15 minutes and could be rapidly displaced by the addition of an excess of unlabeled THP. The KD calculated from experimentally derived kinetic rate constants (k1 and k2) was of a similar order of magnitude (0.9 x 10(-9) M) to that generated from Scatchard plots. In addition 125I-THP bound specifically to PMN plasma membrane immobilized on nitrocellulose filters, a process which could be inhibited by unlabeled monomeric THP. Chemical modification of unlabeled THP abolished its capacity to inhibit binding. Specific inhibition studies showed that N-acetylneuraminic (sialic) acid dose dependently displaced the binding of 125I-THP to immobilized PMN membranes at concentrations up to 100 mM. These results indicate that the reported activation of human PMN by THP is mediated through a single class of sialic acid-specific cell surface receptors.

Carbohydrate Metabolism↗
PubMed1993

Lactation and the risk of epithelial ovarian cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

The relationship between lactation and the development of epithelial ovarian cancer was assessed in data from seven countries that were collected for a multinational hospital-based case-control study conducted between 1979 and 1988. Three hundred and ninety-three cases of ovarian cancer were compared to 2565 controls matched on age, hospital, and year of interview. A non-significant reduction in risk with short-term lactation was observed but no further reduction in risk was seen with long-term lactation. The reduction in risk associated with months of lactation was not as great as the reduction with months of pregnancy, which may be a result of lactation being a less effective form of ovulation suppression than pregnancy. The short-term lactation that takes place in developed countries, may provide as great a reduction in risk as the long-term lactation practised in the developing countries included in this study.

Breast Feeding↗
PubMed1993

Breast cancer and prolonged lactation. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

The possible relationship between breastfeeding and risk of breast cancer was assessed in multinational hospital-based case-control study that was conducted from 1979 to 1986 in 10 countries, including some in which many women lactated for long periods of time. Data were collected by personal interviews of 2336 cases and 14,900 controls. No statistically significant trends in relative risk estimates with duration of lactation were observed in all women combined, in women who were pre-or postmenopausal, in women of various ages at diagnosis, in women with different numbers of livebirths, or in women characterized by the presence or absence of other risk factors for breast cancer. No trends in risk were observed with mean number of months that a woman lactated per breastfed child, or with number of pregnancies followed by treatment with oral or injectable medication to suppress lactation. In premenopausal women, and in those with two or more livebirths, most risk estimates for women who lactated for various lengths of time > 6 months, relative to the risk in women who breastfed for < or = 3 months, were less than unity, but the 95% confidence intervals of all estimates included one. Long-term lactation may reduce slightly the risk of breast cancer, but the evidence for this from the present and prior investigations is not strong.

Adult↗
PubMed1993

Fecundity and oviposition in laboratory colonies of the screwworm fly (Diptera: Calliphoridae).

The screwworm fly is mass-produced using an artificial larval diet and an artificial oviposition substrate. On the artificial diet, mean fecundity was 185 eggs per female, whereas host-reared flies averaged 280 eggs per female. Host-reared flies were generally larger (head capsule width [HCW] > 3.6 mm) than laboratory-reared flies (HCW < 3.6 mm). Larger flies are generally more fecund, and size is related to larval nutrition. Only 75-89% of females reared on artificial diet and maintained at 30 degrees C were gravid at 6 d of age compared with 100% of host-reared females tested at 5-6 d. When gravid females were offered artificial substrate for oviposition, approximately 28% failed to oviposit and another 11% laid only partial clutches. Among all females tested for oviposition, 25% of the total egg production was withheld. Fecundity influenced oviposition, because the more mature eggs a female had, the more likely she was to oviposit. Supplementing the adult diet of honey and water with raw meat increased fecundity by 14% under normal laboratory conditions, but by as much as 350% in flies in which larval feeding was curtailed by removal of the larvae from the media 1 d before the normal completion of development. Many females became gravid in 4-5 d at 30 degrees C versus 8-9 d at 22 degrees C. But fecundity and oviposition rate were more variable (less synchronous) in colonies maintained at the higher temperature. This suggests that there may be greater selection for laboratory adaptation at the higher maintenance temperatures.

Animals↗
PubMed1993

Breast cancer in men.

Epidemiologic studies of breast cancer in men have provided insights into the pathogenesis and etiology of breast cancer in both sexes. Individual carcinomas from both the male and female breast are histologically indistinguishable, but histologic types of ductal origin occur relatively more frequently in men than in women, and those of lobular origin are very uncommon in men, reflecting the absence of lobular structures in the normal male breast. The same variations in incidence and mortality rates of breast cancer among countries and racial and ethnic groups that have been observed in women also occur in men, clearly indicating that the causes of these variations are not primarily risk factors related to being female. Risk of breast cancer in men increases with age, with no change in the rate of increase at the usual age of menopause; this supports the assumption that the midlife change in the rate of increase with age in women is due to the reduction in ovarian hormone production at menopause. Incidence rates of breast cancer in men have remained stable over time, suggesting that the temporal increase in rates in women is a result of either enhanced detection due to screening or changes in risk factors that are sex-specific. In men, an increase in risk of breast cancer has been associated with testicular pathology and dysfunction, and a decrease in risk has been related to high fertility, a history of prostate cancer, and exogenous androgens. These observations suggest that risk may be enhanced by low levels, and reduced by high levels, of androgens. Conversely, high estrogen levels probably increase risk of breast cancer in men, since risk has been associated with several conditions that may result in hyperestrogenism. These conditions included obesity, rapid weight gain, elevated blood cholesterol, gallstones, non-insulin-dependent diabetes, and chronic liver diseases. Studies of the role of endogenous hormones in the etiology of breast cancer in women have tended to focus on estrogens (71). These observations on breast cancer in men suggest that the relative levels of androgens and estrogens may be of etiologic importance, and that additional studies in women should include measurements of androgens. A history of breast cancer in a first-degree relative is associated with about a doubling of the risk of breast cancer in both men and women.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgens↗
PubMed1993

Exogenous progestins and breast cancer.

More research on the effect of exogenous progestins on breast cancer risk is clearly needed. Biologic evidence that progestins may act synergistically with estrogen to enhance proliferation of breast epithelial cells emphasizes the importance of further exploration of this issue, particularly given the increasing prevalence of exposure to contraceptive and noncontraceptive progestins. No specific type or dose of progestin in monophasic combination oral contraceptives has been linked to breast cancer. Based on the few epidemiologic studies of progestin-only oral contraceptives, there also is no evidence that they increase risk of breast cancer. Two studies found that longer-term use of progestin-only pills was associated with a decreased risk of breast cancer. However, given the low prevalence of use of minipills, it is unlikely that this exposure substantially affects the incidence of breast cancer in the population as a whole. Use of the injectable contraceptive DMPA has been positively associated with risk of breast cancer in some subgroups of women, although no significant overall adverse effect has been observed in the two largest studies conducted to date. There is suggestive evidence that use at an early age or prior to a first term birth and recent use may increase risk of breast cancer. It remains unclear, however, whether or not surveillance bias may explain the positive association observed in recent users. Additional research on DMPA and breast cancer incidence is needed, since studies published to date have lacked sufficient power to evaluate risk in relation to long-term use. Future studies of breast cancer in relation to use of other long-acting progestational agents such as Norplant will also be important. There is concern about the relation between breast cancer incidence and use of combined estrogen-progestin replacement therapy, especially extended periods of use. At the present time, only one study (45) has estimated risk according to duration of use, and it remains uncertain whether the reported elevation in risk seen in long-term users of combined therapy is due to enhanced surveillance for breast cancer among exposed women. Further research will be required before any definitive conclusions can be reached about the potential effect of estrogen-progestin replacement regimens on breast cancer incidence. Future studies should attempt to determine the circumstances under which progestins may alter risk of breast cancer and whether such effects vary by duration of use, dosage, type of preparation, concomitant use of estrogens, regimen of exposure, and the timing of progestin use in relation to age and menstrual and reproductive events.(ABSTRACT TRUNCATED AT 400 WORDS)

Breast Neoplasms↗
PubMed1993

Release of gelatinase and superoxide from human mononuclear phagocytes in response to particulate Tamm Horsfall protein.

This study describes the in vitro activation of human mononuclear phagocytes by particulate Tamm Horsfall protein (THP). Peripheral blood monocytes phagocytosed THP particles with the accompanying release of superoxide radicals, N-acetyl-beta-D-glucosaminidase, and neutral metalloproteinase. Immunoprecipitation and substrate gel analysis identified the neutral proteinase as a 95-kd gelatinase. A comparison with other particulate ligands highlighted the specificity of the response to THP and showed that the magnitude of the response was comparable with that obtained with lipopolysaccharide (100 micrograms/ml). Parallel studies using peritoneal macrophages resulted in a similar pattern of enzyme release and reactive oxygen species synthesis. THP has been implicated in the pathogenesis of tubulointerstitial nephritis associated with reflux nephropathy. The present study indicates that an inflammatory response initiated by a neutrophil-THP interaction may be extended into a chronic phase via the activation of mononuclear phagocytes. The subsequent release of reactive oxygen metabolites and proteinases may contribute to the tissue damage and fibrosis associated with chronic immune-mediated tubulointerstitial nephritis.

Chemical Precipitation↗
PubMed1992

Human papillomaviruses, herpes simplex viruses, and the risk of oral cancer in men.

A population-based case-control study was conducted in western Washington state to examine the relations between infection with human papilloma viruses (HPV), herpes simplex viruses (HSV), and risk of oral squamous cell cancer in men. Interviews were completed on 131 oral cancer cases diagnosed between January 1985 and December 1989 and 136 controls frequency matched to cases on age and date of diagnosis who were obtained by random digit dialing. The risk for oral cancer among men with 30 or more sexual partners was 2.4 times that of men with four or fewer partners (95% confidence interval (CI) 1.0-5.9). Men who ever practiced oral sex had lower risk for oral cancer relative to men who never practiced oral sex (relative risk (RR) = 0.4, 95% CI 0.2-0.8). Analyses of exfoliated oral cavity cells for the presence of HPV-6 DNA with polymerase chain reaction revealed that men with an oral HPV-6 infection had 2.9 times the risk for oral cancer of noninfected men (95% CI 1.1-7.3), whereas men with an oral HPV-16 infection had 6.2 times the risk for oral cancer of noninfected men (crude RR = 6.2, 95% CI 0.7-52.2). Relative risks associated with serologically detected HSV-1 and HSV-2 infections were 0.8 (95% CI 0.3-1.7) and 1.8 (95% CI 0.7-4.6), respectively. The authors conclude that HPV-6 is associated with oral cancer. Although men infected with HPV-16 and HSV-2 were at elevated risk, these associations may have been due to chance. The role of specific sexual practices in the transmission of viruses to the oral cavity remains unclear.

Antibodies, Viral↗
PubMed1992

Breast cancer in men: risk factors with hormonal implications.

Cases included in a population-based case-control study of breast cancer in men were recruited from 10 geographic areas of the United States from 1983 to 1986. Controls, matched to cases on age and geographic area, were selected by random digit dialing for men under age 65 years and from Health Care Financing Administration files for older men. Results are based on responses from 227 cases and 300 controls to questions asked in a standardized personal interview. An increased risk of breast cancer was most strongly associated with undescended testes and was also related to orchiectomy, orchitis, testicular injury, late puberty, and infertility; and a decreasing trend in risk was observed with an increasing number of children. Relative risk estimates were also elevated in relation to a history of high blood cholesterol, rapid weight gain, benign breast conditions, and possibly obesity. These findings suggest that breast cancer in men develops in response to androgen deficiency associated with testicular dysfunction and under conditions associated with excess estrogen. Risk was also found to be elevated in men with a history of amphetamine use, diabetes, and cigar smoking and reduced in men with prior head trauma.

Adult↗
PubMed1992

Electric power, pineal function, and the risk of breast cancer.

Breast cancer is the leading cause of cancer death in women in the industrialized world, and the rates of breast cancer incidence are rising. Although risk is high in industrialized societies, it is low in nonindustrialized areas. The search for the causes of breast cancer has not yet yielded a convincing explanation for the geographic and temporal patterns in the occurrence of breast cancer. Generation of electric power is a hallmark of industrialization, and two products of electric power, light-at-night (LAN) and electromagnetic fields (EMF), may affect breast cancer risk. Exposure to either LAN or EMF can decrease production of melatonin by the pineal gland. Melatonin, in turn, has been shown to suppress mammary tumorigenesis in experimental animals. Moreover, recent epidemiological findings indicate an increased risk of breast cancer in workers occupationally exposed to EMF. On the basis of these considerations, it is proposed that the use of electrical power accounts, in part, for the higher risks of breast cancer in industrialized societies.

Animals↗
PubMed1992

Reproductive factors in the etiology of hepatocellular carcinoma. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

Data from a hospital-based case-control study conducted in four developing countries were analyzed to evaluate the role of reproductive factors in the etiology of liver cancer. Eighty-three patients newly diagnosed with primary liver cancer and 596 matched controls between the ages of 15 and 56 years completed study interviews. The relative risk of hepatocellular carcinoma was elevated significantly in women of high gravidity, an association that was attributable to the effects of full-term pregnancies. The adjusted relative-risk estimate in women who had ever had a full-term pregnancy was 1.6 (95 percent confidence interval = 0.6-4.1), and risk increased directly with the number of full-term pregnancies (P for trend = 0.03), rising to 3.8 among women with seven or more births compared to women with one to two births. Induced abortions and a history of miscarriage were unrelated to risk. These findings were unchanged after adjustment for a history of jaundice, lifetime number of sexual partners, or age at first sexual intercourse--variables which may be related to hepatitis B virus (HBV) exposure. Serum samples to determine HBV status were not collected, however, and it is not known whether the observed associations are independent of prior HBV infection.

Adolescent↗
PubMed1992

Accuracy of recall of use of an intrauterine device.

Within a case-control study of the relationship between oral contraceptives and breast cancer, information on other contraceptive practices, including use of an intrauterine device (IUD) was obtained through interviews of study subjects and from the records of gynaecologists. Information from these two sources was compared for 239 women who had ever used an IUD. The results showed that agreement on total duration, number of IUD episodes, and time since first and time since last IUD use was excellent. As approximately 75% of IUDs used were unknown, agreement on brands could not be investigated. Studies investigating the effects of individual types of IUDs should use physician records as an additional source of information.

Female↗
PubMed1992

US regulatory hurdles: towards international harmonization.

What regulatory requirements must be met before a new medical device can be marketed in the USA? In this article, David Thomas reviews the regulations, examines the impact of recent legislation and looks at the emerging trend towards international harmonization of the regulation of health care products.

Biosensing Techniques↗
PubMed1992

High-dose and low-dose combined oral contraceptives: protection against epithelial ovarian cancer and the length of the protective effect. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

The relations between use of high-dose and low-dose combined oral contraceptives and epithelial ovarian cancer were compared in an international hospital-based case-control study. 393 cases from seven countries were compared with 2561 matched controls. The odds ratio (OR) was somewhat lower for women who used high-dose oestrogen oral contraceptives (OR = 0.68) than for women who used low-dose preparations (OR = 0.81) although the difference could have occurred by chance. After controlling for time since last use, risk was slightly lower for long-term users of high-dose preparations than for long-term users of low-dose pills. Both high-dose and low-dose oral contraceptives protect against ovarian cancer, but the degree of protection may be slightly weaker for the newer, low-dose products.

Case-Control Studies↗
PubMed1992

Breast cancer and specific types of combined oral contraceptives. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

Data on 2,754 cases and 18,565 controls from a multinational hospital-based, case-control study were analysed to determine whether observed associations between combined oral contraceptives and breast cancer are similar for oral contraceptives with varying types and doses of oestrogens and progestins. After stratifying on duration of use, risk was found to be increased in current and recent users, and to decline with time since last use. These associations, of similar strength, were observed for users of products that contain mestranol and ethinyl estradiol, for women who used preparations with progestins derived from 19-nortestosterone and 17-alpha-hydroxyprogesterone, and for those who took preparations with relatively higher and lower doses of oestrogen. When products with equal doses of the same oestrogen or progestin and varying doses of the other hormonal constituent were considered, slightly higher relative risks per year of use were estimated for users of products with relatively higher than lower doses of either the constituent oestrogen or progestin, but the differences in relative risk could readily have occurred by chance. This study provides no evidence that risk of breast cancer in users of oral contraceptives varies by the type of oestrogen or progestin consumed.

Breast Neoplasms↗