Biomedical subjects

D B Thomas

Publications and source records attributed to D B Thomas.

At least 19 recordsLinked to original sources

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↗

PubMed1992

Class II (I-Ad) restricted T-cell recognition of the V3 loop region of HIV-1 gp120.

A CD4+ and gp120-specific T-cell line, and subclone, were established from BALB/c mice following immunization with recombinant gp120, using an adjuvant formulation (alum) acceptable for use in the human. The recognition specificity was determined against a panel of synthetic peptides corresponding to the primary sequence of the HXB2 strain of human immunodeficiency virus (HIV). An epitope was identified, corresponding to amino acid residues 322-341, and a further series of truncated peptides established the minimum determinant to be 327-341. Possible reasons for the immunodominance of the V3 loop, and adjacent regions, for both antibody and T-cell recognition are discussed.

Amino Acid Sequence↗

PubMed1992

Do antigenic drift residues in influenza hemagglutinins of the H3 subtype qualify as contact sites for MHC class II interaction?

We have previously reported that a majority of hemagglutinin-specific and class II (Ak or Ad)-restricted T cell clones, elicited by natural infection with X31 virus (H3N2 subtype), focus on regions of the HA1 subunit that have featured in antigenic drift and exhibit extensive diversity in their ability to discriminate between variant viruses with amino acid substitutions in these sites. The structural basis for the loss of recognition of a major antigenic site, HA1 120-139, was investigated by (i) comparing the effects of amino acid substitutions in mutant hemagglutinins (HA1 129 Gly----Glu; 132 Gln----Glu; 135 Gly----Arg) with the corresponding substitutions in synthetic peptides or (ii) by assessing the effects of single amino acid substitutions (to Ala) in the alpha k chain (residues 50-79) on the ability of Ak transfectants to present peptides. Despite the failure to recognise mutant viruses, mutant peptides were recognised as efficiently as wild-type peptides in association with wild-type Ak. However, the mutant Ak transfectants identified a different set of alpha k residues (positions 56, 65, and 72) as being critical for presentation of mutant peptides. Taken together with our previous findings that defects in antigen presentation of mutant hemagglutinin are reversed by single substitutions in the alpha k chain (residues 56 and 62), it would seem that the antigenic drift residues in mutant hemagglutinins alter the profile of contact sites with class II.

Amino Acid Sequence↗

PubMed1992

Persistence of sterile screwworm (Diptera: Calliphoridae) flies at a release site.

Studies to determine the persistence of released, sterile screwworms, Cochliomyia hominivorax (Coquerel), were conducted in Belize, Central America, in 1987-1988. A total of nine releases were made, each consisting of 4,000 females marked with a fluorescent dust. Previous similar studies with baited fly traps indicated that flies died or dispersed from the release site within 3-4 d. For this study, flies were recaptured at sentinel animals. Recapture rates varied greatly between releases, a result that was not correlated with any weather parameter. The pattern of recapture indicated a sharp drop in the released population after 9-10 d, with a few flies persisting in the release area for up to 3 wk. The results suggest that survival of released sterile flies is comparable with estimated survival rate and life span of wild, native flies.

Animals↗

PubMed1992

Kinetic development and decline of antiscrewworm (Diptera: Calliphoridae) antibodies in serum of infested sheep.

Sheep infested with screwworms, Cochliomyia hominivorax (Coquerel), produced specific serum antibodies detectable by ELISA. Significant antibody levels were found beginning at 1 wk after infestation and persisting for 2 mo, with peak levels at 3 wk after infestation. Mean response values and corresponding larval survivorship were similar over a range of 25 to 200 larvae per individual sheep. Anomalous seropositive responses in some noninfested sheep suggested the possibility of cross-reactivity between antigens of screwworm and those of related myiasigenic blowflies.

Animals↗

PubMed1992

A case-control study of occupational risk factors for laryngeal cancer.

To determine whether specific jobs and occupational exposures are associated with laryngeal cancer lifetime occupational histories from a population-based case-control study in western Washington were examined. The study included 235 cases diagnosed between September 1983 and February 1987, and 547 controls identified by random digit dialing. After controlling for alcohol use, cigarette smoking, age and education, significantly increased risks were found for painters in construction (odds ratio (OR)) = 2.8, (95% confidence interval (95% CI) 1.1-6.9), supervisors and miscellaneous mechanics (OR = 2.3, 95% CI 1.1-4.8), construction workers (OR = 3.4, 95% CI 1.4-8.1), metalworking and plastic working machine operators (OR = 2.6, 95% CI 1.3-4.9) and handlers, and equipment cleaners and labourers (OR = 1.5, 95% CI 1.0-2.2). Allowing for a 10 year induction and latent period did not have a consistent effect on the associations. Potential exposures to asbestos, chromium, nickel, formaldehyde, diesel fumes, and cutting oils were assessed by using a job exposure matrix developed for this study. Three measures of exposure were examined--namely, peak, duration, and an intensity weighted exposure score. No significantly raised risks were seen, although increased risk was suggested among those exposed long term to formaldehyde in jobs with the highest exposures.

Adult↗

PubMed1992

Assessment of the carcinogenicity of the nonnutritive sweetener cyclamate.

The weight of the evidence from metabolic studies, short-term tests, animal bioassays, and epidemiological studies indicates that cyclamate (CHS) is not carcinogenic by itself; however, there is evidence from in vitro and in vivo studies in animals that implies it may have cancer-promoting or cocarcinogenic activity. Epidemiological studies indicate that the use of nonnutritive sweeteners (CHS and saccharin) has not resulted in a measurable overall increase in the risk of bladder cancer in individuals who have ever used these products. No epidemiological information exists on the possible associations of these sweeteners and cancers other than those of the urinary tract. It is recommended that (1) no further studies on the metabolism of CHS to evaluate its carcinogenicity are required since no potentially hazardous metabolites have been appreciably detected in humans; (2) no further animal bioassays to test for the carcinogenicity of CHS by itself are necessary; (3) the studies in rodents that suggest a promotional or cocarcinogenic effect of CHS should be repeated because they cannot be ruled out; (4) because the significance to human health of a positive outcome of such studies is uncertain, additional research aimed at understanding the predictive value for human health of such results and more generic studies to develop well-validated systems that can be relied on in the assessment of cancer-promoting agents are recommended; (5) in populations where CHS continues to be used, epidemiological monitoring should be continued to determine whether there is an increased risk of cancer in humans who are heavy or long-term users or for those observed long after first exposure. In such monitoring, other cancer sites--in addition to the bladder--should be considered.

Animals↗

PubMed1992

Oxidant-evoked release of acetylcholine from enteric neurons of the rat colon.

In the presence of halides, granulocytes generate hypochlorous acid and, subsequently, chlorinated amines (chloramines). These lipophilic, potent reactive oxygen metabolites may contribute to the mucosal pathophysiology associated with inflammatory bowel disease. A common symptom of inflammatory bowel disease is mucosal secretion of fluid and electrolytes, leading to diarrhea. Because acetylcholine (Ach) can stimulate colonic fluid secretion, we determined the effect of monochloramine (NH2Cl) on Ach release by mucosal/submucosal nerves. Mucosa from the rat colon was separated from outer muscle layers and minced before incubation with [14C]choline to label stores of Ach in cholinergic neurons. Release of [14C]Ach was evoked with NH2Cl in the absence and presence of 5-aminosalicylic acid, glutathione, nordihydroguaiarectic acid or the cyclooxygenase inhibitor piroxicam. NH2Cl produced concentration-related increases in [14C] Ach release into the medium; greater than 100% over base line was observed at 0.5 mM. Glutathione inhibited the NH2Cl-evoked release in a concentration-dependent fashion. Release induced by 0.1 mM NH2Cl was abolished by 5-aminosalicylic acid and significantly inhibited by nordihydroguaiarectic acid. Piroxicam also prevented the effect of NH2Cl on release of [14C] Ach. None of these agents alone had any effect on base line [14C]Ach release. Tetrodotoxin (5 microM) did not significantly inhibit the NH2Cl-evoked transmitter release. We conclude that NH2Cl, at concentrations believed to exist in inflamed tissue, causes the release of Ach from mucosal/submucosal nerves primarily through nonspecific neural membrane injury. Endogenous prostaglandins, possibly liberated as a consequence of the injury, may be involved in the Ach release process.

Acetylcholine↗

PubMed1991

Underutilization of breast-conserving surgery and radiation therapy among women with stage I or II breast cancer.

OBJECTIVE: To identify time trends and factors associated with breast-conserving surgery (BCS) and delivery of postoperative radiation therapy among women with stage I or II breast cancer. DESIGN: Survey. SETTING: Population-based cancer registry in the Seattle-Puget Sound (Wash) region. PARTICIPANTS: The study included 8095 women diagnosed with stage I or II breast cancer (American Joint Committee on Cancer staging criteria) from 1983 through 1989. MAIN OUTCOME MEASURES: Breast-conserving surgery with or without radiation therapy vs mastectomy, and, among women with BCS, a comparison of radiation therapy vs no therapy. RESULTS: In 1985 when results from a US randomized clinical trial of BCS were published, the frequency of BCS peaked (46.3% of stage I; 30.1% of stage II) followed by a return to levels before 1985 for women with stage II breast cancer and a more moderate decline for stage I breast cancer. The likelihood of BCS decreased with increasing age (P less than .001), with stage II disease, and with residence outside the region's major urban center, and it increased with education (P less than .001) or median income (P less than .001) by census tract. The proportion of women who received radiation therapy after BCS decreased with age (P less than .001), was lower for women with stage II than stage I disease, and was lowest in counties without radiation therapy facilities. CONCLUSIONS: Despite scientific evidence of the equivalent efficacy of BCS with radiation therapy and mastectomy, BCS is not performed on the majority of women with stage I or II breast cancer as recommended by the National Institutes of Health, and factors are associated with its use that differ from selection criteria outlined by the National Institutes of Health.

Aged↗

PubMed1991

Hormonal content of combined oral contraceptives in relation to the reduced risk of endometrial carcinoma. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

The relationship between the strength of the estrogenic and progestational components of combined oral contraceptives and risk of endometrial carcinoma was examined in a multinational hospital-based case-control study comparing 220 cases from 7 countries with 1,537 age- and hospital-matched controls. Oral contraceptives were classified according to their relative content of estrogen and progestin. The risk was not altered in women who used preparations containing high-dose estrogen/low-dose progestin compounds [odds ratio (OR) = 1.10, 95% CI = 0.13-9.96]. In contrast, the risk among users of low-dose estrogen/high-dose progestin oral contraceptives was greatly decreased (OR = 0, 95% CI = 0-1.08). Risks observed for users of high-dose estrogen/high-dose progestin (OR = 0.15, 95% CI = 0.045-0.50) and low-dose estrogen/low-dose progesterone (OR = 0.59, 95% CI = 0.26-1.30) preparations were intermediate between those for users of the 2 other types of preparation. A significantly lower risk was observed for high-dose progestin users than for low-dose users [ratio of odds ratios (ROR) = 0.21, 95% CI = 0.05-0.84]. Although the numbers are small, findings from this study suggest that combined oral contraceptives with varying strengths of estrogen and progestin have different effects on the risk of endometrial carcinoma.

Case-Control Studies↗

PubMed1991

Occupational exposure to electromagnetic fields and breast cancer in men.

Data from a population-based case-control study of breast cancer in men were used to examine the hypothesis that occupational exposure to electromagnetic fields increases the risk of breast cancer. Incident cases (n = 227) diagnosed between 1983 and 1987 were obtained from 10 population-based cancer registries of the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Controls (n = 300) were selected by random digit dialing and from Medicare eligibility lists. Exposure status, defined as ever having been employed in a job which has been classified as involving potential exposure to electromagnetic fields, was assigned without knowledge of case/control status. An elevated risk was found for any job with exposure (odds ratio (OR) = 1.8, 95 percent confidence interval (CI) 1.0-3.7), and risk was highest among electricians, telephone linemen, and electric power workers (OR = 6.0, 95 percent CI 1.7-21) and radio and communications workers (OR = 2.9, 95 percent CI 0.8-10). Risk did not vary with duration of exposed employment. The risk was highest among subjects who were first employed in jobs with exposure before the age of 30 years and who were initially exposed at least 30 years prior to diagnosis. These results lend support to the theory that electromagnetic fields may be related to breast cancer in men. The hypothesis warrants evaluation in women.

Adult↗