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Biomedical subjects

D J Thompson

Publications and source records attributed to D J Thompson.

16 recordsLinked to original sources
PubMed1992

Renal transplacental carcinogenicity of 3,3-dimethyl-1-phenyltriazene in rats: relationship of renal mesenchymal tumor to congenital mesoblastic nephroma and intralobar nephrogenic rests.

Exposure of rat embryos to 3,3-dimethyl-1-phenyltriazene (DMPT) results in numerous malformations, but the urogenital system is not affected. In contrast, exposure of rat fetuses to DMPT has been reported to result in renal neoplasms, which were not further classified. To better understand this discrepancy in organotropism of the teratogenic and transplacental carcinogenic processes, the present study was undertaken to characterize the neoplasms induced in rat fetuses exposed to DMPT in utero. Renal neoplasms and persistent mesenchyme were observed in 19.2 and 11.5%, respectively, of the offspring of rats treated with 1 mg DMPT/kg body weight intraperitoneally on gestation days 16, 18, and 20. The majority of these renal lesions were observed in females. The renal neoplasms were mixtures of various types of mesenchymal tissue derivatives including smooth muscle and fibrous connective tissue. These neoplasms would be classified as renal mesenchymal tumors in rats. Brain neoplasms (numerous types), compound odontomas, and micrognathism were observed predominantly in male offspring from the same group. This treatment also resulted in decreased body weights, increased incidence of sudden loss of body weight, tremors and ataxia, and hypoplastic testes. Exposure to single intraperitoneal doses of DMPT on gestation day 20 did not produce a classic dose-response pattern: Minimal effects were observed with 10 mg DMPT/kg (occasional renal mesenchymal tumors and brain neoplasms), marked effects were observed with 30 mg DMPT/kg (lower incidence rate of most of the alterations observed with 1 mg/kg on gestation days 16, 18, and 20), and no effects were observed with 60 mg DMPT/kg. DMPT administered intraperitoneally at 1 mg/kg body weight on gestation days 16, 18, and 20 is an animal model of transplacental chemically induced renal neoplasms, which provide lesions with similarities to both intralobar nephrogenic rests and congenital mesoblastic nephroma of humans. Why the kidney is a carcinogenic target and not a teratogenic target remains unknown.

Animals↗
PubMed1979

Interaction of divalent cations with beta-galactosidase (Escherichia coli).

Although the addition of various divalent metals to beta-galactosidase resulted in apparent activation, only Mg2+ and Mn2+ actually did activate. The apparent activation by the other divalent metals was shown to be due to Mg2+ impurities. Calcium did not activate, but experiments suggested that it did bind. Other divalent metals which were studied failed to bind. The dissociation constants for Mg2+ and Mn2+ were 2.8 X 10(-7) and 1.1 X 10(-8) M, respectively, and in each case one ion bound per monomer. These constants corresponded very closely to apparent values which were obtained from activation studies. The apparent binding constant for Ca2+, obtained from competition studies, was 1.5 X 10(-5) M. Data were obtained which showed that Mg2+, Mn2+, and Ca2+ all compete for binding at a single site. Of interest and of possible molecular biological importance was the observation that, while Mg2+ bound noncooperatively (n = 1.0), Mn2+ did so in a highly cooperative manner (n = 3.4). The binding of Mn2+ (as compared to Mg2+) resulted in a twofold drop in the Vmax for the hydrolysis and transgalactosylis reactions of lactose but had little effect on the Vmax of hydrolysis of allolactose, p-nitrophenyl beta-D-galactopyranoside (PNPG), or o-nitrophenyl beta-D-galactopyranoside (ONPG); Km values were not effected differently for any of the substrates by Mn2+ as compared to Mg2+. When very low levels of divalent metal ions were present (0.01 M EDTA added) or when Ca2+ was bound with lactose as the substrate, a greater decrease was observed in the rate of the transgalactosylic reaction than in the rate of the hydrolytic reaction, and the Km values for lactose and ONPG were increased. Of the three divalent metal ions which bound to beta-galactosidase, only Mn2+ had significant stabilizing effects toward denaturing urea and heat conditions.

Calcium↗
PubMed1979

Nontreatment of fever in extended-care facilities.

In a study of decisions not to treat febrile patients, we reviewed the medical records of 1256 people admitted to nine extended-care facilities in Seattle during 1973. Fever, defined as two temperatures of 38.33 degrees C to 38.83 degrees C (101 to 101.9 degrees F), within 24 hours or one temperature greater than or equal to 38.88 degrees C (102 degrees F), developed in 190 patients before two years of stay. Active treatment, defined as antibiotics or hospitalization (or both), was ordered for fever in 109 patients, of whom 10 (9 per cent) died. Active treatment was not ordered for 81 patients, of whom 48 (59 per cent) died. The pre-decision factors that showed a significant relation (P less than 0.05) to such nontreatment were: diagnosis, mental status, mobility, pain, narcotics prescribed, size of the facility, relation of the physician to the patient and medical-record statements documenting the patient's deterioration or plans for nontreatment in general. This pattern of nontreatment suggests that physicians and nurses did not intend to treat these patients actively and that high mortality was expected.

Aged↗
PubMed1979

Acoustic admittance and the aging ear.

Tympanograms were acquired from 60 subjects, 20 through 79 years of age, with normal hearing and no history of otic pathology. Acoustic conductance and acoustic susceptance at the tympanic membrane (GTM and BTM) were derived and acoustic admittance (YTM) was calculated. Statistical analysis of GTM, BTM and YTM showed no significant variation in values across age decades. Comparison of these data with previous reports suggests that the effect(s) of age on measures of static acoustic admittance, and presumably acoustic impedance, is complex.

Acoustic Impedance Tests↗
PubMed1979

Peripheral neuropathy in arsenic smelter workers.

We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls.

Adult↗
PubMed1978

Teratogenicity of adriamycin and daunomycin in the rat and rabbit.

The antitumor drugs adriamycin and daunomycin were evaluated for effects on embryonal and fetal development in the rat and rabbit. Doses of adriamycin ranging from 1-2 mg/kg/day or daunomycin ranging from 1-4 mg/kg/day were administered ip to pregnant rats on days 6-15, 6-9, 9-12 or 12-15 of gestation. Both drugs were teratogenic in the rat, particularly when administered on days 6-15 or 6-9 of gestation. Relatively few anomalies resulted from treatment on days 9-12 or 12-15. On a mg/kg basis, adriamycin was the more potent teratogen, producing major anomalies at doses as low as 1.25 mg/kg. Similar anomalies, but at a lower incidence, were produced by daunomycin at dose levels of 4 mg/kg. Characteristic malformations included esophageal and intestinal atresia, tracheo-esophgeal fistula, hypoplasia of the urinary bladder and various cardiovascular anomalies. Neither drug was teratogenic when given iv to rabbits at doses up to and including 0.6 mg/kg/day on days 6-18 of gestation, but a high incidence of abortion occurred in rabbits treated with adriamycin.

Abnormalities, Drug-Induced↗
PubMed1977

History and status of the Cancer Surveillance System of Western Washington.

A cancer registry for a population of over 2 million people was established in 1973. Although the population is predominantly white, the presence of people of Oriental stock provides a potential for migrant studies and international comparisons. Over 7,900 resident cancer cases are detected annually, and a good system for evaluating completeness of reporting and quality of collected data has been devised. To utilize the resources that the registry represents, we have a competent staff of epidemiologists and biostatisticians with academic appointments at the University of Washington and interests in cancer etiology, evaluation of care, and teaching.

Adolescent↗
PubMed1975

Association of exogenous estrogen and endometrial carcinoma.

To determine the association between the incidence of endometrial cancer and the use of estrogen in menopausal and post-menopausal women, we retrospectively compared 317 patients with adenocarcinoma of the endometrium with an equal number of matched controls having other gynecologic neoplasms; 152 patients used estrogen, as compared to 54 of 317 controls. Thus, the risk of endometrial cancer was 4.5 times greater among women exposed to estrogen therapy. When estrogen use was adjusted for concomitant variables such as obesity, hypertension, diabetes, parity, referral pattern, age at diagnosis, year of diagnosis and other gynecologic neoplasms, the magnitude of the increased relative risk was associated with several of these variables, and was highest in patients without obesity and hypertension. Exogenous estrogen therapy is associated with an increased risk of endometrial carcinoma, but this increased relative risk is less apparent in patients with physiologic characteristics previously associated with an increased risk.

Adenocarcinoma↗
PubMed1975

Impact of integration of mental health service and comprehensive medical care.

Effect of the introduction of mental health services into a comprehensive prepaid medical care facility was studied. The subjects were two independent subsamples of all individuals seen in the mental health service for the first time in 1967, and two comparison groups not seen in the mental health service. Data consisted of medical visits from 1962 through 1969 and mental health visits from 1967 through 1969. Insufficient support was found for the assertion that mental health services produce savings of medical care. Some of the complex interactions between care for somatic and mental health treatment variables, and points for future study are noted.

Comprehensive Health Care↗