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Biomedical subjects

D J Thompson

Publications and source records attributed to D J Thompson.

At least 19 recordsLinked to original sources

Trace metal accumulation by the shrew Sorex araneus. I. Total body burden, growth, and mortality.

A laboratory feeding trial is described in which a known trace metal accumulator, the shrew Sorex araneus, was presented with an artificial diet containing high levels of copper and cadmium. Methodological difficulties relating to feeding trials on first generation offspring of insectivorous small mammals caught in the wild are described. There was no relationship between copper or cadmium intake and mortality during the trials. Sex differences in growth were apparently not influenced by metal intake. At the end of the trials there was a significant negative correlation between body weight and total cadmium burden. Whole body concentrations and burdens of cadmium increased with estimated intake. There was a significant negative correlation between percentage of cadmium retained as body burden and estimated cadmium intake. There was no discernible relationship between copper burden and intake.

Animals

Trace metal accumulation by the shrew Sorex araneus. II. Tissue distribution in kidney and liver.

The distributions of trace metals in tissues of shrews in a series of feeding trials are described. The relationship between body cadmium burden and organ weight was directly related to differences in body weight. Organ weight expressed as a percentage of body weight was constant in the kidney, but was correlated with cadmium burden for the liver. Liver and kidney accounted for up to 80% of total body cadmium. The proportion of the body cadmium burden found in the kidney ranged from 8 to 17%. Copper and zinc concentrations in the kidney increased in response to cadmium accumulation. Hepatic zinc concentrations increased with cadmium accumulation. Exposure to a copper-contaminated diet resulted in increased liver copper levels. High liver concentrations were correlated with high kidney concentrations. At the lowest levels of exposure to metals liver and kidney concentrations were similar, but as exposure increased so did liver concentrations and much more so than in the kidney.

Animals

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

Teratogenicity of 3,3-dimethyl-1-phenyltriazene: distribution in rats and rat embryos.

3,3-Dimethyl-1-phenyltriazene (DMPT) is a methylating agent which is carcinogenic, teratogenic and mutagenic which, in the rat, provides a reproducible animal model with which to study the basis of chemically-induced micrognathism. The basis of teratogenic organotropism of DMPT and other methylating teratogens is unknown. The present study was undertaken to determine if limited chemical distribution within the embryo was responsible for the organotropism of DMPT. Whole-embryo autoradiographs and liquid scintillation analysis indicated that although DMPT may have some limitations of chemical distribution within the embryo, these limitations are not sufficient to explain its teratogenic organotropism.

Animals

Feasibility of a randomized trial of a low-fat diet for the prevention of breast cancer: dietary compliance in the Women's Health Trial Vanguard Study.

The Women's Health Trial Vanguard Study was conducted to examine the feasibility of a nationwide, randomized multicenter intervention trial to test the hypothesis that a low-fat diet followed for a period of 10 years will reduce breast cancer risk. Women ages 45-69 years at increased risk of breast cancer were randomized into intervention (low-fat diet, n = 184) and control (usual diet, n = 119) groups. On the basis of 4-day food records, baseline fat intakes were comparable in the two groups, averaging 1,718 kcal with 39% of energy as fat. Intervention women reported substantially lower fat intake at 6 (20.9% kcal), 12 (21.6%), and 24 months (22.6% kcal). In contrast, control women reported only slight reductions in fat intake (37.3% kcal at 12 months and 36.8% kcal at 24 months). Evidence that these women were indeed complying with the low-fat dietary intervention comes from (a) the reasonable nature of reported nutrient changes within food groups in the intervention women and (b) agreement between observed and expected differences in plasma total cholesterol between the control and the intervention groups. At 12 months, the observed control - intervention plasma cholesterol difference was 13.1 +/- 4.6 mg/dl while the expected difference based on the Keys equation was 15.1 +/- 1.1 mg/dl; at 24 months, the observed difference was 15.5 +/- 4.3 mg/dl and the expected difference was 12.0 +/- 1.2 mg/dl. These analyses indicate that the intervention women made substantial dietary changes and have successfully maintained these changes over a 2-year period. This study thus demonstrates the feasibility of a randomized trial with an intensive low-fat dietary intervention.

Aged

Vaginal perforation due to jet ski accident.

A case of full thickness vaginal perforation into the peritoneal cavity resulting from a jet-skiing accident is presented. Attention is drawn to the previously reported cases of similar injuries due to high speed water sports, and the need for adequate protective clothing in all people undertaking such sports.

Adult

Comparisons among SPLs in real ears, 2 cm3 and 6 cm3 couplers.

Sound pressure levels (SPLs) were measured in the ear canals of 30 adult subjects with standard audiometric earphones (TDH-39) and insert earphones (Etymotic ER-3A) and compared to those generated in 2 cm3 and 6 cm3 couplers. Transfer functions are shown for real ear to 2 cm3 coupler, real ear to 6 cm3 coupler, 6 cm3 to 2 cm3 coupler, and dB HL under standard earphones to 2 cm3 coupler SPL. In general, the data agreed rather well with published transfer functions that in most cases were derived by adding together a series of partial transfer functions from various studies. The conversion values from dB HL to 2 cm3 coupler SPL could be useful in selection of certain hearing aid parameters, but the intersubject variability may limit their usefulness somewhat.

Adult

Prophylactic insulin in the management of gestational diabetes.

One hundred eight gestational diabetics were randomized to receive either diet alone or diet plus insulin (20 units NPH and 10 units regular) for glycemic control. Blood glucose levels were evaluated weekly in a high-risk clinic where medical and nutritional support and counseling were provided. Among 68 women successfully treated for a minimum of 6 weeks, the mean birth weight, macrosomia rate, and ponderal index were reduced significantly in the insulin-treated group. Insulin reduced birth weights significantly in women with a delivery weight of 200 lb or more (4060 +/- 342 versus 3397 +/- 640 g) and in those with a delivery weight less than 200 lb (3324 +/- 448 versus 3047 +/- 394 g). No patient with good glucose control and a maternal delivery weight under 200 lb had a newborn over 4000 g. Patients failing glycemic control were at greatest risk (30%) for fetal overgrowth whether initially receiving insulin or not. Maternal obesity or failure to achieve glycemic control should alert the clinician to a substantially increased risk of macrosomia.

Adult

Results of a randomized feasibility study of a low-fat diet.

A 2-year randomized clinical trial was conducted to test whether free-living women aged 45 to 69 years can reduce the fat content of their diet from the typical US level of approximately 39% to 20% of energy from fat, using readily available foods, when given nutritional and behavioral counseling and social support. Three clinical units randomized 303 selected volunteers into intervention (low-fat eating plan) or control (customary diet) groups. The two groups were comparable at baseline. The intervention group received nutrition instruction and behavioral counseling largely in permanent groups of 12 to 15 participants meeting weekly, then biweekly, and finally monthly. At 6 months, they had substantially reduced the mean proportion of total energy from fat from 39.1% to 20.9%, compared with the control group's nonsignificant reduction from 39.0% to 38.1%. At 12 and 24 months, they sustained the reduction of energy from fat. Weight loss and plasma cholesterol level changes in the intervention group supported the self-recorded dietary intake changes. Attendance at intervention sessions averaged 75% during the first 6 months and, subsequently, 60% to 70%. Four-day food records for the randomized women were obtained at 6 and 12 months from approximately 95% and at 24 months from 87%. A clinical trial of a low-fat diet is feasible in women.

Aged

Teratogenicity of 3,3-dimethyl-1-phenyltriazene in the rat: gross malformations including micrognathism.

3,3-Dimethyl-1-phenyltriazene (DMPT), an alkylating agent, has been reported to be teratogenic in chickens, mice, and rats. One of the most commonly affected structures is the mandible; however, a complete description and incidence rates of all malformations produced have not been published. Rats were treated on day 12 of gestation (day 0 = sperm in vaginal smear) with a single intraperitoneal injection of 30 mg DMPT/kg. Fetuses were examined on each subsequent day of gestation for external and skeletal abnormalities. Standard soft tissue examinations were performed on day-20 fetuses. A high percentage (greater than or equal to 80%) of treated litters contained numerous fetuses with micrognathism, cleft palates, syndactyly, adactyly, and misshapen digits and limbs. Lordosis, cerebellar and cerebral hypoplasia, decreased fetal size, and generalized delayed ossification were also observed. Dams exposed to DMPT had decreased food consumption and weight gains, although clinicopathologic and histopathologic evaluations failed to indicate other evidence of maternal toxicity. DMPT caused numerous permanent structural alterations that were not attributed to maternal toxicity.

Abnormalities, Drug-Induced

Teratogenicity of 3,3-dimethyl-1-phenyltriazene in the rat: histopathologic and ultrastructural alterations.

3,3-Dimethyl-1-phenyltriazene (DMPT) is a methylating agent which is teratogenic, carcinogenic, and mutagenic. A single intraperitoneal injection of 30 mg DMPT/kg given to pregnant rats on day 12 of gestation produces malformations with minimal maternal toxicity. Malformations include skeletal deformities such as micrognathism, cleft palate, and digital malformations, as well as central nervous system hypoplasia. The purpose of the present study was to characterize the light and electron microscopic alterations produced by DMPT. Electron microscopy (EM) revealed that at 4 hr postinjection of DMPT, rare cells of the neural tube contained few membrane-bound aggregations of organelles and condensed chromatin; this change was consistent with apoptosis, a type of cell death characterized by morphologic and biochemical alterations distinct from necrosis. At 8 hr postinjection, apoptosis was more prominent in the neural tube and also observed in the mandibular process. At 16 hr postinjection, numerous apoptotic cells were interspersed with unaffected cells that contained phagocytized apoptotic bodies. Light microscopic examination of DMPT-exposed conceptuses showed apoptosis in the neural tube at 24 hr postinjection. Forty-eight hours postinjection, apoptosis, in decreasing order of severity, was observed in the neural tube, craniofacial processes, limb buds, and somites and liver. Apoptosis was absent in all tissues by 72 hr postinjection. Nervous tissues failed to achieve proper histologic organization, but all other tissues appeared microscopically normal from 72 hr postinjection until the end of gestation. There appeared to be some degree of tissue specificity to the effects of DMPT.

Abnormalities, Drug-Induced

Anti-M antibody in pregnancy.

Our three cases represent the spectrum of findings when maternal anti-M is present. In the first case, the father's genetic makeup (NN) indicated no disease would occur. In the second case, despite antibody capable of crossing the placenta, the infant did not become sick. In the third case, hemolytic anemia required transfusion of the newborn, despite a negative direct Coombs' (DAT). In summary, anti-M antibody is an uncommon cause of hemolytic disease of the newborn. When anti-M, IgG optimally reactive at 37 degrees C, is identified in the maternal blood, the paternal blood must be checked for the presence of M antigen. If the father has M antigen the fetus may be at risk. Since there is no documented body of experience that titers of anti-M predict severity of disease, our recommendation is that amniotic fluid bilirubin studies be done, in spite of the fact that only one prior case of hemolytic disease due to anti-M was found reported from the United States. Anti-M is an unpredictable antibody and serial antibody titers are not reliable. After delivery the infant's MN antigen status should be determined, because a negative direct Coombs' test may be found even when M antigen is present in the infant and hemolysis is occurring. Further studies are needed to determine the clinical impact of anti-M antibody on unrecognized hemolytic disease of the newborn.

Antibodies

Temporal characteristics of aural acoustic-immittance instruments.

Temporal response to a simulated rapid change in acoustic immittance was recorded from 13 aural acoustic-immittance devices. Ten measures of latency were obtained from the responses. The derived temporal data showed considerable variance across instruments. The variance was affected by the site from which the temporal response was recorded in the instrument and in one case by differences among samples of the same model.

Acoustic Impedance Tests

No episiotomy?!

A method is presented which with careful manipulation of the vagina around the crowning head reduces the incidence of an episiotomy or a perineal tear. Using the method described, the overall result obtained was an intact perineum in 68% of vaginal deliveries (which included forceps deliveries). An episiotomy was performed in only 7% of deliveries--all associated with the use of forceps.

Episiotomy

Hysterical personality disorder. The process of diagnosis in clinical and experimental settings.

A study of the case notes of 52 patients with a diagnosis of hysterical personality disorder showed that 27 had no recorded features of that condition, but were frequently described as aggressive, uncooperative, or attention-seeking. Although 60% were recorded as depressed, only 17% received antidepressant treatment. In an experimental study, the core traits of the disorder were found to have a low inter-rater reliability. Two patients, who had received hospital diagnoses of hysterical personality disorder, were shown to display behaviour that caused psychiatrists to make a diagnosis on wholly inadequate information.

Adult