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Biomedical subjects

T Smith

Publications and source records attributed to T Smith.

At least 703 records · Page 39Linked to original sources
PubMed1986

The pathogenicity of long versus short fibre samples of amosite asbestos administered to rats by inhalation and intraperitoneal injection.

For many years it has been accepted that fibre dimensions are the most important factor in the development of asbestos related disease with long fibres being more dangerous than short for all types of asbestos. This information has been derived from in vitro experiments and injection or implantation experiments since the kilogramme quantities of specially prepared dusts that are necessary for long term inhalation have not been available. The present study has taken advantage of the availability of a sample of amosite produced so that almost all fibres were less than 5 micron in length. The effects of this dust were compared to dust prepared from raw amosite that contained a very high proportion of long fibres. Previous data from studies with UICC amosite, which was intermediate in length, were also available for comparison. At the end of 12 months of dust inhalation, significantly more short fibre amosite was present in the lung tissue compared to the long but while the long fibre dust caused the development of widespread pulmonary fibrosis, no fibrosis at all was found in animals treated with short fibre. One third of animals treated with long fibre dust developed pulmonary tumours or mesotheliomas but no pulmonary neoplasms were found in animals treated with short fibre dust. Following intraperitoneal injection, the long fibre amosite produced mesotheliomas in 95% of animals with a mean induction period of approximately 500 days. With short fibre dust, only a single mesothelioma developed after 837 days. In previous inhalation studies with UICC amosite, relatively little pulmonary fibrosis had developed and only two benign pulmonary tumours. This would suggest that to produce a significant carcinogenic response in rat lung tissue amosite fibres must be longer than those in the UICC preparation. Following the injection of UICC amosite, however, mesotheliomas developed in the same proportion of animals and with the same mean induction period as with long fibre dust. From this it would appear that while very short fibres exhibit little carcinogenicity to either lung or mesothelial tissues, mesotheliomas can be produced by dust preparations consisting of shorter fibres than are needed to produce tumours.

Animals↗
PubMed1986

A subchronic study of the effect of etodolac on the gastric mucosal prostaglandin levels in the rat.

The effect of 7 consecutive days dosing with anti-inflammatory drugs on rat gastric mucosal PGE2 and 6-keto-PGF1 alpha concentrations were studied. Normal adult rats were given daily, single oral doses of etodolac (3 or 8 mg/kg/day), naproxen (3 mg/kg/day), or aspirin (300 mg/kg/day). Two hours after administration of the last dose, the animals were killed and the gastric mucosal PGE2 and 6-keto-PGF1 alpha were extracted and measured by radioimmunoassay. At equieffective anti-inflammatory doses in the rat, etodolac (3 mg/kg/day) did not significantly lower the concentrations of either PGE2 or 6-keto-PGF1 alpha, whereas both 3 mg/kg/day of naproxen and 300 mg/kg/day of aspirin significantly lowered the concentrations of both prostaglandins. The effects of naproxen and aspirin on the 6-keto-PGF1 alpha concentrations were also significantly different from that of etodolac at 3 mg/kg/day. At a higher dose of 8 mg/kg/day, etodolac did significantly lower the concentrations of PGE2 (by 33%) but not of 6-keto-PGF1 alpha. Our present data thus supports the hypothesis that the relatively weak inhibiting effect of etodolac on the gastric mucosal prostaglandin concentrations may contribute to its excellent GI profile observed in man.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Structural and biochemical differentiation of the guinea-pig colon during foetal development.

We have studied some aspects of the morphological and biochemical differentiation of the foetal guinea-pig colonic epithelium. At day 40 the epithelium was organised in ridges and appeared pseudo-stratified. Folding of the epithelium, followed by villus formation, occurred between days 45 and 55, and by day 50 mucus-secreting goblet cells appeared at the bases of the colonic villi. By day 55 most epithelial cells, including goblet cells, possessed numerous microvilli which, by day 65, had become organised into well developed brush-borders. Between day 55 and term (day 65-68) mucosal depth increased markedly and the colon attained its final glandular morphology. Biochemical studies showed the specific activities of the microvillar hydrolases to be much lower in the washed colon than in either foetal meconium or small intestine at all times during development. Furthermore, a membrane fraction highly enriched in microvillus hydrolase activities was prepared from foetal colonic meconium using techniques originally devised to isolate the foetal small intestinal microvillus membrane. This meconial subfraction was almost identical in polypeptide composition to the highly-purified foetal small intestinal microvillus membrane. Identification of the colonic microvillus membrane was hampered by the absence of reliable membrane markers. Nevertheless, a fraction 14-fold enriched in aminopeptidase activity was prepared from day 40 foetal colon and its polypeptide composition compared by SDS-PAGE to that of the small intestinal microvillus membrane at the same age.

Aminopeptidases↗
PubMed1985

Plasma lipid peroxidation in hyperlipidemic chickens.

Laying and genetically defective non-laying hens were evaluated for plasma lipid and plasma peroxidation levels. The non-layers developed extreme hyperlipidemia as well as greatly increased levels of lipid peroxidation. It was concluded that the concurrent presence of lipid peroxidation products must be considered when evaluating hyperlipidemic causes of atherosclerosis in the chicken.

Animals↗
PubMed1985

Angiotoxicity in swine of a moderate excess of dietary vitamin D3.

The effects of five different dietary levels of vitamin D3 on the coronary arteries of groups of 17-60 2-month old weanling Yorkshire swine were studied. Four groups were fed the following levels of vitamin D3 per ton of ration continuously for 4 months: group I--100,000 IU, group II--300,000 IU, group IV--2,000,000, and group V--4,000,000 IU. Swine in group III were fed the diet containing 100,000 IU of vitamin D3 per ton of ration for the first 2 months of the study after which they were fed a diet supplemented with 4,000,000 IU of vitamin D3 per ton of ration for the remaining 2 months of the study. The highest degree of intimal thickening of the coronary arteries was observed among group V. The thickened areas contained numerous lipid-containing cells and degenerate cells without stainable lipid. Electron microscopic examination revealed a greater frequency of degenerate cells without stainable lipid in the coronary arteries of groups III and IV than in groups I and II. These results suggest a possible link between excessive daily intake of vitamin D3 and the development of human coronary atherosclerosis.

Animals↗
PubMed1985

Effect of tolrestat on red blood cell sorbitol levels in patients with diabetes.

The effect of the aldose reductase inhibitor, tolrestat, on red blood cell (RBC) sorbitol levels was studied in 23 patients with diabetes after oral dosing with tolrestat, 25 or 100 mg b.i.d. The mean (+/- SE) RBC sorbitol levels (measured 12 hours after the preceding dose) after 3, 7, and 13 days of dosing decreased after both dose levels. After 25 mg tolrestat the RBC sorbitol levels fell from 25.1 +/- 4.0 to 20.0 +/- 5.7 nmol/gm hemoglobin (21%) and after 100 mg tolrestat the level fell from 26.7 +/- 3.7 to 11.4 +/- 1.7 nmol/gm hemoglobin (57%; P less than 0.001). This latter RBC sorbitol concentration is similar to levels in individuals without diabetes. At both dosage levels the maximum decrease in RBC sorbitol levels occurred after only 3 days of dosing. Tolrestat had no effect on plasma glucose or hemoglobin A1 concentrations. The overall mean plasma unbound drug concentration measured 12 hours after 100 mg tolrestat (11.7 +/- 3.0 ng/ml; 3.3 X 10(-8) mol/L) was similar to the median inhibitory level (3 X 10(-8) mol/L) of tolrestat for sorbitol accumulation in human RBCs incubated in a high-glucose medium. Our results demonstrate the systemic bioavailability of tolrestat and its aldose reductase inhibitory activity in erythrocytes of patients with diabetes.

Administration, Oral↗
PubMed1985

Total body potassium and water, and exchangeable sodium, in muscular dystrophy.

Total body potassium (40K method) and total body water and exchangeable sodium (both by isotope dilution) were determined in 26 boys, aged 5-17 years, with muscular dystrophy. Total body potassium values were compared with measurements in a large series of normal boys on the basis of height. Total body potassium was reduced even in the youngest patients and was only slightly higher in the older boys, despite their considerably greater height. Exchangeable sodium increased with increasing height in a way similar to that of normal boys. Total body water was also reduced but increased with growth, although to a lesser extent than expected for normal boys. The total body water measurements indicated that many of the affected boys were very obese, despite an apparently normal body weight. An intravenous bolus of 22Na distributed at a similar rate in boys with muscular dystrophy to that in normal males. In relation to the predicted values, total body potassium and 24 h urinary creatinine excretion of the affected boys both declined at a rate of 4% per year.

Adipose Tissue↗
PubMed1985

Performance of dairy cows offered isonitrogenous diets containing urea or fishmeal in early and in mid-lactation.

Sixteen Friesian cows were used in Expt 1 to measure the effect of substituting urea-N with fishmeal-N either in early lactation (Part 1) or in mid-lactation (Part 2). In Part 1 (days 15-84 of lactation) the major N constituent of the concentrate was urea (U), urea-N: fishmeal-N in the ratio 2:1 (UF) or 1:2 (FU), or fishmeal (F). In Part 2 (days 84-175 of lactation) only urea (UM) and fishmeal (FM) were used. Replacement of urea-N with fishmeal-N significantly (P less than 0.05) increased yield of milk protein both in early and in mid-lactation. At both stages of lactation the cows were, by calculation, in positive energy balance. In mid-lactation replacement of urea-N by fishmeal-N significantly depressed (P less than 0.001) the concentration of fat in milk. Blood urea concentration decreased with increasing fishmeal inclusion (P less than 0.05) from U to FU. In Expt 2 the diets used in Expt 1, Part 1, were offered at a maintenance level of feeding to non-pregnant, non-lactating heifers in a 4 X 4 Latin square design experiment. Digestibility of dry matter, organic matter and cell-wall constituents increased progressively (P less than 0.05) with the first two increments of fishmeal inclusion. A major effect of replacing urea-N with fishmeal-N was to increase digestible organic matter intake (DOMI) and differences in DOMI between treatments in Expt 1, Part 1, accounted for observed differences in performance.

Animals↗
PubMed1985

Leprosy associated with HLA-DR2 and DQw1 in the population of northern Thailand.

A study of the frequency of HLA-DR2 and DQw1 was performed in leprosy patients and controls in northern Thailand. HLA-DR2 was found in 100% (17/17) of patients with sporadic tuberculoid leprosy and in over 90% (30/32) of all tuberculoid leprosy patients, as compared to 62% (20/32) of controls (p = .02). These strong associations had relative risks of 21.4 for sporadic and 7.4 for all tuberculoid leprosy, and etiologic fractions of 1.0 and 0.84, respectively. There was also a statistically significant and strong association between tuberculoid leprosy and DQw1. These data add to the growing body of evidence that products of HLA class II determinants or closely linked genes may play a role in determining the clinical manifestations of M. leprae infection.

Adult↗
PubMed1985

Intensive combination chemotherapy (ROAP 10) and splenectomy in the management of chronic myelogenous leukemia.

To investigate the role of intensive chemotherapy in chronic myelogenous leukemia (CML), we treated 37 patients who had Philadelphia-positive benign-phase disease with rubidazone 300 mg/m2/d 1 (or daunorubicin 30 mg/m2/d X 4), cytosine arabinoside 80 mg/m2/d X 10, vincristine 2 mg/d 1, and prednisone 100 mg/d X 5 (ROAP 10), every four weeks for a median of three cycles. This treatment was followed by splenectomy and by subsequent maintenance therapy with 1 to 5 g hydroxyurea daily in intermittent courses. After a median follow-up of 42 months (range, 24 to 54 months), 20 patients (54%) remain in benign phase. The projected median survival is 52 months, and the three-year survival rate is 67%. Six patients (16%) developed blastic crisis, and eight died in the benign phase. A significant cytogenetic response, defined as a fall in the percentage of Philadelphia-positive cells to less than or equal to 30%, occurred in 18 (53%) of 34 patients who had serial cytogenetic studies. Six patients (18%) had reductions to 35% to 90%, whereas ten remained 100% positive. Cytogenetic response lasted for a median of six months from the time of maximal response (range, 1 to 18 months). Blastic crisis or accelerated disease developed in seven (44%) of the 16 patients who manifested minimal or no cytogenetic response, compared to only two of the 18 patients (11%) who achieved a significant cytogenetic response. Toxicity, which resulted in one death, was due to myelosuppression and consisted of febrile episodes during neutropenia (24% of courses), documented infections (8% of courses), and bleeding (8% of courses). ROAP 10 intensive therapy produces moderate survival improvement for CML patients compared to a matched historical control group of patients treated at our institution, but it has considerable myelosuppressive toxicity. The Philadelphia chromosome response is an important treatment-related prognostic factor.

Adolescent↗
PubMed1985

EMS performance management.

Our development of a performance analysis system requires that we provide not only great detail about an EMS system's dynamic needs but also that we develop a means to manage our minute to minute resources. We thus had to develop software that was complementary in nature. These applications can be used together or by themselves to give an EMS provider tools for getting the maximum performance from their system.

Computers↗
PubMed1985

The use of antithrombotic therapy in the elderly.

The elderly are predisposed to atherosclerosis and venous thrombosis, the conditions for which anticoagulants are used. Anticoagulants can be used safely in the elderly with little or no more risk of bleeding than exists in younger patients. The prescribing physician must know the mechanism of drug action, be attentive to potential side effects, and monitor drug activity adequately. The authors emphasize the oral anticoagulants and heparin because, in general, their use is associated with a greater degree of risk and more clearly defined benefits than would apply for the antiplatelet agents.

Aged↗