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Biomedical subjects

A B Smith

Publications and source records attributed to A B Smith.

At least 163 records · Page 9Linked to original sources
PubMed1987

Morbidity from repetitive knee trauma in carpet and floor layers.

Carpet layers comprise less than 0.06% of the United States workforce yet they submit 6.2% of compensation claims for traumatic knee inflammation. Their work involves multiple sources of acute and chronic knee trauma including kneeling, pressure from sharp objects, and use of a device called a "knee kicker" to stretch wall to wall carpet. To characterise the knee morbidity in carpet layers and to identify occupational risk factors, a questionnaire was completed by 112 carpet and floor layers, 42 tile and terrazo setters, and 243 millwrights and bricklayers (MWBL). The MWBL comparison workers seldom kneel and do not use a knee kicker. Physical and xray examinations were conducted on a subset of 108 respondents to validate the questionnaire responses. Compared with the MWBL, carpet layers reported more frequent bursitis (20% v 6%), needle aspiration of knee fluid (32% v 6%), and skin infections of the knee (7% v 2%). A score indicating frequency of using the knee kicker was the only statistically significant predictor of bursitis, whereas the score for kneeling was one of several predictors of knee aspiration and skin infections of the knee. These data suggest that carpet and floor layers experience substantially more knee morbidity than other occupational groups, and that kneeling and use of the knee kicker are risk factors providing opportunities for prevention.

Adult↗
PubMed1987

Amphipathic dithiocarbamates as cadmium antagonists: N-cyclohexyl-N-sulfonatoalkyl derivatives.

Disodium salts of the substituted dithiocarbamates (DTCs) N-cyclohexyl-N-(2-sulfonatoethyl) DTC, N-cyclohexyl-N-(3-sulfonatopropyl) DTC, and N-cyclohexyl-N-(2-hydroxy-3-sulfonatopropyl) DTC were synthesized and assessed as complexing agents for reducing organ concentrations of cadmium (Cd) in mice. At least one week after mice were given 0.03 mg of CdCl2.2.5 H2O containing 1.0 microCi of 109CdCl2 ip they were treated ip with various doses of each DTC. Administration of 4.44 mmoles/kg of each analog q2dx4 produced about a 60% reduction in the whole-body Cd burdens. There was approximately a 50% reduction of renal Cd concentrations and a greater than 90% reduction of hepatic Cd. There was no significant effect on the Cd levels in pancreas, spleen, testes, or brain. Mobilization of organ Cd stores led to excretion of Cd principally in the feces; treatment with 2.22 mmoles/kg of each analog qdx3 promoted a cumulative excretion of 32-40% of the administered metal. Rational design of potential Cd complexing agents is discussed with reference to the relative aqueous and lipid solubilities of the N,N-substituents on DTC congeners.

Animals↗
PubMed1987

Acetaminophen-induced hepatotoxicity: antagonistic action of caffeine in mice.

Studies of interactions in mice between acetaminophen (ACM) and caffeine (CAF) revealed that CAF given immediately after ACM antagonized the acute toxicity of ACM and reduced the severity of ACM-induced hepatic necrosis as assessed grossly and microscopically. It also attenuated the elevations of SGOT and SGPT levels following ACM administration. CAF reduced significantly the magnitude of ACM-induced mobilization of cadmium from hepatic cadmium-metallothionein stores and the extent of binding of 3H-ACM to hepatic proteins. CAF did not restore hepatic GSH levels toward control values in ACM-treated mice; administration of CAF alone led to a reduction of hepatic GSH concentrations. It was concluded that the antagonistic action by CAF of ACM toxicity in mice is not mediated through a salutary effect on endogenous hepatic sulfhydryl levels. The significance of these observations was discussed in terms of possible interactions at the level of ACM and CAF biotransformation and the potential for interactions of CAF with other xenobiotics.

Acetaminophen↗
PubMed1986

Effects of 5,8-dideazaisopteroylglutamate (IAHQ) on L1210 leukemia in mice when given alone and in combination with methotrexate, probenecid, or verapamil.

The folate analogue 5,8-dideazaisopteroylglutamate (IAHQ; NSC-289517) inhibits the growth of a variety of human tumor cells in vitro such as colon, breast and osteosarcoma. Since IAHQ has only modest activity against L1210 leukemia in mice, it was tested in combination with methotrexate (MTX), probenecid, or verapamil in an effort to enhance efficacy. Single drug or drug combinations were administered every other day 3 or 5 times beginning on day 1 following the administration of 10(6) L1210 cells per animal. The combination of IAHQ (100 mg/kg) plus MTX (10 mg/kg) produced a decrease in mean survival time compared to that of MTX alone, regardless of whether the drugs were initiated on the same day or whether either one was started 2 days prior to the other. IAHQ (150 mg/kg) plus verapamil (5, 10, or 20 mg/kg) did not alter significantly the results produced by IAHQ alone. However, the combination of IAHQ (150 mg/kg) plus probenecid (250 mg/kg) augmented the increase in mean survival time above that produced by IAHQ alone by 82% (p = less than 0.001). The results suggest that probenecid could be used to enhance the effectiveness of IAHQ against solid tumors such as colon adenocarcinoma.

Animals↗
PubMed1986

Effects of acetaminophen on cadmium metabolism in mice.

Acetaminophen (ACM) administration to mice of the (C57BL/6 X DBA/2)F1 strain produced a typical hepatic centrilobular necrosis similar to that observed in rodents and humans. To determine the effects of this drug-induced necrosis on cadmium (Cd) metabolism, mice were given a sublethal dose of CdCl2 . 2.5 H2O containing 109CdCl2 and maintained for a period of time sufficient for Cd-metallothionein (Cd-MT) to be synthesized and distributed. Subsequent administration of ACM ip or po evoked a marked redistribution of Cd from livers to kidneys of mice, and increased the amount of Cd excreted in urine and feces. There were only minimal or no effects on Cd concentrations in other organs assessed. The effect of ACM on Cd redistribution was antagonized by administration of cysteine, a glutathione precursor, and was enhanced by pretreatment with phenobarbital, a potent inducer of the cytochrome P-450 mixed-function oxidase system. Pretreatment of mice with ACM 6 or 24 hr prior to Cd administration caused aberrations of the normal Cd distribution pattern, but no effect was noted when Cd administration was delayed for 48 hr after ACM injection, indicating recovery of the mechanisms of Cd-MT synthesis and sequestration. Sephadex G-75 gel filtration chromatography of serum from ACM-treated mice showed that most of the Cd was associated with high-molecular-weight proteins, and only a minor portion was present as Cd-MT. Cd excreted in urine was predominantly in a low-molecular-weight form, but there was evidence of two minor components of higher molecular weight, neither of which eluted as Cd-MT. Cd excreted in feces was insoluble following homogenization in 0.25 M sucrose solution. Cd in livers and kidneys of ACM-treated mice eluted as Cd-MT. It was concluded that persons who have a moderately high Cd burden may be at risk of Cd nephrotoxicity if they incur hepatic necrosis subsequent to ACM abuse.

Acetaminophen↗
PubMed1986

Effects of monoalkyl dithiocarabamates on mobilization of cadmium in the mouse.

Monoalkyl dithiocarbamates are capable of mobilizing cadmium from aged intracellular deposits in which the cadmium is largely present in metallothionein. The sodium salts of monomethyl, ethyl, n-propyl, and n-butyl dithiocarbamates have been prepared, characterized, and examined for their relative ability to mobilize cadmium from such aged deposits in the kidneys, liver, spleen, testes, brain, and pancreas as well as from the whole body, using sodium diethyl dithiocarbamate as the positive control. Alterations in the structure of the dithiocarbamates can be correlated with alterations in organ cadmium levels. The acute toxicity of these compounds is sufficiently greater than disubstituted dithiocarbamates that their use would appear to possess few advantages, although they do seem to be more effective in reducing testicular cadmium levels.

Animals↗
PubMed1986

Comparative antidotal effects of diethyldithiocarbamate, dimercaptosuccinate, and diethylenetriaminepentaacetate against cadmium-induced testicular toxicity in mice.

The compounds diethyldithiocarbamate (DDTC, Dithiocarb), 2,3-dimercaptosuccinic acid (DMSA), and diethylenetriaminepentaacetic acid (DTPA) were evaluated for effectiveness in protecting mouse testes following administration of an LD100 dose of CdCl2 X 2.5 H2O (Cd). Toxicologic responses were assessed by light microscopic techniques. DTPA gave the most effective testicular protection of the three compounds when given within 30 minutes prior to Cd, but only DDTC was effective when given 30 minutes or longer after Cd. Degenerative changes were minimal when DDTC was given as late as three hours after Cd, and were mild following a four-hour interval. However, the changes were marked, but less severe than in mice receiving Cd only, when DDTC was administered five hours after Cd.

Animals↗
PubMed1986

Effects of diethyldithiocarbamate and selected analogs on lead metabolism in mice.

Diethyldithiocarbamate (DDTC) and certain of its N,N-disubstituted analogs were evaluated for effectiveness in reducing organ concentrations and whole body burdens of lead (Pb) in mice which had received 0.06 mg of Pb(II) acetate along with 2.0 microCi of 210Pb 9 days earlier. CaNa2EDTA was used as a positive control for studies in which the compounds were administered ip, and meso-2,3-dimercaptosuccinic acid (DMSA) was used as a positive control for po studies. DDTC was more effective than EDTA in lowering the whole body Pb burdens after 5 ip injections, while N-methyl-N-dithiocarboxyglucamine (MDCG) was less active than EDTA. The other 4 analogs tested were inactive. When DDTC (1.5 mmoles/kg) was coadministered with EDTA (1.5 mmoles/kg), the reduction of total body Pb burdens was significantly greater than that attained with either compound alone at 3.0 mmoles/kg. DDTC was particularly effective in reducing hepatic and splenic Pb concentrations, but was less active than EDTA in lowering the Pb content of bone, kidneys, and brain. Excretion of Pb following ip treatment with EDTA, DDTC, or MDCG was predominantly by the fecal route. DDTC was significantly more effective than DMSA at an equimolar dose in reducing whole body Pb burdens when each was given po. However, po administration of DDTC caused a substantial increase in brain Pb levels.

Animals↗
PubMed1986

Comparative effects of parenteral and oral administration of selected dithiocarbamates on body burdens and organ distribution of cadmium in mice.

Diethyldithiocarbamate (DDTC), N-methyl-N-dithiocarboxyglucamine (MDCG), and 4-carboxamidopiperidine-N-dithiocarboxylate (CAP-N-DTC) were compared at equimolar doses administered by the ip and po routes for effectiveness in mobilizing metallothionein (MT)-bound cadmium (Cd) using 109Cd in mice. DDTC was highly effective by both routes in lowering hepatic, renal, and splenic Cd levels, but enhanced redistribution of Cd to testes and brain. While MDCG and CAP-N-DTC were much less active by the oral route, each effected a significant reduction of renal Cd levels, and MDCG reduced the testicular Cd burden. Neither analog lowered hepatic Cd levels impressively when given po.

Administration, Oral↗
PubMed1986

Effects of caffeine on acetaminophen-induced hepatotoxicity and cadmium redistribution in mice.

When caffeine (CAF) was given ip to BDF1 mice immediately after an otherwise hepatotoxic dose of acetaminophen (ACM), the hepatotoxic action of ACM was abolished and there was no concomitant redistribution of previously-administered cadmium (Cd) from livers to kidneys as occurred in mice which received ACM only. These observations were not in accord with the recently reported enhancement of ACM hepatotoxicity by CAF following coadministration in rats (Toxicology 34, 95-101, 1985). Conversely, pretreatment of mice with CAF for 3 days followed by ACM injection enhanced the hepatotoxicity of ACM and caused a greater mobilization of Cd from livers to kidneys than was found in mice given ACM alone. The ACM-CAF interaction in mice is thus similar to the ACM-ethanol interaction in rats (Gastroenterology 80, 140-148, 1981; J. Pharmacol. Exptl. Therap. 218, 805-810, 1981). It is proposed that CAF interferes with the metabolism of ACM when administered concomitantly, but induces the microsomal mixed function oxidase system when used in a pretreatment regimen, leading to a more rapid rate of formation of the hepatotoxic arylating ACM biotransformation product.

Acetaminophen↗
PubMed1985

Computerized pattern recognition: a new technique for the analysis of chemical communication.

Computerized pattern recognition techniques can be applied to the study of complex chemical communication systems. Analysis of high resolution gas chromatographic concentration patterns of the major volatile components of the scent marks of a South American primate, Saguinus fuscicollis, demonstrates that the concentration patterns can be used to predict the gender and subspecies of unknown donors.

Animals↗
PubMed1985

Proportionate mortality study of workers in the garment industry exposed to formaldehyde.

In order to evaluate the human carcinogenicity of formaldehyde, we conducted a proportionate mortality study of garment workers engaged in the production of shirts from formaldehyde-treated cloth. This study included three plants, and was based upon 256 deaths identified from a death-benefit insurance fund. No deaths due to nasal cancer were observed, and the mortality from respiratory cancer (11 cases, PMR = 95) was slightly less than expected. Statistically significant (p less than .05) elevations in proportionate mortality were observed for malignant neoplasms of the "buccal cavity" (three cases, PMR = 750), for "biliary passages and liver" (four cases, PMR = 313) and for "other lymphatic and hematopoietic sites" (four cases, PMR = 400). A proportionate cancer mortality (PCMR) analysis also was conducted, and cancer of the "buccal cavity" (three cases, PCMR = 682), and other "lymphatic and hematopoietic sites" (four cases, PCMR = 342) were still significantly elevated. The observed excesses in cancer mortality were primarily experienced by white females, who made up the major portion of the workforce, and workers with more than 10 years of latency and duration of exposure, a criterion for inclusion for most workers in the study group. The neoplasms observed were not equally distributed among the three facilities included in the study. Because of the small number of deaths involved and the lack of consistency with other studies, we believe that these findings should be viewed cautiously, pending the outcome of more definitive studies.

Adolescent↗
PubMed1985

Skin effects of occupational kneeling.

To evaluate chronic knee trauma associated with kneeling, we conducted a cross-sectional questionnaire survey among floorlayers and tilelayers, two trades that require kneeling. Bricklayers and millwrights were studied for comparison. Approximately 28% of the 432 questionnaire respondents volunteered for a subsequent medical examination. Ultimately, data were analyzed for 112 floorlayers, 50 tilesetters, and 235 "comparison" workers. We found that the history of past skin infection in the knee area was about four times more prevalent among floorlayers (7.1%) than among workers in the other two categories combined (1.8%). Unilateral or bilateral patellar skin thickening and erythema were found to be more prevalent among those who kneel: 79% of floorlayers and 98% of tilelayers vs 35% of the control group were found to have skin thickening; 52% of floorlayers and 49% of tilelayers vs 24% of the control group were found to have erythema on the frontal aspect of the knee.

Erythema↗
PubMed1985

Renal toxicity in uranium mill workers.

Although the kidney is the critical organ limiting occupational exposure to soluble uranium compounds, there have been no adequate studies evaluating renal tubular dysfunction in chronically exposed workers. The present investigation evaluated kidney function among 39 uranium mill workers and 36 local cement plant workers of equivalent age, sex, and race. The uranium workers showed a significantly higher excretion of beta-2-microglobulin and five amino acids than the reference group. Although the levels of tubular proteinuria were mild, a dose-effect relation existed between the clearance of beta-2-microglobulin, relative to that of creatinine, and the length of time that the uranium workers had spent in the yellowcake drying and packaging area, the work area with the highest exposures to soluble uranium. Age did not account for this relationship. Glomerular function was significantly better among the uranium workers than among the referents, though this may have been the result of differences in the physical activity of the groups during the collection period. The data presented suggest reduced renal proximal tubular reabsorbtion of amino acids and of low molecular weight proteins, consistent with uranium nephrotoxicity.

Adult↗
PubMed1985

Effects of diethyldithiocarbamate and selected analogs on cadmium metabolism following chronic cadmium ingestion.

Effects of ip treatment with diethyldithiocarbamate (DDTC), 4-carboxamidopiperidine-N-dithiocarboxylate (CAP-N-DTC), and N-methyl-N-dithiocarboxyglucamine (MDCG) on cadmium (Cd) levels in selected mouse organs and tissues were assessed after mice were offered deionized water containing 0.05 mg/ml of CdCl2 X 2.5 H2O, 10 mg/ml of sucrose, and 0.125 microCi/ml of carrier-free 109-CdCl2 as the sole drinking fluid for 15 days. Only 0.31 +/- 0.01 % of the ingested Cd was absorbed. Data obtained following treatment were compared with those obtained earlier in similar studies following ip Cd injection. In contrast to its action when administered after ip Cd injection, DDTC enhanced hepatic Cd burdens in mice which received Cd po. DDTC did, however, reduce renal Cd levels markedly after Cd ingestion, while enhancing brain Cd levels. CAP-N-DTC and MDCG, which were shown earlier to have no effect on Cd levels in striated muscle following ip Cd administration, effected significant reduction of muscle Cd concentrations after Cd administration po, while also reducing hepatic and renal Cd levels significantly. It was concluded that certain dithiocarbamates effectively mobilize and promote excretion of Cd which has been absorbed from one of the natural portals of entry.

Administration, Oral↗
PubMed1985

Effects of substituted dithiocarbamates on distribution and excretion of inorganic mercury in mice.

Diethyldithiocarbamate (DDTC) and six of its N,N-disubstituted congeners were evaluated for their relative efficacies in mobilizing and promoting excretion of mercury (Hg++) using mice which had been given 203Hg++; D-penicillamine (PEN) was used as a positive control compound. While none was as effective as PEN when compared on a molar dose basis, significant activity as assessed by reduction of whole body 203Hg burden, was observed following treatment with three of the analogs. The order of effectiveness was PEN greater than N-methyl-N-dithiocarboxyglucamine (MDCG) greater than di(carboxymethyl)dithiocarbamate (DCDC) greater than di(hydroxyethyl)dithiocarbamate (DHDC).

Animals↗
PubMed1985

Effects of diethyldithiocarbamate and N-methyl-N-dithiocarboxyglucamine on murine hepatic cadmium-metallothionein in vitro.

A study was made of the effects of diethyldithiocarbamate (DDTC) and N-methyl-N-dithiocarboxyglucamine (MDCG) on partially purified cadmium-metallothionein (Cd-MT) in vitro obtained from livers of mice previously injected with CdCl2 containing 109CdCl2. Analytical Sephadex G-75 gel filtration showed that MDCG effected a time-dependent removal of Cd from MT, and 99% of the Cd was recovered as the soluble Cd(MDCG)2 complex after 24 hr of incubation. Only a portion of Cd of Cd-MT was complexed by DDTC after 24 hr of incubation; 44% remained as Cd-MT, and the net loss following centrifugation prior to application of the samples to the column corresponded to 56% of the Cd originally present. It was proposed that MDCG complexes the 4 g-atoms of Cd in cluster A of MT as well as the 3 g-atoms in cluster B, while DDTC complexes only the 4 g-atoms of Cd in cluster A.

Animals↗