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Biomedical subjects

A McDonald

Publications and source records attributed to A McDonald.

At least 19 recordsLinked to original sources
PubMed1996

Methanol potentiation of carbon tetrachloride hepatotoxicity: the central role of cytochrome P450.

Evidence to explain the enhanced hepatotoxicity of carbon tetrachloride (CCl4) following methanol exposure by inhalation is presented. Hepatic microsomes prepared from male F344 rats exposed to methanol at concentrations up to 10,000 ppm showed increased p-nitrophenol hydroxylase activity but no increase in pentoxyresorufin-O-dealkylase or ethoxyresorufin-O-deethylase activities. Hepatic antioxidant levels, glutathione levels and glutathione-S-transferase activity in methanol-treated animals were not different from controls. In vitro metabolism of CCl4 was also increased in microsomes from methanol-treated animals. Pretreatment with allyl sulfone, a specific chemical inhibitor of cytochrome P450 2E1, abolished the difference in microsomal metabolism between exposed and control animals. This study shows that methanol exposure induces cytochrome P450 2E1, which appears to be the principal toxicokinetic mechanism responsible for the increased metabolism and thus the increased hepatotoxicity of CCl4.

Animals↗
PubMed1996

Age-specific HIV incidence among homosexually active men in Australia.

OBJECTIVE: To estimate age at HIV infection among homosexually active men in Australia. DESIGN: Age-specific back-projection estimates of HIV incidence. METHODS: Monthly counts of AIDS among homosexually active men diagnosed by 30 June 1994 and reported by 31 March 1995 were obtained from the National AIDS Registry and were adjusted for reporting delays. The progression rate to AIDS was estimated from a large cohort study of HIV-infected homosexual men, with adjustment for the effect of age at HIV infection and the effect of antiretroviral and prophylactic treatments. RESULTS: The median age at HIV infection was estimated to have decreased from 31 years of age between 1982 and 1984 to between 23 and 27 years in the periods 1987 to 1989 and 1990 to 1994. Despite the trend to a younger median age at HIV infection during the current epidemic, HIV incidence was estimated to have declined in all age groups from a peak in the mid-1980s. This decline was more pronounced in the older age groups, with more modest reductions in age groups under 30 years. CONCLUSION: Most HIV infections among homosexually active men since 1987 appear to have occurred in men aged under 30 years. This has implications for education programs aimed at preventing HIV infection among homosexually active men.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Pulmonary aspiration in a long-term care setting: clinical and laboratory observations and an analysis of risk factors.

OBJECTIVE: To determine the incidence and risk factors associated with aspiration in a high risk group in a long-term care setting. DESIGN: A prospective study of demographic, nutritional, clinical, dental, and survival characteristics in 69 patients who suffered 98 aspirations events from May 1, 1990, to December 31, 1990. Demographic and nutritional data from 192 patients who did not aspirate were collected from September 1991 to December 1991. SETTING: A long-term care VA facility. PATIENTS: Long-term care residents, most of whom were neurologically debilitated. MEASUREMENTS: The incidence of aspiration was measured and the clinical and microbiological characteristics of aspiration-associated nosocomial pneumonia described. Mortality and demographic, clinical, and nutritional characteristics were compared between patients who aspirated and those who did not. MAIN RESULTS: Twenty-five percent of the study group aspirated during the 8-month observational period, and 56% of the aspiration events progressed to roentgenographically proven cases of nosocomial pneumonia. Six bacteremic episodes were documented, and results of sputum cultures were consistent with mixed Gram-positive and Gram-negative infections. During the study period, patients who aspirated were at three times the risk of dying compared with patients who did not aspirate. Three years later, only 17% of the original group of patients who aspirated were still alive compared with 60% of the patients who had not aspirated. Multivariate analysis identified tube feeding, presence of a hyperextended neck or contractions, malnutrition, and the use of benzodiazepines and anticholinergics as risk factors. CONCLUSIONS: Pulmonary aspiration is a common and serious event in neurologically impaired long-term care patients. Some risk factors are amenable to change.

Aged↗
PubMed1995

Sperm motility in the presence of boundaries.

The fluid dynamics of sperm motility near both rigid and elastic walls is studied using the immersed boundary method. Simulations of both single and interacting organisms are presented. In particular, we find that nearby organisms originally undulating with a 90 degree phase shift may adjust their relative swimming velocities and phase-lock. Comparisons with previous analytical results are also discussed. The tendency of a near-wall to attract organisms is demonstrated.

Animals↗
PubMed1995

Potentiation of carbon tetrachloride hepatotoxicity by inhaled methanol: time course of injury and recovery.

Increases in the use of methanol (MeOH) as a transportation fuel would result in greater potential for inhalation exposure. Because oral exposure to MeOH potentiates the hepatotoxicity of carbon tetrachloride (CCl4), we examined the ability of inhaled MeOH to potentiate CCl4 hepatotoxicity and the time course of injury and recovery. Adult male F-344 rats were exposed to 0 or to 10,000 ppm MeOH by inhalation for 6 h and gavaged with 0.075 ml CCl4/kg 24 h later. Hepatotoxicity was assessed 0.5, 1, 1.5, 2, 3, 7, 15, 30, and 61 d after CCl4 exposure. For CCl4 alone, hepatotoxicity was most severe at 0.5 and 1 d, when minimal centrilobular hepatocellular necrosis and predominately mild centrilobular hepatocellular vacuolar degeneration occurred. By d 3, the livers from the CCl4 rats were histologically normal. For MeOH+CCl4, peak severity of hepatic injury was at 1 and 1.5 d, when moderate centrilobular necrosis and moderate/marked centrilobular degeneration occurred. MeOH+CCl4 resulted in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that were increased, relative to CCl4 alone, 171- and 113-fold, respectively, on d 1, and 166- and 140-fold, respectively, on d 1.5. Significant serum elevations in MeOH+CCl4 rats, relative to CCl4 alone rats, were present until d 7 and d 15 for AST and ALT, respectively. By d 3 and d 7, degeneration and necrosis, respectively, due to MeOH+CCl4 were essentially resolved. On d 7, the MeOH+CCl4 hepatic injury consisted mainly of chronic inflammation and centrilobular fibrosis. By d 30, the livers of MeOH+CCl4 rats were histologically normal. These data demonstrate that inhaled MeOH potentiates the hepatotoxicity of orally ingested CCl4, increasing the severity of CCl4 hepatotoxicity as well as the time required for recovery.

Administration, Inhalation↗
PubMed1995

No evidence for a general change in contractile responsiveness of the mesenteric artery with aging.

Rings of human mesenteric artery (1-3 mm diameter) suspended in Krebs solution were contracted (maximal contraction relative to KCl 80 mM = 100%) by the thromboxane mimetic U46619 (190 +/- 10%), noradrenaline (162 +/- 9%), angiotensin II (107 +/- 11%), and 5-hydroxytryptamine (5-HT) (96 +/- 10%). Reducing extracellular Ca2+ strongly inhibited the maximal contraction to angiotensin II and 5-HT and moderately inhibited the maximal contraction to noradrenaline, but had less effect on the maximal contraction to U46619 (contraction in Ca2+ 1.3 microM was reduced to 24 +/- 5, 20 +/- 3, 38 +/- 4 and 52 +/- 4% respectively of the contraction in 2.5 mM Ca2+). Reducing extracellular Ca2+ lowered sensitivity to 5HT, angiotensin II, and U46619, but did not alter sensitivity to noradrenaline. The EC50 and maximal contraction for each of the 4 agonists did not change with patient age at 2.5 mM Ca2+ or in reduced extracellular Ca2+. It is concluded that aging does not affect the responsiveness of mesenteric arterial smooth muscle to physiological vasoconstrictors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Setting air quality standards for carcinogens: an alternative to mathematical quantitative risk assessment--discussion paper.

1. It has been accepted in many countries that the regulation of ambient air quality should involve the use of health-based air quality standards. 2. Setting standards for air pollutants which are genotoxic carcinogens presents difficult problems to the regulator, in that the prediction of the effects on health of low levels of exposure is suspected to be inaccurate, and is not presently amenable to either experimental or epidemiological verification. 3. In some countries, techniques of Mathematical Quantitative Risk Assessment (MQRA) have been adopted to calculate acceptable levels of exposure to, or the unit risk factors for, genotoxic carcinogens. We regard these approaches as unsatisfactory. 4. An alternative approach, based upon a number of argued premises, a strategy which identifies decision points and the cautious application of uncertainty factors, is described.

Air↗
PubMed1994

Cholecystokinin corticostriatal pathway in the rat: evidence for bilateral origin from medial prefrontal cortical areas.

The anterograde tracer Phaseolus vulgaris-leucoagglutinin was used to examine the organization of the projections to the striatum from medial prefrontal and frontal cortical areas in the rat with reference to their relation to cholecystokinin-like immunoreactivity in the striatum. Medial prefrontal cortical areas projected bilaterally, with an ipsilateral predominance, to the striatum. Most of the positive fibres were found in medial and ventral areas of the caudate-putamen and in the nucleus accumbens. Labelled fibres formed distinct patch-like arrangements throughout the dorsomedial striatum, whereas more ventrally the fibres were densely packed and spread to lateral areas. Almost no fibres were found in the dorsolateral aspects of the caudate-putamen. Cholecystokinin-like immunoreactivity in the striatum was diffusely distributed in the medial aspects, in fine punctate elements as well as in patches of fibres. Overlapping of corticostriatal clusters of fibres, from medial prefrontal cortex, with cholecystokinin-immunoreactive patches was found at all rostrocaudal levels studied, but predominantly in rostral areas. The overlap was present both in the ipsilateral and the contralateral side. Often the cluster of corticostriatal fibres was completely and precisely overlaid by a cholecystokinin-immunoreactive patch. At more caudal planes the overlap was only partial and in some instances cholecystokinin-positive patches "avoided" zones of dense corticostriatal fibre terminations. Frontal cortex injections of tracer gave rise to a network of fibres in the lateral aspects of the striatum, sparing the medial areas. No overlap with cholecystokinin-immunoreactive patches was found in these cases. These results suggest that a large number of cholecystokinin-containing striatal fibres originate in medial prefrontal cortical areas.

Animals↗
PubMed1994

A comparison of two methods to ascertain dietary intake: the CARDIA Study.

Data on dietary intake were collected in the Coronary Artery Risk Development in Young Adults (CARDIA) Study at the baseline examination in 1985-86 and again at the second examination 2 years later. At baseline, a diet history questionnaire developed for the CARDIA study was used; at the second exam the NCI (Block) food frequency questionnaire was used. The purpose of the present report is to compare the estimated nutrient intakes obtained with the two instruments; to compare correlations of nutrient intakes obtained at the two exams with those observed for other lifestyle and physiological variables also measured 2 years apart; and to assess ability to test hypotheses relating 2-year changes in risk factors to between-exam differences in reported nutrient intakes. Mean levels of reported intake were generally greater for both blacks and whites on the CARDIA diet history than on the Block food frequency. Rank order correlations of reported nutrient intakes between the two questionnaires indicated greater consistency between instruments for whites (r's ranging between 0.35 and 0.52) than for blacks (r's ranging between 0.29 and 0.45). Correlations over time for nutrients were smaller than those observed for body size measures and lipid levels but were similar in magnitude to those for blood pressure, physical activity, and life events. At both exams, total caloric intake was positively associated with physical activity (range of r's for CARDIA were 0.07 for white women to 0.23 for black men, the range of r's for Block were 0.06 for women to 0.11 for white men). Using data from the two examinations, 2-year changes in total plasma cholesterol were significantly related to 2 year changes in Keys scores. The results of this comparison are useful in that they show similarities and differences between two instruments developed to gather dietary intake data. The study also illustrates the need to monitor young adults during a time when rapid changes occur in many lifestyle and physiologic factors.

Adult↗
PubMed1994

Toxicology studies of a chemical mixture of 25 groundwater contaminants: hepatic and renal assessment, response to carbon tetrachloride challenge, and influence of treatment-induced water restriction.

Because groundwater contamination is an important environmental concern, we examined the hepatic and renal effects of repeated exposure to a mixture of 25 chemicals frequently found in groundwater near hazardous-waste disposal sites and the effect of such exposure on carbon tetrachloride (CCI4) toxicity. Adult male F-344 rats received ad libitum deionized water and feed (Ad Lib Water) or ad libitum 10% MIX (referring to 10% of a technically achievable stock mixture) and feed for 14 d. Because exposure to the 25-chemical mixture via the drinking water resulted in decreased water and feed consumption, restricted deionized water and feed controls (Restricted Water) were included. On d 14, rats were gavaged with 0, 0.0375, 0.05, 0.075 or 0.15 ml CCl4/kg, and hepatic and renal toxicity assessed 24 h later. Little or no hepatic and renal toxicity was observed in rats exposed to 10% MIX alone. No hepatic or renal lesions occurred that could be attributed to 10% MIX alone. Slight but statistically significant alterations, of uncertain biological significance, resulted from the water treatments: 10% MIX increased alanine aminotransferase, urea nitrogen (BUN), and BUN/creatinine ratio; Restricted Water increased 5'-nucleotidase and decreased alkaline phosphatase. Relative kidney weight was increased by both 10% MIX and Restricted Water. CCI4 resulted in significant dosage-dependent hepatotoxicity in all three water treatment groups but had little or no effect on renal indicators of toxicity. Relative to Ad Lib Water, significantly greater hepatotoxicity occurred in both 10% MIX and Restricted Water rats. The response to CCI4 in the Restricted Water rats was similar to that of 10% MIX rats, indicating that a substantial portion of the effect of 10% MIX on CCI4 hepatotoxicity is due to decreased water and feed intake.

Analysis of Variance↗
PubMed1994

Prognostic significance of nucleolar organizer regions (NORS) in malignant melanoma.

Nucleolar organizer regions (NORs) are loops of ribosomal DNA (rDNA) in the nucleolus and are associated with acidic proteins. They are seen in routinely processed paraffin sections by using a one-step colloidal silver (Ag) staining method; they appear as black dots termed "AgNORs". The quantitative assay of AgNORs has been used to differentiate benign from malignant neoplasms. Melanocytic lesions differ significantly in AgNOR counts between malignant melanoma and nevi. However, conflicting results have been reported as to AgNORs' prognostic value in melanoma. A recent study showed AgNOR counts to be a more accurate prognostic indicator than Breslow's thickness. In this study, we counted the AgNORs in 26 patients with primary cutaneous melanomas (CMM) between 2.0 mm and 2.5 mm thick. Of these, 14 are alive without disease (AN) at 5 years after diagnosis (group 1) and 12 are dead of disease (DD) in less than 5 years (group 2). The AgNORs were scored in 30 nuclei per tumor, and the means were calculated. For group 1, the mean number of AgNORs per nucleus was 6.88, ranging from 3.73 to 12.70. For group 2, the mean number was 6.97, ranging from 3.63 to 11.67. Statistical analysis using analysis of variance (ANOVA) showed no significant difference between the groups (p = 0.33). In our study, AgNOR counts did not prove to be of prognostic value in malignant melanoma.

Adult↗
PubMed1994

Hypothyroidism presenting with cardiac tamponade.

Two cases of cardiac tamponade initially suspected to be secondary to malignancy are presented. Primary hypothyroidism can cause pericardial effusions and thyroid function tests confirmed this diagnosis in these cases. Hypothyroidism should be considered as an underlying cause of pericardial effusion in cardiac tamponade.

Aged↗