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Biomedical subjects

J F Williams

Publications and source records attributed to J F Williams.

At least 55 records · Page 3Linked to original sources
PubMed1996

Brugia pahangi-induced contractility of bovine mesenteric lymphatics studied in vitro: a role for filarial factors in the development of lymphedema?

Products generated by filarial nematodes depress vascular reactivity by mechanisms involving endothelial cells. We hypothesized that comparable filarial-induced alterations might occur in lymph vessels. Experiments were designed to test the hypothesis that spontaneous contractions of bovine mesenteric lymphatics studied in vitro are altered by the filarial parasite Brugia pahangi. Rings of bovine mesenteric lymphatics were suspended in tissue baths and spontaneous contractions were evaluated for rate, rhythm, and amplitude. Rings that met inclusion criteria (rate > 1.8/min, regular rhythm, and an amplitude > 500 mg) were randomly exposed to B. pahangi or used as controls. Parasites were added to the bath at time zero. Changes in rate, rhythm, and magnitude of spontaneous contractions were evaluated every 10 min. Comparisons were made within control or Brugia-infected groups over time and between groups (B. pahangi versus controls). The presence of B. pahangi significantly depressed the frequency of spontaneous contractions when compared with controls. Control rings were stable over time, without changes in rate, rhythm, or amplitude. However, B. pahangi alter both the rate and rhythm of spontaneous contractions. Since spontaneous contractile activity is likely to be important in the propulsion of lymph, alterations of contractile activity could result in lymphedema. Thus, filarial factors may be responsible, in part, for altered lymphatic function seen in lymphedema. Pharmacologic intervention aimed toward influencing host-parasite metabolic interactions may, in this complicated scenario, prove useful.

Animals↗
PubMed1996

Effect of heartworm infection on fade of norepinephrine-induced constriction in canine pulmonary vein.

OBJECTIVE: To test the possible role of endothelial cells in mediating fade of norepinephrine-induced constriction and the effect of heartworm infection on these responses. DESIGN: Rings of pulmonary vein from control and heartworm-infected dogs were constricted with norepinephrine (10(-5.5)M) and followed over 65 minutes. Time profiles were established by measuring active tension every 2 minutes for the first 10 minutes, then every 5 minutes for 15 minutes, then every 10 minutes for 40 minutes. Time profiles were done in pulmonary vein rings with and without endothelial cells, and in the presence and absence of N-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase inhibitor), mefenamic acid (cyclooxygenase inhibitor), or methylene blue (guanylate cyclase inhibitor). ANIMALS: 12 noninfected control and 11 heartworm-infected dogs. RESULTS: Pulmonary vein constricted with norepinephrine spontaneously loses tension (fades) over time. Fade was not different between control and heartworm-infected dogs. In pulmonary vein from control dogs, methylene blue decreased fade while L-NAME and mefenamic acid did not. In pulmonary vein from heartworm-infected dogs, L-NAME and methylene blue significantly decreased fade, but mefenamic acid did not. CONCLUSION: Nitric oxide, but not cyclooxygenase products, mediates fade of norepinephrine-induced constriction in pulmonary vein from heartworm-infected dogs. In control dogs, neither nitric oxide nor cyclooxygenase products appear to be involved in fade. We conclude that in canine pulmonary vein, fade of norepinephrine-induced constriction is mediated, in part, by endothelial cells. CLINICAL RELEVANCE: Altered production of endothelium-derived relaxing factors may be important in the pathogenesis of heartworm disease.

Animals↗
PubMed1996

Microbial contamination of dental unit waterlines: current preventive measures and emerging options.

Various approaches to prevention and control of microbial contamination of dental unit water are evolving. Currently available methods and emerging technologies are reviewed here in the context of contemporary federal regulatory and advisory agency positions on water quality in the dental operatory. Clean water systems, fully autoclavable systems, and a variety of devices designed to provide physical barriers to the influx and accumulation of microbial contaminants can all be used to assure satisfactory quality for coolant and irrigant water. There is one important proviso: all require a commitment to maintenance if they are to be deployed successfully. Stricter adherence to American Dental Association/American National Standards Institute standards in manufacturing and production and compliance with federal regulatory marketing procedures for equipment and devices would do much to advance the cause of dental unit water quality control.

Biofilms↗
PubMed1996

Microbial contamination of dental unit waterlines: origins and characteristics.

Microbial adherence to the internal surface of dental tubing and the formation of a highly protective biofilm layer is predictable, given the ideal growth conditions in the tubing. The slime layer is the most common cause of dental water contamination. Various environmental and human-derived potential pathogens have been reported worldwide. Dental equipment such as retracting shut-off valves, antiretracting valves that tend to fail, or waterlines that are inaccessible contribute to a situation in which virtually every standard dental unit contains contaminated water. While exposure to Pseudomonas, Moraxella, Staphylococcus, and Legionella has been linked to dental water, the medical risk of dental unit waterline contamination is most significant to immune-deficient individuals. Regulations and technological devices are emerging to manage dental water quality.

Animals↗
PubMed1995

Differential effect of cytokines on the phenobarbital or 3-methylcholanthrene induction of P450 mediated monooxygenase activity in cultured rat hepatocytes.

Cultured rat hepatocytes have been used to compare the relative activities of cytokines to inhibit the phenobarbital (PB) or 3-methylcholanthrene (MC) induction of cytochrome P4502B1 and 2B2 (P4502B1/2) or P4501A1 and 1A2 (P4501A1/2), respectively. Recombinant cytokines tested were human interleukin-6 (IL-6), interleukin-1 alpha and -beta (IL-1 alpha and IL-1 beta, respectively), and rat gamma-interferon (INF gamma). Hepatocytes were cultured in the presence of 2 mM PB or 1 microgram MC/mL culture medium for 24 hr with or without the cytokines. Benzyloxyresorufin and ethoxyresorufin O-dealkylase (BROD and EROD, respectively) activities were determined as indices of P4502B1/2 and P4501A1/2, respectively. All cytokines produced a concentration-dependent inhibition of the PB induction of BROD activity. IL-1 beta and IL-6 were approximately equipotent with IC50 values of 1-2 U/mL, causing greater than 90% inhibition of PB induction of BROD activity at a concentration of 50 U/mL culture medium. IL-1 alpha tended to be less active. PB induction of BROD activity was also inhibited by INF gamma, but higher concentrations (62.5 to 500 U/mL culture medium) were required. All cytokines were less effective in inhibiting the MC induction of EROD activity than the PB induction of BROD activity. IL-1 beta and IL-6, at 50 U/mL culture medium, inhibited EROD induction by only 35% compared with the greater than 90% inhibitory effect on the PB induction of BROD activity. INF gamma was ineffective in inhibiting EROD activity at the concentrations studied. Western immunoblot analysis indicated that the cytokines prevented the ability of the inducers to increase the expression of P4502B1/2 and P4501A1/2 immunoreactive proteins, and this effect correlated with their inhibitory effect on induction of enzyme activity. The results suggest that inducible isoforms of cytochrome P450 differ in their susceptibility to regulation by the cytokines, and that cytokines possess differential activity to inhibit the induction of P450 isoforms, with IL-1 beta and IL-6 being the most effective.

Animals↗
PubMed1995

Mixed-function oxidase activity in sepsis.

Hepatic dysfunction is a major contributor to death in multiple organ system failure. To evaluate whether this dysfunction increases with the length of sepsis, we studied the effect of fulminant CLP peritonitis with hyperoxia on mixed-function oxidase-MFO (cytochrome P450 content and activity) and lipid peroxidation in rat livers. Livers were harvested at 18, 21, 24, and 27 hr, homogenized, and microsomal fractions prepared. Cytochrome P450 concentration was determined by assay and P450 activity was determined by the metabolism of ethoxyresorufin and ethoxycoumarin. Lipid peroxidation was estimated by measuring malondialdehyde content. Septic rats showed decreases in P450 levels and activity, which worsened with duration of sepsis. These decreases were partially lessened by hyperoxia. Although there was a trend toward increased lipid peroxidation, this effect was not statistically significant. This study suggests that while MFO content and activity decrease with sepsis, these decreases do not appear to be related to the production of oxygen-derived free radicals. Furthermore, hyperoxia actually appears to have a protective role in this instance.

Animals↗
PubMed1995

African-American and white patients admitted to the intensive care unit: is there a difference in therapy and outcome?

OBJECTIVE: To evaluate variations in patient characteristics, hospital mortality, intensive care unit (ICU) length of stay, and treatment among African-American and white patients admitted to the ICU. DESIGN: Prospective, inception cohort study. SETTING: Forty-two ICUs at 40 U.S. hospitals, including 26 hospitals that were randomly selected and 14 volunteer institutions, primarily large university or tertiary care centers. PATIENTS: A consecutive sample of 17,440 ICU admissions. MEASUREMENTS AND MAIN RESULTS: Selected demographic, physiologic, and treatment information for an average of 415 admissions at each ICU, and payor information at 36 of 40 hospitals. Outcomes were compared using the ratio of observed to risk-adjusted predicted hospital mortality rate, ICU length of stay, and resource use during ICU day 1 and the first seven ICU days. Compared with 14,006 white patients admitted to the ICU, 2,450 African-American patient admissions were significantly (p < .0001) younger, had a higher mean severity of disease, and a greater proportion of nonoperative and emergency department admissions. African-Americans had fewer life-threatening Acute Physiology and Chronic Health Evaluation III (APACHE III) comorbidities, but a higher prevalence of severe compromise in activities of daily living, diabetes mellitus, chronic renal disease, and intravenous drug abuse. There was no significant racial difference in risk-adjusted hospital mortality rate. For African-Americans, adjusted ICU length of stay was significantly (p < .0003) shorter, and the first 7 days of resource use was significantly (p < .0004) lower, but the differences were small (3% to 4%). CONCLUSIONS: After adjusting for variations in patient characteristics at ICU admission, race has no significant effect on hospital survival. The small but statistically significant differences in adjusted ICU length of stay and resource use could indicate undertreatment for African-Americans or overtreatment for whites.

APACHE↗
PubMed1995

Legionella contamination of dental-unit waters.

Water samples collected from 28 dental facilities in six U.S. states were examined for the presence of Legionella pneumophila and other Legionella spp. by the PCR-gene probe, fluorescent-antibody microscopic, and viable-plate-count detection methods. The PCR and fluorescent-antibody detection methods, which detect both viable and viable nonculturable Legionella spp., gave higher counts and rates of detection than the plate count method. By the PCR-gene probe detection method, Legionella spp. were detected in 68% of the dental-unit water samples and L. pneumophila was detected in 8%. Concentrations of Legionella spp. in dental-unit water reached 1,000 organisms per ml or more in 36% of the samples, and 19% of the samples were in the category of 10,000/ml or above. L. pneumophila, when present in dental-unit water, never reached concentrations of 1,000/ml or more. Microscopic examination with fluorescent-antibody staining indicated that the contamination was in the dental-unit water lines rather than in the handpieces. Legionella spp. were present in 61% of potable water samples collected for comparative analysis from domestic and institutional faucets and drinking fountains; this percentage was not significantly different from the rate of detection of Legionella spp. in dental-unit water. However, in only 4% of the potable water samples did Legionella spp. reach concentrations of 1,000 organisms per ml, and none was in the 10,000 organisms-per-ml category, and so health-threatening levels of Legionella spp. in potable water were significantly lower than in dental-unit water. L. pneumophila was found in 2% of the potable water samples, but only at the lowest detectable level.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA Probes↗
PubMed1995

The use of risk predictions to identify candidates for intermediate care units. Implications for intensive care utilization and cost.

OBJECTIVE: To develop a predictive equation that estimates the probability of life-supporting therapy among ICU monitor admissions and to explore its potential for reducing cost and improving ICU utilization. DESIGN: Prospective inception cohort analysis. PARTICIPANTS: Forty-two ICUs in 40 US hospitals with more than 200 beds and a consecutive sample of 17,440 ICU admissions. INTERVENTIONS: A multivariate equation was developed to estimate the probability of life support for ICU monitoring admissions during an entire ICU stay. MEASUREMENTS: Demographic, physiologic, and treatment information obtained during the first 24 h in the ICU and over the first 7 ICU days. RESULTS: The most important determinants of subsequent risk for life-supporting (active) treatment were diagnosis, the acute physiology score of APACHE III, age, operative status, and the patient's location and hospital length of stay before ICU admission. Among 8,040 ICU monitoring admissions, 6,180 (76.8%) had a low (< 10%) risk for receiving active treatment during the ICU stay; 95.6% received no subsequent active treatment. Review of outcomes and the type and amount of therapy received suggest that most low-risk ICU monitor admissions could be safely cared for in an intermediate care setting. CONCLUSION: Objective predictions can accurately identify groups of ICU admissions who are at a low risk for receiving life support. This capability can be used to assess ICU resource use and develop strategies for providing graded critical care services at a reduced cost.

APACHE↗
PubMed1994

Dirofilaria immitis: heartworm products contract rat trachea in vitro.

Subtle decreases in racing performance have been noted in asymptomatic greyhounds with heartworm burdens insufficient to obstruct pulmonary outflow, suggesting that alternative mechanisms may be involved in the pathogenesis of canine heartworm disease. Endothelium-dependent relaxation is depressed in the in vivo femoral artery of heartworm-infected dogs, in the in vitro pulmonary artery from heartworm-infected dogs, and in the in vitro rat aorta exposed to heartworms, heartworm-conditioned medium, and serum from heartworm-infected dogs. These findings suggest that circulating filarial factors may play a role in the pathogenesis of heartworm infection. We examined the effect of Dirofilaria immitis, the canine heartworm, on acetylcholine-induced contraction of rat tracheal rings. In epithelium-intact rings, both heartworms and heartworm-conditioned medium increased acetylcholine-induced contraction. Pretreatment of the parasites with aspirin prevented the filarial-induced increase in acetylcholine-induced contraction, suggesting that parasite cyclooxygenase products are responsible for the effect. In addition, heartworms caused contraction in both epithelium-intact and denuded rings and this effect was markedly decreased by pretreatment of the worms with aspirin. Filarial cyclooxygenase metabolites may cause airway hyperreactivity and parasite-derived factors could play a role in the subtle changes in exercise performance seen in asymptomatic greyhounds with low worm burdens. Comparable mechanisms may be operating in other filarial diseases, including those that affect humans in tropical countries.

Acetylcholine↗
PubMed1994

Dirofilaria immitis: depression of endothelium-dependent relaxation of canine femoral artery seen in vivo does not persist in vitro.

In heartworm-infected dogs, circulating filarial factors appear to be responsible for the seasonal depression of endothelium-dependent responses seen in the in vivo femoral artery. The effect of heartworm infection on vascular responses of the femoral artery in vitro, when the vessel is not constantly exposed to circulating factors, is unknown. Experiments were designed to test the hypothesis that in vivo exposure to circulating filarial factors leads to changes in the magnitude and mechanism of endothelium-dependent relaxation that are demonstrable in vitro. Rings of femoral artery from heartworm-infected and noninfected control dogs were suspended in muscle baths, and dose-response relationships to endothelium-dependent (methacholine) and -independent (sodium nitroprusside) vasodilators were done. To determine the mechanism of relaxation, dose-response relationships were also done in the presence of an inhibitor of nitric oxide synthase (L-NAME), an inhibitor of guanylate cyclase (methylene blue), or an inhibitor of cyclooxygenase (mefenamic acid). Heartworm infection did not depress endothelium-dependent relaxation of the femoral artery in vitro. Furthermore, the mechanism of relaxation in heartworm and control femoral artery is identical. These data suggest that the effect of circulating filarial factors that alter the magnitude and mechanism of relaxation in systemic vessels in heartworm-infected dogs rapidly disappears in their absence. This results has important bearing on the dynamics of heartworm-induced pathophysiological changes during infection and could influence the nature and chronology of responses to therapy.

Animals↗
PubMed1994

Evidence that prostaglandins modulate lipogenesis in cultured lymphocytes--a comparison with its effect on macrophages and tumour cells.

Lipogenesis is essential for the rapid proliferation of cells and it is established that the biosynthesis of selected lipids precedes S-phase, DNA synthesis and the initiation of cell division. Pyruvate was previously shown to be an important lipid precursor for lymphocytes, macrophages and tumour cells. This study now reports the role of prostaglandins (PG) on the regulation of lipogenesis from [3-14C] pyruvate in 24-h cultured lymphocytes. It is shown that indomethacin (10 microM) and ibuprofen (10 microM), both inhibitors of PG biosynthesis, increased [3-14C] pyruvate incorporations into phospholipid and cholesterol fractions in resting lymphocytes but reduced its incorporation into these fractions in concanavalin A (Con A)-stimulated lymphocytes and tumour cells. These two agents also affected [2-14C] thymidine incorporation into the DNA of these cells in the same manner. Lipids produced from [3-14C] pyruvate and exported into the cell culture medium were also measured. The PG biosynthesis inhibitions reduced the transfer to culture medium of arachidonic acid, phospholipids, cholesterol and fatty acids higher than C20 by lymphocytes and tumour cells. Although macrophages are not proliferative cells, the cytoplasmic export measurement is important because these cells have a high capacity for lipid secretion. The results show that the PG biosynthesis inhibitors do not affect the export of phospholipids and cholesterol in macrophages. They do however markedly change the export of arachidonic acid and fatty acids higher than C20 produced from [3-14C] pyruvate in macrophages. It is also reported that a cell-stimulating response diminished the above fatty acid outcome in resting cells and augmented it in thioglycollate-stimulated macrophages. The findings suggest that PG modulation of lipogenesis may depend on cell cycle phase as well as the intrinsic lipid metabolic diversity and capacity.

Acetates↗