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J F Inciardi

Publications and source records attributed to J F Inciardi.

14 recordsLinked to original sources

Effect of antibiotic-loaded hydrophilic stent in the prevention of bacterial adherence: a study of the charge, discharge, and recharge concept using ciprofloxacin.

BACKGROUND: Ciprofloxacin prophylaxis significantly prolonged stent patency in cats, but human studies produced conflicting results, possibly due to varying drug levels in bile. The uptake (charge) and release (discharge) of ciprofloxacin from a hydrophilic stent (HS) in an antibiotic solution and the effect of a ciprofloxacin-loaded stent (CHS) in inhibiting Escherichia coli adherence were tested. The adjuvant effect of ciprofloxacin perfusion (recharge) in the inhibition of E coli adherence was also tested. METHODS: Uptake: segments of HS were immersed in 5 mL of ciprofloxacin solutions for 24 hours. Ciprofloxacin remaining in solution was measured to determine the uptake by the HS. Release: CHS were placed in 5 mL water for 24 hours, and released ciprofloxacin was measured. CHS were placed on culture plates with E coli and incubated; diameters of inhibited zones were measured. CHS 0.5 cm in length were incubated in separate 5 mL E coli suspension (10(7) colony forming units [CFU]/mL) in 2% ox bile for 4 hours. E coli adhered on CHS were measured and compared with control HS. An E coli (10(6) CFU/mL) suspension was perfused through a modified Robbins device (MRD)-containing CHS. Stents were removed at regular intervals and processed to determine the adherence of E coli; non-loaded HS served as controls. The experiment was repeated by using CHS together with perfusion of ciprofloxacin solution (0.3 microg/mL) into the MRD for up to 7 days; normal saline solution was used as a control in a second MRD. Stents were removed daily to determine the adherence of E coli. RESULTS: Uptake and release of ciprofloxacin by HS and CHS, respectively, were related to concentration of ciprofloxacin. Between 50% to 90% of the drug was released in 24 hours. Zonal inhibition of E coli growth was proportional to the concentration of ciprofloxacin on the CHS. There was an initial 10-fold reduction in attached E coli on CHS compared with controls, but this effect diminished after 24 hours. With ciprofloxacin perfusion, there was a 100-fold reduction in adhered E coli on CHS, although there was no change in E coli concentration in bile. CONCLUSIONS: There was a free exchange (uptake and release) of ciprofloxacin along a concentration gradient between the antibiotic solution and HS. CHS reduced the number of adhered E coli, but the effect was short-lived. Perfusion of ciprofloxacin offers an adjuvant benefit by enhancing inhibition of E coli adherence on CHS.

Anti-Bacterial Agents↗

Expression of bacterial beta-glucuronidase in human bile: an in vitro study.

BACKGROUND: Bacterial beta-glucuronidase causes deconjugation of bilirubin diglucuronide resulting in the precipitation of calcium bilirubinate, which contributes to biliary sludge and stone formation. This process is attributed to enzyme activity produced by the aerobic enterobacteriaceae such as Escherichia coli and Klebsiella sp. The presence of Clostridium sp. was detected in 48 of 56 intrahepatic stones by using polymerase chain reaction techniques and cultured Clostridium perfringens from 14 of 18 unblocked biliary stents. Such bacteria are reported to produce beta-glucuronidase activity. The aim of this study was to determine the proportion of biliary bacteria isolated from pigment stones and stents that produce beta-glucuronidase and to compare the enzyme activity expressed by the different bacteria in human bile. METHODS: A total of 202 bacteria were isolated from blocked and unblocked biliary stents and pigment ductal stones recovered from patients. Of these, 61 bacteria expressed beta-glucuronidase activity in brain heart infusion broth. These 61 bacteria were subsequently grown in human bile under aerobic or anaerobic conditions to the early stationary phase and assayed for beta-glucuronidase activity by using rho-nitrophenyl beta-D glucuronide as substrate. Results were normalized and reported as units of enzyme activity per milligram protein of the bacteria. RESULTS: C. perfringens produced beta-glucuronidase enzyme activity that was 34-fold higher than that for E coli, Staphylococcus, Corynebacterium sp., Bacillus sp., Enterococcus sp., Acinetobacter sp., Streptococcus sp., and Klebsiella sp. CONCLUSION: C. perfringens with its higher enzyme activity is more important in the deconjugation of bilirubin diglucuronide than E coli and Klebsiella sp.

Bacteria, Anaerobic↗

Incidence trends for colorectal cancer in California: implications for current screening practices.

PURPOSE: The sensitivities of different screening methods for precancerous adenomas may affect the anatomical distribution of colorectal cancers. We used statewide data from California to describe time trends in the distribution of colorectal carcinoma. SUBJECTS AND METHODS: Between 1988 and 1996, 110,378 cases of colorectal cancer were recorded in the California Cancer Registry database. Tumors proximal to, but not including, the sigmoid colon were termed "right-sided." The remaining tumors, excluding the anus, were termed "left-sided." Multivariable analyses were used to determine the effects of age, sex, and race on changes in tumor location over time. RESULTS: During the study period, the annual incidence of colorectal cancer decreased steadily, from 200 to 162 cases per 100,000 residents. The decrease in left-sided tumors was about twice that observed on the right (-24.3% vs -11.6%). This disparity remained significant when adjusted for age, sex, and race (P = 0.0001). CONCLUSION: The incidence of colorectal cancer in California is decreasing, particularly for left-sided (distal) tumors. Current screening recommendations, which emphasize examination of the distal colon, may need to be expanded to include the entire colon.

Age Distribution↗

In vitro evaluation of antibiotic prophylaxis in the prevention of biliary stent blockage.

BACKGROUND: Bacterial adherence and biofilm formation are important factors in the blockage of biliary stents. Clinical studies with oral antibiotic prophylaxis to prevent stent blockage have produced conflicting results. The aim of this study was to evaluate the in vitro effect of single antibiotic (ciprofloxacin, ceftazidime, or ampicillin) treatment on adherence of Escherichia coli and Enterococcus to plastic stents. METHODS: Selected clinical isolates of E coli and Enterococcus were perfused through a modified Robbins device containing segments of polyethylene stents. The stents were removed daily and the number of bacteria attached was measured. The effect of antibiotic treatment on bacterial adherence was tested by the perfusion of individual antibiotics into separate modified Robbins devices using a side-arm adaptor and the results were compared with saline controls. RESULTS: Compared with the saline controls, ciprofloxacin and ceftazidime caused a 10- to 100-fold reduction in the number of E coli attached to the stents, whereas ampicillin had no effect on adherence of E coli. Ampicillin caused a 5- to 10-fold reduction in Enterococcus adherence but there was no change with ceftazidime. Sustained reduction in E coli adherence was observed with prolonged ciprofloxacin perfusion. CONCLUSION: Timely treatment with appropriate antibiotics reduced bacterial adherence in vitro and may be potentially beneficial in the prevention of stent blockage.

Ampicillin↗

Is there a synergistic effect between mixed bacterial infection in biofilm formation on biliary stents?

BACKGROUND: Biliary sludge which forms as a result of bacterial adherence and biofilm formation in the biliary system is a recognized cause of blockage of plastic stents. Bacteriological cultures of sludge have revealed a mixed infection with gram-positive and gram-negative bacteria. Animal studies have shown that prophylactic ciprofloxacin, which selectively suppress gram-negative bacteria, results in prolonged stent patency despite colonization of the stents by gram-positive bacteria. METHODS: We tested a possible synergistic effect between gram-negative and gram-positive bacteria in adherence and biofilm formation on plastic stents. Clinical isolates of Escherichia coli and Enterococcus were cultured in separate chemostats to achieve a steady growth. Adherence of the two bacteria on plastic stent surface were tested separately by perfusing infected bile with the respective bacteria through different modified Robbins devices containing 10F polyethylene stent pieces up to 4 days. In a second experiment, Enterococcus was perfused through stent pieces precolonized with E. coli for 24 hours. The stent pieces were then removed daily and analyzed by bacteriologic culture and scanning electron microscopy for bacterial adherence and biofilm formation. RESULTS: Gram-negative E. coli were more adherent than gram-positive Enterococcus. Precolonization with E. coli facilitates subsequent attachment of Enterococcus. CONCLUSIONS: We concluded that there is a synergistic effect between gram-positive and gram-negative bacteria in adherence and biofilm formation.

Animals↗

The relationship between antecedent antibiotic use and resistance to extended-spectrum cephalosporins in group I beta-lactamase-producing organisms.

Gram-negative pathogens are increasingly resistant to extended-spectrum cephalosporins (ESCs). Using a prospective, case-controlled observational study, we examined the prevalence and the risk factors for development of resistance to ESCs in group I beta-lactamase-producing organisms. Of the 386 isolates of Enterobacter species, Pseudomonas aeruginosa, Citrobacter species, and Serratia marsescens from 340 consecutive patients, 70 (18.1%) were resistant to ESCs; the highest rates of resistance were found among Citrobacter freundii (40.9%), Enterobacter cloacae (31.1%), and Enterobacter aerogenes isolates (18.9%). Patients' prior antibiotic use and the mean number of antibiotics used were significantly greater in association with resistant vs. susceptible isolates. Resistance was associated with prior use of ceftizoxime or cefotaxime (P = .008), ceftazidime (P = .004), and piperacillin (P = .001). Other antibiotics were not associated with resistance. Resistance was less frequent in patients receiving ESCs and an aminoglycoside. We conclude that prior use of ESCs is associated with the isolation of resistant group I beta-lactamase-producing organisms. Concomitant use of an aminoglycoside may decrease this risk.

Adult↗

Assessing random error in the international normalized ratio.

Changes in the international normalized ratio (INR) following warfarin administration may be explained not only by the attendant anticoagulant effect but also, in part, by random errors normally associated with laboratory assays. Thus, a patient's true INR will differ from the reported value by some random error related to the variability in the prothrombin time (PT) assay. By employing a statistical technique known as the delta method, the error expected in an INR for a particular institution can be estimated by taking the product of the international sensitivity index (ISI) and the coefficient of variation (CV) for the PT assay.

Drug Monitoring↗

Nonparametric approach to population pharmacokinetics in oncology patients receiving aminoglycoside therapy.

A nonparametric expectation maximization approach to the study of population pharmacokinetics is described for an aminoglycoside antibiotic. The method is used to explore population estimates for gentamicin clearance (liters per hour per creatinine clearance) and volume of distribution (liters per kilogram) in tumor patients. Joint and marginal probability distributions are plotted and further characterized by using standard descriptors such as mean, median, mode, standard deviation, skewness, and kurtosis. Results of additional analyses using hematologic or solid tumor subpopulations agree with those of a recent larger study which found no significant pharmacokinetic differences between these groups. Nonparametric maximum-expectation analyses are convenient and allow exploratory analysis of population estimates directly from routine laboratory information.

Adult↗

Setting confidence intervals for drug concentrations from pharmacokinetic parameters.

OBJECTIVE: To describe and illustrate a convenient method of forecasting drug concentrations with confidence intervals (CIs) using the means and standard deviations of relevant pharmacokinetic parameters (e.g., clearance and volume of distribution). DESIGN: Using summary statistics from previously published reports, a Monte Carlo technique employing a SAS random number generator creates an arbitrarily large "sample" of each pharmacokinetic parameter. A related "sample" of drug concentrations is provided by inserting the parameters into the appropriate model. A point estimate of the mean drug concentration with a CI is calculated using standard statistical methods. Both the one- and two-compartment body models are illustrated using previous investigations of gentamicin and lidocaine, respectively. RESULTS: One-compartment simulations describe CIs for gentamicin concentrations that vary widely depending on the source of the clearance and volume of distribution parameters. Lidocaine CIs using a two-compartment analysis indicate a range of concentrations quite different from the expected mean. CONCLUSIONS: CIs provide a perspective of drug therapy that is considerably more informative than a simple point estimate of the mean concentration.

Confidence Intervals↗

The effect of acetaminophen on zidovudine metabolism in HIV-infected patients.

The concomitant administration of acetaminophen to HIV-positive patients receiving zidovudine (AZT) therapy has previously been thought to increase the likelihood of the toxicity of AZT due to increased serum levels, resulting from hypothesized metabolic competition. We measured serum AZT and metabolite levels by HPLC in HIV-infected patients taking regular doses of AZT with and without acetaminophen administration. In all patients, serum levels of AZT and the glucuronidated metabolite (GAZT) were similar with and without acetaminophen administration. AZT serum levels were not increased (p less than 0.05). We believe that the rationale for withholding acetaminophen from patients receiving AZT should be re-evaluated.

Acetaminophen↗

Effects of 3'-deoxycytidine on rRNA synthesis in toad bladder: analysis of response to aldosterone.

Previous studies showed that aldosterone augments transepithelial active Na+ transport and the incorporation of [3H]uridine into polyadenylated RNA (poly(A)(+)-RNA) (putatively mRNA) early in the latent period. Soon thereafter, incorporation of [methyl-14C] groups, as well as [3H]uridine into rRNA is also increased. To evaluate the role of rRNA in mineralocorticoid action, the inhibitor 3'-deoxycytidine was used in studies on the urinary bladder of the toad Bufo marinus. 3'-deoxycytidine suppressed the incorporation of [methyl-14C] and [3H]uridine into nuclear precursors of rRNA and subunits of cytoplasmic rRNA. In contrast, 3'-deoxycytidine inhibited incorporation of ]3H]uridine into cytoplasmic poly(A)(+)-RNA minimally. In control experiments, 3'-deoxycytidine had no significant effect on Na+ transport, measured as the short-circuit current (scc), when given alone. 3'-Deoxycytidine also had no significant effect on the aldosterone-dependent increase in scc. In the presence of 3'-deoxycytidine, aldosterone enhanced both the scc and the incorporation of [3H]uridine into poly(A)(+)-RNA significantly. We conclude that during the first 3 h, the mineralocorticoid action of aldosterone is not sensitive to inhibition of rRNA synthesis. Previous studies, however, implicate mRNA synthesis in this early response.

Aldosterone↗

Estimating phenytoin concentrations by the Sheiner-Tozer method in adults with pronounced hypoalbuminemia.

OBJECTIVE: To assess the performance of the Sheiner-Tozer equation when used to evaluate total phenytoin concentrations in patients with pronounced hypoalbuminemia. DESIGN: Patients with phenytoin concentrations drawn at least 5 days after initiation of therapy and with serum albumin concentrations of less than 25 g/L were identified during routine daily monitoring. Phenytoin samples were frozen at -30 degrees C, batched, and later thawed for total and free phenytoin assay. Separation of free phenytoin concentration was performed at 37 degrees C using a Centrifree micropartition filter. SETTING: A 400-bed university teaching hospital. PATIENTS: Twenty-nine adults with hypoalbuminemia receiving phenytoin therapy. Patients receiving drugs known to displace phenytoin, or those with renal failure, abnormal liver enzymes, or increased bilirubin concentrations were excluded. MAIN OUTCOME MEASURE: Precision and bias of the normalized result using the Sheiner-Tozer equation were assessed with respect to observed phenytoin concentrations. RESULTS: The Sheiner-Tozer equation underpredicts the measured free concentration by approximately 12.4%. The equation provides a small but statistically significant bias (-2.7 mg/L) and a root mean squared error significantly different from 0. For most of our patients these departures appear small enough to warrant an initial empiric appraisal of hypoalbuminemia using the Sheiner-Tozer method. CONCLUSIONS: The Sheiner-Tozer equation can normalize total phenytoin concentrations reliably in patients with low albumin concentrations at our institution.

Adult↗