A computational fluid dynamics simulation framework for ventricular catheter design optimization.

In this research an optimization methodology and 3D computational fluid dynamics algorithm were coupled to reach an important design objective for ventricular catheters: uniform inlet flow distribution. The optimized catheter design presented significantly improves on previous designs explored in the literature and on standard catheter designs used clinically. The automated, iterative fluid simulation framework described in this work can be used to rapidly explore design parameter influence on other flow-related objectives in the future.

Pharmacokinetic and tissue distribution study of [14C]fluasterone in male Beagle dogs following intravenous, oral and subcutaneous dosing routes.

The purpose of this work was to compare the pharmacokinetics (PK) and tissue distribution of [14C]fluasterone following intravenous (iv), subcutaneous (sc) and oral (po) administration in male Beagle dogs. The main goal of the investigation was to discover if non-oral routes would alter parameters observed in this study following the administration of [14C]fluasterone. The oral formulation had a lower bioavailability (47%) compared to the sc formulation (84%). Po and sc administration resulted in a similar t(max); however, the observed C(max) following sc dosing was less than half of that after oral dosing. The sc route had the greatest overall exposure (AUC(0-infinity)). Tissue distribution analysis 2 h post-intravenous dosing showed that connective tissue (adipose and bone), liver, and skeletal muscle accumulated relatively high levels of fluasterone. The majority of the dose was retained during the first 24 h. Elimination of [14C]fluasterone-derived radioactivity following intravenous dosing resulted in urine and feces containing 7.6% and 28%, respectively, of the total dose over the first 24 h. Elimination of [14C]fluasterone-derived radioactivity following subcutaneous dosing resulted in 4.6% in urine and 7.8% in feces of the total dose over the first 24 h. Following oral dosing, elimination resulted in 3.8% in urine and 36% in feces over the first 24h. In conclusion, the sc route of administration offers some advantages to po and iv due to the prolonged release and increased retention through 24 h.

Identification of [14C]fluasterone metabolites in urine and feces collected from dogs after subcutaneous and oral administration of [14C]fluasterone.

The objective of this research was the identification of the metabolic profile of fluasterone, a synthetic derivative of dehydroepiandrosterone, in dogs treated orally or subcutaneously with [4-(14)C]fluasterone. Separation and characterization techniques used to identify the principal metabolites of fluasterone in urine and feces included high-performance liquid chromatography (HPLC), liquid scintillation spectrometry, HPLC/tandem mass spectrometry, and NMR. In urine, the majority of the radioactivity was present as two components that had apparent molecular weights consistent with their tentative identification as monoglucuronide conjugates of 4alpha-hydroxy-16alpha-fluoro-5-androsten-17beta-ol and X(alpha or beta)-4alpha-dihydroxy-16alpha-fluoro-5-androsten-17beta-ol. The identification of the monoglucuronide conjugate of 4alpha-hydroxy-16alpha-fluoro-5-androsten-17beta-ol was also supported by NMR data. In support of this identification, these metabolites were cleaved with glucuronidase enzyme treatment, which gave rise to components with molecular weights again consistent with the aglycones of a monohydroxylated, 17-keto reduced (dihydroxy) fluasterone metabolite and a dihydroxylated, 17-keto reduced (trihydroxy) fluasterone metabolite. In feces, nonconjugated material predominated. The primary metabolites eliminated in feces were the two hydroxy fluasterone metabolites arising from 17-reduction (16alpha-fluoro-5-androsten-17beta-ol and 16alpha-fluoro-5-androsten-17alpha-ol) and 4alpha-hydroxy-16alpha-fluoro-5-androsten-17beta-ol that was present in urine in glucuronide form.

Cost-effectiveness of the radial versus femoral artery approach to diagnostic cardiac catheterization.

BACKGROUND: The radial approach to cardiac catheterization is increasingly popular due to shorter procedural and recovery times and greater patient comfort. METHODS: Comparative cost analysis between radial or femoral (with or without closure device) approaches were performed. RESULTS: Radial (R), femoral (F), and femoral with a closure device (F +/- C) approaches were used in 70, 62 and 49 consecutive cases, respectively. Group R had higher access equipment cost (93.0 dollars +/- 9.5 vs. 40.5 dollars) in group F (p < 0.001), but lower catheter cost (19.7 dollars +/- 12.7 vs. 31.1 dollars +/- 9.3; p < 0.001) than Group F, and lower contrast cost (26.9 dollars +/- 17.0 vs. 42.9 dollars +/- 25.0) in Group F +/- C (p < 0.001). There was a lower postprocedure recovery cost (185.2 dollars +/- 52.7) in Group R compared to 337.5 dollars +/- 59.0 in Group F (p < 0.001) and 208 dollars +/- 70.4 in Group F +/- C (p < 0.001), with a median recovery time of 126.0 +/- 36.0 minutes in group R vs. 240.0 +/- 42.0 minutes, and 150.0 +/- 48.0 minutes in groups F and F +/- C, respectively (both p < 0.05). The total variable procedural cost, which includes approach-dependent equipment and recovery room stay, was significantly lower in the Radial group than in the Femoral group (369.5 dollars +/- 74.6 vs. 446.9 dollars +/- 60.2 and 553.4 dollars +/- 81.0; p < 0.001). CONCLUSION: The radial artery approach to diagnostic cardiac catheterization is clearly more cost effective than the femoral approach, with or without the use of a femoral closure device.

Outcomes of unexplained syncope in the elderly.

The objective of this study was to determine whether syncope of unknown etiology (SUE) influences mortality in the elderly. Patients with SUE at 65 years or older were identified retrospectively and their outcomes were compared with an age-, sex-, and comorbidity-matched group of patients drawn from the same population. All-cause 3-year mortality was analyzed using the Kaplan-Meier method and the log-rank test. SUE was identified in 150 of 304 patients (49%) with syncope. Patients with SUE and controls experienced mortality rates (1/1000 person-years [95% confidence interval]) of 147.8 (112.6-193.9) and 153.4 (117.5-200.3), P=.7, respectively. Of all the recorded characteristics of SUE, only the inpatient status was associated with higher all-cause mortality (Cox model adjusted hazard ratio [95% confidence interval] of inpatients vs outpatients with SUE: 2.2 [1.1-4.1], P=.017). New-onset SUE is not an independent predictor of mortality in elderly patients.

Methicillin-resistant Staphylococcus aureus infection and colonization among hospitalized prisoners.

We assessed methicillin-resistant Staphylococcus aureus (MRSA) infection and colonization in hospitalized prisoners. Of 434 admission surveillance cultures, 58 (13%) were positive for MRSA. The sensitivity of admission surveillance cultures of samples from the anterior nares was 72% and increased to 84% when the calculation included cultures of wound samples. Hospitalized prisoners are at high risk for MRSA infection and colonization, and surveillance should include cultures of nares and wound samples.

Nonemergent percutaneous coronary interventions in a veterans affairs medical center without onsite cardiac surgery.

BACKGROUND: Percutaneous coronary intervention (PCI) performed in centers without onsite cardiac surgery remains controversial. Advances in PCI techniques and medical therapy have markedly decreased postprocedural complications. Our aim was to assess the efficacy and safety of performing PCI in the Veterans Affairs patient population in a hospital without onsite cardiac surgery. METHODS: We prospectively evaluated 401 consecutive patients who underwent elective PCI or PCI after admission for acute coronary syndrome. Patients who had ST-elevation myocardial infarction or were hemodynamically unstable were classified as emergent and had their PCI performed elsewhere and were therefore excluded from our analysis. Our cardiac surgery backup was a community hospital 8 miles away. RESULTS: The patient's mean age was 65.6 +/- 10 years, and most were men (99.5%). Patients had high-risk clinical and angiographic profiles, with diabetes mellitus in 44%, prior myocardial infarction in 41%, comorbid conditions in 45% and type B or C angiographic lesions in 83%. Of 401 patients, 338 (84%) received a stent, and 86 (21%), a drug eluting stent. Percutaneous coronary intervention success rate was 97%. There were no periprocedural or inhospital deaths, and no patients required emergency transfer for cardiac surgery. At 1 and 6 months of follow-up, total mortality was 1.5% and 3.5%, respectively; target vessel revascularization rate was 0% and 1.7%. CONCLUSIONS: Nonemergent PCI can be performed effectively and safely in patients with higher clinical and angiographic risk without onsite backup cardiac surgery. This has significant implications for most hospitals that have an invasive but not an interventional program.

Clinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy men.

BACKGROUND: Soy isoflavones are potential cancer chemoprevention treatments. OBJECTIVE: We conducted safety studies of purified unconjugated genistein, daidzein, and glycitein, and defined pharmacokinetic parameters for their absorption and metabolism. DESIGN: Thirty healthy men ingested a single dose of 1 of 2 isoflavone preparations purified from soy. The delivered doses of genistein (1, 2, 4, 8, or 16 mg/kg body wt) were higher than those previously administered to humans. Formulation A was composed of 90 +/- 5% genistein, 10% daidzein, and 1% glycitein. Formulation B was composed of 43% genistein, 21% daidzein, and 2% glycitein. RESULTS: We observed no clinically significant behavioral or physical changes after treatment. We observed elevations in lipoprotein lipase and hypophosphatemia that were possibly related to the treatment but that were associated with no clinical toxicity. Considerable quantities of isoflavones were excreted in urine as conjugates. The terminal elimination rate, elimination half-life, area under the curve, maximum plasma concentration, apparent systemic clearance, and volume of distribution were estimated for genistein and daidzein. The mean elimination half-lives with both formulations were 3.2 h for free genistein and 4.2 h for free daidzein. The mean pseudo half-lives were 9.2 h for total genistein and 8.2 h for total daidzein. CONCLUSIONS: Dietary supplements of purified unconjugated isoflavones administered to humans in single doses exceeding normal dietary intake manyfold resulted in minimal clinical toxicity. Genistein and daidzein (free and total) were rapidly cleared from plasma and excreted in urine.