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L Fox

Publications and source records attributed to L Fox.

At least 109 records · Page 6Linked to original sources
PubMedDate not supplied

Potential role for P-glycoprotein in the non-proportional pharmacokinetics of UK-343,664 in man.

1. UK-343,664 is a potent and specific PDE5 inhibitor. Following single oral doses to human volunteers, it exhibited non-proportional pharmacokinetics over the dose range 30-800 mg. Over this 27-fold dose range, Cmax and AUCt increased 247- and 287-fold respectively. The half-life (4-6 h) was similar at all doses. No systemic exposure was quantifiable at doses <10 mg. 2. UK-343,664 is a lipophilic molecule (log D7.4 = 3.1) and as such is expected to be cleared mainly by metabolism. Based on studies with expressed human P450 enzymes it was concluded that the metabolism of UK-343,664 was predominantly mediated by CYP3A4. With a moderate Km = 76 microM for this enzyme, saturation of first-pass metabolism alone was considered unlikely to account for the non-proportional pharmacokinetics. 3. UK-343,664 showed high affinity for P-glycoprotein in vitro, with a Km = 7.3 microM. In transport studies in LLC-PK1 cell monolayers transfected with P-glycoprotein, UK343,664 showed marked polarized transport which was concentration dependent. 4. The high affinity of UK-343,664 for P-glycoprotein is considered to be the primary source of the non-proportional pharmacokinetic profile observed in man.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMedDate not supplied

Protein catabolic rate in patients on continuous peritoneal dialysis. A multivariate predictive model.

Protein catabolic rate (PCR) and PCR normalized to standard weight (PCRN) are important indices of nutrition in patients on continuous peritoneal dialysis. The purpose of this study was to test whether urea clearance is among the predictors of PCR and PCRN in a multivariate analysis. Stepwise logistic regression was used to develop separate models for low PCR and low PCRN on a set of 143 urea kinetic studies in 92 patients on continuous peritoneal dialysis. The regression models were tested on an independent sample of 189 urea kinetic studies in 102 patients on continuous peritoneal dialysis by deriving the area under a receiver operating characteristic curve. In the derivation set, low serum urea, high serum creatinine, low urine and dialysate drain volumes, and low body surface area were identified as predictors of PCR < or = 50 g daily. The area under the receiver operating characteristic curve in the validation set was 0.930 (95% confidence interval: 0.915-0.945). Low serum urea, male gender, high body mass index and low urea fractional clearance (KT/V) were predictors of PCRN < or = 0.80 g/kg daily. The receiver operating characteristic area for this model was 0.948 (95% confidence interval: 0.926-0.970). Logistic regression analysis was repeated twice after adding urea nitrogen excretion normalized to standard weight (UNEN) as a candidate variable. This process identified low UNEN, male gender, and obesity as the predictors of low PCRN, and low UNEN, male gender, low urine volume, low drain volume normalized by body water, and high serum albumin as predictors of low KT/V urea. The authors conclude that PCR and PCRN can be predicted by models that incorporate serum azotemic indices, body size and composition, and direct or indirect measurements of urea clearance. Small body size and lean body composition predict low PCR but high PCRN values. Both PCRN and KT/V urea are predicted by UNEN. Multivariate analysis cannot, therefore, rule out the hypothesis that PCRN and KT/V are linked mathematically.

Body Weight↗
PubMedDate not supplied

Variation in the process of pediatric asthma care.

In May 1994, the continuous quality improvement team at Hermann Children's Hospital in Houston, TX, began to study the structure, process, and outcome of asthma care for pediatric patients. The team's immediate goals were to identify variation in the treatment of pediatric asthma and to determine the most cost-effective interventions. This article details the team's development of a clinical pathway to reduce variation in patient care; use of the pathway led to a reduction in length of stay and a corresponding reduction in costs.

Adolescent↗
PubMedDate not supplied

Adverse ocular effects of acetate hemodialysis.

In order to better define ocular dynamics during hemodialysis, we studied intraocular pressure (IOP) and anterior chamber depth (ACD) serially during both acetate and bicarbonate hemodialysis in 10 stable hemodialysis patients. IOP did not change significantly in any patient during dialysis. In contrast, however, ACD decreased significantly during acetate but not bicarbonate dialysis. ACD could be maintained during acetate dialysis by concomitant administration of mannitol. We conclude that acetate dialysis might adversely affect ocular dynamics in susceptible patients with glaucoma or recent ocular surgery. In such individuals administration of mannitol or use of a bicarbonate dialysate should be considered.

Acetates↗
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Under guarantee.

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Health Care Rationing↗
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Personal service.

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Humans↗
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Creatinine clearance in continuous peritoneal dialysis: dialysis dose required for a minimal acceptable level.

OBJECTIVES: To identify the most advantageous formula for estimating creatinine clearance (CCr) and to establish a dose of dialysis that will ensure minimal acceptable levels of creatinine clearance in patients on continuous peritoneal dialysis (CPD). DESIGN: Analysis of all CCr studies performed in CPD patients over 40 months. SETTING: All four dialysis units following CPD patients in one city. One dialysis unit is government-owned, one is university-affiliated, and two are community based. PARTICIPANTS: One hundred and ninety-four patients representing almost the entire CPD population in Albuquerque. INTERVENTIONS: Creatinine and urea clearance studies were performed in 24-hour urine and drained dialysate samples. Creatinine clearance (peritoneal plus urinary) was normalized to either 1.73 m2 body surface area (CCr) or body water estimated by the Watson formulas (KT/VCr). CCr and KT/VCr were either corrected by averaging urinary creatinine and urea clearances or were not corrected. Two dialysis units were designated as the training set (92 patients, 143 clearance studies) and the other two units as the validation set (102 patients, 181 clearance studies). MAIN OUTCOME MEASURES: Minimal acceptable creatinine clearance levels were determined in the training set by computing the creatinine clearance value corresponding to 1.70 weekly KT/V urea by linear regression. Logistic regression models predicting low creatinine clearance were developed in the training set and were tested in the validation set. RESULTS: The following weekly creatinine clearance values corresponded to 1.70 KT/V urea: corrected CCr 52.0 L/1.73 m2, uncorrected CCr 54.4 L/1.73 m2, corrected KT/VCr 1.46, uncorrected KT/VCr 1.53. Logistic regression identified as predictors of low creatinine clearance low daily urine volume (UV) and low daily dialysate drain volume/body water (DV/V) for all four creatinine clearance formulas, plus low/low-average peritoneal solute transport (only for uncorrected CCr) and serum creatinine (for both KT/VCr formulas). In the validation set, the predictive models produced an area under the receiver operating characteristic (ROC) curve between 0.835 and 0.919 indicating very good predictive accuracy. For corrected CCr and anuria, the regression model produced a minimal normalized drain volume (DV/V) value consistent with minimal acceptable CCr equal to 0.305 L/L per 24 hours. This DV/V cutoff detected low corrected CCR in validation set anuric subjects (n = 55) with a sensitivity of 85% and a specificity of 71%. For uncorrected CCR and anuria, DV/V cutoffs were 0.273 L/L per 24 hours (high/high-average peritoneal solute transport) and 0.420 L/L per 24 hours (low/low-average transport). Sensitivity and specificity of these cutoffs in validation set anuric subjects were 87% and 85%, plus 86% and 33%, respectively. CONCLUSIONS: The uncorrected CCr appears to be the most advantageous creatinine clearance formula in CPD, because it allows the use of peritoneal solute transport type in the calculation of the minimal required normalized drain volume. The minimal acceptable uncorrected CCr is 54.4 L/1.73 m2 weekly. To achieve this uncorrected CCr in anuria, the required minimal normalized drain volume is 0.273 L per liter of body water daily if peritoneal solute transport is high or high-average and around 0.420 L per liter of body water daily if peritoneal solute transport is low or low-average. The required total daily drain volume is computed by multiplying the required normalized drain volume by body water.

Biological Transport↗
PubMedDate not supplied

Physicians' views on pediatric preventive dental care.

Physicians who provide primary care for children are considered to be in a unique position to provide dental preventive care to their patients. No literature relates the amount of preventive oral health education that physicians receive during training. The purpose of this study was to assess the knowledge, attitudes, and beliefs of pediatricians and family physicians toward preventive dental care in children. A questionnaire was mailed to 398 pediatricians and 632 family physicians licensed to practice in the state of Alabama. The response rate after one mailing and a reminder was 46%. Physician's knowledge about many aspects of preventive dental care was good, but areas of great concern were identified. Overall, most respondents received 2 hr or less of preventive dental education during medical and specialty training. Pediatricians were better informed than family physicians in the areas of general dental knowledge and prevention counseling related to oral health (P < 0.05).

Adult↗