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PubMed1988

Comparison of single-point phenytoin dosage prediction techniques.

To dose the anticonvulsant phenytoin (PHT) in a clinical situation is difficult because of the non-linear metabolism of the drug. Therefore many techniques have been advocated to aid dosage adjustments based on a single-point PHT concentration determined at steady-state (ss). We retrospectively investigated six methods in a population of 130 out-patients treated with PHT. The dose needed to achieve a desired PHT concentration at ss was calculated based on an observed ss dose-concentration pair using a Bayesian feedback method (B), the Richens and Dunlop nomogram (RD), the Rambeck nomogram (R), the Martin nomogram (M), a population clearance equation (PC), and the Wagner equation (W). The mean prediction error (ME), mean absolute error (MAE), and root mean squared error (RMSE) were separately calculated for each method, and served as a measure of prediction bias and precision. The MEs for B, RD, R, M, PC, and W, respectively, were -0.4, 1.2, 6.9, 3.4, -1.8, and 0.0 mg/day. The MAEs were 33.9, 38.5, 44.3, 50.4, 43.5, and 53.7 mg/day. The RMSEs were 43.7, 53.1, 65.2, 63.5, 56.0, and 68.2 mg/day. The MAE and RMSE showed lowest values for method B, followed by method RD. Therefore, we assume that method B is the most accurate in making routine PHT dosage adjustments.

Adolescent↗
PubMed2002

International validation of a preoperative nomogram for prostate cancer recurrence after radical prostatectomy.

PURPOSE: We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents. METHODS: Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification-based risk quadrants were compared with actual Kaplan-Meier plots. RESULTS: The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low-risk group), 39% (intermediate-high-risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram. CONCLUSION: The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.

Adult↗
PubMed2006

Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma.

PURPOSE: Different prognostic factors stratify patients with pancreatic adenocarcinoma. The purpose of this study was to determine whether preoperative CA19-9 levels can predict stage of disease or survival and whether a change in preoperative to postoperative CA19-9 or the postoperative CA19-9 predicts overall survival. PATIENTS AND METHODS: Four hundred twenty-four consecutive patients with pancreatic adenocarcinoma underwent resection between January 1, 1985 and January 1, 2004. Of the patients with a bilirubin less than 2 mg/dL, 176 had preoperative CA19-9 values, and 111 had pre- and postoperative CA19-9 values. Survival was measured from the first postoperative CA19-9 level measured (median, 39 days) until death or last follow-up. A multivariate failure time model was fit using clinical, operative, pathologic, and adjuvant treatment characteristics, and a categorization was defined by the values and changes in CA19-9 before and after surgery. RESULTS: Of the 176 patients, 128 (73%) had T3 lesions, and 99 (56%) had N1 disease; 138 patients (78%) underwent pancreaticoduodenectomy. Median preoperative CA19-9 levels were lower in N0 patients compared with patients with positive nodes (nine v 164 U/mL, respectively; nonparametric P = .06) and in T1/T2 patients versus T3 patients (41 v 162 U/mL, respectively; P = .03). Median follow-up time (n = 111) was 1.8 years (range, 1 to 12.9 years), with overall actuarial 1-, 3-, and 5-year survival rates of 70%, 36%, and 30%, respectively. Significant predictors of survival on multivariate analysis included a decrease in CA19-9 (P = .0005), negative lymph nodes (P = .001), lower T stage (P = .0008), and postoperative CA19-9 less than 200 U/mL (P = .0007). CONCLUSION: In patients with pancreatic adenocarcinoma, preoperative CA19-9 correlates with stage of disease. Both a postoperative decrease in CA19-9 and a postoperative CA19-9 value of less than 200 U/mL are strong independent predictors of survival, even after adjusting for stage. CA19-9 levels should be included in a patient's perioperative care and should be considered for prognostic nomograms.

Adenocarcinoma↗
PubMed2005

Sonographic evaluation of spleen size in tall healthy athletes.

OBJECTIVE: The purpose of this study was to establish the range of spleen sizes in tall healthy athletes. SUBJECTS AND METHODS: Sonographic measurements of spleen size and left renal length were performed on 129 college athletes (82 men, 47 women). Length, width, and thickness of the spleen and left renal length were obtained. In addition, the height, weight, and age of each athlete were recorded. Pearson's product moment correlation coefficients were calculated, and linear regression analysis was used to create a model for calculating normative values. RESULTS: The mean body height for men was 74.3 (189 cm) +/-(SD) 3.7 inches (9 cm) and for women was 69.3 (176 cm) +/- 3.7 inches (9 cm). Spleen length was greater than 12 cm in 31.7% of the men (mean spleen length, 11.4 +/- 1.7 cm) and in 12.8% of the women (mean spleen length, 10.3 +/- 1.3 cm). In women, height correlated with spleen length (r = 0.3, p = 0.05), width (r = 0.4, p = 0.01), and volume (r = 0.3, p = 0.02) but not with thickness (r = 0.08, p = 0.6). Spleen length did correlate with left renal length (r = 0.5, p = 0.0005). In men, height correlated with spleen length (r = 0.4, p = 0.0003), width (r = 0.5, p = 0.0001), and volume (r = 0.4, p = 0.0002) and less with thickness (r = 0.3, p = 0.01). Spleen length and left renal length were poorly correlated (r = 0.2, p = 0.04). Regression analysis showed that in women taller than 5 ft 6 inches (168 cm), the mean splenic length of 10 cm increased by 0.1 cm for each 1-inch incremental increase in height. In men taller than 6 ft (180 cm), the mean splenic length of 11 cm increased by 0.2 cm for each 1-inch incremental increase in height. CONCLUSION: Spleen size correlates with height in tall healthy athletes. Nomograms from this data can be used to gauge the risk of returning to play after episodes of acute splenomegaly, as with infectious mononucleosis.

Adult↗
PubMed2003

Weak correlation between bladder outlet obstruction and probability to void to completion.

OBJECTIVES: To investigate the weak correlation between bladder outlet obstruction (BOO), as diagnosed using the provisional International Continence Society nomogram for the definition of BOO in men, and postvoid residual urine volume. METHODS: The relationship between voiding to completion and several indexes for bladder outlet resistance and bladder contractility was studied in 131 pressure flow studies in male patients using multivariate logistic regression analysis. RESULTS: The International Continence Society nomogram and the related BOO index weakly predict for postvoid residual urine volume (areas under the receiver operating characteristic curve 0.63 and 0.64, respectively). The BOO index primarily measures bladder outlet resistance. If the nomogram or BOO index is augmented with bladder contractility information, the postvoid residual urine volume can be predicted significantly better (eg, area under the receiver operating characteristic curve [0.89] for the combination of the BOO index and bladder contractility information). CONCLUSIONS: The weak correlation between BOO and postvoid residual urine volume is related to the fact that emptying the bladder to completion depends on bladder contractility, as well as bladder outlet resistance. It is possible to estimate the probability to void to completion quite accurately on the basis of bladder outlet resistance and bladder contractility. We named this probability "relative bladder outlet resistance." A high probability of a postvoid residual urine volume may be assumed to indicate "relative BOO." By its very nature, the correlation between "relative BOO" and postvoid residual urine volume is good.

Area Under Curve↗
PubMed2001

[Excimer surface photoablation versus Lasik for correction of mild myopia].

INTRODUCTION: Above -6 diopters, Lasik procedure has shown its superiority in term of predictibility, efficacy and stability. In the adverse, in the field of low myopia, Lasik and surface excimer photoablation (PRK) are very controversial. We compare quantitative and qualitative outcome achieved in series of 25 PRK operated patients and 25 Lasik. MATERIAL AND METHOD: 2 homogeneous groups were constituted: group A for Excimer patients and group B for Lasik. Initial ametropia had to be ranged between -2 and -6 diopters (D), eventually associated to a myopic astigmatism that needed to be under -1,75 D. Excimer laser model was a Visx (Visx 20/20 or Star S2). In case of Lasik, flap was performed with an Automated corneal shaper microkératom (Baush & Lomb) or with a Flap Maker (Ioltech). Evaluation of refraction and visual results was associated to measurements of contrast and glare sensitivities and collection of functional complaints. RESULTS: A retrospective analysis is performed with a 2 years follow-up. At that term, rate of eyes, that achieved 20/20 or better is comparable in the two groups (62% in group A and 64% in group B). However, profile of visual recovery goes faster after Lasik. Best corrected visual acuity is favorably preserved in two groups, but is altered with glare in Lasik group. Cycloplegic refraction shows a tendency to regression more important in case of surface ablation (10% versus 4%), especially above -4 D (28%). No significant difference is noted concerning contrast sensitivity, correctly unchanged in the two groups. No case of severe complication is mentioned after both surgical methods. DISCUSSION-CONCLUSION: In the field of low myopia, PRK and Lasik appear to guarantee same predictibility and safety, in conditions of preliminary learning curve. Stability and visual recovery are earlier achieved after Lasik, in addition to postoperative indolence. However, application of this technique to all degrees of myopia requires its perfect control and an adjustment of ablation nomograms.

Adult↗
PubMed2005

Toward cost-benefit analysis of acute behavioral effects of toluene in humans.

There is increasing interest in being able to express the consequences of exposure to potentially toxic compounds in monetary terms in order to evaluate potential cost-benefit relationships of controlling exposure. Behavioral effects of acute toluene exposure could be subjected to cost-benefit analysis if the effects of toluene were quantitatively compared to those of ethanol ingestion, which has been monetized for applied contexts. Behavioral effects of toluene and ethanol were quantified by meta-analysis of studies from the peer-reviewed literature describing their effects on choice reaction time (reaction time in a test requiring a subject to choose among two or more alternatives before responding). The internal doses of these compounds were estimated by a general physiological and toxicokinetic (GPAT) simulation from exposure parameters provided in the reports. The reported effects were converted to a common metric (proportion of baseline) and related to the estimated internal doses of toluene and ethanol, from which dose-effect equations were fitted. The estimated effect of toluene was compared to the estimated effect of ethanol on the same dependent variable by deriving a dose-equivalence equation (DEE) to express the dose of toluene as an equivalent dose of ethanol on the basis of equal effect magnitude. A nomogram was constructed by GPAT simulation to relate the environmental exposure concentration of toluene to the equivalent effect magnitude of a range of ethanol internal doses. Behavioral effects and their evaluation are determined by internal doses, which in turn are determined by a variety of variables. In addition to concentration and duration of exposure, which determine internal dose by pharmacokinetic processes, the activity level of exposed persons is a major factor. This analysis provides a continuous function of the consequences of toluene exposure expressed as ethanol-equivalent doses within confidence limits. The resulting function has the potential to estimate the monetary values of behavioral deficits caused by a range of exposures to toluene from existing monetized information on ethanol.

Administration, Inhalation↗
PubMed2001

Individualising aminoglycoside dosage regimens after therapeutic drug monitoring: simple or complex pharmacokinetic methods?

Measurements of aminoglycoside concentration in serum are used to individualise dosage regimens (dose per administration and/or administration interval) with the goal of attaining the desired therapeutic range as quickly as possible. Therapeutic range is defined in terms of peak concentration (to monitor effectiveness) and trough concentration (to avoid toxicity). This article focuses on methods to individualise aminoglycoside dosage regimens in the context of extended dosage intervals. Simple pharmacokinetic methods involve linear dosage adjustment based on peak or trough concentrations or area under the concentration-time curve, or nomograms. The once daily aminoglycoside nomogram determines the dosage interval for aminoglycosides given as a fixed dose per administration, based on a single concentration measurement drawn 6 to 14 hours after the start of the first infusion. This is a preferred method because of its simplicity, strong pharmacodynamic rationale and prospective validation in a large population. However, it does not work when the fixed dose assumed is not relevant, for example for patients with burns, cystic fibrosis, ascites or pregnancy. Furthermore, it has not been validated in children. In these cases, a more sophisticated method is required. Complex pharmacokinetic methods require dedicated software. Non-Bayesian least-squares methods allow the optimisation of both the dose and the dosage interval, but require aminoglycoside concentrations from two or more samples taken in the post-distributive phase during a single dosage interval. With Bayesian least-squares methods, only one concentration measurement is required, although any number of samples can be taken into account. In the Bayesian maximum a posteriori (MAP) method, the parameter estimates are taken as the values corresponding to the maximum of the posterior density. In 'full' Bayesian approaches (also called stochastic control), all the information about the parameters revealed by the posterior distribution is taken into account, and the optimal regimen is found by minimising the expected value of the weighted sum of squared deviations between predicted and target concentrations. If the population model is reasonably well known, Bayesian methods (MAP or stochastic control) should be used because of their good predictive performance. Although only one concentration measurement is required, better precision is afforded by a two-sample strategy, preferably drawn 1 and 6 hours after the start of the first infusion. If the population model is not known, then the non-Bayesian least-squares method is the method of choice, because of its robustness and lack of requirement for prior information about the distribution of parameters in the population.

Aminoglycosides↗
PubMed2004

Percent of cores positive for cancer is a better preoperative predictor of cancer recurrence after radical prostatectomy than prostate specific antigen.

PURPOSE: We examined the prognostic significance of clinical and pathological variables on outcome following radical retropubic prostatectomy (RRP) in a cohort of patients in the post-prostate specific antigen (PSA) era. MATERIALS AND METHODS: We reviewed the clinical and pathological data on a cohort of 476 patients who underwent RRP for localized prostate cancer between January 1990 and July 2001 by 1 urologist (WCD). Median age, preoperative PSA and followup were 61 years, 5.8 ng/ml and 49 months, respectively. We used Cox proportional hazard modeling to evaluate the prognostic significance of clinical and pathological variables for cancer recurrence, defined as 2 successive PSA determinations 0.3 ng/ml or greater. RESULTS: Of the 476 patients 53 (11%) had recurrence. Estimated cancer nonprogression probability was 86% (95% CI 83 to 90) and 76% (95% CI 68 to 86) at 5 and 10 years, respectively. Two multivariate analyses were performed. The first analysis, using only preoperative indicators, found that the percent of biopsy cores positive for cancer and biopsy Gleason score were the best predictive indicators of recurrence. The second multivariate analysis, using preoperative and postoperative indicators, found that the percent of biopsy cores positive for cancer, RRP Gleason score and the combined pathological stage/margin status variable were the best predictive indicators of recurrence. PSA was not found to be an important predictor of recurrence on either multivariate analysis. Patients with a percent of biopsy cores in the upper half of the distribution (greater than 28% positive) were at significantly increased risk for recurrence compared with those in the lower half of the distribution (28% or less positive) (HR 3.86, p <0.001). CONCLUSIONS: The percent of cores positive for cancer was a better predictor of cancer recurrence than PSA in this post-PSA era RRP series. In addition, surgical Gleason score and pathological stage/surgical margins were also independent predictors of cancer recurrence after RRP. These 3 predictors are displayed in a nomogram-type format to summarize estimated 5 and 10-year recurrence-free probabilities.

Adult↗
PubMed1990

Increased aminoglycoside dosage requirements in hematologic malignancy.

Aminoglycoside pharmacokinetic parameters were studied prospectively in 27 patients with an underlying hematologic malignancy and fever associated with neutropenia and in 18 control patients. Pharmacokinetic parameters and dosages were determined by linear regression analysis of a one-compartment model by the method of Sawchuk et al. (R. J. Sawchuk, D. E. Zaske, R. J. Cippolle, W. A. Wargin, and R. G. Strate, Clin. Pharmacol. Ther. 21:362-369, 1976). Significant differences between the study and control groups were found for aminoglycoside volume of distribution (0.40 +/- 0.1 versus 0.27 +/- 0.05 liter/kg [mean +/- standard deviation], respectively; P less than 0.0001), clearance (116.6 +/- 48.9 versus 68.6 +/- 26.7 ml/min, respectively; P less than 0.0001), half-life (2.27 +/- 0.66 versus 3.5 +/- 1.8 h, respectively; P less than 0.0001), and elimination rate constant (0.33 +/- 0.11 versus 0.24 +/- 0.09 h-1, respectively; P less than 0.001). The percentage of bone marrow blast cells (at the time of diagnosis) in patients with acute leukemia significantly correlated with increased aminoglycoside clearance (R2 = 36.98%; P = 0.0001). Patients with stage IV lymphomas (Hodgkins disease and non-Hodgkins lymphoma) had a significantly increased clearance compared with patients with lower stages of lymphomas (105.1 +/- 18.5 versus 84.1 +/- 14.9 ml/min; P = 0.014). Fever, leukocyte count, or chemotherapy, among other clinical and laboratory parameters that were studied, had no significant correlation or effect on aminoglycoside disposition. The average dose of amikacin required to maintain peak concentrations in serum above 20 micrograms/ml in patients with a hematologic malignancy was 27.5 +/- 8.43 mg/kg per day. Pharmacokinetic parameters and dosages for the control patients were comparable to general literature standards. we conclude that the dosages recommended by the manufacturers or those derived from nomograms underestimate the aminoglycoside volume of distribution and clearance in patients with a hematologic malignancy and result in suboptimal peak aminoglycoside concentrations in serum. We recommend that in febrile neutropenic patients with an underlying hematologic malignancy, amikacin be initiated at 7.5 to 10 mg/kg per dose every 8 h (2 to 2.5 mg/kg per dose every 8 h for gentamicin) and adjusted within 24 h based on individual pharmacokinetic analysis.

Adult↗
PubMed2002

Influence of acute and chronic alcohol intake on the clinical course and outcome in acetaminophen overdose.

BACKGROUND: Animal studies on acetaminophen toxicity suggest that chronic alcohol intake affects the outcome adversely, whereas acute alcohol intake seems protective. Few clinical data are available. METHODS: We studied 209 consecutive patients with single-dose acetaminophen overdose. The combined influence of independent variables (gender, age, dose, delay to antidote treatment, chronic and acute alcohol intake and nomogram risk group) on dependent variables (death, development of hepatic encephalopathy and biochemical liver markers) was studied using multiple or logistic regression analysis. RESULTS: Fifty-seven (27.3%) patients had chronic alcohol intake and 45 (21.5%) patients had acute alcohol intake. Forty-four (21.1%) patients developed hepatic coma and 20 (43.5%) of these patients died. Chronic alcohol intake was significantly and independently associated with the development of hepatic coma, with a lower prothrombin index, lower platelet count, higher creatinine and higher bilirubin. The relative risks for hepatic coma and death were 5.3 (95% confidence interval, 2.2-12.4) and 1.4 (95% confidence interval, 0.5-3.9), respectively, in the chronic alcohol intake group compared with the no chronic alcohol intake group. Acute alcohol intake was not significantly associated with any of the dependent variables studied. CONCLUSIONS: Chronic alcohol intake enhances acetaminophen hepatotoxicity, whereas acute alcohol intake does not affect the clinical course.

Acetaminophen↗
PubMed2005

Influence of nerve-sparing (NS) procedure during radical prostatectomy (RP) on margin status and biochemical failure.

PURPOSE: To evaluate whether nerve-sparing procedure itself is a risk factor for biochemical recurrence in carefully selected patients. MATERIAL AND METHODS: We compared patients of our historical series who in retrospect were candidates for nerve-sparing (NS) procedure with a contemporary cohort of patients. With respect to stage migration and selection bias between these two groups we performed a multivariate analysis adjusting for all explanatory variables in the model. NS was performed in n = 723 patients (bilateral n = 359, unilateral n = 364) in comparison to n = 620 patients undergoing non-NS RP, comprising n = 756 patients within the favorable pT2 category. We examined the association of clinical and histopathological parameters in relation to PSA recurrence in uni- and multivariate analyses including NS as a variable. Furthermore, for each prostate lobe separately we determined whether surgical procedure (nerve-sparing vs. non-nerve-sparing RP) resulted in a positive margin. RESULTS: In univariate analysis there was no difference in pT2 (log rank p = 0.091), pT3a (log rank p = 0.171) and pT3b (log rank p = 0.110) cancers between patients treated with NS compared to non-NS surgery. The 3- and 5-year recurrence free survival rate for patients with pT2, pT3a and pT3b cancers treated by NS vs. non-NS were 96.3/94.9 vs. 94.9/90.8, 75.0/61.8 vs. 73.4/55.0 and 46/30 vs. 38/23. Multivariate regression analysis showed no association with PSA failure (p = 0.798) for patients who underwent NS. Capsular penetration (p < 0.001), lymph-node status (p < 0.001), seminal vesicle invasion (p < 0.001), surgical margin status (p = 0.0130), Gleason score (p < 0.001) and preoperative PSA (p = 0.005) were significantly associated with risk of failure. The positive margin rate per each prostate lobe in pT2 cancers was 6.5% vs. 5.1% in NS and non-NS cases, 10.3% vs. 17.3% in patients with extracapsular extension and 15.0% vs. 25.1% in cases with seminal vesicle invasion respectively. CONCLUSION: NS RP is an oncologically safe procedure provided that appropriate preoperative selection of patients by means of a validated nomogram is performed. Moreover, evaluation of positive margins in patients undergoing NS and non-NS RP revealed no evidence that adequacy of tumor excision is compromised by NS procedure.

Aged↗
PubMed2004

Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL-1), CD44v6 and microvessel density for prostate cancer.

Despite the development of nomograms designed to evaluate a prostate cancer (PCa) patient's prognosis, the information has been limited to PSA, clinical stage, Gleason score and tumor volume estimates. We compared the prognostic potential of 4 histologic markers, hyaluronic acid (HA), HYAL-1-type hyaluronidase (HAase), CD44v6 and microvessel density (MVD) using immunohistochemistry. HA is a glycosaminoglycan that promotes tumor metastasis. CD44 glycoproteins serve as cell surface receptors for HA, and the CD44v6 isoform is associated with tumor metastasis. HYAL-1-type HAase is expressed in tumor cells and, like other HAases, degrades HA into angiogenic fragments. Archival PCa specimens (n=66) were obtained from patients who underwent radical prostatectomy for clinically localized PCa and had a minimum follow-up of 72 months (range 72-131 months, mean 103 months). For HA, HYAL-1 and CD44v6 staining and MVD determination, a biotinylated HA-binding protein, an anti-HYAL-1 IgG, an anti-CD44v6 IgG and an anti-CD34 IgG were used, respectively. HA and HYAL-1 staining was classified as either low- or high-grade. CD44v6 staining and MVD were evaluated quantitatively and then grouped as either low- or high-grade. Using 72 months as the cut-off limit for evaluating biochemical recurrence, HA, HYAL-1, combined HA-HYAL-1, CD44v6 and MVD staining predicted progression with 96%, 84%, 84%, 68% and 76% sensitivity, respectively. Specificity was, 61% (HA), 80.5% (HYAL-1), 87.8% (HA-HYAL-1), 56.1% (CD44v6) and 61% (MVD). Sensitivity and specificity values for each marker did not change significantly in a subset of 45 patients for whom follow-up of longer than 112 months was available. In univariate analysis using the Cox proportional hazards model, preoperative PSA, Gleason sum, margin status, seminal vesicle, extraprostatic extension (EPE), HA, HYAL-1, HA-HYAL-1 and MVD, but not CD44v6, age and clinical stage, were significant in predicting biochemical recurrence (p < 0.05). In multivariate analysis using stepwise selection, only preoperative PSA (hazard ratio/unit PSA change=1.086, p < 0.0001), EPE (hazard ratio=6.22, p=0.0016) and HYAL-1 (hazard ratio=8.196, p=0.0009)/HA-HYAL-1 (hazard ratio=5.191, p=0.0021) were independent predictors of biochemical recurrence. HA was an independent predictor of prognosis if HYAL-1 staining inference was not included in the multivariate model. In our retrospective study with 72- to 131-month follow-up, EPE, preoperative PSA and HYAL-1 either alone or together with HA (i.e., combined HA-HYAL-1) were independent prognostic indicators for PCa.

Biomarkers, Tumor↗
PubMed1986

Comparison of four single-point phenytoin dosage prediction techniques using computer-simulated pharmacokinetic values.

The predictive abilities of the following four single-point phenytoin dosage adjustment methods were compared using computer-simulated data: the Bayesian feedback method of Vozeh et al. (B), a linearized version of the Bayesian method (LB), the population-clearance method of Graves et al. (G), and the Rambeck nomogram (R). A series of 512 "subjects" with normally distributed values for volume of distribution, weight, and the Michaelis-Menten variables Vmax and Km were simulated. The steady-state serum concentration (SSSC) resulting from the administration of a standard dose of phenytoin sodium (5 mg/kg/day) was calculated, and "subjects" with SSSCs less than or equal to 12 mg/L or greater than or equal to 17 mg/L were entered in the study. If the concentration was greater than 50 mg/L or the standard dosage exceeded Vmax, the dosage was reduced empirically by 25%. Normally distributed random errors were introduced into the SSSC values to simulate actual patient data. The pharmacokinetic values, dosages, and SSSCs were used for predicting the dosage required to attain an SSSC of 14.9 mg/L. In the unstratified population, the mean error and mean-squared error were lowest for methods G and B, followed by methods LB and R. Methods B and LB gave the highest percentages of satisfactory dosage predictions based on the resultant SSSC value. The performance of all methods was superior at initial SSSCs greater than 8 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1988

[Assessment of tissue and intracellular pH following cold-induced vasogenic brain edema--in vitro and in vivo study].

Acid-base balance is closely related to the brain function and various methods have been applied to estimate the intracellular, extracellular or tissue pH. Umbelliferone, a fluorescent pH indicator, has been used to study either intracellular or tissue pH. In the present study, umbelliferone was used for histochemically estimating the tissue pH in the rat brain. The pH nomograms were made from the difference between fluorescent intensities at 450 nm on both excitations at 370 nm and 340 nm at different tissue water contents and different umbelliferone concentrations. Linear correlations were noted under each condition but 0.125% w/v umbelliferone provided the best estimation of tissue pH because of the least influence of water contents. Using this concentration of umbelliferone, a histochemical study was done to estimate the sequential changes in tissue pH following cold-induced vasogenic brain edema in rats. The results revealed a clear delineation of brain edema and the mild alkalosis in the edematous tissue, which probably reflects the pH of leaked plasma fluid. While the pH in the cortex around the lesion was neutral in the histochemical study, it was acidic in the in vivo study. This discrepancy is probably due to the former indicating the tissue pH while the latter the intracellular pH. Thus, the alkalosis in the edema fluid and the intracellular acidosis in the cortex around the lesion were noted in the cold-induced vasogenic edema.

Acid-Base Equilibrium↗
PubMed1993

Uterine artery Doppler velocity waveforms in twin pregnancies.

OBJECTIVE: To compare uterine artery resistance index values in twin and singleton pregnancies, to examine eventual modifications of these values in twin pregnancies complicated by gestational hypertension and preeclampsia, and to determine whether resistance index values in twin pregnancies could predict the development of gestational hypertension and preeclampsia. METHODS: In a cross-sectional study, reference limits for gestation were constructed for the uterine artery resistance index (higher, lower, and mean values) in 96 uncomplicated twin pregnancies and compared to the reference limits constructed from 315 normal singleton pregnancies. Uterine artery resistance indexes obtained in 53 twin pregnancies complicated by either gestational hypertension or preeclampsia were compared with the newly established nomograms. The clinical efficacy of the uterine artery resistance index to predict hypertensive complications was evaluated prospectively in 64 twin pregnancies studied at 20-24 weeks' gestation. RESULTS: In both singleton and twin pregnancies, uterine artery resistance indexes decreased linearly with advancing gestation. However, twin pregnancies showed significantly different slopes and constant values, resulting in lower resistance indexes at all gestational ages examined. No significant differences were found when comparing resistance indexes in all patients with gestational hypertension or preeclampsia to the reference limits. Statistically significant differences were obtained for the higher (P < or = .05) and mean (P < or = .01) resistance indexes when the comparison was restricted to preeclamptic patients. In the twin pregnancies studied at 20-24 weeks' gestation, the diagnostic efficacy of the uterine artery resistance index for predicting the development of gestational hypertension and/or preeclampsia was disappointingly low (k < 0.10). CONCLUSIONS: Resistance index values in the uterine artery are lower in twin pregnancies than in singleton pregnancies. Gestational hypertension and preeclampsia may occur in twin pregnancies despite normal uterine artery velocity waveforms, suggesting a limited role of this measurement in the management and prediction of hypertensive complications in twin pregnancies.

Arteries↗
PubMed2006

Electrocardiographic left ventricular hypertrophy and arterial stiffness: the Ohasama study.

BACKGROUND: Whether arterial stiffness per se contributes to left ventricular hypertrophy (LVH) independently of blood pressure (BP) remains unknown. We examined the relationship between pulse wave velocity (PWV) and LVH in a large population. METHODS: The PWV was measured between the brachial and ankle regions (baPWV) of 798 individuals. We diagnosed LVH using electrocardiographic criteria: Cornell voltage-duration product >2440 mm x msec or Sokolow-Lyon voltage >38 mm. The participants were initially separated into those with and without LVH [LVH(+) and LVH(-) groups, respectively]. To determine theoretical baPWV, we first constructed a nomogram for the LVH(-) group, calculated the PWV index (measured baPWV - theoretical baPWV) for each individual and then compared the two groups. We also examined the factors associated with LVH(+) using multivariate analyses. RESULTS: Linear regression analysis revealed that the theoretical baPWV (m/sec) = 0.20 x age (years) + 0.13 x Mean arterial pressure (MAP) (mm Hg) + 0.05 x Heart rate (beats/min) - 11.74 (R(2) = 0.56). The PWV index was greater in the LVH(+) than in the LVH(-) group (P = .025). The baPWV was independently related to LVH(+) along with MAP, medication for hypertension, and for diabetes; a 1 SD (4.3 m/sec) increase in baPWV was associated with a 26% increase in the risk of LVH(+) (P = .022). When LVH(+) risk factors were defined as hypertension, diabetes, and high baPWV (> or =14.6 m/sec), the prevalence of LVH(+) linearly increased with the number of concomitant LVH(+) risk factors (P < .001). CONCLUSIONS: Arterial stiffness is independently related to electrocardiographically determined LVH in the general population.

Adult↗
PubMed2004

SaGAS, the Short and Graphic Ability Score: an alternative scoring method for the motor components of the Multiple Sclerosis Functional Composite.

The timed performances of the 10-m timed walk (TMTW) and the nine-hole peg test (NHPT) of 881 consecutive patients with multiple sclerosis (MS) undergoing a rehabilitation stay, were expressed as a logarithmic function of time in two subscores to form a composite score called the Short and Graphic Ability Score (SaGAS). The subscores (sS) were constructed in such a way that any interval of 0.5 unit corresponds to a change of 25% in the tests. The SaGAS was computed as the mean of four subscores: SaGAS = (2 x TMTWsS + NHPTsS right hand + NHPTsS left hand). With the aid of a nomogram, the timed values of the tests are easily transformed into the corresponding subscores, which are then displayed graphically to facilitate follow-up over time. The correlation coefficients between the SaGAS and the two motor components of the MS Functional Composite (MSFC) (r = 0.987), the Expanded Disability Status Scale (EDSS)(r = -0.83), the Nottingham EADL Index (r = 0.80) and the Rivermead Mobility Index (RMI) (r = 0.90) were all statistically significant (P < 0.001), supporting the validity of the measure. SaGAS had a similar sensitivity to the RMI, but was significantly more sensitive than the EDSS in detecting changes occurring during the rehabilitation stay (14.9% versus 5.0%; P < 0.001) and over a one-year follow-up (35.3% versus 19.7%; P < 0.001). Compared with the motor components of the MSFC, with which it shares several features, SaGAS has several advantages: it does not depend on the stratification of the study population; it does not skew the results of the NHPT towards improvement at the lower end; and it offers an independent assessment of both hands. SaGAS is a simple, intuitive, nonphysician-based measure, which could provide consistent scoring in future clinical trials.

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