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Estimating urea clearance in patients on continuous ambulatory peritoneal dialysis: a multivariate analysis.

The purpose of this study was to determine if Kt/V urea in continuous ambulatory peritoneal dialysis (CAPD) could be estimated by a multivariate model based upon simple clinical observations. The study included 439 clearance studies in 301 CAPD patients followed in 8 dialysis centers. Weekly urea clearance, 24 h urine volume and 24 h drain volume were normalized to body water by the formulae of Watson (Kt/V, UV/V and DV/V respectively). Adequate dialysis was defined as Kt/V > or = 2.0 weekly. Subjects at 2 units were used to derive the models, while others were used for model validation. Stepwise multiple linear regression was performed on the derivation set (DS) to identify the clinical variables that correlated with Kt/V. The model was then used to estimate Kt/V for the validation set (VS). In the DS, 110 clearance studies were performed in subjects with residual renal function. Multiple linear regression showed that weekly Kt/V was defined by the expression: Kt/V=1.48 + 24.1 (UV/V) + 2.92(DV/V) - 0.049 (serum creatinine) (r=0.750, p<0.001). In 204 VS studies, the correlation between estimated and measured Kt/V was 0.633. There were marked differences in the proportion of adequately dialyzed patients when Kt/V estimated from the formula shown was <2.0, between 2.0 and 2.3, and >2.3 weekly (7.9%, 54.7% and 79.7%, respectively; p 2.3 weekly (8.1%, 68.8%, and 100%, respectively; p<0.001). The risk of low Kt/V can be estimated by multivariate linear models requiring only simple clinical measurements.

Female↗

Properties of electroretinographic intensity-response functions in retinitis pigmentosa.

Dark-adapted electroretinogram (ERG) b-wave amplitudes and implicit times were recorded as a function of stimulus luminance for 15 retinitis pigmentosa (RP) patients and 15 normal subjects. B-wave amplitude as a function of log stimulus luminance was fit by non-linear regression with the Naka-Rushton equation, which has 3 independent parameters: The maximum response (Rmax), slope (n) and half-saturation constant (K). B-wave implicit-time as a function of log stimulus luminance was fit by linear regression. Compared to normal, the RP Rmax values were markedly reduced, suggesting response compression; the RP K values were elevated by an average of 0.76 log unit, suggesting relatively small losses in retinal sensitivity. There was no correspondence between Rmax and visual field area for the RP patients (coefficient of correlation = -0.02). All but 2 of the 15 RP patients had normal or shallower-than-normal implicit-time intensity-response functions, indicating that over most of the dynamic range of the ERG, the implicit-times were either normal or faster-than-normal. These results are discussed in terms of possible RP disease mechanisms.

Adolescent↗

Identification of the time-point which gives a plasma rabeprazole concentration that adequately reflects the area under the concentration-time curve.

OBJECTIVE: The purpose of this study is to evaluate whether a simple formula using limited blood samples can predict the area under the plasma rabeprazole concentration-time curve (AUC) in co-administration with CYP inhibitors. METHODS: A randomized double-blind placebo-controlled crossover study design in three phases was conducted at intervals of 2 weeks. Twenty-one healthy Japanese volunteers, including three CYP2C19 genotype groups, took a single oral 20-mg dose of rabeprazole after three 6-day pretreatments, i.e., clarithromycin 800 mg/day, fluvoxamine 50 mg/day, and placebo. Prediction formulas of the AUC were derived from pharmacokinetics data of 21 subjects in three phases using multiple linear regression analysis. Ten blood samples were collected over 24 h to calculate AUC. Plasma concentrations of rabeprazole was measured by an HPLC-assay (l.l.q.=1 ng/ml). RESULTS: The AUC was based on all the data sets (n=63). The linear regression using two points (C3 and C6) could predict AUC(0-infinity) precisely, irrespective of CYP2C19 genotypes and CYP inhibitors (AUC(0-infinity)=1.39xC3+7.17xC6+344.14, r (2)=0.825, p<0.001). CONCLUSION: The present study demonstrated that the AUC of rabeprazole can be estimated by the simple formula using two-point concentrations. This formula can be more accurate for the prediction of AUC estimation than that reflected by CYP2C19 genotypes without any determination, even if there are significant differences for the CYP2C19 genotypes. Therefore, this prediction formula might be useful to evaluate whether CYP2C19 genotypes really reflects the curative effect of rabeprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Prospective evaluation of the oxygen uptake efficiency slope as a submaximal predictor of peak oxygen uptake in aged patients with ischemic heart disease.

BACKGROUND: The purpose of this study was to evaluate the oxygen uptake efficiency slope (OUES) as a predictor of peak oxygen consumption (VO2) in aged patients with coronary artery disease (CAD) and to compare its predictive value to that of ventilatory anaerobic threshold (VAT). METHODS: A total of 160 aged (>60 years) patients with stable CAD performed a maximal cardiopulmonary exercise test. The equations were computed by using data of 85 randomly selected patients and were validated in the remaining 75 patients. Bland-Altman (BA) analysis was used to assess the agreement between measured and predicted peak VO2. RESULTS: In the first 85 patients, peak VO2 correlated best with VAT and OUES per kilogram (P < .001). The linear regression to predict peak VO2 for OUES per kilogram was peak VO2 = 4.591 + 0.64 x OUES/kg (SEE = 2.61 mL kg(-1) min(-1)). The BA 95% limits of agreement were -29% and +30% of the predicted value. For VAT, the linear regression to predict peak VO2 was peak VO2 = 2.995 + 1.251 x VAT (SEE = 2.26 mL kg(-1) min(-1)). The BA 95% limits of agreement were -23% and +33% of the predicted value. Cross-tabulation analysis in 3 subgroups with different exercise capacities showed significant relationship between predicted and measured peak VO2 (all P < .001). OUES per kilogram showed the best measure of agreement with measured peak VO2, resulting in high sensitivity and specificity scores. CONCLUSION: OUES is not able to acceptably predict peak VO2 in aged patients with CAD but is at least as performant as VAT in categorizing patients into subgroups with different exercise capacities. Therefore, the objectively measurable OUES is the preferred submaximal predictor of functional capacity in the assessment of aged patients with CAD.

Acridines↗

Brain natriuretic peptide predicts serious cardiac allograft rejection independent of hemodynamic measurements.

BACKGROUND: Serum brain natriuretic peptide (BNP) has been reported to be elevated in heart transplant recipients with both cellular and vascular rejection. Whether BNP can be used to help predict the severity of rejection is not well established. METHODS: We analyzed serial BNP measurements obtained during endomyocardial biopsy procedures in consecutive heart transplant patients occurring >45 days after transplantation. To eliminate potential confounding from prior rejection episodes, we included only observations in which the previous biopsy grade was 0 or 1A. Multivariable linear regression was performed examining the outcome of increasing seriousness of rejection, defined as grade 0 < 1A < 2 < 1B < 3A < vascular rejection. A univariable logistic regression model was performed using log-transformed BNP as a predictor of vascular rejection. RESULTS: There were 77 patients, with 161 separate observations. Median time between transplantation and first assessment was 6.0 months (interquartile range, 2.1, 31.6). Using multivariable linear regression, 3 factors were significantly associated with biopsy score: pulmonary capillary wedge pressure (p < 0.0001), BNP (p = 0.003), and heart rate (p = 0.01). Even after other significant univariable predictors (including pulmonary capillary wedge pressure) were forced into the model, BNP remained a significant predictor of biopsy score (p = 0.02). Log BNP was a significant univariable predictor of vascular rejection, with an odds ratio of 12.55 (per 1 unit increase, 95% confidence interval 3.43-45.84; p = 0.0001) and a model c-statistic of 0.91. CONCLUSIONS: BNP predicts new episodes of serious cardiac allograft rejection, particularly vascular rejection, independent of hemodynamic measurements, and may be a useful part of rejection surveillance.

Adult↗

Estimating third molar extraction difficulty: a comparison of subjective and objective factors.

PURPOSE: The purpose of this study was to compare and contrast subjective and objective assessments of variables associated with third molar (M3) extraction difficulty. MATERIALS AND METHODS: To address the research purpose we implemented a prospective cohort study and enrolled a sample of surgeons removing M3s in an ambulatory care setting. Predictor variables were categorized as demographic, anatomic, or operative. The outcome variables were subjective and objective rankings of the importance of the variables in terms of estimating M3 extraction difficulty. Subjective rankings were made by surveying the surgeons and asking them to rank each variable's importance on a scale ranging from 0 (not important) to 100 (extremely important). Objective rankings of each variable's importance were made using the absolute values of coefficients derived from a multivariate linear regression model with extraction time as the outcome. Appropriate uni-, bi-, and multivariate statistics were computed. RESULTS: The sample consisted of 14 surgeons who removed 450 M3s from 150 subjects from June 2002 to August 2003. Based on the multivariate linear regression model, variables associated with M3 extraction time were gender, arch location, Winter's classification, tooth morphology, number of teeth extracted, procedure type, and surgical experience. For these variables, there was a strong, statistically significant correlation (r = 0.86; P <.01) between the standardized coefficient absolute values and the surgeons' estimates of importance. CONCLUSION: There was a large, positive correlation between variables that surgeons consider most important in determining M3 extraction difficulty and those exhibiting the most influence over extraction times in a multivariate model.

Adult↗

Antenatal steroid treatment prevents severe hyperkalemia in very low-birthweight infants.

BACKGROUND: Hyperkalemia is seen quite often in very low-birthweight (VLBW) infants and concentrations sometimes become high enough to cause cardiac arrhythmia. The purpose of the present study was to identify factors that increase serum concentrations of potassium in VLBW infants. METHODS: Retrospective comparative analysis was performed on 140 VLBW infants who had been admitted to the Toho University Perinatal Center between January 1993 and December 1999 and needed mechanical ventilation for respiratory distress. Serum concentrations of potassium at 24 and 48 h of age were compared in two groups of infants, those whose mothers did and did not receive antenatal steroid treatment. Risk factors for severe hyperkalemia were analyzed by multiple linear regression models and Pearson's partial correlation analysis. RESULTS: Antenatal steroid treatment reduced serum potassium concentrations significantly at 24 and 48 h, as well as the incidence of cardiac arrhythmia and necessity for glucose insulin treatment for severe hyperkalemia. Multiple linear regression showed the serum potassium concentration at 24 h of age was associated with antenatal steroid hormone treatment, 24 h fluid intake volume, serum sodium concentrations at 24 h, gestational weeks and sampling site. Serum concentration of potassium at 48 h of age was associated with blood urea nitrogen, gestational week, serum sodium concentration at 48 h of age and fluid intake between 24 and 48 h of age. Urine output volume and serum creatinine concentrations were not correlated with potassium concentrations at either age. CONCLUSION: Antenatal steroid hormone treatment can reduce early hyperkalemia in VLBW infants and also the incidence of cardiac arrhythmia and the use of glucose insulin treatment.

Female↗

Tracking individual fish from a moving platform using a split-beam transducer.

Tracking of individual fish targets using a split-beam echosounder is a common method for investigating fish behavior. When mounted on a floating platform like a ship or a buoy, the transducer movement often complicates the process. This paper presents a framework for tracking single targets from such a platform. A filter based on the correlated fish movements between pings is developed to estimate the platform movement, and an extended Kalman filter is used to combine the split-beam measurements and the platform-position estimates. Different methods for gating and data association are implemented and tested with respect to data-association errors, using manually tracked data from a free-floating buoy as a reference. The data association was improved by utilizing the estimated velocity for each track to predict the location of the next observation. The data association was more robust when estimates of platform tilt/roll were used. Other techniques to estimate position and velocity, like linear regression and smoothing splines, were implemented and tested on a simulated data set. The platform-state estimation improved the estimates for methods like the Kalman filter and a smoothing spline with cross validation, but not for robust methods like linear regression and smoothing spline with a fixed degree of smoothing.

Animals↗

Adenosine as a mediator of postcontraction hyperemia in dog gracilis muscle.

The role of adenosine in postcontraction hyperemia (PCH) following sustained, maximal isometric contractions was studied in free-flowing dog gracilis muscles. The hemodynamic responses to contraction were examined in the presence and absence of dipyridamole (an adenosine transport inhibitor), erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, an adenosine deaminase inhibitor), or alpha, beta-methyleneadenosine-5'-diphosphate (AOPCP, an inhibitor of 5'-nucleotidase). Each muscle was stimulated to contract for 1, 3, 5, and 10 s during saline and drug infusions. For each contraction, the tension-time integral (TT), excess flow (EQ), and excess oxygen consumption (EVo2) were computed. Linear regression analyses were then performed on EQ vs. TT, EVo2 vs. TT, and EQ vs. EVo2. An alteration of the PCH response by the drug was determined as any significant change from the saline control in the slope of the linear regression of EQ vs. EVo2. Dipyridamole and EHNA caused increases of 73 and 48%, respectively, in the slope of EQ vs. EVo2, whereas AOPCP decreased the slope by 41%. The changes in the PCH produced by these drugs are consistent with the hypothesis that an increase in interstitial adenosine during muscular contraction contributes to PCH.

Adenine↗

Stereoselective pharmacokinetics and pharmacodynamics of disopyramide and its metabolite in rabbits.

The extent to which interactions between enantiomers of disopyramide and between disopyramide and its metabolite, mono-N-dealkylated disopyramide (MND), contribute to stereoselectivity of the anti-arrhythmic effect has been investigated in rabbits by measuring the prolongation of the QUc interval. The plasma unbound fraction of disopyramide enantiomers was constant at a concentration range of 1.44-28.9 microM. An intravenous infusion study of the disopyramide enantiomer or racemate suggested that the S-enantiomer had a pharmacological effect, determined by linear regression analysis, approximately 3.3-times more potent than that of the R-enantiomer. Furthermore, the effect caused by racemic disopyramide was the sum of that elicited by both enantiomers individually. No significant difference was observed between the slope of linear regression analysis of intravenous infusion and that of intravenous bolus injection. Single intravenous bolus injection of MND did not affect the QUc intervals. In conclusion, the S-enantiomer of disopyramide was approximately 3.3-times more potent pharmacologically than the R-enantiomer. The relationship between plasma concentration of the disopyramide enantiomers and pharmacological effect was the sum of each enantiomer individually.

Action Potentials↗

Novel features of tumors that secrete both growth hormone and prolactin in acromegaly.

The most prominent previously reported clinical features of growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas associated with acromegaly have included the high incidence of galactorrhea in women and a generally more favorable response to dopamine agonist therapy. The authors analyzed a consecutive series of 62 acromegalic patients treated with transsphenoidal microsurgery. GH-PRL tumors were found in 30% of the patients. There was a significant difference in sex distribution between acromegalics with the GH-PRL tumor subtype and all other acromegalics. Women represented 73% of the GH-PRL immunostain subtype, as compared with the overall sex distribution of 33 women (53%) and 29 men (47%) for the entire series of acromegalic patients. Individuals with the GH-PRL subtype had significantly higher postoperative GH levels than those with the GH subtype, and significantly higher postoperative GH levels when compared with all other acromegalics with a variety of immunostain subtypes. Linear regression analysis of the pre- and postoperative GH data revealed that the increased postoperative GH levels in the GH-PRL immunostain subtype were independent of the invasiveness of the tumor and of sex of the subject. When the same linear regression technique was used, lower preoperative levels of thyroxine and thyroid-stimulating hormone were observed in the GH-PRL subtype. These data suggest inherent differences characteristic of tumors that secrete both growth hormone and prolactin.

Acromegaly↗

QSBR study of substituted phenols and benzoic acids.

The biodegradability of 30 substituted phenols and benzoic acids was determined by BOD technique. The molecular weight (Mw), heat of formation (Hf) and the energy of the highest occupied molecular orbital (E(Homo)) of the studied compounds were calculated by the quantum chemical method MOPAC6.0-AMI. The quantitative structure-biodegradability relationships (QSBRs) were developed by the linear regression method and neural network approach, respectively. It has been shown that the neural network method is able to provide a superior fit to the training set data and test set data and produce a lower prediction error than the linear regression method.

Benzoates↗

Exercise blood pressure response, cardiac output and 24-hour ambulatory blood pressure monitoring in children after aortic coarctation repair.

BACKGROUND: The aim of this study was to assess blood pressure at rest, the response to exercise and the 24-hour ambulatory blood pressure monitoring (ABPM) profile in children operated for aortic coarctation. METHODS: Twenty children were operated upon for aortic coarctation. The patients' data were compared with those obtained from 19 healthy controls of the same age. Treadmill exercise testing was performed and cardiac output was determined using the acetylene-rebreathing method and indexed for the body surface area; ABPM was performed only in the patients group. The main outcome measures were the time of exercise, systolic (SBP) and diastolic (DBP) blood pressure both at rest and at peak exercise, maximal heart rate, total peripheral vascular resistance at rest and at peak exercise, and the pulse pressure (PP = SBP-DBP) at rest, at peak exercise and at ABPM. The Mann-Whitney test (non-parametric) and linear regression analysis were used when appropriate. RESULTS: Patients compared with healthy controls showed significant differences in SBP and PP at rest, and in DBP, cardiac index, total peripheral vascular resistance and PP at peak exercise. In the patients group only, linear regression analysis showed a significant correlation between PP and cardiac output, both at rest and at peak exercise, and between the arm-leg gradient at rest and PP at ABPM. CONCLUSIONS: These findings suggest that blood pressure abnormalities could be due both to the altered baroceptor reflex control mechanism, resulting in cardiac output and total peripheral vascular resistance abnormalities, and to the progressive increase in resistance during exercise at the site of the repair, resulting in the higher PP, that may be related to a local loss of the natural aortic elasticity.

Adolescent↗

Retinal blood flow changes in type I diabetes. A long-term follow-up study.

PURPOSE: The authors previously reported that blood speeds in the retinal arteries were significantly lower in patients with type I diabetes than in controls without diabetes. The purpose of this long-term, follow-up study was to characterize the natural course of changes in blood speed and blood flow in these patients. METHODS: Twenty-four patients were followed up with serial annual measurements of the blood flow in a temporal retinal artery using the bidirectional laser Doppler technique and monochromatic photography. The follow-up period ranged from 2 to 6 years (mean, 3.8 years). Using standardized color fundus photography and fluorescein angiography, a retinopathy score was generated for each eye studied. Linear regression analysis was used to compute the slope of the change in retinal blood flow for each patient during the follow-up period. RESULTS: Retinal blood flow slopes were negative in 15 patients and positive in 9 patients. Multiple linear regression analysis showed that the retinal blood flow slopes were significantly related to the retinal blood flow measured at entry to the study and to the median duration of diabetes during the follow-up period (R2 = 0.56; P = 0.0002). There was a positive correlation between the retinal blood flow slopes and the median retinopathy score during the follow-up period (P = 0.47; P = 0.02). CONCLUSIONS: As duration of diabetes becomes longer and retinopathy becomes more severe, there is a transition from negative to positive retinal blood flow slopes. This bimodal relationship between the change in retinal blood flow and the duration of diabetes reflects the complex pathologic alterations that occur in the diabetic retina.

Adult↗

Nutritional, socioeconomic, and reproductive factors in relation to female breast cancer mortality: findings from a cross-national study.

Using data from 66 countries, we conducted an international comparison study to identify the most important predictors of female breast cancer mortality rates. This study was unique in that it included data on per capita tobacco disappearance, alcohol consumption, socioeconomic status (SES), reproductive factors, and a wide array of nutritional data. Results of correlation and single independent-variable linear regression models indicated that breast cancer mortality was most strongly associated with dietary factors typically associated with affluence, especially animal products. The strongest negative (i.e., protective) associations were with those variables related to increased fertility and population growth. A multiple linear regression that accounted for all important predictors simultaneously explained 91% of the variability in mortality rates across these countries. This model indicated a strong positive association between breast cancer mortality and calories from animal sources. Fish and cereal products as well as annual percentage growth in population appeared to exert protective effects. Despite the limitations of this type of analysis, the observed effect of high meat and animal product consumption, the major contributor to variability in dietary fat, as well as the protective effect of increased fertility are consistent with the known biology of breast cancer. The protective effect of fish and cereal consumption that we observed will require further study.

Aged↗

Method for improved accuracy in endogenous urea recovery marker calibrations for microdialysis in tumors.

INTRODUCTION: Urea has been proposed as an endogenous recovery marker for microdialysis for absolute concentration calculations of analytes in microdialysis samples. Previously we demonstrated a linear relationship between urea concentrations in a rat mammary carcinoma and that in plasma, validating its use as a recovery marker for that particular tumor. In this paper, we have extended the validation to two other tumor lines, thereby providing confidence that the calibration is constant across tumor types. To improve the accuracy in the determination of the plasma/tumor urea relationship from no net flux calibrations, we extended the range of the calibration by adding exogenous urea to tumor bearing animals. This method enabled more accurate calculations of absolute recovery from plasma and dialysate urea concentrations. We confirm that by using this method the calibration is valid across three different tumor lines. The existence of a common calibration between tumors provides rationale for using plasma urea as a recovery marker for clinical trials. The existence of a common calibration between tumor types bypasses the need to perform time consuming calibrations for each patient. This makes the procedure much more practical for clinical studies. METHODS: The no net flux technique was used to determine the plasma vs. tumor urea relationship for the R3230Ac mammary carcinoma, 9 L glioma, and a fibrosarcoma (FSa), grown in Fischer 344 rats. Plasma urea was stably increased beyond the normally occurring concentration for some of the data points by subcutaneous bolus administration to extend the range of data for the no net flux calibration. RESULTS: Urea recovery was unaffected by plasma urea concentration and was consistent with other reported values. The relationship between plasma and tumor urea was fit by a line, and linear regressions of the data with the extended plasma urea range had better R2 values than we reported previously. Statistical comparison of the regressions suggests that within reasonable uncertainty limits, they are the same for the different tumor types. DISCUSSION: Increasing the plasma urea concentration range for no net flux calibrations of urea as an endogenous recovery marker in tumors resulted in more accurate determination of the plasma/tumor urea relationship. A single linear regression may describe the relationship between plasma and tumor urea concentration across tumor lines for a given set of microdialysis parameters.

Animals↗

Long-term disorders of the blood-aqueous barrier after small-incision cataract surgery.

PURPOSE: To determine the long-term function of the blood-aqueous barrier after small-incision cataract surgery with implantation of a foldable intraocular lens. METHODS: The blood-aqueous barrier function in 74 eyes of 62 patients who underwent cataract surgery was examined using a laser flare-cell meter. The measurements were performed pre-operatively and post-operatively between 12 and 35 months after surgery. For statistical analysis a linear regression was used. The study was designed as a single cohort study, with comparison of pre- and post-operative values. RESULTS: Highly statistically significant differences (p < 0.0001) were found between pre-operative flare values and those measured at the final visit. The linear regression model showed significantly higher flare values post-operatively compared with those measured pre-operatively. Other variables such as incision technique, sex, operation time, phaco time and systemic disease had no influence on this outcome. CONCLUSION: The results suggest that there is persistent blood-aqueous barrier dysregulation even several years after cataract surgery.

Aged↗

Three dimensional CT angiography for patients with congenital heart disease: scanning protocol for pediatric patients.

The objective of our study was to determine the contrast attenuation level that yields high quality cardiac three-dimensional (3-D) images and to predict the contrast injection rate (IR), from body weight, to reach this attenuation level. Enhanced electron beam computerized tomography (EBCT) with 3-D reconstruction is useful in delineating cardiac anatomy in complex congenital heart disease (CHD). The current experience of using electron beam angiography (EBA) in pediatric CHD is limited. Well-defined contrast injection protocols, specifically the contrast IR, have not been standardized when compared to those for adults. Establishing the contrast IR is essential in obtaining high quality 3-D images. We retrospectively analyzed the studies of 115 pediatric patients with CHD. EBA images were divided into group 1 with good quality 3-D images and group 2 with poor quality. The mean of measured enhancement level, expressed in Hounsfield units (HU), and contrast IR were analyzed in both groups. Spearman correlation was used to examine the relationship between weight and IR. The IR was predicted from weight using simple linear regression analysis. The mean level of enhancement was 344 +/- 91 and 174 +/- 31 HU for group 1 and group 2, respectively. Group 1 consisted of 103 patients (90%) and the IR strongly correlated with weight (rho = 0.861, P < 0.01). The IR was estimated from the linear regression equation IR = 0.59 + 0.056 x weight. Necessary contrast enhancement level for quality 3-D reconstruction should be greater than 250 HU, and the IR can be estimated from patient's weight.

Adolescent↗