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Biomedical subjects

D Malhotra

Publications and source records attributed to D Malhotra.

At least 37 records · Page 2Linked to original sources
PubMed1998

Peritoneal urea and creatinine clearances in continuous peritoneal dialysis patients with different types of peritoneal solute transport.

We studied whether anuric subjects on continuous ambulatory peritoneal dialysis (CAPD) who achieve the target Kt/V urea of 2.0 weekly will also achieve the target normalized creatinine clearance (NCCr) of 60 liter/1.73 m2 weekly, and the reasons of discrepancy between the two clearances in anuric subjects, by analyzing 476 clearance studies performed in 309 CAPD patients within 12 months of the performance of a peritoneal equilibration test (PET). On the basis of the PET, peritoneal solute transport was classified as low (37 clearance studies), low-average (199 studies), high-average (186 studies) and high (54 studies). We found that weekly values of Kt/V urea in the low transport group (LTG) was 1.74 +/- 0.51, in the low-average transport group (LATG) was 1.66 +/- 0.41, in the high-average transport group (HATG) 1.68 +/- 0.41, and in the high transport group (HTG) 1.73 +/- 0.46 (NS, variance analysis). Weekly values for NCCr, liter/1.73 m2 were: LTG, 37.8 +/- 9.0; LATG, 44.0 +/- 9.2; HATG, 49.2 +/- 10.0; HTG 56.8 +/- 13.3 (P < 0.0001). The ratios of raw (not-normalized) peritoneal creatinine clearance to peritoneal urea clearance were: LTG, 0.65 +/- 0.14; LATG, 0.76 +/- 0.09; HATG, 0.84 +/- 0.09; HTG, 0.91 +/- 0.12 (P < 0.0001). Linear regression with Kt/V urea as x and NCcr as y revealed the following results: LTG, y = 19.486 + 10.500x, r = 0.591 [if x = 2.0, y = 15.004 + confidence interval (95% CI) of y 25.3 to 55.7]; LATG, y = 15.0004 + 17.482x, r = 0.774 (if x = 2.0, y = 50.0, 95% CI of y 38.4 to 61.6); HATG, y = 15.285 + 20.162x, r = 0.829 (if x = 2.0, y = 55.6, 95% CI of y 44.4 to 66.8); HTG, y = 14.945 + 24.134x, r = 0.839 (if x = 2.0, y = 63.2, 95% CI of y 48.4 to 78.1). Peritoneal solute transport type has a major effect on peritoneal creatinine clearance, but an insignificant effect on peritoneal urea clearance. Consequently, the majority of anuric patients who achieve a weekly Kt/V urea of 2.0 will have a weekly NC cr lower than 60 liter/1.73 m2 and will require a Kt/V urea much higher than 2.0 to achieve the target NCcr of 60 liter/1.73 m2 weekly. The current targets of urea and creatinine clearance are not compatible in anuric patients on CAPD.

Adult↗
PubMed1998

Gender, degree of obesity, and discrepancy between urea and creatinine clearance in peritoneal dialysis.

The effect of gender and degree of obesity on the size indicators V, used to normalize urea clearance (Kt/Vur), and body surface area (BSA), used to normalize creatinine clearance (Ccr), in peritoneal dialysis was studied by: (1) mathematical comparison of the formulae used to estimate V (Watson and Hume) with the Dubois formula used to estimate BSA in peritoneal dialysis; and (2) comparison of percent deviation of BSA (delta BSA%) and V (delta V%) from ideal weight estimates in 933 clearance studies performed in actual patients (555 in men and 378 in women on continuous ambulatory peritoneal dialysis). V was estimated by the Watson formulae and BSA by the Dubois formula in these studies. delta BSA% and delta V% were stratified in 10% increments in deviation of body weight from ideal (delta W%) in these studies. Mathematically, the relationship between V and BSA is not linear. In the same subject, as obesity develops (delta W% increases) and BSA increases in a linear manner, V increases exponentially. In addition, there are substantial differences in the relationship between V and BSA caused by gender. For the same height and BSA, men have a larger V than women. In the clearance studies performed in actual continuous ambulatory peritoneal dialysis patients, the difference between delta V% and delta BSA% increased significantly (P < 0.0001) from the wasted to the obese subjects by one-way ANOVA in both men and women. Normalization of urea and creatinine clearances by different size indicators creates two types of mathematical distortion in the relationship between the two clearances. One distortion is caused by the degree of obesity. The second distortion is caused by gender. Use of the same size indicator to normalize both urea and creatinine clearances would eliminate these distortions.

Analysis of Variance↗
PubMed1997

Decreased total antioxidant capacity but normal lipid hydroperoxide concentrations in sera of critically ill patients.

Oxidative stress (when free radical generation exceeds antioxidant defense) occurs in many human diseases and makes significant contributions to their pathogenesis. We automated assays estimating the antioxidant status of serum, and lipid hydroperoxide concentrations using the Monarch analyzer. In this assay, the antioxidant status of serum is measured by its ability to inhibit generation of free radicals from 2,2'-amino-di-[3-ethylbenzthiazole sulphonate] by metmyoglobin and hydrogen peroxide. The assay for measuring lipid peroxidation products in serum utilizes the ability of lipid hydroperoxides to generate methylene blue from 10N-methylcarbamyl 3,7-dimethylamino 10H-phenothiazine. We detected no lipid hydroperoxide in sera obtained from 24 controls. The mean antioxidant status was 1.69 mmol/l (SD; 0.20 mmol/l) in controls. The antioxidant capacity of serum was significantly reduced in sera of critically ill patients in the medical intensive care unit (mean = 1.05, SD = 0.26 mmol/l) with p value less than 0.05 by independent t-test, two tailed. Lipid peroxidation products were not significantly elevated in critically ill patients, however lipid peroxidation products were significantly elevated in hemodialysis patients (mean = 1.40, SD = 0.47 mumol/l) and in some kidney transplant recipients. We conclude that antioxidant capacity of sera in critically ill patients is significantly reduced.

Antioxidants↗
PubMed1997

Nondialysis management of chronic renal failure.

Chronic renal failure is a complex syndrome encompassing clinical manifestations from all the organs in the body. The aims of conservative management are to prevent and treat the important clinical manifestations and to prevent the progression of renal failure.

Acid-Base Imbalance↗
PubMed1997

High-dose chemotherapy with autologous transplantation for persistent/relapsed ovarian cancer: a multivariate analysis of survival for 100 consecutively treated patients.

PURPOSE: To examine the prognostic factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in 100 consecutively treated women undergoing autologous stem-cell transplant for advanced ovarian cancer. PATIENTS AND METHODS: From October 1989 to February 1996, we transplanted 100 patients with ovarian cancer following chemotherapy with high-dose carboplatin, mitoxantrone, and cyclophosphamide with or without cyclosporine (n = 70); melphalan and mitoxantrone with or without paclitaxel (n = 25); or other regimens (n = 5). Their median age was 48 years (range, 23 to 65), 70% had papillary serous histology, 72% had grade III tumors, 66% were platinum-resistant, and 61% had > or = 1 cm bulk. The median number of prior regimens was two (range, one to six). Univariate and multivariate analyses were performed to examine age (< v > or = mean), stage, initial bulk, histology, grade, response to initial therapy, number of prior regimens, time from diagnosis to transplant, transplant regimen, platinum sensitivity, and bulk (< v > or = 1 cm) at transplant. RESULTS: The median PFS and OS times for the 100 patients were 7 and 13 months. A stepwise Cox proportional hazards model identified tumor bulk (P = .0001), and cisplatin sensitivity (P = .0249) as the best predictors of PFS. Age (P = .0017), bulk at transplant (P = .0175), and platinum sensitivity (P = .0330) provided the best prediction of OS. The median PFS and OS times for the 20 patients with platinum-sensitive, < or = 1-cm disease were 19 and 30 months. No differences in OS were seen when chemotherapy or surgery was used to achieve a minimal disease state. CONCLUSION: Before consideration of high-dose therapy for recurrent/persistent advanced ovarian cancer, patients should undergo debulking surgery or chemotherapy to achieve a minimal disease state. Patients with platinum-resistant, bulky disease should not be transplanted. The optimal patients for this therapy may be those with minimal disease responsive to initial chemotherapy.

Adult↗
PubMed1997

Estimating the daily dialysate drain volume required in CAPD for a target peritoneal creatinine clearance by body water and peritoneal transport characteristics.

Stepwise logistic regression performed in 324 clearance studies in 194 patients identified daily drain volume normalized by body water (DV/V) and peritoneal solute transport type as the predictors of peritoneal creatinine clearance (CCrp) in continuous ambulatory peritoneal dialysis (CAPD). Solution of the regression model for DV/V provided DV/V values predicted to provide a desired CCrp at different probabilities. The ability of the predicted DV/V to detect desired CCrp values was tested in a new set of 359 clearance studies in 217 CAPD patients who had a peritoneal equilibration test within 12 months of the clearance study. No patient with low transport had a CCrp exceeding 54 L/1.73 m2 weekly. The following DV/V values detected CCr > or = 54 L/1.73 m2 weekly with a probability of at least 80%: for low-average transport, 0.406 L/L per 24 hours; for high-average transport, 0.339 L/L per 24 hours; for high transport, 0.241 L/L per 24 hours. Corresponding DV/V values for a CCrp of 60 L/1.73 m2 weekly were as follows: for high-average transport, 0.351 L/L per 24 hours; for high transport, 0.271 L/L per 24 hours. For high-average transport, maximal body surface area (BSA) estimates allowing a CCrp of 60 L/1.73 m2 weekly at a CAPD schedule of four daily exchanges with 3-L exchange volume and 1.5 L/24 hour ultrafiltration volume, and with the specified DV/V values were 2.03 m2 in women and 1.77 m2 in men. Corresponding BSA estimates for high peritoneal solute transport were 2.58 m2 in women and 2.21 m2 in men. The delivered dose of CAPD, expressed as DV/V, required to achieve a target CCrp can be calculated from multivariate statistical models taking into account the peritoneal solute transport type. Multiplication of the required DV/V by V provides an estimate of the required daily exchange volume. Maximal BSA estimates allowing a target CCrp can be calculated for each gender and peritoneal solute transport type.

Biological Transport↗
PubMed1997

An analysis of the determinants of urinary urea and creatinine clearance in patients on continuous peritoneal dialysis.

The relative contribution of urinary volume (UV) and urine-to-plasma concentration ratios for urea (U/PUr) and creatinine (U/PCr) to urinary Kt/V urea (Kt/VU) and urinary uncorrected creatinine clearance (CCrU), respectively, was studied by simple and multiple linear regression analysis in 236 urea kinetic studies and 233 creatinine kinetic studies performed in 135 patients on continuous peritoneal dialysis (CPD). The following simple regressions were obtained: Kt/VU = 0.09 + 0.72 (UV), r = 0.75; Kt/VU = -0.01 + 0.11 (U/PUr), r = 0.55; CCrU = 12.06 + 56.46 + 46.46 (UV), r = 0.62; CCrU = 3.51 + 3.40 (U/PCr), r = 0.58. All r values were significant (p < 0.001). According to these regressions, a loss of 0.2 L/24 hours in UV leads to a loss of 0.15 weekly in Kt/VU and 11.3 L/1.73 m2 weekly in corrected CCrU (approximately 8 L/1.73 m2 weekly in corrected CCrU). By multiple linear regression, (1) Kt/VU = -0.38 + 0.70 (UV) + 0.10 (U/PUr). Standardized coefficients were 0.72 for UV and 0.51 for U/PUr (2) CCrU = -33.36 + 59.83 (UV) + 3.63 (U/PCr). Standardized coefficients were 0.65 for UV and 0.61 for U/PCr. UV is the most important determinant of both urea and creatinine urinary clearances in CPD patients. The contribution of the U/P ratios to the urinary clearances is important, but less than that of UV. The primary dependence of urinary clearances on UV allows the use of UV, which can be easily monitored by patients, as a first approximation index of changing residual renal function in CPD.

Creatinine↗
PubMed1997

Serum albumin in continuous peritoneal dialysis: absence of universal predictors.

Factors shown to affect serum albumin concentration in continuous peritoneal dialysis (CPD) were compared between two CPD populations residing in Greece (patient n = 108) and the United States (patient n = 194). Compared to the U.S. group, the Greek CPD population had higher serum albumin levels (35.1 +/- 4.6 vs 33.9 +/- 5.0 g/L, p = 0.031), was older (61.2 +/- 12.0 vs 52.7 +/- 16.5 years, p < 0.001), and had a greater number of high or high-average peritoneal solute transport types (69.4% vs 52.1%, p = 0.003). The American CPD population had a higher number of diabetics (53.1% vs 27.8%, p < 0.001), higher total Kt/Vurea (2.06 +/- 0.57 vs 1.93 +/- 0.46 weekly, p = 0.046), and higher total creatinine clearance (76.3 +/- 38.7 vs 63.4 +/- 23.5 L/1.73 m2 weekly, p < 0.001), while normalized protein nitrogen appearance values were comparable (0.95 +/- 0.21 in the Greeks vs 0.94 +/- 0.22 g/(kg x 24 hr) in the Americans, NS). A logistic regression model developed in the United States identified advanced age, diabetes, and high/high-average peritoneal solute transport as the predictors of hypoalbuminemia (serum albumin < 35 g/L). This model generated the following areas with 95% confidence intervals (CI) under the receiver operating characteristic (ROC) curve: in the Greek CPD population, ROC area 0.594 (95% CI 0.486-0.702); in the American CPD population, ROC area 0.850 (95% CI 0.810-0.890). In Greek CPD patients serum albumin appears to be affected by factors other than those identified in North America. This complicates comparisons of serum albumin, and probably morbidity and mortality, between CPD populations residing in different parts of the world.

Creatinine↗
PubMed1996

The effect of cetirizine and loratadine on codeine-induced histamine release in human skin in vivo assessed by cutaneous microdialysis.

OBJECTIVE AND DESIGN: To determine whether or not cetirizine and loratadine inhibit codeine- induced histamine release in human skin in vivo, we conducted a placebo-controlled double-blind trial in which histamine release was assessed by dermal microdialysis. SUBJECTS: A group of ten normal volunteers were studied, each subject visiting the laboratory on three occasions with intervals of at least 2 weeks between visits. TREATMENT: Cetirizine, loratadine (both 10 mg) or placebo was given orally 4 h before provocation of weal and flare responses in the skin by intradermal injection of 25 microliters of 3 or 10 mg/ml codeine 1 mm from the centre of individual 216 microns diameter microdialysis fibres inserted in the dermis. METHODS: Dialysate was collected at 2 min intervals for 4 min before and 20 min after codeine injection and histamine assayed spectrofluorometrically. Weal and flare responses to codeine were assessed in the opposite arm. RESULTS: Histamine concentrations in the microdialysis fibre outflow with 3 and 10 mg/ml codeine were maximal at 2-4 min when 910 +/- 156 and 1194 +/- 304 nM respectively were found in the placebo group. Cetirizine and loratadine did not modify either the kinetics or total histamine release while significantly (p < 0.01) inhibiting weal and flare responses. CONCLUSIONS: Neither cetirizine nor loratadine inhibited codeine-induced histamine release or modified the time course of its release in human skin in vivo when given in clinically used doses which are sufficient to significantly reduce weal and flare responses.

Adult↗
PubMed1996

Serum albumin in continuous peritoneal dialysis: its predictors and relationship to urea clearance.

We investigated the predictors of serum albumin and the relationship between serum albumin and urea kinetic indices in continuous peritoneal dialysis (CPD). In a training set (TS) of 143 urea kinetic studies performed in 92 CPD patients, stepwise logistic regression identified high/high-average peritoneal solute transport, diabetes, advanced age and high daily drain volume normalized by body water as predictors of low serum albumin (< 35 g/liter). This analysis was then substantiated in a validation set (VS) of 187 kinetic studies performed in another 102 CPD patients. The calculated area under the receiver operating characteristic (ROC) curve by this logistic regression model was 0.782 (95% CI, 0.745 to 0.819). Logistic regression was repeated in the TS using only the first kinetic study from each patient, and it identified high/high-average peritoneal solute transport, diabetes, and advanced age as predictors of low albumin. Using only the first kinetic study from each patient in the VS, the second logistic regression model calculated an area under the ROC curve equal to 0.850 (95% CI, 0.810 to 0.890). The relative risk (RR) of serum albumin < 35 g/liter was computed for all kinetic studies after combining the TS and the VS and using non-diabetic CPD subjects aged < or = 61 years with low/low average peritoneal solute transport as the reference group. The RR with only one risk factor present ranged from 1.076 (age > 61 years) to 6.792 (high/high-average transport). The RR with two risk factors present ranged from 5.200 to 9.729. The RR with all three risk factors present was 9.100 (95% CI, range 3.923 to 21.111). A subset of 37 CPD patients had a second urea kinetic study 8 +/- 5 months after an increase in the amount of dialysis due to low urea clearance and/or uremic symptoms. The weekly KT/V urea increased from 1.40 +/- 0.24 to 2.10 +/- 0.31 after the increase in the CPD dose. With the increase in dialysis, the protein catabolic rate increased substantially; however, the mean serum albumin remained stable (from 33.9 +/- 4.6 to 33.3 +/- 6.2 g/liter; decrease 18; increase 15; same 4). In comparison to the subjects who had a decrease in serum albumin after the increase in KT/V, those with the increase in serum albumin were younger (44.2 +/- 11.2 vs. 54.3 +/- 16.2 years, P = 0.044) and had a higher serum urea after the increase in the dose of CPD (22.4 +/- 7.8 vs. 17.0 +/- 6.0 mmol/liter, P = 0.037). We conclude that the major predictors of low serum albumin in CPD are advanced age, diabetes, and high/high-average peritoneal solute transport, but not urea kinetic studies. An increase in the dose of dialysis does not cause a consistent rise in serum albumin in underdialyzed CPD subjects. However, a subset of younger patients may be able to increase their serum albumin in response to the increase in KT/V.

Adult↗
PubMed1996

Diminished protein binding capacity of uremic sera for valproate following hemodialysis: role of free fatty acids and uremic compounds.

We previously reported higher free phenytoin concentration in predialysis serum compared to postdialysis serum. In our present study with valproic acid, we observed an opposite effect, where free valproic acid concentration was higher in postdialysis serum. The increased free valproic acid concentrations in postdialysis sera (15.4-77.4% higher in postdialysis sera) were probably related to a 2-to 4-fold increase in free fatty acid concentrations in postdialysis sera. On the other hand, when an aliquot of predialysis serum pool was subjected to in vitro equilibrium dialysis and then both undialyzed and dialyzed serum pools were supplemented with valproic acid and incubated, the concentration of valproic acid in dialyzed serum was significantly lower than the undialyzed serum. This is probably related to removal of some uremic compounds during in vitro dialysis. Treatment of both pre- and postdialysis sera with activated charcoal corrected the binding deficiency of valproic acid due to removal of both uremic compounds and free fatty acids.

Anticonvulsants↗