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Biomedical subjects

D Malhotra

Publications and source records attributed to D Malhotra.

At least 73 records · Page 4Linked to original sources
PubMed1983

Intercalation of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene enantiomeric isomers with dinucleoside dimers: a basis for alkylation of the 2-amino group in guanine.

The minimum-energy intercalation-complex geometries of the (+/-)enantiomers of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (I) with two dinucleoside dimers were determined. The purpose of these calculations was to see if I could intercalate into DNA in such a way that the observed alkylation of the 2-amino group of guanine could occur subsequent to intercalation. For both dinucleoside dimer sequences, it was found that the (+)-(9 alpha, 10 alpha) isomer could form a stable intercalation complex in which the orientation and distance of the epoxide of I to the 2-amino group of guanine was close to the calculated critical transition-state geometry for the alkylation reaction. The (-)enantiomers can intercalate, but not in a manner close to the transition-state geometry necessary for the alkylation of the 2-amino group of guanine.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1981

Inhibition of dihydrofolate reductase: structure-activity correlations of quinazolines based upon molecular shape analysis.

A quantitative structure-activity relationship (QSAR) investigations of a set of 35 substituent-diverse quinazolines spanning an activity range of 4.16 log (1/I50) units was carried out using molecular shape analysis (MSA). I50 is the molar concentration necessary for 50% inhibiton of rat liver dihydrofolate reductase (DHFR). A correlation equation, analogous in descriptor form to those developed for two sets of 2,4-diaminotriazines which are also DHFR inhibitors, was constructed. The correlation coefficient, r, is 0.965, and the standard deviation, s, is 0.360. A second correlation equation was developed to explain the activities of the quinazolines on the basis of their shape similarity to a 2,4-diaminotriazine in its postulated active conformation as determined in a previous study. This correlation equation is again identical in descriptor form with those previously constructed for the triazines and quinazolines; r = 0.945 and s = 0.451 for this correlation equation. The ability to quantitatively explain activity in a congeneric set of compounds using a structurally diverse reference compound indicates the potential to design new lead compounds using MSA.

Chemical Phenomena↗
PubMed1980

Conformational flexibility of dinucleoside dimers during unwinding from the B-form to an intercalation structure.

Intra-dinucleoside dimer conformational energy calculations were performed on a series of conformations corresponding to the unwinding of a dinucleoside dimer from the B-form type structure. Conformational states were characterized in terms of the distance, d, between parallel bases. All 16 possible sequences for (G) and (C) and/or (A) and (T) bases were considered. Both free space, and free space plus aqueous solvation energies were computed. It was found that the B-form like conformer is the most stable structures in free space and in an aqueous medium. However, the energy as function of d is base pair sequence dependent. This sequence dependence suggests a possible inherent specificity for intercalation of the dinucleoside dimer with a drug molecule.

Base Composition↗
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

Estimates of interdialytic sodium and water intake based on the balance principle: differences between nondiabetic and diabetic subjects on hemodialysis.

Whether salt or water intake is the primary cause of interdialytic weight gain (deltaW) has important implication for the design of measures to prevent large deltaW. In 17 hemodialysis patients dialyzed against a bath containing 140 mmol/L of sodium, monthly predialysis serum sodium was compared with post dialysis serum sodium. A decrease in serum sodium in the interdialytic period would indicate that primary water consumption accounts for at least part of the deltaW. Interdialytic sodium intake, isotonic fluid gain (deltaW(isotonic)) and net pure water gain (deltaWH2O) were calculated by balance formulae. Serum sodium concentration was corrected in diabetic subjects to the value corresponding to euglycemia (100 mg/dl). Estimated interdialytic sodium intake was compared with the prescribed sodium intake and, in seven subjects, to sodium intake estimated from dietary records. Results for nondiabetic subjects (N = 9): [Na]post 139.3 +/- 1.9 mmol/L, [Na]pre 140.1 +/- 2.1 mmol/L (NS), deltaW 1.15 +/- 0.55 L/24 hr, deltaW(isotonic) 1.33 +/- 0.57 L/24 hr, deltaWH2O -0.20 +/- 0.58 L/24 hr, estimated sodium intake 206 +/- 75 mmol/24 hr, prescribed sodium intake 121 +/- 29 mmol/24 hr (p = 0.028). Results for diabetic subjects (N = 7): [Na]post 140.1 +/- 2.5 mmol/L, [Na]pre 137.7 +/- 3.1 mmol/L (p < 0.01), deltaW 1.26 +/- 0.38 L/24 hr, deltaW(isotonic) 0.59 +/- 0.63 L/24 hr, deltaWH2O 0.66 +/- 0.39 L/24 hr, estimated sodium intake 160 +/- 81 mmol/24 hr, prescribed sodium intake 124 +/- 30 mmol/24 hr (NS), glycosylated hemoglobin 9.7 +/- 2.8% (normal, 4.1-5.7%). In seven subjects, estimates of sodium intake from balance formulae (233 +/- 113 mmol/24 hr) were not different from estimates from dietary records (212 +/- 87 mmol/24 hr). Sodium intake accounted for all the interdialytic weight gain in nondiabetic subjects. In diabetic patients, only approximately half of the interdialytic weight gain was accounted for by sodium intake. The other half was due to pure water gain, probably caused by hyperglycemia.

Adult↗
PubMedDate not supplied

Dependence of peritoneal clearances on body size in continuous ambulatory peritoneal dialysis: effect of the normalizing size indicator.

In peritoneal dialysis (PD), small solute clearances are normalized by body water (V) and body surface area (BSA). The purpose of this study was to identify if V or BSA produced stronger associations between body size and normalized clearances. We studied the relationship between four size indicators (V, BSA, height, and weight) and either peritoneal urea clearance normalized to V (Kt/V(ur)) and BSA (C(ur)) or creatinine clearance normalized to V (Kt/V(cr)) and BSA (C(cr)). A total of 613 clearance studies were performed in subjects on continuous ambulatory peritoneal dialysis (CAPD) with four daily exchanges and a 2 L fill volume. As size increased, the normalized peritoneal clearances decreased in a nonlinear fashion (regression: y = b0 + b1x(-1), where x is a size indicator and y is a normalized clearance). Significant (p < 0.001) negative correlations were found between each normalized clearance and each size indicator. However, in each case, the correlation was higher when V, rather than BSA, was used. For example, BSA correlated more closely with K/V(ur)(-0.660) than C(ur)(-0.556), and also with Kt/V(cr)(-0.579) than C(cr)(-0.446). Normalized clearances are smaller in large subjects on CAPD because one mathematic determinant of the clearance, the drain volume (Dv) normalized by V (Dv/V) or BSA (DV/BSA), decreases as size increases. The relationship between Dv/V or Dv/BSA and the size indicators was studied by the same nonlinear regression model. The correlations of the size indicators with Dv/V were also consistently higher than the corresponding correlations with Dv/BSA. In subjects who were on the same PD schedule, the dependence of clearances on size was consistently higher when V, rather than BSA, was the normalizing parameter. Because prescription of the dose of PD is based on body size, there is a practical advantage by using V as the sole normalizing parameter for both urea and creatinine clearance.

Body Surface Area↗
PubMedDate not supplied

Body mass index in amputees.

Whereas estimates of percent deviation of body weight from ideal (F delta weight) are corrected for amputation, those of body mass index (BMI) are not, creating discrepancies in evaluating obesity. A correction of the BMI formula for amputation is proposed. The formula for BMI was corrected for amputation mathematically. The mathematical model predicts that the uncorrected BMI formula underestimates body fat in unilateral amputees and overestimates body fat in subjects with bilateral amputations at the same length of the legs. F delta weight and corrected and uncorrected BMI estimates were computed in 15 subjects with unilateral leg amputation and in 8 subjects with multiple amputations. BMI estimates were as follows: in unilateral amputees, corrected 24.1 +/- 4.1 kg/m2, uncorrected 22.2 +/- 3.9 kg/m2 (p < .001); and in multiple amputees, corrected 21.6 +/- 2.4 kg/m2, uncorrected 32.6 +/- 11.8 kg/m2 (p = .043). Linear regressions of F delta weight obtained from standard nutrition assessment on F delta weight computed from uncorrected and corrected BMI values were as follows: in unilateral amputees, uncorrected F delta weight = -0.079 + 0.932 x actual F delta weight, r = .974, p < .01, and corrected F delta weight = 0.002 + 1.005 x actual F delta weight, r = .997, p < .01; in multiple amputees, uncorrected F delta weight = 0.528 + 1.930 x actual F delta weight, r = .607, p is not significant, and corrected F delta weight = -0.010 + 0.920 x actual F delta weight, r = .936, p < .01.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMedDate not supplied

Gender differences in normalized clearances in CAPD: role of body size and normalizing parameters.

OBJECTIVE: To compare raw (not normalized) and normalized urea and creatinine clearances between women and men on continuous ambulatory peritoneal dialysis (CAPD). To study whether potential gender differences are due to the normalization process. DESIGN: Retrospective analysis of clearance studies. SETTING: Dialysis units of four academic medical centers. PARTICIPANTS: The study included 302 subjects (135 women and 167 men) on CAPD with four daily exchanges and a 2-L exchange volume. INTERVENTION: Measurement of urea and creatinine clearances (261 in women, 352 in men) by standard methods. Body water (the volume of distribution, V, for both urea and creatinine) was estimated by the Watson anthropometric formulas. MAIN OUTCOME MEASURES: Comparison of raw and normalized clearances between women and men. Urea clearance was normalized by V (Kt/Vur), while creatinine clearances was normalized by both V (Kt/Vcr) and body surface area (BSA) (Ccr). RESULTS: Mean values of weekly total (peritoneal plus renal) raw clearances were higher in men (urea clearance: women 67.1 L, men 77.4 L; Ccr: women 61.7 L, men 78.3 L). Raw renal clearances were higher in men, while raw peritoneal clearances were comparable. Mean weekly total Kt/Vur was higher in women (2.19 vs 1.94 in men), mean weekly total Kt/Vcr did not differ between the genders (women 2.01, men 1.95), while mean weekly Ccr was higher in men (73.0 vs 64.7 L/1.73 m2 in women). When clearances differed, the differences were significant at p < 0.001. Men had greater height and weight, while women had greater body mass index. On the average, V in men exceeded V in women by 31%, while BSA in men exceeded BSA in women by only 12%. CONCLUSIONS: Normalization of clearances by V creates relatively higher clearance values in women, while normalization by BSA creates relatively higher clearance values in men. Thus the normalization process may create artificial differences in the normalized clearances between genders.

Body Constitution↗
PubMedDate not supplied

Normalization of clearances in peritoneal dialysis using a formula for body water derived from an end-stage renal disease population.

OBJECTIVE: To compare body water (V) estimates from the Chertow formula (Vc), which was derived in an end-stage renal disease population, to V estimates from the Watson formulas (Vw) in continuous ambulatory peritoneal dialysis (CAPD) patients. To identify CAPD patients in whom Vc is preferred to Vw for clearance studies. DESIGN: Retrospective analysis of clearance studies. SETTING: Dialysis units of four academic medical centers. PARTICIPANTS: 302 subjects on CAPD. INTERVENTION: 613 clearance studies by standard methods. MAIN OUTCOME MEASURES: Comparisons between Vc and Vw, and between urea clearance normalized by Vc [(KtVc)ur] and Vw [(Kt/Vw)ur]. RESULTS: Vc exceeded Vw by 3.5 +/- 1.6 L (p < 0.001), or 9.6% on average. This degree of overestimation of Vw is in the range of body water estimates found in CAPD subjects with severe volume overload (> 5% of body weight) in previous studies. Total (Kt/Nw)ur exceeded total (Kt/Vc)ur by 8.6%. By linear regression, Vc = -0.589 + (1.112 x Vw), r = 0.983. Vw exceeded Vc in only 12 studies. Young age, short height, low body weight, and low prevalence of diabetes characterized the studies with Vw > Vc. Total (Kt/Vw)ur was adequate (> or = 2.0 weekly) in 276 studies. Among these, 74 studies had inadequate total (Kt/Vc)ur (< 2.0 weekly). By logistic regression, the predictors of inadequate (Kt/Vc)ur, when (Kt/Vw)ur was adequate, included the presence of diabetes, great height, and long duration of CAPD. CONCLUSIONS: Vc provides estimates of body water exceeding those provided by Vw in a great majority of CAPD patients. Consequently, approximately 25% of the clearance studies that are adequate when Vw is used as the normalizing parameter may be inadequate when Vc is used. Vc may provide a more appropriate estimate of body water than Vw in CAPD patients with volume overload.

Body Water↗
PubMedDate not supplied

Urea kinetic modeling in continuous peritoneal dialysis patients. Effect of body composition on the methods for estimating urea volume of distribution.

Body composition can have a significant effect on methods for estimating urea volume (V) and fractional clearance (KT/V) in patients with renal failure. These effects were examined in 27 men on continuous ambulatory peritoneal dialysis (CAPD). Urea volume was calculated as 0.6% of body weight (V.6), by the Watson formula (VW) and by the Hume formula (VH). Patients were classified as obese (> 120% of ideal body weight), normal (90%-120% of ideal weight), or wasted (< 90% of ideal weight). A patient was considered adequately dialyzed if his weekly KT/V urea exceeded 1.70. Only 75% of subjects were classified as adequately or inadequately dialyzed by all three methods. Six subjects had KT/V0.6 < 1.70 and KT/VW > 1.70; five subjects had KT/VH < 1.70 and KT/VW > 1.70; and two subjects had KT/V0.6 < 1.70 and KT/VH > 1.70. In the obese group, KT/V0.6 (1.62 +/- 0.67) was significantly less than KT/VW (1.93 +/- 0.76; p < 0.001) and KT/VH (1.92 +/- 0.78; p < 0.001). Fractional errors in V and KT/V between any two methods were highly correlated with percent deviation from ideal body weight (r = 0.81 or higher). In peritoneal dialysis patients, excessive body weight affects the estimates of V and KT/V urea by certain methods, and may lead to erroneous impressions about the adequacy of CAPD.

Adult↗
PubMedDate not supplied

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

Continuous peritoneal dialysis in heavyweight individuals: urea and creatinine clearances.

OBJECTIVE: To study whether or not continuous peritoneal dialysis (CPD) can provide acceptable levels of normalized urea and creatinine clearance in heavyweight individuals. DESIGN: Retrospective analysis of urea and creatinine clearance studies. SETTING: CPD patients followed in four dialysis units in Albuquerque, two dialysis units in Thessaloniki, and two dialysis units in Athens. PARTICIPANTS: One hundred and ninety-nine patients on CPD with 266 clearance determinations between 1991 and 1995. INTERVENTIONS: The heavyweight group consisted of 22 patients (24 clearance studies) weighing 100 kg or more (109 +/- 8.7 kg) at the time of the clearance study. All subjects were obese. The reference group consisted of 177 CPD subjects (242 clearance studies) of normal weight (68.7 +/- 12.2 kg). Urea fractional clearance (KT/V) and normalized creatinine clearance (Ccr) were compared between the heavyweight and the reference groups. MAIN OUTCOME MEASURES: The lowest acceptable weekly levels were set at 1.70 for KT/V and 54.4 L/1.73 m2 for Ccr. RESULTS: Weekly KT/V was 1.75 +/- 0.41 in the heavyweight group and 1.94 +/- 0.52 in the reference group (p = 0.047). Corresponding weekly Ccr levels were 64.0 +/- 24.3 and 77.6 +/- 40.3 L/1.73 m2, respectively (p = 0.021). In the heavyweight group, 13 studies (54.2%) had acceptable KT/V values compared to 160 studies (66.1%) in the reference group (NS). Corresponding values for acceptable Ccr were 17 (70.8%) and 165 (68.2%), respectively (NS). Drain volume was 12.96 +/- 4.40 L/24 hours in the heavyweight group and 9.63 +/- 2.58 L/24 hours in the reference group (p = 0.001). High daily exchange volume was delivered by a combination of daily continuous ambulatory peritoneal dialysis (CAPD) and nocturnal automated peritoneal dialysis (APD) in 13/16 heavyweight studies. This combination was tolerated better than any other method of delivering a large daily exchange volume. CONCLUSION: Although normalized urea and creatinine clearances are lower in obese, heavyweight individuals than in lean CPD subjects with lower weight, approximately equal percentages of these two groups achieve acceptable clearance levels. However, heavyweight individuals require larger-than-usual daily exchange volumes. The preferred way to deliver these large dialysate volumes is a combination of daily CAPD and nocturnal APD.

Body Weight↗