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PubMed2006

The influence of mode of delivery and ACE genotype on serum angiotensin converting enzyme (ACE) activity in the mother and infant at term.

OBJECTIVE: Angiotensin converting enzyme (ACE) and its genotype have been shown to play a role in the pathophysiology of pregnancy complications such as pre-eclampsia and intrauterine growth restriction and possibly in adult onset chronic diseases. The physiological changes of ACE and the influence of its genotype during the intrapartum period are not well known. Hence the aim of this study was to assess serum ACE activity and its genotype in mothers and infants at term in relation to labour and mode of delivery. STUDY DESIGN: A cross sectional study of 99 women who laboured and 27 women who delivered by elective caesarean section after 36 completed weeks gestation with uncomplicated pregnancies. Venous cord bloods were obtained immediately after delivery of the placenta for serum ACE activity, ACE genotype and acid-base status. Maternal venous samples were obtained just after delivery for analysis of ACE activity and ACE genotype. Univariate analyses were performed using parametric tests for normally distributed data and nonparametric tests for the data that were not normally distributed. A multiple regression model was developed to adjust for potential confounding factors. RESULTS: The umbilical venous ACE activity was similar for infants delivered following labour compared to those delivered by elective caesarean section, 47.2 U/L (35-64) versus 40.1 U/L (31-60) (adjusted p=0.21). Maternal ACE activities were 28.9 U/L (22-35) and 32.1 U/L (22-40) respectively (adjusted p=0.17). The ACE activity in infants was higher than that of mothers 46 U/L versus 22 U/L, respectively (p= or <0.001). Neither the mode of delivery nor the presence of suspected fetal compromise influenced maternal or infant ACE activity. There was no influence of the infants' genotype on ACE activity in relation to mode of delivery. The DD genotype was associated with higher ACE activity in mothers (p=0.001) but not in infants (p=0.56). CONCLUSIONS: This study shows that intrapartum events do not affect ACE activity. These results will enhance our ability to investigate the role of ACE and its genotype in abnormal fetal growth and in subsequent adult onset chronic disease.

Acidosis↗

PubMed1993

Vla-3 distribution in normal and neoplastic non-lymphoid human tissues.

Using monoclonal antibody (mAb) M-Kid 2 to the alpha 3 beta 1 heterodimer, we have evaluated immunohistochemically the in vivo expression of the Vla-3 integrin in normal and transformed non-lymphoid human tissues. In normal tissues the alpha 3 beta 1 complex displays a polarized distribution at the baso-lateral aspect of most keratinizing and glandular epithelia. In addition the integrin is detected in perineurium, basal lamina of smooth muscular fibers, vascular media, podocytes and Bowman's capsule, myoepithelial cells of the parotid and breast, and in pulmonary alveoli. Neoplastic transformation is associated with qualitative and quantitative changes in expression of this integrin. The loss of polarized distribution often occurs in various malignancies. Furthermore, a significant decrease in expression occurs in 13% of the colon-rectum carcinomas, 75% of the ductal invasive, and 40% of the lobular invasive breast carcinomas. Among the lung malignancies tested, the small cell lung carcinomas (SCLC) were found to be consistently unreactive with mAb M-Kid 2. Analysis of Vla-3 expression in established tumor cell lines demonstrated that the integrin is almost invariably expressed by the plastic adherent cell subpopulations.

Antibodies, Monoclonal↗

PubMed2004

Multimedia fate model for hexachlorocyclohexane in Tianjin, China.

A level III fugacity model was applied to characterize the fate of gamma-HCH in Tianjin, China, before the 1990s when the contamination reached its maximum at steady state. Geometric means were used as model inputs. The concentrations of gamma-HCH in air, surface water, soil, sediment, crops, and fish as well as transfer fluxes across the interface between the compartments were derived under the assumption of steady state. The calculated concentrations were validated by independent data collected from the literature. There was generally good agreement between the estimated and the observed concentrations, and the differences were all less than 0.6 log units for air, water, soil, sediment, and fish and approximately 1 order of magnitude for crops. Around 97% of gamma-HCH accumulated in soil and sediment. Wastewater irrigation was not an important pathway for delivering gamma-HCH to soil as compared to the dominant source of agricultural application. Degradation and advective airflow carried much gamma-HCH out of the system. Sensitivities of the model estimates to input parameters were tested, and a coefficient of variation normalized sensitivity coefficient was defined for the test. The most influential parameters were degradation rates in sediment and soil, application rates, concentrations in wastewater, and adsorption coefficients. Monte Carlo simulation was conducted for model uncertainty analysis. The model was run 20 000 times using randomly generated data from predefined log-normal distribution density functions. All calculated concentrations and fluxes were log-normally distributed. The dispersions of the calculated and observed concentrations were compared in terms of coefficients of variation to distinguish between true variability and model uncertainty.

Air↗

PubMed1979

Role of environmental variability in the evolution of life history strategies.

We reexamine the role of environmental variability in the evolution of life history strategies. We show that normally distributed deviations in the quality of the environment should lead to normally distributed deviations in the logarithm of year-to-year survival probabilities, which leads to interesting consequences for the evolution of annual and perennial strategies and reproductive effort. We also examine the effects of using differing criteria to determine the outcome of selection. Some predictions of previous theory are reversed, allowing distinctions between r and K theory and a theory based on variability. However, these distinctions require information about both the environment and the selection process not required by current theory.

Journal Article↗

PubMedDate not supplied

Repigmentation of vitiliginous skin by cultured cells.

Epidermal cells from pigmented areas of a patient with vitiligo were cultured in MCDB-153 medium, which supports the clonal growth of undifferentiated keratinocytes and melanocytes. The cells were grown on collagen-coated substrata. After the cells reached semiconfluence, the composite of substratum and cells was emplaced onto dermabraded vitiliginous areas as a graft. Re-epithelialization of the grafted areas was complete after 2 weeks. Repigmentation was evident after 1 month and continued over the observation period of several months. There was complete and normal differentiation of the graft, including a normal distribution of melanocytes in the basal layer. Ultrastructural studies showed a normal distribution of melanosomes in the melanocytes and showed keratinocytes that were indistinguishable from the uninvolved skin.

Antibodies↗

PubMed1995

Genetic and environmental sources of fibrinogen variability in Israeli families: the Kibbutzim Family Study.

Genetic and environmental determinants of plasma fibrinogen were investigated in a sample of 82 kindreds residing in kibbutz settlements in Israel. The sample included 223 males and 229 females ages 15-97 years. Fibrinogen levels were first adjusted for variability in sex and age. There was a significant familial aggregation of adjusted fibrinogen levels, as indicated by inter- and intraclass correlation coefficients significantly different from zero. Commingling analysis implied that in this population a mixture of two normal distributions fit the adjusted fibrinogen levels better than did a single normal distribution. Complex segregation analysis was first applied to these sex- and age-adjusted data. Heterogeneous etiologies for individual differences were suggested. There was evidence for a nontransmitted environmental major factor in addition to polygenic genes that explained the mixture of distributions. In parallel, a single recessive locus with a major effect that explained the adjusted variation in fibrinogen could not be rejected. However, when the regression model for sex and age allowed coefficients to be ousiotype (class)-specific, the recessive genetic model was rejected and the mixed environmental one was not. These results suggested that particular ousiotypes determined by the major environmental factor are associated with a steeper increase of fibrinogen with age. While at the age of 20 years, the major environmental factor contributed 10% to fibrinogen variability, and 48% was explained by polygenic loci, at 80 years of age, the major factor explained 64% and only approximately 20% was explained by polygenic factors.

Adolescent↗

PubMed2006

Improving the power of association tests for quantitative traits in family studies.

Association mapping based on family studies can identify genes that influence complex human traits while providing protection against population stratification. Because no gene is likely to have a very large effect on a complex trait, most family studies have limited power. Among the commonly used family-based tests of association for quantitative traits, the quantitative transmission-disequilibrium tests (QTDT) based on the variance-components model is the most flexible and most powerful. This method assumes that the trait values are normally distributed. Departures from normality can inflate the type I error and reduce the power. Although the family-based association tests (FBAT) and pedigree disequilibrium tests (PDT) do not require normal traits, nonnormality can also result in loss of power. In many cases, approximate normality can be achieved by transforming the trait values. However, the true transformation is unknown, and incorrect transformations may compromise the type I error and power. We propose a novel class of association tests for arbitrarily distributed quantitative traits by allowing the true transformation function to be completely unspecified and empirically estimated from the data. Extensive simulation studies showed that the new methods provide accurate control of the type I error and can be substantially more powerful than the existing methods. We applied the new methods to the Collaborative Study on the Genetics of Alcoholism and discovered significant association of single nucleotide polymorphisms (SNP) tsc0022400 on chromosome 7 with the quantitative electrophysiological phenotype TTTH1, which was not detected by any existing methods. We have implemented the new methods in a freely available computer program.

Alcoholism↗

PubMed1986

Population study of triazolam pharmacokinetics.

The kinetics of a single 0.5 mg oral dose of the triazolobenzodiazepine hypnotic triazolam, were studied in 54 healthy young men aged 20-44 years, with a mean body weight of 77 kg. Triazolam kinetics were determined from multiple plasma concentrations measured during 14 h post-dose. The overall mean +/- s.e. mean (with range) kinetic variables were: peak plasma concentration, 4.4 +/- 0.3 (1.7-9.4) ng ml-1; time of peak, 1.3 +/- 0.1 (0.5-4.0) h after dose; elimination half-life, 2.6 +/- 0.1 (1.1-4.4) h; total AUC: 19.1 +/- 1.1 (4.4-47.7) ng ml-1 h; oral clearance, 526 +/- 38 (175-1892) ml min-1. All kinetic variables were consistent with Poisson distributions, based on the Kolmogorov-Smirnov Goodness of Fit test. None of the variables fit normal distributions. Four of five were consistent with a log normal distribution. Peak plasma level was highly correlated with clearance (r = -0.85, P less than 0.0001), and AUC (r = 0.85, P less than 0.0001) but not with body weight (r = 0.21, NS). Clearance and body weight were not correlated (r = -0.01). Triazolam clearance may vary widely even within a homogeneous group of healthy young men.

Adult↗

PubMed1991

Lactate dehydrogenase activity and isoform distribution in normal and hypertrophic smooth muscle tissue from the rat.

The lactate dehydrogenase (LDH) activity and isoform distribution of LDH were investigated in tissue samples from the rat portal vein, aorta and urinary bladder. In addition, samples were obtained from hypertrophic urinary bladder. The total LDH activity per unit smooth muscle volume was higher in the urinary bladder compared to that in portal vein and aorta. Five LDH isoforms, reflecting different combinations of the two polypeptide chains denoted H and M, could be separated by agarose gel electrophoresis. The aorta contained more of the H form compared to the portal vein and urinary bladder. This difference suggests that the aorta, which is a slow smooth muscle, is more adapted for aerobic metabolism than the faster muscles of portal vein and urinary bladder. In the hypertrophic urinary bladder a shift in LDH isoform pattern towards less of the H form was found, which correlates with a better maintenance of contraction in anoxia in this type of hypertrophic smooth muscle.

Animals↗

PubMed1984

Clinical DNA flow cytometry.

Modal DNA values of tumours from various sites may exhibit (1) a diploid-near diploid distribution, (2) an exponential distribution in the tetraploid to triploid range, or (3) a log-normal distribution in the triploid to tetraploid range. Examples of these various types of distribution are non-Hodgkin's lymphoma (1), aneuploid prostate carcinoma (2), aneuploid colon, breast, cervix and testicular carcinomas (3). These differences indicate dissimilarities in tumour development. In aneuploid tumours from the same site both tetraploid exponential and triploid-tetraploid log-normal distributions may occur. In bladder carcinoma these are related to grade. Modal DNA values in tumours are 10% higher than would be expected from modal chromosome numbers. This difference seems not to be due to a relative increase in large-sized chromosomes or due to technical shortcomings. Chromosome studies also show the possibility of the existence of near diploid malignant cells in grossly aneuploid tumours. Modal DNA values are connected with functional tumour properties by the proportion of S-phase cells. The significance of the latter is exemplified by follow-up of patients with bladder and cervix carcinoma.

Cell Division↗

PubMed2003

Central auditory processing assessment: a French-speaking battery.

Based on the American Speech-Language-Hearing Association (ASHA) Consensus Statement on central auditory processing and models for their exploration, a battery of audiological tests (Bilan Auditif Central--BAC) has been designed in French. The BAC consists of four types of psycho-acoustic tests: a speech-in-noise test, a dichotic test, a temporal processing test and a binaural interaction test. We briefly describe the rationale of these tests. The BAC is available in digital format. Descriptive statistics were computed on data obtained from 668 subjects divided into 15 age-groups ranging from 5 to 85 years old or over. All subjects had no complaints regarding hearing loss, normal tonal audiometry, and normal intelligence. Tests scores of the speech-in-noise test, the dichotic test and the binaural interaction test showed a normal distribution. Test scores of the temporal processing test did not follow a normal distribution. Effects of maturation and involution were clearly visible for all tests. The low correlation between scores obtained from the four tests pointed to the need for a battery of several tests to assess central auditory processing. We claim that the reported scores represent standard norms for the normal French-speaking population, and believe that the tests will be useful for evaluation of central auditory processing.

Adolescent↗

PubMedDate not supplied

Profiles of neuromuscular diseases. Duchenne muscular dystrophy.

One hundred and sixty-two patients with Duchenne muscular dystrophy (DMD) were followed over a 10-yr period to provide a profile of impairment and disability. The median height and weight of DMD boys were normally distributed before ages 9-10, but during the second decade height was markedly reduced, and weight was no longer normally distributed. Younger boys gained more weight than normals, whereas older individuals actually showed weight loss. Manual muscle test (MMT) measurements showed loss of strength in a fairly linear fashion from ages 5-13 yr, -0.25 MMT units per year. Upper extremity muscles were stronger than lower extremity muscles, proximal muscle groups were weaker than distal muscle groups, and extensor muscles were weaker than flexor muscles. There was no side dominance. There was a change in the rate of strength loss at 14-15 yr, and the decline slowed to only -0.06 MMT units per year. Although MMT and quantitative strength measurement profiles were similar, the latter were far more sensitive. In general, by the time strength declined to MMT grade 4, isometrically measured strength was 40-50% of normal control values. Joint contractures were rare before age 9, increased in frequency and severity with age, and were present in most individuals older than 13. Lower extremity contractures were strongly related to onset of wheelchair reliance, but there was no association between muscle imbalance around a joint. The prevalence of scoliosis increased between ages 11 and 16, with about 50% of the boys acquiring scoliosis between ages 12 and 15, corresponding to the onset of the adolescent growth spurt. Wheelchair reliance and scoliosis were both age-related. Percent predicted forced vital capacity declined at different yearly rates: ages 7-10, -0.3%; ages 10-20, -8.5%; after age 20, -6.2%. There was a direct relationship between percent predicted FVC and MMT scores. Decreased airway pressures, especially maximal expiratory pressure, appeared earlier than reductions in FVC but followed the same pattern. Thirty percent of the DMD boys had a history of respiratory complications, and the frequency increased with age. Spine deformity did not have a significant additive effect on the age-related decrement in pulmonary function. There was a high occurrence (79%) of abnormal electrocardiograms with age-related progression of some abnormalities, but only 30% of the patients had a history of cardiovascular complications. Functional level grades and timed motor performance measurements had a nonlinear relationship with strength and age.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed2005

Aniseikonia testing in an adult population using a new computerized test, "the Aniseikonia Inspector".

PURPOSE: To determine the measurement characteristics of a new computerized test, the Aniseikonia Inspector Version 1, on a sample of clinic patients. METHODS: Aniseikonia was measured in the vertical, horizontal, and oblique meridians on 320 patients (mean 55 years old, range 17-89 years) prior to their optometric exam using the psychometric methods programmed into the Aniseikonia Inspector Version 1. Statistical analyses were performed to determine the distribution of aniseikonia in the sample of patients and the relationships between the amount of aniseikonia and patients' habitual refractive correction, visual acuity, stereopsis and binocular alignment status. The characteristics of the individual measurements were also examined. RESULTS: The means and standard deviations of the measured aniseikonia in the vertical, horizontal, and oblique meridians were -0.5% (2.5%), -0.1% (3.3%) and 0.3% (2.8%) respectively. The means in the vertical and oblique meridians were significantly different from 0.0 (p=0.0001, p=0.0314) while that in the horizontal was not (p=0.61). The distributions of aniseikonia showed that 65.6%, 57.5% and 64.3% had within +/-1.0% aniseikonia in the vertical, horizontal and oblique meridians, respectively. Correspondingly, 16.9%, 25.6% and 25.8% had aniseikonia of +/-3.0% or greater. The discrepancy between these percentages and those expected in a normal distribution indicate that the distributions were significantly more peaked than a normal distribution. This departure from normal is due to a few extreme values in the tails. The magnitude of aniseikonia had no statistically significant relationship with the patients' habitual refractive correction, visual acuity or stereopsis. The effect of phoria on the amount of aniseikonia was significant, more so for measurements in the horizontal meridian. The individual measurements, which are the average of two trials using the method of adjustment, showed no significant bias, no relationship between the means and differences in the two readings, but large differences between the two readings. Measurements in the vertical direction seem to be more stable than those in the other two meridians. CONCLUSION: As measured with the Aniseikonia Inspector 1.0, the majority of the patients sampled in this study exhibited 1.0% or less aniseikonia and were therefore not likely to have symptoms related to aniseikonia. At least 17% of patients had 3.0% or greater aniseikonia measured in the vertical meridian. The Aniseikonia Inspector warrants further evaluation in a clinical setting because of the large limits of agreement between the two settings that are average to determine the magnitude of the aniseikonia. These limits differ considerably from those established by the designers and, therefore, raise questions regarding the actual resolution of the instrument as compared to the nominal resolution.

Adolescent↗

PubMed1985

Involucrin, a marker of squamous and urothelial differentiation. An immunohistochemical study on its distribution in normal and neoplastic tissues.

Involucrin is a soluble protein precursor of the cross-linked envelope present in the submembranous zone of human stratum corneum, and subsequently demonstrated in stratified squamous epithelia. The immunoperoxidase technique was used to assess the distribution of involucrin in 107 normal and 318 abnormal tissues. With few exceptions, involucrin was restricted to squamous epithelia, urothelium, some skin appendages and thymic Hassall's corpuscles. In normal squamous epithelium and normal urothelium, staining was most intense in the superficial layers where it was concentrated at the cell periphery and gradually decreased toward the basal layer. This orderly staining pattern was maintained in benign squamous and urothelial lesions and in grade I papillary urothelial carcinomas. Higher grade papillary urothelial carcinomas, infiltrating urothelial and squamous carcinomas, and in situ urothelial and squamous carcinomas demonstrated abnormal staining patterns for involucrin that are described. Foci of squamous differentiation in adenocarcinomas and other epithelial malignancies stained intensely for involucrin. Brenner tumours of the ovary and Walthard rests of the fallopian tube, lesions of uncertain histogenesis but possibly urothelial-related, also stained for involucrin. Results of this study suggest that involucrin is a sensitive and specific marker for squamous and urothelial differentiation, staining patterns for involucrin may be helpful in distinguishing benign from malignant urothelial and squamous lesions, and presence of involucrin may be helpful in determining the histogenesis of selected lesions.

Carcinoma in Situ↗

PubMed1995

Body mass index: a measure of fatness or leanness?

The relationship between body fat and stature-adjusted weight indices was explored. Assuming the term height2 is a valid indicator of a subject's lean body mass, height2/weight was shown to be an accurate measure of percentage lean body mass and, as such, a better predictor of percentage body fat than the traditional body mass index (BMI; weight/height2). The name, lean body mass index (LBMI), is proposed for the index height2/weight. These assumptions were confirmed empirically using the results from the Allied Dunbar National Fitness Survey (ADNFS). Using simple allometric modelling, the term heightp explained 74% of the variance in lean body mass compared with less than 40% in body weight. For the majority of ADNFS subjects the fitted exponent from both analyses was approximately p = 2, the only exception being the female subjects aged 55 years and over, where the exponent was found to be significantly less than 2. Using estimates of percentage body fat as the dependent variable, regression analysis was able to confirm that LBMI was empirically, as well as theoretically, superior to the traditional BMI. Finally, when the distributional properties of the two indices were compared, BMI was positively skewed and hence deviated considerably from a normal distribution. In contrast, LBMI was found to be both symmetric and normally distributed. When height and weight are recorded in centimetres and kilograms respectively, the suggested working normal range for LBMI is 300-500 with the median at 400.

Actuarial Analysis↗

PubMed1989

Effects of interferon-gamma on expression of cell surface receptors for collagen and deposition of newly synthesized collagen by cultured human lung fibroblasts.

We used cultured human diploid lung fibroblasts as a model system to examine the effects of recombinant IFN-gamma on synthesis of collagen, matrix deposition of newly synthesized collagen, and the expression of cell surface receptors for collagen. Using [3H]proline-labeled cells we found that IFN-gamma resulted in dose-dependent inhibition of fibroblast collagen synthesis. Pulse-chase experiments to analyze compartmentalization of newly synthesized collagen showed that the decrease in collagen synthesis was confined to the soluble pool of procollagen in the medium, while extracellular matrix associated collagen was not changed, indicating that a larger proportion of newly synthesized collagen was deposited into the matrix in IFN-gamma exposed fibroblasts (34.2 vs. 25.3%). This increase in the efficiency of collagen matrix deposition was associated with enhanced expression of a cell surface receptor for collagen as detected by indirect immunofluorescence labeling and analysis by flow cytometry. Fibroblasts (IMR-90) cultured in the presence of IFN-gamma (1,000 U/ml) exhibited a twofold increase in mean linear fluorescence intensity compared with cells cultured under control conditions. The distribution of log fluorescence intensity in both control and IFN-gamma exposed cells was normally distributed about the mean, indicating that discrete subpopulations with respect to receptor expression were not present. Increased fluorescence intensity and log normal distribution of fluorescence intensity also were identified in IFN-gamma-treated lung fibroblasts from a normal adult individual and two strains obtained from patients with pulmonary fibrosis. These results indicate that IFN-gamma modulates fibroblast collagen matrix deposition as well as collagen synthesis. The associated increase in collagen receptors suggests that cytokine-mediated modulation of the cell surface maybe a contributing factor in regulation of fibroblast collagen accumulation in the extracellular matrix or in cellular interaction with collagen-containing matrix. Such an effect could modulate the interaction of fibroblasts with extracellular matrix at sites of inflammation and play an important role in the remodeling of matrix during repair from tissue injury.

Adult↗

PubMed2005

Effect of correlation on combining diagnostic information from two images of the same patient.

We have shown previously, in the context of computer-aided diagnosis (CAD), that information derived from multiple images of the same patient can be used to improve diagnostic performance. In that work, we ignored the correlation among multiple images of the same patient. In the present study, we investigate theoretically, within the framework of receiver operating characteristic (ROC) analysis, the effect of correlation on three methods for combining quantitative diagnostic information from two images: taking the average, the maximum, and the minimum of a pair of normally distributed decision variables. We assume, as in our previous work, that the quantitative diagnostic information obtained from the two images of a given patient can be transformed monotonically to two latent decision variables that are normally distributed. Similar to the situation of uncorrelated images, we found that (1) the average always improves the area under the ROC curve (AUC) compared to the single-view image; (2) the maximum and the minimum can also, but not always, improve the AUC; and (3) each method can be the best method in certain situations. In addition, as the correlation strength increases, the average performs the best less often, whereas the maximum and the minimum perform the best more often. These theoretical results are illustrated with analysis of a mammography study.

Area Under Curve↗

PubMed1986

Exaggerated response to gentamicin-induced nephrotoxicity in Sprague-Dawley rats: identification of a highly sensitive outlier population.

A number of factors have been shown to predispose patients treated with aminoglycosides to nephrotoxicity. In a previous study in our laboratory investigating the interaction of prior renal dysfunction with gentamicin toxicokinetics, 9.4% of rats in all treatment groups were relatively more sensitive to gentamicin-induced nephrotoxicity. To determine if these outliers had an underlying disease or physiological abnormality, serum was collected from 99 Sprague-Dawley rats prior to daily treatment with 75 mg/kg gentamicin for seven days. Urea nitrogen, creatinine, Na, K, Ca, Mg, P, total protein, albumin, aspartate transaminase, serum osmolality, total white and red blood cell count, hematocrit, hemoglobin, blood gases, and thyroxine were measured. Blood was collected one and four hours after the first dose of gentamicin for pharmacokinetic analysis. Elevations in post-treatment creatinine and nitrogen were significantly greater in the outliers (4.10 +/- 0.24 mg/dl (n = 12) vs 1.92 +/- 0.06 mg/dl (n = 87) and 146.4 +/- 7.2 mg/dl (n = 12) vs 71.5 +/- 2.0 mg/dl (n = 87); both p = 0.0001) and served as criteria for identifying this subgroup. Post-treatment creatinine and urea nitrogen were not normally distributed in the entire study population. However, when the population was divided into normal and sensitive subgroups, both subgroup values were normally distributed. The gentamicin pharmacokinetic profiles were similar in both groups. Postmortem histopathology showed significant increases in tubular casts and tubular necrosis (p = 0.01) in the sensitive rats, compared to the normally responding subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗