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Biomedical subjects

J D Mahan

Publications and source records attributed to J D Mahan.

At least 19 recordsLinked to original sources
PubMed2004

The Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry: design, development and data assessed.

Many issues plague the pediatric ARF outcome literature, which include data only from single center sources, a relative lack of prospective study, mixture within studies of renal replacement therapy modality without stratification and inconsistent use of methods to control for patient illness severity in outcome analysis. Since January 2001, the Prospective Pediatric CRRT (ppCRRT) Registry Group has been collecting data from multiple United States pediatric centers to obtain demographic data regarding pediatric patients who receive CRRT, assess the effect of different CRRT prescriptions on circuit function and evaluate the impact of clinical variables on patient outcome. The aim of the current paper is to describe the ppCRRT Registry design, review the decision process and rationale for the options chosen for the ppCRRT format and discuss the analysis plan and future projects envisioned for the ppCRRT Registry.

Acute Kidney Injury↗
PubMed2000

Infarction of the choledochus, liver, gallbladder, and pancreas: a unique complication of the hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) is associated with multiple nonrenal manifestations. A unique case is described of a 3-year-old boy who presented with a classic diarrheal prodrome followed by massive necrosis of the biliary tree and common bile duct, pancreas, and the left lobe of his liver. This complication of HUS has not been reported in the English-language literature.

Child, Preschool↗
PubMed2000

Proximal tubular epithelial hyperplasia in patients with chronic glomerular proteinuria.

BACKGROUND: Proteinuria is known to affect the proximal tubular epithelial structure and function. The present study tested the hypothesis that chronic proteinuria leads to hyperplasia of proximal tubular epithelium. METHODS: This hypothesis was tested by morphometric analysis of the renal biopsy specimens in two groups of patients. Group A (N = 15) was composed of patients with chronic glomerular proteinuria who, for clinical indications, underwent renal biopsy of their native kidneys on two separate occasions. The proteinuria was sustained during the first and second renal biopsies in all but two of the patients with minimal change nephrotic syndrome who experienced transient remission. Group B (N = 10) was composed of patients with little or no proteinuria who underwent renal biopsy because of unexplained hematuria and whose renal biopsy showed only thin glomerular basement membrane (GBM) disease. RESULTS: In Group A, the mean number of epithelial cell nuclei per proximal tubule cross-section increased significantly from the first to the second renal biopsy (11.0 +/- 2.7 vs. 13.0 +/- 2.2, P = 0.005, paired t-test). Also, those with severe proteinuria showed proximal tubules with reactive epithelium (large pale nuclei with a high nucleus to cytoplasm ratio) and marked hyperplasia (double and triple layers of epithelium). Such changes were not seen in group B renal biopsies. Compared with group A biopsies, group B biopsies showed a lower mean value for proximal tubular epithelial cell nuclei per tubular cross-section (P = 0.056) and a higher mean proximal tubular volume (P = 0.049). As a consequence, the mean number of nuclei per relative tubular volume was significantly greater in group A compared with group B (0.55 +/- 0.14 vs. 0.40 +/- 0.06, P = 0.003, by Wilcoxon rank sum). CONCLUSIONS: Chronic heavy proteinuria is associated with hyperplasia of proximal tubular epithelium and contraction of proximal tubular volume. These events may impair glomerular filtration and represent another mechanism of progression of renal disease.

Adolescent↗
PubMed1999

Efficacy of amlodipine in pediatric patients with hypertension.

We designed a study to determine the efficacy and safety of amlodipine given once daily in the pediatric population. Twenty-one patients (mean age 13.1 years) with either essential (n=160) or renal (n=5) hypertension, and newly diagnosed (n=15) or poorly controlled or intolerant on existing antihypertensive therapy (n=6), were included. Patients received amlodipine once daily at a starting mean dose of 0.07+/-0.04 mg/kg per day. The total daily dose of amlodipine was increased 25%-50% every 5-7 days if the mean home blood pressure measurements (HBPM) were above the 95th percentile for age and gender. A baseline followed by a repeat 24-h ambulatory blood pressure monitor study (ABPM) was performed in 20 patients when the mean HBPM was below the 95th percentile goal. The mean titrated dose required to control BP was 0.29+/-0.11 mg/kg per day for those < 13 years, 0.16+/-0.11 mg/kg per day for those > or = 13 years, 0.23+/-0.14 mg/kg per day for essential, hypertension and 0.24+/-0.13 mg/kg per day for renal hypertension. The ABPM demonstrated that amlodipine provided effective BP control as primary therapy in 14 essential patients. Adverse effects included fatigue (n=6), headache (n=5), facial flushing (n=4), dizziness (n=3), edema (n=3), abdominal pain (n=3), chest pain (n=2), nausea (n=1), and vomiting (n=1). Quality of life appeared to improve during therapy. Amlodipine was an effective once daily antihypertensive agent with an acceptable safety profile. Higher doses of amlodipine were required for younger patients, and monotherapy was effective in patients with essential hypertension.

Administration, Oral↗
PubMed1997

Evaluation of hematuria, proteinuria, and hypertension in adolescents.

Signs or symptoms of renal disease in adolescents deserve prompt attention and appropriate evaluation. Adolescents are susceptible to a variety of urinary tract disorders. The key issue in the evaluation of hematuria or proteinuria in adolescents is the existence of concomitant signs of renal disease. For isolated hematuria or proteinuria, demonstration of persistence and a reasoned evaluation are in order. Hypertension in adolescents must be carefully documented and, when present, considered seriously. The fact that most teens with persistent elevated blood pressures have essential hypertension is still a great concern because for most of these adolescents the hypertension will be lifelong and, if left untreated, can be associated with significant morbidity and mortality in the adult years.

Adolescent↗
PubMed1997

Effect of enalapril therapy on glomerular accumulation of immune complexes and mesangial matrix in experimental glomerulonephritis in the nonhuman primate.

The present study is a prospective, controlled, blinded trial of enalapril therapy in experimental immune complex (IC)-mediated glomerulonephritis (GN) in the nonhuman primate (cynomolgus monkey [CYN]). Two groups of CYNs were studied: those with established GN (study A) and those in which GN was being induced (study B). In study A, 12 CYNs had GN established by 8 or 10 weeks of daily intravenous infusion of bovine gamma-globulin (BGG). These CYNs were then assigned to either 4 weeks of daily oral enalapril therapy (n = 6) or daily oral placebo therapy (n = 6). The daily BGG infusions were continued during the 4 weeks of enalapril or placebo therapy. At the start of the enalapril/placebo protocol, the two groups were similar with respect to proteinuria and level of precipitating antibody to BGG, which determined the daily BGG dose. Renal biopsy was performed in each CYN at the start and end of the 4-week period of enalapril/placebo protocol. In study B, 15 normal CYNs were immunized to BGG over a period of 4 weeks. The CYNs were then assigned to daily oral enalapril therapy (n = 8) or placebo therapy (n = 7) based on level of precipitating antibody to BGG. At this point, daily intravenous BGG was begun along with daily enalapril or placebo for 8 weeks. Renal biopsy was performed in each CYN before and at the end of this 8-week period. In study A, enalapril therapy was associated with a significant decrease in mesangial matrix volume (mean change, -27.7%; P = 0.031) and a trend toward decreased mesangial matrix deposits (mean change, -34.1%; P = 0.188). By contrast, in CYNs receiving placebo therapy, mesangial matrix volume increased compared with the enalapril group (P = 0.002) and mesangial deposits were unchanged. In study B, both the enalapril and placebo groups showed significant increases in mesangial matrix volume, mesangial deposits, mesangial cell volume, and capillary wall deposits during the 8 weeks of daily BGG infusion. However, none of the differences between the groups achieved statistical significance. Changes in mesangial cell volume and capillary wall deposits were also evaluated in study A and study B, but were not found to be different between the enalapril and placebo groups. In both study A and study B, blood pressure was lower in the enalapril groups. In conclusion, in the initial phase of IC-GN induction (0 to 8 weeks), enalapril therapy does not significantly influence the glomerular accumulation of mesangial matrix or immune deposits. However, in established IC-GN (after 8 weeks of GN induction), enalapril therapy significantly decreases the further accumulation of mesangial matrix and may decrease the further accumulation of mesangial deposits. Whether this benefit of enalapril therapy was related to lower blood pressure or to other effects of angiotensin-converting enzyme (ACE) inhibition was not determined in this study.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effects of TNF alpha on verocytotoxin cytotoxicity in purified human glomerular microvascular endothelial cells.

In the pathogenesis of the hemolytic uremic syndrome (HUS), endothelial damage of glomeruli and arterioles of the kidney appears to play a central role. Previous studies have shown that verocytotoxin-1 (VT-1) cytotoxicity on human vein endothelial cells require additional stimuli, in particular the inflammatory mediator tumor necrosis factor alpha (TNF alpha). In this study the effects of VT on human glomerular microvascular endothelial cells (GMVEC) were examined. A reproducible method was developed for the isolation and purification of large numbers of highly purified GMVEC. The obtained GMVEC were over 99% pure; their endothelial origin was demonstrated by the expression of the endothelial antigens von Willebrand factor, EN-4, PECAM-1 and V,E-cadherin. Upon stimulation with TNF alpha the cells expressed the endothelial-specific adhesion molecule E-selectin. A limited number of fenestral structures was observed by scanning electron microscopy (SEM), suggesting glomerular origin of the endothelial cells. Cytotoxicity of VT-1 to GMVEC was evaluated by determination of the number of viable adherent cells and by assay of overall protein synthesis after exposure to varying concentrations of VT-1. In non-stimulated GMVEC, cytotoxicity of VT-1 was inversely related to the degree and duration of confluence, subconfluent cells being the most sensitive. In highly confluent GMVEC, VT cytotoxicity required pre-exposure of the cells to the inflammatory mediator TNF alpha, which induced an increase in the number of VT receptors on GMVEC. Thin layer chromatography of extracted glycolipids from the GMVEC showed binding of VT-1 to globotriaosylceramide (Gb3), known to be the functional receptor for VT. There were no major differences in protein synthesis inhibition with equal concentrations VT-1 and VT-2. In conclusion, in this study we provide a reproducible method to isolate, purify and culture well characterized human GMVEC on a routine basis. In vitro studies with these GMVEC demonstrate that VT cytotoxicity depends on the degree of confluence and the additional preexposure to the inflammatory mediator TNF alpha. These observations provide further insight into the complex events that may occur in glomeruli in the pathogenesis of HUS.

Bacterial Toxins↗
PubMed1996

A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant), or oral contraceptives.

OBJECTIVE: To examine bone density among adolescents receiving different forms of hormonal contraception along with that of control subjects. METHODS: Baseline and 1-year measures of lumbar vertebral bone density were obtained in girls receiving depot medroxyprogesterone acetate (Depo-Provera) (n = 15), levonorgestrel (Norplant) (n = 7), or oral contraceptives (n = 9) and in girls receiving no hormonal treatment (n = 17). In a subsample of Depo-Provera users (n = 8), Norplant users (n = 3), and control subjects (n = 4), bone density measurements were repeated after 2 years. Bone density was measured by dual-energy x-ray absorptiometry. RESULTS: Body mass indexes, level of pubertal development, substance use, and reproductive histories were not significantly different among the groups. More black girls were represented in the initial Depo-Provera group (p < 0.02), girls in the Norplant group exercised more hours per week (p < 0.02), and control subjects were older (p < 0.01) than those in the other groups. These variables did not significantly affect bone density results. After 1 year, bone density decreased 1.5% in Depo-Provera users, compared with increases of 2.5% in Norplant users, 1.5% in oral contraceptive users, and 2.9% control subjects (p < 0.02). After 2 years, bone density increased a total of 9.3% in Norplant users and 9.5% in control subjects but decreased a total of 3.1% in Depo-Provera users (p < 0.0001). CONCLUSION: These data suggest that Depo-Provera may, at least temporarily, suppress the expected skeletal bone mineralization in adolescents, whereas Norplant and oral contraceptives are associated with the expected increase in bone density in this population.

Adolescent↗
PubMed1995

Diabetic nephropathy in an aerobically trained rat model of diabetes.

The purpose of this study was to determine the effects of aerobic training on indices of glycemic control, blood pressure, serum lipids, and diabetic nephropathy (DN) in an animal model of insulin deficient diabetes mellitus. Thirty-four male Sprague-Dawley rats made diabetic with streptozocin were randomly assigned to a trained group or a sedentary group. Fifteen sedentary-nondiabetic rats served as a control group. The animals were trained on a treadmill at 18 m.min-1, 8 degrees incline for 120 min.d-1, 5 d.wk-1. Blood and 24 h urine collections were obtained at various intervals throughout the study. At 21 wk of age systolic blood pressure was measured and kidney tissue was obtained for light and electron microscopy. Analysis of variance was used to detect differences among the groups (P < or = 0.05). The diabetes produced in this investigation resulted in hyperglycemia, increased urine albumin and total protein excretion, elevated systolic blood pressure, increased fractional volume of the mesangium, and widening of the glomerular basement membrane in the sedentary-diabetic animals. Aerobic training significantly reduced the increase in fractional volume of the mesangium and fructosamine. Most importantly, aerobic training did not augment the renal damage seen in DN.

Animals↗
PubMed1994

Complications of intestinal augmentation and substitution cystoplasty.

The content of these papers has been heavily weighted towards reconstructions performed utilizing segments of stomach. This was not done to place a value judgment on this type of reconstruction, rather it helps establish an awareness of: (1) potentially serious metabolic and gastrointestinal complications not previously reported in children and (2) particularly frequent symptomatic disturbances collectively included in the hematuria-dysuria syndrome. Recognition of problems specifically associated with a certain type of intestinal segment, as well as complications generally accompanying any form of intestinal reconstruction, will hopefully provide pediatric urologists and nephrologists with a better understanding of the issues that must be addressed in using these newer surgical techniques and focus attention on the specific indications and contraindications for incorporating intestinal segments into the urinary tract. Although long-term follow-up information still remains sparse, it appears that regular surveillance programs are required and both pediatric nephrologists and urologists need to be part of these programs.

Child↗
PubMed1994

Angiotensin-converting enzyme inhibition partially prevents diabetic organomegaly.

The present study was conducted to evaluate whether captopril prevents the organomegaly and accumulation of matrix proteins that normally accompanies the diabetic state. The following groups of rats were studied: normal rats, normal rats treated with captopril (30 mg/kg/d orally), streptozotocin diabetic rats, and diabetic rats treated with captopril. All rats were killed at 10 weeks for histologic and morphometric evaluation of tissues. Compared with the normal rats, the diabetic rats demonstrated significant hepatomegaly, nephromegaly, and cardiomegaly, and the increase in organ size was directly related to increasing levels of protein glycosylation. The development of organomegaly was partially prevented by captopril. We determined by morphometry that the hepatomegaly seen in the diabetic rats was due to an increase in cell size and number, while the nephromegaly seen in the diabetic rats was due to an increase in tubular and glomerular cell size and is associated with glomerular hypertrophy. Captopril prevented the development of hepatic and renal cell hypertrophy and glomerular hypertrophy. These effects of captopril were not associated with detectable changes in body weight or levels of glucose, protein glycosylation, glycosuria, or renal histologic changes secondary to glycosuria. The diabetic rats demonstrated significant glomerular mesangial matrix expansion, and captopril treatment partially prevented that expansion. In conclusion, captopril prevents, in part, the development of organomegaly in diabetic rats, and this effect is due mainly to the prevention of the development of cellular hypertrophy. The present findings are most consistent with a direct effect of captopril on cell metabolism during diabetes mellitus.

Analysis of Variance↗
PubMed1994

Effect of chronically increased erythrocyte complement receptors on immune complex nephritis.

Experimental studies in humans and other primates have shown that the erythrocyte (E) complement receptor Type 1 (CR1), which is unique to the primate, plays an important role in clearing immune complexes (IC) from the circulation by binding C3b/C4b opsonized immune complexes and carrying the IC to liver and spleen for disposal. The results of these acute experiments suggest that increasing E-CR1 levels chronically should protect against IC-mediated glomerulonephritis (IC-GN) induced by chronic formation of IC in the circulation. In the present study this hypothesis was tested in the cynomolgus monkey (CYN). IC-GN was induced by daily bolus intravenous infusion of BGG into immunized CYN for 8, 10, or 14 weeks. Prior to and during the daily bolus infusions of BGG, sustained differences in E-CR1 levels were achieved between the experimental group (increased E-CR1 levels) and the control group (maintained or decreased E-CR1 levels), by one of two methods: (1) Twice weekly exchange transfusion. The CYN donors were blood type compatible with the recipients and had either constitutive high E-CR1 expression (3,000 to 5,000 CR1/E) or constitutive low E-CR1 expression (< 100 CR/E). The recipients of the exchange transfusions (N = 2) had constitutive mid-level E-CR1 expression. (2) Weekly phlebotomy (PL) or sham PL. CYN with mid-level E-CR1 expression were randomly assigned to receive weekly either PL (causing increased E-CR1 expression by stimulating erythropoiesis) (N = 8) or sham PL (which has no effect on E-CR1 expression (N = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Platelet involvement in experimental immune complex-mediated glomerulonephritis in the nonhuman primate.

Abundant glomerular platelet deposition is a hallmark of certain animal models of immune complex (IC)-mediated glomerulonephritis (GN). By contrast, conspicuous platelet deposition is uncommon in the IC-GN seen in humans. This could result from intrinsic differences between human and animal platelets, which are known to be present. To assess whether abundant glomerular platelet deposition can occur in humans with IC-GN, the present studies were undertaken in nonhuman primates (cynomolgus monkeys, CYN), with active experimental IC-GN induced by 12 weeks of daily intravenous infusion of bovine gamma globulin (BGG). CYN are appropriate for these studies because, like humans, CYN platelets do not express the C3b receptor but do express receptors for the Fc region of IgG (FcR gamma II). Furthermore, in this model of IC-GN, which is indistinguishable from IC-GN seen in humans, it is possible to time the biopsy to coincide with a period of peak activity of the GN. The present studies proceeded as follows: ten CYN were studied before and after intravenous infusion of BGG sufficient to achieve conditions near antigen/antibody equivalence for circulating precipitating antibody to BGG. The infusion of BGG, which was given over 10 minutes, resulted in an acute reduction in circulating platelets (mean 43% +/- 5 SE, P < 0.001). However, renal biopsies performed before and five minutes after the acute reduction in circulating platelets showed that relatively few of the platelets removed from the circulation lodged in glomeruli (platelets/glomerular cross section: 0.2 +/- 0.06 before BGG vs. 0.88 +/- 0.31 after BGG, P = 0.035). In five of the CYN studied under the above protocol, autologous platelets were labeled with 111In and reinfused into the CYN just prior to the BGG infusion. These studies confirmed the paucity of platelet deposition in kidney but showed major uptake of the 111In-labeled platelets by liver and spleen (mean +/- SE 111In CPM/mg of tissue: kidney cortex 18 +/- 8, liver 132 +/- 42, and spleen 808 +/- 127, P = 0.038, comparing kidney to liver or spleen by paired t-test). Thus, the platelets removed from the circulation were taken up at the sites which are also the principal sites of IC uptake (liver and spleen), and over the time interval that coincides with the period of maximum uptake of IC by liver and spleen, after BGG infusion. In vitro studies, discussed herein, showed that BGG anti-BGG IC bind to CYN platelets via FcR gamma II.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Cefotaxime and metabolite disposition in two pediatric continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: To characterize the pharmacokinetics of cefotaxime and desacetylcefotaxime in pediatric patients undergoing continuous ambulatory peritoneal dialysis (CAPD) after intraperitoneal administration of cefotaxime. DESIGN: Case series. SETTING: Ambulatory children from Children's Hospital nephrology clinic, Columbus, Ohio. PATIENT POPULATION: Two adolescents without peritonitis. METHODS: A single intraperitoneal dose of cefotaxime 500 mg per 1 L dianeal was given during CAPD. Cefotaxime and desacetyl-cefotaxime were measured in plasma, urine, and dialysate by HPLC. RESULTS: Maximum plasma concentration (Cmax) of cefotaxime was 11.94 and 13.08 mg/L and that of desacetylcefotaxime 5.73 and 5.33 mg/L. Time to reach maximum concentration (Tmax) of cefotaxime was 2.22 and 4.08 h, and that of desacetylcefotaxime was 5.33 and 5.73 h after instillation of the intraperitoneal cefotaxime dose. Systemic absorption of cefotaxime was 56.6 and 64.8 percent. Total clearance of cefotaxime was 62 and 79 mL/min/1.73 m2. Nonrenal clearance accounted for nearly 95 percent; renal and CAPD clearance contributed approximately 5 percent of the total clearance. Renal and CAPD clearance measurements of desacetylcefotaxime were similar to those for cefotaxime. Cefotaxime half-life was 1.83 and 2.49 h and desacetylcefotaxime half-life was 8.14 and 11.0 h. CONCLUSIONS: Cefotaxime was well absorbed and therapeutic serum concentrations were achieved after intraperitoneal administration. Renal and CAPD clearances for cefotaxime and desacetylcefotaxime were low. Cefotaxime nonrenal clearance was unaffected. Further studies are needed to establish appropriate intraperitoneal dosing guidelines of cefotaxime in pediatric CAPD patients.

Adolescent↗
PubMed1991

Experimental immune complex-mediated glomerulonephritis in the nonhuman primate.

This study was undertaken to develop a model of immune complex (IC)-mediated glomerulonephritis (GN) in the nonhuman primate that could be used in subsequent studies to examine critically the role of the erythrocyte complement receptor (E-CR) in the pathogenesis of IC-mediated disease. Cynomolgus monkeys were chosen for study because they constitutively express E-CR levels that are either less than, equal to, or greater than that seen in normal man. After immunization with bovine gamma globulin (BGG), the GN induction protocol was begun in 10 cynomolgus by initiating daily i.v. administration of BGG in amounts sufficient to achieve or exceed antigen/antibody equivalence (assessed by the quantitative precipitin assay) for precipitating antibody present in the plasma volume. We found that within eight weeks of daily BGG administration of all the cynomolgus developed IC-mediated GN, irrespective of the initial E-CR level of the animals. However, the high E-CR cynomolgus tended to receive the higher BGG doses because of higher initial antibody levels to BGG. When the total number of glomerular deposits (determined by morphometric studies) per total BGG dose for each animal was plotted against the initial CR/E of that animal, there was a tendency for the animals with higher CR/E levels to have a lower number of glomerular deposits/BGG dose (r = 0.62, P = 0.06). Also, the total number of glomerular deposits correlated with the severity of the GN. During the early weeks of the GN induction protocol, the IC that formed in vivo (assessed by infusion of 125I-BGG) bound in large amounts to the circulating erythrocytes of the cynomolgus with medium or high E-CR levels. However, when tested after the onset of heavy proteinuria, which occurred between weeks 5 and 8 of daily BGG administration, the IC that formed in the circulation bound only poorly to circulating erythrocytes. By this time the E-CR levels had declined to 43 +/- 9% of initial values (P less than 0.01). This study demonstrates that: 1) A workable model of IC-mediated GN has been developed in the nonhuman primate. 2) During the induction of GN, CR/E and the ability of the erythrocyte to bind IC in vivo are decreased significantly. This suggests that an intact E-CR system could play a role in the protection against IC-mediated disease. However, further study will be needed to test that hypothesis critically. The present model should be useful in such studies.

Animals↗
PubMed1991

Pharmacokinetics of cefotaxime and its active metabolite in children with renal dysfunction.

We studied cefotaxime (CTX) and desacetylcefotaxime (dCTX) pharmacokinetics in 19 children (ages, 7 to 16 years) with various degrees of renal function. The patients were stratified into three groups according to 24-h urinary creatinine clearance (CLCR) values: group I, CLCR greater than 80 ml/min/1.73 m2 (n = 7); group II, CLCR from 30 to 80 ml/min/1.73 m2 (n = 6); and group III, CLCR less than 30 ml/min/1.73 m2 (n = 6). A single 50-mg/kg dose of CTX was given intravenously to each patient after which blood and urine samples were collected and analyzed for CTX and dCTX by high-performance liquid chromatography. Safety was assessed by pre- and poststudy blood chemistries and urinalysis. The mean values for total body clearance of CTX for groups I, II, and III were 158.1 +/- 38.8, 118.3 +/- 50.8, and 84.8 +/- 11.7 ml/min/1.73 m2, respectively (P less than 0.01). Renal clearance also decreased across groups, I, II, and III, with values of 77.5 +/- 20.2, 41.3 +/- 18.5, and 11.4 +/- 7.7 ml/min/1.73 m2 respectively (P less than 0.0001). Both the CTX fraction nonrenally cleared and elimination half-life increased with decreasing renal function. The CTX volume of distribution at steady state was not affected by renal disease. The renal clearance values of dCTX were 146.4 +/- 71.4, 64.5 +/- 32.1, and 14.4 +/- 8.7 ml/min/1.73 m2 for groups I, II, and III, respectively (P less than 0.0004). Elimination half-life values were 2.04 +/- 0.39, 3.87 +/- 1.93, and 6.19 +/- 3.22 h for the respective groups (P less than 0.006). Both the maximum concentration of dCTX in plasma and time to reach the maximum concentration of dCTX in plasma were increased with decreased CLCR. The results of this study indicate that dosage adjustment may be necessary for CTX in children with renal dysfunction. On the basis of the pharmacokinetics and antimicrobial activities of the parent drug and its metabolite, dosage reductions of 25 to 50% in children with moderate renal impairment (CLCR from 30 to 80 ml/min/1.73 m2) and 50 to 75% in children with severe renal impairment (CLCR < 30 ml/min/1.73 m2) are recommended.

Adolescent↗
PubMed1991

Bone mass in healthy children: measurement with quantitative DXA.

Dual-energy x-ray bone densitometry was used to study the lumbar vertebral bone mass in 218 healthy children (134 girls and 84 boys) aged 1-19 years. Vertebral bone mass increased with weight, age, and pubertal Tanner stage. Results of multiple regression analyses showed that Tanner stage and weight were the best predictive indicators of bone mass and bone mineral density. The influences of age, sex, race, physical activity, and diet were not significant when Tanner stage and weight were controlled. Two tables of predictive intervals for lumbar vertebral bone mineral density in healthy children (one based on Tanner stage and weight; the other, on age and weight) are presented. With normative data now available for use with this precise technique, clinicians can better detect abnormal bone mineral density in children and evaluate changes in mineralization over time.

Absorptiometry, Photon↗