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Biomedical subjects

E S Moore

Publications and source records attributed to E S Moore.

At least 19 recordsLinked to original sources

Serum immunologic markers in multiple sclerosis patients on continuous combined therapy with beta-interferon 1a, prednisone and azathioprine.

Break-through symptoms (BTS) in multiple sclerosis (MS) patients on beta-interferon (beta-IFN) monotherapy are most frequently treated with a brief administration of steroids. Here, we report the results of monitoring serum immunologic markers recorded at three-month intervals for 1.5 years in responders to beta-INF 1a (Avonex) monotherapy (n =21) and MS patients placed on Avonex with prednisone (n =83) and Avonex, prednisone and azathioprine (AZA) (n =21) because of BTS. Compared to 23 healthy controls, patients on Avonex monotherapy and Avonex with prednisone, in individuals on Avonex, prednisone and AZA, a significant decrease in serum concentration of soluble intercellular adhesion molecule-1 (sICAM-1) (P=0.001) was established. Combined therapy with Avonex, prednisone and AZA was associated with a significant increase in the serum level of interleukin (IL)10 (P <0.001). Compared to Avonex monotherapy, combined therapy suppressed the serum level of IL12p40, antagonized elevation in the serum concentration of soluble IL2 receptor (sIL2R) and inhibited an increase in the serum soluble CD95 (sCD95) molecule. In patients studied, no significant differences in the serum level of IL18 and tumor necrosis factor-alpha (TNF-alpha) were established. These findings are important in understanding some of the immunoregulatory mechanisms induced by combined therapy in MS.

Adult↗

The subtle facial signs of prenatal exposure to alcohol: an anthropometric approach.

OBJECTIVES: The purpose was to demonstrate that an objective, multivariate case definition of fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (PFAS) can be derived by means of craniofacial anthropometry. STUDY DESIGN: Craniofacial measurements (n = 21) were taken of 100 individuals who had been exposed to alcohol before birth (41 FAS, 59 PFAS) and 31 members of a control group. Multivariate discriminant analysis was used to identify craniofacial measurements that best differentiated the 3 groups (FAS, PFAS, and control). RESULTS: Both the FAS and PFAS groups had a unique craniofacial phenotype that could be accurately discriminated from that of the control group. Stepwise discriminant analysis identified 6 craniofacial measurements that could differentiate individuals with and without prenatal alcohol exposure with 96% accuracy, 98% sensitivity, and 90% specificity. CONCLUSIONS: Individuals with FAS and PFAS have a distinctive facial phenotype that can be characterized anthropometrically. The phenotypic case definition could be used as a screening tool to identify individuals prenatally exposed to alcohol who do not exhibit a "classic" FAS phenotype but exhibit a more subtle craniofacial dysmorphia.

Adolescent↗

Urinary tract infection in children associated with idiopathic hypercalciuria.

OBJECTIVE: The aim of this study was to evaluate the association of symptomatic non-calculous idiopathic hypercalciuria (IH) with urinary tract infection (UTI) in children. MATERIAL AND METHODS: This was a retrospective case review of children who had urinary calcium excretion greater than 2 mg/kg/day or random urine calcium-creatinine ratio (UCa/UCr) greater than 0.18 mg/mg. RESULTS: One hundred and twenty-four consecutive children with clinical complaints and elevated urine calcium excretion were reviewed. Fifty children (40%) had UTI of which 39 (78%) had recurrent UTI. There was no difference in age between children with UTI and those without UTI. Twenty-four-hour urine calcium and random UCa/UCr were also not different. Only 4 children (8%) had renal stones whereas hematuria, abdominal pain and urine incontinence were frequent associated findings. Six of the children with recurrent UTI (15%) had an anatomical urinary tract abnormality. Therapy in all children consisted of increased fluid intake and reduction in diet sodium and oxalate; however, 14 of the 39 children with recurrent UTI (36%) required therapy with a thiazide diuretic. Recurrent UTI was abolished in 24 children, one child had a single recurrence and 4 children had no response to treatment. CONCLUSIONS: We propose that non-calculous IH may be an important contributing factor to recurrent UTI in children.

Adolescent↗

Recurrent abdominal and flank pain in children with idiopathic hypercalciuria.

OBJECTIVE: To evaluate the role of idiopathic hypercalciuria (IH) as a cause of recurrent abdominal pain (RAP) in children. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 124 children referred for various complaints who had 24-h urine calcium excretion greater than 2 mg/kg/d or random urine calcium-creatinine ratio greater than 0.18 mg/mg. RESULTS: Fifty-two children with various clinical complaints had RAP or flank pain. These comprised of 22 males and 30 females, 9 mo to 15.9 y of age, mean 6.7 +/- 3.5 y. A family history of urolithiasis was present in 50% of all the children. Only 6 of the 52 children with abdominal pain had renal stones. In addition to abdominal pain, 27 children had hematuria and 10 had urinary incontinence. Mild metabolic acidosis was present in three children, parathyroid hormone activity elevated in two and serum vitamin D activity was increased in nine. All children were treated with increased fluid intake and a reduction in dietary sodium and oxalate and some required treatment with thiazide and antispasmodics. Forty-five cases responded to treatment, 5 failed to improve from therapy, and 2, which were not followed up as patients, were not available. CONCLUSION: We describe 52 children with RAP or back pain due to IH and recommend that IH be considered in the differential diagnosis of RAP in childhood.

Abdominal Pain↗

Heterogeneity in Wiedemann-Beckwith syndrome: anthropometric evidence.

Wiedemann-Beckwith syndrome (WBS) has attracted a great deal of attention because of its genetic complexity. Individuals with WBS can be identified objectively by anthropometric analysis. Craniofacial anthropometry in conjunction with multivariate statistical analysis can be used to define patterns of variability that appear to relate to specific modes of inheritance that have been proposed for WBS. Our data on 19 affected individuals and their first-degree relatives indicate that the pattern of inheritance rather than the age of subjects may be responsible for the highly variable craniofacial phenotype found in individuals diagnosed with WBS.

Adolescent↗

Urinary calcium excretion in healthy Thai children.

The objective of this study was to determine age-specific reference values for urinary calcium/creatinine ratios (UCa/Cr) of children in southern Thailand. Non-fasting urine samples were collected from a random population of 488 healthy children (282 males, 206 females) ranging in age from 17 days to 15 years. Samples were divided into six groups by age. Subjects whose calcium levels exceeded the 95th percentile within each age group were classified as having hypercalciuria. Pyuria, hematuria, proteinuria, urinary sodium, and potassium levels in children with normal UCa/Cr were compared with levels in children with high UCa/Cr. The 95th percentiles for UCa/Cr (mg/mg) by age were: <6 months, 0.75; 6 months to <12 months, 0.64; 12 months to <2 years, 0.40; 2 years to <5 years, 0.38; 5 years to <10 years, 0.29; and 10 years to <15 years, 0.26. Pyuria, hematuria, and proteinuria were no more prevalent in the 22 children with hypercalciuria than in children with normal urinary calcium levels. Urinary sodium/creatinine ratios (UNa/Cr) and urinary sodium/potassium ratios (UNa/K) were correlated with UCa/Cr (r=0.41, P<0.0001 and r=0.24, P<0.0001, respectively). Urinary potassium/creatinine ratios (UK/Cr) were not (r=0.05, P>0.1)). Children with high UCa/Cr ratios also had higher UNa/Cr and UNa/K (5.6+/-7.1 vs. 2.6+/-1.5, P<0.001 and 5.4+/-2.3 vs. 2.5+/-0.23, P<0.05, respectively). The study established reference values for random, non-fasting UCa/Cr for healthy Thai children and indicated that urinalysis is not a good indicator of hypercalciuria.

Adolescent↗

Angiogenesis and macrophage activation in endometriosis.

Recent studies suggest that the symptoms associated with endometriosis are the result of local peritoneal inflammation. Increased concentrations of activated pelvic macrophages and lymphocytes and the elevated levels of specific cytokines and growth factors reviewed above support this hypothesis. The precise roles of these soluble factors are currently unknown, but we propose that a complex network of endometrial cytokines are normally regulated by hormones produced during the ovulatory cycle. Ectopic endometrial implants also are subject to these same endocrine cues. The secretion of these proinflammatory proteins by endometriosis lesions into the peritoneal microenvironment appears to cause a recruitment of capillaries and activated inflammatory cells to the implant. Future therapeutic strategies directed to ameliorate the inflammatory reaction associated with endometriosis should not ignore the likely physiological actions of many of the same bioactive molecules in normal eutopic endometrial function.

Cells, Cultured↗

Comparison of four enzyme immunoassays for detection of human T-cell lymphotropic virus type 2 antibodies.

Four licensed enzyme immunoassay (EIA) kits for the measurement of antibody to human T-cell lymphotropic virus (HTLV) type 1, one from Organon Teknika Corp. (OTC), one from Cambridge Biotech Corp. (CBC), and two from Abbott Laboratories (the 1993 modification [Abb 93] and the 2.0 version licensed in 1995 [Abb 95]), were evaluated for sensitivity and specificity in the detection of HTLV type 2 antibody, and the results were compared with those previously obtained with earlier kit versions. The CBC, Abb 95, Abb 93, and OTC kits had sensitivities of 99.7, 97.6, 96.8, and 96.2%, respectively, compared with sensitivities of 89.1 and 60% for the Abbott and CBC (previously DuPont) kits, respectively, licensed in 1988. Thus, the abilities of commercial kits to detect HTLV antibody have improved. The relative specificities of the CBC, Abb 95, Abb 93, and OTC kits with negative blood donor specimens that had been reactive with the 1988 CBC EIA kit were 92.9, 64.5, 78.8, and 62.6%, respectively. Compared with those of the 1988 versions, the specificity of the Abbott EIA has decreased and the specificity of the CBC kit has been significantly improved.

Blood Donors↗

Acute renal failure in a child associated with acyclovir.

A 9-year-old boy developed acute renal failure following intravenous acyclovir (30 mg/kg per day) administered for 6 days to treat herpetic encephalitis. Physical findings and urine output were normal, except for increasing blood urea nitrogen (BUN), serum creatinine and mild proteinuria. Acyclovir was discontinued. However BUN and serum creatinine continued to increase and peaked on the following day at 8.6 mmol/l of urea (24 mg/dl) and 194 mumol/l (2.2 mg/ml), respectively. Conservative treatment and hydration were carried out. The kidney function returned to normal within 1 week. The use of acyclovir when necessary in renal failure patients is discussed.

Acute Kidney Injury↗

Urinary incontinence due to idiopathic hypercalciuria in children.

Idiopathic hypercalciuria is known to cause many nonstone urinary tract disorders in childhood. In addition to being the most common cause of microhematuria in children, our study demonstrates that idiopathic hypercalciuria is also frequently associated with urinary incontinence of all types. Of 124 children evaluated for idiopathic hypercalciuria 28 (23%) had urinary incontinence. Of the 28 children 15 (54%) had nocturnal, 6 (21%) diurnal, and 7 (25%) nocturnal and diurnal incontinence. The random urinary calcium-creatinine ratio, which was used to screen for hypercalciuria, should be part of the initial evaluation for urinary incontinence in children. Diagnosis may be confirmed by quantitative urinary calcium excretion. Most urinary incontinence in children that is due to idiopathic hypercalciuria responds to a combination of general treatment for hypercalciuria or thiazide diuretics.

Adolescent↗

Effects of ethanol and delta 9-tetrahydrocannabinol on phencyclidine disposition in dogs.

A three-way crossover study was performed to determine the influence of delta 9-tetrahydrocannabinol (THC) and ethanol (EtOH) separately upon phencyclidine (PCP) disposition in dogs. Seven dogs were given three single dose treatments: 1.5 mg PCP kg-1 i.v., 1.5 mg PCP kg-1 i.v. with 0.4 mg kg-1 THC i.v., and 1.5 mg PCP kg-1 i.v. with 1.25 g EtOH kg-1 i.v. PCP was measured in plasma samples collected for 24 h after administration of each treatment, with several pharmacokinetic parameters calculated from the plasma concentration vs time data. The PCP serum Cls values were significant change in V beta or t1/2. EtOH did not induce significant changes in any PCP pharmacokinetic parameter, although mean Cls and V beta were increased. These results confirm the observed THC inhibition of PCP metabolism, and suggest that the enhanced pharmacologic action of PCP by THC may result from higher serum PCP concentrations. These results further suggest that enhanced PCP actions by acute EtOH administration may result from increased PCP distribution to the CNS.

Animals↗

Evaluation of three theophylline dosing methods in pediatric patients.

Three methods used for individualizing theophylline dosing were prospectively evaluated in 34 pediatric patients to compare the methods' ability to accurately predict steady-state serum theophylline concentrations (STCs) from non-steady-state data. Methods evaluated included a Bayesian weighted sum of squares regression program, an algebraic method developed by Chiou, and a commonly used population-based pediatric dosing algorithm. An expanded retrospective evaluation was also done to further compare the Bayesian and Chiou methods. Patients (aged 1-11 y) admitted to the hospital for acute bronchospasm refractory to inhaled beta agonists and with physician's orders to receive intravenous aminophylline were eligible for participation. Study patients received a 6-mg/kg loading dose aminophylline, followed by a 0.8-1.0 mg/kg/h constant aminophylline infusion. STCs were obtained 0.5 and 5.5 hours postinfusion. Subjects were randomized to one of three dosing method groups (Bayesian, Chiou, or pediatric algorithm). Doses were calculated using the assigned method to attain a target steady-state STC. Predictions from each dosing method were compared with actual serum concentrations for bias and precision. Additionally, analysis of fit-to-the-line-of-identity for predicted versus observed STCs was evaluated for each method. Precision of methods was also compared with regard to their ability to predict within 20 percent of their observed steady-state STC. Results from the prospective evaluation showed no significant difference between the three methods tested. Predicted STCs fell within 20 percent of their observed steady-state concentrations for 18 percent (2/11) of patients in the algorithm group, and 45 percent (5/11) of patients in the Chiou group and 17 percent (2/12) of the patients in the Bayesian group met this criterion. Retrospective analysis of all 34 patients demonstrated that the Bayesian and Chiou methods had similar bias and precision and no statistical difference was found between them. The results from this evaluation suggest that the pediatric dosing algorithm is equivalent in predictive bias and precision to the Bayesian and Chiou methods as well as in its ability to identify doses that result in steady-state STCs within 20 percent of their target values. Given the relative inaccuracy of these methods, cautious use of these techniques is recommended when evaluating non-steady-state STCs obtained from children during the acute stages of reactive airway disease.

Algorithms↗

Estimation of theophylline clearance during continuous arteriovenous hemofiltration.

Pharmacologic agents and other non-protein-bound compounds smaller than 5,000 daltons have the potential to be removed by continuous arteriovenous hemofiltration (CAVH). A proposed method for estimating drug clearance by CAVH (ClCAVH) equates ultrafiltrate clearance to the product of the sieving coefficient and the average ultrafiltration rate. This simplified approach for estimating ClCAVH would be a clinically useful method for calculating replacement doses, as it economizes on the sampling and analytical requirements associated with the conventional method. Presented are some theoretical considerations and a brief evaluation of the accuracy of this proposed method. The evaluation was conducted using an animal model whereby CAVH was performed in four male beagles. During the hemofiltration period, an i.v. bolus of theophylline, 6 mg/kg, was administered over 15 s. Samples for analysis of theophylline were collected from the arterial, venous, and ultrafiltrate ports at 0, 5, 15, 30, 45, 60, 90, 120, 180, 240, 360, and 480 min following dosage administration. The volume of ultrafiltrate produced during each collection interval was measured. Theophylline serum concentrations were determined by a high performance liquid chromatography assay. Statistically, the simplified method was found to result in significantly (p less than 0.05) larger estimates of ultrafiltrate clearance when compared to the conventional method. However, the average magnitude of difference was only 9% and does not constitute a clinically significant margin between the two methods.

Animals↗

The population pharmacokinetics of theophylline in neonates and young infants.

The population pharmacokinetics of theophylline were evaluated using 391 theophylline serum concentration measurements from 108 neonates and young infants (postnatal age 0-26 weeks), who received theophylline for the treatment of neonatal apnea. A one-compartment pharmacokinetic model with first-order elimination was used, with intravenous aminophylline and oral theophylline administration modeled as zero-order infusions. The effect of a variety of developmental and demographic factors on clearance (CL) and volume (V) were investigated. Hypothesis testing to evaluate potentially significant factors produced a final model in which clearance was based on weight (kg) raised to an exponential power and postnatal age (weeks), with CL (ml/hr) = 17.5 (weight)1.28 + 1.17 (postnatal age). Clearance was reduced by 12% for patients receiving parenteral nutrition. Volume of distribution in this population was adequately described using only weight, with V (L) = 0.858 L/kg. Bioavailability of orally administered drug was not significantly less than unity. Interindividual variability in clearance was modest, with a coefficient of variation for clearance of 16%. An estimate of interindividual variability in volume could not be obtained. As a measure of residual variability in theophylline serum concentrations, the coefficients of variation for theophylline serum concentrations of 5.0, 10.0, and 13.0 mg/L were found to be approximately, 25, 12, and 9%, respectively. The identification of influential patient factors and the quantification of their influence on theophylline disposition allow for a priori estimates of theophylline pharmacokinetic parameters in these patients.

Aging↗