Biomedical subjects

C N Ou

Publications and source records attributed to C N Ou.

At least 55 records · Page 3Linked to original sources

PubMed1995

Intestinal function and injury in acquired immunodeficiency syndrome-related cryptosporidiosis.

BACKGROUND/AIMS: The pathogenesis of the diarrhea in acquired immunodeficiency syndrome (AIDS)-related cryptosporidiosis is not known. The hypothesis of this study was that the intestinal dysfunction and injury are related to the number of organisms infecting the intestinal mucosa. The aim of this study was to study the influence of intensity of infection on intestinal function and injury in AIDS-related cryptosporidiosis. METHODS: In 16 patients with AIDS with intestinal Cryptosporidium infection, the intensity of infection was quantified by counting the total number of fecal oocysts excreted in 24 hours and by determining the percent of duodenal epithelium covered by organisms. Intestinal function was assessed by vitamin B12 absorption and serum D-xylose test. Intestinal injury was assessed by morphology of duodenal mucosa, differential urinary excretion of lactulose and mannitol, and fecal alpha 1-antitrypsin clearance. Measurements were repeated after treatment with paromomycin. RESULTS: Vitamin B12 and D-xylose absorption negatively correlated with intensity of infection. Villus atrophy occurred only in patients with oocyst excretion of > 10(8) oocyst/24 hours. Lactulose/mannitol urinary excretion ratio showed a positive correlation with intensity of infection. Intestinal function and injury improved in patients whose oocyst counts were reduced by treatment with paromomycin. CONCLUSIONS: Cryptosporidium infection in patients with AIDS causes malabsorption and intestinal injury in proportion to the number of organisms infecting the intestine.

AIDS-Related Opportunistic Infections↗

PubMed1995

Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type I.

Hereditary tyrosinaemia type I, a severe autosomal recessive metabolic disease, affects the liver and kidneys and is caused by deficiency of fumarylacetoacetate hydrolase (FAH). Mice homozygous for a FAH gene disruption have a neonatal lethal phenotype caused by liver dysfunction and do not represent an adequate model of the human disease. Here we demonstrate that treatment of affected animals with 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3-cyclohexanedione abolished neonatal lethality, corrected liver function and partially normalized the altered expression pattern of hepatic mRNAs. The prolonged lifespan of affected animals resulted in a phenotype analogous to human tyrosinaemia type I including hepatocellular carcinoma. The adult FAH-/- mouse will serve as useful model for studies of the pathophysiology and treatment of hereditary tyrosinaemia type I as well as hepatic cancer.

Amino Acid Metabolism, Inborn Errors↗

PubMed1994

Stability and activity of intravenous immunoglobulin with neonatal dextrose and total parenteral nutrient solutions.

OBJECTIVE: To determine in vitro the compatibility of reconstituted intravenous immunoglobulin (IVIG) (Gammagard, Baxter-Hyland) with five different neonatal and pediatric intravenous solutions in Viaflex polyvinyl chloride bags. DESIGN: In vitro compatibility study. INTERVENTIONS: Samples were taken at time = 0, 10, 30, 60, 90, and 120 minutes and at 4, 8, 12, and 24 hours and assayed for total immunoglobulin G content and antibodies to hepatitis B surface antigen. Type III group B Streptococcus (GBS) and opsonic activity for type III GBS were analyzed at time = 0, 60, and 120 minutes and 12 and 24 hours. All results were compared with those from pure IVIG. RESULTS: Our results demonstrate that mixing IVIG with intravenous solutions commonly used in the care of premature infants (dextrose 5% in water [D5W], D15W, D5W/NaCl 0.225%, and total parenteral nutrition [TPN]) does not significantly alter total immunoglobulin G concentrations or concentration of antibodies to hepatitis B surface antigen or type III GBS. As well, the in vitro functional activity for type III GBS of the IVIG, when mixed with these solutions for up to 24 hours, remained intact. An apparent decrease in bactericidal killing was seen with the IVIG/central TPN mixture. This apparent decrease was found to be an artifact of the high concentration of glucose (20 percent) in the solution. CONCLUSIONS: We propose that Gammagard may be mixed with these solutions through Y-site connections without loss of antibody content or functional activity of the IVIG.

Antibodies, Bacterial↗

PubMed1993

Loss of fumarylacetoacetate hydrolase is responsible for the neonatal hepatic dysfunction phenotype of lethal albino mice.

Mice homozygous for the c14CoS albino deletion die as neonates as a result of liver dysfunction. Previous mapping studies have associated this defect with a 310-kb fragment encoding the hepatocyte-specific developmental regulation locus (alf/hsdr-1). The gene encoding fumarylacetoacetate hydrolase (Fah), a metabolic enzyme that catalyzes the last step of tyrosine catabolism, also maps to the same deletion interval. To test whether the neonatal defects found in the albino deletion mutants are attributable to loss of Fah, and not to another gene mapping to the deletion, we have generated Fah mutant mice by gene targeting in embryonic stem cells. Fah-deficient mice die within 12 hr after birth from hypoglycemia and liver dysfunction. In addition, the same pattern of altered liver mRNA expression found in the albino deletion mutants was also found in affected animals. We conclude that the neonatal lethal and liver dysfunction phenotype of the alf/hsdr-1 deletion is entirely attributable to loss of Fah.

Albinism↗

PubMed1993

Use of intravenous rifampin in neonates with persistent staphylococcal bacteremia.

Ten neonates with persistent staphylococcal bacteremia (positive blood cultures for > or = 5 days despite appropriate antibiotic therapy) received intravenous (i.v.) rifampin in combination with vancomycin with or without aminoglycoside. Their mean birth weight and length of gestation were 900 g and 27 weeks, respectively. Their ages at the time of infection ranged from 6 to 64 days (mean, 26 days). The staphylococcal isolates were methicillin-resistant Staphylococcus aureus (five isolates), methicillin-susceptible S. aureus (two isolates), and coagulase-negative staphylococci (three isolates). The mean number of bacteremia days prior to administration of i.v. rifampin was 8.3 (range, 5 to 15 days), despite a mean peak vancomycin concentration of 33 micrograms/ml. The dosing of rifampin varied from 2.5 to 10 mg/kg of body weight every 12 h. The mean duration of the rifampin course was 9.7 days (range, 3 to 16 days). Of the 10 neonates, 8 (80%) had sterile blood cultures within 24 h, 1 (10%) had a sterile blood culture within 48 h, and 1 (10%) had a sterile blood culture within 5 days of being placed on i.v. rifampin. No adverse effects were noted in this small group of infants. Seven of the 10 neonates survived; three died from unrelated complications. The MIC ranges of amikacin, vancomycin, and rifampin for the isolates were 2.0 to 16, 0.5 to 2.0, and 0.0013 to 0.04 micrograms/ml, respectively. We also studied eight infants, with a mean age of 23 days, who were receiving i.v. or oral rifampin at a dose of 10 mg/kg/day. For i.v. administration, the peak serum concentration of rifampin (mean +/- standard deviation) was 4.02 +/- 1.22 microgram/ml. The mean trough level at 12 h postifution was 1.11 +/- 0.48 micrograms/ml. For oral administration, the concentrations of rifampin in serum ranged from 0.59 to 2.86 micrograms/ml (mean, 1.86 +/- 0.96 microgram/ml) at 2 h postingestion, increasing to a peak concentration of 2.8 micrograms/ml at 8 h postingestion. The mean 12-h postingestion level was 0.77 +/- 0.03 microgram/ml. From the study of this limited series of neonates, rifampin appears to be a safe and effective addition to therapy when staphylococcal bacteremia is persistent despite vancomycin treatment.

Amikacin↗

PubMed1993

Rapid analysis of hemoglobin variants by cation-exchange HPLC.

We investigated the use of a 3.5 x 0.46 cm HPLC column packed with 5-microns particles of porous (100 nm) silica coated with polyaspartic acid for hemoglobin analysis. A 13-min gradient was produced between two mobile phases. The method is capable of separating more than 35 commonly encountered hemoglobin variants within 12 min. Hemoglobin variants identified include Bart's, acetyl F, H, A1c, F, Camden, N-Baltimore, J-Baltimore, N-Seattle, Grady, Fannin-Lubbock, A G-Georgia, Lepore-Baltimore, P-Galveston, G-Coushatta, Lepore-Boston, E, Osu Christiansborg, A2, G-Philadelphia, Korle Bu, Russ, Richmond, D-Los Angeles, Deer Lodge, Montgomery, S, Q-Thailand, G-San Jose, A2', Hasharon, Q-India, Tampa, GS hybrid, C-Harlem, O-Arab, British Columbia, and C. Between-run precision of an in-house pooled hemoglobin control material, AFSCA2, gave CVs of 2-5% for the A, F, S, and C and 8% for the A2 over a 6-month period. The simplicity of sample preparation, high resolution of the system, and high accuracy of the method, combined with complete automation, make this an ideal methodology for the routine diagnosis of hemoglobin disorders in a clinical laboratory.

Cations↗

PubMed1993

Targeting of the rasT24 oncogene to the proximal convoluted tubules in transgenic mice results in hyperplasia and polycystic kidneys.

Five families of transgenic mice were derived from one-cell-stage embryos injected with gamma GT-rasT24, a fusion gene consisting of the gamma-glutamyl transpeptidase (gamma GT) 5' flanking region containing promoter I linked to a mutated (codon 12) human H-ras oncogene. The transgene was expressed selectively in the kidneys, eyes, and brains of all families as determined by reverse transcription-polymerase chain reaction, nuclease protection assays, and in situ hybridization. In two of five families, kidney lesions consisting of proximal tubular hyperplasia, renal cysts, and microadenomas developed in male animals; males also expressed higher levels of gamma GT/rasT24 RNA. Early lesions consisted of proximal tubular hyperplasia as defined by alkaline phosphatase histochemistry, gamma GT immunohistochemistry, and electron microscopy and could be correlated with the presence of rasT24 RNA within the cystic proximal tubular epithelium by in situ hybridization. Advanced lesions also involved other segments of the nephron and consisted of cysts lined by a flattened unicellular layer of attenuated epithelium. No rasT24 could be identified within cystic lesions of the distal nephron and collecting tubules by in situ hybridization, and they most likely arise by external compression. Animals from the two transgenic strains exhibiting cystic lesions die of renal failure beginning at 8 months of age. No difference in cell-cycle parameters or DNA ploidy between transgenic and control kidneys was identified by flow cytometric analysis. No renal carcinomas developed. The primary renal effects of the H-rasT24 oncogene in this model system consist of proximal tubular hyperplasia and polycystic kidneys. This model appears to provide a useful in vivo system for the study of ras oncogene function and control of renal cell proliferation.

Animals↗

PubMed1993

The effect of gestational age and fetal indomethacin levels on the incidence of constriction of the fetal ductus arteriosus.

OBJECTIVE: To determine the effects of gestational age and fetal serum indomethacin levels on constriction of the ductus arteriosus after maternal indomethacin administration. METHODS: Twenty-five pregnant Rh-sensitized patients were given a 50-mg oral dose of indomethacin 6 hours before fetal serum indomethacin levels were determined at the time of 50 diagnostic or therapeutic funipunctures. The ductus arteriosus was evaluated with Doppler ultrasound immediately before 40 of the procedures. Constriction of the ductus arteriosus was defined as a peak diastolic flow greater than 35 cm/second. Least-squares regression and multiple regression were used for statistical analysis. RESULTS: The peak diastolic velocity of the fetal ductus arteriosus after maternal indomethacin ingestion was constant at 25 cm/second before 27 weeks, increased between 27-30 weeks to a mean of 39 cm/second, and was stable thereafter (R2 = 0.35; P < .05). There was no significant correlation between constriction of the ductus and fetal serum indomethacin levels (P = .17). CONCLUSIONS: The constrictive effect of maternal indomethacin ingestion on the fetal ductus arteriosus begins as early as 27 weeks' gestation. Constriction of the ductus arteriosus is independent of fetal serum indomethacin levels.

Blood Flow Velocity↗

PubMed1992

Comparisons of home blood glucose testing and glycated protein measurements.

We examined the relationships between 4 glycated protein assays and home blood glucose monitoring (HBGM) in 26 children with poorly-controlled insulin-dependent diabetes mellitus (IDDM) during a period of improved management. At 2 week intervals for 6 visits (12 weeks in total), HBGM records were collected and a blood sample was obtained for measurement of glycated proteins and glucose. Assays included glycated hemoglobin (GHb) and glycated serum proteins (GP) by boronate affinity chromatography, hemoglobin A1C by PolyCAT A high performance liquid chromatography (HAC) and fructosamine (FA). All 4 glycated protein levels declined significantly over the 12 week period. Significant correlations between the glycated proteins and HBGM were observed over 2 week intervals. None of the 4 assays were affected by the glucose level in the sample. Changes in mean HBGM readings over 2 week intervals were correlated with both FA and GP with wide prediction intervals. Over cumulative 2 week intervals, which may more accurately reflect longitudinal trends, all 4 glycated proteins were correlated with mean HBGM readings. At each cumulative interval, GHb and GP showed the largest variation with MBG, while FA showed the least variation with MBG. Our data indicate that of the 4 assays tested, FA has limited clinical values as compared to other glycated protein assays, whereas assays based on boronate affinity chromatography (GHb and GP) provide the most useful clinical indicators of short-term changes in glycemic control. The clinical utility of a new HPLC method for determination of glycated hemoglobins is also demonstrated.

Adolescent↗

PubMed1990

Placental transfer of indomethacin in the human pregnancy.

Little is known about the placental transfer of indomethacin in the human pregnancy. Twenty-six pregnant patients (gestational age, 29.4 +/- 0.5 weeks) were given a 50 mg oral dose of indomethacin 6.08 +/- 0.07 hours before 42 cordocenteses undertaken for standard indications. Maternal serum, fetal serum, and amniotic fluid levels were measured at the time of each procedure. Maternal indomethacin levels were not significantly different from corresponding fetal levels (218 +/- 21 vs 219 +/- 13 ng/ml). The maternal/fetal serum ratio (0.97 +/- 0.07) was not found to vary with gestational age (R = -0.07, p = 0.66). Fetal serum levels were significantly higher than corresponding amniotic fluid levels (219 +/- 16 vs. 21 +/- 2 ng/ml; p less than 0.001). The fetal/amniotic fluid ratio (10.0 +/- 1.2) did not vary with gestational age (R = 0.33, p = 0.11). Indomethacin crosses the human placenta easily throughout gestation; only small amounts of the unchanged drug are found in the amniotic fluid.

Amniotic Fluid↗

PubMed1990

Liquid-chromatographic determination of amiodarone and N-desethylamiodarone in serum.

We have developed a stable and simple normal-phase liquid-chromatographic method for simultaneously measuring amiodarone and its metabolite, N-desethylamiodarone, within 8 min. The chromatographic system consists of a 15 cm x 3.9 mm Waters "Resolve" silica column and a mobile phase of ammonium sulfate (17 mmol/L, pH 6.8) and methanol (8/92 by vol), pumped at 1.8 mL/min and monitored at 254 nm. After 250 microL of serum is mixed with 100 microL of 0.36 mol/L NaH2PO4, 100 microL of the internal standard solution (L8040, 6 mg/L), and 200 microL of isopropyl ether, the mixture is vortex-mixed and centrifuged. Fifty microliters of the organic layer is injected onto the column. Relative recovery was 100% over the assay range of 0.1 to 20.0 mg/L for both compounds. Within-run and total (day-to-day) CVs were 3% and 7% for amiodarone and 5% and 8% for N-desethylamiodarone, respectively.

Amiodarone↗

PubMed1989

Bilirubin and the laboratory. Advances in the 1980s, considerations for the 1990s.

The limitations of current methods of measuring bilirubin are well established and relate to the broad dynamic range and inability of the technique to determine different but structurally similar bilirubin species. New instrumentation and methodology circumvent these limitations, and clinical studies are beginning to reveal their increased diagnostic usefulness. Nevertheless, in several clinical situations, for example, the prediction of kernicterus, better bilirubin determinations may not eliminate the controversy surrounding appropriate therapeutic interventions.

Bilirubin↗

PubMed1989

Prostaglandin E1-associated pathology of pulmonary microvasculature in newborn pups: similarity to findings in prostaglandin E1-treated human newborns.

Prostaglandin E1 (PGE1) administration is a useful therapeutic measure for short-term maintenance of ductal patency in patients with obstructions to pulmonary or systemic blood flow. Such treatment is not without complications, however, and a report of three infants from our institution with abnormalities of the pulmonary microvasculature after varying periods of PGE1 therapy was recently published (Heffelfinger et al., Pediatr Pathol 1987;7:165-73). The vascular abnormalities appeared to be temporally related to the PGE1 administration. To test this hypothesis, we investigated the effects of PGE1 in newborn beagles by infusing PGE1 for periods of up to 21 days in four experimental pups. Two control pups were infused with saline for the same period of time. Five of the animals developed respiratory infection during the course of the infusions. One PGE1-treated pup was not infected. Both the PGE1- and saline-treated pups had bronchopneumonias of similar severity; however, pulmonary arteritis occurred only in the PGE1-treated pups. The severity of the arteritis varied with the amount of pulmonary parenchymal inflammation and not with the duration of PGE1 administration. Inflammatory and vascular lesions were found in organs other than the lung only in two pups receiving longer courses of PGE1 treatment. We conclude that systemic PGE1 infusion at therapeutic levels plays a role in the development of arterial lesions in small muscular arteries and that this is potentiated by the presence of infection.

Alprostadil↗

PubMed1989

Concurrent measurement of flecainide acetate and propranolol by normal-phase high-performance liquid chromatography.

This simple, isocratic, normal-phase liquid-chromatographic method concurrently measures flecainide acetate and propranolol in 100 microL of serum within 8 min. The chromatographic system consists of a Waters "Resolve" column packed with 5-microns silica spheres and a mobile phase of ammonium sulfate (10 mmol/L, pH 6.8)/methanol (22/78 by vol), pumped at 0.9 mL/min and monitored by a fluorometer (excitation at 225 nm and emission at 340 nm). After 100 microL of serum is mixed with 200 microL of the internal standard solution [N-(2-piperidylmethyl)-2,3-bis(2,2,2-trifluoroethoxy)-benzamide HCl, 2500 micrograms/L] and 200 microL of 0.2 mol/L sodium carbonate, the sample is extracted into butanol/hexane (20/80 by vol). The organic layer is separated and evaporated, and the residue is redissolved in 200 microL of methanol; 50 microL of this is injected onto the column. Relative recovery was 100% over the assay range of 25-2000 micrograms/L for flecainide and 10-2000 micrograms/L for propranolol. Within-run CVs were less than 2% for flecainide and less than 5% for propranolol; day-to-day CVs ranged from 5.0% to 6.5% for flecainide and from 3% to 12% for propranolol.

Blood Chemical Analysis↗

PubMed1988

Indomethacin in the treatment of premature labor. Effects on the fetal ductus arteriosus.

Indomethacin is a potent agent in the treatment of premature labor, but its use has been limited because of concern about its constrictive effects on the fetal ductus arteriosus. To study these effects we used serial fetal echocardiography in 13 pregnant women in premature labor who received indomethacin according to three different dose schedules, ranging from 100 to 175 mg per day, for a maximum of 72 hours. The gestational ages of the fetuses ranged from 26.5 to 31.0 weeks. The detection of ductal constriction in 7 of the 14 fetuses by echocardiography led to the discontinuation of indomethacin. Three fetuses also had tricuspid regurgitation. There was no statistically significant difference between the mean (+/- SEM) gestational age of the fetuses with ductal constriction and that of those without constriction (29.3 +/- 0.59 and 28.4 +/- 0.52, respectively). There was no relation between serum indomethacin levels in the mothers and ductal constriction. In all seven fetuses affected, ductal constriction had resolved by the time they were restudied 24 hours after the discontinuation of indomethacin. Persistent fetal circulation was not detected in any of the 11 neonates studied after delivery. Indomethacin used to treat premature labor appears to cause transient constriction of the ductus arteriosus in some fetuses, even after short-term use.

Adolescent↗

PubMed1988

Alterations in cerebral availability of metabolic substrates after severe head injury.

Cerebral and systemic metabolism of oxygen, glucose, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, and amino acids were studied in 27 comatose patients during the first 7 days after a head injury. Systemic oxygen consumption was elevated initially and gradually returned toward normal over the week of study. In contrast, cerebral oxygen consumption was depressed and decreased further over the week of study. Cardiac output and cerebral blood flow were increased with respect to systemic and cerebral metabolic requirements, and remained elevated for the entire week of study. Systemic hyperglycemia and lactic acidosis were present. The injured brain often made a sizeable contribution to the lactic acidosis. The arterial concentrations of pyruvate, beta-hydroxybutyrate and acetoacetate were low. The early postinjury arterial amino acid profile was typically an increased level of alanine, taurine, glutamic acid, and a reduced concentration of valine, leucine, isoleucine, threonine, serine, ornithine, and arginine. At 3-4 days postinjury, as the early abnormalities were returning toward normal, glutamine, lysine, phenylalanine, tyrosine, and methionine became elevated. These late increases in amino acids occurred at the time of the peak in plasma catecholamine concentrations. The net cerebral flux of amino acids followed the same general pattern of evolution over time as did the arterial concentration of amino acids. On days when the availability of the individual amino acid was increased, the net cerebral flux tended to be positive; when the availability was decreased, the net cerebral flux was zero or there was a net efflux of the amino acid. There was a significant linear relationship between the arterial concentration and the net flux of 13 of the 17 amino acids studied. Unlike the fasting state in normal man, in which beta-hydroxybutyrate and acetoacetate are important metabolic substrates, cerebral metabolism after head injury is almost totally dependent upon the aerobic and anaerobic metabolism of glucose. This is at least in part due to injury-induced limitations in the variety of substrates that are available for the brain to extract.

Adolescent↗

PubMed1988

Influence of short-term indomethacin therapy on fetal urine output.

Eight pregnancies ranging from 27-32 weeks' gestation were treated for preterm labor with oral indomethacin. The dosage regimen was 25 mg every four hours in four patients and 25 mg every six hours in the other four patients. The maximum duration of indomethacin therapy was 72 hours. In three patients, fetal ductus arteriosus constriction mandated discontinuation of indomethacin at 24 hours. Sonographic assessment of hourly fetal urine output was performed before therapy, at multiple regular intervals during therapy, and 24 hours after the last dose of indomethacin. A dramatic decline was noted from the mean baseline fetal urine output of 11.2 mL/hour. The mean fetal urine output at five, 12, and 24 hours during therapy was 2.2, 1.8, and 1.8 mL/hour, respectively (P less than .05). Twenty-four hours after completion of indomethacin therapy, the mean fetal urine output was 13.5 mL/hour. Poor correlation (r = 0.14, P less than .05) was noted between maternal serum indomethacin levels and hourly fetal urine output. This significant decline in urine output is consistent with other results in neonatal and adult animals and humans. Furthermore, it implies a role for prostaglandins in controlling urine output during fetal life.

Constriction, Pathologic↗

PubMed1986

Conjugated bilirubin versus direct bilirubin in neonates.

Conjugated and direct bilirubin were measured in 288 samples from 107 neonates less than 15 days old. Retrospective analysis of the medical records showed that 53 neonates were hepatobiliary-normal, 42 patients had no obvious evidence of hepatobiliary disease but had received total parenteral nutrition, and 12 were clearly hepatobiliary-abnormal. Neither the mean values nor the distributions of either the conjugated bilirubin, as measured by a multilayered slide, or the direct bilirubin, measured by a solution diazo procedure, differed when comparing the hepatobiliary-normal population to that receiving total parenteral nutrition. However, as would be predicted, the hepatobiliary-abnormal population differed significantly from both of these groups using either direct bilirubin or conjugated bilirubin results. Samples obtained from hepatobiliary-abnormal neonates were reviewed in chronologic sequence if direct bilirubin results differed from conjugated bilirubin with respect to classification of normality/abnormality. In two of three neonates with developing cholestasis, conjugated bilirubin exceeded its upper limit of normal earlier than did direct bilirubin. Conjugated bilirubin returned to normal earlier than direct bilirubin for two neonates with an improving clinical status. Conjugated bilirubin measurement was judged to be more responsive to developing or resolving cholestasis then direct bilirubin. In addition, conjugated bilirubin measurement from the slide is known to agree well with that determined by high performance liquid chromatography fractionation of bilirubin and is less susceptible to interference than is direct bilirubin measurement, characteristics that recommend its use over direct bilirubin analysis in a clinical setting.

Biliary Tract Diseases↗