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Biomedical subjects

M J Nowicki

Publications and source records attributed to M J Nowicki.

At least 37 records · Page 2Linked to original sources
PubMed1997

The 13C-xylose breath test for the diagnosis of small bowel bacterial overgrowth in children.

BACKGROUND: We evaluated the clinical utility of the 13C-xylose breath test for the diagnosis of small bowel bacterial overgrowth in children. METHODS: To determine the optimal dose of 13C-xylose, 29 healthy children, 3 to 12 years old, were randomly assigned to receive one of three doses of 13C-xylose (10, 25, or 50 mg). After an overnight fast, the oral dose of 13C-xylose was administered, and breath samples were collected every 30 minutes for 4 hours. Samples were analyzed for 13CO2 by gas chromatography with mass spectrometry. Using the 50 mg dose, we then performed nine breath tests with concurrent duodenal bacterial cultures in 6 children, 3 to 12 years old, with short-bowel syndrome (n = 2), immunodeficiency states (n = 1), and motility disorders (n = 3). RESULTS: Excretion of 13CO2 in breath peaked at 2.5 hours in all three control groups. The 50-mg dose produced the highest median peak and the smallest range of 13CO2 excretion in breath within each time period. The time of peak 13CO2 excretion in breath varied among the diseased children; however, the six patients with small-bowel bacterial overgrowth (2 x 10(5)-3.5 x 10(5) gram negative rods) all had peak 13CO2 that exceeded the maximum breath 13CO2 level in breath of the control subjects at the corresponding time period (100% sensitivity). Of the three patients with negative cultures, two had negative breath test results and one had positive results (67% specificity). One subject had normalization of both duodenal culture and breath test results after antibiotic treatment of small-bowel bacterial overgrowth. CONCLUSIONS: Our preliminary results suggest that with a dose of 50 mg 13C-xylose, breath test results reliably predict small-bowel bacterial overgrowth in susceptible children.

Bacteria↗
PubMed1997

Glucocorticoids upregulate taurocholate transport by ileal brush-border membrane.

The regulation of the enterohepatic circulation of bile acids has not been fully elucidated. Substrate availability has been shown to have a regulatory role on the ileal uptake of taurocholate (TC) by a positive feedback mechanism. Other mechanisms are likely to be involved in regulating ileal bile acid uptake. The present study was designed to test the hypothesis that the ileal bile acid transporter (iBAT) is glucocorticoid sensitive and that changes in expression are mediated by changes in iBAT synthesis. Adult Sprague-Dawley rats (300-400 g) received intraperitoneal injections with either corticosterone (5 mg/ 100 g body weight) or an equivalent vehicle (control) daily for 3 days. On day 4, ileal brush-border membrane vesicles (BBMV) and hepatic basolateral membrane vesicles (BLMV) were prepared, and TC transport was performed using the rapid filtration technique. Initial velocity was measured at selected time points, and kinetics were calculated over a range of TC concentrations. Ileal RNA was isolated, and Northern analysis of steady-state iBAT mRNA levels was determined. Western blot analysis was performed to quantitate the level of the 48-kDa iBAT protein. The initial velocity of Na(+)-dependent TC uptake at 30 s by ileal BBMV was higher in treated animals (264.3 +/- 64.6 pmol/mg protein) compared with control animals (148.3 +/- 41.1 pmol/mg protein; P = 0.07). The maximal velocity of uptake (Vmax) was significantly higher in treated vs. control animals (1,091 +/- 62.7 vs. 689.1 +/- 55.0 pmol.min-1.mg protein-1, respectively; P = 0.002), whereas there was no significant difference in the Michaelis constant (Km) between the control and treated animals (43.3 +/- 7.2 vs. 35.3 +/- 8.7 microM, respectively; P = not significant). Steady-state iBAT mRNA levels were increased twofold in the treated vs. control groups. Western blot analysis showed that the abundance of the 48-kDa iBAT protein was eightfold higher in the treated animals compared with control. Kinetic analysis of hepatic Na(+)-dependent TC uptake revealed nearly identical Vmax and Km between the study and control animals. Therefore, we conclude that TC transport by ileal BBMV is upregulated by administration of glucocorticoids. The increase in BBMV transport Vmax corresponds to an increase in both iBAT transcript and protein.

Animals↗
PubMed1996

Donor levels of serum alanine aminotransferase activity and antibody to hepatitis B core antigen associated with recipient hepatitis C and non-B, non-C outcomes.

BACKGROUND: Hepatitis virus(es) that are neither hepatitis B (HBV) nor hepatitis C (HCV) (non-B, non-C [NBNC]) may be transmitted by transfusion. The present study assessed donor values for alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti-HBc) for their association with HCV and NBNC hepatitis outcomes among allogeneic blood recipients. STUDY DESIGN AND METHODS: Data on blood donors and recipients enrolled in the Transfusion- Transmitted Viruses Study in four United States cities from 1974 through 1980 were supplemented by anti-HBc testing of donors and anti-HCV evaluation of recipients. Two statistical approaches estimated the value of these indirect tests in detecting donors associated with HCV seroconversion and NBNC hepatitis in recipients. RESULTS: For HCV cases, donor ALT alone (at > or = 60 IU/L) had a sensitivity and a specificity of 30 and 96 percent, respectively, and anti-HBc alone (at > or = 60% inhibition) had a sensitivity and specificity of 53 and 86 percent, respectively. The two markers combined had a sensitivity and a specificity of 69 and 83 percent. For NBNC hepatitis cases, each measure had low sensitivity (20%) that was not improved by using both (28%) [corrected]. CONCLUSION: The indirect tests proved to be equal in sensitivity to the first-generation anti-HCV tests. The positive predictive power of these indirect tests in the 1980s was sufficient to affect HCV incidence in studies during that period. Improved anti-HCV assays, however, replaced the need for indirect tests. The sensitivity of indirect tests for NBNC hepatitis contributed little.

Alanine Transaminase↗
PubMed1995

Absence of hepatitis B and C viruses in pediatric idiopathic membranoproliferative glomerulonephritis.

The blood-borne hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV), have similar epidemiological features. The association of chronic HBV infection and glomerulonephritis is well established, particularly in children. Recent reports have shown an association between HCV infection and glomerulonephritis in adults. In order to assess the role of these hepatotropic viruses in membranoproliferative glomerulonephritis (MPGN) we screened 34 children with idiopathic MPGN for the presence of HBV and HCV infection using highly sensitive polymerase chain reaction techniques for the detection of HBV DNA and HCV RNA. Also, enzyme-linked immunosorbent assays were used to detect the presence of antibody to hepatitis B surface antigen and antibody to HCV. No evidence of HBV or HCV infection was demonstrated in any of the patients. We conclude that HBV and HCV are not significant causes of idiopathic MPGN in children in the United States.

Adolescent↗
PubMed1995

Hepatitis B virus core promoter sequence analysis in fulminant and chronic hepatitis B.

BACKGROUND & AIMS: It was recently reported that two point mutations within the hepatitis B virus (HBV) core promoter region (A to T at position 1762 and G to A at position 1764) are associated with fulminant hepatitis and lead to hepatitis B e antigen (HBeAg)-negative phenotype. The aim of this study was to correlate core promoter sequence variations with HBeAg status and clinical outcome in various forms of HBV infection. METHODS: Core promoter region of HBV was amplified by polymerase chain reaction and directly sequenced in 94 patients: 37 patients with fulminant hepatitis, 20 with acute self-limited hepatitis, 30 with chronic hepatitis, and 7 patients with end-stage cirrhosis. RESULTS: Core promoter region was found to be heterogenous and no specific changes correlated with HBeAg/anti-HBeAg status or survival in patients with fulminant hepatitis. Substitutions at positions 1762 and 1764 were found in HBV strains from 4 patients (10%) with fulminant hepatitis, 2 patients (10%) with self-limited hepatitis, 8 patients (27%) with chronic hepatitis, and in 5 of 7 patients with end-stage cirrhosis. The majority of these patients were HBeAg positive. CONCLUSIONS: Mutations at positions 1762 and 1764 are rarely observed in HBV strains from patients with fulminant hepatitis B in the United States but are common in patients with chronic hepatitis. Even when present, they seem to be insufficient to lead to the HBeAg-negative phenotype.

Base Sequence↗
PubMed1994

The prevalence of hepatitis C virus (HCV) in infants and children after liver transplantation.

Hepatitis C virus (HCV) is an important cause of liver injury following liver transplantation in adults. We hypothesized that the prevalence of HCV infection in children following liver transplantation would be lower than the prevalence in adults after liver transplantation because HCV-related liver disease leading to liver transplantation in children is low and children require less blood products than adults during transplantation. We therefore performed a cross-sectional study to determine the prevalence of HCV infection in children who had undergone liver transplantation. Serum samples were obtained from 62 of 65 (95.4%) consecutive patients surviving for more than six months after transplantation. Using a second-generation enzyme-linked, immunosorbent assay (ELISA-2) and a second-generation recombinant immunoblot assay (RIBA-II), antibodies to HCV were detected in 5.1% (3 of 59) of the subjects. Using a single-step, polymerase chain reaction (PCR), HCV RNA was detected in 6.2% (4 of 62). All HCV-positive children had undergone liver transplantation before the initiation of routine screening for HCV in blood donors; overall 30 patients were transplanted prior to routine screening of blood products for HCV. The prevalence of HCV in infants and children after liver transplantation in our study is substantially less than the rates reported in adults. This difference may be due, in part, to the lower volume of blood product exposure and to the fact that children, as opposed to adults, rarely have chronic HCV infection as a cause of end-stage liver disease.

Adolescent↗
PubMed1994

Naturally occurring hepatitis B virus mutants with deletions in the core promoter region.

A novel class of hepatitis B virus mutants in patients with chronic hepatitis B is described. The predicted effect of the mutations is to disrupt the X open reading frame. The location of the genetic alterations within the putative precore promoter also suggests that they may ameliorate precore transcription, which would provide an alternate mechanism for HBeAg(-) escape variation. Definitive conclusions regarding the effects of these mutations must await additional in vitro and in vivo studies.

Adult↗
PubMed1994

Transfusion transmission of retroviruses: human T-lymphotropic virus types I and II compared with human immunodeficiency virus type 1.

BACKGROUND: The incidence of transfusion transmission of human T-lymphotropic virus type I (HTLV-I) and HTLV type II (HTLV-II) has not been compared directly or to that of human immunodeficiency virus type 1 (HIV-1). The effects of refrigerator storage of the blood component on infectivity of the viruses needs definition. STUDY DESIGN AND METHODS: The circumstances influencing the transmission of HTLV-I, HTLV-II, and HIV-1 via blood of donors whose sera were stored in a repository and who were retrospectively documented as having been infected at blood donation were examined. Confirmation and typing of anti-HTLV positivity in donors and recipients used polymerase chain reaction, supplemented by specific peptide testing. RESULTS: Overall, 27 percent (26/95) of the recipients of blood components from anti-HTLV-I- and -II-positive donors became infected (9 with HTLV-I and 17 with HTLV-II). No recipients of acellular blood components became infected with HTLV-I or -II. There was no probable transmission by components stored > 10 days. The rates of transmission for both viruses were similar: 0 to 5 days' storage, 17 (74%) of 23; 6 to 10 days, 8 (44%) of 18; and 11 to 14, 0 (0%) of 10 (trend, p = 0.0002). In comparison, 89 percent (112/126) of the recipients of anti-HIV-1-positive blood were infected regardless of component type, and no effect on transmission occurred with storage for < 26 days. CONCLUSION: Transfusion-transmitted HTLV-I and -II are similar. The data suggest that a donor's lymphocytes become noninfectious when they lose the ability to be activated or to proliferate.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Hepatitis A virus transmission by blood products in the United States. Transfusion Safety Study Group.

To address the question of HAV prevalence and seroconversion in relation to clotting factor concentrates, we assayed an early serum for 339 hemophiliacs followed every 6 months by the Transfusion Safety Study in the period from mid-1985 until mid-1992. We found 58.4% positive around entry, with an age-specific prevalence that did not vary with age. In comparison to rates for anti-HIV-negative blood donors, they were significantly higher. Based on testing of subsequent sera, 11 hemophiliacs (7.8% of 141 susceptibles) changed their anti-HAV status from negative to positive. In 9 instances, positivity immediately followed the first dose of intravenous immune globulin. A possible seroconversion followed treatment with blood components, and a possible seroconversion followed intermediate-purity, solvent/detergent(SD)-treated factor VIII concentrate. Neither of these 2 patients was anti-HAV IgM positive, so that passively transferred antibody is possible. The high prevalence among hemophiliacs at entry must be further investigated by determining the expected background rate in a US population similar to the hemophilia patients, and by comparing anti-HAV prevalence associated with SD-treated and heat-inactivated concentrates.

Adolescent↗
PubMed1993

Nucleotide sequence analysis of the precore region in patients with fulminant hepatitis B in the United States.

BACKGROUND: A precore defective hepatitis B virus (HBV) mutant unable to produce hepatitis B e antigen (HBeAg) has been associated with fulminant hepatitis B. We have studied the etiologic contribution of precore mutants among North American patients with this disorder. METHODS: We studied 39 patients with fulminant hepatitis B. The precore and proximal core regions of HBV from 37 of 39 patients were sequenced. RESULTS: Four patients (10.8%) harbored nonsense mutants likely to produce an HBeAg negative HBV infection; two such mutants had a G to A substitution at position 1896, one lost the precore initiation codon, and one harbored a stop codon immediately downstream of the precore initiation codon. Recovered sequences from seven additional patients displayed silent or missense mutations in these regions. All delta coinfected patients harbored known wild type strains of HBV. A significantly poorer survival was associated with antibody to HBe positivity and presence of nucleotide substitutions in the precore/core region. CONCLUSIONS: The prevalence of precore mutations in 37 patients from the United States was lower than reported elsewhere; only two patients were found to have the G to A transition mutation in the precore region at position 1896. We conclude that HBeAg negative HBV mutants do not play a predominant etiologic role among North American patients with fulminant hepatitis B.

Adenine↗