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Biomedical subjects

M Nowicki

Publications and source records attributed to M Nowicki.

At least 37 records · Page 2Linked to original sources
PubMed2001

Exposure of hepatitis C virus (HCV) RNA-positive recipients to HCV RNA-positive blood donors results in rapid predominance of a single donor strain and exclusion and/or suppression of the recipient strain.

We have analyzed three cases of hepatitis C virus (HCV)-infected recipients who received blood from HCV-infected donors. Two recipients were exposed to two different HCV RNA-positive donors, and one was exposed to a single donor. All parental genomes from the actual infecting units of blood and the recipients were defined, and their presence in the follow-up serum samples was determined using sensitive strain-specific assays. The strain from one of the donors was found to predominate in all recipients' serum samples collected throughout the follow-up period of 10 to 30 months. In two recipients exposed to two infected donors, the strain from the second donor was occasionally found at very low level. However, the original recipients' strains were not detected. Our observations show that HCV-infected individuals can be superinfected with different strains, and this event may lead to eradication or suppression of the original infecting strain. Furthermore, our findings demonstrate that simultaneous exposure to multiple HCV strains may result in concomitant infection by more than one strain, although a single strain could rapidly establish its dominance. The results of the present study suggest the existence of competition among infecting HCV strains which determines the ultimate outcome of multiple HCV exposure.

Adult↗
PubMed2001

Managing impossible missions: ethical quandaries and ethical solutions.

Healthcare financial managers are confronted daily with ethical and practical conflicts, particularly with regard to meeting the conflicting and unduly restrictive laws and regulations with which their organizations must comply. Sometimes the right course of action is not clear, as an examination of the 72-hour rule, safe harbor provisions, and legal interpretations of the False Claims Act reveals. Healthcare financial managers have an ethical duty, based on healthcare codes of ethics and ethical theories, to oppose laws and regulations that put their organizations in untenable legal and ethical situations.

Conflict, Psychological↗
PubMed2001

[Platelet activation in relapse idiopathic nephrotic syndrome in children].

The role that platelets play in pathogenesis and thromboembolic complications of the idiopathic nephrotic syndrome (INS) in children still remains unclear. The aim of the study was to analyse of platelet activation in whole blood during first 8 weeks of ins. Study group comprised 24 children with 34 relapses of INS by ISKDC (group A). Obtained results were compared to 16 healthy children (group B). We assessed activation by the count of platelet aggregates, microparticles and surface expression of selected markers--CD62P (P-selectin), CD42b (part of von Willebrand factor receptor) at the onset INS, after 2 weeks of therapy. We found the increased counts of platelet aggregates and microparticles at the onset of INS with a systematic decrease in following 2 weeks. Furthermore, expression of CD42b was significantly lower at the beginning of therapy. There were no clear correlation between markers of activation and biochemical parameters in the study group. According to these findings we conclude that increased activation of blood platelets is an independent risk factor of thromboembolic complication in the early stages of relapse of INS. The role of platelets in pathogenesis or induction of ins relapse remains the matter for further investigation.

Adolescent↗
PubMed2001

[Congenital hyperammonemia in neonates treated with hemodiafiltration].

Inborn defects of urea cycle often results in life-threatening hyperammonemia in neonates. The initial therapy of this disease comprises administration of benzoate sodium, arginine, lactulose, neomycin, and restrictive alimentation based on carbohydrates. Renal replacement therapy for ammonia removal should be considered for the most severe cases. We present a case report of two neonates with very rare inborn urea cycle disorders--deficiency of argininosuccinate lyase and carbamyl-phosphate synthetase, treated with spontaneous arterio-venous haemodiafiltration.

Female↗
PubMed2000

Selection by indication of potent antiretroviral therapy use in a large cohort of women infected with human immunodeficiency virus.

To characterize selection factors related to therapy initiation, the authors investigated the extent to which key markers of human immunodeficiency virus (HIV) disease severity were associated with initiation of potent antiretroviral therapy (ART). Logistic regression was used to determine the effects of CD4+ cell count and HIV RNA level on potent ART initiation during 6-month periods among 2,059 HIV-infected US women enrolled in the Women's Interagency HIV Study. Low CD4+ counts and high HIV RNA levels were significantly (p < 0.05) associated with initiation of potent ART. During all periods between April 1996 and March 1998, CD4+ counts were more strongly associated with potent ART initiation than HIV RNA levels were; however, during the last period, both were associated (odds ratio per 100 CD4+-count decrease = 1.17, p < 0.01; odds ratio per 1 log10 increase in HIV RNA level = 1.48, p < 0.05). For a CD4+ count of 500 cells/ml and an HIV RNA level of 5,000 copies/ml, the probability of potent ART initiation increased from 0.5% to 16.8% between October 1995-March 1996 and October 1997-March 1998, suggesting earlier initiation of potent ART. Given the documented occurrence of confounding by indication, prospectively collected, time-dependent data on markers of disease progression and therapy use should be considered when making population-level comparisons before and after introduction of potent ART.

Adult↗
PubMed2000

Detection of active hepatitis C virus and hepatitis G virus/GB virus C replication in bone marrow in human subjects.

We have analyzed the presence of hepatitis C virus (HCV) and hepatitis G virus (HGV) sequences in bone marrow and serum samples from 48 patients of a hematologic outpatient clinic. HCV RNA was detected in 18 (38%) and 15 (31%) and HGV RNA was detected in 6 (13%) and 9 (19%) of serum and bone marrow samples, respectively. In 3 patients, HGV RNA was detectable in bone marrow but not in the serum; 2 of these patients were negative for the presence of specific antibodies. Using a highly strand-specific Tth-based reverse transcriptase-polymerase chain reaction (RT-PCR), the presence of HCV RNA and HGV RNA negative strand was demonstrated in 4 and 5 bone marrow samples, respectively. Our study shows that HCV and HGV can replicate in bone marrow; in the case of HGV, analysis of serum may underestimate the true prevalence of infection. (Blood. 2000;95:3986-3989)

Adult↗
PubMed2000

Serum albumin as a predictor of survival in HIV-infected women in the Women's Interagency HIV study.

BACKGROUND: The level of serum albumin is associated with mortality in a wide variety of chronic diseases. However, few studies have examined the relationship between serum albumin and survival in HIV-1 infection. OBJECTIVES: To determine whether the serum albumin level is associated with survival in HIV-1 infected women. DESIGN: Prospective cohort study. Patients were interviewed and examined at 6 month intervals. SETTING: A North American multi-institutional cohort of HIV-infected women from five geographical areas. PARTICIPANTS: A total of 2056 HIV-infected women at various stages of disease. MEASUREMENTS: Mortality during the first 3 years of follow-up. The relative risk of death by serum albumin level was estimated using a proportional hazards ratio adjusted for CD4 cell count, HIV-1-RNA level and other relevant covariates. RESULT: Three year mortality for women in the lowest serum albumin category (< 35 g/l) was 48% compared with 11% in the highest category (> or = 42 g/l; P < 0.001). The adjusted relative hazard (RH) of death was 3.1 times greater for those in the lowest albumin category (P < 0.01). The excess risk associated with lower serum albumin levels remained when subjects with moderate to severe immunosuppression and abnormal kidney and liver function were excluded (P < 0.01). CONCLUSION: The baseline serum albumin level is an independent predictor of mortality in HIV-1-infected women. The serum albumin level may be a useful additional marker of HIV-1 disease progression, particularly among asymptomatic women with little or no evidence of immunosuppression.

Adult↗
PubMed2000

Hepatitis C virus in lymphoid cells of patients coinfected with human immunodeficiency virus type 1: evidence of active replication in monocytes/macrophages and lymphocytes.

It has been reported that hepatitis C virus (HCV) may be lymphotropic in the setting of human immunodeficiency virus type 1 (HIV-1) coinfection. The present study was undertaken to determine the phenotype of lymphoid cells harboring replicating HCV in HIV-1-positive subjects. By means of highly strand-specific thermostable enzyme Tth-based reverse-transcriptase polymerase chain reaction, the presence of viral RNA-negative strand was sought in different subpopulations of peripheral blood mononuclear cells from 10 HIV-positive patients. HCV RNA-negative strand was most commonly present in monocytes/macrophages (4 cases), followed by CD8+ and CD4+ lymphocytes (2 cases) and CD19+ cells (1 case). In 2 cases that were further analyzed, viral-negative strand remained detectable in monocytes/macrophages cultured for 3 weeks. Moreover, monocyte/macrophage- and serum-derived viral sequences differed in the 5' untranslated region. These findings imply that, in HIV-infected subjects, HCV may replicate in the same cells as HIV-1, which raises the possibility of direct interactions between these pathogens.

5' Untranslated Regions↗
PubMed2000

Detection and quantitation of human immunodeficiency virus type 1 in the female genital tract. The Division of AIDS Treatment Research Initiative 009 Study Group.

Human immunodeficiency virus type 1 (HIV-1) was detected in the genital tracts of 59% of 225 women by RNA PCR and in 7% of the women by culture. In a comparison of two sampling methods, endocervical swabs were more sensitive than cervicovaginal lavage for HIV-1 RNA detection by PCR but not by culture and their sensitivity was independent of the concentration of HIV-1 RNA.

Cross-Sectional Studies↗
PubMed2000

Comparison of two amplification technologies for detection and quantitation of human immunodeficiency virus type 1 RNA in the female genital tract. Division of AIDS Treatment Research Initiative 009 Study Team.

Human immunodeficiency virus type 1 (HIV-1) RNA levels in female genital tract and peripheral blood samples were compared using two commercial amplification technologies: the Roche AMPLICOR HIV-1 MONITOR test and either the Organon Teknika nucleic acid sequence-based amplification (NASBA-QT) assay or the NucliSens assay. Estimates of HIV-1 RNA copy number were derived from internal kit standards and analyzed unadjusted and adjusted to a common set of external standards. We found a discordance rate of approximately 18% between the two technologies for the detection of HIV-1 in either the genital tract or peripheral blood samples. Detection discordance was not consistent among specimens or among women. There were no significant differences in adjusted or unadjusted estimates of HIV-1 RNA copy number in the genital tract samples using the AMPLICOR HIV-1 MONITOR test and either the NASBA-QT assay or the NucliSens assay. In addition, the estimated HIV-1 RNA copy number in peripheral blood samples did not differ when tested with the NucliSens assay and the AMPLICOR HIV-1 MONITOR test using kit standards. However, there was a significant difference in estimated RNA copy number between the NASBA-QT assay and the AMPLICOR HIV-1 MONITOR test for internal kit standards, which, as we have previously shown, was eliminated after adjustment with the external standards. Our results suggest that the Roche and Organon Teknika assays are equivalent for quantifying HIV-1 RNA in female genital tract specimens, although variation in detection does exist.

Cross-Sectional Studies↗
PubMed2000

Uneven distribution of hepatitis C virus quasispecies in tissues from subjects with end-stage liver disease: confounding effect of viral adsorption and mounting evidence for the presence of low-level extrahepatic replication.

We have found differences among the populations of hepatitis C virus sequences in serum, peripheral blood mononuclear cells (PBMCs), and various tissues in patients with chronic hepatitis C. These results are compatible with the existence of independent viral compartments in the infected host. Our results also suggest that PBMCs, and probably various tissues, can selectively adsorb viral subpopulations differing in the E2 region.

5' Untranslated Regions↗
PubMed1999

Effects of acute euglycemic hyperinsulinemia on urinary nitrite/nitrate excretion and plasma endothelin-1 levels in men with essential hypertension and normotensive controls.

Insulin stimulates the production of endothelin-1 (ET-1) and nitric oxide (NO) by isolated endothelial cells. Additionally, insulin-dependent glucose transport and insulin-mediated NO production partially share common elements in signal transduction. There are discordant data on plasma ET-1 levels during acute euglycemic systemic hyperinsulinemia in normotensive men and men with essential hypertension (EH) (known to be insulin-resistant), as well as on the relations between insulin sensitivity and vascular function. Our aim was to assess the response of approximate measures of whole-body generation of NO and ET-1 to acute euglycemic hyperinsulinemia in EH patients and controls. We studied 17 newly diagnosed untreated men with uncomplicated EH and 10 normotensive controls. Plasma ET-1 and urinary excretion of nitrite plus nitrate, stable NO metabolites (Uno(x)), were measured before and during a 3-hour hyperinsulinemic-euglycemic clamp. Both in hypertensives and normotensives, plasma ET-1 levels were reduced after 2 hours of the clamp (EH: baseline, 3.1+/-1.9 pg/mL; 2 hours, 1.9+/-1.2 pg/mL, P = .04 v baseline; controls: baseline, 4.2+/-2.6 pg/mL; 2 hours, 2.8+/-1.4 pg/mL, P = .04 v baseline). No significant changes in Uno(x) during the clamp were observed. Changes in Uno(x) during the clamp (deltaUno(x)) and differences in plasma ET-1 measured before the end and before the beginning of the clamp (deltaET-1) were correlated in the controls (r = .75, P = .01) but not in EH (r = -.01, P = .97). No parameter of glucose metabolism correlated with basal Uno(x), basal plasma ET-1, deltaUno(x), and deltaET-1, whether absolute or percent values, in either group. Thus, acute euglycemic hyperinsulinemia produces a decrease in plasma ET-1 in both EH patients and controls. The lack of correlation between deltaUno(x) and deltaET-1 under these conditions in EH may suggest an impairment of systems governing interactions between the NO-dependent pathway and ET-1. In addition, insulin actions on glucose metabolism and on the endothelial mediators appear dissociated.

Acute Disease↗
PubMed1999

Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of asymmetric dimethylarginine in men with essential hypertension.

Our aim was to investigate systemic nitric oxide (NO) production and its potential determinants such as insulin resistance, dyslipidemia, and circulating methylated analogs of L-arginine in uncomplicated essential hypertension (EH). Nineteen newly diagnosed, untreated male subjects with mild pure uncomplicated EH and 11 normotensive controls were studied at rest after an overnight fast. The groups had comparable age, body mass index, creatinine clearance, cholesterol, fasting glucose, and insulin. In hypertensives, the urinary excretion rate of nitrite plus nitrate (Unox), an index of endogenous NO production, was depressed (56+/-17 vs. 77+/-23 micromol/mmol creatinine; p < 0.05), whereas plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis, were increased (2.4+/-1.1 vs. 1.1+/-0.7 microM; p < 0.005). Circulating concentrations of symmetric dimethylarginine were similar in both groups (1.4+/-1.3 vs. 1.5+/-1.1 microM; p = NS). The L-arginine-to-ADMA ratio was reduced in hypertension (3.3+/-0.5 vs. 4.5+/-0.8; p < 0.001 for In-transformed data). There was no correlation between Unox and either the magnitude of insulin resistance or dyslipidemia in EH. Thus in male subjects with EH, endogenous systemic NO formation appears depressed, which is unrelated to accompanying insulin resistance or dyslipidemia. Circulating ADMA levels are increased in uncomplicated EH, which may be of potential relevance.

Adult↗
PubMed1998

Association between hepatitis B virus core promoter rearrangements and hepatocellular carcinoma.

Hepatitis B virus (HBV) is the major etiological agent of hepatocellular carcinoma (HCC). Whether any particular viral variants are associated with HCC is unknown. We studied 53 Gambian patients with HCC and 33 HBsAg positive controls. A functional part of HBV core promoter and whole precore region were sequenced directly and/or after cloning. HBV DNA was amplified from sera from 27 HCC patients and in all controls. Fourteen (52%) patients and 12 (36%) controls (NS) were found to harbor an HBV strain with G to A transition mutation at position 1896 leading to HBeAg negative phenotype. Nine (33%) HCC patients and 2 (6%) controls (p < 0.01) harbored a mixture of wild type and HBV strains with deletions/insertions; strong consensus sequences for topoisomerase I breakage were located in the vicinity of these changes. In Africa, HCC is associated with HBV strains that have deletions/insertions in the HBV core promoter region.

Base Sequence↗