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PubMed2000

Isolation and characterization of IIAChb, a soluble protein of the enzyme II complex required for the transport/phosphorylation of N, N'-diacetylchitobiose in Escherichia coli.

N,N'-Diacetylchitobiose is transported/phosphorylated in Escherichia coli by the (GlcNAc)(2)-specific Enzyme II permease of the phosphoenolpyruvate:glycose phosphotransferase system. IIA(Chb), one protein of the Enzyme II complex, was cloned and purified to homogeneity. IIA(Chb) and phospho-IIA(Chb) form stable homodimers (). Phospho-IIA(Chb) behaves as a typical epsilon2-N (i.e. N-3) phospho-His protein. However, the rate constants for hydrolysis of phospho-IIA(Chb) at pH 8.0 unexpectedly increased 7-fold between 25 and 37 degrees C and increased approximately 4-fold with decreasing protein concentration at 37 degrees C (but not 25 degrees C). The data were explained by thermal denaturation studies using CD spectroscopy. IIA(Chb) and phospho-IIA(Chb) exhibit virtually identical spectra at 25 degrees C (approximately 80% alpha-helix), but phospho-IIA(Chb) loses about 30% of its helicity at 37 degrees C, whereas IIA(Chb) shows only a slight change. Furthermore, the T(m) for thermal denaturation of IIA(Chb) was 54 degrees C, only slightly affected by concentration, whereas the T(m) for phospho-IIA(Chb) was much lower, ranging from 40 to 46 degrees C, depending on concentration. In addition, divalent cations (Mg(2+), Cu(2+), and Ni(2+)) have a dramatic and differential effect on the structure, depending on the state of phosphorylation of the protein. Thus, phosphorylation destabilizes IIA(Chb) at 37 degrees C, potentially affecting the monomer/dimer transition, which correlates with its chemical instability at this temperature. The physiological consequences of this phenomenon are briefly considered.

Biological Transport↗
PubMed2004

Effect of niacin on the choroidal circulation of patients with age related macular degeneration.

AIM: To investigate the effects of niacin on choroidal blood flow in age related macular degeneration (AMD). METHODS: 12 AMD patients with bilateral drusen and visual acuity of 20/40 or better in the study eye received a single oral dose of niacin (six subjects received 500 mg and six received 250 mg) or matching placebo on two separate occasions. Laser Doppler flowmetry was used to assess relative choroidal blood velocity (ChB(Vel)), volume (ChB(Vol)), and flow (ChB(Flow)) in the foveola of the study eye at baseline, 30, and 90 minutes after dosing. RESULTS: In comparison with placebo, a statistically significant 24% increase in ChB(Vol) was observed 30 minutes after niacin administration (ANOVA, p = 0.01). In comparison with placebo, a significant decrease in ChB(Vel) of 23% was observed in the 500 mg group (p = 0.04) and no significant change in ChB(Vel) was seen in the 250 mg group at 30 minutes. No significant changes in ChB(Flow) were detected at 30 or 90 minutes. Also, there were no statistically significant changes in ChB(Vol) or ChB(Vel) at 90 minutes. CONCLUSION: In comparison with placebo, a significant 24% increase in ChB(Vol) was observed 30 minutes after niacin administration. Owing to simultaneous decrease in ChB(Vel), however, no significant change in ChB(Flow) was detected.

Administration, Oral↗
PubMed2000

Role of multidrug resistance protein 1 (MRP1) and glutathione S-transferase A1-1 in alkylating agent resistance. Kinetics of glutathione conjugate formation and efflux govern differential cellular sensitivity to chlorambucil versus melphalan toxicity.

We investigated the role of phase II (conjugation) and phase III (efflux) detoxification of the anticancer drugs melphalan (MLP) and chlorambucil (CHB). Although both drugs are substrates of Alpha-class glutathione S-transferases (GST) and the monoglutathionyl conjugates formed in these enzymatic reactions are transported by MRP1, we found that GSTA1-1 and MRP1 acted in synergy to confer resistance to CHB but not to MLP (Morrow, C. S., Smitherman, P. K., Diah, S. K., Schneider, E., and Townsend, A. J. (1998) J. Biol. Chem. 273, 20114-20120). To explain this selectivity of MRP1/GST-mediated resistance, we report results of side-by-side experiments comparing the kinetics of MLP- versus CHB-glutathione conjugate: formation, product inhibition of GSTA1-1 catalysis, and transport by MRP1. The monoglutathionyl conjugate of CHB, CHB-SG, is a very strong competitive inhibitor of GSTA1-1 (K(i) 0.14 microM) that is >30-fold more potent than that of the corresponding conjugate of MLP, MLP-SG (K(i) 4.7 microM). The efficiency of GSTA1-1-mediated monoglutathionyl conjugate formation is more than 4-fold higher for CHB than MLP. Lastly, both CHB-SG and MLP-SG are efficiently transported by MRP1 with similar V(max) although the K(m) for CHB-SG (0.37 microm) is significantly lower than for MLP-SG (1.1 microM). These results indicate that MRP1 is required for GSTA1-1-mediated resistance to CHB in order to relieve potent product inhibition of the enzyme by intracellular CHB-SG formed. The kinetic properties of MRP1 are well suited to eliminate CHB-SG at pharmacologically relevant concentrations. For MLP detoxification, where product inhibition of GSTA1-1 is less important, GSTA1-1 does not confer resistance because of the relatively poorer catalytic efficiency of MLP-SG formation. Similar analyses can be useful for predicting the pharmacological and toxicological consequences of MRP and GST expression on cellular sensitivity to various other electrophilic xenobiotics.

ATP-Binding Cassette Transporters↗
PubMed1999

Health care costs associated with chronic hepatitis B.

The long-term health care costs of patients with chronic hepatitis B (CHB) were compared with those of patients without CHB. Patients with laboratory markers for CHB were identified from an HMO database and matched with up to four control patients (either not tested for hepatitis B infection or with negative test results). Cost data were collected retrospectively for both groups of patients for the period up to 30 days before identification of the first marker for hepatitis B (prediagnosis), 30 days before identification of the first marker through 180 days after the identification (peridiagnosis), and 181 days after identification through the end of the six-year study period. Costs were categorized as emergency room, inpatient, short-stay inpatient, laboratory, radiology, office visit, pharmacy, outside claim, or other and were analyzed as ratios of the costs of each patient with CHB to the median of the corresponding control patients. Eighty-eight patients were identified as having CHB; there were 342 control patients. In the seven months surrounding the appearance of their first diagnostic marker, the patients with CHB had costs 3.3 times those of the corresponding control patients and, after the first seven months, 2.9 times those of the control patients per month. Peridiagnosis costs in the categories of laboratory, radiology, office visits, and pharmacy were significantly higher for patients with CHB than for control patients. Except for emergency room costs, postdiagnosis costs per month of the patients with CHB were significantly higher than those of the corresponding control patients. Examination of an HMO database showed that, compared with patients without CHB, patients with CHB had significantly higher health care costs around and after the CHB diagnosis.

Adult↗
PubMed2004

Relationship of maternal autoimmune response to clinical manifestations in children with congenital complete heart block.

OBJECTIVE: To study the autoimmune response in mothers of children with congenital heart block (CHB) diagnosed at different ages and with different clinical manifestations. PATIENTS AND METHODS: Clinical data and sera for the determination of immunological tests were available from 104 mothers of 113 children born between 1950 and 2000 and diagnosed with CHB before the age of 16 y. Prenatal diagnosis was performed in 74 (65%) children of 65 mothers, and 39 (35%) children had postnatal diagnosis of CHB. Maternal antibodies to 52 kd and 60 kd SS-A, and to 48 kd SS-B were determined by time-resolved fluoroimmunoassay (TR-FIA) and to antinuclear antibodies (ANA) by immunoflurescense (IF). RESULTS: Out of the 65 mothers of children with in utero diagnosed CHB, 88% had antibodies to 52 kd SS-A and 83% had ANA. Antibodies to 60 kd SS-A and 48 kd SS-B were less frequently present, in 48% and in 54% of the mothers, respectively. Seven (11%) of the mothers were negative by all immunoassays. Of the 13 mothers of children with in-infancy diagnosed CHB, one mother had high-titer ANA. After 1 y of age, CHB was diagnosed in 26 children; at 1 to 6 y in 16 and after 7 y in 10 children; 1/16 and 1/10 patients had positive antibodies. In all twin pregnancies (n = 4) and in all families with recurring cases of CHB (n = 5), maternal antibodies were positive in at least one assay. The titer of 48 kd anti-SS-B antibodies was significantly higher in children with cutaneous neonatal lupus (98.1 vs 41.0; p = 0.02). All mothers whose children died before the age of 4 y (n = 8) and 85% (11/13) of mothers whose children developed cardiomyopathy had elevated antibody titers in at least one assay. However, we could not find any prognostic value of maternal antibody levels or specificities on the clinical outcome of the children with CHB. CONCLUSIONS: Although rare, late detection or postnatal progression of CHB in antibody-mediated CHB should be taken into consideration. Maternal antibody levels or specificities have prognostic effect neither on the clinical outcome of the child with CHB nor on the risk of reappearance in the same family.

Autoantibodies↗
PubMed2024

Intrahepatic Exhausted Antiviral Immunity in an Immunocompetent Mouse Model of Chronic Hepatitis B.

BACKGROUND & AIMS: Targeting exhausted immune systems would be a promising therapeutic strategy to achieve a functional cure for HBV infection in patients with chronic hepatitis B (CHB). However, animal models recapitulating the immunokinetics of CHB are very limited. We aimed to develop an immunocompetent mouse model of CHB for intrahepatic immune profiling. METHODS: CHB mice were created by intrahepatic delivery of the Sleeping Beauty transposon vector tandemly expressing the hepatitis B virus (HBV) genome and fumarylacetoacetate hydrolase (FAH) cDNA into C57BL/6J congenic FAH knockout mice via hydrodynamic tail vein injection. We profiled the viral and intrahepatic immune kinetics in CHB mice with or without treatment with recombinant IFNα or the hepatotropic Toll-like receptor 7 agonist SA-5 using single-cell RNA-seq. RESULTS: CHB mice exhibited sustained HBV viremia and persistent hepatitis. They showed intrahepatic expansion of exhausted CD8+ T (Tex) cells, the frequency of which was positively associated with viral load. Recruited macrophages increased in number but impaired inflammatory responses in the liver. The cytotoxicity of mature natural killer (NK) cells also increased in CHB mice. IFNα and SA-5 treatment both resulted in viral suppression with mild hepatic flares in CHB mice. Although both treatments activated NK cells, SA-5 had the capacity to revitalize the impaired function of Tex cells and liver-recruited macrophages. CONCLUSIONS: Our novel CHB mouse model recapitulated the intrahepatic exhausted antiviral immunity in patients with CHB, which might be able to be reinvigorated by a hepatotropic TLR7 agonist.

Animals↗
PubMed2004

[Congenital heart block associated with maternal anti SSA/SSB antibodies :a report of four cases].

Congenital heart block (CHB) associated with maternal anti-SSA/SSB antibodies: a report of four cases. CHB detected in utero is strongly associated with maternal antibodies to SSA (Ro) and SSB (La). Their pathogenic role in the development of CHB has been established in several studies. The mothers of affected infants frequently had autoimmune disease (systemic lupus erythematosus, Sjögren's syndrome) or were entirely asymptomatic. It is very difficult to identify pregnant asymptomatic mothers carrying anti-SSA/SSB antibodies. We report four cases of infants born to asymptomatic mothers with anti-SSA/SSB antibodies, three of them developed isolated congenital cardiac heart block and one with no evidence of CHB. All three CHB are detected during pregnancy between 16 and 24 weeks of gestation. All maternal sera contained antibodies to SSA alone or the both SSA and SSB. Three of four subsequent pregnancies were complicated by heart block. One child affected died in utero. While the two other newborns with CHB required pacemaker insertion during the first 3 months of life. Although the association of anti-SSA/SSB with CHB is widely accepted, the precise mechanism by which these antibodies cause cardiac conduction abnormalities remains to be defined. Antibodies to SSA/SSB have been proposed to be a serologic marker for neonatal lupus syndrome and CHB. Fetal and neonatal diseases are presumed to be due to the transplacental passage of these IgG autoantibodies from the mother into the fetal circulation. Since these antibodies may have a pathogenic role in CHB, screening of infants with isolated CHB or neonatal lupus and their mothers for the presence of anti-SSA and anti-SSB is strongly recommended.

Adult↗
PubMed2004

Separation of hepatic and gastrointestinal signals from the common "hepatic" branch of the vagus.

Anatomic studies show that the common hepatic branch (CHB) of the vagus contains afferent fibers that innervate sites outside the hepatoportal region, primarily in the gastrointestinal tract. In the current experiments on the anesthetized rat, the source of signals from the CHB was determined by recording CHB neurophysiological responses before and after transection of the gastroduodenal branch (GDB) of the CHB. Serotonin [5-hydroxytryptamine (5-HT)] and CCK-8 were used as probes to stimulate the CHB. Most of the CHB afferent fibers were 5-HT sensitive (56%), and 35% of these were also sensitive to CCK-8. Portal vein vs. jugular vein infusion of 5-HT and CCK-8 and GDB transection showed that 5-HT- and CCK-sensitive fibers innervate the hepatoportal region and areas outside the hepatic hilus (e.g., the gastrointestinal tract). Suppression of basal nerve activity by a 5-HT(3) receptor antagonist (Y-25130) suggests that approximately 50% of CHB afferent fibers contain 5-HT(3) receptors, but none of these fibers appears to be in the hepatoportal region because only in rats with an intact GDB did Y-25130 reduce nerve activity. In summary, these data are in close agreement with anatomic observations on the distribution of the CHB fibers and indicate that neurophysiological studies of the CHB must be carefully evaluated given the prominent role of nonhepatoportal afferent signals recorded from the CHB.

Animals↗
PubMed2004

Adefovir dipivoxil in the treatment of chronic hepatitis B.

OBJECTIVE: To evaluate properties of the new acyclic nucleotide analog adefovir dipivoxil in the treatment of chronic hepatitis B (CHB). DATA SOURCES: MEDLINE and PubMed searches from 1966 to December 2003 were performed with the headings chronic hepatitis B, interferon alfa-2b, lamivudine, liver transplant, and adefovir dipivoxil. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled studies and meta-analyses were evaluated in detail. A manual search was performed using references from retrieved primary literature, review articles, editorials, postgraduate course syllabi from national meetings, and textbooks. Emphasis was placed on controlled, prospective, randomized trials. National meeting abstract presentations were included if the information offered was original. DATA SYNTHESIS: CHB is a major viral infection with an estimated 400 million carriers worldwide. Medications available to treat CHB include interferon alfa-2b and lamivudine, both agents having significant limitations. Adefovir dipivoxil is a novel nucleotide analog which, when given at 10 mg/day for 48 weeks, improved liver histology in 28% more patients with hepatitis B e antigen (HBeAg)-positive CHB, and in 31% more patients with HBeAg-negative CHB compared with placebo (p < 0.001). Additionally, adefovir dipivoxil therapy significantly improved virologic and biochemical parameters in both HBeAg-positive and -negative CHB patients. Adefovir dipivoxil offers important advantages over other CHB treatment options: it maintains activity against lamivudine-resistant CHB, has good efficacy against HBeAg-negative CHB, and has minimal adverse effects at the 10-mg/day Food and Drug Administration-approved dose. CONCLUSIONS: Approved medications for the treatment of CHB have many limitations, and adefovir dipivoxil provides a new important option as an initial treatment, as well as treatment in lamivudine-resistant patients.

Adenine↗
PubMed1990

Complete heart block in fetal lambs. I. Technique and acute physiological response.

Prenatally diagnosed complete heart block (CHB), without associated cardiac anomalies, is often refractory to attempts to increase heart rate and cardiac output by medical therapy, and results in fetal death. We developed a model of CHB in fetal lambs in order to evaluate the acute physiological consequences of CHB and to assess the feasibility of fetal cardiac ventricular (V) and atrioventricular (AV) pacing. After hysterotomy and fetal sternotomy AV-sequential pacing leads were placed on the right atrium and ventricle (RV). Electromagnetic flow transducers were placed around the pulmonary artery and the ascending aorta to measure combined ventricular output (CVO) in normal sinus rhythm (NSR), CHB, AV, and V pacing. CHB block was successfully induced in 19 of 21 (90%) fetal lambs at 100 to 110 days' gestation by injection of formalin into the interventricular septum. Two fetuses were refractory to CHB despite multiple injections. The mean ventricular escape rate was 52 +/- 3 (+/- SEM) beats/min (range, 45 to 60 beats/min). CHB lasted for the period of study (1 to 8 hours), and spontaneously reverted to NSR in one fetus after 3 hours. Combined ventricular output in NSR was 470 +/- 31 mL/min (+/- SEM), which fell to 213 +/- 13 mL/min in CHB, 45% of normal CVO (P less than .0001). CVO during AV-sequential and V pacing was 77% (P = .02) and 62% (P less than .001), respectively, of combined ventricular output in NSR. Both RV (27%) and left ventricles (LV) (37%) showed compensatory increase in stroke volume during CHB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The relationship of vehicle to target organ toxicology induced by the naturally occurring nitrile 1-cyano-2-hydroxy-3-butene.

The effects of gavage vehicle on the acute toxicity of the naturally occurring nitrile 1-cyano-2-hydroxy-3-butene (CHB) were investigated by oral administration of 200 mg/kg body wt/day CHB to male CDF (F-344/Crl BR) rats for 2 days. The vehicles studied here were distilled water, 5% aqueous Tween 20, and corn oil. Liver, kidney, and pancreas were examined histologically and the differences in lesion incidence and severity were assessed. The effects of gavage vehicle on nitrile-induced elevations of daily urinary thiocyanate excretion and tissue glutathione concentrations were also assessed. The pancreatotoxicity of CHB was present regardless of vehicle and consisted of apoptosis of pancreatic acinar cells, infiltration of pancreatic lobules by macrophages, and acinar atrophy and disorganization. CHB in water alone was associated with the least pancreatotoxic effect, whereas the aqueous Tween vehicle was associated with more severe CHB-induced pancreatic lesions. CHB-induced elevations of tissue nonprotein thiol and glutathione concentrations occurred in all treatment groups, but the values were elevated significantly less in the pancreata of CHB/Tween-treated rats than in those of rats given CHB in water or corn oil. By contrast, the greatest elevation in daily urinary thiocyanate excretion occurred in rats given CHB in aqueous Tween, indicating increased biotransformation of CHB to cyanide when Tween 20 was used as a vehicle. These results illustrate the difficulty of identifying suitable vehicles for administration of lipophilic compounds in toxicology studies.

Alkenes↗
PubMed1997

Concentrations and accumulation patterns of organochlorine contaminants in the blubber of harbour porpoises, Phocoena phocoena, from the coast of Newfoundland, the Gulf of St Lawrence and the Bay of Fundy/Gulf of Maine.

Concentrations of 99 organochlorine compounds were measured in the blubber of 196 harbour porpoises, Phocoena phocoena, killed in commercial gill net fisheries in the western North Atlantic. PCBs and chlorinated bornanes (CHB) were the dominant contaminants in all porpoises. Mean concentrations (with standard deviations) of PCBs and CHBs from the three regions were as follows: Bay of Fundy/Gulf of Maine, PCB males 17.3 +/- 11.2 microg/g, PCB females 11.4 +/- 4.8 microg/g, CHB males 11.5 +/- 6.6 microg/g, CHB females 8.4 +/- 5.3 microg/g; Gulf of St Lawrence, PCB males 10.6 +/- 5.4 microg/g, PCB females 7.2 +/- 3.9 microg/g, CHB males 14.1 +/- 8.8 microg/g, CHB females 9.0 +/- 6.3 microg/g; southeast Newfoundland, PCB males 5.2 +/- 2.5 microg/g, PCB females 5.5 +/- 4.4 microg/g, CHB males 7.0 +/- 2.2 microg/g, CHB females 5.5 +/- 3.0 microg/g. The relative composition of the major contaminant groups found in male and female harbour porpoise blubber from the three locations varied. In order of decreasing concentration, porpoises from Fundy/Maine had PCBs > CHB > DDT > chlordanes (CHL), whereas Gulf of St Lawrence and Newfoundland porpoises had CHB > PCB > DDT > CHL. Significant increases with age were observed for most contaminants in male harbour porpoises, and significant decreases were observed in females. Females lose about 15% of their contaminant burden per birth. PCB and DDT levels in porpoises from the Bay of Fundy are significantly lower than those recorded in the 1970s.

Journal Article↗
PubMed2004

Maternal and sibling microchimerism in twins and triplets discordant for neonatal lupus syndrome-congenital heart block.

OBJECTIVE: Neonatal lupus syndrome-congenital heart block (NLS-CHB) is an acquired autoimmune disease in which maternal autoantibodies are necessary but not sufficient for disease. Maternal myocardial cells have been found in the hearts of patients with NLS-CHB, suggesting that maternal microchimerism may also play a role. In this study we asked whether levels of microchimerism in the blood are associated with NLS-CHB in discordant twins and triplets. METHODS: Human leucocyte antigen (HLA)-specific and Y-chromosome-specific real-time quantitative polymerase chain reaction (PCR) was used to quantitatively assay maternal and sibling microchimerism in peripheral blood. Because of HLA allele sharing in families, it was not always possible to distinguish between multiple sources of microchimerism. RESULTS: In one family, maternal and/or sibling microchimerism was detected in two triplets who had CHB, but not in the triplet with transient hepatitis. Levels ranged from 4 to 948 genome-equivalents of foreign deoxyribonucleic acid per million host genome-equivalents (gEq/million). Over the first year levels of sibling microchimerism decreased in the triplet with complete CHB and increased in the triplet who progressed from first- to second-degree CHB. In a second family, maternal and/or sibling microchimerism was detected in the healthy twin (1223 gEq/million) but not in the twin with CHB. CONCLUSIONS: Maternal and/or sibling microchimerism was detectable in the blood of infant twins and triplets discordant for NLS. Microchimerism in the blood was not specific for NLS-CHB, although in one family levels correlated with disease. Thus, microchimerism in the blood and/or tissues may be involved in the pathogenesis or progression of NLS-CHB, but additional factors must also contribute. Further investigation is warranted.

Chimerism↗
PubMedDate not supplied

Combination of Peginterferon alpha-2b (12 kDa) and Lamivudine in difficult-to-treat chronic hepatitis B- an Indian experience.

INTRODUCTION: Treatment strategies for chronic hepatitis B (CHB) using either interferon or Lamivudine can achieve sustained response in 30-40 % in HBeAg positive CHB. Retreatment of treatment failure in CHB and treatment of HBeAg negative patients pose major therapeutic challenge. Because of success story of Peginterferon in hepatitis C and some preliminary data in CHB, we undertook this open-labeled prospective study to study the response of Peginterferon alpha-2b (PegIFN) and Lamivudine combination in patients of CHB. MATERIALS AND METHODS: Following 4 groups of patients of CHB with persistently elevated transaminases were treated with Lamivudine 100 mg PO daily and PegIFN 1.5 microg/kg SC once a week- 1) HBeAg negative treatment naive patients- for 12 months 2) HBeAg negative patients who were nonresponsive to at least two treatment regimens for 12 months, 3) HBeAg positive treatment naive patients- for 6 months 4) HBeAg positive patients who were treatment failure at least with two regimens- for 6 months. Patients were tested for LFT, HBeAg, antiHBe, quantitative HBVDNA (only in HBeAg negative CHB) and liver biopsy when possible at inclusion. During treatment period, LFT was tested at monthly interval and HBeAg, antiHBe and HBVDNA (in HBeAg negative CHB) at 3 monthly intervals. End of treatment response (EOR) was assessed at end of treatment period and sustained response (SR) at 6 months post treatment. Treatment response was defined in HBeAg positive patients with normalization of enzymes and disappearances of HBeAg & in antiHBe positive patients with normalization of enzymes and loss of detectable HBVDNA. RESULTS: Total 25 patients with CHB were included in this study with mean age of 37.9 +/- 4.6 years (range 20-56) and male: female= 11.5:1. 1) In HBeAg negative treatment naive patients, 4/6 patients achieved EOR (66.6%), whereas in 3/6 patients (50%) had SR. 2) In HBeAg negative treatment failure group, 4/5 patients had EOR (80%) and 3/5 patients achieved SR (60%), of which 1 patient lost HBsAg. 3) In HBeAg positive treatment naive patients, 4/5 patients achieved EOR (80%) and 3/5 patients obtained SR (60%). One patient in this group lost HBsAg. 4) In HBeAg positive treatment failure group, 5/9 patients achieved EOR (55.5%), whereas 3/9 patients (33.3%) obtained SR. CONCLUSION: Overall, in difficult-to-treat patients (considering groups 1, 2 & 4- total 20 patients) with combination of PegIFN and Lamivudine, EOR was seen in 13 patients (65%), SR was obtained in 9 patients (45%) and loss of HBsAg was seen in 1 patient (5%).

Adult↗
PubMed1987

Risk of developing complete heart block during bedside pulmonary artery catheterization in patients with left bundle-branch block.

We examined the incidence of complete heart block (CHB) as a complication of pulmonary artery catheterization with balloon-tipped, flow-directed catheters in patients with left bundle-branch block (LBBB). The study group included 47 consecutive critically ill patients with LBBB in the medical intensive care and coronary care units, who underwent a total of 82 pulmonary artery catheterizations. Twenty-six patients had an acute myocardial infarction, 34 patients had severe congestive heart failure (Killip class III or class IV), and 15 patients died during their hospitalization. Thirty patients had an old LBBB (more than one month in age), nine patients had a new LBBB, and the age of the LBBB was indeterminate in eight patients. There were five episodes of CHB in the group of patients with old LBBB. However, none of these episodes were related to the pulmonary artery catheterization, since CHB occurred either prior to catheterization (one case) or from one to 16 days after the pulmonary artery catheter had been removed (four cases). There were no episodes of CHB related to the pulmonary artery catheterization procedure in the patients with either old LBBB or indeterminate-aged LBBB. There were two episodes of CHB in patients with new LBBB. In both patients, the CHB occurred one day after the pulmonary artery catheter had been inserted. In both patients, CHB developed after episodes of ventricular tachycardia that eventually resulted in their deaths. Although it is unlikely, we could not rule out the possibility that the CHB was related to the presence of the pulmonary artery catheter. We conclude that the incidence of CHB complicating pulmonary artery catheterization with balloon-tipped, flow-directed catheters in critically ill patients with old or indeterminate-aged LBBB is extremely low. Therefore, we do not recommend the routine placement of a temporary transvenous pacemaker in all patients with LBBB prior to pulmonary artery catheterization.

Aged↗
PubMedDate not supplied

Early and late postoperative complete heart block in pediatric patients submitted to open-heart surgery for congenital heart disease.

The incidence of complete heart block (CHB) following open-heart surgery for congenital heart disease is about 1%. Most of postoperative CHBs are the consequence of procedures involving the closure of ventricular septal defect; they usually occur immediately after surgery or early in the postoperative period; in few cases they also may occur many months or years after surgery. Early postoperative CHB can be transient or permanent. Permanent pacing is generally not recommended in the former. On the contrary, if CHB persists after at least two weeks of temporary pacing, permanent pacing is needed because the block is usually due to His bundle damage or to trifascicular damage and this is associated with excessive bradycardia and risk of asystole. Late postoperative CHB can be due to the recurrence of previous transient early postoperative CHB or to the progression of postoperative His-Purkinje conduction troubles suggesting trifascicular damage. Permanent pacing is obviously needed in case of documented late postoperative CHB. The prophylactic use of permanent pacing in patients at risk of late postoperative CHB is still a controversial point. Electrophysiologic studies should be performed in such patients. The occurrence of second degree AV block within or below the bundle of His during atrial pacing at rate lower than 200/min can be considered a good marker of impending CHB. In this case prophylactic permanent pacing should be recommended, especially in patients with coexisting problems of troublesome or malignant tachyarrhythmias who have to be treated with antiarrhythmic drug therapy that may favour the progression to CHB.

Adolescent↗
PubMed2005

Maternal antibody responses to the 52-kd SSA/RO p200 peptide and the development of fetal conduction defects.

OBJECTIVE: To identify a finer level of antibody specificity for risk of congenital heart block (CHB) than reactivity to 52-kd SSA/Ro (Ro 52). METHODS: Serum from mothers enrolled in the Research Registry for Neonatal Lupus and the observational PR Interval and Dexamethasone Evaluation (PRIDE) study was evaluated for reactivity against peptide aa200-239 of Ro 52 (p200), recently reported to be associated with a higher risk of CHB. RESULTS: The majority of 156 Ro 52-positive sera tested were reactive with p200 (>3 SD above control), irrespective of the clinical status of the child. Optical density (OD) values of p200 did not differ significantly among mothers of children with CHB (mean +/- SD 0.187 +/- 0.363), mothers of children with rash (mean +/- SD 0.176 +/- 0.356), and mothers of children without neonatal lupus (mean +/- SD 0.229 +/- 0.315). Reactivity against p200 was found in 80 of 104 mothers of children with CHB (77%), 24 of 30 mothers of children with rash (80%), and 21 of 22 mothers who delivered healthy children and had no children with neonatal lupus (95%) (P not significant for all comparisons). Sera from 4 mothers of children with CHB with varied p200 titers (OD range 0.025-1.818) bound to the surface of non-permeabilized apoptotic, but not proliferating, human fetal cardiocytes. In 32 Ro 52-positive women who completed the PRIDE study (22 with no child with neonatal lupus, 7 with a child with CHB, and 3 with a child with rash) in whom p200 levels were determined during pregnancy, the correlation between level of p200 (OD range 0.000-1.170) and maximal fetal PR interval (range 115-168 msec) was not significant (rho = 0.107, P = 0.58). CONCLUSION: Reactivity to p200 is a dominant but not uniform anti-Ro 52 response in women whose children have CHB. Since exposure to this antibody specificity was observed with a similar frequency in children without CHB born to mothers with anti-Ro 52, additional factors are necessary to convert risk to disease expression.

Antibodies, Antinuclear↗
PubMed1994

Signal-averaged electrocardiographic late potentials in children with complete heart block.

The purpose of this study was to examine signal-averaged electrocardiographic (SA-ECG) late potentials to predict ventricular arrhythmias during intrinsic cardiac rhythm and during ventricular pacing in children with complete heart block (CHB). Recordings of SA-ECG were obtained from eight patients (aged 3-18 years) with documented CHB. The etiology of CHB was congenital in four cases and acquired in four cases. Six of these patients underwent permanent pacemaker implantation. Comparisons of the SA-ECG were made before and during ventricular pacing. Abnormalities of SA-ECG during intrinsic cardiac rhythm were noted in four patients, all of whom were older than 14 years. Although there was no significant difference in SA-ECG parameters between patients with congenital CHB and acquired CHB, abnormal SA-ECG was noted in one of four patients with congenital CHB and in three of four patients with acquired CHB. Two patients without permanent pacemaker implantation had normal SA-ECG, but four of six patients with permanent pacemaker implantation had abnormal SA-ECG. Three of the four patients had abnormal SA-ECG during ventricular pacing, but the abnormal SA-ECG in one patient had normalized during ventricular pacing. It is important to record SA-ECG before and during ventricular pacing to detect late potentials in patients with CHB. It may be useful to record SA-ECG while changing the pacing site to find ideal sites for electrode implantation for the potential prevention of ventricular arrhythmias.

Action Potentials↗