Epidemiology and transmission of hepatitis B and C viruses in Kazakhstan

AIM: To investigate the epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in the two major ethnic groups in Kazakhstan. METHODS: A cross-sectional prospective study of HBV and HCV seroprevalence was performed among individuals born in Kazakhstan with no history of chronic hepatitis or liver disease. RESULTS: There were 290 volunteers (140 Russians and 150 Kazakhs) aged 10 to 64 years, males accounted for 46%. Active HBV infection (HBsAg positive) was present in 3.8%, anti-HBc in 30%. The prevalence was similar in females and males (33% vs 25%) (P = 0.18). The prevalence of anti-HBc increased from 19% in 10-29 years old volunteers to 53% in 50-years and older volunteers. The prevalence of HBV infection was higher in married than in single adults (38% vs 26%, respectively) (P = 0.2) and more common in Kazakhs (35%) than in Russians (24%) (P = 0.07). HCV infection was present in 9 subjects (3.2%), 5 of them also were positive for anti-HBc in the absence of HBsAg. CONCLUSION: The frequency of active HBV infection (3.8%) coupled with a high prevalence of HBV exposure in those > 50 years of age increases with age, which suggests that horizontal transmission likely relates tothe use of contaminated needles. The low prevalence of HCV infection suggests that HBV and HCV are acquired differently in this group of subjects.     

Intermediate lymphocytic lymphoma: immunophenotypic and cytogenetic findings

A detailed immunohistologic and cytogenetic analysis of 12 cases of intermediate lymphocytic lymphoma was performed. The characteristic immunophenotype of intermediate lymphocytic lymphoma was: surface IgM and IgD+, BA1+, B1+, BA2-, B2-, B4+, Leu 14+, Leu 1+, HLA-DR+, and common acute lymphocytic leukemia associated (CALLA) antigen negative. Clonal chromosome abnormalities were identified in ten cases, with structural or numerical abnormalities of chromosomes 11 or 12 in nine cases. Five cases had structural abnormalities involving the long arm of chromosome 11; three of these had translocations with chromosome 14 at band q32. Three cases had trisomy 12, and one case had a translocation involving the long arm of chromosome 12. The tenth case had a translocation involving the long arms of chromosomes 7 and 9. These characteristic immunophenotypic and cytogenetic findings suggest a close lineage relationship between intermediate lymphocytic lymphoma and small lymphocytic (well differentiated) lymphoma/chronic lymphocytic leukemia. Their differing clinical, cytologic, and architectural features suggest, however, that intermediate lymphocytic lymphoma should be considered a separate category of lymphocytic lymphoma in the International Working Formulation.     

High-dose therapy and autologous peripheral blood stem cell transplantation for patients with lymphoma

Forty patients with refractory Hodgkin's disease (24 patients) or non- Hodgkin's lymphoma (16 patients) who were considered for high-dose therapy but not for autologous bone marrow transplantation (ABMT) due to BM metastases, previous pelvic irradiation, a history of marrow involvement by tumor or hypocellular marrow in conventional harvest sites received high-dose therapy and autologous peripheral blood (PB) hematopoietic stem cell transplantation. Disappearance of circulating neutrophils and development of RBC and platelet transfusion-dependence was followed, in the evaluable patients, by reappearance of 0.5 x 10(9)/L circulating granulocytes and sufficient platelets to obviate the need for platelet transfusions at a median of 25 days after transplantation. Twenty-three patients experienced a clinical complete remission (CR). The projected 2-year event-free survival was 24% for all 40 patients and 49% for the non-Hodgkin's lymphoma patients. The projected 18-month event-free survival for the Hodgkin's disease patients was 15%. PB stem cell transplantation provided an opportunity to administer high-dose salvage therapy to patients with refractory lymphoma who otherwise were not candidates for such therapy. For some of those patients, the high-dose therapy produced prolonged survival, free of tumor progression.     

In vitro autoradiographic and in vivo scintigraphic localization of somatostatin receptors in human lymphatic tissue

Receptors for the neuropeptide somatostatin (SS) were evaluated in vitro and in vivo in various human lymphatic tissues, ie, thymus, spleen, and lymph nodes; thymic carcinoids and thymomas were also tested. The receptors were measured in vitro using receptor autoradiography on tissue sections incubated with the SS analog 125I- [Tyr3]-octreotide or 125I-[Leu8,D-Trp22,Tyr25]-SS-28. All tissues were SS-receptor positive for either radioligand, except the thymomas. In thymic tissue, the receptors were diffusely located in the medulla, presumably on epithelial cells. In the spleen, the red pulp was strongly labeled. In the lymph nodes, the germinal centers were preferentially labeled. In all tissues, the receptors were of high affinity (kd thymus, 0.84 nmol/L; kd spleen, 1.6 nmol/L; kd lymph node, 0.62 nmol/L) and specific for SS. Displacement by nanomolar concentrations of SS-14, SS-28, and octreotide was observed, as was guanosine triphosphate dependency. The in vivo visualization of somatostatin receptors was performed after injection of 111In-DTPA- octreotide and gamma-camera scintigraphy. The spleen, but not thymus or lymph nodes, were visualized. These data suggest an important role for SS in regulating immune functions through SS receptors in thymus, spleen, and lymph nodes. Furthermore, SS may regulate neuroendocrine functions in the thymus.     

Randomized controlled trial of recombinant alpha-2a-interferon for chronic hepatitis C

We enrolled 32 patients with chronic hepatitis C into a randomized, controlled trial to evaluate the efficacy of recombinant alpha-2a-interferon treatment. Sixteen patients were randomized to receive 1.5 million units of recombinant alpha-2a-interferon subcutaneously, thrice weekly, for six months while the remaining 16 patients were randomized to a control group that received no treatment. The mean serum alanine aminotransferase (ALT) level during the six-month study period, expressed as a percentage of the prestudy baseline value, was 82% for the control group compared to 56% for the treatment group (P=0.014). One fourth of the treatment group normalized their serum ALT level compared to only 6% of the controls (P=0.05). During posttherapy follow-up, 86% of responders clinically relapsed. Loss of anti-HCV IgM and HCV RNA occurred exclusively in interferon-treated responders. Anti-interferon antibodies developed in 32% of all treated patients. Forty percent of nonresponders developed anti-interferon antibodies compared to only 14% of responders (P=NS). We conclude that recombinant alpha-2a-interferon is clinically effective in patients with chronic hepatitis C. However, most responders in this trial of low-dose interferon relapsed upon cessation of treatment.     

Genotype does not affect pattern of HCV RNA decrease among responders during interferon treatment of chronic hepatitis C. Consensus Interferon Study Group

We assessed differences in the pattern of HCV RNA decrease for HCV genotypes 1, 2, and 3 during interferon treatment to determine if the lower response rates observed among genotype 1 patients were related to a slower decrease in HCV clearance. Serum HCV RNA values of 472 chronic hepatitis C patients treated with either consensus interferon (CIFN) or interferon alfa-2b (IFN alfa-2b) were evaluated. Neither virological sustained responders nor relapsers differed in the pattern of serum HCV RNA decrease based on genotype. Virological sustained responders infected with genotype 1 cleared HCV RNA as rapidly as sustained responders who were infected with genotype 2 or 3. Relapsers had a slower rate of serum HCV RNA decrease than did virological sustained responders. Nonresponders differed in the pattern of serum HCV RNA decrease based on genotype: HCV genotype 3 patients had the greatest decrease in serum HCV RNA; genotype 2 patients had an intermediate decrease; and genotype 1 patients had the least serum HCV RNA decrease. HCV genotype 1 patients treated with CIFN had a greater decrease in serum HCV RNA during therapy than did patients treated with IFN alfa-2b. However, there was no difference in the magnitude of serum HCV RNA decrease between the two interferon treatments for patients infected with genotype 2 or 3. In summary, both genotype and ultimate response to treatment are determinants of the pattern and rate of serum HCV RNA change during interferon therapy of chronic hepatitis C.     

Successful Results of a Bipolar Active Fixation Lead for Atrial Application: An Interim Analysis

Adequate atrial lead performance consists of stable sensing and pacing properties. To evaluate whether the CPI 4269 bipolar lead, covered with mannitol (Sweet Tip), in the atrial position encounters these properties, we performed a prospective study of this lead. After complete dissolution of the mannitol helix, mapping of the atrium to obtain the highest electrogram and lowest threshold was followed by screw-in into the endocardium. Intraoperative measurements were performed and long-term follow-up was scheduled every 6 to 12 months to measure threshold and perform an intracardial electro-gram. Between February 1993 and December 1996, a total number of 73 leads in the atrial position in a consecutive series of patients was implanted. Implantation was performed in 28 patients receiving an AAIR and 45 patients a DDDR pacemaker. Reason for pacemaker implantation was a third-degree AV block in 37% of patients, type II second-degree AV block in 25%, sick sinus syndrome in 35%, and drug refractory paroxysmal atrial fibrillation following His-bundle ablation in 3%. The intraoperative bipolar atrial electrogram had a mean voltage of 4.25 ± 2.1 mV. The acute atrial bipolar threshold was 0.63 ± 0.43 V, and current was 1.35 ± 0.81 mA at a 1.0-ms pulse duration. The mean acute resistance of the lead was 572 ± 86 Ohm. After a mean follow-up of 18.3 months, the bipolar intracardial electrogram was 3.37 ± 2.00 mV, the mean atrial threshold measured at the last outpatient clinic visit was 0.99 ± 0.74 V and the mean impedance was 640 ±127 Ohm. A sensing problem due to traction of the atrial lead occurred in only one patient. Acute and late dislodgement did not occur. The CPI 4269 (Sweet Tip) lead is manufactured with a dissolvable capsule covering the helix tip electrode, permitting a safe passage through the venous system. This interim analysis shows that this lead in the atrial position has favorable acute and chronic results.