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Biomedical subjects

A Eid

Publications and source records attributed to A Eid.

At least 37 records · Page 2Linked to original sources

Human interleukin-6 facilitates hepatitis B virus infection in vitro and in vivo.

BACKGROUND AND AIM: Research on hepatitis B virus (HBV) infection in vivo has been limited due to the absence of a suitable animal model. We have developed a human-mouse radiation chimera in which normal mice, preconditioned by lethal total body irradiation and radioprotected with SCID mouse bone marrow cells, are permissive for engraftment of human hematopoietic cells and solid tissues. This resulting human-mouse model, which comprises three genetically disparate sources of tissue, is therefore termed Trimera. This study was aimed at assessing the effect of human IL-6 on HBV infection in vivo in Trimera mice. METHODS: Trimera mice were transplanted with human liver tissue fragments or with HepG2-derived cell lines, which had been previously infected ex vivo with HBV in the presence or absence of human interleukin-6 (hIL-6) and in the presence of anti-IL-6-neutralizing antibodies. RESULTS: HBV sequences appeared in the sera of animals in which the liver tissue was incubated with both HBV and hIL-6 prior to transplantation. A similar result was obtained when a human hepatoblastoma cell line (HepG2), expressing the hIL-6 receptor, was infected ex vivo with HBV in the presence of hIL-6 prior to their injection into spleens of Trimera mice. However, when liver fragments were infected ex vivo and simultaneously treated with neutralizing antibodies against hIL-6 or were incubated with HBV prior to transplantation without hIL-6, the rate of mice positive for HBV DNA in their sera was lower. Human mononuclear cells are also permissive for HBV infection in vitro: in the presence of hIL-6 the infection of these cells is enhanced; and this infection is suppressed by the chimeric protein named Hyper-IL-6, generated by the fusion of hIL-6 to the soluble hIL-6 receptor (sIL-6Ralpha, gp80). CONCLUSION: hIL-6 facilitates HBV infection in vitro and in vivo.

Animals↗

Laparoscopic cholecystectomy: what does affect the outcome? A retrospective multifactorial regression analysis.

BACKGROUND: The association between various factors and the postoperative outcome has not been thoroughly studied in laparoscopic cholecystectomy (LC). The aim of this retrospective study was to determine which factors significantly affect patients outcome after LC. METHODS: The medical and operative records of all consecutive patients who underwent LC at our institution from 1991 to 1996 were reviewed. The effect of age, medical and surgical history, duration of procedure, and setup (urgent or elective) on the postoperative complication rate and on the length of postoperative hospital stay (LOS) were analyzed using multiple linear regression and logistic regression analysis. Overall, 601 patients were included in the study. RESULTS: The factors that significantly prolonged LOS were age (p = 0.0145), acute cholecystitis (p = 0.0006), history of ischemic heart disease (p = 0.0332), and duration of procedure (p < 0.0001). A significantly higher postoperative morbidity rate was noted in patients who had a procedure longer then 2 h than in patients whose surgery required less the 2 h (13.6% vs 3.6%, respectively; p < 0.0001). Similarly, higher morbidity was noted in elderly patients than in younger patients (16% vs 6.1%; p = 0.0005). Other factors that significantly increased postoperative morbidity included acute cholecystitis (p = 0.023), a history of cholangitis (p = 0.018), and diabetes (p = 0.05). CONCLUSIONS: According to this study, advanced age, longer duration of procedure, and acute cholecystitis significantly increase both the postoperative morbidity and the LOS. History of ischemic heart disease significantly increases LOS, but does not increase morbidity after LC.

Adolescent↗

Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees.

Two human monoclonal antibodies (mAbs) against hepatitis B surface antigen (HBsAg) generated in the Trimera mouse system are described. Both mAbs 17.1.41 and 19.79.5 are of the IgG1 isotype and have high affinity constants for HBsAg binding in the range of 10(-10) mol/L. Monoclonal antibody 17.1.41 recognizes a conformational epitope on the a determinant of HBsAg whereas mAb 19.79.5 recognizes a linear one. The 2 mAbs bind to a panel of hepatitis B virus (HBV) subtypes with distinct patterns. The neutralizing activity of these antibodies was tested in 2 different animal model systems. Administration of each mAb to HBV-Trimera mice, a system that provides a mouse model for human hepatitis B infection, reduced the viral load and the percentage of HBV-DNA-positive mice in a dose-dependent manner. These 2 mAbs were more effective than a polyclonal antibody preparation (Hepatect; Biotest Pharma, Dreieich, Germany) in both inhibition of HBV liver infection and reduction of viral load. A single administration of a mixture of these mAbs into HBV chronic carrier chimpanzees resulted in immediate reduction in HBsAg levels followed by recurrence to initial levels within few days. Thus, these mAbs may be potential candidates for preventive therapy or in combination with other antiviral agents against HBV. Further studies in humans are needed to assess these mAbs in various clinical indications.

Animals↗

Bacteremic and nonbacteremic pneumococcal pneumonia. A prospective study.

We prospectively identified cases of pneumococcal pneumonia and used stringent criteria to stratify them into bacteremic and nonbacteremic cases. Although patients were distributed among racial groups in proportion to all patients seen at this medical center, the proportion of African-Americans with bacteremic disease was significantly increased. All patients had at least 1 underlying condition predisposing to pneumococcal infection, and most had several. Although the mean number of predisposing factors was greater among bacteremic patients than nonbacteremic patients, only alcohol ingestion was significantly more common. Nearly one-third of patients had substantial anemia (hemoglobin < or = 10 g/dL) on admission, which may have predisposed to infection. In the case of other laboratory abnormalities, such as albumin, creatinine, and bilirubin, it was difficult to determine which abnormality might have predisposed to pneumococcal infection and which might have resulted from it. The radiologic appearance was varied. Airspace consolidation and air bronchogram on chest X-ray were highly associated with bacteremic disease, as was the presence of pleural effusion. Although the Pneumonia Patient Outcomes Research Team (PORT) risk score was a predictor of mortality, it did not help to predict the presence of bacteremia in an individual case. Most patients who died in the first week in hospital were bacteremic, and a high PORT risk score with bacteremia reliably predicted a high likelihood of a fatal outcome. Eleven patients had extrapulmonary disease with meningitis, empyema, and septic arthritis predominating; all of these patients were bacteremic. The antibiotic susceptibility of our strains correlated well with those that have been reported in the United States during the years of this study. The use of numerous antibiotics of different classes in many patients, especially those who were the most ill, precluded analysis of outcome based on antibiotic therapy. Only 17 patients had been vaccinated. Since nearly all patients had conditions for which pneumococcal vaccine is recommended and more than one-third had been hospitalized in the preceding 6 months, the low rate of vaccination can be regarded as a missed opportunity to administer a potentially beneficial vaccine.

Adult↗

Extension of the organ pool in kidney transplantation: first year experience of the Israel Transplant Center.

BACKGROUND: Over a 12 month period, the Israel Transplant Center doubled the number of donors by assigning a nurse coordinator to each of 22 hospitals around the country and by using kidneys from elderly donors. OBJECTIVE: To evaluate the impact of our "marginal donors" policy on the results immediately following transplantation. METHODS: Between October 1997 and September 1998, 140 cadaveric kidney transplantations from 72 donors were performed in Israel. We defined two groups of recipients: patients with immediate graft function and patients with either delayed graft function requiring > 1 week of dialysis post-transplant or with primary graft non-function. We compared the following parameters between groups: donor and recipient age and gender, cause of donor's death, length of stay in the intensive care unit, vasopressor dosage and creatinine levels before harvesting, cold ischemic time, and the number of recipient grafts. RESULTS: There were 102 recipients (72.8%) with immediate graft function and 38 with either PNF (n = 13, 9.3%) or DGF (n = 25, 17.9%). On regression analysis, donor age > 50 year and retransplantation were significant risk factors for PNF or DGF (odds ratio 4.4 and 2.8, respectively). Of the 56 kidneys from donors > 50 years old, 21 (37.5%) developed either PNF (n = 9) or DGF (n = 12). CONCLUSIONS: We conclude that kidneys from donors over age 50 are at increased risk for graft non-function or delayed function. Better assessment of functional capacity of kidneys from "aged" donors may help to choose appropriate donors from that pool.

Adolescent↗

The hepatitis B virus-trimera mouse: a model for human HBV infection and evaluation of anti-HBV therapeutic agents.

Previous studies have demonstrated the feasibility of implantation of human blood cells or tissues in lethally irradiated mice or rats, radioprotected with SCID mouse bone marrow cells: The Trimera system. In the present study, we describe the development of a mouse Trimera model for human hepatitis B virus (HBV) infection. In this model, viremia is induced by transplantation of ex vivo HBV-infected human liver fragments. Engraftment of the human liver fragments, evaluated by hematoxylin-eosin staining and human serum albumin mRNA expression, was observed in 85% of the transplanted animals 1 month postimplantation. Viremia levels were determined in these mice by measuring serum HBV DNA using polymerase chain reaction (PCR), followed by dot-blot hybridization. HBV DNA is first detected 8 days after liver transplantation. Viremia attains a peak between days 18 and 25 when HBV infection is observed in 85% of the transplanted animals. The HBV-Trimera model was used to evaluate the therapeutic effects of human polyclonal anti-HBs antibodies (Hepatect) and of two reverse-transcriptase inhibitors, lamivudine (3TC) and beta-L-5-fluoro-2',3'-dideoxycytidine (beta-L-5FddC). Treatment of HBV-Trimera mice with these drugs effectively reduced both the percentage of infected animals and the viral load in their sera. Treatment cessation resulted in rebound of viral load, indicating HBV replication upon drug withdrawal. These results show that the HBV-Trimera model represents a novel experimental tool for simulating human HBV infection and evaluating potential anti-HBV therapeutic agents.

Animals↗

Dynamics of protein 27 of avian leukosis virus and transforming growth factor beta2 in lymphoid leukosis susceptible and resistant broiler chicken breeding stock.

The dynamics of the serum concentration of protein 27 (P27) of avian leukosis virus and transforming growth factor beta2 (TGF-beta2) were compared during the period between 29 and 59 weeks of age in two flocks of broiler chicken breeding stock undergoing outbreaks of severe lymphoid leukosis (LL) associated with persistent high mortality (susceptible) and in another two flocks of breeding stock with the presence of avian leukosis virus in association with low mortality due to LL (resistant). The average mean concentration of serum P27 in the LL-susceptible flocks was significantly higher (p<0.05) than that in the LL-resistant flocks in six out of seven samplings performed at 5-week intervals, between 29 and 59 weeks of age. The peak in the average rise of serum P27 in the LL-resistant flocks (309 pg/ml) was associated with the highest level of TGF-beta2 (1282 pg/ml) among all flocks and at all sampling times. The significance of TGF-beta2 in inhibition of lymphoid tumour development is discussed.

Animals↗

Combination of intra-articular tenoxicam, lidocaine, and pethidine for outpatient knee arthroscopy.

BACKGROUND: Studies of intra-articular non-steroidal anti-inflammatory drugs have revealed an analgesic effect equivalent to that of intra-articular local anaesthetic agents and morphine. The aim of this study was to evaluate the analgesic effect of intra-articular lidocaine, pethidine and tenoxicam compared with that of lidocaine and pethidine on postoperative pain after arthroscopy. METHODS: After day-case knee arthroscopy, 60 patients were randomly allocated to one of three groups to receive 20 ml of a solution containing 0.9% saline (group S), 2% lidocaine and 10 mg preservative-free pethidine (group LP) and 2% lidocaine, 10 mg preservative-free pethidine and 20 mg tenoxicam (group LPT). Postoperative pain was assessed using a visual analogue scale and measuring analgesic requirements. RESULTS: Pain scores were significantly lower in the LP group than in the S group at 1 and 2 h after surgery. From 4 h until the end of the first postoperative day, pain scores were significantly lower in the LPT group of patients at rest and on knee flexion than in the other two groups; these patients also used less oral analgesics (P<0.05). CONCLUSION: The combination of 20 ml lidocaine 2%, 10 mg pethidine and 20 mg tenoxicam given intra-articularly provided superior analgesia and reduced oral analgesic requirement during the first day after arthroscopy compared with lidocaine and pethidine alone.

Administration, Oral↗