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Biomedical subjects

R Safadi

Publications and source records attributed to R Safadi.

At least 19 recordsLinked to original sources
PubMed2005

Adoptive transfer of small numbers of DX5+ cells alleviates graft-versus-host disease in a murine model of semiallogeneic bone marrow transplantation: a potential role for NKT lymphocytes.

Natural killer T (NKT) lymphocyte cells are a subset of regulatory lymphocytes with important immunemodulatory effects. Our aim was to evaluate the effect of transplantation of NKT lymphocytes on graft versus host disease (GVHD) in a murine model of semiallogeneic BMT. GVHD was generated by infusion of 2 x 107 splenocytes from C57BL/6 donor mice into irradiated (C57BL/6 x Balb/c)F1 recipient mice. Adoptive transfer of increasing numbers of DX5+ cells was performed. Recipient mice were followed for histological parameters of GVHD-associated liver, bowel, and cutaneous injury. Intrahepatic and intrasplenic lymphocytes were isolated and analyzed by FACS for CD4+ and CD8+ subpopulations. It was seen that adoptive transfer of 4.5 x 106 DX5+ cells significantly alleviated GVHD-related hepatic, bowel, and cutaneous injury, and improved survival (85% survival on day 28). In contrast, depletion of DX5+ cells led to severe GVHD-associated multiorgan injury and 100% mortality. A direct correlation with the number of transplanted DX5+ cells was noted (maximal effect with transplantation of 4.5 x 106 DX5+ cells). Tolerance induction was associated with an increased peripheral CD4/CD8 ratio, intrahepatic trapping of CD8 lymphocytes and a shift towards a Th2-type cytokine profile, manifested by decreased IL-12/IL10, IL-12/IL-4, IFNgamma/IL-10, and IFNgamma/IL-4 ratios. Transplantation of DX5+ cells holds promise as a novel therapeutic measure for GVHD.

Adoptive Transfer↗
PubMed2004

Lamivudine treatment for acute severe hepatitis B: a pilot study.

BACKGROUND: Experience with lamivudine treatment of immunocompetent patients with acute hepatitis B is limited. AIM OF STUDY: To evaluate the safety and efficacy of lamivudine for the treatment of acute severe hepatitis B virus (HBV) infection in immunocompetent adults. PATIENTS AND METHODS: Fifteen patients (10 men, 5 women, mean age 34.3+/-7.3 years) with severe acute HBV infection were treated with lamivudine 100 mg daily for 3-6 months, starting 3-12 weeks after onset of infection. Prior to treatment, 5 patients had grade 1-4 encephalopathy; all patients had severe coagulopathy (mean INR was 4.5+/-6.4), and all patients had evidence of severe hepatocyte lysis (mean alanine aminotransferase 3738+/-1659 U/L, and mean total serum bilirubin 18+/-6.8 mg/dl). All patients had evidence of highly replicative HBV (mean HBV DNA 13.5 x 10(6)+/-11 x 10(6) copies/ml). RESULTS: Thirteen patients (86.6%) responded to treatment. Encephalopathy disappeared within 3 days of treatment and coagulopathy improved within 1 week. Serum HBV DNA was undetectable (by polymerase chain reaction) within 4 weeks, and serum liver enzyme levels normalized within 8 weeks. Two patients in whom lamivudine therapy was delayed developed fulminant hepatitis and underwent urgent liver transplantation. (One died of vascular complications 1 month later). The 11 patients who were serum HBeAg-positive before treatment seroconverted, and HBeAb developed within 12 weeks in 9 of them; HBsAg was undetectable in all 11 tested patients, and protective titer of HBsAb developed within 12-16 weeks in 9 of them. Therapy was well tolerated in all cases. CONCLUSIONS: These data indicate that lamivudine induces a prompt clinical, biochemical, serological and virological response in immunocompetent patients with de novo HBV infection. Lamivudine may prevent the progression of severe acute disease to fulminant or chronic hepatitis and should be considered for use in selected patients. A large randomized controlled, double-blind prospective study is needed.

Acute Disease↗
PubMed2004

Radiation safety considerations in GliaSite 125I brain implant procedures.

The traditional approach to treatment of certain malignant brain tumors involves permanent implantation of I seeds sequential to tumor's resection. This approach has recently been changed for patients with unifocal recurrent gliomas. What began during the 1990's as a large clinical trial utilizing GliaSite Radiotherapy System, is currently becoming standard of care. This radiotherapy system consists of an inflatable balloon catheter, 2, 3, or 4 cm diameter, which is surgically placed in the tumor resection cavity; its positioning and the level of conformity within the cavity are verified via MRI imaging with contrast. The balloon is then filled with appropriate volume of I in the liquid form. Radiation treatment prescription dose ranges from 40 to 60 Gy (4,000 to 6,000 rads). This is accomplished by allowing 2.77 to 16.6 GBq (75 to 450 mCi) of I to remain in the balloon for 3-5 d. Numerous technical, dosimetric, and logistical considerations arise when handling large quantities of iodine necessary to perform GliaSite procedures. They require coordination of efforts of several hospital departments and the institution's RSO-in our case, two RSOs, at the University of Colorado Hospital and University of Colorado Health Sciences Center hold separate radioactive materials licenses. Based on our experiences and those of others, we conclude that, with appropriate guidance and care, these procedures can be performed safely without excessive restrictions.

Brachytherapy↗
PubMed2001

Impairment of the metabolism of dipyrone in asymptomatic carriers of the hepatitis-B virus does not occur in rapid acetylators.

OBJECTIVE: We previously found that, compared with healthy subjects. asymptomatic hepatitis-B virus (HBV) carriers displaying slow acetylator phenotype demonstrate a significant prolongation of the elimination half-life of 4-methylaminoantipyrine (MAA) and a decrease in the clearance of formation of 4-aminoantipyrine (AA) and 4-formylaminoantipyrine (FAA). However, the formation of 4-acetylaminoantipyrine (AAA) was unchanged. The present study was designed to examine the effect of the asymptomatic HBV carrier state on the metabolism of dipyrone. as a model drug, in rapid acetylators. METHODS: The plasma and urine concentrations of the metabolites of dipyrone were measured in eight asymptomatic HBV carriers and eight healthy subjects who had normal liver function tests, all displaying the rapid acetylation phenotype and genotype, after the administration of a 1.0-g oral dose of dipyrone. RESULTS: The following pharmacokinetic parameters were evaluated: peak plasma concentration, time to peak plasma concentration, elimination rate constant, area under the plasma concentration-time curve (0-->infinity), amount excreted (0-->infinity), renal and non-renal clearances for MAA and the clearances of formation for AA, FAA and AAA. No significant differences were found between the two subject groups. CONCLUSION: The effect of hepatic viral carrier state on drug metabolism may vary according to metabolic pathways and genetic polymorphism.

Acetylation↗
PubMed2001

Lack of known hepatitis virus in hepatitis-associated aplastic anemia and outcome after bone marrow transplantation.

Viral infection has been shown to induce aplastic anemia, unidentified types of hepatitis being the most common cause for aplastic anemia-associated viral hepatitis. The survival rate for this group of patients after bone marrow transplantation with stem cells from an HLA-matched sibling is not well known. The aim of this study was to determine the prevalence of hepatitis G virus (HGV) and transfusion transmitted virus (TTV) infection in non-A, non-B, non-C hepatitis associated-aplastic anemia (HAAA) patients, and to define the role of bone marrow transplantation (BMT) as a therapeutic modality for this disease. Sixty-eight patients (43 males and 25 females) with aplastic anemia, underwent allogeneic BMT at the Hadassah University Hospital between 1981 and 1997. Onset of hepatitis was defined as jaundice and elevated alanine aminotransaminase (ALT) levels. Onset of aplastic anemia was defined as the first date on which varying degrees of pancytopenia occurred: hemoglobin level below 10 g/dl, WBC below 2 x 10(9)/l and low platelet count 10 x 10(10)/l. Serial serum samples from HAAA patients were assayed for virological and/or serological markers of hepatitis A, B, C, D, E, G viruses, TTV and parvovirus B19. Seventeen of the 68 patients with aplastic anemia (25%) suffered from hepatitis, 12 males and five females, ages 5 to 36 years. The mean interval between onset of hepatitis and first indication of aplastic anemia was 62 days (range 14-225 days). The development of aplastic anemia was unrelated to age, sex or severity of hepatitis. Ten of the 17 patients (59%) achieved complete ALT recovery prior to the diagnosis of aplastic anemia. Serum samples were available for 15 patients; none had evidence of acute or active hepatitis A, B, C, D, E, G and TTV virus infection at the time of diagnosis. Parvovirus B19 DNA sequences were not detectable in 10 of 12 tested cases; two positive results were detected in serum samples obtained after blood transfusion, making the analysis of these positive results difficult. All 17 patients underwent BMT. The mean post-BMT follow-up period was 38 months (range 1 day-123 months), five patients (30%) died 1 to 160 days post BMT, and 12 (70%) are alive 31 to 123 months after BMT. Relapsing hepatitis was not observed in any of the patients. In conclusion, HAAA is a disease of the young and the etiologic agent associated with HAAA remains unknown. HGV, TTV and parvovirus B19 sequences were not detected in any of the HAAA cases. The survival rate after BMT with stem cells from an HLA-matched sibling is similar to that for patients with non-hepatitis-associated aplastic anemia.

Adolescent↗
PubMed2001

Liver transplantation and nursing care in Israel.

The Liver Unit in Hadassah Medical Center has been following patients before and after transplantation in a process combining medical and nurse care. Since 1991, 145 patients have been studied. This article reviews the study methods associated with the liver transplantation process, including etiology of basic liver disease, drug adverse effects, complications, and survival rates. The value of the nursing coordinator in liver transplantation is discussed.

Adolescent↗
PubMed2000

Bcl-2 rearrangement in patients with chronic hepatitis C associated with essential mixed cryoglobulinemia type II.

Hepatitis C virus (HCV) infection is found in 80% to 90% of patients with essential mixed cryoglobulinemia (EMC) type II, which is associated with monoclonal IgMk produced by monoclonal B cells. It was investigated whether bcl-2 rearrangement is associated with the clonal B-cell proliferation of EMC induced by hepatitis C. The study groups were composed of 15 patients with HCV and EMC, 12 patients with HCV without EMC, and 7 patients with chronic liver disease (CLD) unrelated to HCV. Fluorescence in situ hybridization with probes was applied to JH and to bcl-2 to study whether JH/bcl-2 translocation was present in these patients. Thirteen of 15 (86%) of patients with HCV-related EMC had the JH/bcl-2 translocation, a significantly higher rate than in HCV patients without EMC (16%; P < .001). Bcl-2 rearrangement was not detected in the patients with CLD not related to HCV. The JH/bcl-2 translocation may constitute a pathogenetic link for the development of NHL in patients with HCV infection. (Blood. 2000;96:2910-2912)

Adult↗
PubMed2000

Pancreatitis following hepatitis A vaccination.

We describe a 23-year-old male patient who presented with epigastric abdominal pain, 8 days following vaccination with inactivated hepatitis A virus (Haverix(R)). Clinical and laboratory data confirmed the diagnosis of pancreatitis. Repeat polymerase chain reaction (PCR) for hepatitis A replication was negative. A comprehensive evaluation ruled out other etiologies for pancreatitis. IgM Hepatitis A antibodies did not develop even after 3 months. Pancreatitis following Hepatitis A is a well-known complication of the viremia, but the exact mechanism is controversial. We suggest that the pancreatitis may have been a cellular immunlogical reaction to one of the antigens of hepatitis A virus vaccine, or it might have been caused by the release of mediators of anaphylaxis such as histamine and leucotriens, induced by HAV antigens, resulting in pancreatitis without development of humoral immunization.

Acute Disease↗
PubMed2000

Hypoglycemia in patients with renal failure.

Of a total of 1545 admissions of end stage renal failure (ESRD) patients, fifty-six (3.6%) were admitted during a ten-year period with hypoglycemia. Thirty-eight of them were diabetic while the others were non-diabetic patients. The most common etiology found to be drug-induced hypoglycemia in 26 (46%) patients. In 22 (39%) cases, sepsis was the contributing cause of hypoglycemia. Severe malnutrition caused 7% of hypoglycemic episodes. Of the patients, 18 (32%) with ESRD eventually died, none of them were from the drug induced group. However, mortality rate in the sepsis induced hypoglycemia group was 66%, and of the malnutrition group 17% of the deaths. Thus, hypoglycemia is frequent in ESRD patients, and is fatal if associated with either sepsis or malnutrition.

Blood Glucose↗