Biomedical subjects

D Shouval

Publications and source records attributed to D Shouval.

At least 109 records · Page 6Linked to original sources

PubMed1992

Relapsing hepatitis A. Review of 14 cases and literature survey.

We have reviewed our experience with 14 cases of relapsing hepatitis A (RH-A), as well as 68 cases reported in the literature. Relapse occurs in 3 to 20% of patients with acute hepatitis A, and rarely takes the form of a polyphasic disease (multiple relapses). After a stage of typical hepatitis A, remission phase ensues, with partial or complete resolution of clinical and biochemical manifestations. Relapse usually occurs after a short period (usually less than 3 weeks). Relapse is usually clinically milder than the first phase, with variable liver function abnormalities and a tendency toward more marked cholestatic features. Not uncommonly, immune manifestations occur during this phase, including purpura, nephritis, and arthralgia, with common laboratory findings of rheumatoid factor as well as false-positive reaction to HCV-EIA tests. The clinical course in relapsing hepatitis A is almost always benign, and uneventful recovery is the rule with few exceptions. Steroid treatment, first reported in the present series, resulted in marked clinical improvement. Preliminary results suggest that R-HA is associated with a continuing viremia as well as shedding of virus in stools during the relapse phase. The pathogenesis of R-HA probably involves an interaction between persistent viral infection and immune mechanisms responding to the continuing antigenic stimulation.

Adult↗

PubMed1992

Serological and molecular analysis of HLA in Israeli primary sclerosing cholangitis patients.

HLA class I and class II were investigated in 15 Israeli primary sclerosing cholangitis patients and compared to healthy controls. None of the well established serological specificities were found to be associated with the disease. HLA-DR52 is serologically defined, but its subtypes DR52a, DR52b, and DR52c cannot be precisely defined by serological means. Therefore, we have used HLA-DNA typing in order to assign the DR52 splits in PSC patients. Genomic DNA was amplified by PCR, dot-blotted and hybridized with sequence specific oligonucleotide probes defining the known HLA-DR52 associated alleles. Only 4 out of the 15 PSC patients tested were found to express DRB3*0101 the allele that encodes DR52a. Of the remaining 11 patients, 9 expressed DRB3*0202 haplotypes, with 2 patients expressing both DRB3*0101 and DRB3*0202, and the remaining 2 patients expressed no DRB3 allele. Our data indicate that there is no apparent association between PSC and the HLA antigens and alleles studied including the alleles of the DRB3 locus in the Israeli population. Thus HLA pheno/genotyping of PSC patients in the Israelis will not be useful for early and/or differential diagnosis of this disease.

Alleles↗

PubMed1992

Cost-benefit analysis of a nationwide neonatal inoculation programme against hepatitis B in an area of intermediate endemicity.

STUDY OBJECTIVE: The aim was to estimate the costs and benefits of a nationwide neonatal vaccination campaign against hepatitis B in Israel for the 1990-2034 period. DESIGN: Using morbidity, mortality, utilisation, and cost data from Israeli and international sources, a spreadsheet model was constructed to carry out the cost-benefit analysis. SETTING: The entire State of Israel, an area of intermediate endemicity. PARTICIPANTS: The population of Israel from 1990-2034. MAIN RESULTS: A policy of immunising all Israeli neonates would, for a cost of $13.8 million, reduce the number of cases of hepatitis B during the 1990-2035 period in the cohort from 359,000 to 166,000 and save the nation around $21.5 million in health resources alone, $16.6 million in averted work absences, and a further $0.6 million in averted premature mortality costs. Even when the savings to the health services ($0.6 million) arising from the reduction in hepatocellular carcinoma are excluded, the direct benefit to cost ratio is 1.51/1, still in excess of unity. CONCLUSIONS: The decision to adopt a nationwide neonatal inoculation policy, starting in January 1992, appears to be not only medically but also economically justifiable.

Cost-Benefit Analysis↗

PubMed1992

Occupational and non-occupational hepatitis B virus infection among hospital employees in Jerusalem: a basis for immunisation strategy.

The present study was designed to assess the risk of hepatitis B virus (HBV) infection among hospital employees, who often contract the infection before the beginning of their employment, and to suggest a prevention strategy. The study population consisted of 2518 subjects working or studying at the two Hadassah University hospitals, on Mount Scopus and at Ein Kerem in Jerusalem. The total prevalence for anti-HBc positivity as an indicator for past or present HBV infection was 17.6%. Several variables, including country of birth, age, and duration of employment significantly affected the rate of anti-HBc positivity. The highest rates for anti-HBc+ were found in personnel of selected departments such as haemodialysis (31.8%), haematology/oncology (28.3%), and the blood bank (24.0%), after adjustment for country of birth, age, and sex. Specific occupations in the hospital were associated with an increased rate of anti-HBc positivity. Thus the highest rate of HBV infection (after adjustment for country of birth, age, and sex) was shown for housekeepers (32.4%) and departmental secretaries (23.6%), who take care of waste products containing blood, or who transfer vials containing blood to the hospital laboratories. By comparison, anti-HBc was positive in 17.2% of nurses, 15.6% of physicians, and only 7.8% of administrative clerks. Israel is a country of immigration, and anti-HBc rates were four times higher in employees born in countries where HBV is more endemic--for example, in north Africa and Mediterranean countries--than in employees born in western Europe or the United States. However, rate of anti-HBc + increased significantly with age as well as duration of employment in the hospital, irrespective of country of birth. These data indicate that although HBV infection often occurs in Israel before commencement of employment in the hospital, hospital employees are at significant risk for contracting HBV infection during their professional lifetime regardless of where they were born. Moreover, paramedical personnel such as housekeepers and departmental secretaries are in the highest risk group for contracting HBV. Finally, as a result of the high background of anti-HBC positivity in selected ethnic groups, mandatory screening for anti-HBc before employment in medical institutions in Israel is recommended for them, then active vaccination against HBV for employees at risk. Employees who immigrated from western Europe and the United States should be immunised without pre-vaccination screening for HBV.

Female↗

PubMed1992

Primary biliary cirrhosis in Israel.

Primary biliary cirrhosis (PBC) is a relatively rare autoimmune disorder leading to the destruction of the interlobular biliary epithelium, which has not been reported in the Middle East. We studied 30 patients with PBC who had been referred to the Liver Unit at the Hadassah Medical Center in Jerusalem. The diagnosis was established by conventional criteria in 28 female and 2 male patients. Twenty-two patients were of Ashkenazic origin and 8 of Sephardic background. Mean serum alkaline phosphatase activity at the time of diagnosis was 911 IU/l gamma-glutamyl transpeptidase 677 u/l, cholesterol 73 mmol/l, albumin 3.2 g/l, bilirubin 72 mmol/l, and prothrombin time was 65%. All patients had positive antimitochondrial and M2 antibodies, and the mean IgM level was 684 mg/dl. The diagnosis was confirmed by liver biopsy in 27 of 30 patients. To the best of our knowledge this represents the first report of primary biliary cirrhosis in the Jewish population in Israel. This retrospective survey raises the question whether the disease is indeed rare in Israel or, alternatively is underdiagnosed.

Academic Medical Centers↗

PubMed1992

Cost-benefit analysis of a nationwide inoculation programme against viral hepatitis B in an area of intermediate endemicity.

The large decrease in the cost of vaccines against hepatitis virus B prompts a re-examination of nationwide vaccination campaign strategies. The present study estimates the costs and benefits that would result from a viral hepatitis B prevention programme (with no prior screening) targeted at all under-16-year-olds in Israel in 1990 and only neonates in the period 1991-2034. Israel is situated in an area of intermediate endemicity, where the majority of HBsAg carriers are anti-HBe positive. Such a policy would reduce the number of cases of viral hepatitis B in the vaccinated cohort from 654,000 to 270,000 over the period 1990-2059, yielding a benefit-to-cost ratio of 1.88: 1 for the health services only. Inclusion also of the indirect benefits of reduced work absences and mortality would increase the benefit-to-cost ratio to 2.77:1. Even when the benefits arising from the reduction in hepatocellular carcinoma and liver transplants were excluded, the benefit-to-cost ratio for the health services alone would still be 1.41:1. The adoption of such a nationwide inoculation policy appears therefore to be not only medically but also economically justifiable.

Adolescent↗

PubMed1991

Prevalence of HBsAg carriers in native and immigrant pregnant female populations in Israel and passive/active vaccination against HBV of newborns at risk.

Israel has no official prevention policy at present against perinatal and horizontal transmission of hepatitis B virus (HBV) infection in newborns and children at risk. The present study was designed to assess the prevalence of HBV carrier state in a population of 11,123 pregnant women at term. Among this population (mean age 29.7 +/- 5.9), 98 women (0.88%) were found to be asymptomatic HBsAg+ carriers, and 97% of these carriers were anti-HBe+. Evidence for HBV replication, as determined by serum HBV-DNA, was established in 6.6% of the HBsAg+/anti-HBe+ population. The HBsAg carrier rate was strongly influenced by religion, continent, and country of birth of the carrier mothers. The highest relative carrier rate was found among women of Moslem origin (4.3%), as compared to Jewish women (0.67%). Most carrier women were born in Israel (56.1%) to mothers who had emigrated from regions with intermediate or high endemicity of HBV, such as North Africa or the Middle East. In these groups, the HBsAg carrier rate ranged between 1.2 and 3.0%. Ninety-three percent of newborns receiving passive/active vaccination against HBV developed protective levels of anti-HBs. Finally, evidence for horizontal transmission of HBV was found in 19.3% of 83 non-vaccinated children in families of HBsAg carriers. The present study therefore establishes HBsAg prevalence rates in specific risk groups of women at term and confirms the need for an official policy on immunization against HBV in Israel. Since over 50% of women at term belong to the defined risk groups, universal active vaccination of the entire newborn population each year is suggested as the most rational and needed policy in Israel.

Adolescent↗

PubMed1991

Localized primary sclerosing cholangitis mimicking a cholecystectomy stricture relieved by an endoprosthesis.

Primary sclerosing cholangitis presenting as a localized stricture affecting a segment of the extrahepatic biliary tree is rarely found. We describe the case of a 39 year old woman with obstructive jaundice, in whom this diagnosis was proven by endoscopic retrograde cholangiography. An endoprosthesis was endoscopically introduced through the stenotic area which led to a dramatic improvement enabling a successful liver transplantation after 2 years.

Adult↗

PubMed1991

Bilirubin conjugates produced by human, dog, and rat hepatocytes transplanted into athymic Gunn rats.

We developed a new hybrid mutant rat (athymic Gunn hybrid strain) that does not form and excrete conjugated bilirubin into bile and accepts xenografts because of T-lymphocyte deficiency. Cryopreserved isolated normal human, dog, or rat liver cells attached to collagen-coated microcarriers were transplanted into the athymic Gunn hybrid rats. Transplantation of human or rat liver cells resulted in biliary excretion of bilirubin conjugates predominantly as glucuronides, whereas isolated dog liver cells likewise transplanted resulted in the excretion of 40% to 50% of the conjugates as a glucoside-glucuronide diconjugate. The biliary bilirubin conjugates of the transplanted athymic Gunn hybrid rats paralleled those of the donor species. The data indicate that the types of bilirubin conjugates excreted by each species are determined by intrinsic properties of the respective hepatocytes rather than nutritional or other environmental factors. The findings also show that conjugation of bilirubin after liver cell transplantation results from functioning of the engrafted cells rather than activation of endogenous uridine diphosphatelucuronosyltransferase activity of the host.

Animals↗

PubMed1990

The effect of anti-alpha-fetoprotein-adriamycin conjugate on a human hepatoma.

Conjugates between chemotherapeutic agents and antibodies, linked by a dextran bridge, were previously shown to be effective in suppression of hepatoma growth in vitro and in vivo. However, scaling up of production of such conjugates may lead to a high degree of variation in molar ratios of drug to antibody in different batches. In this study, an alternative link between drug and antibody was evaluated. A conjugate between adriamycin and murine IgGI monoclonal antibodies to human alpha-fetoprotein was prepared using a polyglutamic-acid bridge. The simple and reproducible method of linking adriamycin to a specific site on the antibody enabled the binding of the drug to alpha-fetoprotein with a high yield (63% to 68%); the molar ratio of drug/antibody was in the range of 110:1 to 120:1. The conjugate retained its capacity to bind to purified alpha-fetoprotein. Incorporation of [3H]-thymidine or [3H]-leucine into hepatoma cells, which express alpha-fetoprotein, was inhibited by the conjugate, compared with unconjugated antibody. Furthermore, 90% of this pharmacological activity was preserved, compared with free adriamycin. In vitro, the inhibitory activity of the polyglutamic acid conjugate was higher than that of a conjugate in which dextran was used as the linker between drug and antibody. In vivo, both conjugates were equally effective in suppression of hepatoma growth transplanted subcutaneously in athymic mice. However, this effect lasted only during the treatment period of 2 to 3 wk. Six days after discontinuation of therapy, reacceleration of tumor growth was observed regardless of the conjugate used.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Postpartum Budd-Chiari syndrome with prolonged hypercoagulability state.

Budd-Chiari syndrome after pregnancy is an extremely rare disease. Reported here is a case of postpartum Budd-Chiari syndrome with unusual features of prolonged hypercoagulability state. The disease occurred 2 weeks after delivery and despite massive anticoagulation treatment the patient developed severe hepatic vein occlusion, renal vein thrombosis, inferior vena cava thrombosis, and femoral artery thrombosis.

Adult↗

PubMed1990

Vasculitis and cryoglobulinemia associated with persisting cholestatic hepatitis A virus infection.

Extrahepatic manifestations are rarely found in hepatitis A viral (HAV) infection. Only a single case of HAV infection associated with cutaneous vasculitis and cryoglobulinemia has been reported. Described here is a patient with a persisting cholestatic type of HAV infection who developed cutaneous vasculitis and cryoglobulinemia during the third month of her illness. Analysis of the cryoglobulins revealed IgM anti-HAV antibodies.

Adult↗

PubMed1989

A common-source outbreak of fulminant hepatitis B in a hospital.

A nosocomial outbreak of fulminant hepatitis B infection at a medical center in Haifa, Israel, between 7 and 26 June 1986, involved five patients who had been hospitalized previously in the medical ward in late April and early May (first generation). This outbreak had an unusual clinical course, with fulminant hepatic failure associated with acute renal failure from acute glomerulonephritis, leading to death within a few days. The onset dates of hepatitis were tightly clustered temporally and incubation periods were short. Extensive laboratory and epidemiologic evaluation showed that the probable common-source vehicle of transmission was a multiple-dose vial of heparin and normal saline flush solution that may have been contaminated by blood of a known HBsAg carrier, who was positive for anti-HBe, hospitalized at the same time. A sixth patient died in August 1986 (second generation), after his initial admission in June that coincided with the terminal hospitalizations of three first-generation patients. Those patients had marked coagulopathies, and transmission to the sixth patient most probably occurred through environmental contamination by patients or through cross-contamination between patients through staff. The unusually high mortality rate (5 of 6) in this outbreak has not been definitely explained.

Aged↗

PubMed1989

[An outbreak of hepatitis B associated with acupuncture].

2 clusters of between 5 and 11 cases of hepatitis B virus infection were associated with acupuncture by a physician late in 1986. The source of the infection is believed to have been an Ethiopian immigrant, a known HBsAg carrier. While he was being operated on a nurse cut her finger on a scalpel blade. During the prodromal period of hepatitis which followed, she was treated by acupuncture. The acupuncture needles were supposedly sterilized by dry heat for 80 minutes at 200 degrees. However, there were apparently breaks in technique which were responsible for the spread of the infection to at least 4 other women, ranging in age from 26 to 80 years. We stress the need for strict enforcement of correct sterilization procedures whenever needles are used to pierce skin. This should be performed only by licensed practitioners of officially recognized occupations, some of which are not as yet covered by our national health regulations.

Acupuncture Therapy↗

PubMed1989

In vivo expression of two novel tumor-associated antigens and their use in immunolocalization of human hepatocellular carcinoma.

We are investigating the antigenic changes on the cell surface of human hepatocytes that distinguish the normal from the transformed phenotype using monoclonal antibodies. In vivo expression of antigens has been directly assessed by in situ radioimmunohistology. This technique allows one to determine the distribution and density of antigen expression at the individual cellular level on fresh hepatoma and adjacent uninvolved liver tissue. We have found two antigens recognized by monoclonal antibodies XF-8 and AF-20 that are uniformly present on 15/15 hepatocellular carcinomas tested thus far. Most if not all tumor cells highly express these antigens. Such antigens were not evident on adjacent normal liver and the XF-8 epitope was not found on other normal human tissues. AF-20 antigen distribution revealed low-level expression on a subpopulation of cells in the zona glomerulosa of the adrenal gland and on crypt cells of the small intestinal tract. We have studied the capability of radiolabeled XF-8 and AF-20 monoclonal antibodies when administered either alone or in combination to localize a hepatitis B virus-related hepatocellular carcinoma cell line (FOCUS) grown as subcutaneous tumors in nude mice. Biodistribution experiments demonstrated an excellent localization to tumor of 15 to 22% of the injected dose of 125I-labeled antibodies. Indeed, it was possible to enhance the delivery of 125I to the tumor cell surface by the use of XF-8 and AF-20 in combination. Nuclear imaging studies showed sharp visualization of tumor and demonstrate that these monoclonal antibodies have sufficient specificity and sensitivity to be strongly considered as immunotargeting agents.

Adenocarcinoma↗

PubMed1989

Hepatitis during measles in young adults: possible role of antipyretic drugs.

Fifty-six per cent of 118 young adults observed during a recent measles epidemic had some disturbance on liver function tests. Five per cent developed overt jaundice. Patients treated for fever with paracetamol were found to have significantly higher rates of transaminase impairment compared to those treated with dipyrone. Sixty-five and 58% of patients given paracetamol had elevated ALT and AST levels, respectively. Only 15% of patients given dipyrone had elevated levels of these two enzymes (p less than 0.01 for ALT and p less than 0.02 for AST). The mean levels of transaminases and bilirubin in the paracetamol-treated patients were significantly higher than those found in the dipyrone-treated patients [92 +/- 86 vs. 42 +/- 49 IU (p less than 0.02) for AST and 12 +/- 6.0 vs. 7.0 +/- 2.0 mumoles per liter (p less than 0.01) for bilirubin]. The cumulative dose of paracetamol in those who had impaired liver function was higher than that ingested by patients who did not develop liver damage, although still within the usual therapeutic range [11.6 +/- 5.8 vs. 7.6 +/- 4.2 gm (p = 0.02)]. The possible ways in which measles infection and paracetamol in combination can lead to hepatic damage are discussed.

Acetaminophen↗

PubMed1989

Detection of hepatitis A virus RNA in serum from patients with acute hepatitis.

Hepatitis A virus (HAV) RNA was extracted from the sera of patients with acute hepatitis and then detected by molecular hybridization using cloned HAV complementary DNA (cDNA). HAV RNA was detected in 20 of 85 patients with acute HAV infection, mainly during the prodromal stage, or early during the icteric phase of the disease; it was detected as long as 21 days after its initial detection. Patients with HAV RNA in the serum had a significantly higher titer of anti-HAV IgM.

Acute Disease↗

PubMed1989

Radioimmunolocation of hepatic and pulmonary metastasis of human colon adenocarcinoma.

We have established a large library of monoclonal antibodies against a human hepatoma cell line called FOCUS. One such monoclonal antibody (SF-25) detects a 125-kilodalton cell surface antigen found on FOCUS cells. As both the liver and the colon are of endodermal origin, we examined the possibility of expression in colon adenocarcinomas. This antigen was found in all 23 colon adenocarcinoma tissues surgically obtained but was absent in the adjacent normal mucosal counterpart as determined by a direct radioimmunohistologic technique. In the present study, we have established a model for human metastatic colon adenocarcinoma using the LS 180 cell line. Athymic mice were further immunosuppressed by intravenous injection of anti-NK cell antibodies (antiasialo GM1). After 24 h, mice were injected with LS 180 cells either via the tail vein or into the spleen followed by splenectomy. Macroscopic pulmonary and lymphatic metastasis developed within 2-3 wk after injection of cells and 9 of 10 mice died with advanced metastatic disease 2-3 wk later. In addition, macroscopic hepatic metastases were evident in 4 of 5 mice 3-4 wk after intrasplenic injection. Both hepatic as well as pulmonary and lymphatic tumor spread was localized by nuclear imaging with 125I-SF-25. Furthermore, micrometastases were detected by autoradiography 5-10 days later. Monoclonal antibody SF-25 is a potential candidate for tumor localization and the experimental metastatic colon cancer animal model may be useful for treatment evaluation of monoclonal antibody SF-25 either alone or in combination with other monoclonal antibodies when conjugated to radionucleotides and chemotherapeutic agents.

Adenocarcinoma↗