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Z Halpern

Publications and source records attributed to Z Halpern.

At least 19 recordsLinked to original sources
PubMed1995

The fate of long-standing intraperitoneal gallstone in the rat.

Gallstones are occasionally spilled into the peritoneal cavity during open and laparoscopic cholecystectomy. Using the rat model, we investigated the long term effect of such retained intraperitoneal gallstones. During a follow-up period of one year, no systemic deleterious outcome could be attributed to the presence of the implanted gallstones except for mild local effects. Based on the rat model we conclude that reasonable effort should be made in order to retrieve an escaped gallstone, but there is no justification whatsoever for a conversion of the laparoscopic procedure to an open laparotomy only for the purpose of retrieving a lost stone.

Animals↗
PubMed1995

Elevated serum iron predicts poor response to interferon treatment in patients with chronic HCV infection.

To date, there are no firm clinical, demographic, biochemical, serologic, or histologic features predicting which patients with chronic hepatitis C are more likely to respond to therapy with interferon-alpha. Serum iron, total iron-binding capacity, transferrin saturation, and ferritin were measured in the fasting state. The amount of stainable iron in liver biopsy specimens was evaluated histochemically as well. All patients received subcutaneous recombinant human IFN-alpha 2a three million units thrice weekly by self-administration. Eleven of 13 (84%) responders had low to normal serum iron levels as compared to one of 26 (4%) nonresponders (P < 0.001). The serum transferrin was similar in both groups, but iron saturation was significantly lower in responders (30 +/- 10%) than in nonresponders (53 +/- 12%) (P< 0.001). Serum ferritin and hepatic iron content were higher in nonresponders (NS). It is suggested that increased serum iron and transferrin saturation blunt the action of interferon, as they have opposite effects on the immune system. Iron overload can thus lead to a poor response to interferon. It remains to be seen whether reducing iron overload will improve the response to interferon therapy.

Chronic Disease↗
PubMed1995

Treatment of immune cell-mediated liver damage by nonpeptidic mimetics of the extracellular matrix-associated Arg-Gly-Asp epitope.

The etiology of T-cell-mediated liver injury involves the migration of immune cells, notably CD4+ T lymphocytes, into liver tissues. This process is mediated primarily by integrin-recognition of the sub-endothelium basement membranes and the extracellular matrix. The Arg-Gly-Asp-containing peptide, a major cell-adhesive ligand of extracellular matrix, is present in various plasma- and matrix-glycoproteins, such as fibronectin. Recently, we have described the design and usage of nonpeptide mimetics of Arg-Gly-Asp which bind specifically to integrins, and thereby, inhibit T cell immunity in vivo. We examined the efficacy of Arg-Gly-Asp-mimetics as potential therapeutic compounds for the treatment of experimental T-cell-mediated liver injury induced in mice by injection of Concanavalin-A. We now report that the Arg-Gly-Asp-mimetics specifically inhibited the binding of murine T cells to fibronectin, but did not affect the proliferative response of these cells in vitro. Intraperitoneal or oral administration of the Arg-Gly-Asp-mimetics but not the Arg-Gly-Asp-containing peptide, inhibited liver damage in mice if given before their inoculation with Con-A, as manifested by a lesser elevation in their serum levels of hepatic enzymes. The inhibitory effect of the Arg-Gly-Asp-mimetics was dose-dependent, the ED50 of the tested molecules being in the range of 100 micrograms per mouse and reaching maximal effect, e.g. approximately 95% inhibition, at 500 micrograms per mice. Thus, the Arg-Gly-Asp-mimetics described here may be used therapeutically to prevent immune-cell-mediated acute or chronic pathological reactions in the liver.

Animals↗
PubMed1995

Post-transfusion etiology and non-cirrhotic histology improve the remission rate of chronic hepatitis C during interferon treatment.

During a 29 month period, 46 patients with chronic hepatitis C virus (HCV) received recombinant human interferon alpha-2a for 6 months and were followed for another 6 months. The dose of interferon was three million units thrice weekly and was increased to six million units if amino transferase levels failed to return to normal after 2 months of therapy. At the end of the treatment 19 patients had a complete response, 6 had a near complete response, 2 patients had breakthrough during treatment, and the remaining 19 did not respond at all. Six months after treatment only 10 of the 19 responders remained in remission. Post-transfusion disease was associated with a significantly higher remission rate than sporadic disease (9/22 vs. 1/24, P < 0.001), as was also found in non-cirrhotic compared to cirrhotic patients (9/27 vs. 1/19, P < 0.001). Age, sex, duration of disease, serum aminotransferase, albumin, bilirubin, alkaline phosphatase, or Child's classification did not correlate with treatment response. Severe side effects necessitating cessation of treatment occurred in six patients, four of whom had major autoimmune phenomena. We conclude that careful selection of HCV patients with favorable response characteristics (post-transfusion etiology and non-cirrhotic liver) and without autoimmune manifestations can improve the remission rate and decrease the complication rate during interferon treatment.

Adult↗
PubMed1994

Increased serum iron and iron saturation without liver iron accumulation distinguish chronic hepatitis C from other chronic liver diseases.

One hundred twenty-three patients with chronic liver diseases of various etiologies were evaluated for their iron status. The patients were divided into four distinct groups: chronic hepatitis C (63), chronic hepatitis B (14), B + C (3) and nonviral chronic liver diseases (43). In 107 patients (87%) the chronic liver disease was confirmed by biopsy. Mean serum iron (+/- SD) levels in the above four groups were: 166 +/- 62, 103 +/- 52, 142 +/- 48, and 115 micrograms/dl; iron-binding capacity was 346 +/- 80, 325 +/- 72, 297 +/- 27, and 374 +/- 75 micrograms/dl, and iron saturation 50 +/- 18, 32 +/- 16, 48 +/- 16, and 28 +/- 10%, respectively. Serum ferritin, increased in all four groups, was highest in HCV; however, no evidence of hepatic iron accumulation could be found in any of the patients. There were no significant differences in liver function parameters measured in the four groups. We conclude that serum iron, iron saturation, and ferritin are increased in patients with hepatitis C in comparison to hepatitis B or other nonviral, nonhemochromatotic liver diseases. The increased iron status in hepatitis C patients is not manifested by increased liver iron. Awareness of these distinct features of chronic hepatitis C is essential in the diagnosis and treatment of chronic liver diseases.

Biopsy↗
PubMed1994

The distribution of the biliary-anionic polypeptide fraction between cholesterol carriers in bile and its effect on nucleation.

The small (7 kD) biliary phospholipid and calcium binding polypeptide (anionic polypeptide fraction/calcium binding protein) has been found in higher concentrations in the bile of patients with pigment stones than in controls. In different model systems it was variously found to promote or retard cholesteral crystalization. In the present study we investigated its distribution between cholesterol carriers in bile and its effect on cholesterol crystalization in native and model biles. On gel chromatography anionic polypeptide fraction/calcium binding protein was found predominantly in three areas: in the vesicular fraction, in the non-vesicular lipid fraction and in another fraction unassociated with biliary lipids. It was much more concentrated in the vesicular than in the non-vesicular fraction, the mean anionic polypeptide fraction/phospholipid molar ratio being 219 +/- 181 vs. 30.4 +/- 16, respectively. Anionic polypeptide fraction/calcium binding protein was added at three dose levels, 0.14, 0.28, 0.42 mg/ml (representing approximately 18%-55% of the physiologic biliary concentration), to 19 human and five model biles. This did not produce any significant changes in the nucleation time. The addition of anionic polypeptide fraction/calcium binding protein at a dose level of 0.42 mg/ml to 13 different human biles did not induce changes in the distribution of cholesterol among its carriers. The present experiments do not support a role for anionic polypeptide fraction/calcium binding protein in the process of cholesterol nucleation in bile. Qualitative changes in the protein molecule, as demonstrated in other human secretions, cannot be excluded.

Apoproteins↗
PubMed1992

The effect of short-term lipid infusion on liver function and biliary secretion in rats.

This study was undertaken to determine the effect of various lipid emulsions on the hepato-biliary system in rats. Rats were randomly divided into six groups and infused continuously for 48 hr with either long-chain triglycerides (LCT), medium-chain triglycerides (MCT) or a mixture of MCT and LCT. One group infused with physiological saline solution served as controls. Throughout this period the rats received a fat free diet ad libitum. During the last hour of lipid infusion bile was collected for determination of bile flow and composition. Subsequently, the rats were sacrificed and the morphology and lipid content of the liver determined. Only LCT lipid emulsions induced morphological changes and increased liver cholesterol content. In two rats infused with radiolabeled LCT, no labeled cholesterol was found in the liver, indicating that the excess hepatic cholesterol level may originate from enhanced cholesterol mobilization to the liver. Biliary cholesterol and phospholipid concentrations in LCT-treated rats were also elevated, as was the lithogenic index, whereas the other emulsions had no such effects. None of the emulsions affected the plasma liver function tests or bile flow. We therefore conclude that the lithogenicity of the bile in rats is directly related to the lipid components of the total parenteral nutrition and the type of triglyceride infused.

Animals↗
PubMed1992

Free fatty acids have nucleating effects in model biles.

Nucleating factors are thought to be responsible for the more rapid nucleation of gallbladder bile from patients with gallstones as compared to controls. Biliary proteins and, in particular, mucus and non-mucus glycoproteins are the focus of current research. Non-protein nucleating factors were not extensively investigated. In this study we studied the role of free fatty acids (FFA) as possible nucleating factors. Palmitic, oleic and linoleic acid were added to model biles in increasing concentrations from 0 to 20 mu mol/ml. The nucleation time of model biles decreased to 45%-60% of the initial following the addition of 0.5 to 1 mu mol/ml of each of the three fatty acids. Only a small further decrease in the nucleation time was noted with higher concentrations of up to 20 mu mol/ml. The pronucleating effect of FFA added to whole model bile was also examined in the isolated vesicular and non-vesicular fractions. The decrease in the nucleation time at each concentration of the three fatty acids was in the following order of magnitude: whole bile greater than vesicular phase greater than non-vesicular phase. The addition of each of the three fatty acids resulted in a partial solubilization of vesicles, with transfer of their lipid contents to the non-vesicular fraction. The effect was more marked with oleic acid and least marked with linoleic acid. The vesicular cholesterol to phospholipid ratio did not change following the addition of exogenous free fatty acids. Studies with labeled FFA showed that they migrated with the non-vesicular fraction on gel chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗
PubMed1992

Effect of lipid infusion on bile composition and lithogenicity in patients without cholesterol gall stones.

A prospective study was performed to investigate the effect of short term lipid infusion on bile composition and its lithogenicity in humans. Thirty five patients shown to be free of cholesterol gall stones participated in the study. Starting 48 hours before surgery they were infused randomly with a lipid emulsion of either long chain triglycerides (LCT) or a mixture of medium and long chain triglycerides (MCT/LCT) (50%/50%) for six hours each 24 hours. A group of patients infused with a solution of 5% glucose in NaCl 0.9% served as a control. Bile samples were obtained by puncture of the gall bladder during operation. Both lipids caused an increase in biliary cholesterol and phospholipids but this effect was more pronounced and significant (p < 0.001) only with the MCT/LCT emulsion. The fatty acid composition of biliary phospholipids was not affected by either lipid infusion. The cholesterol saturation index increased significantly (p < 0.005) with the MCT/LCT emulsion and there was shortening in the nucleation time but this was not significant. There was no effect on the distribution of cholesterol between micelles and vesicles. This study shows that infusion of MCT/LCT lipid emulsion can cause lithogenic changes in bile composition in humans and may thus contribute to sludge formation and cholelithiasis during long term parenteral nutrition.

Bile↗
PubMed1992

The differential leukocyte count in adults with acute gastroenteritis.

The total and differential leukocyte count of 4 groups of patients, admitted to the hospital because of acute gastroenteritis was evaluated. The 4 groups included: (a) 131 adult patients with positive stool culture for shigella; (b) 23 children (age less than 15 years) with positive stool culture for shigella; (c) 52 adult patients with positive stool culture for salmonella; (d) 43 adult patients with negative stool culture for bacterial pathogens. The total leukocyte count did not contribute to the differential diagnosis between shigella gastroenteritis and gastroenteritis of other etiology. However, the absolute band count was significantly higher in adults with shigella gastroenteritis. Moreover, a band to total neutrophil ratio further increased the diagnosis specificity. The differential leukocyte count can contribute to early diagnosis of shigellosis in adult patients.

Acute Disease↗
PubMed1992

Prostaglandin E2 in duodenal ulcer complications.

Prostaglandins are presumed to have cytoprotective properties and may play a role in the pathogenesis of duodenal ulcer and its complications. To evaluate this hypothesis, 35 patients with either duodenal ulcer bleeding (18 patients) or gastric outlet obstruction (17 patients) were investigated. Biopsies were taken from gastroduodenal tissues and secretions for prostaglandin E2 (PGE2) levels. These levels were compared to those taken from the same areas during a later endoscopy. A correlation was found between the severity of the clinical endoscopic findings and PGE2 levels. Increased levels of PGE2 were found in the quiescent phase and decreased levels found during the deteriorated phase. These differences of PGE2 levels were found to be of significant value (P less than 0.002). Furthermore, the patients in which the PGE2 levels were decreased at second endoscopy needed surgery. PGE2 may, thus, be a factor in duodenal ulcer pathogenesis and its complications, and be used as a prognostic marker and guide.

Acute Disease↗
PubMed1991

A controlled trial of beclomethasone versus betamethasone enemas in distal ulcerative colitis.

Steroid enemas are widely used in distal inflammatory bowel disease (IBD). They are partly absorbed and suppress adrenocortical function. Beclomethasone dipropionate (BD) is a topically active steroid that undergoes rapid first-pass inactivation in the liver and is practically devoid of systemic side effects. We treated 32 consecutive patients with active distal ulcerative colitis (40 attacks) with 0.5 mg BD and/or 5 mg betamethasone phosphate (BP) enemas for 28 days. Clinical, laboratory, sigmoidoscopic, and histologic data were recorded before, during, and after the trial. The clinical efficacy of both treatments was similar. Betamethasone was slightly more effective in relation to the histologic improvement and disappearance of blood from the stools. Clinical signs of steroid overdosage were noted in patients on BP but not in patients on BD. Mean fasting plasma cortisol at the end of the trial was 2.9 micrograms/dl in the BP group and 15.3 micrograms/dl in the BD group. The adrenocorticotropin test was markedly suppressed in the BP group but not in the BD group. The absence of systemic steroid side effects makes BD enemas a useful addition in the therapy of IBD. Its oral administration should also be considered.

Adult↗
PubMed1991

Pulse oximetry in the evaluation of the painful hand after arteriovenous fistula creation.

Five patients with a side-to-side arteriovenous fistula complaining of pain, numbness, and cold sensation were evaluated by pulse oximetry. Low SaO2 was noticed in all five. Closure of a major proximal venous collateral vessel eliminated the steal and resulted in SaO2 correction and was followed by clinical amelioration. Pulse oximetry proved to be a helpful adjunct in the evaluation of the painful hand after creation of an arteriovenous fistula. By applying the pulse oximeter to the patient's affected limb, we were able to determine whether the pain was a result of ischemia and if the correction of the steal improved oxygenation.

Arteriovenous Shunt, Surgical↗
PubMed1990

Polyamines--potential nucleating factors in bile.

Lithogenicity of human bile is dependent not only on cholesterol saturation, but also on the presence of nucleating and antinucleating factors. Most of the research in this field is directed toward biliary proteins, particularly glycoproteins. In the present study we have shown that spermine, spermidine, cadaverine and putrescine have a nucleating effect in model bile as well as in native human bile. These findings are based on 183 mixing experiments using biles from 10 patients and model biles. The effect seems to be dose dependent at concentrations up to 10 mmol/l. It is not accompanied by a shift in cholesterol distribution between its vesicular and micellar carriers. It is at present uncertain whether these effects are pharmacologic or physiologic. These findings emphasize, however, the potential importance of non-protein compounds in the cholesterol nucleation process in bile.

Bile↗
PubMed1990

Stability of mixed micellar systems made by solubilizing phosphatidylcholine-cholesterol vesicles by bile salts.

Complete solubilization of phosphatidylcholine and cholesterol by bile salts in the form of stable mixed micelles requires that the effective ratio of bile salt/lipids in the mixed micelles (Re = ([bile salt] - critical micellar concentration)/([phosphatidylcholine] + [cholesterol]) will exceed a critical value. This equilibrium solubilizing ratio is an increasing function of the cholesterol/phosphatidylcholine ratio. In contrast, the concentration of sodium cholate required for solubilization of vesicles made of phosphatidylcholine and cholesterol does not increase by increasing the cholesterol/phosphatidylcholine ratio. Consequently, the latter solubilization procedure yields metastable mixed micelles whenever the cholate concentration is higher than that required for vesicle solubilization but lower than that needed for establishing a micellar equilibrium. These metastable mixed micelles undergo partial revesiculation to form cholesterol-rich vesicles that subsequently aggregate. Cholesterol crystallization appears to occur through its reorganization within these aggregated vesicles. The overall rate of the above series of processes increases sharply with the total lipid concentration and with the cholesterol/phosphatidylcholine ratio. The dependence of the rate on the effective ratio of bile salts/lipids is very complex: at any given ratio of cholesterol/phosphatidylcholine within the range of 0.3 to 0.5, increasing the cholesterol/phosphatidylcholine ratio requires higher cholate concentrations for the formation of stable mixed micelles (higher equilibrium solubilizing ratio). On the other hand, the metastable mixed micellar larsystems are long-lived whenever the effective ratio of cholate/lipids is lower than a critical value.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗