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Biomedical subjects

Z Halpern

Publications and source records attributed to Z Halpern.

At least 73 records · Page 4Linked to original sources
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

Gastric Mucosal Changes following Gastroplasty: A Comparative Study Between Vertical Banded Gastroplasty and Silastic Ring Vertical Gastroplasty.

BACKGROUND: Long-term changes of gastric mucosa following surgery for morbid obesity have never been studied, to the best of our knowledge. As 31 patients in our series presented with various gastrointestinal complaints following surgery, we used this opportunity to study mucosal changes. METHODS: Thirty-seven gastroscopies were performed on 31 patients, 20 patients following Vertical Banded Gastroplasty (VBG) and 11 patients following Silastic Ring Vertical Gastroplasty (SRVG) with various gastrointestinal complaints. Macroscopic appearance of the gastric mucosa was examined and biopsies taken from the proximal gastric pouch, the transitional zone and distal stomach. RESULTS: In most patients, macroscopic appearance of the proximal and distal pouches was normal. Pathological findings were mainly located in the transitional zone and were found mainly in the VBG group. CONCLUSIONS: This study indicates that damage to the gastric mucosa is related to the surgical technique, and mainly to the strip of mesh used in the VBG patients. Since hyperplasia and metaplasia were among the microscopic findings, a question is raised about the possibility of malignant transformation. We suggest that routine post-operative gastroscopies be considered, especially following VBG.

Journal Article↗
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↗
PubMed1994

Ileitis after colectomy for ulcerative colitis or carcinoma.

An ileitis developing years or months after ileostomy was recognised and described many years ago but has rarely been mentioned since. We describe nine patients with a non-specific preanastomotic ileitis that developed years after colectomy in patients operated on for ulcerative colitis or carcinoma. The disease developed after various types of reconstruction: ileorectal, ileoanal, with or without pouch. The diseased ileum showed inflammation, erosions, ulcerations, and sometimes strictures. The disease course ranged from asymptomatic to severe pain and diarrhoea. No specific cause could be shown. Granulomas, infectious agents or ischaemic changes were not found. The anastomosis was always patent. Three patients have had numerous episodes of intestinal obstruction presumably because of adhesions. Seven of nine patients were female. The response to steroids, 5-aminosalicylic acid preparations, and methotrexate was poor, three patients responded well to azathioprine. The condition is not rare and the cause remains unknown.

Adult↗
PubMed1993

[Laparoscopic cholecystectomy].

80 patients underwent laparoscopic cholecystectomy, of whom 64 were females and 16 males (age range 20-70 years) and 15 had undergone previous abdominal operations. 3 of the 80 operations were converted to open cholecystectomy. In 11, preoperative ERCP was performed, in 2 of whom common bile duct stones were detected. In 7 intraoperative cholangiography was performed. The average hospital stay was 2.2 days. Based on this and other studies, laparoscopic cholecystectomy seems to be the operation of choice for symptomatic cholelithiasis.

Adult↗
PubMed1993

Bile and plasma lipid composition in non-obese normolipidemic subjects with and without cholesterol gallstones.

A two-stage study was carried out to characterize the bile and plasma lipid composition in normolipidemic non-obese patients with and without cholesterol gallstones. The first stage involved 11 patients with cholesterol gallstones admitted for elective cholecystectomy and a control group of 16 patients without cholesterol gallstones undergoing elective laparotomy. Bile samples were obtained intraoperatively by aspiration from the gallbladder. The bile of all the gallstone patients was supersaturated with cholesterol and its nucleation time was much shorter than that of bile in the control group (2.5 days vs 22.5 days, respectively, P < 0.001). The biliary fatty acid profile of phosphatidylcholine (PC) and free fatty acids (FFA) of gallstone patients was similar to that of the control group. C-22 fatty acids were found in a higher concentration in the FFA than in the PC fatty acids (P < 0.05) in both groups of patients. Plasma triglyceride levels in the gallstone patients were significantly higher than those in the control group and the biliary cholesterol level correlated with that of plasma triglycerides. In the second stage of the study, plasma lipid profiles were obtained in two additional groups of patients, 20 patients with and 24 patients without cholesterol gallstones, for an in-depth characterization of the differences in plasma lipid profiles. The gallstone patients were found to have not only significantly higher concentrations of plasma triglycerides but increased cholesterol and phospholipid level as well. These differences were essentially due to a higher lipid content of the plasma VLDL fraction, similar to the pattern of patients with type IV hyperlipoproteinemia.

Bile↗
PubMed1993

Effect of phospholipids and their molecular species on cholesterol solubility and nucleation in human and model biles.

Much research in the pathophysiology of gall stones has been devoted to various molecular species of bile salts. Recent findings have shown the importance of phospholipids in biliary pathophysiology. In the present study the addition of increasing doses of egg lecithin to human and model biles progressively prolonged the nucleation time. Concurrently biliary cholesterol was shifted from the vesicular to the non-vesicular carrier(s) while the cholesterol/phospholipid ratio of the remaining vesicles was progressively lowered. Model bile solutions of identical lipid concentration were prepared using phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine as the only phospholipid. With phosphatidylethanolamine most of the cholesterol was shifted to the vesicular carrier while phosphatidylserine shifted most of the cholesterol to the non-vesicular carrier(s). With phosphatidylcholine the cholesterol was distributed in both carriers. Phosphatidyl choline species composed of various acyl fatty acids in the sn-1 and sn-2 positions were used as the sole phospholipid in otherwise identical model bile solutions. With palmitic acid in the sn-1 position and arachidonic acid in the sn-2 position most of the cholesterol was found in the non-vesicular carrier. When stearic acid was used in sn-2 position instead of arachidonic acid most of the cholesterol was found in the vesicular carrier. These and other variations in phospholipid molecular species shifted cholesterol among its carriers and also modified the nucleation time of model biles. Most of these effects were also found upon addition of the various phospholipid species to human biles. These findings show the importance of phospholipid species in biliary pathophysiology and may be useful when trying to manipulate cholesterol carriers and solubility in bile.

Bile↗
PubMed1993

Extracorporeal shock wave lithotripsy of gallstones: early experience in an Israeli population.

Fifty-four patients with symptomatic gallbladder stones were treated by extra-corporeal shock wave lithotripsy (ESWL) and oral bile acids on an outpatient basis. In 49 patients (90%), the stones were successfully fragmented to fragments < 5 mm on follow-up ultrasonography. Patients underwent 1-3 lithotripsy sessions with 7,500-9,750 shock waves per session. The gallbladder clearance rate of fragments was dependent mainly on the number of stones and reached 59% for patients with one or two stones, compared to 34% for patients with more than two stones after 9 months follow-up. The only side effects noted were mild abdominal pain, transient microscopic hematuria and minimal impairment in liver function tests. There were no serious complications such as cholecystitis, bile duct obstruction, or pancreatitis. These results, which are comparable with those of other groups using the same shock wave lithotriptor, indicate that this therapy may become an alternative treatment for selected patients with symptomatic gallbladder stones, especially those who are at high risk for surgical treatment.

Administration, Oral↗
PubMed1993

Anionic polypeptide fraction in bile of patients with and without gallstones.

With the demonstration of pronucleating and antinucleating proteins, the role of biliary proteins became of considerable research interest. Anionic polypeptide fraction is the third most abundant biliary protein; it is found in association with biliary lipids, has antinucleating properties for calcium and is found in gallstones. Its levels in various human biles have not been studied as of this writing. In this investigation the concentration of anionic polypeptide fraction in gallbladder bile was measured in 16 subjects without gallstones, 19 subjects with cholesterol stones and 15 subjects with pigment stones in Tel Aviv. Anionic polypeptide fraction concentrations in bile (mean +/- S.D.) were 0.76 +/- 0.09 gm/L in controls and 0.81 +/- 0.25 gm/L (which was not significant) in patients with cholesterol gallstones. They were significantly higher 1.03 +/- 0.23 (p < 0.05) in patients with pigment gallstones. The anionic polypeptide fraction/phospholipid ratio and the anionic polypeptide fraction/total lipid ratio were significantly higher in patients with pigment gallstones (p < 0.005 and 0.05, respectively). The anionic polypeptide fraction lipid ratios were insignificantly elevated in biles of patients with cholesterol stones compared with the ratios in biles of controls. Only the anionic polypeptide fraction/phospholipid ratio was significantly higher in biles of patients with pigment stones compared with those with cholesterol gallstones. The values were similar although higher in a small group of gallstone patients from Marseilles. The role of anionic polypeptide fraction in the pathogenesis of gallstones, particularly pigment gallstones, requires further study.

Adult↗
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↗