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Biomedical subjects

Z Halpern

Publications and source records attributed to Z Halpern.

At least 37 records · Page 2Linked to original sources

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

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

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

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

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

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

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

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

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

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

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

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

Biliary micellar cholesterol nucleates via the vesicular pathway.

Biliary cholesterol nucleates primarily from phospholipid vesicles. In this study, we investigated the mode of nucleation of micellar cholesterol. Ten biles (four human and six model) were examined. The vesicular and micellar fractions of each bile were separated by gel chromatography. The whole biles and their isolated carriers were incubated at 37 degrees C until nucleation time. In whole human biles, the proportion of total cholesterol in vesicles rose throughout the incubation (from zero time to nucleation time) from 15.5 +/- 8.6% to 28.0 +/- 12.5%, and in model biles from 46.8 +/- 22.4% to 75.5 +/- 8.2%. The vesicular isolated fraction remained unchanged throughout incubation. In isolated micelles devoid of vesicles at zero time, new vesicles formed during incubation, carrying increasing proportions of cholesterol. At nucleation time, these vesicles contained 11.0% of originally micellar cholesterol in human biles, and 41.2% in model biles. The new vesicles formed in whole bile and in the micellar fraction were chromatographically and chemically similar to the vesicles originally present in bile. These data suggest that micellar cholesterol nucleates via the neoformation of phospholipid vesicles, which seem to be the final common pathway for cholesterol nucleation in bile.

Bile

Prostaglandin E2 in pyloric stenosis.

Prostaglandins are presumed to have many cytoprotective properties that play a role in the pathogenesis of duodenal ulcer and its complications where decreased levels of prostaglandin E2 (PGE2) impair gastric motility, oppose ionic membrane influx, and enhance obstructive changes. These are just some of the mechanisms that may cause pyloric obstruction and may result from decreased PGE2 levels. To evaluate this hypothesis, 17 patients with duodenal ulcer complicated by pyloric stenosis were examined. Biopsy specimens were obtained from the duodenal bulb, ulcer margins, gastric antrum, fundus, and gastric secretions. Prostaglandin E2 levels were measured and compared with those taken from the same areas during a second endoscopy in a later quiescent or exacerbated phase. During the active phase of pyloric stenosis, decreased levels of PGE2 were found in the gastroduodenal tissues and secretions were compared with levels found during convalescence. These level differences were statistically significant. A correlation between the severity of the clinical and endoscopic findings and the PGE2 levels was found. A further decrease in PGE2 levels in the second endoscopy were indicative of the presence of scar tissue, representing an irreversible obstructive peptic disease.

Aged

Shigellosis in adults: epidemiologic, clinical, and laboratory features.

One hundred and sixteen cases of adult patients hospitalized for shigellosis have been reviewed. The most common presentation included diarrhea (most frequently watery), fever, and abdominal pain, while dysentery has been less frequent. S. flexneri infection, as compared to S. sonnei, was more common in elderly patients and in males, and was characterized by a more prolonged clinical course. Abnormalities of serum electrolytes and hepatic enzymes were the most common laboratory complications, most often seen in elderly patients. Most isolates exhibited susceptibility to the common antimicrobial agents used in shigellosis therapy.

Anti-Bacterial Agents