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Biomedical subjects

F M Konikoff

Publications and source records attributed to F M Konikoff.

11 recordsLinked to original sources
PubMed1996

Lithogenicity of human bile is reduced by freezing and thawing.

We examined the effects of freezing and thawing upon the nucleation time and the distribution of cholesterol between micelles and vesicles in 9 human gallbladder and 7 hepatic biles. The nucleation time was significantly longer after freezing when compared to fresh samples (22.4 +/- 2.6 vs. 7.4 +/- 1.9 days, respectively). Concomitantly, a substantial shift of cholesterol from vesicles to micelles was noted, with the proportion of vesicular cholesterol decreasing from 26.5% +/- 6.0% in fresh biles to 8.6% +/- 2.3% after freezing. These effects were observed in all types of human biles, regardless of origin, cholesterol saturation or initial presence of cholesterol crystals, and were most notable after the first week of freezing. The decrease in vesicular cholesterol in all biles and the increase in nucleation time of gallbladder biles correlated with the time the samples had been in a frozen state. It is concluded that the lithogenic properties of human bile are not maintained during storage at -20 degrees C. Freezing results in a shift of cholesterol from vesicles to micelles and reduces the tendency of cholesterol to crystallize from bile samples.

Bile↗
PubMed1996

The effects of dietary phospholipids enriched with phosphatidylethanolamine on bile and red cell membrane lipids in humans.

The role of phospholipids in biliary cholesterol solubilization and crystallization has only recently begun to be appreciated. Phospholipid vesicles are believed to be the metastable carrier from which cholesterol nucleates. Cholesterol crystallization is influenced by the phospholipid species in bile. Feeding rats and hamsters with diets enriched in phospholipids or their precursors, especially ethanolamine, resulted in reduced cholesterol saturation of bile. Although whole phospholipids are normal dietary constituents, the effects and safety of phospholipid components have not been tested in humans. In the present study, we have evaluated the effects of a dietary phospholipid mixture, enriched with phosphatidylethanolamine, on human bile and red blood cell membrane lipid composition. Five ambulatory volunteers having a chronic indwelling T-tube, with an intact enterohepatic circulation, were investigated. Thirty-six grams of phospholipids (54% phosphatidylethanolamine, 54% linoleyl acyl chains) were added to their daily diet for fourteen days. Biliary nucleation time, cholesterol carriers, as well as plasma, red blood cell membrane, and bile lipid compositions, were monitored. Following phospholipid supplementation, the proportion of linoleyl chains (18:2) in biliary phospholipids increased significantly from 31.1 +/- 1.2 to 37.7 +/- 5.3%, while that of oleyl chains (18:1) decreased from 11.4 +/- 1.6 to 9.6 +/- 1.1%. These changes were accompanied by an increase of linoleate and its metabolite, arachidonate, in red cell membranes. Phospholipid feeding did not cause any side effects, and no significant changes in biliary nucleation time, cholesterol, phospholipid, or bile salt concentrations, or in the distribution of cholesterol within micelles or vesicles. We conclude that phospholipid feeding is safe, and can be effective as a vehicle for lecithin fatty acyl chain modulation of bile and lipid membranes. These findings may provide a basis for a controlled modulation of biliary phospholipids to increase cholesterol solubility in bile.

Adult↗
PubMed1995

High Helicobacter pylori numbers are associated with low eradication rate after triple therapy.

This study tested the influence of pretreatment bacterial density on the eradication rate of Helicobacter pylori with triple therapy. One hundred and thirty two patients with endoscopically confirmed H pylori positive, duodenal ulcer or antral gastritis were treated with triple therapy (colloidal bismuth/metronidazole/amoxicillin) for two weeks. Pretreatment urease activity was assessed by the 14C-urea breath test (UBT) in all patients. The mean (SD) pretreatment UBT concentration was similar in patients with duodenal ulcers (318.4 (175.0)) and patients with antral gastritis (288.9 (165.5)). Overall eradication of H pylori was achieved in 85 of 132 patients (64.4%), but was significantly different between patients with high, intermediate, or low pretreatment urease activity (37.5%, 69.5%, and 87.8% respectively). The mean post-treatment UBT value of patients in whom eradication failed was in direct correlation with the pretreatment UBT values. In conclusion, bacterial density, as assessed by urease activity, is an important factor in predicting H pylori eradication. It is suggested that the pretreatment UBT has the potential to identify patients who require modification of the standard therapeutic regimen.

Amoxicillin↗
PubMed1994

Direct visualization of lipid aggregates in native human bile by light- and cryo-transmission electron-microscopy.

The evolution of microstructures present in human gallbladder and hepatic bile was observed simultaneously by video-enhanced light microscopy (VELM) and transmission electron microscopy of vitrified specimens (cryo-TEM), as a function of time after withdrawal from patients. Fresh centrifuged gallbladder bile samples contained small (6 nm) spherical micelles in coexistence with vesicles (40 nm). Out of the seven bile samples investigated four contained, in addition, two types of elongated aggregates that have not been previously described. Uncentrifuged gallbladder bile also contained a mixture of ribbon- and plate-like crystals seen by VELM, but not by cryo-TEM. In aged (3-6-week-old) gallbladder bile samples VELM also revealed spiral and helical crystal structures. No such crystals were present in hepatic bile samples, although microcrystals, not observable by VELM were seen by cryo-TEM in addition to micelles and vesicles. The similarity of these observations to those observed in bile models lends strong support for the validity of the model systems. Furthermore, the presence of microcrystals in hepatic bile samples, apparently devoid of crystals by light microscopy, indicates that under certain conditions the common criterion of 'nucleation time' (NT), based on light microscopy, does not represent the real time of nucleation. In the human bile samples investigated in this study the dissociation between NT and the time of observation of microcrystals was seen in hepatic but not in gallbladder bile samples. Hence, crystal growth may be rate limiting only in dilute biles.

Bile↗
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

An eight year experience with upper gastrointestinal bleeding: diagnosis, treatment and prognosis.

Bleeding from the upper gastrointestinal tract is one of the most common medical emergencies. Admission of patients to a specialized care unit may reduce morbidity and mortality. All patients admitted to the Tel Aviv Medical Center, between January 1, 1983 and December 31, 1990 with acute upper gastrointestinal bleeding, or those who bled while in the hospital, were seen and assessed by a senior member of the gastrointestinal service. Endoscopy was performed within 24 hr of admission. A total of 1110 endoscopies were performed. Duodenal ulcer was the main source of bleeding (40.0%). Injection of a vasoconstrictor was used for very small blood vessels. Thermal methods were used for small or medium sized vessels, or for oozing from a margin ulcer; both with equal rates of success. 153 (13.8%) surgical procedures were performed. Three (0.37) patients had endoscopic cardiovascular complications; one of them died. The in-hospital mortality was 5.9%. Increasing age, other medical problems, rebleeding and an admission hemoglobin of 8 g/dL or less, were associated with increased mortality. Our policy of early clinical and endoscopic assessment, and rapid surgical intervention in those at high risk, markedly improved survival.

Adolescent↗
PubMed1994

Phospholipid molecular species influence crystal habits and transition sequences of metastable intermediates during cholesterol crystallization from bile salt-rich model bile.

Despite its importance in cholesterol gallstone formation, crystallization of cholesterol from bile is poorly understood, especially with respect to the influences of other biliary lipids. We reported recently (Konikoff et al. J. Clin. Invest. 1992. 90: 1155-1160) that cholesterol can crystallize from model and native biles as filamentous crystals covered by a surface layer of lecithin molecules. During growth, filamentous crystals transformed via metastable intermediates into classical plate-like cholesterol monohydrate crystals. Using the same dilute (1.2 g/dl total lipid) bile salt-rich (97.5 moles %) model bile supersaturated with cholesterol, we have studied the effects of natural egg yolk, soy bean as well as single molecular species of lecithins, other phospholipids and related lipid classes on early filamentous cholesterol crystallization, as well as transformations between crystal habits and their growth to equilibrium cholesterol monohydrate plates. After extraction and derivatization, HPLC analysis revealed that the surfaces of filamentous crystals were enriched preferentially with lecithin molecular species having longer and more saturated sn-1 and sn-2 acyl chains compared to mixed lecithin species of whole bile. In contrast, the molecular species distribution of lecithins on equilibrium plate-like crystals resembled that of whole bile. After incubation of pre-formed anhydrous cholesterol and cholesterol monohydrate crystals in cholesterol-free lipid solutions, we demonstrated that surface-adsorbed lecithins were not preferentially enriched excluding nonspecific lecithin adsorption. Time-sequences and transformations between metastable crystalline intermediates were altered markedly by specific phospholipid species: model biles composed of saturated short-chain, medium-chain, and polyunsaturated long-chain lecithins induced rapid precipitation of short filamentous crystals that became plate-like slowly by an "arborization pattern." Long-chain saturated lecithins and natural sphingomyelins retarded cholesterol crystallization markedly, and filamentous as well as metastable intermediate crystals made transient appearances only after plate-like crystals had formed. These observations suggest that phospholipid molecular species and class influence the earliest events in cholesterol crystallization from bile salt-rich model bile. Furthermore, as the molecular species of lecithins adsorbed onto filamentous cholesterol crystals were more saturated than in whole bile and essentially identical to those in biliary vesicles, this finding provides chemical evidence for a vesicular origin of the critical cholesterol nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Adsorption↗
PubMed1994

Seasonal variation in the frequency of Helicobacter pylori infection: a possible cause of the seasonal occurrence of peptic ulcer disease.

OBJECTIVES: The seasonal variation of duodenal ulcer disease and its complications have been repeatedly demonstrated in Israel by several independent studies. The aim of this study was to determine possible seasonal variations in the occurrence of H. pylori infection among dyspeptic patients in Israel. METHODS: All 14C-urea breath tests performed in dyspeptic patients at the gastroenterology department in the Tel Aviv Medical Center from January 1991 to December 1992 were reviewed. The monthly variation in the proportion of patients with H. pylori infection was determined, and compared with that of an unrelated 14C-cholyl-glycine breath test. RESULTS: Altogether, 702 patients were examined, and 371 (52.8%) of them were found to be infected with H. pylori. During summer months (July-September), a significant decrease in the percentage of patients infected with H. pylori was found, compared with winter months (December-January, 42.3% vs. 60.9%, p < 0.007). No seasonal variation was found in the results of 14C-cholyl-glycine test. The fluctuations in H. pylori infection were highly correlated with the seasonal occurrence of peptic ulcer disease in Israel. CONCLUSIONS: The frequency of H. pylori infection in dyspeptic patients in Israel is significantly increased during the winter months and decreased in the summer. This seasonal variation is identical to that found in duodenal ulcer disease. Thus, the seasonal variation of peptic ulcer disease could be explained by H. pylori infection, as seen in other communicable infectious diseases.

Breath Tests↗
PubMed1993

Elastic free energy of anisotropic helical ribbons as metastable intermediates in the crystallization of cholesterol.

We report measurements of the geometrical structure and temporal evolution of metastable helical intermediates in the pathway for cholesterol crystallization in native and model biles. We find that the lecithin component in the bile can dramatically affect the kinetics along this pathway. We also present a theoretical description of these helical intermediates using an elastic free energy appropriate for anisotropic bilayers of tilted chiral amphiphiles, which provides a quantitative description of the observed helical ribbon geometry and insight into the relative free energies of the observed metastable intermediates.

Bile↗
PubMed1992

Filamentous, helical, and tubular microstructures during cholesterol crystallization from bile. Evidence that cholesterol does not nucleate classic monohydrate plates.

Precipitation of cholesterol in gallbladder bile is believed to produce platelike cholesterol monohydrate crystals directly. We report complementary time-lapse microscopic studies of cholesterol crystallization from model bile that reveal initial assembly of filamentous cholesterol crystals covered by a monomolecular layer of lecithin. Over a few days, the filaments evolved through needle, helical, and tubular microstructures to form classical platelike cholesterol monohydrate crystals. Similar crystallization phenomena were observed in human gallbladder biles from cholesterol but not pigment stone patients. Synchrotron x-ray diffraction of the earliest filaments suggested a cholesterol monohydrate polymorph or admixture with an anhydrous cholesterol precursor. However, density gradient centrifugation of filamentous crystals revealed that their density was 1.032 g/ml, consistent with anhydrous cholesterol. Conventional x-ray diffraction of transitional crystalline forms was consistent with pure cholesterol monohydrate crystals, as were the equilibrium platelike crystals. These novel findings suggest that crystalline cholesterol in bile may not be completely mature or hydrated initially, but undergoes a series of transformations to become thermodynamically stable monohydrate plates. These observations have important implications for understanding the control of cholesterol crystallization in bile, as well as explaining putative crystal cytotoxicity during gallstone formation.

Bile↗