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S M Strasberg

Publications and source records attributed to S M Strasberg.

At least 73 records · Page 4Linked to original sources

A method for sequential excision biopsies of rat liver in an isolated perfused system.

We describe a simple method of performing sequential excision biopsies during liver reperfusion in the isolated perfused rat liver. After hepatectomy, four ligatures (5.0 silk) tied with a slip knot are placed around the pedicles of: (1) the inferior and (2) the superior parts of the caudate lobe, as well as (3) the inferior and (4) the superior parts of the right lateral lobe. At the time of biopsy, the prepared 5.0 silk ties are tightened with sufficient force to occlude the vascular pedicle, preventing leakage of circulating perfusate. The procedure provides four biopsies of more than 350 mg each without alteration of perfusate transaminases and tissue ATP contents. The total tissue removed by this method comprises 20-25% of the whole liver weight.

Animals↗

Rapid donor liver nutritional enhancement in a large animal model.

Organ donors are typically subject to acute hyponutrition that might affect postpreservation liver function. Livers from nutritionally supplemented rats function better after preservation than livers from fasted rats. We have developed a method to glycogenate the liver of large animals in the temporal context of a human donor liver operation and have studied the fate of glycogen stores during preservation. Starved anesthetized pigs were infused with a hexose solution (glucose, fructose or galactose) by way of the superior mesenteric vein for 3 hr. Regular porcine insulin was infused to maintain a hyperglycemic hyperinsulinemic arterial glucose clamp at 12 to 16 mmol/L. Liver biopsy specimens and blood samples were taken before infusion and hourly. At 3 hr the liver was excised, stored for 24 hr at 1 degrees C in University of Wisconsin solution and biopsied. It was then placed at 20 degrees C for 1 hr to simulate the reimplantation stage of transplantation. Glycogen and nucleotide levels were measured, and results were corrected for starch in the University of Wisconsin solution. A 20% glucose infusion produced rapid hepatic glycogenation without side effects. Greater glycogenation was obtained with 20% fructose but at the cost of lactic acidosis and a fall in pH. A combination of 15% glucose and 5% fructose produced intermediary glycogenation without significant side effects. Galactose (20%) was less efficient than glucose alone. The addition of alanine and glutamine (20 mmol/L) did not significantly improve glycogenation. Metabolism of glycogen at 1 degree C did occur. Glycogen content fell 0.15% +/- 0.05% dry weight liver per hour during cold preservation and 5.49% +/- 2.15% per hour during ischemic rewarming.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

Complications of laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is an extremely safe procedure. The most common serious complications are bile-duct injury and injury to vessels or bowel secondary to the insertion of trocars. These complications may be avoided with appropriate precautions. Indirect complications of surgery, such as pulmonary and cardiac complications, appear less common than with open cholecystectomy.

Cholecystectomy↗

Proposed classification of complications of surgery with examples of utility in cholecystectomy.

Lack of uniform reporting of negative outcomes makes interpretation of surgical literature difficult. We attempt to define and classify negative outcomes by differentiating complications, sequelae, and failures. Complications and sequelae result from procedures, adding new problems to the underlying disease. However, complications are unexpected events not intrinsic to the procedure, whereas sequelae are inherent to the procedure. Failures are events in which the purpose of the procedure is not fulfilled. We propose a classification of complications based on four grades: Grade I complications are alterations from the ideal postoperative course, non-life-threatening, and with no lasting disability. Complications of this grade necessitate only bedside procedures and do not significantly extend hospital stay. Grade II complications are potentially life-threatening but without residual disability. Within grade II complications a subdivision is made according to the requirement for invasive procedures. Grade III complications are those with residual disability, including organ resection or persistence of life-threatening conditions. Finally, grade IV complications are deaths as a result of complications. To illustrate the relevance of the classification, we reviewed 650 cases of elective cholecystectomy. Risk factors for development of complications were determined, and the classification was also used to analyze the value of a modified APACHE II as a preoperative prognostic score. Both supported the relevance of the proposed classification. The advantages of such a classification are (1) increased uniformity in reporting results, (2) the ability to compare results of two distinct time periods in a single center, (3) the ability to compare results of surgery between different centers, (4) the ability to compare results of surgical versus nonsurgical measures, (5) the ability to perform adequate metaanalysis, (6) the ability to identify objective preoperative risk factors, and (7) the ability to establish preoperative prognostic scores.

Adult↗

Immunoglobulins as nucleating proteins in the gallbladder bile of patients with cholesterol gallstones.

The gallbladder bile of patients with cholesterol gallstones contains pronucleating proteins which accelerate precipitation of cholesterol crystals from bile. In this study we have improved the purification procedure developed earlier for these nucleating proteins and have now identified the nature of these proteins. Gallbladder bile from patients with cholesterol gallstones was applied to concanavalin A affinity columns. The ConA-binding glycoprotein fractions containing the nucleating proteins were then separated by FPLC (fast protein liquid chromatography) using a Superose 12 gel filtration column. Nucleating activity was detected in the high molecular weight (FPLC-1) as well as in the low molecular weight fractions (FPLC-3). Investigation of the high molecular weight fraction by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by electroelution and amino acid sequencing suggested that these proteins were immunoglobulins. Immunostaining of Western blots with specific monoclonal antibodies identified the presence of immunoglobulin (Ig) M and IgA in the FPLC-1 fraction. These immunoglobulins were further purified by affinity chromatography employing an antibody exchanger (ABx) column which specifically binds immunoglobulins. There was no reduction in the cholesterol nucleating activity in the Abx-bound fraction compared to FPLC-1. Additional studies showed that the FPLC-1 fraction was significantly more potent than the ConA glycoproteins from either rapid and slow nucleating biles. Also the number of crystals formed was significantly greater in the FPLC-1 fraction isolated from cholesterol gallstone biles than from the FPLC-1 fraction from control patient biles. Commercially obtained IgM and IgA had no effect on nucleation, but IgM isolated from the serum of patients with Waldenstrom's macroglobulinemia did accelerate the nucleation of cholesterol. We conclude that the IgM and possibly IgA are pronucleating proteins and may be important in the pathogenesis of cholesterol gallstones in man.

Bile↗

Effect of colectomy on bile composition, cholesterol crystal formation, and gallstones in patients with ulcerative colitis.

Bile composition and the presence of cholesterol crystals in bile were studied in bile samples obtained at the time of surgery in patients with ulcerative colitis. Some patients were sampled before colectomy and others at a second operation months to years after a colectomy. Patients in the precolectomy group were found to have bile composition similar to control patients without gallstones, and few had crystals in their bile. In the postcolectomy group, cholesterol concentrations were very high, all biles were supersaturated, and almost all patients had cholesterol crystals in their bile. These findings are similar to those found in persons with cholesterol gallstones. Twenty patients have been followed for at least 3 years after colectomy and to date three have formed cholesterol gallstones.

Adult↗

Correlation of donor nutritional status with sinusoidal lining cell viability and liver function in the rat.

We have demonstrated that the sinusoidal lining cell injury sustained by rat liver allografts during hypothermic storage is a critical determinant of graft viability. The present study was designed to examine the effect of donor nutritional status on hepatic microcirculation and graft function. Rat livers from four nutritional groups (group I, fasted; group II, fed; group III, intraperitoneal glucose; and group IV, fed plus intraperitoneal glucose) were excised and stored for 24 hr in Marshall's isotonic citrate solution. Then the livers were perfused under anoxic conditions with trypan blue. The percentage of nonviable SLC in each group was 26.7 +/- 8.1, 24.9 +/- 7.9, 17.6 +/- 6.9, and 5.9 +/- 1.9 in groups I, II, III, and IV respectively; i.e., there was a significant improvement in SLC viability with nutritional repletion in group IV. Electron microscopy was performed on livers from groups I and IV following 30-hr preservation in University of Wisconsin solution and after 16-hr preservation in Marshall's isotonic citrate solution. Biopsies were taken at the end of storage and after 1 hr of reperfusion at 37 degrees C. At the end of preservation group IV livers contained glycogen and had much more normal liver ultrastructure than group I livers. After reperfusion there was partial recovery of normal SLC morphology in both groups and depletion of glycogen in group IV. Liver function was studied on the isolated perfused rat liver system at 37 degrees C following 30-hr storage in UW solution. Transaminase release into the perfusate was significantly lower in nutritionally repleted livers than in livers from fasted animals. A significant reduction in perfusate platelet count occurred only in livers from fasted animals. The results show that nutritional repletion can reduce the injury of cold preservation to both hepatocytes and endothelial cells and improve liver function in the postpreservation period.

Alanine Transaminase↗

Effect of cold preservation on lymphocyte adherence in the perfused rat liver.

A study was designed to determine if cold preservation induces an increase in lymphocyte adherence to liver sinusoids on reperfusion. Rat livers were stored at 1 degree C in University of Wisconsin solution for 45 min, 8 hr, or 30 hr, and then reperfused for 90 min at 37 degrees C in an isolated perfused rat liver apparatus. Just prior to reperfusion, isogeneic rat lymphocytes prepared on a Ficoll-Paque gradient were added to the perfusate. In some studies lymphocytes were labeled with a fluorescent lipophilic membrane marker. There was no change in the number of circulating lymphocytes in an anhepatic circuit. When livers were present in the circuit, lymphocytes were lost from the perfusate into the liver in all studies, with the most rapid decrease occurring within 10 min of reperfusion. The length of preservation had a marked and statistically significant effect on the rate of disappearance of lymphocytes from the perfusate. Reduction by 50% of the number of lymphocytes infused did not affect the results when expressed as percent lymphocytes remaining in perfusate. To exclude the possibility that the loss of lymphocytes into the liver was due to a damaged subpopulation of lymphocytes, two livers stored 3 for 45 min were put into the circuit in sequence. The percent reduction in cells due to exposure to a second liver was not significantly different from that observed when cells were exposed only to a single liver. Histological studies showed fluorescence-labeled lymphocytes adherent in sinusoids, and the number of labeled cells was directly related to the length of preservation. Cold preservation induces an increase in lymphocyte adherence in the reperfused liver, which might be important in graft malfunction and rejection.

Animals↗

Pathogenesis of cholesterol gallstones.

Cholesterol gallstone disease is extremely common. Three major stages are recognized for stone formation, namely bile that becomes supersaturated with cholesterol, cholesterol nucleation leading to crystal formation and finally retention of the crystals in the gallbladder resulting in stone formation. Supersaturation is common but nucleation into crystals probably requires protein nucleating factors. Impaired motility of the gallbladder causes crystal retention and is probably very important in stone formation.

Bile↗

Phospholipid lamellae are cholesterol carriers in human bile.

Cholesterol solubility and precipitation in bile are major factors in the pathogenesis of cholesterol gallstones. At present, mixed micelles and phospholipid vesicles are considered to be the only cholesterol carriers in bile. In this study we present evidence showing that phospholipid lamellae are major cholesterol carriers in human bile. Lamellae are a known aggregational form in pure phospholipid model systems. In the present study, lamellae were demonstrated by electron microscopy after negative staining and by small-angle X-ray diffraction in all human gallbladder bile samples examined. During diffraction experiments, cholesterol was found to crystallize from these lamellae. Cholesterol carriers in bile were separated by high-resolution chromatography and by prolonged ultracentrifugation. Lamellae were shown to solubilize most of the biliary cholesterol; vesicles solubilized a lesser amount; while micelles solubilized only a minor portion. Our data suggest that phospholipid aggregates are the main cholesterol carriers in bile. Bile salts may control the equilibrium between the various aggregational forms of cholesterol-carrying phospholipids.

Bile↗

Albumin absorption and protein secretion by the gallbladder in man and in the pig.

To study albumin absorption by the gallbladder in man, an in vitro model was first established in the pig and compared with in vivo function in the same species. Water and electrolyte transport and 125I-albumin absorption and protein secretion in vivo and in vitro were compared. Then similar in vitro studies were performed on human gallbladders obtained at surgery. The in vivo study in the pig was performed without disturbing the gallbladder except to tie a cannula in the cystic duct end. The in vitro model was identical in the pig and human gallbladders. Gallbladders were excised using a technique causing minimal injury and anoxia. They were oxygenated on both mucosal and serosal surfaces in a temperature-controlled environment. Luminal and external bath test solutions consisted of modified Ringers bicarbonate with added glucose; luminal solutions also contained 125I-albumin from different species, depending on the study. Active absorption of sodium and water occurred in both types of studies in the pig but in vivo absorption rates were considerably greater than in vitro rates. Albumin absorption in vivo was substantial; although present in vitro, the absorption of albumin was diminished relatively more than electrolyte transport rates. Protein secretion rates into the gallbladder were similar in vitro and in vivo. The results of studies in the human gallbladders in vitro were similar to the pig, except albumin absorption was greater. Some human gallbladders were obtained from control patients and some from patients with cholesterol gallstones. There were no significant differences between the two groups for any of the variables studied; however, the numbers were small and some control gallbladders were not normal gallbladders.

Absorption↗

High protein and total lipid concentration are associated with reduced metastability of bile in an early stage of cholesterol gallstone formation.

Previous studies from this laboratory suggested that high gallbladder protein concentrations as well as excessive dehydration of bile might reduce the normal metastability of human gallbladder bile. This study attempted to identify persons in an early stage of stone formation, when there are crystals but no stones, and to determine the composition of bile under these conditions of reduced metastability. Two hundred twenty-seven patients were studied, 96 without gallstones. Twenty-three of 96 control patients had cholesterol crystals in their bile. Total protein concentration, total lipid concentration, and cholesterol saturation index were greater in control patients with crystals in bile. To determine whether or not cholesterol saturation index alone could account for the presence of crystals, control patients with cholesterol saturation index above the median value of 1.04 were studied. In this case there was no difference in cholesterol saturation index between the 19 crystal-positive (1.27) and 29 crystal-negative patients (1.26), but the difference in total protein and lipid concentrations persisted. Total protein and total lipid concentrations were even higher in crystal-positive sediments containing large numbers of crystals. Sludge seen by ultrasonography was more common in patients with crystal-positive sediments. High protein and lipid concentrations are associated with reduced metastability of bile.

Bile↗

Early experience with reduced-size liver transplants.

Scarcity of small donors results in a high mortality rate for children on liver transplant waiting lists. To alleviate this problem, we have recently started to reduce the size of livers from older donors to use in children. In the last year, a total of 20 liver transplants were performed in 17 patients, including seven reduced-size liver transplants (RSLT) in six children. Mortality on the waiting list has been reduced to negligible amounts compared with a mortality rate of 25% before starting RSLT in patients with acute liver failure or those whose weight was less than 10 kg. Children undergoing RSLT weighed 10.8 +/- 8.5 kg compared with 20.9 +/- 20.3 for all others (NS). Cold ischemia time was significantly longer in the RSLT group (9.5 +/- 3.0 v 6.0 +/- 2.8 hours, P less than .05) as was intraoperative blood loss (9.4 +/- 9.4 v 3.0 +/- 3.5 blood volumes). There was no significant difference in postoperative aspartate aminotransferase and prothrombin time between the two groups. Four children received a RSLT as a primary procedure and three have survived with good liver function. Two patients were retransplanted with RSLT after a failed first transplant and both died of nonhepatic complications. This compares with 11 of 13 survivors in the whole liver transplant group. Causes of death in children who died after RSLT include cytomegalovirus sepsis (2) and myocardial infarction(1).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Biliary cholesterol transport and precipitation: introduction and overview of conference.

Cholesterol is secreted into bile as cholesterol-phospholipid vesicles. The cholesterol and phospholipid are subsequently exposed to the bile salts contained in the bile, which leads to the process of micellation. Two situations may arise depending on whether there is enough bile salt in proportion to cholesterol to complete this "maturation" process. If the cholesterol saturation is low, at equilibrium the bile salts will have completely micellized the vesicles. On the other hand, if bile is saturated with cholesterol, the micellation process is incomplete and vesicles and micelles will be present at equilibrium. The residual vesicle in this latter situation may have a higher cholesterol/phospholipid ratio because of the greater propensity of phospholipid to be micellized. This situation may result in cholesterol nucleation. The mechanism of nucleation from vesicles and the possible role of nucleating and antinucleating proteins in this process have been discussed.

Animals↗

Bile sampling, processing and analysis in clinical studies.

Obtaining a proper bile sample for investigative purposes is of utmost importance to obtain valid results. Bile can be collected by direct aspiration of the gallbladder, by duodenal intubation or by T-tube drainage. The optimal method of collection depends on the investigative question, as well as on the resources available to the investigator. The procedures for obtaining, processing and analyzing human bile (gallbladder and hepatic) are summarized, pointing out the disadvantages and pitfalls that may occur.

Bile↗