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Biomedical subjects

S M Strasberg

Publications and source records attributed to S M Strasberg.

At least 55 records · Page 3Linked to original sources

Diffusion of substances into human cholesterol gallstones.

BACKGROUND/AIMS: The possibility that substances penetrate gallstones and accumulate after stones have formed has not been examined. The specific aims of this study were to determine whether cholesterol gallstones are permeable and, if so, the effect of molecular weight on permeability. METHODS: Cholesterol gallstones from patients with multiple stones were collected during surgery and incubated in fluorescein solution or in solutions of fluoresceinated albumin or immunoglobulin (Ig) G. To determine egress from the stones, some stones were removed from the fluoresceinated solution after incubation and placed in bicarbonate buffer. The total area of the stone and the area of dye that had diffused into the calculi were calculated. To determine mass of penetrating IgG, stones were powdered after incubation, and IgG was measured by an enzyme-linked immunosorbent assay. RESULTS: All substances penetrated stones. Although all compounds tested diffused back out of the stones when they were replaced in buffer, proteins did so more slowly than fluorescein. CONCLUSIONS: Substances of different molecular weights can diffuse into and out of cholesterol gallstones. These findings must be taken into account when considering the role of substances contained in stones on stone formation and growth.

Cholelithiasis↗

Risk factors in elective laparoscopic cholecystectomy for conversion to open cholecystectomy.

BACKGROUND: Most cholecystectomies can be performed using a laparoscopic approach. However, 3 to 10 percent of laparoscopic cholecystectomies (LC) must be converted to open cholecystectomies (OC) and preoperative factors that predict risk for conversion are still not defined. STUDY DESIGN: Preoperative and intraoperative data were collected and analyzed from 628 patients who were scheduled for elective LC by two surgeons in an academic institution. Logistic regression was performed on data from two groups of patients: LC completed, 596 patients (95 percent) and LC converted, 32 patients (5 percent). RESULTS: Elective LC was accomplished with no common bile duct injuries, low morbidity rate (7.3 percent), and zero mortality rate. Both patient and surgeon factors predicted conversion from LC to OC. Older patients (65 years of age or older, (p < 0.01), males (p < 0.01), and patients with multiple attacks (ten or more) of biliary colic (p < 0.01), or a documented history of acute cholecystitis (p < 0.01) had a greater risk for conversion. Both surgeons had higher rates of conversion (p < 0.05) during the learning phase (fewer than 50 LC) of their experience. CONCLUSIONS: Risk factors for conversion may be predicted and awareness of these factors should help in the selection of the appropriate procedure for patients and in selection of cases for resident training.

Adult↗

Effect of human biliary immunoglobulins on the nucleation of cholesterol.

We have previously identified that either biliary immunoglobulin IgA or IgM is a pronucleating protein which can accelerate the precipitation of cholesterol from bile. In this study we purified the biliary immunoglobulins (IgA, IgG, and IgM) to homogeneity by affinity chromatography to investigate the relative cholesterol nucleating potency of each immunoglobulin. Each immunoglobulin was added to slow nucleating heated abnormal biles in a dose-response manner to give a final concentration of protein in the range of 62.5-625 micrograms/ml bile. Cholesterol-nucleating activity was measured by noting the first day of cholesterol crystal formation as well as the number of crystals formed over the observation period. Biliary IgM and IgG appear to be more potent pronucleators than IgA. Isolated serum IgM from patients with Waldenstrom's macroglobulinemia as well as serum IgG from patients with and without cholesterol gallstones were shown to have pronucleating activity and acted in a dose-response manner. Commercial IgG unlike commercial IgM retains nucleating activity. The concentration of biliary immunoglobulins was measured by an enzyme-linked immunoassay (ELISA) in the gallbladder bile of patients with and without cholesterol gallstones. Biliary IgG concentrations in bile were higher in cholesterol gallstones patients than in pigmented gallstone patients and controls. We conclude that immunoglobulins particularly IgG and IgM are important pronucleating proteins and could play a role in the pathogenesis of cholesterol gallstones.

Albumins↗

Overview of therapeutic modalities for the treatment of gallstone diseases.

The management of gallstone diseases has been revolutionized in less than 2 years by the advent of laparoscopic cholecystectomy (LC). However, the rapid adoption of LC has occurred without comparative randomized trials with other available therapies. Thus, the evaluation of LC versus other therapies can only be based on case series. The criteria used for this evaluation are clinical effectiveness, cost-effectiveness, and the patient's level of acceptance and satisfaction with the procedure. The techniques of both LC and open cholecystectomy (OC) have the advantage over other approaches, such as extracorporeal shock-wave lithotripsy or bile acid therapy, of eliminating not only the gallstones but also the gallbladder, thereby preventing recurrence of the disease. Additionally, medical therapies are effective in only a subgroup of patients. Since the complications of surgery are more frequent and more severe in older patients and, due to life expectancy, the risk of recurrence is lower in this population, cost-effectiveness analyses have shown that medical therapies may be preferable in older patients in the subgroup eligible for the respective medical therapies. Compared with OC, LC results in a reduction in hospital stay and time to return to work, in lower cost, and in higher patient satisfaction with the procedure. However, a major concern with the laparoscopic approach has been an increase in the incidence of bile duct injury, particularly during the learning phase of the procedure. Clearly, this problem must be solved. The development of training courses in laparoscopy and the adoption of rigorous criteria for ductal identification are critical in preventing such injuries. Bile duct injury can probably be reduced at least to the level of OC (about 1 in 1,000). Acute cholecystitis may also be treated by LC, but the safety and timing of surgery should be conclusively evaluated. Patients with gallbladder stones and choledocholithiasis are usually treated by endoscopic sphincterotomy either before or soon after laparoscopic surgery. Laparoscopic techniques of common bile duct exploration that will obviate the need for endoscopic sphincterotomy are in the developmental stages. When such a technique is available, comparative trials with endoscopic sphincterotomy will be necessary to assess the best approach.

Acute Disease↗

Evidence of the existence of a soluble mediator of cold preservation injury.

A study was designed to determine whether soluble mediators of injury are released during cold preservation. A first set of livers consisting of three groups was stored in cold Euro-Collins solution. These were a control group stored for 10 min (group 1), an experimental group stored for 16 hr (group 2), and an "antiprotease" group to which a cocktail of antiproteases had been added, which was also stored for 16 hr (group 3). The preservation solution in these livers was washed out at the end of preservation, and this effluent was concentrated and infused into a second set of livers that were all cold-stored for 4 hr. Then, the second-set livers were either perfused-fixed at 4 degrees C with universal fixative or reperfused at 37 degrees C for 180 min in the isolated perfused rat liver (IPRL). Morphometric assessment of sinusoidal lining cells (SLC) on light and electron microscopy showed an increased degree of microcirculatory injury in livers preserved with concentrates from livers of the experimental group. On light microscopy, only 2.2 +/- 0.4% (mean +/- SD) of the SLC had a normal flattened morphology compared with 11.9 +/- 2.0% in the control group, and 10.7 +/- 2.3% of the SLC appeared completely detached from the underlying hepatocytes compared with 2.6 +/- 0.8% in the control group, the differences being statistically significant (P < 0.05). This injury was prevented by the addition of antiproteases to EC solution. Similar results were obtained in the IPRL model, in which a number of typical changes related to cold preservation injury were noted in livers preserved with concentrates from the experimental group. Compared with controls, livers preserved with concentrates from the experimental group had early and significant alterations in markers of microcirculatory injury, including a reduction in portal flow and an increase in creatinine kinase-BB isoenzyme release, followed by an increase in perfusate transaminases, LDH, and a decrease in bile production. Again the injuries were largely prevented by the addition of antiproteases. There were no differences among groups in the degree of white cell and platelet adherence during reperfusion. Experiments using UW solution showed similar results, indicating that the soluble mediator(s) is not specific for a particular preservation solution. These observations are consistent with the hypothesis that soluble mediators are produced during the hypothermic period, and are responsible for a significant part of cold preservation injury, and that proteolytic reactions are involved in this type of injury.

Alanine Transaminase↗

Prediction of the outcome of transplantation in man by platelet adherence in donor liver allografts. Evidence of the importance of prepreservation injury.

We examined platelet adhesion in thirty human donor livers to determine if the degree of platelet adhesion could predict outcome of transplantation. Wedge liver biopsies were taken at the start of the donor operation (biopsy 1) and 1 hr after reperfusion in the recipient (biopsy 2). Biopsies were stained with a monoclonal antibody against platelet glycoprotein Ib and graded for platelet adhesion. Hematoxylin and eosin-stained sections were examined for polymorphonuclear leukocyte adhesion and necrosis. Platelet adhesion was much more frequent and extensive than expected in biopsy 1. Nine of 30 biopsies showed moderate or high-grade platelet adhesion. Thus in this study endothelial cell damage was present in about one-third of donors before the donor operation. The injury was not detectable by routine microscopic or clinical examination or biochemical tests. The degree of platelet adhesion in biopsy 1 predicted development of PMN adhesion and necrosis in biopsy 2 and postoperative transaminase concentrations and prothrombin times in recipients. During preservation and implantation some livers converted from low to either moderate or high grades of platelet adhesion. The grade of platelet adhesion in biopsy 2 predicted postoperative outcome as measured by transaminase and PT levels. Patients whose platelet grade converted to a higher level during preservation and implantation did not do as well as patients who remained at a low adhesion grade. These findings strongly suggest that the degree of platelet adhesion is an important determinant in assessing outcome and may provide a means of measuring the status of liver allografts prior to transplantation.

Age Factors↗

Laparoscopic versus open cholecystectomy: a matched study.

To determine the efficacy of laparoscopic cholecystectomy (LC) in the treatment of gallstone disease, all patients who underwent elective surgery for cholelithiasis during three consecutive periods (1989, 1990 and 1991) were studied. There were 121 patients in each period. All patients in the first period underwent open cholecystectomy (OC), whereas 70 (58%) patients underwent laparoscopic procedures in the second period (OC-LC). LC was the treatment of choice in the third period. Multiple factors, including sex, age, clinical and biochemical presentation of the disease and modified Apache II score were comparable among the three groups. The authors found significant differences in length of hospitalization (6.4 +/- 4.2 days in the OC group, 3.6 +/- 2.4 days in the OC-LC group and 2.4 +/- 1.7 days in the LC group, p < 0.01 when compared with the OC group) and return to work after surgery (5.8 +/- 2.8 weeks, 2.8 +/- 1.2 weeks and 1.3 +/- 1.8 weeks respectively, p < 0.01 when compared with the OC group). There was no significant difference in postoperative complications among the groups, but complications in the OC patients were more severe. Although operative time increased significantly after the introduction of LC, it returned to the range of OC after 36 procedures. Nine patients (5%) with LC required conversion to OC. Benefits of LC include a shorter hospital stay and a shorter recovery period. There were no deaths, very low morbidity, a substantial decrease in overall cost and a high degree of patient satisfaction with LC.

Adult↗

Cholelithiasis: seven critical questions.

The management of cholelithiasis is usually straightforward, but there are a few special situations and questions which arise repeatedly. This paper deals with management of patients with asymptomatic stones, diabetic patients with stones, the relationships between stones and cancer, and patients without stones but who have typical pain. It also considers certain surgical topics of interest to primary care specialists, including that of safety of laparoscopic surgery, pain after surgery, and the role of incidental cholecystectomy.

Cholecystectomy↗

Multiple intrahepatic cholesterol stones.

The authors report a case of multiple intrahepatic cholesterol stones found in an asymptomatic patient who had undergone cholecystectomy 12 years before. Biochemical abnormalities and radiologic and pathologic findings are noted. The patient underwent liver resection with Roux-en-Y choledochojejunostomy and received ursodeoxycholic acid postoperatively. Recovery was uncomplicated, and the patient was well at 1-year follow-up. Intrahepatic cholesterol lithiasis is rare but can be diagnosed preoperatively. Treatment depends on the presence of complications and the distribution of the stones.

Adult↗

Role of platelets in hepatic allograft preservation injury in the rat.

Cold preservation of liver allografts injuries hepatic sinusoidal lining cells. This injury is exacerbated on reperfusion, in part because of adhesion of leukocytes. Platelets also adhere to activated endothelial surfaces. In this study we examined the role of platelets in preservation injury. Our specific aim was to determine whether the degree of platelet adhesion on reperfusion of preserved rat livers was related to duration of cold or warm ischemia and whether platelet adhesion resulted in injury to allografts. We also examined the effect of prior activation of platelets on adhesion and injury. Rat livers were preserved at 1 degree C for different time periods in University of Wisconsin solution and then reperfused for 3 hr on the isolated perfused rat liver system with Krebs-Henseleit solution to which unactivated isolated rat platelets were added. Other livers were rewarmed before reperfusion or reperfused with activated platelets. Platelets were lost from the circulation in all studies; the percentage reduction of circulating platelets was dependent on the length of preservation. The initial platelet concentration did not affect the rate of reduction of platelets in the circuit. Rewarming before reperfusion increased platelet adherence, and prior activation also increased adherence. With electron microscopy we determined that platelets adhered in small aggregates to endothelial cells or endothelial cell remnants. Adherent platelets appeared more activated and contained fewer granules than did unperfused platelets. Liver injury as measured by release of transaminases into perfusate was worsened by longer periods of cold preservation and by addition of rewarming to the protocol. The presence of platelets under these circumstances aggravated injury. Prior activation of platelets also increased the extent of injury. These studies show that platelets have an important role in cold preservation-reperfusion injury.

Alanine Transaminase↗

Lymphocyte adherence in the reperfused rat liver: mechanisms and effects.

Leukocyte adhesion may play a central role in the pathogenesis of preservation-reperfusion injury to liver grafts. We previously showed that lymphocyte adhesion to sinusoids is dependent on the length of cold ischemia. In the present study we examined the mechanisms of lymphocyte adherence after harvesting combined with a short and a long preservation time. The effects of lymphocyte adherence on liver function were also examined. Rat livers were stored at 1 degrees C in University of Wisconsin solution for 45 min or 30 hr and then reperfused at 37 degrees C in the isolated perfused rat liver with isogeneic lymphocytes in an asanguineous perfusate. The role of reactive oxygen intermediates was investigated with allopurinol, a vitamin E analog and ascorbate or superoxide dismutase and catalase. For us to determine the role of Kupffer cells, Kupffer cell blockade was produced by gadolinium chloride. Leukotriene B4 effects were examined with the lipooxygenase inhibitor, nordihydroguaiaretic acid. We evaluated the possible presence of mechanical obstruction by studying flow rates and the circulation of red blood cells. We examined the role of adhesion molecules by pretreating lymphocytes with trypsin or neuraminidase and by exposing livers to arabinogalactan. We investigated the effects of lymphocyte adhesion on liver function by comparing perfusate liver enzymes in livers reperfused with and without lymphocytes, with trypsinized lymphocytes and with an increased number of lymphocytes. Allopurinol significantly reduced hypoxanthine degradation, and nordihydroguaiaretic acid inhibited leukotriene B4 release into the perfusate. The ability of gadolinium chloride to inhibit Kupffer cells was shown by colloid carbon uptake. In livers harvested and preserved for 45 min, lymphocytes decreased about 40% during reperfusion. In livers preserved for 30 hr, the reduction was significantly greater (about 80%). Lymphocyte adherence was lessened in livers preserved for 45 min by all three of the reactive oxygen intermediate protectants and by gadolinium chloride. In contrast, neither reactive oxygen intermediate protectants nor gadolinium chloride reduced adherence in livers preserved for 30 hr. Nordihydroguaiaretic acid had no effect in livers preserved for either 45 min or 30 hr. Portal flow in livers preserved for 45 min and 30 hr was similar, suggesting an absence of mechanical obstruction, and this finding was supported by a complete absence of red cell trapping. Trypsinization of lymphocytes and exposure of livers to arabinogalactan significantly lessened lymphocyte adherence in livers preserved for 30 hr but not in those preserved for 45 min.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Changes in bilirubin pigments secreted in bile after liver transplantation.

The species of bile pigments secreted in T-tube fistula bile after liver transplantation were ascertained by high-performance liquid chromatography in 15 patients for 10 days after liver transplant. Nine glycosidic conjugates and unconjugated bilirubin were resolved by the analytical procedure. The principal pigments in bile and their proportions in normal patients were the following: bilirubin diglucuronide = 83.0% +/- 3.1% (S.D.); bilirubin monoglucuronide = 9.7% +/- 1.4% (S.D.); bilirubin monoglucuronide monoglucoside = 4.0% +/- 2.8% (S.D.); and bilirubin monoglucuronide monoxyloside = 1.5% +/- 1.8% (S.D.). All of the other possible glucuronide, glucose and xylose monoconjugates and diconjugates and unconjugated bilirubin were also found, but each was normally less than 1% of the total. In 13 of the 15 transplant patients, a significant depression in proportions of bilirubin diglucuronide and elevation in proportions of bilirubin monoglucuronide were found after the transplant, with an accompanying but generally small increase in the proportions of the minor conjugates. In two patients with rejection of the transplant, the changes were of larger magnitude, with improvement occurring only with recovery from the rejection. In one of these patients, kidney failure was present, and in addition to the diglucuronide and monoglucuronide conjugates, diglucoside and monoglucoside monoxyloside conjugates were found in plasma. The underlying metabolic abnormalities are not clear but likely reflect underlying abnormal intracellular cofactor levels for conjugation. Glycogen depletion with reduction of UDP-glucuronate levels or reduced UDP-glucuronate formation from UDP-glucose, secondary to elevation of UDP-xylose, could potentially account for the changes in pigment excretion.

Adult↗

Effect of intraportal glucose infusion on hepatic glycogen content and degradation, and outcome of liver transplantation.

Recent animal studies suggest that nutritional repletion may improve function of liver allografts, and the authors have found that intraportal glucose infusion in pigs produces rapid and substantial hepatic glycogenation. A controlled prospective randomized study in 32 patients was done to determine glycogen content and degradation in human livers during transplantation, and the effect of intraportal glucose-insulin infusions during the donor operation on these variables and on outcome of transplantation. Peripheral blood glucose concentrations were "clamped" at 14 mmol/L during the glucose-insulin infusion. Liver biopsies were taken at various stages of the procedure. Liver glycogen decreased 2.0 +/- 1.2 g/100 g dry weight liver (mean +/- standard error of the mean) in controls, but increased 6.8 +/- 1.8 g/100 g dry weight in glucose-infused donors. In both groups there was glycogen degradation during periods of cold preservation, anoxic rewarming, and after reperfusion with portal blood. Degradation rates were greater in the glucose-infused group than in controls in all three periods (p less than 0.05). Despite wide variation in postoperative aspartate aminotransferase (AST) levels among recipients in both groups, the difference in peak postoperative AST levels approached significance (p = 0.06). In addition, peak AST levels were closely correlated to anoxic rewarming time in both groups, but the slope of the relationship was much lower (3834 versus 734, p less than 0.01) in the glucose-infused group. Thus at anoxic rewarming times over 90 minutes, glycogenation was protective of liver function. Peak postoperative AST was significantly correlated to glycogen degradation in the cold preservation and rewarming periods in the glucose-infused group only. Intraoperative glucose infusions in humans can reglycogenate the liver, increase glycogen degradation, and improve certain outcome measures in liver transplantation.

Adult↗

Recent results of elective open cholecystectomy in a North American and a European center. Comparison of complications and risk factors.

Results of elective open cholecystectomy in 1252 patients treated in a North American and a European center were examined using a recent standardized classification of complications. Although there were significant differences between centers in population age, rate of concomitant disorders, and numbers of operators, the frequency and severity of complications were comparable. There were no deaths, but 12% and 14% of the patients developed complications in the two centers. About 6% of the patients developed grade I complications. Grade II complications were noted in 6% and 8%, and grade III in 0% and 0.3%. Using univariate and multivariate analysis, individual risk factors for developing complications were found to be different in the two centers. Two preoperative scoring systems, ASA and a simplified APACHE II, were predictive for complications in both centers, but did not account for all risk in these patients. Data from the two centers could not be combined because of significant interaction between risk factors and center. Elective open cholecystectomy is a safe procedure, particularly in terms of highly morbid complications and death. Generalization of risk factors identified in a particular center may be misleading because local conditions may significantly affect risk factors for complications. The data also demonstrate the advantages of a uniform way of reporting surgical complications, which may permit meaningful comparisons among centers.

Adolescent↗