Conjugated and delta bilirubin determinations in early liver allograft rejection.
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Adult↗
Biomedical subjects
S M Strasberg
Publications and source records attributed to S M Strasberg.
Nucleation of cholesterol from vesicles isolated from bile of patients with and without cholesterol gallstones.
Bile was obtained from patients with and without cholesterol gallstones at surgery. Biliary vesicles were separated from micelles by gel filtration. The cholesterol/phospholipid ratio in vesicles was much higher than in micelles. Cholesterol crystals nucleated from vesicular fractions, but nucleation from the micellar fractions was slow or did not occur at all. Cholesterol nucleated from vesicles obtained from bile of control patients as rapidly (2.4 days +/- 0.7) as from patients with stones (2.4 days +/- 0.9) and there was no difference in the vesicular cholesterol/phospholipid ratio. The effect of alteration of the bile salt environment was studied by changing the concentration of sodium cholate in the eluting buffer. At low concentrations (5 mM) only vesicles were eluted from the column. These vesicles had a relatively low cholesterol/phospholipid ratio and cholesterol nucleated slowly from these vesicles. At higher concentrations the proportion of micelles increased. The proportion of vesicles decreased progressively but their cholesterol/phospholipid ratio increased and the nucleation time fell. These studies demonstrate that cholesterol nucleates from vesicles in the absence of micelles, that control vesicles are not protected by tightly bound antinucleating substances and that exposure of vesicles to micelles strips relatively more phospholipid than cholesterol from the vesicular fraction, resulting in vesicles with higher cholesterol/phospholipid ratios and shorter nucleation times.
Bile↗
Biliary proteins and the nucleation defect in cholesterol cholelithiasis.
A study was performed to determine whether differences in gallbladder proteins might be present in patients with rapidly nucleating bile. Gallbladder and hepatic bile protein concentrations were measured using a fluorometric assay. The method was validated by an independent technique, i.e., hydrolysis and amino acid analysis. Persons with cholesterol gallstones had significantly higher gallbladder bile protein concentrations than patients without gallbladder disease or patients with pigment stones. The protein concentration correlated with the in vitro nucleation time in the cholesterol stone group. Gallbladder bile proteins were also purified by chromatography and gradient ultracentrifugation. Proteins from patients with cholesterol gallstones accelerated the nucleation time of control bile, whereas protein from controls had little effect. Hepatic bile protein concentrations were similar in persons with and without cholesterol gallstones. The gallbladder-to-hepatic bile ratios of a variety of solutes were examined. The ratio for protein in the cholesterol gallstone group can be explained straightforwardly by water reabsorption in the gallbladder, whereas the very low ratio in patients without cholesterol gallstones suggests that their gallbladders reduce protein mass by a process such as protein absorption or degradation during water absorption in the gallbladder.
Adult↗
Markers of allograft viability in the rat. Relationship between transplantation viability and liver function in the isolated perfused liver.
The relationship between transplant viability and liver function has been examined. Wistar rat livers were preserved at 4 degrees C for increasing intervals and then transplanted into Wistar rat recipients. Two critical times were identified, the longest preservation period with 100% transplantation success (4 hr) and the shortest preservation period with 100% transplant failure (8 hr). The comparable critical times were also identified in livers preserved at 37 degrees C (1 hr and 2 hr). Liver functions were studied by the isolated perfused liver technique in other rat livers stored at 4 degrees C or 37 degrees C for the critical times. Two liver function tests, AST and LDH concentration in perfusate, discriminated between viable and nonviable livers across as well as within preservation groups. AST gave the best separation between viable and nonviable livers. Some functions such as ALT concentration in perfusate separated viable from non viable allografts only within preservation groups. Other liver functions were more sensitive to preservation temperature than allograft viability. Oxygen consumption after cold preservation for either critical time was about twice control levels. Urea production was far below control levels in warm-preserved livers but almost normal in cold-preserved livers. Our results indicate that AST release into perfusate can be used as a screening technique to optimize preservation methods, reserving transplantation for confirming the most promising results.
Animals↗
Effect of binding of ionised calcium on the in vitro nucleation of cholesterol and calcium bilirubinate in human gall bladder bile.
Biliary calcium may be a nucleating agent in cholesterol cholelithiasis. A study was designed to determine the effect of binding of ionised calcium on in vitro nucleation time. Ultracentrifuged and microscopically clear gall bladder bile from cholesterol gall stone patients was divided into two aliquots. One aliquot served as control and ionised calcium was bound in the second aliquot by addition of EDTA. Nucleation time was observed for the two groups. Addition of EDTA had no effect on lipid composition of the biles. EDTA bound all ionised calcium. Calcium bilirubinate precipitated from all controls on day 1 but was absent in all samples with EDTA. Addition of EDTA had no effect on cholesterol crystal nucleation time; nucleation time was rapid in both the controls and samples with EDTA. Ionised calcium is essential for calcium bilirubinate precipitation but is not responsible for the rapid nucleation time of bile from cholesterol gall stone patients.
Adult↗
Quantitative and qualitative comparison of gall bladder mucus glycoprotein from patients with and without gall stones.
Human gall bladder mucus glycoprotein was isolated by Sepharose 4B gel filtration followed by caesium chloride density gradient ultracentrifugation from four groups: patients with cholesterol gall stones, patients with pigmented stones, patients with complete obstruction of the cystic duct and patients with no biliary tract abnormalities (controls). Mucus glycoprotein concentrations in cholesterol gall stone bile (203 micrograms/ml +/- 199 SD, n = 17), pigment gall stone bile (110 micrograms/ml +/- 77 SD, n = 6) and control gall bladder bile (96 micrograms/ml +/- 98 SD, n = 11) were not significantly different. While bile from patients with complete obstruction of the cystic duct contained significantly higher concentrations of mucus glycoprotein (6220 micrograms/ml +/- 4130, n = 4). In vitro cholesterol nucleation time was not correlated to gall bladder mucus glycoprotein concentrations. Qualitative analysis of the carbohydrate and amino acid composition showed a basic structure typical of mucus glycoproteins in general. It is unlikely that either quantitative or qualitative differences in mucus glycoproteins are responsible for the rapid in vitro nucleation time characteristic of cholesterol gall stone patients.
Amino Acids↗
Bile salt dependent bile flow in the rabbit: evidence for the importance of an amiloride inhibitable pathway.
Bile salt dependent flow and electrolyte secretion in response to two bile salts were studied in awake rabbits. It was found that sodium glycodeoxycholate had a much greater choleretic and cholioneretic efficiency than sodium taurocholate. The effect of the bile salts on flow and electrolyte secretion was not linear across the range of bile salt secretion rates studied. When amiloride was administered significant decreases in choleretic and cholioneretic efficiencies occurred, but furosemide had no effect. It is concluded that bile salts stimulate electrolyte transport via amiloride inhibitable cellular processes, and that this electrolyte transport is in part responsible for bile salt dependent bile flow.
Amiloride↗
Local hepatic tuberculosis, the cause of a painful hepatic mass: case report and review of the literature.
Local hepatic tuberculosis is an unusual form of extrapulmonary tuberculosis. The authors describe the case of a 39-year-old woman with this disease who posed diagnostic difficulties. She presented with abdominal pain, minimal constitutional symptoms, hepatomegaly and radiologic findings of a focal hepatic lesion. Laparotomy was required for diagnosis. A literature review revealed that most individuals with local hepatic tuberculosis have fever, night sweats and weight loss. Hepatomegaly is often the only abnormal physical sign. Minimally elevated serum bilirubin and alkaline phosphatase levels are common. Ultrasonography and computerized tomography will demonstrate a lobulated, hypoechoic liver mass. Definitive diagnosis requires demonstration of acid-fast bacilli in biopsy material obtained by percutaneous techniques or at laparotomy. Cultures of the diseased liver are usually negative. Antituberculous drug therapy appears to be the preferred method of treatment.
Abdomen↗
Effect of sodium taurocholate on amiloride-inhibitable sodium uptake and on intracellular pH of isolated rat hepatocytes.
Evidence is accumulating that bile salts affect cellular mechanisms for the transport of inorganic electrolytes. We investigated the effect of amiloride on 22Na+ uptake rates in the presence and absence of sodium taurocholate (NaTC) and the effect of NaTC on intracellular pH (pHi) in isolated rat hepatocytes. Initial 22Na+ uptake rates (nanomoles per milligram of protein per minute) were significantly suppressed by amiloride (0.6 mmol/L), although the effect was small. NaTC significantly increased 22Na+ uptake rates. The amiloride-sensitive portion of 22Na+ uptake was significantly increased in the presence of NaTC (0.36 +/- 0.07 SEM nmol/mg protein/min vs. 0.20 +/- 0.07 nmol/mg protein/min, P less than 0.02). The pHi was estimated by using the pH probes carbon 14-labeled 5,5'-dimethyloxazolidinedione and acridine orange. NaTC caused intracellular alkalinization. Amiloride caused intracellular acidification, and the reduction of pHi by amiloride was enhanced in the presence of NaTC, although this enhancement is difficult to interpret because of the large effects of amiloride on pHi relative to those of NaTC. Our results indicate that NaTC affects sodium uptake by isolated hepatocytes probably by stimulating the Na+-H+ antiport.
Acridine Orange↗
So you wanted to do surgery and they keep talking about research: a discussion for the surgical resident and intern.
Surgical residents and interns frequently misunderstand the relation between surgery and research, and the contribution of surgical research to clinical practice. The problem is that the effects of research must be viewed in the long term. Once the resident can do this, the importance of research to surgery is evident and surgical research can be seen for what it is, the growing surface of surgery. Training to do surgical research has many parallels with clinical training. A core-training period in investigation provides the resident with the right mental approaches to investigation so that training in a specific area of research may be done later. Surgical scientists must be excellent clinicians as well as scientists and so long training periods are required. Four years of clinical practice training and 3 of research training are probably ideal. Shorter periods of research training may be valuable for many surgical residents, particularly those who have had little research experience. Training should be tailored to the trainee's desired role in surgery.
Canada↗
Effect of mucous glycoprotein on nucleation time of human bile.
The purpose of this study was to determine whether mucous glycoprotein is the nucleating factor responsible for the rapid in vitro nucleation time of gallbladder bile from persons with cholesterol gallstones. Ultracentrifugation and ultrafiltration of abnormal bile removed all detectable mucous glycoprotein, yet bile that had been filtered exhibited as rapid a nucleation time as unfiltered bile. When abnormal bile was heated to 95 degrees C for 60 min, nucleation time was significantly prolonged. Rapid nucleation time could be restored to heated abnormal bile by addition of small volumes of unheated bile. Purified human mucous glycoprotein accelerated nucleation time of human bile, but mucous glycoprotein from control patients was as effective as that from gallstone patients. There was a direct relationship between mucous glycoprotein concentration and effect on nucleation time. Mucous glycoprotein may be important in the early stages of stone formation, but it is probably not the agent responsible for the sharp discrimination between control bile and gallbladder bile from patients with cholesterol stones found in the in vitro nucleation time test. The markedly prolonged nucleation time of heated abnormal bile is preliminary evidence that the nucleating factor may be a heat-labile protein other than mucous glycoprotein.
Adult↗
Etiology of choledochal cysts: two instructive cases.
The etiology of choledochal cysts is controversial. The authors report two cases which show that type 1 cysts (axial dilatation of the common bile duct and common hepatic duct) may be caused by a biliary web and that some choledochoceles (type 3 cyst) may actually be duodenal duplications (i.e., having an outer wall of smooth muscle lined with gastrointestinal mucosa and being adherent to the gut).
Adult↗
Fasting canine biliary secretion and the sphincter of Oddi.
This study correlates duodenal bile acid delivery with motility of the sphincter of Oddi during the fasting state. Dogs were prepared with a functional cholecystectomy, a duodenal cannula for direct vision cannulation of the common bile duct, and 12 bipolar electrodes serosally implanted from stomach to terminal ileum. In one set of experiments, the bile acid pool was depleted, and during a continuous i.v. infusion of sodium taurocholate (20 mumol/min), duodenal bile acid delivery was assessed over 6 h by a marker perfusion technique. In other experiments, a double-lumen continuously perfused manometry catheter was placed to record motility in the bile duct and sphincter of Oddi for a period of 6 h. Station pull-throughs of the sphincter of Oddi were performed in each phase of the migrating motor complex. Bile acid secretion rates fluctuated about the i.v. infusion rate during duodenal phase I and II, peaked in late phase II, and then fell to barely detectable levels during duodenal phase III. There was no peristaltic contractile activity in the common bile duct in any phase of the migrating motor complex. The sphincter of Oddi maintained a baseline pressure above common bile duct pressure. It was highest during phase III. Phasic contractions of the sphincter of Oddi were intermittent during phase I, increasingly frequent during phase II, and continuous during duodenal phase III of the migrating motor complex. Contractions were frequently peristaltic. We concluded that the occurrence and amplitude of phasic peristaltic contractions of the sphincter of Oddi are cyclically coordinated with the fasting intestinal motor pattern (migrating motor complex), and with cyclical variations in the delivery of bile acids into the duodenum. Both resting pressure and phasic contractions of the sphincter appear to play a role in coordinating the cyclic delivery of bile acids into the duodenum with the migrating motor complex. Intense phasic motor activity appears to impede bile flow, and less intense activity allows or facilitates flow.
Action Potentials↗
Re-establishing continuity after the Hartmann's procedure using the EEA stapler.
The use of the EEA stapler transanally for end-to-side coloproctostomy permits simplified re-establishment of intestinal continuity following the performance of the Hartmann's procedure.
Humans↗
Nucleation of cholesterol monohydrate crystals from hepatic and gall-bladder bile of patients with cholesterol gall stones.
Nucleation time and cholesterol saturation index of hepatic and gall-bladder bile were measured in 16 patients with cholesterol gall stones to determine whether a gall bladder or liver defect was responsible for the rapid nucleation time of gall-bladder bile in such patients. Although hepatic bile was consistently more saturated than gall-bladder bile, the in vitro nucleation time of gall-bladder bile was more rapid. Dilution of gall-bladder bile to hepatic bile concentrations did not affect nucleation time. The results indicate that the gall bladder plays an important role in the production of the rapidly nucleating bile which is found in patients with cholesterol gall stones, and that this role is not simply concentration of bile by the gall bladder. Normal and abnormal gall-bladder biles were also compared in a larger group of patients. The view that there is a nucleation defect in cholesterol cholelithiasis which is independent of cholesterol saturation was confirmed. Subgroups of normal and gall-stone population were defined by the nucleation time and saturation index. Results suggested that solitary stones may be produced under different conditions than multiple stones. Some putative nucleating factors were examined but none was found to distinguish between normal and gall-stone bile.
Bile↗
Regulation of the fasting enterohepatic circulation of bile acids by the migrating myoelectric complex in dogs.
UNLABELLED: The purpose of this study was to correlate the fasting enterohepatic circulation (EHC) of bile acids with the migrating myoelectric complex. Four dogs were surgically provided with a functional cholecystectomy, a duodenal cannula for direct vision cannulation of the common bile duct, and 12 bipolar electrodes implanted from stomach to terminal ileum. Bile was collected in equal-volume, timed aliquots over 6 to 10 h. Aliquots were sampled and either returned to the duodenum for study of the intact EHC, or collected and retained in order to study the time course of the bile acid pool washout. In the washout experiments boluses of radiolabeled taurocholic acid were instilled into the duodenum before and after duodenal phase III of the migrating motor or myoelectric complex (MMC). In another group of experiments the bile acid pool was washed out and during a continuous duodenal infusion of taurocholic acid bile was collected to study the pattern of hepatic secretion. RESULTS: (a) In all experiments, a single broad peak of bile flow and bile acid secretion occurred at 35-55% of the MMC migration time. At this time the MMC had migrated to a point 70-85% of the distance along the small intestine. (b) During bile acid pool washout the peak of bile flow and bile acid secretion occurred with the distal migration of the first MMC and then bile flow and bile acid secretion rates decreased to a minimum and stabilized. (c) In bile acid pool washout experiments the radiolabeled bile acids instilled into the duodenum prior to duodenal phase III were secreted and peaked with peak endogenous bile acid secretion. The secretion of radiolabeled bile acids instilled into the duodenum after duodenal phase III was delayed until the subsequent cycle of the MMC. 88% of the bile acid pool collected over 6 h was secreted during the distal migration of the first MMC (2.4 +/- 0.4 h). (d) After bile acid pool washout and during continuous duodenal infusion of taurocholic acid, hepatic bile flow and bile acid secretion continued to fluctuate with the same pattern observed with the EHC intact. CONCLUSIONS: (a) In the fasting state, the transport of intestinal bile acids to the liver is pulsatile rather than continuous and is determined by the MMC. Maximum hepatic secretion occurs when phase III of the MMC propels the intraluminal bile acid pool to its site of absorption in the distal small bowel. (b) The "housekeeping" action of the MMC is very efficient and clears 88% of the 6-h washout bile acid pool in one pass.
Animals↗
Bile salt-associated electrolyte secretion and the effect of sodium taurocholate on bile flow.
Sodium taurocholate has a remarkably varied effect on bile flow. Preisig et al. showed that a portion of electrolyte secretion is related to bile salt secretion, and other studies have suggested that this fraction of electrolyte secretion is important in bile salt--dependent flow. In the present study in the baboon and the dog, it was found that the magnitude of bile salt-associated electrolyte secretion was closely correlated to the effect of sodium taurocholate on bile flow. Theophylline, an agent widely used to alter cellular electrolyte transport, simultaneously reduced the fraction of biliary electrolyte secretion related to bile salts and the effect of the bile salt on flow. The study suggests an important role for electrolyte secretion in the modulation of the effect of bile salts on bile flow.
Animals↗
Evidence for a potent nucleating factor in the gallbladder bile of patients with cholesterol gallstones.
A study was performed to determine whether the rapid nucleation time of gallbladder bile obtained from patients with cholesterol gallstones was due to the addition of a nucleating agent or the removal of an antinucleating agent by the gallbladder. Isotropic phases of gallbladder bile from normal controls (control bile) and from patients with gallstones (abnormal bile) were mixed 50:50 (vol/vol) and the nucleation times of the mixtures and parent biles were determined. The mixtures had rapid nucleation times, similar to those of the gallbladder bile from gallstone patients, indicating that a nucleating factor was present in the abnormal bile. Experiments were then performed using mixtures in which the proportion of abnormal bile was reduced. These studies showed that the nucleating agent was potent. The results were not due to changes in cholesterol saturation or total lipid concentration. The conclusions reached in the first study were supported in a second set of similar experiments in which hepatic bile from gallstone patients was mixed with their own gallbladder bile. It was also found that filtration of abnormal bile through an XM-300 Amicon filter did not eliminate its nucleating potency, indicating that the results could not be explained by the presence of residual microcrystals in the abnormal bile.
Bile↗