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A lipoprotein characterizing obstructive jaundice. I. Method for quantitative separation and identification of lipoproteins in jaundiced subjects.

Three immunochemically and electrophoretically distinct lipoproteins, LP-A, LP-B, and LP-X,(1) were isolated from the low density lipoprotein fraction (1.006-1.063 g/ml) in plasma from patients with biliary obstruction by a separation procedure which combines ultracentrifugation, heparin precipitation, and ethanol fractionation. This method, here described, permits the quantitative determination of individual plasma lipoprotein families on the basis of their protein moieties, rather than on the basis of their lipid moieties or density. The chemical composition of the unique lipoprotein, LP-X, was similar to that of an abnormal lipoprotein, OLP, isolated by Russ et al. (29) and by Switzer (30). In obstructive jaundice plasma, the combined LP-X and LP-B accounted for 98% and the LP-A for only 2% of the total protein content of the LDL fraction. This study indicates that the plasma lipoprotein pattern in obstructive jaundice is characterized by (a) a decreased concentration of HDL, (b) an increased concentration of LDL, and (c) the presence in the LDL fraction of varying amounts of a specific lipoprotein, LP-X, immunochemically and chemically distinct from LP-A and LP-B. LP-X, with its characteristically high content of unesterified cholesterol and phospholipids, is primarily responsible for the unusual protein and lipid content of the LDL fraction. Screening tests in 61 patients with various forms of jaundice indicated that a characteristic immunoelectrophoretic precipitin are between plasma samples and purified antibodies to LP-X was observed only in patients with obstructive jaundice. This simple immunochemical test may represent a valuable new tool in the differential diagnosis of obstructive and nonobstructive jaundice.

Animals↗

Effect of glucagon infusion on plasma cyclic AMP in patients with cholestatic hepatitis and obstructive jaundice. New test of hepatic cholestasis.

Plasma cyclic AMP concentration during glucagon infusion at various time intervals was determined in 8 normal subjects, 9 patients with extrahepatic obstructive jaundice and 10 patients with cholestatic hepatitis (hepatitis A and B). Plasma cyclic AMP concentrations (pmol/ml) during glucagon infusion in patients with both obstructive jaundice and cholestatic hepatitis were found to be greater than those in control subjects. In addition, a significant difference in plasma cyclic AMP concentrations was found between patients with cholestatic hepatitis and obstructive jaundice at the 10th minute of glucagon infusion. These results indicate that plasma cyclic AMP levels at the 10th minute of glucagon infusion represent a reliable diagnostic index of cholestatic jaundice.

Cholestasis↗

Experimental and clinical studies on the effect of biliary drainage in obstructive jaundice.

Mitochondrial respiratory function, ketogenesis and collagen metabolism of the liver in biliary obstruction and after its relief were investigated in dogs and patients with obstructive jaundice. In dogs, it was found that hepatic mitochondrial respiratory function decreased significantly with prolongation of biliary obstruction, but recovered to varying degrees depending on both the duration of obstruction and of the period after the relief of obstruction. Ketogenesis was also impaired by biliary obstruction and its recovery was found in a slight degree only in cases with short-term obstruction. Hepatic collagen content and the synthetic ability significantly increased in biliary obstruction, and returned to normal levels with a relatively short period after the relief. Analogous results were obtained in clinical cases, but the decrease in serum bilirubin was somewhat delayed and increased hepatic collagen content continued after relief of the obstruction. When major surgery is required in patients with obstructive jaundice, biliary drainage should be carried out first 4 to 6 weeks before the performance of major operations. In cases with biliary obstruction for 12 weeks or more, it is desirable to wait for more than 6 weeks after biliary drainage since recovery of hepatic function, especially mitochondrial function, will be extremely slow.

Animals↗

[Obstructive Jaundice: diagnostic and therapeutic management].

The purpose of this article is to provide an update on imaging techniques for diagnosis and staging of clinical conditions leading to obstructive jaundice. Clinical and imaging findings of the most frequent diseases presenting as obstructive jaundice will be reviewed in order to optimize imaging strategies. Imaging and treatment strategies will be discussed in order to provide an optimal diagnosis and staging with the least invasive techniques in order to minimize complications in these patients.

Adenocarcinoma↗

Significance of serum delta bilirubin during obstructive jaundice in dogs.

BACKGROUND: delta-Bilirubin, a nonenzymatic covalently bound complex with albumin, is nonenzymatically formed in serum and has a long half-life irrespective of hepatorenal function. The aim was to examine if delta-bilirubin reflects the duration of obstructive jaundice and efficacy of biliary drainage. MATERIALS AND METHODS: Obstructive jaundice was developed in 17 dogs either for 4 (short term; n = 9) or 11 (long term; n = 8) days and then external biliary drainage was performed. Serum total, direct, and delta-bilirubin fractions were analyzed by high-performance liquid chromatography. RESULTS: delta-Bilirubin was not detectable in serum before biliary obstruction. The serum total and direct bilirubin levels increased rapidly and reached a plateau within 2 days after the biliary obstruction, whereas the concentration and proportion of delta-bilirubin gradually increased and significantly correlated with the duration of obstructive jaundice. Before biliary drainage, the proportion of delta-bilirubin was 28.9 +/- 2.4% in the short-term and 42.5 +/- 2.4% in the long-term obstruction group. The decline indices of serum total, direct, and total minus delta-bilirubin in the short-term group (-0.17, -0.19, and -0.26, respectively) were significantly (P < 0.05) greater than those in the long-term obstruction group (-0.10, -0.10, and -0.13). The decline index of delta-bilirubin itself was similar between the groups. CONCLUSIONS: The concentration and proportion of delta-bilirubin in serum reflect the duration of jaundice. Because delta-bilirubin is not excreted into bile and urine and is not toxic to organs, a decline index of total bilirubin minus delta-bilirubin, the excretable bilirubin fraction might be better to assess the efficacy of biliary drainage.

Alanine Transaminase↗

Exocrine pancreatic function in obstructive jaundice rats: studies with isolated dispersed pancreatic acini.

This study was conducted to investigate pancreatic exocrine function and pancreatic growth in rats with obstructive jaundice (OJ). OJ was produced in adult male Sprague-Dawley rats by bile duct ligation; control rats underwent laparotomy only. Induction of OJ was associated with significant hyperplasia and hypertrophy of the pancreas in rats as shown by increased DNA and RNA contents of pancreatic tissue. Factors associated with pancreatic growth in OJ rats were further examined in isolated dispersed pancreatic acini from OJ rats and the data were compared with those for control rats. Studies with isolated dispersed acini from OJ rats showed that pancreatic growth was accompanied by significant increases in total cellular amylase content; however, amylase release (percentage of initial) in response to cholecystokinin octapeptide was significantly decreased in OJ rats compared to control rats. Total amylase output in response to 100 pM cholecystokinin (CCK) was higher in the OJ group when compared to the control group (8.6 U/mg protein versus 6.4 U/mg protein), as calculated from the total amylase content and percentage of amylase released. Receptor binding data showed that the capacity of CCK receptors in OJ rats was significantly lower when it was compared with control. In addition, plasma levels of CCK were significantly elevated in OJ rats when compared to controls. These results suggest that obstructive jaundice induces pancreatic growth that is associated with alteration of exocrine pancreatic function. Abnormally high levels of stored amylase in pancreatic acini may be implicated in the development of pancreatitis as often seen in obstructive jaundice patients.

Amylases↗

Obstructive jaundice in patients with pancreatitis without associated biliary tract disease.

Jaundice occurring in patients with pancreatitis is usually due to hepatocellular injury or to associated biliary tract disease. Common duct obstruction is occasionally caused by pancreatic fibrosis, edema or pseudocyst in patients who have neither hepatocellular injury nor biliary tract disease. We have studied 7 patients with obstructive jaundice due to pancreatitis who demonstrated no other known cause for jaundice. The difficulty in making the differential diagnosis between benign and malignant disease in these patients, particularly when no pain is associated with obstructive jaundice, is discussed. In view of the fact that the terminal common duct traverses the pancreas, it is uncertain why obstructive jaundice associated with chronic pancreatitis does not occur more often unless the condition is sometimes transient and overlooked. Operative intervention is required in those patients in whom jaundice is persistent. Operation is intended to decompress the biliary tract and the pancreas. The approach used will be dictated by the operative findings in each patient.

Acute Disease↗

CT findings of cystic duct carcinoma two years before obstructive jaundice.

We describe a case of cystic duct carcinoma, the computed tomography findings of which had been incidentally obtained several times over the preceding three years before obstructive jaundice appeared. Under the diagnosis of extrahepatic bile duct carcinoma, a 75-year-old man underwent surgery. Two years before obstructive jaundice appeared, the arterio-portal phase of enhanced computed tomography demonstrated an ovoid mass with peripheral rim enhancement, measuring 1.5 cm in diameter, beside the extrahepatic bile duct. One year later, a repeat enhanced computed tomography consistently showed the ovoid mass with peripheral rim enhancement, and the lower slice of the contiguous computed tomography scan revealed a uniformly enhanced mass compressing the neck of the gallbladder. Four months before obstructive jaundice, the uniformly enhanced mass beside the extrahepatic bile duct markedly infiltrated the surrounding tissues with spicula-formation. At laparotomy, a solid and hard tumor was localized on the right side of the extrahepatic bile duct, in the cholecystic duct and the neck of the gallbladder. Of 29 reported cases fulfilling Farrar's criteria in the English literature other than autopsy cases, computed tomography imaging was only performed in two cases, and the computed tomography findings of cystic duct carcinoma in its early stages, have never been fully described.

Aged↗

Bile salts and cholesterol in the pathogenesis of target cells in obstructive jaundice.

Free cholesterol is in rapid equilibrium between serum lipoproteins and red cells. The level of red cell cholesterol is influenced by bile salts, which shift the serum/cell partition of free cholesterol to the cell phase and which inhibit the cholesterol-esterifying mechanism. During incubation in normal serum possessing an active cholesterol-esterifying mechanism, red cells lose cholesterol and surface area and thereby become more spheroidal and less resistant to osmotic lysis. When exposed to serum from patients with obstructive jaundice or to normal serum with added bile salts, red cells accumulate cholesterol and increase their surface area, thereby acquiring a flattened shape and an increased resistance to osmotic lysis. The described gains and losses of red cell cholesterol and surface area do not involve metabolic injury and occur with no significant change in phospholipid content. The red cells of patients with obstructive jaundice are flat and osmotically resistant and have an increased cholesterol:phospholipid ratio. When transfused into normal subjects these "target cells" rapidly lose their osmotic resistance. Similarly, normal cells acquire osmotic resistance in the circulation of patients with obstructive jaundice. These reversible changes in shape occur with half-times of about 9 and 24 hr, respectively, and occur without impairing cell viability. These studies indicate that the red cell membrane accumulates cholesterol in obstructive jaundice as a consequence of the elevated levels of bile salts. The resulting increment in red cell surface area is responsible for the physical properties and appearance of target cells. These observations substantiate Murphy's findings in vitro indicating that cholesterol is an important determinant of red cell shape and that its content in the cell membrane may vary independently from the phospholipids. Presumably any process or disorder affecting cholesterol exchange in vivo is capable of critically modifying the shape and behavior of red cells.

Bile Acids and Salts↗

Changes in extrathymic T cells in the liver and intestinal intraepithelium in mice with obstructive jaundice.

Recently, T cells were classified into two categories: intrathymic T cells (ITCs; thymus-derived T cells) and extrathymic T cells (ETCs). ETC, localized in the liver and intestinal intraepithelium (IE), play an important immunologic role in the suppressed condition of T-cell development in the thymus. Given the fact that complications of surgery in patients with obstructive jaundice are often related to immunosuppression in the gut-liver circulation, we attempted to investigate the changes in the proportion of ETCs in mice with obstructive jaundice. Three mice models were prepared ( n = 10 per group): sham group with simple laparotomy; ligation group with common bile duct ligation; deoxycholic acid (DCA) group with an oral intake of DCA as a model of the presence of bile salts in the gut lumen. In each model, total mononuclear cells (MNCs), ITCs in the thymus, and ETCs in the liver and IE were counted using monoclonal antibodies in conjunction with a two-color immunofluorescence test by flow cytometry. In the ligation group the number of MNCs was reduced in the thymus and IE, and only those in the IE recovered after oral intake of DCA. A decrease of ITCs in the thymus and the increase in ETCs in the liver and IE occurred simultaneously during the early phase of biliary obstruction. At day 7 after biliary obstruction, ETCs in the livers of the DCA and ligation groups decreased to nearly the level in the sham group. However, on day 7 the ETCs in the IE remained significantly higher in the DCA group than in the ligation group. These results suggested that ETCs can act in place of ITCs at an early phase of obstructive jaundice, and the presence of bile in the gut lumen may be associated with the consumption of ETCs in the IE, a reaction that may bring about improved immunoreactivity.

Animals↗

[A patient with obstructive jaundice due to recurrence after gastric cancer surgery responding remarkably to FLP combination therapy].

The patient was a 67-year-old man who had undergone distal gastrectomy because of early gastric cancer without lymph node metastasis two years earlier. The postoperative course was uneventful, but he was admitted again to our hospital because of abrupt jaundice. A CT scan of the abdomen showed obstructive jaundice due to the enlargement of the lymph nodes around the hepatoduodenal ligament, pancreas head, portal vein, and celiac axis. After percutaneous transhepatic cholangio-drainage (PTCD), 5 cycles of FLP combination therapy (5-fluorouracil, leucovorin, cisplatin) were performed. Consequently, the tumor marker level returned to the normal range and the shrinkage of the metastatic lymph nodes was remarkable. A reopening of the biliary tract was attained, so the PTCD tube could be removed. As an outpatient without recurrence he has received oral administration of uracil plus tegafur. The FLP combination therapy was effective for obstructive jaundice due to intraperitoneal lymph node recurrence of the gastric cancer.

Aged↗

Hepatic functional reserve in patients with obstructive jaundice: an assessment by the redox tolerance test.

PURPOSE: Hepatic mitochondrial response to oral glucose load (redox tolerance test) was evaluated as an indicator of hepatic functional reserve of patients with obstructive jaundice. PATIENTS AND METHODS: The redox tolerance test was performed in 29 patients with obstructive jaundice before percutaneous transhepatic biliary drainage and 2 weeks after the procedure. RESULTS: The redox tolerance index (RTI) before drainage was not related to conventional parameters other than albumin, but was significantly associated with bilirubin half-life (P < 0.01). Of 19 patients with an RTI > or = 0.5 before drainage, all maintained similar values after drainage and experienced satisfactory clinical courses, even after major surgery. Of 10 patients with an RTI < 0.5 before drainage, 5 showed improvement and 5 deteriorated after drainage. Four of the latter 5 died within 60 days after drainage. The hospital mortality was significantly greater in patients with initial RTI < 0.5 than in patients with RTI > or = 0.5 (P < 0.01). CONCLUSION: The redox tolerance test is useful for evaluating hepatic functional reserve and prognosis in patients with obstructive jaundice.

Adult↗

Obstructive jaundice in adult Ethiopians in a referral hospital.

Forty-nine adult Ethiopians with obstructive jaundice were studied. Right upper quadrant pain was the main presenting complaint (89%). Most (94%) of the jaundiced patients had right upper quadrant tenderness. In 87% the obstruction was corroborated by ultrasonographic examination, but causal factors were identified in only 39%. Operative findings showed that choledocholithiasis (41%) and malignant conditions (22%) were the two important causes of obstructive jaundice among the adult patients seen at a referral hospital in Addis Ababa. The causes and the outcome of the different types of surgical procedures used in the management are discussed.

Abdominal Neoplasms↗

Hemodynamic function in dogs with chronic obstructive jaundice: effects of radiocontrast medium.

Chronic obstruction of the biliary tract alters circulatory function. The effects of radiocontrast medium (iothalamate meglumine) on systemic and renal hemodynamics were studied in normal dogs and dogs with chronic common bile duct ligation (CBDL). After intravenous injection of radiocontrast, cardiac output and stroke volume were not altered in normal and CBDL dogs; arterial pressure was stable in normal dogs but decreased significantly in CBDL dogs and was accompanied by reduced systemic vascular resistance. In normal and CBDL dogs the renal hemodynamic responses to radiocontrast medium were characterized by initial vasoconstriction (independent of renal renin release) and later vasodilation. This vasodilatation in CBDL dogs was particularly striking as it occurred despite reduced renal perfusion pressure and the augmented renin-angiotensin system. Inhibition of prostaglandin synthesis with indomethacin in CBDL dogs abolished both the hypotensive and the renal vasodilator responses to radiocontrast medium. We conclude that enhanced prostaglandin activity contributes to the labile hemodynamic function noted in obstructive jaundice.

Animals↗

Obstructive jaundice complicating pyeloplasty.

The development of obstructive jaundice associated with the formation of a renal pseudocyst in 2 patients undergoing pyeloplasty on the right side is discussed. We emphasize the importance of proper drainage of the retroperitoneal area to prevent this complication.

Adolescent↗

Stones in a long pancreaticobiliary common channel: a rare cause of obstructive jaundice and pancreatitis.

A case of obstructive jaundice associated with acute pancreatitis is reported. The underlying cause was a dilated long pancreaticobiliary common channel impacted with stones and bile debris. There was no stone in the rest of the biliary system except for one in the lowest part of the common bile duct and the overall appearance of the stones suggested that they originated within the common channel itself. A long common channel may be an underlying cause of various pathological conditions in the pancreaticobiliary system. Early operative intervention is recommended when such a diagnosis is made.

Acute Disease↗

Obstructive jaundice in pancreatitis.

Twelve patients with obstructive jaundice as a direct result of pancreatitis or its complications are described. The value of ultrasonography in the diagnosis of this condition is stressed. The criteria for surgical intervention and the operation of choice are discussed.

Adult↗

[Clinical study on the immune function of patients with obstructive jaundice].

Twenty-five patients with obstructive jaundice were investigated for immune function. Jaundiced patients' lymphocyte transformation (LCT), skin immune function (SIF) were lower than that of non-jaundiced patients, IgA, IgG and chemiluminescence (CL) of white blood cells were higher than that of non-jaundiced patients. LCT, lymphocyte count (LC), E-rosettes forming percentage (ERFP), SIF, IgA, IgG of the jaundiced patients were decreased with in 2 weeks after operation, CL was in a high level as compared to that of pre-operation. The immune function disturbance may be a reason of postoperative complications in jaundiced patients.

Adult↗