Bile acid synthesis and excretion following release of total extrahepatic cholestasis by percutaneous transhepatic drainage

Abstract. Urinary, biliary and serum bile acids were studied in three patients before and after percutaneous transhepatic drainage for total bile duct obstruction.
Before drainage high urinary excretion often different bile acids occurred. The percentage distribution was: cholic and chenodeoxycholic acid (66–86%), hyo-cholic (3–16%), 3β 12α-dihydroxy-5-cholenoic (3–6%) and 3β-hydroxy-5-cholenoic acid (2–8%). These acids were regularly found in serum. In addition small amounts (less than 2%) of norcholic, allocholic, 3β, 7α-dihydroxy-5β-cholanoic, 3α, 7α-dihydroxy-5α-cholanoic and lithocholic acid were excreted in urine. Trace amounts of these bile acids were found in serum.
After start of drainage biliary bile acid excretion increased rapidly during the first day, dropped to a minimum during the second or third day and then slowly increased again. In spite of normal volumes of bile produced, the total serum bile acids and the urinary excretion of bile acids remained increased during a drainage period of 19 days. The bile acids were of the same type as observed during cholestasis. In serum the increase was mainly due to high concentrations of chenodeoxycholic and 3β-hydroxy-5-cholenoic acid, as sulphate esters.
Glycine and taurine conjugates of cholic, chenodeoxycholic and hyocholic acid were mainly excreted in bile. Bile acid sulphate esters were only present in trace amounts in bile and were mainly excreted in urine. This, combined with low renal clearance, explains the elevated serum levels of sulphate esters of chenodeoxycholic and 3β-hydroxy-5-cholenoic acid conjugates.     

The effect of vasodilatation and sympathetic nerve activation on net water absorption in the cat's small intestine

The rate of net water uptake from the feline small intestine has been investigated during control conditions, during graded infusions of the vasodilator drug isopropylnoradrenaline, and during electrical stimulation of the regional sympathetic nerve fibres to the gut. Net water absorption rate was largely unaffected by intestinal vasodilatation. The fraction of the absorbate transported via the lymphatics remained also constant at 20–40% of the total absorption regardless of blood flow rate. Stimulating the sympathetic nerve fibres to the small intestine increased, however, net water absorption rate. The increase was particularly pronounced when blood pressure was kept constant during the period of stimulation. The absorption rate was on an average almost doubled at a stimulation frequency of 8 Hz during constant pressure conditions. The mechanism(s) explaining this nervous control of water absorption are tentatively discussed.     

T cell receptor (TCR) V gene segment use in HLA-typed Japanese healthy subjects

The expression of 13 different α and β V gene segments of the T cell receptor for antigen (TCR) was examined, using V gene-specific MoAbs, on human peripheral blood T lymphocytes from 32 healthy Japanese subjects. In addition, to examine associations between TCR V gene products and HLA alleles, the HLA class I and class II types of all subjects were serologically determined. The reactivities of the anti-TCR V-specific MoAbs were, with some significant exceptions, similar to those previously described in healthy Caucasian subjects. We found a non-random V gene usage as well as a statistically significant bias of the expression of eight Vβ gene products towards the CD4⁺ subpopulation, and a significant skewness in the usage of Vα12 towards the CD8⁺ population. Some subjects showed increased reactivities (above 10%) of certain MoAbs, mainly in the CD8⁺ subpopulation. We found no distinct correlation between any certain HLA class I or II allele and TCR V gene usage in the CD8⁺ or CD4⁺ subpopulations, respectively. In conclusion, the pattern of anti-TCR V-specific MoAb reactivities found in CD4⁺ and CD8⁺ subsets of peripheral blood lymphocytes of healthy Japanese subjects was in general found to match that previously described in healthy Caucasian subjects.     

Glucocorticosteroids in Renal Transplantation

In a previous clinical trial we demonstrated that, by increasing the postoperative administration of methylprednisolone from 1.0 to 3.5 mg/kg/day, the onset of the first inflammatory rejection episode was significantly delayed and the size of the inflammation was reduced. The 'high initial' steroid treatment specifically depleted blast cells and macrophages from the in situ inflammatory infiltrate. In this trial we demonstrate that the 'high initial' glucocorticosteroid administration significantly improves 1-year cadaver allograft survival from 44% to 68% (P = 0.003) without increasing the number of complications. Although the 'high initial' steroid administration only partially overcomes the impact of HLA-AB incompatibility, it seems to overcome entirely the impact of absence of blood transfusions. The 'high initial' steroid administration also makes the first episodes of inflammation easier to overcome: less steroids are needed to counteract the first rejection, and, as a consequence, only 30% more steroids were used in the 'high initial' versus the 'low initial' steroid programme.     

Socio-economic versus obstetric risk factors for drug addiction in offspring

Two possible risk factors for drug addiction were weighed against each other: (1) perinatal factors associated with obstetric medication at time of birth; and (2) factors associated with familial socio-economic conditions at time of birth. The subjects comprised 200 amphetamine addicts and 200 opiate addicts born in Stockholm 1945–1966. In a matched case control study, addicts were compared to their siblings with regard to possible obstetric risk factors by means of conditional logistic regression controlling for socio-economic level and civil status. Administration of opiates, barbiturates and nitrous oxide to mothers during labour was associated with drug addiction in offspring, hence confirming results from earlier studies. In a cohort study the risk associated with birth at a given hospital and familial socio-economic level was analysed by means of loglinear analysis using 7100 controls from the general population. For amphetamine addicts, a low socio-economic level at time of birth might be of importance for the infant subsequently becoming an addict. This could not be demonstrated for the opiate addicts. An uneven distribution of births among the hospitals, most pronounced for the amphetamine addicts, is in agreement with the hypothesis that obstetric practices may be risk factors for adult drug addiction.     

Clinical trial: factors associated with resolution of heartburn in patients with reflux oesophagitis – results from the EXPO study

Background The ability to predict symptom response to reflux oesophagitis‐healing therapy may optimize treatment decisions. Aim To identify factors associated with heartburn resolution in patients receiving acid‐suppressive therapy for reflux oesophagitis. Methods In this multicentre, randomized, double‐blind trial (EXPO; AstraZeneca study code: SH‐NEG‐0008), patients with endoscopically confirmed reflux oesophagitis and reflux symptoms received once‐daily proton pump inhibitor therapy [esomeprazole 40 mg (n = 1562) or pantoprazole 40 mg (n = 1589)] for ≥4 weeks. Factors associated with heartburn resolution after 4 weeks were identified by multiple logistic regression analysis. Results Esomeprazole therapy, positive Helicobacter pylori status and greater age were associated with an increased likelihood of heartburn resolution [odds ratio (95% confidence interval): 1.31 (1.12, 1.54), 1.44 (1.19, 1.74) and 1.013 (1.007, 1.019) per year, respectively; all P < 0.001]. Men and patients with no acid regurgitation or epigastric pain pre‐treatment were also more likely to achieve heartburn resolution (all P < 0.05). Conclusions The use of esomeprazole rather than pantoprazole increases the probability of achieving resolution of heartburn during reflux oesophagitis‐healing therapy. Other factors, including H. pylori status, age, gender and symptom profile may be helpful in determining the likelihood of heartburn resolution in such patients.