Haemophilic patients with hepatitis C have higher viral load compared to other well-defined patient groups.

Comparison of hepatitis C viral load between different patient populations has been hampered by the use of different technology in individual studies. We had the impression that haemophilic (HAEM) patients had a higher serum load of hepatitis C virus (HCV) compared to other HCV-infected patients. We therefore studied viral load and genotypes in active illicit drug users (IDU), HAEM patients and patients with post-transfusion hepatitis (PTH). The study comprises 225 HCV-RNA positive patients, 117 IDU, 60 HAEM patients and 48 PTH patients. All patients were anti-HIV negative. HCV-RNA was measured with a quantitative reverse transcription polymerase chain reaction (RT-PCR) method, HCV-genotypes were determined with genotype specific primers in RT-PCR in 221 patients. Four patients could not be genotyped with our assay and were excluded. Overall viral load was higher in genotypes 1 and 2 compared to genotype 3, median values of HCV-RNA were 1,400 x 10(3) geq ml(-1), 2,700 x 10(3) geq ml(-1) and 270 x 10(3) geq ml(-1), respectively. HAEM patients had significantly higher viral load for both genotypes 1 and 3 compared to the IDU and PTH patients. In a multiple linear regression model HCV-RNA viral load was independently associated with HAEM and genotype, but not to age, gender or disease duration. In conclusion, HAEM patients have higher viral load than IDU and PTH patients. The reason for this is unknown, but it may be due to host factors or mode of transmission with multiple inoculations.

Evaluation of the applicability of the SeHCAT test in the investigation of patients with diarrhoea.

For the assessment of ileal bile acid conservation the retention of orally administered 75Se-23-selena-25-homotaurocholic acid (SeHCAT), a gamma-ray-emitting radioisotope-labelled synthetic bile acid, was measured by an uncollimated abdominal gamma camera in 89 patients with various gastrointestinal disorders and in 20 persons without gastrointestinal complaints. A significant differences in retention was observed between patients with and without previously detected ileal disease. However, it was not possible by use of the test to differentiate between the various types of diarrhoea. Hence the test is not recommended in the routine investigation of patients with diarrhoea.

Errors in inhalation technique and efficiency in inhaler use in asthmatic children.

256 asthmatic children receiving regular inhalation therapy demonstrated how they used their inhalers. Pulmonary function measurements (PFM) were made before and after the demonstrations, and errors in technique were recorded. 242 children had reversible airway obstruction on the day of study. In only 109 (45%) did the inhalation result in an increase in FEV1 greater than or equal to 15% (efficient technique). An efficient inhalation technique was found in 46% of children who demonstrated a pressurized aerosol, 59% who demonstrated a tube spacer aerosol and 46% who demonstrated a rotahaler, and the frequency of efficient technique varied from 17% to 84% between six different groups of instructors. 87% of children controlled and 25% not controlled with PFM at the time of prescription had an efficient technique. Children under 6 years had a more inefficient and a more faulty technique than older children, but otherwise age did not influence the result. Neither was time since instruction of any importance for efficiency or number of errors. The errors recorded that seem to influence efficiency most were: coordination problems, rapid inspirations, ceasing to inspire when the aerosol was fired, and inhalation through the nose. The results emphasize the paramount importance of clear instructions and control of inhalation technique at the time the treatment is prescribed.

Platelet number and volume during myocardial infarction in relation to infarct size.

Platelet number and mean platelet volume (MPV) were measured in 100 patients with acute chest pain, 41 with acute myocardial infarction (AMI), 33 with angina pectoris (AP) and 26 with non-coronary event (NCE), and compared with 21 controls. We found no significant difference in platelet count on admission in the patient groups, but it was lower compared with controls. There were no significant differences in MPV between the patient groups nor between patients and controls. Thirty patients with AMI were followed for 10 days and showed an initial 12% fall in platelet count followed by a 36% increase. Initially there was an increase in MPV (2%) followed by a fall (8%). The fall in platelet count and increase in MPV correlated with infarct size (maximum activity of lactate dehydrogenase (LDH)) and might reflect consumption of platelets. The precise role of platelets in the process of infarction is still unknown.

Platelet number and platelet volume in healthy young men during exercise and changes in posture.

In ten healthy young men, alterations in platelet number (B-Thro) and mean platelet volume (MPV) during 15 min of moderate exercise on a bicycle ergometer and 30 min of rest in supine position were determined. During exercise B-Thro increased 10.9% and MPV increased 1.5%. During rest in supine position B-Thro decreased 8.7% whereas MPV was unchanged. From concomitant alterations in leucocyte number, erythrocyte number and concentration of albumin it is concluded that part of the alterations in B-Thro is caused by transfer of water between the vascular system and the interstitial compartment and part is the result of a release of platelets from reservoirs during exercise and a sequestration of platelets in reservoirs during rest in supine position. The alteration in MPV during exercise is explained by a larger average volume of platelets being released from reservoirs when compared with the average volume of platelets already circulating.

Eicosapentaenoic acid potentiates the production of prostacyclin-like material in the arachidonic acid perfused human umbilical vein.

The production of prostacyclin (PGI2)-like material in human umbilical veins perfused continuously at 37 degrees C with Hanks buffer solution with 1% human albumin (HBA) was studied by bioassay. Subsequent perfusion resulted in a time dependent significant decrease in production of PGI2-like material. After addition of 20 mumol/l arachidonic acid (HBA-AA) the production of PGI2-like material increased significantly. The production of PGI2-like material was significant greater when the vein was perfused with HBA-AA than when perfused with HBA with 20 mumol/l eicosapentaenoic acid (HBA-EPA). Examination of the HBA-EPA perfusate by thin layer chromatography showed that it contained a substance that comigrated with genuine 6-keto-PGF1 alpha and a substance that comigrated with delta 17-6-keto-PGF1 alpha. Finally, perfusion with HBA containing 10 mumol/l AA plus 10 mumol/l EPA resulted in a significant greater production of PGI2-like material than perfusion with HBA-AA alone. These results support the hypothesis that EPA has beneficial antithrombotic properties in human.

Assessment of ileal function by abdominal counting of the retention of a gamma emitting bile acid analogue.

In eight patients without gastrointestinal complaints and 30 patients with various gastrointestinal disorders ileal bile acid conservation was assessed by oral administration of 75Se 23-selena-25-homocholic acid (SeHCAT) followed by abdominal gamma counting (SeHCAT-test). The results of the test correlated fairly well with the clinical features and with the [1-14C]-cholylglycine breath test including faecal 14C measurements (breath test). Of the two bile acid absorption tests the new is perhaps the more sensitive and is the one most easily performed.

The diagnostic value of fasting serum total bile acid concentration in patients with suspected liver disease. A prospective, consecutive study.

To assess the diagnostic value of fasting serum total bile acids (STBA) in liver disease, STBA together with serum bilirubin (BIL), serum alkaline phosphatase (AP), and serum aspartate aminotransferase (ASAT) were measured in 66 consecutive patients who had a liver biopsy. Twenty-four of the patients who had normal liver histology all had normal STBA values (less than 8 mumol/l). In the remaining 42 patients with abnormal liver histology STBA values were elevated in 21, corresponding to a sensitivity of 0.50. The same figures for BIL, AP, and ASAT were 0.52, 0.76, and 0.79, respectively. The predictive values of elevated (PVpos) and normal (PVneg) STBA for disclosing or excluding liver disease, respectively, were not better than the figures for BIL, AP, and ASAT. None of the tests were suited for distinguishing among various liver diseases. It is concluded that STBA had no diagnostic advantage as compared with the commonly used liver function tests BIL, AP, and ASAT.

Human umbilical blood vessel converts all cis-5, 8, 11, 14, 17 eicosapentaenoic acid to prostaglandin I3.

All cis-5, 8, 11, 14, 17 eicosapentaenoic acid (EPA) is presently being evaluated for dietary prophylactic use in thrombo-embolic disorders. EPA inhibits the production of TXA2 and platelet aggregation. We here present results demonstrating that human umbilical arteries convert 14c-EPA to a substance that in aqueous solutions decomposes to 14C-delta 17-6-keto-PGF1 alpha . The conversion rate in rat aortic tissue was found substantially lower. These results in combination with earlier data indicating that EPA does not influence the conversion of arachidonic acid (AA) into PGI2 in human vascular tissue, encourage further research along the lines initiated by the findings of high EPA/AA ratio and low incidence of myocardial infarction in Greenland Eskimos.

Semiquantitative measurement of lithocholic acid compounds in bile from patients with gallstones, before and during treatment with chenodeoxycholic acid.

A method for two-dimensional thin-layer chromatography of unprocessed bile is described. The method gives distinct spots from lithocholic acid and its compounds with glycine, taurine, and sulfuric acid. The size of the spots is estimated by comparison with standard spots, and the concentrations of individual bile acids are expressed as a fraction of the total content of bile acids in the sample. The concentration of total lithocholic acid was found to be 1-3 (mean 1.5) per cent of the total concentration of bile acids in duodenal bile from 14 healthy persons. It was slightly higher in bile from 6 untreated patients with gallstones, and still higher, 3-7 (mean 4.0) per cent, in bile from the same patients during treatment with chenodeoxycholic acid. The difference between the concentrations of total lithocholic acid in the bile samples from healthy persons and from patients treated with chenodeoxycholic acid was statistically significant. Nearly all the lithocholic acid was conjugated with glycine or taurine, and approximately half of it was sulfated. The increase in total lithocholic acid concentration in the bile from patients consisted of glycine conjugates.

Turnover of plasma cholesterol in patients with cholesterol gallstones.

Following the i.v. injection of about 30 muCi of 1-alpha-2-alpha-3H-cholesterol, the specific activity decay of plasma cholesterol has been analysed in terms of a 2-pool model in eight patients with radiolucent gallstones and two healthy controls. In each subject some kinetic parameters were calculated, including the input into and the size of the rapidly exchangeable cholesterol pool. The results were compared with those in 16 controls from another study. Statistical analysis failed to demonstrate significant differences in any of the parameters between the gallstone patients and the combined controls, indicating that patients with cholesterol gallstones have normal input into and size of the rapidly exchangeable cholesterol mass. The conclusion is discussed in relation to similar studies, and it is speculated that gallstone patients may have decreased absorption of exogenous cholesterol.

Kinetics and pool size of chenodeoxycholic acid in cholesterol gallstone patients.

The pool size, half life, and daily production rate of chenodeoxycholic acid (CDCA) was determined by the isotope dilution method upon intravenous injections of about 10 muCI OF 24-14C-CDCA in 7 patients with radiolucent gallstones in functioning gallbladders, and 9 healthy controls. Bile was obtained by duodenal intubation. The method also allowed measurement of the CDCA percentage of total bile acids (TBA) and an indirect calculation of the TBA pool size. The pool size and daily production rate of CDCA were slightly, but not significantly, diminished in the gallstone patients. The half life of CDCA was almost equal in the 2 groups. The CDCA percentage of TBA was significantly higher in the gallstone patients (0.02 less than P less than 0.05), and the TBA pool size was significantly reduced (P less than 0.01) in the gallstone patients. It is concluded that the CDCA metabolism is similar to that of cholic acid in gallstone patients. Thus the formation of gallstones is hardly due to specific alterations in CDCA metabolism, suspected on account of the specific cholelitholytic effect of CDCA ingestion. The significance of increased CDCA percentage in bile is discussed in relation to the results from other study groups, and it is pointed out that a relative increase in the bile content of dihydroxy bile acids may lead to reduced cholesterol holding capacity of bile, and thus favor the formation of gallstones.