Julia Cullen

1. The bile acids and bile acid sulphates in the urine, serum and bile of eight cholestatic patients were studied quantitatively by gasliquid chromatography and gas-liquid chromoatography/mass spectrometry. 2. The primary bile acids (cholic acid and chenodeoxycholic acid) comprised on average 94% of the total bile acids in bile, 70% in the serum and 64% in urine. 3. The percentage composition of bile acids in bile was relatively constant and was not influenced by the degree of cholestasis. In contrast, in the serum only the primary bile acids were increased, the concentrations of the secondary bile acids (deoxycholic acid and lithocholic acid) and the minor bile acids remaining constant. 4. The data do not support the hypothesis that monohydroxy bile acids accumulate in cholestasis and are related to the pathogenesis of this syndrome. 5. The pattern of bile acid urinary excretion was similar to that in the serum. But in one patient, 3alpha, 7beta, 12alpha-trihydroxy-5beta-cholan-24-oic acid was a principal urinary bile acid, although very low concentrations of the compound were found in that patient's serum, suggesting that some of the minor bile acids in urine may originate by epimerization in the kidney. 6. In bile only a small proportion of the bile acids was sulphated (range 2.1-4.6%) and in serum the degree of sulphation was very variable (9-50%). However, in urine, sulphate esters accounted for a large proportion of the total bile acids (33-72%). 7. The output of bile acid sulphate in the urine was related to the urine total bile acid output but the serum concentration of bile acid sulphate remained relatively constant. Consequently, in contrast to the non-sulphated bile acids, whose renal clearance was relatively constant, the renal clearance of sulphated bile acids was directly related to the urine total bile acid output. This finding is inconsistent with the earlier hypothesis that their predominance in urine was due to a high renal clearance. It may indicate renal synthesis of some of the bile acid sulphates in the urine and/or inhibition of active renal tubular reabsorption of sulphated bile acids by non-sulphated bile acids.

Chenodeoxycholic acid (1 g daily) was administered to 10 patients with gallstones and three patients with biliary stricture and recurrent cholangitis. Four gallstone patients showed diminution or disappearance of stones including one patient whose stone was in the common bile duct. The patients with recurrent cholangitis showed marked improvement in symptoms during treatment. Serum bile acid levels were significantly elevated in 8 gallstone patients during treatment. Liver biopsy in eight gallstone patients during treatment revealed minor changes in five. Lithocholic acid and bile acid sulphates were found in only small amounts in the bile of patients during treatment. No significant trend in biliary lipid composition during treatment was observed. There was no overall trend in the group of patients whose stones disappeared or diminished. Changes in biliary bile acid composition and in bile acid pool sizes were variable following treatment and could not be correlated with the clinical results of treatment. A further trial of chenodeoxycholic acid is recommended in patients with stones in the biliary tree and recurrent cholangitis who are not amenable to surgical treatment.

Summary The ability of pig alveolar macrophages to phagocytose Actinobacillus pleuropneumoniae HK 361, which produces both haemolysin II (Apxlll) and pleurotoxin (Apxlll), has been studied. Macrophages incubated with HK 361 in the presence of normal pig serum were rapidly killed. Incubation of the macrophages with a haemolysin-deficient mutant (HK 361 e), which possesses only cytotoxic activity (Apxlll), also caused gross damage to the macrophages. A mutant (HK 361 h) which produces neither Apxll nor Apxlll in its culture supernatant allowed longer survival of the macrophages than did either the parent strain or mutant e when incubated with normal pig serum. Prolonged incubation with mutant h resulted in an increase in the number of damaged macrophages, but not to the same extent as with either HK 361 or mutant e. The number of mutant h cells phagocytosed in the presence of normal pig serum was low. The addition of either hyperimmune rabbit serum, raised against whole formalin-treated HK 361 cells, or convalescent pig serum from a pig recovering from a serotype 3 infection, which contained antibody against both Apxll and Apxlll, did not increase the survival of macrophages incubated with either HK 361 or mutant e. However, incubation of mutant h with convalescent pig serum did result in damage-free macrophages. This serum, which possessed neutralizing capabilities against the toxic activities of Apxll and Apxlll, enhanced the number of mutant h cells phagocytosed compared to the numbers phagocytosed in normal pig serum. Killed bacteria were rapidly phagocytosed and did not damage macrophages. The number of phagocytosed killed bacteria appeared to be similar to that seen with live mutant h cells when incubated in the presence of convalescent pig serum. The presence of a toxic activity associated with the haemolysin-and cytotoxin-negative mutant may represent an additional cell-associated toxin which is not present in its culture supernatant. It appears therefore, that in the absence of extracellular Apxll and Apxlll and in the presence of convalescent pig serum A. pleuropneumoniae is readily phagocytosed.

Disposition kinetics of indocyanine green (ICG) were used to evaluate hepatic function in healthy Beagles (group 1; n = 6) and Beagles with progressive hepatic disease induced by oral administration of dimethylnitrosamine, a hepatospecific toxin. Three classes of hepatic disease were defined by histologic features: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of ICG was studied 3 weeks following the last dose of toxin. A rapid IV injection of 0.5 mg of ICG/kg was administered and serum samples were obtained at certain intervals during 60-minute periods. Serum ICG was analyzed by use of visible spectrophotometry. Disposition kinetics were determined from serum ICG concentrations vs 15- and 60-minute time curves and compared between one another and among groups. Data based on 60-minute time curves were not significantly different from those based on 15-minute curves. Area under the curve for ICG was greatest in group 3. Clearance of ICG was decreased and mean resident time was increased in groups 3 and 4, compared with those in groups 1 and 2. When disposition data (60 minutes) were normalized for differences in hepatic weight among dogs, group-3 mean resident time was significantly greater than that of group 4. This study supports the diagnostic benefits of using ICG disposition kinetics as a method of evaluating hepatic function in dogs with progressive liver disease.

BACKGROUND: There is significant underutilisation of allocated health service resources when a scheduled flexible cystoscopy (FC) is cancelled because a pre-cystoscopy urinalysis (PCU) suggests "infection", despite patients being asymptomatic for urinary tract infection (UTI). OBJECTIVE: To evaluate the risk of UTI or urinary sepsis when FC is performed in asymptomatic patients with a PCU positive for leucocyte esterase and/or nitrites. DESIGN SETTING AND PARTICIPANTS: A prospective cohort study was conducted in a high-volume UK centre recruiting all patients undergoing outpatient FC. INTERVENTION: A protocol was developed to guide response to PCU performed prior to FC, which was performed regardless of the result, unless patients were symptomatic for UTI. All patients completed a questionnaire to identify risk factors and were followed up via a telephone survey and a review of electronic clinical records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Post-FC UTI was defined as hospital admission with UTI/urinary sepsis or if patients were symptomatic for UTI with receipt of antibiotics or with positive urine culture and sensitivity. An analysis of the association was performed. RESULTS AND LIMITATIONS: = 0.005). No patient with a positive PCU developed urinary sepsis. The main limitation of this study was the lack of pre-protocol control. CONCLUSIONS: We observed a clinically low and acceptable risk of UTI, with no incidence of sepsis, when FC was performed in asymptomatic patients with a PCU suggesting "infection". Routine cancellation of these patients is unnecessary and may worsen the burden on health service resources. PATIENT SUMMARY: We evaluated the safety of performing flexible cystoscopy when the urine dipstick on the day suggested presence of an "infection" but the patient had no symptoms of urinary tract infection (UTI). Our study in over 2000 patients demonstrated a low incidence of UTI, and none of these patients developed sepsis. We therefore recommend that flexible cystoscopy should not be cancelled automatically on the basis of the dipstick result alone, as it might delay a time-sensitive crucial diagnosis.