Biliary lipid composition in cholesterol microlithiasis.

BACKGROUND: Little information is available on the pathogenesis of cholesterol microlithiasis, and it is not clear if biliary lipid composition in these patients is similar to changes seen in cholesterol gall stone patients. AIMS: To measure biliary lipid composition in patients with cholesterol microlithiasis. PATIENTS: Eleven patients with cholesterol microlithiasis, 20 cholesterol gall stone patients, and 17 healthy controls. METHODS: Duodenal bile was collected in the fasting state during ceruletide infusion. Biliary cholesterol, phospholipids, and total bile acids were analysed by enzymatic assays, and conjugated bile acids by high pressure liquid chromatography. RESULTS: Patients with microlithiasis had a cholesterol saturation index significantly higher than controls (mean value 1.30 (95% confidence interval 1.05-1.54) v 0.90 (0.72-1.08)) but similar to gall stone patients (1.51 (1.40-1.63)). This was due to a significant decrease in per cent phospholipid (10.0% (7.1-12.8)) compared with controls (21.4% (18.1-24.6)) and gall stone patients (24.9% (20.5-29.3)). Per cent cholesterol was similar in patients with microlithiasis and controls (5.3% (4.5-6.1) and 5.6 % (4.3-6.8), respectively) but was significantly increased in gall stone patients (10.9% (9.3-12.4)). Bile acid composition in patients with microlithiasis was similar to controls whereas in gall stone patients deoxycholic acid was significantly increased: 27.3% (24.8-29.7) v 19.0% (15.7-22.2) in controls and 20.6% (14.9-26.2) in patients with microlithiasis. CONCLUSION: Patients with cholesterol microlithiasis have biliary cholesterol supersaturation, similarly to cholesterol gall stone patients. Whereas in the latter this is due to increased per cent cholesterol, in patients with microlithiasis this is caused by phospholipid deficiency, with normal per cent cholesterol and normal biliary bile acid composition.

Serum interferon gamma in primary biliary cirrhosis: effect of ursodeoxycholic acid and prednisone therapy alone and in combination.

BACKGROUND: Interferon-gamma may have immunopathogenic importance in primary biliary cirrhosis, stimulating aberrant expression on biliary epithelium of class II major histocompatibility molecules and inter-cellular adhesion molecule-1. Liver transcripts for interferon-gamma are found in primary biliary cirrhosis. Its serum level is increased in pretransplantation stages and decreases after transplantation. OBJECTIVES: (1) To verify whether serum interferon-gamma levels are increased in non-cirrhotic stages of primary biliary cirrhosis. (2) To evaluate the effect of ursodeoxycholic acid and prednisone alone and in combination on serum levels of interferon-gamma and soluble inter-cellular adhesion molecule-1. METHODS: Nine non-cirrhotic, anicteric patients with primary biliary cirrhosis (patient test group), 14 healthy, negative controls and 14 positive controls, with chronic hepatitis related to hepatitis C virus were studied in basal condition. Primary biliary cirrhosis patients were treated with ursodeoxycholic acid, prednisone and the association of the two drugs for three 4-week periods, each period separated by a 4-week wash-out. Interferon-gamma and soluble inter-cellular adhesion molecule-1 were measured in serum by commercially available immuno-enzymatic kits. RESULTS: Median interferon-gamma levels were increased in patients with primary biliary cirrhosis compared with healthy controls (44 vs 19 pg/ml; P < 0.01) but similar to those in chronic hepatitis patients (47 pg/ml). Serum soluble inter-cellular adhesion molecule-1 was significantly reduced by ursodeoxycholic acid, and an even greater reduction was obtained on addition of prednisone. No treatment affected interferon-gamma levels. CONCLUSION: Serum interferon-gamma is increased in noncirrhotic patients with primary biliary cirrhosis, but this is not disease-specific. Neither ursodeoxycholic acid, nor prednisone, nor the combination of the two drugs influenced this immunological pathway of primary biliary cirrhosis.

Hospitalization for peptic ulcer bleeding: evaluation of a risk scoring system in clinical practice.

BACKGROUND: Upper gastrointestinal tract haemorrhage is a common cause of hospitalization: resource utilization in management of peptic ulcer bleeding varies considerably with no apparent effect on patient outcome. Several risk score systems based on endoscopic and clinical data have been proposed and validated in order to aid patient management. AIM: To assess clinical reliability of a scoring system and to define guidelines to improve efficiency of patient management without reducing efficacy METHODS: We considered all patients admitted to our unit for bleeding peptic ulcer over a one-year period. Every patient had an early endoscopy (within 12 hours) and therapy according to the appearance of the ulcer defined by Forrest classification. All subjects were classified into low-, intermediate- and high-risk patients on basis of clinical and endoscopic features according to "Cedar Sinai Medical Center predictive index" which was applied retrospectively in first six months then perspectively for the last period using the results obtained from first semester. For each risk group, we compared Length of Hospital Stay number of blood units used in transfusion, rebleeding rate, need for surgery as well as mortality in the two periods, using Student t test. We correlated Length of Hospital Stay and every score parameter by applying analysis of variance to results over the one-year period. RESULTS: Study population consists of 91 patients. Recurrent bleeding was observed in only three entering the high-risk group, only one of whom needed surgery Overall mortality was 9.8% (9 patients, only one for rebleeding). Variance analysis showed that the only parameter of the "Cedar Sinai Medical Center predictive index" which correlated with Length of Hospital Stay was comorbidity (p < or =0.05). Comparing the two periods, a close application of the score in the last six months allowed Length of Hospital Stay to be reduced in low-risk patients (t test with p=0.004) resulting in early discharge of 33% of cases without affecting patient outcome. CONCLUSIONS: This study confirms the reliability of the "Cedar Sinai Medical Center predictive index" in clinical practice improving the strategy of applying economic resources. Longer Length of Hospital Stay of intermediate- and high-risk groups is influenced more by comorbidities than by endoscopic findings. Early discharge was possible in one third of low risk patients. An accurate evaluation clinical para meters on admission together with early endoscopy may achieve the goal of reducing costs with a correct patient management.

[Use of virtual endoscopy with computerized tomography in the identification of colorectal neoplasms. Prospective study with symptomatic patients]. / Impiego dell'endoscopia virtuale con Tomografia Computerizzata nell'identificazione delle neoplasie colorettali. Studio prospettico in pazienti sintomatici.

INTRODUCTION: Aim of this study was to evaluate the sensitivity of virtual colonoscopy (CT colonography) in the identification of colorectal cancer and to define the limitations and the advantages of this imaging modality, as well as indications to the examination. MATERIAL AND METHODS: We examined prospectively 62 symptomatic patients aged 36 to 82 years (28 women and 34 men). All patients underwent both conventional and virtual colonoscopy on the same day; the conventional examination allowed exploration of the entire colon. RESULTS: Conventional colonoscopy identified 89 lesions 3-50 mm in diameter, namely 84 benign and 5 malignant lesions. No lesions were identified in 12 patients. CT colonography identified 52 of the 89 lesions, with 57.1% diagnostic accuracy. There were 11 false positives (82.5% positive predictive value and 52.2% specificity) and 37 false negatives (24.5% negative predictive value and 58.4% sensitivity). Sensitivity was significantly higher (85.7%) for polyps > or = 1 cm. CONCLUSIONS: Virtual colonoscopy is an imaging modality with good diagnostic yield, well tolerated by patients and with great potentials for further development. We suggest that the examination be performed in symptomatic patients who cannot undergo total colonoscopy or refuse the other imaging modalities. Further studies are warranted in larger series of patients, possibly introducing it in screening programs.

Biliary bile acid composition in gastric cancer.

Bile reflux into the stomach has been considered carcinogenic. Secondary bile acids, and in particular deoxycholic acid, have been shown to act experimentally as co-carcinogens in the colon and are increased in patients with colorectal adenocarcinoma. No information is available with respect to biliary bile acid composition in patients with gastric cancer. We studied biliary bile acid composition in 11 patients with gastric cancer and 23 healthy controls. Bile acids were measured using high-performance liquid chromatography. The site of gastric cancer was the antrum in 6 patients and body in 5. There were 6 intestinal-type and 5 diffuse adenocarcinomas. Only 2 patients had Helicobacter pylori infection. Deoxycholic acid constituted 24% +/- 2% of biliary bile acid in gastric cancer patients versus 22% +/- 2% in healthy controls (NS). Similarly, no differences were found between the two groups for all other bile acids. Deoxycholic acid constituted 23% +/- 3% of biliary bile acid (NS vs. controls) in patients with antral adenocarcinoma and 25% +/- 2% (NS vs. controls) in patients with intestinal-type gastric adenocarcinoma. Gastric adenocarcinoma is not associated with an increase in the more-toxic secondary bile acids, and deoxycholic acid in particular. This reduces the importance of bile acid composition as a promotor in gastric carcinogenesis.

Age-related transcranial Doppler findings in the evaluation of cerebral circulation during postprandial and postural tests.

We used transcranial Doppler (TCD) to investigate whether there are cerebral circulation differences between young and elderly subjects in response to postprandial postural changes. Preprandial and postprandial systolic and diastolic blood pressure, heart rate, mean middle cerebral artery (MCA) velocity (Vmean MCA), systolic/diastolic MCA velocity ratio (Vs/Vd MCA) and pulsatility index (PI) were determined in 15 healthy elderly subjects (mean age 74.3 +/- 6.5 years) and in 10 younger subjects (mean age 31.6 +/- 7. 2 years) in the supine position and after a postural change. As compared with young subjects, elderly ones showed a greater postprandial systolic pressure decline (p < 0.05) associated with a significant decrease of Vmean MCA (p < 0.05), and a greater increase of Vs/Vd and PI (p < 0.05 both). We conclude that, as compared with young subjects, elderly ones have reduced cerebrovascular adaptive response to pressure modifications induced by postprandial postural changes.

Biliary lipid composition in idiopathic bile acid malabsorption.

BACKGROUND: Chronic diarrhoea is the clinical hallmark of patients presenting with idiopathic bile acid malabsorption. Its pathogenesis is unknown; colonic water secretion can be induced by dihydroxy bile acids, but it is not known whether enrichment of the bile acid pool with these bile acids occurs in such patients. Furthermore, bile acid malabsorption is known to affect biliary lipid composition, but no information is available for the idiopathic type. AIMS: To verify: (a) whether diarrhoea in patients with idiopathic bile acid malabsorption is associated with enrichment of the bile acid pool with dihydroxy bile acids; and (b) whether supersaturation with cholesterol of duodenal bile occurs in such patients as a result of chronic bile acid depletion. PATIENTS: Thirteen patients with idiopathic bile acid malabsorption diagnosed according to abnormal 75SeHCAT test and absence of other organic diseases, and 23 control subjects. METHODS: Bile rich duodenal fluid was collected during intravenous ceruletide infusion in the fasting state. Biliary lipids were analysed by enzymatic assays and bile acids by high performance liquid chromatography. RESULTS: Patients with idiopathic bile acid malabsorption had a cholesterol saturation index similar to controls. Bile acid composition showed only a decrease in percentage cholic acid (29 (2)% versus 36 (2)%; p<0.05); the dihydroxy:trihydroxy bile acid ratio was similar to controls. CONCLUSIONS: Patients with idiopathic bile acid malabsorption do not have an increased risk of forming cholesterol gallstones. The mechanism of diarrhoea does not seem to depend on an enrichment of the bile acid pool with dihydroxy bile acids.

Pre-treatment levels of anti-HCV core IgM antibodies are closely associated with response to alpha interferon therapy in chronic hepatitis C patients.

OBJECTIVES: To investigate the relationship between pre-treatment levels of anti-hepatitis C virus (HCV) immunoglobulin M (IgM) antibodies and the outcome of interferon therapy, and also the relationship with genotypes and quantitative viraemia. PATIENTS: One hundred and four patients with biopsy-proven chronic hepatitis C without cirrhosis, consecutively enrolled in three general hospitals in Turin, Italy, and treated according to the same interferon schedule (3 MU of recombinant alpha-2b interferon three times a week for 6 months). Anti-HCV IgM were measured by a second-generation enzyme-linked immunoassay and results expressed as sample-cutoff ratio. In 30 patients, determination of viraemia by branched DNA (bDNA) and genotyping were performed and the correlation with anti-HCV IgM ratios was assessed. RESULTS: According to univariate analysis, anti-HCV IgM ratios, age, serum gamma-glutamyltranspeptidase (gamma-GT) and ferritin levels were significantly associated with sustained response to therapy. A log-linear model, testing the effect of these variables on response to therapy, showed that anti-HCV IgM ratio was the only independently associated variable (P=0.00057). Anti-HCV IgM were associated with viraemia levels (r=0.57), but not with genotype distribution. Patients with anti-HCV IgM ratio less than 1 were sustained responders to the 'standard therapy' in 65% of cases. By contrast, among patients with a ratio greater than 3, sustained response was achieved in only one patient (3%), while 73% were non-responders; the majority of relapsers were found among patients with a ratio between 1 and 3. CONCLUSION: Anti-HCV IgM antibodies provide an easily accessible and cheap serological marker of active viral replication, and are significantly related to the outcome of interferon therapy in patients with chronic hepatitis C.

[Cerebral vasomotor reactivity: functional tests]. / Reattività vasomotoria cerebrale: test funzionali.

The evaluation of cerebrovascular reactivity provides quantitative and qualitative information about cerebral hemodynamics in patients with external and internal cerebrovascular disease. Cerebrovascular reactivity is defined as the capability of the intracerebral arterioles to dilate; it may be diminished or exhausted in patients with insufficiently collateralized stenoses or with occlusions of the arteries supplying the brain. Its evaluation by different tests may provide important informations about therapeutic approach.

Serum levels of anti-hepatitis C virus IgM core antibodies may predict the response to interferon-alpha therapy in chronic hepatitis C.

We measured the optical densities (OD) of serum anti-hepatitis C virus IgM core antibodies in 40 HCV-positive patients (24 males and 16 females) with histologically proven chronic active hepatitis but without cirrhosis. All patients were treated with i.m. injections of 3 MU thrice weekly of interferon-alpha (IFN-alpha) for 6 months and followed-up monthly. Optical densities were evaluated in thawed sera before beginning treatment and 6 months after completion, and in fresh sera obtained at the end of an 8-12-month follow-up period. Patients were grouped into three categories according to the OD obtained: < 0.3 (negative test); 0.3-0.6 (intermediate positivity); > 0.6 (high positivity). According to the response to treatment during the follow-up period, patients were further divided into three classes: sustained responders; relapsers or partial responders; non-responders. In each patient, the OD values were similar in the three determinations before, after therapy and at the end of the follow-up period. All patients with an intermediate positive test for anti-HCV IgM core antibodies were relapsers or partial responders, and all patients with high OD values were non-responders. Conversely, 71% of the patients with a negative test were sustained responders. We conclude that this cheap and easily performed test may be useful in predicting the response to IFN therapy.

[Evaluation of pre- and postoperative cerebral hemodynamics in extracranial carotid surgery using transcranial Doppler. Preliminary note]. / Valoración de la hemodinámica cerebral pre- y postoperatoria en la cirugía de las carótidas extracraneales mediante Doppler transcraneano. Nota preliminar.

The Authors report their preliminary experiences concerning the use of transcranial Doppler (TCD) in the pre- and postoperative monitoring of extracranial carotid surgery. TCD is a non invasive method of investigation able to give informations about the distribution of cerebral blood flow and about the mechanisms of compensation of Willis' circle. Furthermore, TCD showed itself to be very useful in the postoperative qualitative evaluation of surgery, pointing out, as a general rule, an increased flow in the middle cerebral artery after thromboendarterectomy of internal carotid artery. This haemodynamic modification, if present, is perceptible since the immediate postoperative period and becomes more evident and definitely stable at a distance of 20-30 days after operation, likewise the definitive stabilization of Willis' circle's haemodynamics.