Structural and elastic anisotropy of crystals at high pressures and temperatures from quantum mechanical methods: The case of Mg2SiO4 forsterite.

We report accurate ab initio theoretical predictions of the elastic, seismic, and structural anisotropy of the orthorhombic Mg2SiO4 forsterite crystal at high pressures (up to 20 GPa) and temperatures (up to its melting point, 2163 K), which constitute earth's upper mantle conditions. Single-crystal elastic stiffness constants are evaluated up to 20 GPa and their first- and second-order pressure derivatives reported. Christoffel's equation is solved at several pressures: directional seismic wave velocities and related properties (azimuthal and polarization seismic anisotropies) discussed. Thermal structural and average elastic properties, as computed within the quasi-harmonic approximation of the lattice potential, are predicted at high pressures and temperatures: directional thermal expansion coefficients, first- and second-order pressure derivatives of the isothermal bulk modulus, and P-V-T equation-of-state. The effect on computed properties of five different functionals, belonging to three different classes of approximations, of the density functional theory is explicitly investigated.

Performance of six functionals (LDA, PBE, PBESOL, B3LYP, PBE0, and WC1LYP) in the simulation of vibrational and dielectric properties of crystalline compounds. The case of forsterite Mg2SiO4.

The performance of six different density functionals (LDA, PBE, PBESOL, B3LYP, PBE0, and WC1LYP) in describing the infrared spectrum of forsterite, a crystalline periodic system with orthorhombic unit cell (28 atoms in the primitive cell, Pbmn space group), is investigated by using the periodic ab initio CRYSTAL09 code and an all-electron Gaussian-type basis set. The transverse optical (TO) branches of the 35 IR active modes are evaluated at the equilibrium geometry together with the oscillator strengths and the high-frequency dielectric tensor ϵ(∞) . These quantities are essential to compute the dielectric function ϵ(ν), and then the reflectance spectrum R(ν), which is compared with experiment. It turns out that hybrid functionals perform better than LDA and GGA, in general; that B3LYP overperforms WC1LYP and, in turn, PBE0; that PBESOL is better than PBE; that LDA is the worst performing functional among the six under study.

The measure of life-time alcohol consumption in patients with cirrhosis: reproducibility and clinical relevance.

Our aims were to design a reproducible method of measuring life-time alcohol consumption in patients with cirrhosis, and to assess the risk of liver decompensation associated with alcohol intake using a case-control design and a multivariate analysis. We studied 439 patients ("cases") with decompensated cirrhosis, and 233 with compensated cirrhosis ("controls"). Mean life-time daily amount and duration of alcohol intake were measured by a standardized questionnaire, whose reproducibility, assessed by interviewing 75 relatives, was 70% for daily alcohol intake and 84% for duration of intake. Better reproducibility was found by re-interviewing patients at discharge from hospital. Daily alcohol intake was significantly higher in males, younger patients and patients with liver decompensation. After stratification according to the average life-time daily alcohol intake, we found a significant increase in the risk of liver decompensation from 125 g ethanol intake per day onwards. No association was found between duration of alcohol intake and risk of liver decompensation. We conclude that alcohol intake can be reliably and reproducibly measured: in patients with cirrhosis, increased alcohol intake is associated with increased risk of liver decompensation, with a significant dose-effect above a daily intake of 125 g ethanol.

Malignant lymphoproliferative disorders in liver cirrhosis.

BACKGROUND: Lymphoproliferative disorders in patients with liver cirrhosis, although uncommon, have been reported in at least 49 cases. Some authors have suggested that the association between chronic liver disease and lymphoma is not coincidental, that immune mechanisms may be pathogenetically involved. PATIENTS AND METHODS: In the present study we calculated the incidence rate of lymphoproliferative disorders in 334 liver cirrhosis patients (201 males, mean age 59 +/- 12; 133 females, mean age 61 +/- 11) treated at the Gastroenterology Department of the Mauriziano Hospital in Turin from January 1987 to September 1990. RESULTS: We diagnosed 12 lymphoproliferative disorders, corresponding to an incidence of 9.56/1,000 person-years, a figure much higher than expected on the basis of the incidence rate registered in the Turin general population. Six of the 12 lymphoproliferative disorders were non-Hodgkin's lymphomas of the stomach, a proportion by far exceeding expectation. CONCLUSIONS: Our data support the hypothesis that the association between chronic liver disease and lymphoproliferative disorders is not just coincidental, and suggest that liver cirrhosis might be considered an immunological disturbance which entails an increased risk of developing lymphoproliferative disorders. Mechanisms causing lymphoproliferative disorders to develop in the course of chronic liver disease have been hypothesized.

Measurement of bile acid half-life using [75Se]HCAT in health and intestinal diseases. Comparison with [75Se]HCAT abdominal retention methods.

The diagnostic values in detecting terminal ileum dysfunction using [75Se]HCAT have been assessed for two different scintigraphic techniques in 58 subjects. The measurement of [75Se]HCAT T1/2 in the enterohepatic circulation by daily gallbladder scintigraphy showed 78% sensitivity, 96% specificity, 96% positive predictive value, and 78% negative predictive value at the optimal cutoff level of 2.0 days; lower--but not significantly different--figures were observed for [75Se]HCAT total abdominal retention four and seven days after isotope administration, at the optimal cutoff levels of 40% and 22%, respectively. [75Se]HCAT T1/2 was then evaluated in 60 patients with various intestinal diseases. Sixty-nine percent (9/13) of patients with diarrhea of obscure origin showed abnormal [75Se]HCAT T1/2. Bile acid malabsorption using [75Se]HCAT can be investigated by the noninvasive measurement of its enterohepatic T1/2 and may play a pathogenetic role in patients with diarrhea of obscure origin.

Alcohol consumption and non-cirrhotic chronic hepatitis: a case-control study.

We carried out a hospital-based case-control study to assess the association of both the daily amount and the duration of alcohol intake with the risk of developing non-cirrhotic chronic liver disease (chronic hepatitis) in 121 chronic hepatitis patients diagnosed by laparoscopy and liver biopsy, and in 242 matched 'controls' randomly selected from inpatients of the same hospital. Alcohol intake was quantified in all subjects using a standardized questionnaire administered by two doctors unaware of the aim of the study. The odds ratio (OR) for chronic hepatitis was estimated by conditional logistic regression and increased exponentially from 1.0 for non-drinkers to 11.4 for daily alcohol intake of 325 g or more. Considering duration of alcohol consumption from up to 10 to up to 30 years, the ORs for chronic hepatitis consistently decreased for the daily alcohol intake categories of 25-50 g (from 74.1 to 0.7 respectively), 75-100 g (from 149.7 to 0.7 respectively) and 125 g or more (from 212.0 to 1.8 respectively). Our results suggest the existence of a dose-dependent individual susceptibility to the damaging effect of alcohol on the liver.

[Diagnosis of bacterial contamination of the small intestine using the 1 g [14C] xylose breath test in various gastrointestinal diseases]. / La diagnosi di contaminazione batterica del tenue mediante il test respiratorio con 1 g di [14C] xilosio in varie patologie gastrointestinali.

The prevalence of the small intestine bacterial overgrowth syndrome has been assessed in 109 in-patients affected by various gastrointestinal disorders using the 1 g [14C]-xylose breath test; 18 healthy subjects acted as a control group: none of them showed abnormal results (100% specificity). None of 14 patients with colonic disease had abnormal results, whereas in 44 patients with ileal diseases the test was positive in 12% to 39% of the cases. Abnormal results were found in 46% of patients who underwent partial gastric resection greater than 20 years before, 29% of patients with irritable bowel syndrome without diarrhoea (faecal wet weight less than or equal to 600 g/72 h), 56% of those with diarrhoea of obscure origin, and 25% of celiac patients. Eight out of 8 patients with altered results showed normalization of the test after antibiotic therapy. Despite its high diagnostic value in the setting of clinical research, the 1 g [14C]-xylose breath test cannot as yet be proposed as a routine investigation.

[Liver cirrhosis and lymphoproliferative diseases: coincidence or association?]. / Cirrosi epatica e malattie linfoproliferative: coincidenza o associazione?

The development of lymphoproliferative disorders in association with a chronic liver disease, although uncommon has been documented in several reports and a review of the available literature yielded a total of 34 cases. It has been suggested that this association is probably not a fortuitous coincidence and several mechanisms explaining the development of lymphoproliferative diseases in the course of liver disease have been offered. We have evaluated the annual cumulative incidence of such an association in the specific population of patients with liver cirrhosis (N.:344) admitted to our Department of Gastroenterology, Mauriziano Hospital, in Turin, within 3.5 years, from January 1987 to June 1990: it resulted to be 9.56/1,000 subjects per year. This figure is much higher than the annual incidence registered in Turin within the years 1985-87 for the same lymphoproliferative disease, 39.6/100,000 inhabitants. Our data add value to the hypothesis that this association is not incidental and suggest that chronic liver disease should be added to the list of the pathological conditions with immunological disturbances associated with lymphoproliferative disorders.

[Intrahepatic cholestasis in hyperthyroidism]. / Colestasi intraepatica in corso di ipertiroidismo.

Three cases of cholestatic liver disease related to hyperthyroidism are reported. Features indicative of a role of the endocrine disease in the pathogenesis of the cholestatic syndrome were the appearance of liver damage in temporal relation with the clinical onset of thyroid hyperfunction and its disappearance with the amelioration of the hyperthyroidism; the absence of congestive heart failure and of infectious, toxic or obstructive agents of liver damage; the pathological and biochemical findings of intrahepatic cholestasis. Hyperthyroidism can be rarely complicated by a severe cholestatic syndrome that may dominate the clinical presentation and course.

Prolonged gastric pH monitoring in responder and nonresponder duodenal ulcer patients: response to placebo and to H2-blocker administration.

We evaluated the circadian pattern of gastric acidity by prolonged intraluminal pHmetry in 15 "responder" and 10 "nonresponder" duodenal ulcer patients after nocturnal administration of placebo, ranitidine, and famotidine. Acidity was measured during predefined periods under the different drug regimens in the two groups of subjects, and a comparison was performed both within and between groups. With placebo, significantly lower median 24-h pH values were detected in patients with resistant ulcer than in responders (1.13 versus 1.63). On the contrary, no statistical difference was detected between the two groups during any time of day after administration of either ranitidine or famotidine. Within each group, no significant difference was noted between the two different H2-blockers. Thus, our data suggest that patients with resistant duodenal ulcer display an increased gastric acidity in control conditions but a "normal" response to administration of antisecretory drugs.

A case-control study on alcohol consumption and the risk of chronic liver disease.

We carried out a hospital based case-control study involving 655 patients with chronic liver disease encompassing chronic hepatitis, asymptomatic liver cirrhosis and symptomatic liver cirrhosis and 655 pair-matched control individuals in order to estimate the dose-response relationship between alcohol consumption and the occurrence of chronic liver disease. Alcohol intake was measured by a questionnaire and expressed as Daily Alcohol Intake (DAI) during the patient life. DAI estimates from patient interviews were in good agreement with those obtained by interviewing a sample of relatives. We found an exponential positive association between DAI and the risk of chronic hepatitis and cirrhosis. However, consuming less than 100g of alcohol every day did not increase the risk of developing chronic liver disease. For asymptomatic cirrhosis the risk was lower than for chronic hepatitis, especially at high DAI, probably because high consumption carried a high probability of liver decompensation. For symptomatic cirrhosis, the risk function showed a similar pattern as for chronic hepatitis. Chronic hepatitis patients were 6-7 years younger than cirrhotics. Our results suggest that the evolution towards cirrhosis once a chronic liver damage has occurred is probably time-dependent, but not or minimally dependent on alcohol intake.

[Antipyrine clearance in liver resections]. / La clearance dell'antipirina nelle resezioni epatiche.

We studied antipyrine clearance (APC1) in 19 healthy controls, 10 cirrhotic patients, 20 patients undergoing partial hepatectomy for liver tumors (14 with cirrhosis and 6 without cirrhosis). The aim of the study was to evaluate if the test represents a measure of the residual hepatic function and a useful index of surgical risk in cirrhotic patients following partial hepatectomy. The APC1 was significantly reduced in cirrhotic patients ws healthy controls. It is reduced following partial hepatectomy in cirrhotic patients (p less than 0.001) and in non cirrhotic patients (n.s.). The APC1 was found to be related with the plasma level of albumin and pseudocholinesterase; it also was related with the Pugh's score for hepatic function. The APC1 is a satisfactory index of residual hepatic function. On the other hand it does not provide more useful information than the Pugh's score for surgical risk in liver resection.

Acute pancreatitis during oral 5-aminosalicylic acid therapy.

Therapy with oral 5-aminosalicylic acid for inflammatory bowel disease has been reported as effective and safe. We report two cases of biochemically proven mild acute pancreatitis occurring 2 and 14 days, respectively, after oral 5-aminosalicylic acid therapy was instituted for inflammatory bowel disease. A hypersensitivity mechanism might be involved, owing to possible erratic systemic absorption of the drug. We suggest clinical and biochemical monitoring for patients undergoing oral 5-aminosalicylic acid therapy in order to confirm its possible association with acute pancreatitis and to assess the actual incidence of such an adverse reaction.

Daily gastric pH in controls and in duodenal ulcer patients: basal condition and response to treatment.

Gastric pH was monitored, by means of a computerized system, in healthy controls (C) and in patients with active duodenal ulcer (ADU) and inactive duodenal ulcer (IDU). The test was performed before treatment and during administration of a single dose of ranitidine 150 mg, cimetidine 400 mg, and pirenzepine 50 mg, in random sequence at 12-h intervals, (10 am, 10 pm). Under basal conditions, progressively lower median pH values were detected in ADU and IDU patients, compared with controls. A significant difference was found between C and ADU during daytime (1.38 vs. 0.85), nighttime (1.29 vs. 0.81), and 24 h (1.35 vs. 0.81) and between C and IDU during 24 h (1.35 vs. 1.11). However, no statistical difference was observed between patients with active and inactive ulcer disease. Administration of ranitidine and cimetidine significantly increased gastric pH during nighttime but not during daytime. Ranitidine, at the doses studied, proved to be more potent than cimetidine in suppressing gastric acidity. Gastric pH was unaffected by pirenzepine in most cases.

Diagnostic value of serum immunoreactive conjugated cholic or chenodeoxycholic acids in detecting hepatobiliary diseases. Comparison with levels of 3 alpha-hydroxy bile acids determined enzymatically and with routine liver tests.

The diagnostic value of the enzymatic fluorometric method for total serum bile acids (TSBA) and for radioimmunoassay measurement for conjugated cholic acid (CCA) or chenodeoxycholic acid was compared with that of routine liver function tests in 223 patients with liver disease, 88 healthy subjects, and 118 patients affected by other diseases. The value of the tests for screening in the general population was assessed by simulation, using estimates of disease prevalence. TSBA was significantly more sensitive (78%) but less specific (94%) than CCA (sensitivity of 69%, specificity of 98%). Aspartate aminotransferase was nearly as sensitive (74%) as TSBA, but significantly less specific (93%) than CCA. CCA provided the highest positive predictivity (98%), even in a screening simulation (32%). With the use of sequential aspartate aminotransferase measurement followed by CCA, this value rose to 100%. This test procedure appears to be the best screening method for liver diseases available at present.

Physiology of ileoanal anastomosis with ileal reservoir for ulcerative colitis and adenomatosis coli.

A physiologic and metabolic assessment was carried out on eight patients six months after total proctocolectomy with ileal reservoir for ulcerative colitis and familial adenomatosis coli. All patients were continent and able to defecate spontaneously, stool frequency ranging from two to five per 24 hours. Anal sphincter resting pressures (35 +/- 14 mmHg) and squeeze pressures (88 +/- 24.2 mmHg) were similar to those of a healthy population, with the exception of one patient's complaint of nocturnal mucous leakage per anus. Biopsies of the ileal mucosa of the reservoirs showed a mild inflammation in seven patients; in one a subtotal villous atrophy (plus glandular pattern) was found. Anthropometric measurements, lymphocyte counts, hemoglobin, albumin, transferrin, iron, B12, and folate were normal in all. In the majority of patients there was no evidence of bacterial overgrowth. Vitamin B12 absorption was reduced slightly in only one patient. Lipid absorption (as judged by the 14C-Triolein breath test) was abnormal in three patients. Fecal clearance of alpha 1 antitrypsin as protein losses index was abnormal in three patients. Bile acid malabsorption was the most important ileal dysfunction observed in the patients.

Comparison of ranitidine and sucralfate in the long-term treatment of duodenal ulcer.

We evaluated long-term treatment with either ranitidine (R) or sucralfate (S) in the prevention of duodenal ulcer recurrences. Fifty-nine patients with healed ulcers were randomly allocated to maintenance treatment with 150 mg R nightly or 2 g/day S. By using a life table analysis, the calculated probable remission rates at 4, 8, and 12 months were 90, 85, and 53% with R, respectively, and 62, 62, and 53% with S, respectively. These differences were not significant at any interval. In both groups ulcer relapse was independent of sex, smoking habit, and alcohol and coffee consumption, whereas a history longer than 5 years was significantly related to a higher probability of recurrence. No relevant clinical or biochemical side effects were encountered with either drug, but compliance rate was higher in the R group. R and S are equally effective in preventing duodenal ulcer relapse over a 1-year period of maintenance treatment, although R proved to be more effective in preventing early relapse.

Presence and origin of IgA1- and IgA2-containing circulating immune complexes in chronic alcoholic liver diseases with and without glomerulonephritis.

Levels of IgA-containing circulating immune complexes (IgAIC) and their content of IgA1 and IgA2 subclasses were determined in chronic alcoholics with various degrees of liver damage and with or without associated glomerulonephritis. In patients with chronic alcoholic liver diseases, significantly increased IgAIC mean values were found independent of the presence of renal involvement, while in chronic alcoholics without biochemical evidence of liver damage IgAIC levels were normal. Both IgA subclasses were evidenced in IgAIC with an IgA pattern similar to that found in secretions, in agreement with the impaired liver clearance of IgAIC derived from intestinal mucosa. Nevertheless, no significant correlation between IgAIC and markers of hepatocytolysis or of cholestasis was found. One cannot therefore rule out the hypothesis of increased IgA synthesis in alcoholic liver disease due to abnormal alimentary antigen challenge and pathologic lymphocytic responsiveness. Finally, high IgAIC levels were found not only in patients with IgA glomerular deposits, but also in patients without clinical evidence of renal involvement.