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We provide a rigorous workflow to quantify the effects of key sources of uncertainty associated with equivalent fracture aperture estimates wconstrained through mud loss information acquired while drilling a well in a reservoir. A stochastic inverse modeling framework is employed to estimate the probability distribution of w. This choice is consistent with the quantity and quality of available data. The approach allows assessing the probability that values of winferred from mud loss events exceed a given threshold. We rely on a streamlined analytical solution to model mud losses while drilling. We explicitly consider uncertainties associated with model parameters and forcing terms, including drilling fluid rheological properties and flow rates, pore fluid pressure, and dynamic drilling fluid pressure. A synthetic scenario is considered to provide a transparent reference setting against which our stochastic inverse modeling workflow can be appraised. The approach is then applied to a real-case scenario. The latter is associated with data monitored on a rig site. A direct comparison of the impact of data collected through two common techniques (respectively, relying on flow meter sensors or pump strokes) on the ensuing probability of wis provided. A detailed analysis of the uncertainty related to the level of data corruption is also performed, considering various levels of measurement errors. Results associated with the field setting suggest that the proposed workflow yields probability distribution of wthat are compatible with interpretations relying on traditional analyses of image logs. Results stemming from direct and indirect flow data display similar shapes. This suggests the viability of the probabilistic inversion methodology to assist quasi-real-time identification of equivalent fracture apertures on the basis of routinely acquired information during drilling.

To improve our knowledge for future hepatitis A virus (HAV) vaccination strategies we carried out a multicentre study on naturally acquired immunological protection against HAV in patients with chronic hepatitis in Italy. We enrolled 830 consecutive patients with chronic hepatitis on their first observation at one of the six Italian liver units participating in the study. Six hundred and fifty-eight patients (79·3%) were positive for total anti-HAV and 172 (20·7%) were negative. The anti-HAV negative patients were younger (median age 33, range 11–78) than the anti-HAV positive (median age 56, 18–87). There was a higher prevalence of cases with circulating anti-HAV among the 508 patients residing in southern Italy than in the 322 residing in northern Italy (88·8% vs. 64%, P < 0·001). No significant difference in the anti-HAV prevalence was observed between patients from northern Italy and those from southern Italy aged 0–30 years or in those over 60 years, while in those 31–60 years old there was a higher prevalence of anti-HAV positive patients from southern Italy (90·2% vs. 65·8%, P < 0·0001). Of the patients with liver cirrhosis in this study, only 3 of the 26 (11·5%) from northern Italy and 8 of the 228 (3·5%) from southern Italy had no immunological protection against HAV infection. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV is substantial in Italy, particularly in the north of the country, and that new vaccination strategies are needed.

Summary During the period from May 1987 through November 1989, the prevalence of antibodies to hepatitis A virus infection (anti-HAV) was assayed by the ELISA method in the serum samples of 5,507 (54% males, 46% females) apparently healthy subjects three to 19 years old in Italy. Subjects were selected by a systematic cluster sampling in five different geographical areas of Italy. The overall prevalence of anti-HAV was 9.5%; it increased from 2.3% among children three to five-years-old to 16.3% in teenagers 17 to 19 years old (p<0.001). A slight preponderance of females was observed (10% versus 9.1%), but the difference was not statistically significant. The prevalence was significantly higher in Southern Italy than in Northern Italy (27.4% versus 4.8%; p<0.01). The prevalence of anti-HAV was inversely related to the fathers' years of schooling (O.R.3.3; 95% C.I.=2.5–4.2) and positively related to the family size (O.R. 2.4; 95% C.I.= 1.9–3.1). These findings indicate that, today, exposure to HAV infection at a young age in Italy is very low. However, sociodemographic factors are still important determinants in the spread of this infection.

Previous reports have indicated that the early induction of interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-alpha), IL-1beta, and IL-10 is crucial for the establishment and regulation of host cell-mediated immunity to the intracellular protozoan parasite Toxoplasma gondii. In this study, we demonstrate that a soluble tachyzoite extract (soluble tachyzoite antigen) can trigger the expression of these four monokines by murine inflammatory macrophages. Further characterization revealed that the parasite molecules in soluble tachyzoite antigen responsible for monokine induction are heat stable at 100 degree C but differ in sensitivity to protease digestion. Thus, the tachyzoite factors that stimulate TNF-alpha and IL-to expression were found to be more resistant to treatment with proteinase K than those responsible for IL-12 and IL-10 induction. Similarly, while the factors responsible for the induction of all four monokines were found to be sensitive to periodate oxidation, the TNF-alpha-stimulating activity was partially resistant to treatment with the compound at a low concentration (1 mM). A further dichotomy in monokine induction signals was inferred from experiments with isoquinoline sulfonamide protein kinase inhibitors. The latter work suggested that the pathways for TNF-alpha and IL-1beta are protein kinase C dependent, while expression of IL-12 and expression of IL-10 share distinct signal transduction mechanisms involving other kinases. Together, these data argue that monokine induction by T. gondii is mediated by glycoproteins that may belong to distinct groups in terms of their biochemical properties and intracellular signaling pathways.

To verify whether improvements in hygiene affect the risk of HBV infection, a seroepidemiological survey on HBV infection was carried out in a home for the elderly with continuous-care accomodation. HBV serum markers were tested in 315 subjects and the results of HBV infection were compared to those observed in two different types of nursing homes for the elderly from an earlier seroepidemiological study carried out in 1978. In addition, results from a cohort of a pre-geriatric population living in their own homes in the same geographical area surveyed in 1980 were compared to the present study. A statistically significant lower prevalence of HBV serum markers in the new home for the elderly compared to the two types studied in 1978 was observed. No difference was found between the new institutionalized study group and the cohort of a pre-geriatric population surveyed in 1980. These results reflect the improved sanitation in homes for the elderly and show that the elderly have very few opportunities to become infected, even in a close cohabitation system.

Clinical and experimental evidence indicates that estrogens are involved in the control of hepatocyte proliferation both in normal and in neoplastic conditions. Thirty-two cirrhotic patients with unresectable or otherwise untreatable hepatocellular carcinoma were allocated to receive either tamoxifen (30 mg/day) or no treatment. The patients in the two groups were matched for age, male/female ratio, Child-Pugh class, approximate tumor volume (US and CT scan), and etiology of the underlying cirrhosis. Survival of the tamoxifen-treated patients (life-table, Wilcoxon-Breslow) was significantly prolonged (P=0.0038), with 35% (vs 0%) survival at 12 months. No difference was observed between males and females or between alcoholic and nonalcoholic cirrhosis. In 40% of tamoxifen-treated patients, the levels of a-fetoprotein declined. In conclusion, the antiestrogen tamoxifen appears to be effective in the palliative treatment of hepatocellular carcinoma. An initial decline in a-fetoprotein levels may represent an early favorable prognostic sign.

To evaluate the effect of ursodeoxycholic acid (UDCA) treatment according to the severity of primary biliary cirrhosis, a long-term prospective open trial in 54 consecutive PBC patients, 19 with histological stage I–II, 24 stage III, and 11 stage IV was carried out. UDCA was administered at a dosage of 250 mg twice a day. Clinical and biochemical assessment (AST, ALT, alkaline phosphatase, GGT, bilirubin) were done initially and every six months. Serum hyaluronate (HY) and type III procollagen amino propeptide (PIIIP) were also evaluated, as they are considered markers of fibrosis and prognosis. All patients were followed-up for at least two years (24–36 months); results were analyzed at 24 months after treatment. The composite pruritus score failed to show significant changes during UDCA treatment, while intensity score demonstrated a significant reduction from the 6th month. Patients with histological stage I–II disease had a significant decrease of liver enzymes (AST, ALT, alkaline phosphatase, GGT) after six months and maintained the levels up to 24 months. The patients with histological stage III disease showed a significant decrease of AST, ALT, alkaline phosphatase (but not GGT) up to month 18; subsequently AST and ALT serum levels increased, reaching values comparable to baseline by 24 months. In patients with histological stage IV disease no significant change in liver enzymes was observed during the follow-up. HY and PIIIP serum levels failed to show significant changes during UDCA treatment in the three groups of patients. In conclusion, although well tolerated in all patients with PBC, UDCA seems to improve itching and liver enzymes only in the pre cirrhotic stage. A long-term remission of the disease is maintained only in the early histological stages.

Unlike adults (60 of cases), it is rare to find the chronic hepatitis B virus (HBV) carrier status with normal transaminases among children. The aim of this study was to investigate whether this status would depend on the duration of HBV infection, that is, whether chronic hepatitis in childhood would lead to the asymptomatic carrier status in later life. We reexamined all of our patients with chronic HBV infection of >10 years' duration and with histologically documented chronic hepatitis during childhood. This was a group of 36 adolescents and young adults. All subjects were screened for tumor using α-fetoprotein assay and hepatic ultrasound. Eight patients with cirrhosis underwent esophageal fiberoptic endoscopy. All patients were in good general condition, with no clinical signs of liver failure. Only two patients had abnormal transaminase levels, both of whom had evidence of delta infection. All but one patient became anti-HBe positive. Five cases had HBsAg clearance. (Seventy-one percent of patients were HBeAg positive and 14 anti-HBe positive at the onset of the disease.) Hepatic ultrasound revealed no tumors in any of the subjects, and fiberoptic endoscopy demonstrated no esophageal varices. This study suggests that (a) chronic hepatitis and asymptomatic carrier status may be subsequent stages of the B virus infection; and (b) chronic hepatitis in childhood is generally benign and may evolve into an asymptomatic carrier status. The main problem with the chronic carrier status is probably the increased risk of hepatocellular carcinoma.

Seroprevalence of Hepatitis C virus (HCV), Hepatitis B virus (HBV) and HIV antibodies was studied in a group of 259 apparently healthy homosexual men of the Veneto Region (Italy). Subjects were recruited between 1987 and 1989 from homosexual men's clubs.

In 1989, the prevalence of IgG antibodies to pertussis toxin (PT) in a sample of 367 unvaccinated apparently healthy children 5–14 years old was estimated by ELISA in Kumba City (Cameroon). Children were recruited using a systematic random sampling from six primary schools located in different districts of the city. The sample was representative of the various socio-economic classes.

In 1990, a case-control study was conducted in Italy to investigate the possible association between HCV infection and hepatocellular carcinoma (HCC). Serum samples from 65 subjects with newly diagnosed hepatocellular carcinoma and 99 hospital control subjects were tested for the presence of anti-HCV by second-generation ELISA test; positive sera were assayed by RIBA anti-HCV second-generation test. In addition, samples were tested for hepatitis B surface antigen (HBsAg), antibodies to the hepatitis B core antigen (anti-HBc), and antibodies to HBsAg (anti-HBs). The presence of HCV and/or HBsAg serologic markers was significantly associated with hepatocellular carcinoma risk: the relative risk (RR) of HCC was 21.3 (95% CI = 8.8–51.5) for anti-HCV positivity in the absence of HBsAg; the relative risk of HCC was 13.3 (95% CI = 5.5–32.2) for the presence of HBsAg in the absence of anti-HCV. A higher risk (77.0) was observed when both markers were present. These findings indicate that HCV and HBsAg are independent risk factors for HCC. The results of multivariate analysis showed that the adjusted RR linking anti-HCV and HCC was 26.9 (95% CI = 9.9–72.5), the adjusted RR linking HBsAg and HCC was 11.4 (95% CI = 3.1–41.4), whereas no association (RR 1.5; 95% CI = 0.6–3.6) was found to link HCC with anti-HBc and/or anti-HBs positivity. Through the computation of population attributable risk we estimate that 25% of HCC cases occurring in Italy could be attributed to anti-HCV positivity alone and 20% to HBsAg carrier state alone. These data provide evidence that HCV infection plays a major role in the development of HCC in Italy.

Unlike adults (>60% of cases), it is rare to find the chronic hepatitis B virus (HBV) carrier status with normal transaminases among children. The aim of this study was to investigate whether this status would depend on the duration of HBV infection, that is, whether chronic hepatitis in childhood would lead to the asymptomatic carrier status in later life. We reexamined all of our patients with chronic HBV infection of >10 years' duration and with histologically documented chronic hepatitis during childhood. This was a group of 36 adolescents and young adults. All subjects were screened for tumor using a-fetoprotein assay and hepatic ultrasound. Eight patients with cirrhosis underwent esophageal fiberoptic endoscopy. All patients were in good general condition, with no clinical signs of liver failure. Only two patients had abnormal transaminase levels, both of whom had evidence of delta infection. All but one patient became anti-HBe positive. Five cases had HBsAg clearance. (Seventy-one percent of patients were HBeAg positive and 14% anti-HBe positive at the onset of the disease.) Hepatic ultrasound revealed no tumors in any of the subjects, and fiberoptic endoscopy demonstrated no esophageal varices. This study suggests that (a) chronic hepatitis and asymptomatic carrier status may be subsequent stages of the B virus infection; and (b) chronic hepatitis in childhood is generally benign and may evolve into an asymptomatic carrier status. The main problem with the chronic carrier status is probably the increased risk of hepatocellular carcinoma.

It has been suggested that molecular mimicry between the antigens of Trypanosoma cruzi and the host could have a role in the onset of the chronic stage of Chagas' disease. In this article, we report on a monoclonal antibody (MAb), CAK20.12 (immunoglobulin G2b), which reacts with a polypeptidic epitope of a 150-kDa antigen expressed on the surface of several strains of T. cruzi. This MAb also causes lysis of bloodstream trypomastigotes. Serum samples from 30 of 30 patients with chronic and 11 of 13 patients with acute Chagas' disease present specific antibodies to this antigen. MAb CAK20.12 reacts, by indirect immunofluorescence, with human and syngeneic murine striated muscle tissue, with the smooth muscle layer of cardiac arteries, with the lamina muscularis mucosae and the external striated muscle layer of the esophagus, and with the smooth muscle cells of the colon from normal syngeneic mice. Reactivity with the small intestine was very weak, and no reactivity with ventricle or atrium tissue was detected. Adsorption with an antigenic fraction from normal murine striated muscle or from T. cruzi epimastigotes confirmed that MAb CAK20.12 recognizes a common epitope present in parasites and host tissues. MAb CAK20.12, lytic for the infective form of T. cruzi, recognizes an epitope expressed in striated and smooth muscle cells of the host tissues affected in the chronic stage of Chagas' disease.

Previous reports have indicated that the early induction of interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-alpha), IL-1beta, and IL-10 is crucial for the establishment and regulation of host cell-mediated immunity to the intracellular protozoan parasite Toxoplasma gondii. In this study, we demonstrate that a soluble tachyzoite extract (soluble tachyzoite antigen) can trigger the expression of these four monokines by murine inflammatory macrophages. Further characterization revealed that the parasite molecules in soluble tachyzoite antigen responsible for monokine induction are heat stable at 100 degree C but differ in sensitivity to protease digestion. Thus, the tachyzoite factors that stimulate TNF-alpha and IL-to expression were found to be more resistant to treatment with proteinase K than those responsible for IL-12 and IL-10 induction. Similarly, while the factors responsible for the induction of all four monokines were found to be sensitive to periodate oxidation, the TNF-alpha-stimulating activity was partially resistant to treatment with the compound at a low concentration (1 mM). A further dichotomy in monokine induction signals was inferred from experiments with isoquinoline sulfonamide protein kinase inhibitors. The latter work suggested that the pathways for TNF-alpha and IL-1beta are protein kinase C dependent, while expression of IL-12 and expression of IL-10 share distinct signal transduction mechanisms involving other kinases. Together, these data argue that monokine induction by T. gondii is mediated by glycoproteins that may belong to distinct groups in terms of their biochemical properties and intracellular signaling pathways.

Background: In a campaign to vaccinate health care workers, a three-dose schedule (0, 1, and 6 months) and a four-dose schedule (0, 1, 2, and 14 months) with hepatitis B (HB) vaccine were used. After primary immunization 26 subjects vaccinated with the 3-dose schedule and 4 subjects vaccinated with the 4-dose schedule had undetectable anti-HBs titres. Methods: All these 30 non-responders received an extra dose of the same vaccine 2 months after primary immunization and a booster dose with a yeast-derived vaccine 6 years later. Anti-HBs levels were evaluated 1 month after the extra dose and after the booster dose. Results: One month after the extra dose 26.9% (7 of 26) of the subjects vaccinated with the 3-dose schedule became positive for anti-HBs. Six years later only two of these subjects had detectable anti-HBs. After the booster dose the seven subjects who responded to the extra dose showed an anamnestic type of response, and five additional subjects became positive for anti-HBs. Responders to the extra dose were significantly younger than the non-responders. In the four-dose group only one subject responded to the extra dose, and that subject maintained protective anti-HBs. Conclusion: About 25% of non-responders to primary HB vaccination could benefit from an extra dose, and these subjects show an anamnestic type of response to HBs antigen even after 6 years. This response seems to be influenced by age.

Zusammenfassung Bei einer Gruppe „gesunder“ HB-Ag (Australia Antigen) Träger und einer Gruppe gesunder, HB-Ag-negativer Probanden wurden die Serumkonzentrationen der Immunglobuline, die Präsenz von zirkulierenden Autoantikörpern, die Zahl der peripheren „atypischen“ Lymphocyten und die Zahl der DNA und RNA synthetisierenden Zellen untersucht.