Oxidant/antioxidant status in patients with chronic HIV infection.

The infection caused by HIV leads to an activation of the immune system, which involves local and systemic oxidative stress. In HIV-positive (HIV+) patients, oxidative damage is the result of HIV infection and its progression through the replication of the virus. We have examined 52 subjects: 26 HIV+ patients, and 26 healthy subjects (NC). Analysis of the parameters of the oxidant/antioxidant status (total antioxidant capacity (TAC), hydroperoxides (free radicals, PRO), thiols as thiolic capacity, TC) was carried out by means of the OXY-Absorbent test, the d-Rom test, and the -SHp test, respectively. Healthy subjects presented the following values: TAC (micromol/ml) 259.5+/-40.5; TC (micromol/l) 434.09+/-18.31; PRO (mg/dl) 54.09+/-7.3; CD4+ cells (cells/ml) 850+/-333. Values of HIV+ patients were the following: TAC 218.73+/-18.55 (ns vs NC; TC 250.88+/-93.11 (p 0.001 vs NC); PRO 110.5+/-23.61 (p 0.0005 vs NC); CD4+ cells 354+/-323.35 (p 0.0005 vs NC). The statistical analysis shows a direct correlation between TAC vs CD4+ cells; an indirect correlation between hydroperoxides vs CD4+ cells; not significant result between thiolic capacity vs CD4+ cells; finally, good correlations between TAC, hydroperoxides, and thiolic capacity vs HIV-RNA. The data obtained have proven that HIV+ patients present a condition of important oxidative stress. We may affi rm that this disease concurs with an increase of extreme stress; a condition in which the antioxidant defences are present, but are insufficient in neutralising the damaging actions of reactive species of oxygen, thus contributing to an acceleration in the natural history of HIV infections.

Prospective study of the effects of concomitant medications on thiopurine metabolism in inflammatory bowel disease.

BACKGROUND: Thiopurines are increasingly used in the treatment of inflammatory bowel disease (IBD), being the most common immunosuppressive therapy; however, potentially harmful interactions between thiopurines and other drugs (especially 5-aminosalicylic acid, 5-ASA) were described. AIM: To explore potential interactions between thiopurines and concomitant medications. METHODS: A total of 183 consecutive IBD patients were enrolled. Clinical characteristics and concomitant medications were recorded. Thiopurine metabolism was analysed with thiopurine S-methyl transferase (TPMT) genetic variants and enzyme activity assays. Comparisons were carried out with stratification of patients according to clinical characteristics and active treatments. RESULTS: Based on TPMT genetics, 95% IBD patients were wild-type homozygous, the remaining being heterozygous. Median TPMT activity was 24.9 U/Hgb g (IQR 20.7-29.5). No difference in TPMT activity was noted according to 5-ASA exposure. IBD patients on thiopurines had higher TPMT activity levels, but no dose-effect was evident. No difference in TPMT activity was observed in 41 (63%) patients co-treated with 5-ASA. In patients on active thiopurines also, 6-TGN and 6-MMP levels were evaluated and no significant difference was observed based on co-medication. TPMT activity was independently associated only with thiopurines dose (P = 0.016). CONCLUSIONS: Our data suggest the absence of significant interactions between thiopurines and 5-ASA.

Study of bone metabolism in patients with chronic HIV infection.

AIMS: Various studies have confirmed the high incidence of skeletal homeostasis modifications in subjects who are carriers of chronic HIV infections, and specific pharmacological treatments, which modify the metabolism and condition both the weight loss and the reshaping of the bones. The presence of a reduction in body mass index seems to contribute to the progressive deterioration of the skeletal framework. The aim of this study was to see whether the presence of HIV-seropositivity could constitute a risk factor for the development of osteoporosis/osteopenia, even in the light of the fact that our group was composed of patients with a concentrated age span well under the limit for both post-menopausal and senile osteoporosis, and with a median age superimposable for both sexes. MATERIALS AND METHODS: Our study involved 26 HIV+ patients with an average duration of infection equal to 6.7 +/- 4.8 years, and a range of seropositive duration between 6 months to 16 years. The prominent ultrasonometrical parameters are as follows: Broadband Ultrasound Attenuation, Speed of Sound, Stiffness Index or Quantitative Ultra-sound Index, Bone Mineral Density, and T-score. The biochemical study was carried out by assessing a marker of neoformation such as seric osteocalcine, and uninary pyridinoline and deoxipyridonoline as resorption markers. RESULTS: The results confirmed the presence of osteoporosis/osteopenia in 46% of the samples (11%, and 35%, respectively), with a progressive reduction in bone mineral density in relation to the duration of HIV infection. Assessment of the marker for bone metabolism showed a significant increase in osteocalcine in the female population compared to the males, without any significant variations in the normal values. CONCLUSIONS: Extreme variability in the morphological appearance at bone level during the course of HIV infection would lead us to believe that in the genesis of various forms, depending on the mechanisms and the time involved only in the parts defined, other attributable factors are responsible, not only for the progression of the core pathology and the possible interference of hormonal factors (behavioural and/or nutritional) directly correlated with the state of infection, but also for the dismetabolic effects of the antiretroviral drugs.

The role of endoscopic assessment in ulcerative colitis in the era of infliximab.

Endoscopic evaluation of mucosal appearance is important for the clinical management of ulcerative colitis patients, as it offers valuable prognostic tools and data useful to change the management and treatment strategies. In the field of severe ulcerative colitis, partial endoscopy and bioptic sampling allows to obtain additional and relevant prognostic information: if severe endoscopic lesions are present, response to standard treatment is less likely, and if CMV superinfection is detected, anti-viral treatment should be added to conventional treatments. When clinical remission is obtained with conventional treatments, distal colonoscopy may add valuable data: the occurrence of complete endoscopic healing is a major predictor of long-term remission with no clinical activity. Finally, biologic treatments, and mainly infliximab, were shown to induce remarkable and significant mucosal healing also in ulcerative colitis, and patients with complete endoscopic healing in response to infliximab were shown to be more likely to experience fewer clinical relapses during the follow-up. Therefore endoscopic evaluation has to be considered a major prognostic marker in ulcerative colitis. In this review data from the Literature supporting this role will be reviewed.

[Endoscopic ultrasound-fine needle aspiration (EUS-FNA) for pancreatic lesions: effectiveness in clinical practice]. / Agoaspirato con ago sottile sotto guida ecoendoscopica nelle lesioni pancreatiche: efficacia nella pratica clinica.

UNLABELLED: Endoscopic ultrasound-fine needle aspiration (EUS-FNA) was shown to be a highly reliable and a very effective diagnostic technique, both based on data from clinical trials and from large clinical practice studies. EUS-FNA results are reported to be in good-to-very good agreement with the final diagnosis, and the agreement significantly exceeded the chance agreement. The overall sensitivity and specificity of EUS and of EUS-FNA are very good. EUS-FNA is an effective diagnostic technique for the evaluation of pancreatic lesions, either reported with other imaging tests or suspected on the basis of clinical and biochemical features. EUS-FNA may be performed in most cases, and the results of EUS-FNA are particularly important for their excellent positive predictive value. Nonetheless, in a few cases EUS-FNA can not be feasible, or can give false negative or inconclusive RESULTS: The main practical consequence is that before referring patients to surgeons or oncologists, EUS-FNA should be considered as the best diagnostic strategy, since tissue is still the issue' . In a prospective two-centers consecutive series from Italy, FNA did not give any false positive diagnoses of malignancy, and reduced the number of indeterminate diagnoses; moreover, FNA significantly increased the specificity of diagnosis, while sensitivity was unchanged.

Endoscopic ultrasound-fine needle aspiration (EUS-FNA) for pancreatic lesions: effectiveness in clinical practice.

BACKGROUND: Diagnosis of pancreatic masses is often difficult. Endoscopic ultrasound-fine needle aspiration has been proposed as the best single-step strategy. AIMS: To prospectively evaluate feasibility, effectiveness and safety of endoscopic ultrasound-fine needle aspiration of pancreatic masses in a consecutive study of unselected patients. METHODS: Two hundred ninety-three patients were enrolled in two referral Hospitals in Northern Italy. All patients were referred either due to the presence of imaging test abnormalities (suspected or evident masses, or features indirectly suggesting the presence of a mass) or due to clinical or biochemical findings suggesting pancreatic cancer in the absence of positive imaging. All patients underwent linear array endoscopic ultrasound and, when indicated, fine needle aspiration. All procedures were recorded prospectively. The final diagnosis was established at the end of follow-up or when the patients underwent surgery or died. RESULTS: Fine needle aspiration was indicated in 246 of 293 cases (84%), considered technically feasible in 232 of 246 cases (94%) and gave adequate samples for histopathological diagnosis in 204 of 232 cases (88%). Endoscopic ultrasound sensitivity, specificity and accuracy were 79, 60 and 72%, respectively; the corresponding figures for endoscopic ultrasound-fine needle aspiration were 80, 86 and 82%. There was good agreement with final diagnosis for endoscopic ultrasound-fine needle aspiration (kappa 0.673, 95%CI 0.592-0.753), greater than that for endoscopic ultrasound alone (kappa 0.515, 95%CI 0.425-0.605). There was one case of intracystic haemorrhage and one case of transient hyperthermia (0.3%). CONCLUSIONS: Endoscopic ultrasound-fine needle aspiration of pancreatic masses seems to be feasible, effective and safe in this consecutive study of patients.

The hazardous burden of Herpesviridae in inflammatory bowel disease: the case of refractory severe ulcerative colitis.

BACKGROUND: Herpesviridae infection or spread may be a hazard in immunodepressed patients. In the field of inflammatory bowel disease, refractory severe ulcerative colitis is a challenging condition, closely associated to immunosuppression both for inanition due to the disease activity and for immunosuppressive treatments. Cytomegalovirus (CMV) has been proposed as a major cause of refractoriness, while other Herpesviridae may be a risk factor in the long-term follow-up. AIM OF THE STUDY: To evaluate the positivity rates of CMV, Epstein-Barr (EBV) and Human herpes virus-8 (HHV8) in a consecutive group of ulcerative colitis patients who underwent colectomy for refractoriness to medical treatment compared to a control group, using state of the art methods. PATIENTS AND METHODS: Colonic specimens from 24 consecutive patients with ulcerative colitis submitted to colectomy for refractoriness and from 20 controls (submitted to colectomy for colorectal cancer) were studied. Standard histology and immunohistochemistry (IHC) for CMV and specific polymerase chain-reaction (PCR) for CMV, EBV and HHV8 were carried out. RESULTS: Regarding CMV, 1 case (4%) was positive at histology and IHC, whereas 3 cases (13%) were positive at PCR, compared to none in the control group (p=0.239). For EBV 2 cases (8%) and 2 controls (10%) were positive at PCR. None of the cases or of controls was positive for HHV8. The only clinical characteristic independently associated to CMV positivity was the white blood cell count at admission, higher among CMV positive patients (p<0.001). At the end of the post-surgery follow-up (median 7.3 years) none of the CMV positive cases experienced pouchitis, compared to 3/21 (14%) of the CMV negative cases (p=1.000). DISCUSSION: Our data suggest that CMV is uncommon (13%), even though PCR techniques, considered to be the most sensitive tools, were used for virus detection and the study population is made by highly selected patients with definite refractoriness. EBV and HHV8 may represent a theoretical risk of immunosuppressive therapy because of their potential role as cancer triggers; however in our study, results seem to be reassuring that UC patients undergoing immunosuppressive therapy are not exposed to an excessive risk of viral infection.

Infliximab in the treatment of Crohn's disease: predictors of response in an Italian multicentric open study.

BACKGROUND: Almost 20% of patients with active Crohn's disease are refractory to conventional therapy. Infliximab is a treatment of proven efficacy in this group of patients and it is not clear which variables predict a good response. AIMS.: To evaluate the role of infliximab looking at the predictors of response in a large series of patients with Crohn's disease. PATIENTS AND METHODS: Five hundred and seventy-three patients with luminal refractory Crohn's disease (Crohn's Disease Activity Index (CDAI)>220-400) (312 patients) or with fistulising disease (190 patients) or both of them (71 patients) were treated with a dose of 5 mg/kg in 12 Italian referral centres. The primary endpoints of the study were clinical response and clinical remission for luminal refractory and fistulising disease. We evaluated at univariable and multivariable analysis the following variables: number of infusions, sex, age at diagnosis, smoking habit, site of disease, previous surgery, extraintestinal manifestations and concomitant therapies, and type of fistulas. RESULTS: Patients with luminal refractory disease: 322 patients (84.1%) had a clinical response and 228 (59.5%) reached clinical remission. Patients with fistulising disease: 187 patients (72%) had a reduction of 50% of the number of fistulas and in 107 (41%) a total closure of fistulas was observed. For luminal disease, single infusion (OR 0.49, 95% CI 0.28-0.86) and previous surgery (OR 0.53, 95% CI 0.30-0.93) predicted a worse response for fistulising disease. Other fistulas responded worse than perianal fistulas (OR 0.57, 95% CI 0.303-1.097). CONCLUSION: In Crohn's disease infliximab is effective in luminal refractory and in fistulising disease. A single infusion and previous surgery predicted a worse response in luminal disease whereas perianal fistulas predicted a better response than other type of fistulas.

Therapeutic ERCP in paediatric patients.

BACKGROUND: Major limitations of endoscopic retrograde cholangiopancreatography in paediatric populations are a low incidence of biliopancreatic disease among children, the equipment dimensions (size of endoscopes and devices) and the increasing role of MR-cholangiopancreatography in the field of diagnostic indications. Aim of this study was to evaluate the diagnostic and therapeutic yields of endoscopic retrograde cholangiopancreatography for biliopancreatic diseases in a paediatric population. METHODS: Between 1996 and 2002, 48 endoscopic retrograde cholangiopancreatographies were performed in 38 children aged 4 weeks to 17 years as part of the diagnostic evaluation for suspected pancreatic or biliary tract disease. Endoscopic retrograde cholangiopancreatography was carried out under general anaesthesia, using prototype paediatric duodenoscopes or standard duodenoscopes in children younger or older than 18 months, respectively. RESULTS: The indications to perform endoscopic retrograde cholangiopancreatography were common bile duct stones (14 children), biliopancreatic abnormalities (8), primary sclerosing cholangitis (2), Wirsung disruption (1), biliary leakage (1), cholestasis (4) and pancreatitis (8). Cannulation was successful in all patients but one. Sphincterotomy together with stone extraction or stent insertion was performed in 30/38 patients. Immediate complications were mild and treated conservatively. CONCLUSIONS: Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography can be used safely and effectively in the management of biliopancreatic diseases in childhood as well. Indications, endoscopic techniques and complications are similar to those reported for adult patients.

The role of endoscopy in inflammatory bowel disease.

Endoscopy is an essential tool for diagnosis, management and prognostic evaluation of inflammatory bowel disease. However dyscomfort, potential risks and costs associated to endoscopic examinations should contribute to the narrowing of indications to those cases in which the result of endoscopy is essential to determine a variation in the management strategy. Ileocolonoscopy performed by an expert endoscopist allows accurate diagnosis of Crohn's disease or ulcerative colitis in up to almost 90% of cases. Colonoscopy has a prognostic role during a severe flare of disease (the occurrence of severe endoscopic lesions have a negative prognostic value with significantly higher risk not to respond to medical treatment) both in ulcerative colitis and in Crohn's disease; moreover in Crohn's disease the evaluation of recurrent lesions at anastomosis after curative surgery has a strong prognostic role (endoscopic recurrence closely correlates with clinical/surgical recurrence) and preliminary data suggest that mucosal healing assessed with endoscopy after biologic treatments could be associated with a better prognosis. Finally colonoscopy is essential for cancer surveillance during the long-term follow-up. Furthermore there are new endoscopic techniques under evaluation in inflammatory bowel disease, like wireless capsule endoscopy or double balloon enteroscopy for the imaging of small bowel, or endoscopic ultrasound for evaluation of strictures or of perianal disease. Finally some operative techniques like balloon dilation could possibly be employed more frequently in the future in the management of Crohn's disease. Future perspectives in endoscopy for IBD are chromoendoscopy and newer endoscopic imaging techniques, possibly leading to an "in-vivo histology".

Review article: Crohn's disease: monitoring disease activity.

A global measurement of Crohn's disease activity, comprising clinical, endoscopic, biochemical and pathological features is not available yet and perhaps is unobtainable. In this review we analyse the most used and validated clinical indices (Crohn's Disease Activity Index [CDAI], Perianal Disease Activity Index [PDAI], fistula drainage assessment), quality of life scores (Inflammatory Bowel Disease Questionnaire [IBDQ]), sub-clinical markers (C-reactive protein, faecal calprotectin, intestinal permeability) and endoscopic indices (Crohn's Disease Endoscopic Index of Severity [CDEIS]/Simple Endoscopic Score for Crohn's Disease [SES-CD], Rutgeeerts' score for postsurgical recurrence). We also review the main advantages and disadvantages of each of these scoring systems. All these indices are rather complex and time-consuming, therefore their use is limited to clinical trials. In everyday clinical practice most gastroenterologists rely on their global clinical judgement, which is less reproducible, but simpler for decision-making.

Effectiveness of Helicobacter pylori eradication treatments in a primary care setting in Italy.

AIM: To evaluate the choice and relative effectiveness of Helicobacter pylori eradication regimens in a primary care setting. PATIENTS AND METHODS: Patients referred to our department, who had been treated for H. pylori infection during the preceding 6 months, were enrolled between September 1998 and July 1999. H. pylori status was assessed by urea breath test. Information on the drugs administered, compliance and side-effects was recorded. RESULTS: The mean eradication rate was 72% in patients receiving their first course of treatment (1863 cases; 45% male; mean age, 53 +/- 14 years); a double therapy regimen was prescribed to 14% of patients, triple therapy to 85% and quadruple therapy to 1%. Maastricht Consensus proton pump inhibitor-based regimens were prescribed in 80% of cases, with a mean eradication rate of 73%. No statistically significant correlation was found between eradication failure and sex, age, endoscopic findings or administered treatment. CONCLUSIONS: In Italy, in a primary care setting, first-line H. pylori eradication therapies reflect international guidelines. The efficacy of such regimens is lower than that reported by controlled trials. These results are relevant when making pharmacoeconomic evaluations of H. pylori management.

Modality of treatment and outcome of Helicobacter pylori infection in primary care. An Italian experience.

BACKGROUND: Aim of the present study was to evaluate the selection and the relative efficacy of H. pylori eradication regimens in primary care setting. METHODS: Patients referred to our Department, treated for H. pylori infection during the last 6 months, were enrolled during September 1998-July 1999. H. pylori status was assessed by urea breath test and recorded together with information about administered drugs, compliance, side effects. RESULTS: In patients undergone the first treatment course (1863 cases, 45% M, mean age 53+/-14 yrs) the mean eradication rate (ER) was 72%: a double therapy was prescribed in 14% of cases, a triple therapy in 85% and a quadruple in 1%. Maastricht Consensus PPI-based regimens were prescribed in 80% of total cases with a mean ER of 73%. No statistical significant correlation was found between eradication failure and sex, age or administered treatment. CONCLUSIONS: In Italy, in primary care setting: 1) first line H. pylori eradication therapies reflect international guidelines; 2) the efficacy of such regimens is lower than the one reported by controlled trials: such data should be kept in mind when pharmacoeconomic evaluations of H. pylori management are drawn.

Impact of urea breath test (UBT) in the management of H. pylori infection in a primary care setting.

BACKGROUND: Aim of the present study was to evaluate the use of UBT in a primary care setting. METHODS: From September 1998 to July 1999 we studied 2810 consecutive patients, referred to the Department of Gastroenterology, Mauriziano Hospital, Torino. A structured questionnaire was used to record information on demographic characteristics and clinical history. 13C-UBT was performed by means of isotope ratio mass spectrometer. RESULTS: The results shown that: 1) the main indication to perform UBT was the evaluation of treatment success (72% of cases); 2) in patients aged less than 45 years and never assessed before for H. pylori infection, UBT was used as first line procedure in 68% of cases: this finding stand for an initial adoption of the ''test and treat'' strategy; 3) first line H. pylori eradication therapies reflect international guidelines. CONCLUSIONS: The effectiveness of therapeutic regimens results to be decreased when translated into routine clinical practice.

[Cerebral hemorrhagic infarction caused by tubercular arteritis in HIV positive patient: a case report] / Considerazioni su di un caso di emorragia cerebrale da arterite tubercolare in soggetto HIV-positivo.

A case of cerebral hemorrhagic infarction caused by tubercular arteritis complicating the course of a tubercular meningitis in an HIV-positive patient is described. The atypical clinical course and histopathologic findings of this rare deadly complication of specific meningeal infection are underlined.