Search

Treatment of Helicobacter pylori infection is becoming a very relevant problem especially in industrialized Countries. Although different therapeutic regimens are currently available, treatment failure remains a growing problem in daily medical practice. Several factors could play a role in the eradication failure, but the most relevant are antibiotic resistance and patient's compliance. While Helicobacter pylori resistance to amoxicillin is rare, clarithromycin and metronidazole resistance varies significantly from close to zero up to 25%. However, metronidazole in vitro resistance exhibits a lower impact on eradication success because resistance in vitro does not reflect that in vivo. Specific guidelines have then been published, mostly based on antibiotic resistance among different geographic areas. Basically, first-line and second-line regimens have been well defined; concerning third-line treatment Maastricht III guidelines suggest to adopt a culture-based approach. Culture is, however, expensive, invasive and available only in few specialized centres. An alternative approach may be to use an empirical strategy, based on the avoidance of repeating similar eradicating schemes in the same patients during the course of different eradicating regimens. For this approach we propose the acronym DANCE (Different Antibiotic No Culture Eradicating) strategy. When correctly applied, this approach showed to reach successful eradication in up to 99.5% of Helicobacter pylori-positive patients.

Abdominal angina is an underrecognized cause of postprandial abdominal pain and weight loss. Diagnosis is often delayed and requires both a careful exclusion of more common causes and a high degree of clinical suspicion, based on the patient's age, the coexistence of multiple risk factors for atherosclerosis, and the presence of vasculopathy in other districts. Appropriate investigations include duplex ultrasound, traditional angiography, magnetic resonance angiography, computed tomography angiography, and tonometry. The purpose of this review is to discuss the pathophysiology and clinical presentation of chronic mesenteric ischemia and to suggest a diagnostic flowchart for this complex condition.

The digestive tract harbours the largest and most complex microbial community of the human body, the intestinal microbiota, including about 800 different bacteria species. The distribution of this microflora is uneven, with highest concentrations in the colon. Bacterial colonization of human gut by environmental microbes, beginning immediately after birth, becomes more complex with increasing age, with a high degree of variability among human individuals. The gastrointestinal tract is the main site where environmental microorganisms and antigens interact with the host, through intensive cross-talks. Gut microbiota is essential for intestinal development, homeostasis and protection against pathogenic challenge; moreover, gut microbes are involved in metabolic reactions, with harvest of energy ingested but not digested by the host; they have also trophic effects on the intestinal epithelium, by favouring the development of intestinal microvilli, and play a fundamental role in the maturation of the host's innate and adaptive immune responses.

Resume La maladie periodique (fievre familiale mediterraneenne) est une maladie hereditaire, a transmission autosomique recessive, faisant partie des maladies auto-inflammatoires. Elle est caracterisee par des episodes recidivants, de courte duree (en moyenne 24 a 72 heures) et de resolution spontanee, comportant de la fievre et l’inflammation d’une sereuse. La maladie periodique est la plus frequente des fievres periodiques au sein des maladies auto-inflammatoires qui constituent un groupe heterogene et recemment identifie, de maladies caracterisees par des acces febriles recidivants, sans auto-anticorps, ni lymphocytes T specifiques de l’antigene. Habituellement, les crises sont declenchees par des stimuli anodins et peuvent etre precedees d’une phase prodromique. Le gene responsable de la fievre familiale mediterraneenne, appelee MEFV, est situe sur le chromosome 16 (16p13) et code pour la proteine pyrine-marenostrine. Le mecanisme physiopathologique precis de la maladie periodique necessite d’etre encore determine. Le nouveau complexe macromoleculaire appele inflammasome, qui semble jouer un role tres important dans le controle de l’inflammation, pourrait etre implique dans la pathogenie de la maladie periodique. La complication la plus severe a long terme est l’amylose AA qui atteint surtout les reins et peut entrainer une insuffisance renale chronique. Des facteurs de risque, a la fois genetiques et non genetiques, du developpement de l’amylose secondaire ont ete identifies. Actuellement, le seul traitement efficace de la maladie periodique est la colchicine. De nouvelles molecules ont ete essayees chez des patients refractaires a la colchicine, mais des etudes supplementaires portant sur des effectifs suffisants sont necessaires avant d’aboutir a des conclusions formelles.

Background The optimal band imaging (OBI) system is a new technology that can select better spectral images decomposed from ordinary endoscopic images. This technology, first introduced as "FUJI Intelligent Color Enhancement," enhances the contrast of the mucosal surface without the use of dyes. Objective This study aimed to evaluate the potential of OBI for predicting the duodenal villous morphologic characteristics in patients with suspected celiac disease. Design This study was designed as an open, prospective, single-center trial. Duodenoscopy was performed with a high-resolution magnification view, in association with OBI spectral processing. Duodenal villous patterns were evaluated and classified as normal, partially atrophic, or markedly atrophic. The endoscopic results were then compared with the histologic diagnosis. Setting Endoscopy unit at the A. Gemelli University Hospital of Rome, Italy. Patients Sixty-one patients undergoing upper endoscopy for clinical history of malabsorption or serologic suspicion for celiac disease were included in the study. Results From OBI sets using red, green, and blue wavelength combinations that ranged from 400 to 580 nm, the endoscopist was able to find marked villous atrophy of the duodenum in 16 subjects, partial villous atrophy in 9 subjects, and normal villi in the remaining 36 subjects. The sensitivity, specificity, and positive and negative predictive values of the OBI-based duodenoscopy were 100% accurate in the evaluation of villous patterns. Conclusions High-resolution magnification endoscopy with OBI allows clear visualization of the duodenal villous pattern. The OBI system may play a potential role in optimizing the diagnostic accuracy of endoscopy in celiac disease.

Introduction Short-chain fatty acids affect enterocyte metabolism and differentiation. Butyric acid in particular is already used in ulcerative rectal colitis, pouchitis and antibiotic-induced diarrhoea. Aims To assess the efficacy of butyrate in the treatment of irritable bowel syndrome (IBS). Patients Fifty patients with IBS were treated using enteric-coated sodium butyrate tablets at a dosage of 1 g/day for 30 days. Methods The patients were divided into two subgroups: constipation-predominant IBS and diarrhoea-predominant IBS. The IBS variant and symptom scores of patients were recorded before and after treatment. Results Treatment with butyric acid reduced in normalisation of status in 68% and 71% of patients in the diarrhoea-predominant IBS group vs. 14% and 16% of patients in the constipation-predominant IBS group (respectively for the intent-to-treat and per-protocol analyses) (p Conclusions Oral administration of butyrate may be effective in regulating status and improving gastrointestinal symptoms in patients with the diarrhoea-predominant irritable bowel syndrome.

In recent years, particular attention has been paid to the role of the intestinal microflora in the multiple functions of the small intestinal (absorbent, secretory, immunological, endocrine, transport, barrier). The demonstrated beneficial effects of certain bacteria on human health has enabled probiotics antibiotics to be used for therapeutic purposes in a number of gastrointestinal diseases. Certain products of bacterial metabolism (e.g. butyrate) could provide further therapeutic weapons in a sector in which treatment has long proved difficult.

Background & Aims: A specific, occupation-related susceptibility of professional singers to experience gastroesophageal reflux was hypothesized. We investigated the prevalence of gastroesophageal reflux symptoms in a series of professional opera choristers in comparison with a general population sample. Methods: A total of 351 professional opera choristers from well-known choirs in different Italian regions were identified and a sample of 578 subjects residing in the same areas with a similar distribution in age and sex was selected. Reflux symptoms in the year preceding the survey together with selected individual characteristics and lifestyle habits were investigated in both study groups through a structured questionnaire. Prevalence rate ratios, adjusted for sex, age, body mass index, smoking status, alcohol consumption, and other confounding factors, were computed. Results: Opera choristers reported a statistically significant higher prevalence of heartburn, regurgitation, cough, and hoarse voice than the population sample, with adjusted prevalent rate ratios of 1.60 (95% confidence interval [CI], 1.32–1.94), 1.81 (95% CI, 1.42–2.30), 1.40 (95% CI, 1.18–1.67), and 2.45 (95% CI, 1.97–3.04), respectively. Regurgitation appeared to be associated consistently with the cumulative lifetime duration of singing activity (P = .04) and with the weekly duration of singing activity (P = .005) when different multivariate models were applied. Conclusions: Opera choristers reported a higher prevalence of reflux symptoms than the population sample. Future studies will be needed to clarify whether gastroesophageal reflux in professional opera choristers is stress-induced and therefore may be considered as a work-related disease.

Background Tissue homeostasis is guaranteed by stem proliferating reserve, depending on dynamic changes in gene expression. A high plasticity is shown by the haematopoietic stem cells, potential source for liver regeneration. Aim We aimed to evaluate the gene expression modifications induced by human haematopoietic stem cell therapy after liver injury in rats. Subjects Rats were sorted as follows: (A) human-haematopoietic stem cell injection after allyl alcohol liver damage; (B) only haematopoietic stem cell injection; (C) only allyl alcohol injection; and (D) sacrifice without any treatment. Methods Livers, spleens and bone marrows were analysed with flow-cytometry. Livers were also studied by reverse-transcription PCR, histology, immunohistochemistry and microarray analysis; selected genes were confirmed by real-time PCR. Results In subset A, haematopoietic stem cells were selectively recruited by liver, with respect to the group B, and they improved the liver regeneration process compared to group C. As regards microarrays, haematopoietic stem cell infusion upregulates 265 genes and downregulates 149 genes. Differentially regulated genes belong to a broad range of functional pathways, including proliferation, differentiation, adhesion/migration and transcripts related to oval-cell activation. Real-time PCR validated array results. Conclusions Our study confirmed the capacity of haematopoietic stem cells to contribute to liver regeneration. Moreover, microarray analysis led to the identification of genes whose regulation strongly correlates with a more efficient process of liver repair after haematopoietic stem cell injection.

Background Liver regeneration is a heterogeneous phenomenon involving the proliferation of different cell lineages in response to injury. Under a strong positive selection pressure bone marrow derived stem cells may be involved in this process, by making a contribution to both parenchymal restoration and endothelial cell replacement. We investigate bone marrow stem cell migration to the liver in patients undergoing hepatectomy or with acute on chronic liver failure. Methods We enrolled 6 patients submitted to hepatectomy, 6 patients to cholecystectomy and 8 patients with acute decompensation of liver cirrhosis. Mobilization of CD34+ cells was evaluated by cytofluorimetry on peripheral blood samples at different time points; baseline, 1, 3, 7, 15 and 30 days after surgery and at admission, 1, 7 and discharge among patients with acute on chronic liver failure. 10 healthy subjects undergoing blood donation were also enrolled to evaluated the basal value of CD34+ cells. Results White blood cell counts remained in the normal range (4.1–9.8 × 10 9 /L) in all groups throughout the follow-up. In all patients of Groups 1, 2 and 3, circulating CD34+ failed to show statistically significant differences both as the absolute number and as the percentage at any time point compared to healthy controls. Conclusions Bone marrow derived cell mobilization can not be detected after hepatectomy or during an acute decompensation on a cirrhotic liver. Under these circumstances liver regeneration can probably call upon mature hepatocytes and endogenous progenitor cells. The involvement of extrahepatic progenitors if any, is a rare and limited phenomenon.

Background and Aim Tissue homeostasis and turnover require reserve stem proliferating cells. Several studies performed on immunodeficient animals have suggested a degree of plasticity by the hematopoietic stem cell compartment that may represent source for liver regeneration. We sought to explore the hepatic differentiation potential of hematopoietic stem cells from human cord blood, after toxic liver damage induced by allyl-alcohol in immunocompetent rats. Materials and Methods Wistar rats were divided into groups (A) allyl-alcohol intraperitoneal injection with hematopoietic stem cell intraperitoneal infusion at 1 day and sacrifice 3 days later; (B) stem cell injection and sacrifice 3 days later; (C) allyl-alcohol infusion and sacrifice 4 days later; and (D) sacrifice without any treatment. Livers, spleens, and bone marrows were analysed for human stem cells using flow-cytometry; livers were also tested by histology and immunohistochemistry to study the pattern of hepatic regeneration after damage and human stem cell conversion into hepatocyte-like cells, respectively. Results Flow-cytometry revealed selective recruitment of human hematopoietic stem cells by damaged livers (group A) compared with control group B. In addition, liver damage was reduced in animals treated with stem cells. Immunohistochemistry demonstrated that human stem cells could convert hepatic cells. Conclusions Our study demonstrated that hematopoietic stem cells selectively recruited by injured livers can contribute to hepatic regeneration after acute toxic damage in immunocompetent recipients.

Background and aim Molecular adsorbent recycling system (MARS) treatment is able to remove both hydrosoluble and small- and medium-sized lipophilic toxins. MARS plays an important role in modifying liver failure complications, such as hepatorenal syndrome and hepatic encephalopathy. We sought to evaluate the clinical efficacy and safety of a MARS device in a consecutive series of hepatic failure patients. Materials Twenty patients with acute liver failure, transplantation failure, or acute on chronic liver failure fulfilled the inclusion criteria of total bilirubin ≥10 mg/dL and at least one of the following: hepatic encephalopathy (HE) ≥II grade, hepatorenal syndrome (HRS) for chronic patients or total bilirubin ≥5 mg/dL and HE ≥I grade for acute patients. Results MARS was able to reduce cholestatic parameters and improve neurologic status and renal function parameters in all treated patients. We also observed an improvement in the 3-month survival rate compared to the expected outcome in patients with MELD scores between 20 and 29, as well as 30 and 39. Conclusions Based on these results, we confirm the safety and clinical efficacy of MARS treatment, with the best results in patients with MELD score of 20 to 29. Further studies are necessary to confirm whether this treatment is able to modify patient outcomes and prognosis.

In the last years, a considerable number of studies have been performed on the correlation between Helicobacter pylori infection and ischaemic heart disease. The reason is the supposed role of some chronic infections in the genesis and development of vessel wall injury and atheromatous plaque, as already reported for Chlamydia pneumoniae and herpes viruses. While this association may be theoretically conceivable, it still remains debated from a practical point of view. Epidemiological and animal studies as well as some eradicating trials gave conflicting results, while studies investigating the specific molecular mimicry mechanisms induced by H. pylori strongly support the association. Moreover, none of the studies performed so far did take into account the effect of the genetic susceptibility to develop ischaemic heart disease or to respond to H. pylori infection. In particular, while the exposure to some known risk factor for atherosclerosis should lead to develop ischaemic heart disease, no condition or exposure, either individual or in combination, completely explains the occurrence and the progression of the disease, as many patients develop ischaemic heart disease in the absence of any risk factor. Based on these concepts, can we state that H. pylori infection may cause the same effect in patients with ischaemic heart disease as in healthy subjects? Further studies are needed in order to clarify this issue.

Background New generation videoendoscopes potentially may visualize duodenal villi. This study compared endoscopic findings with this type of instrument to the histopathologic evaluation of duodenal villi. Methods A total of 191 patients underwent upper endoscopy for the purpose of obtaining duodenal biopsy specimens. The findings were assessed independently by 3 experienced observers by using a commercially available, high-resolution, high-magnifying (×2) videoendoscope. The duodenal villous profile was determined by endoscopic magnification and by endoscopic magnification after filling the duodenum with water. With both endoscopic magnification and endoscopic magnification after filling the duodenum with water, villous patterns were scored as the following: definitely present, partially present, or definitely absent. Villous patterns also were histopathologically scored as the following: normal, partial villous pattern, or total villous atrophy. Results Interobserver variability was excellent (κ=0.93). The concordance between either endoscopic magnification or endoscopic magnification after filling the duodenum with water and histology was 100% for presence/absence of villi. The sensitivity, the specificity, and the positive and negative predictive values of endoscopic magnification for detection of any villous abnormality were 95%, 99%, 95%, and 99%, respectively; the respective values of endoscopic magnification after filling the duodenum with water were 95%, 98%, 92%, and 99%. Conclusions High-resolution magnifying upper endoscopy can reliably predict the presence or the absence of duodenal villi.

Background. Several studies have demonstrated that bone marrow contains a subpopulation of stem cells capable of participating in the hepatic regenerative process, even if some reports indicate quite a low level of liver repopulation by human stem cells in the normal and transiently injured liver. Aims. In order to overcome the low engraftment levels seen in previous models, we tried the direct intraperitoneal administration of human cord blood stem cells, using a model of hepatic damage induced by allyl alcohol in NOD/SCID mice. Methods. We designed a protocol based on stem cell infusion following liver damage in the absence of irradiation. Flow cytometry, histology, immunohistochemistry and RT-PCR for human hepatic markers were performed to monitor human cell engraftment. Results. Human stem cells were able to transdifferentiate into hepatocytes, to improve liver regeneration after damage and to reduce the mortality rate both in both protocols, even if with qualitative and quantitative differences in the transdifferentiation process. Conclusions. We demonstrated for the first time that the intraperitoneal administration of stem cells can guarantee a rapid liver engraftment. Moreover, the new protocol based on stem cell infusion following liver damage in the absence of irradiation may represent a step forward for the clinical application of stem cell transplantation.

Background. Ascites is one of the most frequent severe complications in patients with liver cirrhosis. The treatment of this chronic disease usually requires the prolonged use of albumin, frequently continued even after patients’ discharge from the hospital. Aims. Aim of the study was to define a consensus among Italian physicians with regard to the use of albumin in patients with decompensated cirrhosis and ascites. Methods. The study adopted the Delphi technique to conduct the consensus activities. All controversial issues related to the use of albumin were identified by the experts’ board and proposed to the 68 participating hepatology centres through two subsequent questionnaires. The questionnaires, returned by the specialists involved, were collected and the answers classified to verify the elements on which a consensus was reached. Results. The home use of albumin can help to improve the patient’s general conditions and well-being. About 77% of the experts involved considered likely that albumin administration could shorten hospital stays or could reduce the number of hospital admissions. The results of the study, along with a socioeconomic analysis, were presented to the Italian Drug Commission, which subsequently removed the specific hypoalbuminemia level as a prerequisite for having the drug reimbursed by the National Health Service. Conclusions. For an outpatient prescription, the hypoalbuminemia limit of 2.5 g/dl or less is not sufficient, while the decision whether to administer the drug requires the evaluation of patient’s overall clinical conditions as an essential criterion for the prescription of a home treatment with albumin.

Aims: There is contrasting evidence on the relevance of chronic infection by Helicobacter pylori ( H. pylori ) as a risk factor for stroke. We performed a meta-analysis of case-control studies to assess association of H. pylori infection and more virulent H. pylori strains, bearing the cytotoxin-associated gene-A (CagA) antigen, with different types of stroke. Methods: Outcome measures were: H. pylori and CagA seroprevalence in (1) patients with stroke versus controls, and (2) patients with stroke due to large vessel stroke versus patients with other types of stroke and controls. Results: Seven cross-sectional, case-control studies were included. Odds ratio for individual case-control studies and pooled OR for the association between H. pylori seropositivity and stroke was 1.49 (95% CI 1.24–1.81), for the association between stroke and anti-CagA positivity was 2.23 (95% CI 1.49–3.36). Patients with large vessel stroke had higher odds for H. pylori infection than patients with other types of stroke (odds ratio 1.65; 95% CI 1.12–2.45), and than controls (odds ratio 1.61; 95% CI 1.13–2.32). Conclusions: Association between H. pylori positivity, anti-CagA positivity and stroke is modest and seems higher with stroke due to large vessel disease. This meta-analysis suggests that the role of CagA positive H. pylori strains in different stroke etiologic subclasses should be the target of future prospective investigation.

Background. Liver surgery techniques have consistently improved and normothermic ischaemia of the liver is considered to be a safe procedure to reduce intraoperative haemorrhage. Hepatic failure, however, remains a significant complication. In liver ischaemia–reperfusion injury, cytokines play a key proinflammatory role. Cytokines may be part of the intercellular signalling that leads to recovery or to failure after major surgery. Moreover, they could be potential predictors of the outcome. Modulation of the pattern of cytokine response in the early postsurgery period could represent a new approach to minimise the impact of these procedures. Aims. The aim of our study was to analyse the cytokine pattern in the hepatic blood outflow in patients undergoing surgical intervention of partial liver resection with clamping of the hepatic pedicle and liver ischaemia, and to correlate the cytokine behaviour with clinical parameters. Patients. We studied eight patients (mean age 55 years) who underwent surgical intervention of liver resection during vascular exclusion of the hepatic pedicle. Patients were monitored for haemodynamic and haematological parameters during the pre-, infra- and postoperative period. Methods. IL-1 α, IL-6, TNF-α and IFN-γ were assayed from peripheral and central vein blood at different times. Blood samples for cytokine assays were also drawn from the supra-hepatic veins after clamping of the porta hepatis. Results. We found a significant increase of the IL-6 levels in the supra-hepatic samples during liver ischaemia, while the trend with IL-1α was less clear; IFN-γ and TNF-α were undetectable with the methods used. IL-6 levels appeared to correlate positively with bilirubin and γ-GT levels and negatively with the degree of acidosis. Conclusions. Our study confirms that during surgical ischaemic stress there is an increase of IL-6 serum levels more relevant in supra-hepatic vein blood. Cytokines could contribute to modulate the inflammatory response to liver ischaemia.

Background. Data concerning the usefulness and type of drugs employed to treat patients with primary sclerosing cholangitis are controversial. Ursodeoxycholic acid has been shown to be a useful agent, however the drug dosage and its effect on the clinical course are still under debate. Aim. To evaluate the efficacy of low-dose ursodeoxycholic acid in the treatment of primary sclerosing cholangitis. Methods. We retrospectively analysed data from 86 patients with primary sclerosing cholangitis from eight centres in Italy between 1987 and 1997: 69 were treated with ursodeoxycholic acid (8–13 mg/kg/day), while 17 received symptomatic treatment and served as controls. The effect of therapy was evaluated by standard liver function tests and symptom analysis. Results. Ursodeoxycholic acid treatment was associated with significant improvement in serum alkaline phosphatase (735±833 vs. 519±448 U/l, p

Background. Various endoscopic markers have been described in coeliac disease, particularly in the second part of the duodenum, with minor attention generally being paid to the duodenal bulb. Aims. To evaluate, prospectively, the presence of all endoscopic markers in the bulb and the second part of the duodenum on a large series of patients submitted to endoscopy for duodenal biopsy. Patients and Methods. A total of 367 consecutive patients, submitted to endoscopy with duodenal biopsy for various indications, were considered. Biopsies were graded as normal, with partial villous atrophy (mild, moderate, severe) or with subtotal villous atrophy. Endoscopic markers and corresponding locations evaluated were: micronodular pattern (bulb and descending duodenum), mosaic appearance (bulb and descending duodenum), scalloped folds (descending duodenum), reduced or absent folds (descending duodenum). Results. In 78 patients, a diagnosis of untreated coeliac disease was made. Endoscopic markers were seen in 73 78 patients, with only a single sign present (bulb or descending duodenum) in 12 patients. In the remaining 289 patients, normal histology and normal endoscopic findings were observed, except in two patients with reduced folds. Sensitivity, specificity, positive and negative predictive values and diagnostic accuracy regarding all endoscopic markers were 93.6%, 99.3%, 97.3%, 98.3% and 98.1 %, respectively. Conclusions. This study confirms the usefulness of endoscopic markers in detecting coeliac disease, underlining the importance of evaluating also abnormalities in the bulb and endoscopic single signs; although endoscopy may not detect all cases of coeliac disease, the recognition of endoscopic markers allows the selection for biopsy of unsuspected patients submitted to endoscopy for non-specific symptoms.

Alcohol withdrawal syndrome is a distressing and at times life-threatening condition in alcohol-dependent patients (1). Usually, symptoms develop within 6 –24 hours after the last drink (2). Early symptoms include raised blood pressure and pulse rate, tremor, hyperreflexia, and anxiety with increased irritability. Clinical management is aimed at symptom relief, prevention of seizures and delirium, and a smooth transition to a treatment program to maintain long-term abstinence from alcohol (3). Benzodiazepines are presently the drug of choice (4). We recently found that baclofen, a -aminobutyric acid (GABA)B receptor agonist used to control spasticity (5), reduced voluntary alcohol intake in alcohol-preferring rats (6), as well as alcohol craving and intake, up to complete alcohol abstinence, in alcohol-dependent patients (7). Furthermore, baclofen suppressed the intensity of alcohol withdrawal syndrome in rats who were physically dependent on alcohol (6). We therefore studied the effects of oral administration of baclofen in patients with severe alcohol withdrawal syndrome.

Background and aims: Interferon-α treatment has been the treatment of choice for chronic hepatitis with unpredictable results. Recently, Lamivudine has been licensed for use against HBV infection with good results. Unfortunately, recurrence of viremia after lamivudine withdrawal is common and prolonged treatment can induce the emergence of resistant mutant strains. It has been shown that vitamin E can increase the host immune response, and this may provide protection against infectious diseases. Methods: We evaluated vitamin E supplementation as therapy for chronic hepatitis B in a pilot study including 32 patients. Patients were randomly allocated to receive vitamin E at the dose of 300 mg twice daily for 3 months (15 patients) or no treatment (17 patients). They were seen monthly during the first 3 months and thereafter quarterly for additional 12 months. Results: The two groups were comparable at enrollment. At the end of the study period, alanine aminotransferase (ALT) normalization was observed in 7 (47%) patients in vitamin E group and only in 1 (6%) of the controls ( P =0.011); HBV-DNA negativization was observed in 8 (53%) patients in the vitamin E group as compared to 3 (18%) in the control group, respectively ( P =0.039). A complete response (normal ALT and negative HBV-DNA) was obtained in 7 (47%) patients taking vitamin E and in none of the controls ( P =0.0019). Conclusion: Vitamin E supplementation might be effective in the treatment of chronic hepatitis B.

The main objective in alcoholism therapy is to achieve and maintain abstinence and to prevent relapse. Pharmacotherapy may be necessary in treating persons who are not helped by group or psychosocial support alone. Among the substances experimented with in the past few years, gamma-hydroxybutyric acid has been effective in preventing alcohol withdrawal syndrome and in inducing a reduction in craving and an increase in the abstinence rate in treated alcoholics, in view of the alcohol-mimicking effects of the drug on the central nervous system. However, a possible development of craving for the drug and the risk of abuse and physical dependence have been reported in subjects who used gamma-hydroxybutyric acid for different reasons, including alcoholism therapy. The present review updates the existing differences in drug abuse behavior, side effects, and poisoning in the use of gamma-hydroxybutyric acid in a treatment alcoholism program and in self nonclinical illicit use.

Dicarboxylic acids (DA) are alternate lipid substrates recently proposed in parenteral nutrition. Two new derivatives of DA, a triglyceride of sebacic (TGC10) and one of dodecanedioic (TGC12) acid have been synthesised in order to reduce the amount of sodium given with the unesterified forms. The present paper describes a rapid and direct high-performance liquid chromatographic method (HPLC) for the analysis of these substances in both plasma and urine. Thirty-six male Wistar rats were rapidly injected with 64 mg of TGC10 or 53 mg of TGC12. The triglycerides and their products of hydrolysis were measured in plasma samples taken at different times. For the dose of 500 ng the intra-assay variations ranged from 6. 80+/-0.35% for TGC10 to 18.6+/-3.20% for TGC12 and the inter-assay variations were from 4.44+/-2.21% for TGC10 to 15.0+/-6.72% for TGC12. The detection limit for both triglycerides was 5 ng. This rapid and direct HPLC method could have practical implications in monitoring the concentration of both triglycerides and free forms of DA in biological samples of patients who might benefit from the administration of these substances during parenteral nutrition regimens.

Summary Background Helicobacter pylori is a common human pathogen implicated in certain gastrointestinal diseases. In the search for new non-invasive techniques to diagnose H pylori infection, we evaluated an EIA for H pylori antigen in stool (HpSA). Methods In a prospective multicentre study, stool specimens from 501 patients (276 men, 225 women; age range 17–88 years, mean 52) undergoing gastroscopy in 11 centres throughout Europe were tested with HpSA and the carbon-13-urea breath test. At endoscopy, four biopsy samples were taken for histology (haematoxylin and eosin) and H pylori detection (giemsa in both antrum and corpus, culture and rapid urease test). Patients were defined as positive for H pylori if histology (antrum, corpus, or both) and urease test were positive, or if culture was positive. Patients classified as having H pylori infection received an eradication regimen; 107 were reassessed 4 weeks after therapy. Findings Of 272 patients with H pylori infection by the predefined criteria, 256 were positive by HpSA (sensitivity 94·1% [95% CI 90·6–96·6]). Of 219 patients without infection, 201 were negative by HpSA (specificity 91·8% [87·3–95·1]). Interpretation The stool assay was a reliable and easy-to-use tool for diagnosis of H pylori infection. The test was accurate even shortly after treatment.

Background: Maculopapular and urticarial rashes are nonimmediate manifestations common during aminopenicillin (AP) treatment, and the former often represent cell-mediated hypersensitivity. Objectives: We sought to determine the significance and incidence of skin test reactions to APs in adults reporting adverse reactions during therapy with these β-lactams and, particularly, to evaluate the potential of patch tests, delayed-reading skin tests, and challenges in the diagnosis of nonimmediate reactions. Methods: We used skin tests with penicilloylpolylysine, minor determinant mixture, benzylpenicillin, ampicillin, and amoxicillin, as well as patch tests with the last 3 drugs. We also performed in vitro assays for specific IgE and challenges with the suspect penicillin in subjects with nonimmediate reactions. Results: Among the 144 patients reporting nonimmediate manifestations (mostly maculopapular rashes), delayed hypersensitivity was diagnosed in 62 on the basis of positive patch test and/or delayed intradermal test results and responses to challenges; negative reactions to challenges allowed us to reasonably exclude the possibility of allergy in 66 subjects, and the challenge confirmed that 1 patient had linear IgA bullous dermatosis. Definitive diagnoses could not be provided for the remaining 15 subjects, who had negative allergologic test results, because they did not consent to challenges. In 40 of 49 immediate reactors, a diagnosis of IgE-mediated hypersensitivity was made. Conclusions: Both patch and intradermal tests are useful in evaluating nonimmediate reactions to APs. Positive patch test and delayed intradermal responses together indicate delayed hypersensitivity. Intradermal testing appears to be more sensitive than patch testing, but the pattern of positive delayed intradermal test responses and negative patch test responses needs further investigation because of false-positive cases. (J Allergy Clin Immunol 1999;103:1186-90.)

Treatment of cardiac dysfunction associated with Churg-Strauss syndrome (CSS) is empiric since the histologic findings provided by endomyocardial biopsy are rare and often nondiagnostic. Myocardial necrotizing vasculitis presenting as restrictive cardiomyopathy has not been reported before. A case of CSS, presenting with fever and progressive heart failure due to pericarditis, eosinophilic endomyocarditis, and myocardial necrotizing vasculitis, is reported. Cardiac involvement assessed by noninvasive (cardiac two-dimensional echocardiogram and nuclear magnetic resonance [NMR] imaging) and invasive (cardiac catheterization, angiography, and biopsy) studies showed a moderate degree of pericardial effusion and left ventricular (LV) dysfunction (ejection fraction 0.40), severe diastolic dysfunction (increased right and LV filling pressure with a dip and plateau pattern) and a severe reduction of cardiac index (1.6 L/min/m2). Histologic characteristics showed marked eosinophilic infiltration of the endocardium and myocardium with myocitolysis and fibrinoid necrosis of arterioles, venules, and capillaries. Combination therapy of steroids and cyclophosphamide resulted in both a clinical (regression of pericardial effusion, normalization of systolic and diastolic dysfunction, and increase of cardiac index to 2.8 L/min/m2) and histologic (sequential endomyocardial biopsies at 1, 3, and 6 months of follow-up) resolution of cardiac involvement. No recurrences were registered at 12-month follow-up with the patient receiving a maintenance drug regimen.

Hereditary angioedema (HAE) is a noninflammatory disorder due to reduced C1-inhibitor level and/or function and characterized by recurrent, circumscribed, and self-limiting episodes of cutaneous and mucous membrane swellings involving different organs. A heterogeneous group of mutations in the C1-inhibitor gene have been found. HAE might present with diverse clinical pictures, even within families with the same mutation, but the cause of this variability is not known yet. We describe the case of type II HAE in a young adult presenting with recurrent abdominal pain for many years, occasionally associated with ascites. We suppose that an early weaning might have influenced his phenotype, making his gastrointestinal tract a “vulnerable organ,” in which hereditary angioedema could express itself.

Although in some cases delayed hypersensitivity may be observed, beta-lactam antibiotics frequently induce immediate allergic IgE-mediated reactions with the specificity localized in the acyl-side chain structure. Generally, delayed immunologic reactions are related to sensitized T lymphocytes and major histocompatibility complex restricted.To investigate the prevalence of HLA class I and II antigens in patients with delayed hypersensitivity to aminopenicillins in order to evaluate a relationship between major histocompatibility complex immune response genes and aminopenicillins hypersensitivity.We assessed 24 patients with history of delayed hypersensitivity to aminopenicillins using (1) skin test with penicilloyl polylysine, minor determinant mixture, benzylpenicillin, amoxicillin, and ampicillin; (2) patch tests with benzylpenicillin, amoxicillin, and ampicillin; (3) RAST for penicilloyls G and V; and (4) oral challenges with amoxicillin, ampicillin, and penicillin V in 18/24 patients. All patients were typed by microlymphotoxicity standard test for HLA class I and II antigens. Statistical analysis by chi2 test 2 x 2 contingency tables, according to Svejgaard, were used for comparison between patients and random Italian population (522 subjects).In the patients group we found higher prevalence of HLA A2 (12/24 = 50%, RR = 6.76 P.001, EF = 0.425), DRw52 (20/24 = 83.3%, RR = 9.28, P.001, EF = 0.74), and lower frequency of DR4 (3/24 = 12% ns).These data suggest that the immune mechanisms involved in adverse reactions to aminopenicillins in vivo are related to genetic markers of immune response and confirms that the presentation of penicillin-hapten determinants to lymphocyte is major histocompatibility complex restricted.

Dodecanedioic acid (C12) is an even-numbered dicarboxylic acid (DA). Dicarboxylic acids are water-soluble substances with a metabolic pathway intermediate to those of lipids and carbohydrates. Previous studies showed that contrary to other DAs, very low amounts of C12 are lost with urine. The effects of 46.6 mmol of C12 intravenous infusion for 195 min on blood glucose levels were investigated in five patients with non-insulin-dependent diabetes mellitus (NIDDM), with a good metabolic compensation, and in five healthy volunteers matched for gender, age, and body mass index. Blood samples were taken every 15 min for a period of 360 min to measure glucose, insulin, C-peptide, ketone bodies, and free fatty acid (FFA) levels, and 24-h urine samples were collected to measure C12 and urea excretion. Plasma and urinary C12 concentrations were determined by high-pressure liquid chromatography (HPLC). Indirect calorimetry was continuously performed both basally and during the study period. The average 24-h urinary excretion of C12 was 6.5% versus 6.7% of the administered dose, respectively, in NIDDM patients and in healthy controls. The area under the curve (AUC) values of plasma C12 were 279.9 +/- 42.7 mumol in NIDDM patients and 219.7 +/- 14.0 mumol in controls (P = ns). Plasma glucose levels significantly decreased in NIDDM patients during C12 infusion (from 7.8 +/- 0.6 to 5.4 +/- 0.8 mM at the end of the study period, P0.05). Lactate plasma concentration decreased in NIDDM patients from 3.5 +/- 0.2 to 1.5 +/- 0.1 mM (P0.001), whereas blood pyruvate increased at the end of the experimental session from 26.0 +/- 11.6 to 99.5 +/- 14.9 microM (P0.01). Free fatty acids decreased in diabetic patients from the beginning until the end of C12 infusion, although this difference did not reach statistical significance. No significant increase was found between basal and final values in VO2 consumption and in the values of nonprotein respiratory quotient in both groups of subjects examined. The experimental data indicate that C12 infusion decreases plasma glucose levels in NIDDM patients to normal range without influencing plasma insulin levels. The balance between pyruvate and lactate was affected by C12 infusion only in diabetics patients. C12 might represent a fuel substrate immediately available for tissue energy requirements, especially in conditions such as diabetes mellitus in which glucose metabolism is impaired.

Summary As in the literature data about the relationships between dementia and nutritional indices in oldest-old people are scarce, we evaluated the nutritional and cognitive status of 27 non-hospitalized, over 90-year-old women living in Bologna. Among them, 15 subjects were demented according to the guidelines of the American Psychiatric Association (DSM-III-R). Body mass index (BMI) was calculated as weight/height (kg/m). Fat mass percentage (FM%) was calculated from anthropometric measurements according to the Durnin-Womersley' formula. Serum albumin, vitamin D (1,25(OH) 2 D), and insulin-like-growth factor 1 (IGF-1) were also measured. No difference between demented and non demented people was found for BMI and serum albumin, whereas demented women had smaller values of FM%, 1,25(OH) 2 D and IGF-1. As demented women were also significantly older and less literate than normal women, the statistical significance of these differences was retested by ANOVA variance analysis adjusting for age and years of education. FM% (p = 0.017), 1,25(OH) 2 D (p = 0.004) and IGF-1 (p = 0.004) were all confirmed being significantly reduced in demented women. The conclusions are: (i) demented over 90-year-old women have an increased risk of mal-nutrition; (ii) although usually used in clinical routine, BMI and serum albumin seem to be less sensible nutritional indicators than the less commonly evaluated skinfold thicknesses, vitamin D and IGF-1.

Several hypotheses have been proposed to explain the nutritional deficiencies seen in Crohn disease patients, including inadequate food intake, decreased assimilation and increased loss of nutrients, and increased energy expenditure. To assess the effect of steroid therapy on body composition, energy expenditure, and fuel selection in Crohn disease, we compared 12 patients (6 men and 6 women) with biopsy-proven ileal Crohn disease with 11 healthy volunteers (6 men and 5 women). Five patients [Crohn's disease activity index (CDAI) = 98.4 +/- 3.78] took no medication and seven patients (CDAI = 283.9 +/- 22.5) were administered 29 +/- 18 mg prednisone/d. Body composition was evaluated by isotopic dilution and bioelectrical impedance analysis, and 24-h energy expenditure and basal metabolic rate were measured in a respiratory chamber. Fat-free mass was not significantly different among groups, whereas fat mass was lower in patients than in control subjects. Energy intake was higher in treated patients than in both untreated patients (P = 0.004) and control subjects (P = 0.005). Fecal losses were not significantly different between untreated patients and control subjects, but were higher (and proportional to the CDAI) in treated patients than in control subjects (P = 0.001). Metabolizable energy was not significantly different among groups, whereas energy balance was significantly higher in treated patients than in both control subjects (P = 0.0057) and untreated patients (P = 0.018). Nitrogen balance was mildly negative in treated patients compared with both control subjects and untreated patients, but not significantly so. In conclusion, prednisone treatment in Crohn disease patients stimulates food intake, promoting an overall positive energy balance despite large fecal nutrient losses.

In order to confirm the efficacy and safety of posatirelin ( l -pyro-2-aminoadipyl- l -leucyl- l -prolinamide), a synthetic peptide having cholinergic, catecholaminergic and neurotrophic activities, a multicentre, double-blind, controlled study versus placebo was planned in elderly patients suffering from Alzheimer's disease and vascular dementia, according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS–ADRDA) and National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS–AIREN) criteria, respectively. The trial consisted of a 2-week run-in phase with placebo administered once a day orally, followed by a double-blind period of 3 months, with posatirelin or placebo administered once a day intramuscularly. Efficacy was assessed using the Gottfries–Brane–Steen (GBS) Rating Scale (primary variable) and the Rey Memory Test (secondary variable). Laboratory tests, vital signs and adverse events were monitored. A total of 360 patients were randomized, the intent-to-treat sample (ITT) being made up of 357 patients and the per protocol sample (PP) of 260 patients. Both pragmatic and explanatory analyses showed significant differences between treatment groups in the GBS Rating Scale and the Rey Memory Test, with no difference in the two types of dementia. No difference between treatments was observed in safety variables, the incidence of adverse events in the posatirelin group being 7.3%. The study confirms previous results showing that treatment with posatirelin can improve cognitive and functional abilities of patients suffering from degenerative or vascular dementia.

Summary Background Autoimmune enteropathy is a condition described in children and characterised by villous atrophy, which is unresponsive to any dietary restrictions, and by the presence of enterocyte autoantibodies. We report two adult patients who fulfilled all the criteria for the diagnosis of this disorder. Methods Over the past 5 years we have seen four adult patients (all women, median age 51·5 [range 38–64] years) with subtotal villous atrophy, which was unresponsive to a gluten-free diet. The patients were HLA-DQ2 positive. IgA antigliadin and antiendomysial antibodies were not found in any of the patients. We did an indirect immunofluorescence search for enterocyte autoantibodies on monkey jejunum and for other autoantibodies for all four patients. Findings Of the four patients, two were positive for enterocyte autoantibodies and one of these two patients was positive for antiactin, antiparietal cell, and antithyroid microsomal autoantibodies. Interpretation To the best of our knowledge the two patients affected by severe enteropathy, who had never responded to any exclusion diet, and who were positive for enterocyte autoantibodies are the first cases of autoimmune enteropathy described in adults. We propose that adult patients whose disorders are unresponsive to a gluten-free diet should be tested for enterocyte autoantibodies.

The sensitivity of liver cells to anoxia is a major problem afflicting liver preservation and transplantation. Intermittent ischemia has been proposed to reduce reperfusion injury. The aim of the study was to assess oxygen free radical formation and cell injury during continuous or intermittent anoxia/reoxygenation in rat hepatocytes. Anion superoxide was measured by lucigenin-enhanced chemiluminescence and cell damage by LDH release and trypan blue uptake. During anoxia, superoxide generation dropped to background level in both groups; trypan blue uptake and LDH release, which increased progressively, were significantly greater in hepatocytes exposed to continuous compared to intermittent anoxia. During reoxygenation, a massive generation of superoxide anion formation, followed by a sharp increase in LDH release, was observed in both groups. However, both oxyradical generation and cell injury were significantly greater in cells exposed to continuous compared to intermittent anoxia. The data, showing that intermittent oxygen deprivation reduce liver cell injury and oxygen free radical formation determined by anoxia/reoxygenation, suggest a novel possible approach to the reduction of reperfusion injury.

Background: interferon-α is able to induce a sustained inhibition of hepatitis B virus replication in about 30–40% of patients with chronic hepatitis B. There is evidence that non-steroidal antiinflammatory drugs can enhance the synthesis of antiviral proteins induced by interferon-α, Aim: to evaluate the efficacy and tolerability of combined therapy with interferon-α plus indomethacin in HBeAg and HBV-DNA positive patients affected by chronic active hepatitis non-responders to a previous interferon-α treatment. Methods: after six months of retreatment with interferon-α (6 MU thrice weekly) six patients were enrolled, without stopping the therapy, to receive interferon-α (with the same schedule) plus indomethacin (25 mg orally twice daily) for an additional six month course. Results: at the end of treatment and after six months of follow-up alanine transaminase normalization was seen in three (50%) and four (66.7%) patients, HBV-DNA loss in one (17%) and three (50%), HBeAg HBeAb serum conversion in one (17%) and two (33%), respectively. The combined therapy was well tolerated and no indomethacin side-effects were observed. The treatment was stopped in one patient after 4 months because of a remarkable increase of alanine transaminase levels, and in another after five months because of hyperthyroidism occurrence. Conclusions: the results of this study, even if obtained in a small number of patients, are encouraging and suggest a randomized controlled trial to be confirmed.

Since no information is available on bone derangements in subclinical coeliac disease (CD), we evaluated bone mineral density (BMD, expressed as z score) at lumbar spine, by X-ray dual-photon absorptiometry, and serum indices of bone metabolism and remodeling in 14 subclinical or silent patients, 10 classical patients, and 15 healthy volunteers all on a gluten-containing diet. In the subclinical group, BMD at lumbar spine was significantly higher than in the classical group (-1.3 +/- 0.8, 73% vs. -2.6 +/- 0.6, 88%, respectively; p < 0.001), but significantly lower than in volunteers (+0.4 +/- 1.1, 104%; p < 0.001). Similar changes were observed in serum calcium, whereas, as regards parathyroid hormone, no significant difference was found between subclinical and classical patients. 25-vitamin D was significantly lower, and 1,25-vitamin D was significantly higher in subclinical and classical patients than in healthy volunteers. Indices of bone remodeling were higher in the subclinical and classical groups than in the volunteers, but lower in the subclinical than in classical patients. Eight subclinical and 8 classical patients were reexamined after a period of gluten-free diet (GFD), and in both groups BMD had significantly improved. Our results show that osteopenia is a frequent feature also in subclinical CD, although the extent of bone and mineral metabolism derangements is lower than in classical CD. GFD is able to normalize BMD in subclinical and to significantly improve it in classical patients.

Male aging is associated with alterations in plasma levels of antioxidants such as Coenzyme Q(10) (CoQ(10)) , and with a decrease of the fat-free body mass (FFM). In order to reveal, whether these changes can affect CoQ(10) metabolism, 73 non-obese, healthy males were studied, in age range 22-100 years, divided in 4 age groups: 20-55 (n = 23); 56-70 (n = 20); 71-90 (n = 8) and 91-100 (n =22). Serum CoQ(10) was measured by HPLC technique. Body composition was assessed by multifrequency bioimpedance analysis. Subjects aged 91-100 years displayed lower serum CoQ(10) levels and FFM than the other age-groups (p

Streptococcus bovis is one of the nonenterococcal species included among the streptococci group D. It is part of the normal bowel flora in humans and animals, but it is also responsible for infectious diseases (10-15% of all cases of bacterial endocarditis). Many cases of bacteremia and metastatic abscesses (spleen, liver, soft tissues, bone, meninges, endocardium) caused by S. bovis were reported as associated with digestive tract diseases, mainly colonic disease, and, in particular colonic neoplasms, or chronic liver diseases. A role in carcinogenesis has been suggested for this microorganism. The authors report two cases of S. bovis sepsis, one associated with colonic neoplasm and the other with liver cirrhosis and gastric carcinoma. Discussion is focused on probable mechanisms that favor gastric colonization and systemic diffusion of S. bovis from the gut in patients with gastrointestinal neoplasms or chronic liver disease and provides clinical recommendations for patients with S. bovis infections.

An improved gas-liquid chromatographic (GLC) method for the direct, simultaneous analysis of both medium chain monocarboxylic acids (MCFA) and medium chain triglycerides (MCT) is reported. The calibration curve of MCFA and MCT is linear in the range from 30 ng to 1000 ng. Five nanograms for tricaproin (MCT-6), 10 ng for tricaprylin (MCT-8) and 15 ng for tricaprin (MCT-9) represent the GLC detection limits of MCT, while those of MCFA range from 40 to 15 ng depending on their chain length: the longer the chain length, the higher the detection limit. The recovery of MCFA range from 79 to 99% and that of MCT from 85 to 99%. An example of plasma concentration curves of MCT and MCFA after an intravenous bolus injection of an MCT emulsion (100 mg MCT/kgbw) in a patient with Crohn's disease is shown.

Background & Aims: Several aspects of the pathogenesis of osteopenia in celiac disease are still unclear. Therefore, bone mass and metabolism were evaluated in adults with celiac disease in a cross-sectional study. Methods: Bone mineral density (BMD), assessed by total body dual-photon absorptiometry, and serum indices of bone metabolism and remodeling were evaluated in 17 patients with untreated celiac disease, 14 with celiac disease on a gluten-free diet, and 24 healthy volunteers. Results: BMD, expressed as a z score, was significantly lower in patients with untreated celiac disease than in patients with treated celiac disease and volunteers and lower in patients with treated celiac disease than in volunteers. Similar changes were observed in serum calcium level, whereas intact parathyroid hormone level was significantly higher in untreated than in treated patients with celiac disease and volunteers, and no difference was found between the latter two groups. 25-Vitamin D level was significantly lower and 1,25-vitamin D level significantly higher in untreated celiac disease than in treated celiac disease and volunteers. Indices of bone remodeling were significantly higher in untreated than in treated patients and volunteers and significantly and positively correlated with iPTH in untreated patients with celiac disease. Conclusions: BMD is almost invariably low in patients with untreated celiac disease. Results in treated patients suggest that gluten-free diet improves but does not normalize BMD. Untreated celiac disease is characterized by high levels of 1,25-vitamin D and by increased bone turnover, caused by the increase in intact parathyroid hormone level.

Coeliac disease is a chronic disease characterized by small bowel villous atrophy which impairs nutrient absorption and improves on withdrawal of wheat gliadins and barley, rye and oat prolamins from the diet. Knowledge of the adult form of coeliac disease has greatly improved in recent years. Although this knowledge is not yet sufficiently widespread among referring clinicians, it has, over the past few years, allowed an increasing number of patients to be diagnosed with subclinical forms characterized by minor, transient or apparently unrelated symptoms. As a consequence, our views on the clinical and epidemiological aspects of this condition, the prevalence of which in the general population is believed to be close to 1 in 300, have changed and are still changing. Since it has been demonstrated that a strict gluten-free diet is protective against the complications of adult coeliac disease, it is important that even subclinical and silent forms are diagnosed and treated as early as possible. Non-invasive screening tests, such as anti-gliadin and anti-endomysium antibody estimation, should therefore be used systematically in groups considered to be at risk of coeliac disease. These include first-degree relatives of coeliac patients and patients with insulin-dependent diabetes mellitus, iron-deficiency anaemia, epilepsy with cerebral calcification, recurrent aphthous stomatitis and dental enamel hypoplasia. Other conditions will probably be identified in the near future.

Background/Aims: We studied the effects of ascites apheress, concentration and reinfusion, a new form of treatment for tense or refractory ascites, on systemic hemodynamics and renal function. Methods: Twelve patients with advanced cirrhosis (two belonging to Child-Pugh's class B and the remainder to class C) were monitored. They were evaluated under baseline conditions, just after the treatment, and 24 and 48 h after baseline assessment. In addition to systemic hemodynamics — as evaluated by Doppler echocardiography — and renal function, indirect markers of effective volemia, such as atrial natriuretic factor, plasma renin activity and aldosterone concentration, and plasma norepinephrine were also measured. Results: The technique led to significant changes in systemic hemodynamics, such as an increase in stroke volume and cardiac output. However, due to a striking reduction in peripheral vascular resistance, mean arterial pressure also declined. The hemodynamic changes were associated with a parallel increase in atrial natriuretic factor. Despite the reduction in arterial pressure, plasma renin activity also significantly declined, while plasma norepinephrine did not undergo significant changes. Although an improvement in glomerular filtration rate and renal sodium excretion occurred, neither change reached statistical significance. All the hemodynamic, renal and neuro-humoral changes described above subsided almost entirely after 48 h, when no significant changes with respect to baseline values were any longer detectable with the exception of a slight reduction in mean arterial pressure. Conclusions: In advanced cirrhosis ascites apheresis, concentration and reinfusion enhance central volemia, but an exaggerated peripheral vasodilation largely wastes the potential favourable effect on arterial volemia. As a result, no significant improvement in renal perfusion and sodium excretion can ensue.

Interferon-α (IFN-α) stimulates the synthesis of antiviral proteins, such as 2′,5′-oligoadenylate synthetase (2′5′-OAS), and activation of arachidonic acid (AA) metabolism seems to constitute the post-receptorial signal induced by this cytokine. We evaluated the in vitro effect of IFN-α, indomethacin (an inhibitor of cyclooxygenase pathway of AA) and IFN-α plus indomethacin on 2′5′-OAS release by cultured liver biopsies of patients with active or inactive HCV infection and uninfected patients with various liver diseases. The results demonstrated that basal 2′5′-OAS release was significantly higher in patients with active HCV infection with respect to uninfected ones. In two HCV-Ab positive but HCV-RNA negative patients, basal 2′5′-OAS was similar to uninfected patients. In HCV-RNA positive patients, indomethacin alone was able to significantly increase the 2′5′-OAS production in a similar fashion to IFN-α alone, while a synergistic effect on 2′5′-OAS increase was seen when biopsies were cultured with IFN-α plus indomethacin. A similar trend was observed in the uninfected and in the HCV-Ab positive but HCV-RNA negative patients, even if the increase did not reach statistical significance. These results confirm the interaction between IFN-α and AA metabolites and suggest an evaluation of the in vivo response of IFN-α plus nonsteroid antiinflammatory drugs combined therapy.

Licorice can induce a hypermineralocorticoid syndrome. Current literature usually refers to the effects of sweets containing glycyrrhizin, but little is known about the consequences of a prolonged intake of "pure licorice". We administered graded daily doses of dried, aqueous extract of licorice root, containing 108, 217, 380 and 814 mg of glycyrrhizin, to 4 groups of 6 healthy volunteers of both sexes for 4 weeks. No significant effects occurred in groups 1 and 2. After 2 weeks, side effects leading to withdrawal from the protocol occurred in a female in group 3 (headache), a male with a family history of hypertension in group 4 (arterial hypertension), and a female also taking oral contraceptives in group 4 (hypertension, hypokalaemia and peripheral edema). In group 4, transient reduction in kalaemia and increase in body weight were found after 1 and 2 weeks, respectively. A depression of plasma renin activity occurred in groups 3 and 4. In healthy subjects, only the highest doses of licorice led to untoward effects. These were favoured by subclinical disease or oral contraceptives, and were less common and pronounced than what has been reported after the intake of glycyrrhizin taken as such or as a flavouring agent in confectionery products.

We recently showed that patients with compensated cirrhosis can dispose of their fluid overload while reclining. In contrast, patients with ascites fail to develop supine-induced natriuresis. To assess the effect of reclining on renal sodium handling in patients with advanced cirrhosis and the mechanisms blunting natriuresis in this situation, renal function and plasma concentrations of atrial natriuretic factor, aldosterone and norepinephrine were evaluated in 10 nonazotemic patients with cirrhosis and ascites and 10 healthy controls standing for 2 h and reclining for 2 h. While standing, all patients showed marked sodium retention and significantly elevated plasma atrial natriuretic factor levels, aldosterone and norepinephrine. Glomerular filtration rate did not differ from healthy controls. The reclining increased renal sodium excretion in both groups, but this change was far less marked in patients; natriuresis only rose to the control range in two of them. An increase in atrial natriuretic factor and a depression of plasma aldosterone and norepinephrine was seen in both controls and patients. In the latter, despite the greater change in atrial natriuretic factor and aldosterone, the aldosterone to atrial natriuretic factor ratio, which was inversely correlated with natriuresis during both standing and reclining remained significantly elevated. In the two patients who achieved normal natriuresis during reclining, reclining was associated with both the normalization of the aldosterone/atrial natriuretic factor ratio, and with an increase in glomerular filtration rate. The supine-induced increase in atrial natriuretic factor was not only preserved but was even enhanced in cirrhosis with ascites. In most cases, however, this was not associated with a large enough shift in the plasma aldosterone/atrial natriuretic factor balance to prime clinically significant natriuresis. To achieve this result, suppression of aldosterone secretion, supernormal release of atrial natriuretic factor and improvement of renal perfusion pressure have to concur.

We assessed the efficacy of treatment with Bacillus subtilis in modifying the clinical symptoms and hydrogen (H 2 )-producing capacity of 17 patients with functional bloating, following ingestion of 20 gm of lactulose. Cumulative H 2 excretion ( P 2 concentration ( P P 4 ) concentrations were higher after therapy, although the increase was not significant. Mouth-to-cecum transit time and fecal pH levels did not change after B subtilis treatment. Our data suggest that in patients suffering from functional bloating, treatment with B subtilis is a new and effective therapeutic approach to treatment. The active mechanism may be the development of CH 4 -producing intestinal flora and thus an increase in H 2 consumption rate.