Randomized, double-blind, placebo-controlled trial to evaluate the effect of Helicobacter pylori eradication on glucose homeostasis in type 2 diabetic patients.

BACKGROUND AND AIMS: Literature data suggest an association between Helicobacter pylori infection and glucose homeostasis. However, a causative link between them has not been demonstrated yet. The aim of this study is to investigate the effect of H. pylori eradication on glucose homeostasis in patients with type 2 diabetes. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled trial was conducted to investigate the effect of H. pylori eradication on glucose homeostasis in 154 patients with type 2 diabetes and who tested positive for H. pylori infection (mean age (SD), 63.1 (8.1) years). Subjects were assigned to H. pylori eradication treatment or placebo. Metabolic and inflammatory parameters were measured in all subjects at baseline and 4 weeks after the treatment. H. pylori eradication led to an improvement in glucose homeostasis, measured by HOMA-IR (p < 0.001) and KITT (0 = 0.041), due to the decrease in fasting insulin levels (p = 0.004). The results also showed that lower levels of inflammatory parameters were present after eradication. CONCLUSION: To our knowledge this is the first randomized, double blind, controlled study where the effect of H. pylori eradication on glucose homeostasis in subjects with type 2 diabetes has been investigated. Our findings demonstrate that H. pylori eradication improves glucose homeostasis in patients with type 2 diabetes through a decrease in pro-inflammatory factors. TRIAL REGISTRATION NUMBER: ACTRN12609000255280 (https://www.anzctr.org.au/).

Infection with Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae in cancer patients.

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) is an emergent pathogen in healthcare-associated infections (HAIs). The aim of this study was to describe HAIs due to KPC-Kp, as well as identify mortality risk factors in cancer patients. In patients diagnosed with HAIs due to KPC-Kp between January 2009 and July 2013, we evaluated only the first infection episode of each patient, analyzing mortality separately for patients treated for ≥48 h with at least one antimicrobial agent proven to display in vitro activity against KPC-Kp. We evaluated variables related to the malignancy, the severity and characteristics of the HAI, and the antimicrobial therapy. We identified 83 HAIs due to KPC-Kp. The 30-day mortality was 57.8 % for all infections and 72.7 % for bacteremic infections. Of the 83 patients, 60 patients received ≥48 h of appropriate treatment and 44 (53 %) developed bacteremia. Ten patients (12 %) were neutropenic at HAI diagnosis and 33 (39.8 %) had infection at the tumor site. The most common HAI was urinary tract infection, seen in 26 patients (31.3 %), followed by primary bloodstream infection, seen in 24 patients (28.9 %). Forty-four patients (73.3 %) received combination antimicrobial therapy, most often including polymyxin (68.3 %). Risk factors for 30-day mortality are high sequential organ failure assessment (SOFA) score, need for intensive care stay at diagnosis of infection, and acute kidney injury; the removal of invasive devices related to infection and treatment with effective antibiotics for KPC-Kp are protective factors. In cancer patients, high mortality is associated with HAI due to KPC-Kp and mortality risk factors are more often related to acute infection than to the underlying disease.

Polymyxin use as a risk factor for colonization or infection with polymyxin-resistant Acinetobacter baumannii after liver transplantation.

INTRODUCTION: Acinetobacter baumannii is a leading agent of healthcare-associated infection. The objective of this study was to evaluate cases of colonization or infection with polymyxin-resistant A. baumannii (PRAB) in liver transplant recipients and to identify the risk factors for the acquisition of PRAB. METHODS: We evaluated all patients undergoing liver transplantation (LT) between January and November of 2011. The exclusion criterion was death within the first 72 h after transplant. Patients were screened for PRAB through weekly rectal and inguinal swabs during their stay in the intensive care unit (ICU) and at ICU discharge. Patients who came from other hospitals or had been treated in the emergency room for >72 h were screened at ICU admission. The minimum inhibitory concentrations (MICs) for polymyxins were determined by broth microdilution, and clonality was determined by pulsed-field gel electrophoresis. The stepwise logistic regression was used to identify risk factors related to acquisition of PRAB, and Cox forward regression used to identify risk factors for 60-day mortality. RESULTS: We evaluated 65 patients submitted to LT, among whom PRAB was isolated in 7, 4 of whom developed infection. The MICs for polymyxin E ranged from 16 to 128 mg/mL. All patients with PRAB required dialysis. The median time of polymyxin use before PRAB isolation was 21 days. These 4 included 1 case of primary bloodstream infection (BSI), which was treated with the carbapenem-polymyxin combination; 1 case of surgical site infection, which was treated with gentamicin, polymyxin, ampicillin-sulbactam, and tigecycline; and 2 cases of pneumonia, treated with the combination of carbapenem-polymyxin. In the case of BSI and in 1 of the cases of pneumonia, the treatment was considered successful. Mortality was 71% among the cases, compared with 33% among the non-cases. CONCLUSION: In the final model of the survival analysis, PRAB colonization or infection after LT was independently associated with mortality. One predominant clone was identified. The only risk factor identified in the multivariate analysis was polymyxin use. PRAB was an agent with high mortality, and the most important risk factor associated with colonization or infection for such bacterium was polymyxin use.

Endemic and opportunistic infections in Brazilian solid organ transplant recipients.

OBJECTIVE: To evaluate the frequency and clinical features of endemic and other opportunistic infections in liver or kidney transplant recipients in four transplant centres in different geographical areas of Brazil. METHODS: Retrospective analysis of medical and laboratory records of four transplant centres on endemic and other opportunistic infections in liver or kidney transplant recipients. Analyses were performed with spss statistical software. RESULTS: From 2001 to 2006, 1046 kidney and 708 liver transplants were registered in all centres. The average age was 42 years. Among 82 (4.7%) cases with infections, the most frequent was tuberculosis (2.0%), followed by systemic protozoal infections (0.7%), toxoplasmosis (0.4%) and visceral leishmaniasis (0.3%). Systemic fungal infections occurred in 0.6%, of which 0.4% were cryptococcosis and 0.2% were histoplasmosis. Dengue was the only systemic viral infection and was registered in two cases (0.1%), of which one was classified as the classic form and the other as dengue haemorrhagic fever. Nocardiosis was described in one case (0.05%). The infectious agents most frequently associated with diarrhoea were Blastocystis sp., Schistosoma mansoni and Strongyloides stercoralis. CONCLUSIONS: Opportunistic Infections in transplant patients have a wide spectrum and may vary from asymptomatic to severe infections with high mortality. A better understanding of the epidemiology of endemic pathogens and clinical manifestations can contribute to the establishment of an early diagnosis as well as correct treatment aimed at decreasing morbidity and mortality.

Fluoroquinolone treatment as a protective factor for 10-day mortality in Streptococcus pneumoniae bacteremia in cancer patients.

To evaluate the prognostic factors in adult cancer patients with pneumococcal bacteremia, describe episode features and the phenotypic characteristics of the isolated strains. We evaluated the episodes in patients admitted to a cancer hospital between 2009 and 2015. The outcomes were defined as 48 h mortality and mortality within 10 days after the episode. The variables evaluated were: age, sex, ethnicity, ECOG, Karnofsky score, SOFA, cancer type, metastasis, chemotherapy, radiotherapy, neutropenia, previous antibiotic therapy, community or healthcare-acquired infection, comorbidities, smoking, pneumococcal vaccination, infection site, presence of fever, polymicrobial infection, antimicrobial susceptibility, serotype and treatment. 165 episodes were detected in 161 patients. The mean age was 61.3 years; solid tumors were the most prevalent (75%). 48 h and 10-day mortality were 21% (34/161) and 43% (70/161) respectively. The 48 h mortality- associated risk factors were SOFA and polymicrobial bacteremia; 10-day mortality-associated risk factors were fever, neutropenia, ECOG 3/4, SOFA and fluoroquinolones as a protective factor. Pneumococcal bacteremia presented high mortality in cancer patients, with prognosis related to intrinsic host factors and infection episodes features. Fluoroquinolone treatment, a protective factor in 10-day mortality, has potential use for IPDs and severe community-acquired pneumonia in cancer patients.

Management and outcomes of hepatic cirrhosis: Findings from the RING study.

BACKGROUND/AIM: Hepatic cirrhosis is a frequent reason for ordinary hospital admission (OA). The RING study collected hospital discharge files (HDF) from Italian hospital gastroenterology units (IGU). This caselist provides a broad picture of the patients admitted for this pathology. MATERIAL/METHODS: More than 50,000 HDF for OA were collected between 2001 and 2004 from 26 IGU. RESULTS: Eight thousand four hundred and eighty-seven HDF (16%) had a diagnosis of hepatic cirrhosis; Child-Pugh classes were 20.2% A, 34.8% B and 45.0% C. Patients' mean age was 63.7+/-12.1 years and 62.5% were male. A 61.1% of the cirrhosis cases had ascites, 29.9% portal-systemic encephalopathy, 29.2% hepatocellular carcinoma (HCC), 10% bleeding varices, 3.0% hepatorenal syndrome (HRS). Mortality for OA for cirrhosis was 5.7% versus 2.6% for other diagnoses. The proportion varied with the severity of the cirrhosis: 0% for Child A, 1.1% B, 10.5% C. Mortality was significantly associated with: Child-Pugh at admission (odds ratio: OR 9.2), HRS (OR 11.7), bleeding varices (OR 2.2), HCC (OR 1.8). CONCLUSIONS: Hepatic cirrhosis was found in 16% of the OA to IGU and mortality was double the rate for all the other pathologies in the same wards. Child-Pugh is a useful prognostic tool, higher classes implying a greater risk of death. HRS and bleeding varices were the complications with most influence on in-hospital mortality.

Gastric emptying and intragastric balloon in obese patients.

BACKGROUND: Intragastric balloons have been proposed to induce weight loss in obese subjects. The consequences of the balloon on gastric physiology remain poorly studied. We studied the influence of an intragastric balloon on gastric emptying in obese patients. PATIENTS AND METHODS: 12 patients were included in the study, with BMI (mean +/- SD) of 38.51 +/- 4.32 kg/m2. The balloon was inserted under light anaesthesia and endoscopic control, inflated with 700 ml saline, and removed 6 months later. Body weight and gastric emptying (T1/2 and T lag) using 13C-octanoic acid breath test were monitored before balloon placement, during its permanence and 2 months after removal. RESULTS: Mean weight loss was: 6.2 +/- 2.3 kg after one month; 12.4 +/- 5.8 kg after 3 months; 14.4 +/- 6.6 kg after 6 months and 10.1 +/- 4.3 kg two months after BIB removal. Gastric emptying rates were significantly decreased in the first periods with balloon in place, and returned to pre-implantation values after balloon removal. T1/2 was: 87 +/- 32 min before BIB positioning, 181 +/- 91 min after 1 month, 145 +/- 99 min after 3 months, 104 +/- 50 min after 6 months and 90 +/- 43 min 2 months after removal. T lag was 36 +/- 18 min before BIB positioning, 102 +/- 82 min after 1 month, 77 +/- 53 min after 3 months, 59 +/- 28 min after 6 months and 40 +/- 21 min. 2 months after removal. CONCLUSIONS: BIB in obese patients seems to be a good help in following the hypo caloric diet, especially during the first three months when the gastric emptying is slower and the sense of repletion is higher. After this period gastric emptying starts to return to normal and the stomach adapts to BIB loosing efficacy in weight loss.

Pharmacokinetic studies of ethylediaminetetraacetic acid (EDTA) in rats.

A gas chromatographic assay of ethylenediaminetetraacetic acid (EDTA) in rat serum and urine has been developed. The procedure involves benzene extraction of the sample, and uses the internal standard technique for determining EDTA concentrations in biological samples. The pharmacokinetics of EDTA was investigated in rats after i.v. injection of 5 and 50 mg/kg or oral administration of 50 and 250 mg/kg. No significant dose-related differences were between the mean biological half-lives (ranging between 21.6 and 22.9 min). EDTA was extracted in rat urine within 24 h of either i.v. dose, and within 80 min of the 50 mg/kg and 3 h of the 250 mg/kg or oral doses. In the applications described the analytical limit of sensitivity is 0.5 microgram/ml of rat serum of urine.

[Odontostomatogenic focal disease; embryologic and clinical causes of autoimmune pathogenesis]. / La malattia focale odontostomatogena; motivazioni embriologiche e cliniche della patogenesi autoimmune.

The autoimmune pathogenesis of the focal odontostomatogenous disease is investigated and emphasis is laid on the different keys of interpretation: at embryologic, clinic and immunologic level. A special attention is paid to the primary meaning of structured or non structured lymphoid tissue of oropharynx, on account of embryologic identity with thymus and bursa of Fabricius, differentiating into sectors of ecto-entodermic stratification. The clinical evidence of the bursa-equivalent significance of Waldeyer ring, appears to lie in the ascertainment of the tonsillar atrophy in course of agammaglobulinaemia of Bruton type. The active chronic irritant phlogistic stimulus in a primary structure could excite the normal production of intolerant clones, so as to exceed the normal physiological homeostasis (giving rise to the autoimmune disease), or alter the mosiac self, inducing a production of autoantibodies.

Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference.

BACKGROUND: Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. AIM: The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. METHODS: Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. RESULTS AND CONCLUSIONS: The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.

Effect of chenodeoxycholic acid on the alterations of biliary lipid secretion induced by ethynylestradiol in the rat.

The role of chenodeoxycholic acid (CDCA) in modifying the biliary secretory alterations induced by ethynylestradiol (EE) was evaluated in male Sprague-Dawley rats. Bile flow and bile acid output were both decreased in rats given EE either alone or with CDCA (EE + CDCA) whereas cholesterol output showed a significant decrease only in animals given the combined treatment. The output of phospholipids remained unchanged in all groups. As a result the lithogenic index was significantly decreased in EE + CDCA-treated rats. In urine, the total bile acid excretion was significantly increased in EE + CDCA-treated animals. The data indicate that in the rat, biliary secretory failure induced by EE is not modified by CDCA, but that CDCA may prevent the increase of biliary cholesterol saturation caused by EE.

The interaction of rifamycin-SV with the hepatic transport and sulfation of taurolithocolic acid in rats.

Sulfated and non sulfated lithocholic acid were analyzed in serum, bile and urine of bile-fistula Sprague-Dawley female rats by gas-liquid chromatography and thin-layer chromatography. In rats (group A) bile was collected during a 3 h saline infusion followed by a 3 h intravenous infusion of taurolithocholate; animals of group B and C were infused with both taurolithocholate and rifamycin-SV, but in the animals of group C the renal pedicles were ligated. Serum bile acids showed a significant increase only in animals of group C, during the infusion of rifamycin-SV. In bile of animals of group A sulfated lithocholic acid represented 18% of total, but was not found in bile of animals of group B and C, while a significant increase of sulfated lithocholic acid was evident in urine of animals of group B. The results indicate that rifamycin-SV probably interferes with the hepatic secretion of sulfated lithocholic acid in the rat.

Bile acid analysis: a rapid and sensitive gas-liquid chromatographic method.

A sensitive and fast method is described for quantitative determination of bile acids by gas-liquid chromatography. Using hexafluoroisopropanol plus trifluoroacetic anhydride for the derivatization of bile acids, several steps are reduced in the preparation of samples, so that the procedure is shortened and the recovery is improved. Free, conjugated and sulfated bile acids can be determined in serum, bile or urine. This method may be used for routine assays of biological fluids and appears sensitive and accurate.

[Structural changes in the jaws. Differential diagnosis]. / Alterazioni strutturali dei mascellari. Diagnosi differenziale.

In this work the Authors have considered the causes of changes in the structure of maxillary bones. They have also discussed the available diagnostic means useful to make a correct diagnosis and the importance of a right differential diagnosis of the causes in order to have a better treatment.

Changes of the Golgi apparatus induced by diethylmaleate in rat hepatocytes.

Ultrastructural studies of the liver of rats given diethylmaleate (DEM) (0.7 ml per kg body, i.p.) weight revealed marked alterations of the configuration of the Golgi complex in all hepatocytes. This consisted in dilatation of the cisternae leading to the formation of large cysts. The alteration was more prominent 15 min after administration of the drug, coincident with a 2-fold increase of bile flow and a decrease of hepatic glutathione to 15% of controls. The morphology returned to normal at 45 min after DEM administration together with a return of bile flow to control values whereas hepatic glutathione level remained markedly depressed for 2 hr, rising slowly afterwards. No other signs of altered hepatic morphology developed up to 5 hr. The morphological changes correlated with altered bile flow induced by DEM, suggesting involvement of the Golgi complex in biliary excretion of osmotically active glutathione conjugates of DEM.

[A report of 2 cases of Turner's syndrome with a ring X chromosome]. / Descrizione di due casi di sindrome di Turner con cromosoma X ad anello.

The authors report two cases of Turner syndrome with clinical evidence of only primitive hypogonadism and short stature. Karyotype analysis showed X ring mosaicism which is present only in 5% of cases of Turner syndrome. The authors agree with the hypothesis suggesting no relationship between break points on the X chromosome and phenotypical aspect. An earlier diagnosis is auspicious so that, using correct therapy, final height should be improved.

In vivo and in vitro inhibition of hepatic microsomal drug metabolism by ketoconazole.

Ketoconazole (KC), a broad spectrum antifungal drug, has been recognized recently as a cause of hepatic injury. The mechanism of the adverse reaction remains unclear: a metabolic idiosincrasy has been suggested. However as a substituted imidazole, KC might be expected to interfere with the hepatic microsomal mixed function oxidases. Ethylmorphine N-demethylase (E-DM) and aniline hydroxylase (A-OH) activities were determined in rat liver microsomes in the presence of increasing amounts of KC. Both were inhibited in an exponential fashion. The E-DM inhibition was almost complete at concentrations greater than 250 microM and was of the mixed type. A much weaker effect was observed for A-OH. A significant inhibition of E-DM was also observed when KC was administered in vivo to rats either orally for 7 days at the dose of 100 mg/kg/day (P less than 0.02) or intraperitoneally for 4 days at the dose of 50 or 100 mg/kg day (P less than 0.01 or P less than 0.001 respectively). A-OH activity was significantly reduced (P less than 0.01) only after ip administration of 100 mg/kg/day of the drug for 4 days. Neither the amount of cytochrome P-450 nor NADPH cytochrome c reductase activity were affected at the doses considered. These data show that KC interferes with hepatic oxidative drug metabolism and suggest that this mechanism might be involved in the unwanted side effects of therapy with KC.

Growth-factor independence of a new differentiated hepatitis B virus DNA-negative human hepatoma cell line.

The establishment of a new, differentiated, hepatitis B virus DNA-negative, human hepatoma cell line (named PLC/AN/2) is described. Neoplastic liver tissue was obtained during hepatectomy in an HBsAg-negative man. The established cell line is negative for alpha-fetoprotein and carcinoembryonic antigen; it has retained in vitro some of the differentiated functions of normal hepatocytes. Additionally, it presents a distinctive rearrangement (translocation) at the long arm of chromosome 4. The high degree of independence from serum growth factor requirements appears to be a major in vitro characteristic of PLC/AN/2 cells, making them a suitable model system for the more precise definition of the human hepatocellular carcinoma phenotype, including mechanisms of growth control.

Five-dimensional structure refinement of natural melilite, (Ca(1.89)Sr(0.01)Na(0.08)K(0.02))(Mg(0.92)Al(0.08)-(Si(1.98)Al(0.02))O(7).

The structure of a crystal of natural melilite from San Venanzo, Umbria (Italy) of the general formula X(2)T1(T2)(2)O(7), where X = Ca(0.945)Sr(0.005)Na(0.04)K(0.01), T1 = Mg(0.92)Al(0.08) and T2 = Si(0.99)Al(0.01), has been solved and refined as an incommensurate structure in five-dimensional superspace. The structure is tetragonal, superspace group P(-)42(1)m:p4mg, cell parameters a = 7.860 (1), c = 5.024 (1) A, modulation vectors q(1) = 0.2815 (3)(a* + b*), q(2) = 0.2815 (3)(-a* + b*). The data collection was performed on a KumaCCD diffractometer. The structure was refined from 7606 reflections to final R = 0.0481. A special modification of the refinement program Jana2000 was necessary to take into account overlapping of satellite reflections m x n = +/-1, which could not be properly separated in the integration procedure. The final model includes modulations of the atomic positions as well as modulations of the thermal parameters. The latter are induced by strong differences in the neighbourhood of the actual modulated positions. The occupational modulation was neither significant for X nor for T1 sites and the sites were supposed to be occupied only by Ca and Mg, respectively. As a consequence of the Ca and O positional modulations six-, seven- and eightfold Ca coordination occur throughout the structure and the thermal ellipsoid changes its shape correspondingly. The positional modulation of the atoms causes variations in the interatomic distances which, however, do not affect bond-valence sums considerably, but induce flattening and rotation in T1 and T2 tetrahedra, respectively.