Recurrent urinary tract infections in kidney transplant recipients during the first-year influence long-term graft function: a single-center retrospective cohort study.

Urinary tract infections (UTIs) after kidney transplantation are associated with significant morbidity. However, data on the impact of UTI on graft survival are controversial. We conducted a retrospective cohort study of 380 kidney transplant patients. Recipients with symptomatic UTIs during the first year after transplantation were categorized into three groups: early (< 3 episodes from months 1st to 6th), late (< 3 episodes during months 7th to 12th) and recurrent (≥ 3 episodes throughout the whole first year). Graft function at three years was considered the primary outcome. Symptomatic UTIs occurred in 184 (48.4%) kidney transplant recipients during the first year; 83 (21.8%) patients developed early UTIs, 50 (13.2%) late UTIs and 51 (13.4%) recurrent UTIs. We observed a significant improvement in graft function after three years in all patients (P < 0.001) except those who had recurrent UTIs. A Kaplan-Meier analysis showed that recipients with recurrent UTIs had worse graft outcome (eGFR value < 60 mL/min/1.73 m2) (P = 0.01). Recurrent UTIs was an independent predictor of graft function at three years in a model adjusted for DGF and episodes of acute rejection (Hazard Ratio, 2.2; 95% CI, 1.3 to 3.5; P = 0.001). Recurrent symptomatic UTIs during the first year after transplantation have negative impact on long-term graft function.

Clarithromycin-resistant genotypes and eradication of Helicobacter pylori.

OBJECTIVE: To compare the eradication rates among the different point mutations and the efficacy of triple therapy and a sequential regimen according to genotypic resistance. STUDY DESIGN: Post hoc retrospective cohort study in a tertiary referral center for pediatric gastroenterology in southern Italy. All 168 children who were positive for Helicobacter pylori were enrolled. Patients had received clarithromycin-based 7-day triple therapy (73 children) or 10-day sequential therapy regimen (95 children). Real-time polymerase chain reaction for assessing clarithromycin resistance was performed on sections of paraffin-embedded gastric biopsy samples. RESULTS: H pylori eradication was achieved in 16 of 32 (50%) children with the A2143G mutation, in 8 of 10 patients with either A2142G or A2142C strains (80%), and in 112 of 116 children with susceptible strains (88.9%). The presence of A2143G mutation was associated with a lower cure rate compared with the rate in the absence of this mutation (50% vs. 89%; P = .001). The sequential regimen achieved a higher cure rate than triple therapy in patients with A2143G mutant strains (80% vs nil; P < .001). CONCLUSIONS: The A2143G mutation confers higher risk of treatment failure. Sequential regimen has higher efficacy than standard therapy, even in children with A2143G mutatant strains.

Helicobacter pylori vacA arrangement and related diseases: a retrospective study over a period of 15 years.

Peptic ulcer disease incidence is decreasing. Both s1m1 and s1m2 vacA gene combinations of Helicobacter pylori have been associated with the development of major gastroduodenal diseases. This study assessed whether H. pylori vacA gene arrangement changed over 15 years in a Southern Italy area. H. pylori-positive patients observed in January-June 1989 and January-June 2005 were selected. Histological specimens were retrieved to extract DNA for vacA arrangement characterization (mid-m and peptide signal-s regions) by using the polymerase chain reaction. Fifty-nine patients in the first period and 56 matched patients in the second period were evaluated. A correlation between s1 presence and intestinal metaplasia at histology was found. Overall, the s1m1 combination increased (P < 0.01) and s2m2 decreased (P < 0.001) during the study period. In detail, s1m1 (P < 0.05) and s1m2 (P < 0.01) increased, and s2m2 decreased (P < 0.001) in dyspeptic patients, while only s1m1 increased (P < 0.01) in peptic ulcer patients. Finally, few cases of s2m1 combination in both series were found. Our results show some unexpected aspects that require confirmation. In detail, the increased prevalence of potential more virulent H. pylori strains contrasts with peptic ulcer incidence reduction.

Exhaled breath condensate cytokines and pH in pediatric asthma and atopic dermatitis.

Some studies have proposed exhaled breath condensate (EBC) as a noninvasive tool for monitoring airway inflammation in children. Moreover, atopic dermatitis (AD) has been considered a risk factor for the development of asthma. This study was designed to assess the EBC pH and the exhaled concentration of cytokines produced by T-helper (Th) 1, Th2, and T regulatory cells in asthmatic children and AD and to verify if their concentrations are affected by a short course of treatment with inhaled corticosteroids (ICS). We assessed the mean levels of pH, interferon (IFN) gamma, interleukin (IL)-4, and IL-10 in EBC of children with asthma (n=20) and AD (n=12) and healthy controls (n=20) by enzyme-linked immunosorbent assay (ELISA). Variations of pH and cytokine concentration in response to ICS (flunisolide, 500 microg/day, for 2 weeks), were also investigated in asthmatic patients. We found that the mean condensate pH value in patients with asthma and AD was significantly lower when compared with that of controls (6.9+/-0.2 and 7.0+/-0.2 versus 7.4+/-0.4; p<0.0001) and it significantly increased in asthmatic patients after treatment (7.2+/-0.2 versus 6.9+/-0.2; p=0.003). In addition, the IL-4/IFN-gamma ratio was significantly higher in children with asthma and in those with AD when compared with controls (9.72+/-2.00 and 9.70+/-2.0 versus 8.04+/-2.6; p<0.001) and that it decreased in asthmatic patients after ICS (6.4+/-5.4 versus 9.72+/-2.00; p<0.01). We observed that exhaled IL-10 levels were significantly higher in children with asthma compared with those of controls (18.8+/-8.9 versus 4.2+/-1.0; p<0.002). IL-10 did not significantly increase after treatment with steroids. No such finding was documented in children with AD. Our data suggest that EBC IL-10 levels are different in asthmatic patients compared with healthy children, but they are insensitive markers in monitoring therapy with ICS. Moreover, children with AD show an EBC pH and an exhaled pattern of Th2/Th1 cytokines similar to that of asthmatic patients.

Prevalence of primary clarithromycin resistance in Helicobacter pylori strains over a 15 year period in Italy.

OBJECTIVES: The frequency of primary clarithromycin resistance in Helicobacter pylori strains is increasing worldwide, and its presence significantly reduces the treatment efficacy of infection. This study aimed to evaluate whether the progression of the prevalence of clarithromycin resistance over a 15 year period has increased and whether a possible change in the distribution of the three most frequent point mutations, which account for the large majority of clarithromycin resistance cases, has taken place. METHODS: Antral biopsies of consecutive H. pylori-positive patients observed between January 1989 and December 1990 and between January 2004 and December 2005 were retrieved. A TaqMan real-time PCR was performed in all cases to assess point mutations involved. RESULTS: Primary clarithromycin resistance was assessed for 147 patients observed in the first period 1989-90 and 178 cases observed in the second period 2004-05. The overall frequency of clarithromycin resistance increased from 10.2% (15 patients) to 21.3% (38 patients) during the study period (P = 0.01). The increase was more evident in females [4 out of 55 patients (7.2%) versus 24 out of 103 patients (23.3%); P = 0.01] and in non-ulcer dyspepsia patients [13 out of 106 patients (12.2%) versus 37 out of 140 (26.4%) patients; P = 0.009]. A2143G was the most frequent point mutation observed in both study periods, and its prevalence rate remained unchanged [11 out of 15 (73.3%) patients versus 27 out of 38 (71%) patients; P = 1]. CONCLUSIONS: A 2-fold increase in primary clarithromycin resistance in H. pylori strains occurred during the last 15 years in Italy. A2143G remains the most prevalent point mutation involved, thus suggesting that new therapeutic strategies are needed.

Functional modification of CD11c+ liver dendritic cells during liver regeneration after partial hepatectomy in mice.

Local immunosuppression within the liver and sex steroid changes, in both blood and tissue during liver regeneration, are well-recognized events. Dendritic cells (DC) play pivotal roles in the induction and regulation of immune responses. Their numbers are expanded markedly in vivo by fms-like tyrosine kinase 3 ligand (Flt3L) administration, without modification of their maturation state. Recent evidence suggests that estrogen can modulate DC function and promote a Th2-type immune response. Few data are available concerning the role of DC in liver regeneration. After 75% partial hepatectomy (PH) in male C57BL/6 mice, CD11c+ liver (L)DC increased significantly within 6 hours and maintained an immature phenotype. Numbers returned to pre-hepatectomy levels by 24 hours. The expanded LDC population showed increased IL-10 and reduced IFN-gamma gene transcription. Using these DC compared with control LDC as T cell stimulators in 72-hour mixed leukocyte cultures, IL-10 production was enhanced and IFN-gamma production reduced. LDC isolated 6 hours after 75% PH exhibited enhanced estrogen receptor (ER) expression, concomitant with increased serum estrogen levels. By contrast, spleen (S)DC isolated before and after PH showed no significant changes in their function (maturation state, T cell stimulatory activity, cytokine production, and ER expression). Increased liver regeneration (more than 50%) was observed 48 hours after 40% PH in the Flt3L-pretreated compared with the PBS group. In conclusion, interstitial LDC may play a key role in local immune regulation during liver regeneration, possibly linking estrogen-mediated immune modulation and hepatocyte proliferation.

Clarithromycin-resistant genotypes and eradication of Helicobacter pylori.

BACKGROUND: Three point mutations (A2143G, A2142G, and A2142C) have been involved in Helicobacter pylori clarithromycin resistance. OBJECTIVE: To compare the eradication rates among the different point mutations and the efficacy of triple therapy and a sequential regimen according to genotypic resistance. DESIGN: Post hoc subgroup study from a multicenter, randomized trial. SETTING: Two hospitals in central and southern Italy between January and December 2001. PATIENTS: 156 patients with H. pylori infection. MEASUREMENTS: Real-time polymerase chain reaction for assessing clarithromycin resistance; histology, rapid urease test, and 13C-urea breath test at entry and after 4 to 6 weeks. INTERVENTION: 7-day triple therapy (20 mg of rabeprazole, 500 mg of clarithromycin, and 1 g of amoxicillin) in 75 patients or a 10-day sequential regimen (20 mg of rabeprazole plus 1 g of amoxicillin for 5 days and 20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of tinidazole for the remaining 5 days) in 81 patients. All drugs were given twice daily. RESULTS: Helicobacter pylori infection was eradicated in 11 of 23 patients (48%) with the A2143G mutation and in 14 of 15 patients (93%) with either A2142G or A2142C strains (difference, 45 percentage points [95% CI, 15 to 65 percentage points]; P = 0.004). The sequential regimen achieved a higher cure rate than triple therapy in A2143G mutate strains (difference, 49 percentage points [CI, 8 to 72 percentage points]; P = 0.024). LIMITATIONS: The post hoc substudy design may require further confirmation. Other limitations are the accessibility to the tool and the cost of investigations (70 euros per patient). CONCLUSIONS: The A2143G mutation seemed to be associated with a very low eradication rate. The sequential regimen achieved a higher cure rate than standard therapy even in patients with these strains.

Claritromycin resistance and Helicobacter pylori genotypes in Italy.

The relationship between H. pylori clarithromycin resistance and genetic pattern distribution has been differently explained from different geographic areas. Therefore, we aimed to assess the clarithromycin resistance rate, to evaluate the bacterial genetic pattern, and to search for a possible association between clarithromycin resistance and cagA or vacA genes. This prospective study enrolled 62 consecutive H. pylori infected patients. The infection was established by histology and rapid urease test. Clarithromycin resistance, cagA and vacA status, including s/m subtypes, were assessed on paraffin-embedded antral biopsy specimens by TaqMan real time polymerase chain reaction (PCR). Primary clarithromycin resistance was detected in 24.1 % of cases. The prevalence of cagA was 69.3 %, and a single vacA mosaicism was observed in 95.1 % cases. In detail, the s1m1 was observed in 23 (38.9 %) patients, the s1m2 in 22 (37.2 %), and the s2m2 in 14 (23.7 %), whereas the s2m1 combination was never found. The prevalence of cagA and the vacA alleles distribution did not significantly differ between susceptible and resistant strains. Primary clarithromycin resistance is high in our area. The s1m1 and s1m2 are the most frequent vacA mosaicisms. There is no a relationship between clarithromycin resistance and bacterial genotypic pattern and/or cagA positivity.

A new semiquantitative method of quantifying Helicobacter pylori in antigen stools.

Stool antigen test for Helicobacter pylori, a noninvasive assay, is emerging as a strong competitor to urea breath test (UBT). Nevertheless, although the UBT delta value is a semiquantitative indicator of H. pylori intragastric load, until now the H. pylori stool antigen test has been used only as a qualitative investigation. We report here the results of a study performed with the aim of obtaining a semiquantitative measurement of bacterial amount in stools. We studied 15 patients with dyspepsia using H. pylori positivity at histology, the rapid urease test, UBT, and the H. pylori stool antigen test. The result of this last test was expressed by a numerical value we obtained by applying the principle of "standard points" to the absorbance units at spectrophotometric reading. This measurement was previously validated by testing probe sampling of H. pylori stool antigen with known pure and stool-mixed bacterial amounts. A numerical result for H. pylori stool antigen was correlated to UBT delta for each patient using Pearson's r test. Finally, a Student t test was performed to investigate possible differences in UBT and H. pylori stool antigen test values between anti-CagA-positive and -negative patients. We obtained a curve of saturation with both known amount of pure and stool-mixed bacteria. Pearson's r test showed a significant correlation between UBT delta value and H. pylori stool antigen measurement (r = 0.77; p < 0.001). Urea breath test delta and H. pylori stool antigen test values were significantly higher in anti-CagA-positive patients. Our data suggest that a numerical estimation of H. pylori stool antigen may be feasible. This evaluation, similarly to UBT delta, may represent a semiquantitative determination of bacterial intragastric load.