STIP1 Tissue Expression Is Associated with Survival in Chemotherapy-Treated Bladder Cancer Patients.

To optimize treatment decisions in advanced bladder cancer (BC), we aimed to assess the therapy predictive value of STIP1 with regard to cisplatin therapy. Cisplatin-based chemotherapy represents the standard first-line systemic treatment of advanced bladder cancer. Since novel immunooncologic agents are already available for cisplatin-resistant or ineligible patients, biological markers are needed for the prediction of cisplatin resistance. STIP1 expression was analyzed in paraffin-embedded bladder cancer tissue samples of 98 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Furthermore, pre-chemotherapy serum STIP1 concentrations were determined in 48 BC patients by ELISA. Results were correlated with the clinicopathological and follow-up data. Stronger STIP1 nuclear staining was associated with worse OS in both the whole patient group (p = 0.034) and the subgroup of patients who received at least 2 cycles of chemotherapy (p = 0.043). These correlations remained significant also in the multivariable analyses (p = 0.035 and p = 0.040). Stronger STIP1 cytoplasmatic immunostaining correlated with shorter PFS both in the whole cohort (p = 0.045) and in the subgroup of patients who received at least 2 cycles of chemotherapy (p = 0.026). Elevated STIP1 serum levels were associated with older patient's age, but we found no correlation between STIP1 serum levels and patients' outcome. Our results suggest that tissue STIP1 analysis might be used for the prediction of cisplatin-resistance in BC. In contrast, pretreatment STIP1 serum levels showed no predictive value for chemotherapy response and survival.

Dissemination of NDM-1 carbapenemase-producer Providencia stuartii strains in Romanian hospitals: a multicentre study.

Several Romanian hospitals have noted increasing isolation of Providencia stuartii strains in recent years, with an alarming rate of carbapenem resistance. In order to provide molecular epidemiological data regarding their dissemination, 77 P. stuartii strains collected from five hospitals located in different regions of Romania were analysed. All strains harboured IncA/C plasmid, and 67 carried the blaNDM-1 gene. Six clonal clusters were differentiated by pulsed-field gel electrophoresis. The predominant subtype was found in all five hospitals. Our study highlights the need for efficient infection-control measures, the optimization of antibiotic use and the targeted surveillance for carbapenemase-producing P. stuartii.

Illumina short-read and MinION long-read WGS to characterize the molecular epidemiology of an NDM-1 Serratia marcescens outbreak in Romania.

Background and Objectives: Serratia marcescens is an emerging nosocomial pathogen, and the carbapenemase blaNDM has been reported in several surveys in Romania. We aimed to investigate the molecular epidemiology of S. marcescens in two Romanian hospitals over 2010-15, including a neonatal NDM-1 S. marcescens outbreak. Methods: Isolates were sequenced using Illumina technology together with carbapenem-non-susceptible NDM-1-positive and NDM-1-negative Klebsiella pneumoniae and Enterobacter cloacae to provide genomic context. A subset was sequenced with MinION to fully resolve NDM-1 plasmid structures. Resistance genes, plasmid replicons and ISs were identified in silico for all isolates; an annotated phylogeny was reconstructed for S. marcescens. Fully resolved study NDM-1 plasmid sequences were compared with the most closely related publicly available NDM-1 plasmid reference. Results: 44/45 isolates were successfully sequenced (S. marcescens, n = 33; K. pneumoniae, n = 7; E. cloacae, n = 4); 10 with MinION. The S. marcescens phylogeny demonstrated several discrete clusters of NDM-1-positive and -negative isolates. All NDM-1-positive isolates across species harboured a pKOX_NDM1-like plasmid; more detailed comparisons of the plasmid structures demonstrated a number of differences, but highlighted the largely conserved plasmid backbones across species and hospital sites. Conclusions: The molecular epidemiology is most consistent with the importation of a pKOX_NDM1-like plasmid into Romania and its dissemination amongst K. pneumoniae/E. cloacae and subsequently S. marcescens across hospitals. The data suggested multiple acquisitions of this plasmid by S. marcescens in the two hospitals studied; transmission events within centres, including a large outbreak on the Targu Mures neonatal unit; and sharing of the pKOX_NDM1-like plasmid between species within outbreaks.

Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer.

OBJECTIVE: The aims of the present study were to examine gene and protein expression of the vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzyme in human papillary thyroid cancer (PTC), furthermore, to investigate the association between CYP24A1 expression and numerous clinical, histological parameters and somatic oncogene mutation status of thyroid tumor tissues. MATERIALS AND METHODS: Gene expression analysis was carried out in 100 Hungarian thyroid samples, both normal and papillary tumor tissue sections of the same patient. The specific mRNA to the selected genes was analyzed by TaqMan probe-based quantitative real-time RT-PCR. The somatic oncogene mutation states of BRAF, NRAS, HRAS and KRAS were also tested. RESULTS: CYP24A1 mRNA expression was markedly increased in 52 cases (52%) of the examined papillary cancers compared with that of normal thyroid tissue. There was a tendency toward difference in the distribution of high-level CYP24A1 in the PTC accompanied with somatic oncogene mutation. Positive correlation was seen between increased CYP24A1 expression rate and a group of variables reflecting tumor malignity (mainly vascular invasion, lymph node metastasis, tumor size, hypothyreosis) by principal components analysis. No significant alteration was seen in CYP27B1 gene expression between neoplastic and normal tissues. CONCLUSIONS: A definite alteration was seen in vitamin D3-inactivating CYP24A1 gene activity in PTC compared to their normal tissues on a relatively large patient population. Our findings raise the possibility that CYP24A1 may also directly be involved in thyroid carcinogenesis.

Attachment insecurity predicts child active resistance to parental requests in a compliance task.

AIM: We studied the effects of early mother-child relationship quality and child temperament on the development of child compliance and active resistance in a large population-based cohort study (n = 534). BACKGROUND: Parenting and the quality of the parent-child relationship can either hamper or support the development of child compliance directly or in interplay with child temperament. METHODS: Mother-infant dyads were observed at 14 and 36 months and maternal and child behaviours were independently coded. The quality of compliance was assessed at 36 months in a clean-up task. Child behaviour was coded using a system differentiating between two dimensions: Compliance and Active Resistance. RESULTS: Controlling for concurrent maternal sensitivity, child temperament, and gender children with a more insecure attachment relationship showed higher levels of active resistance during Clean-Up than more securely attached children. The effect was stronger for boys than for girls and mainly driven by attachment avoidance. CONCLUSIONS: Early attachment is an important contributor to child socialization of moral behaviour.

Comparison of transpulmonary thermodilution, transthoracic echocardiography and conventional hemodynamic monitoring in neonates and infants after open heart surgery: a preliminary study.

BACKGROUND: Transpulmonary thermodilution (TPTD) is an increasingly popular method used to monitor the complex hemodynamic changes in critically ill children. The purpose of our study was to examine the relationship between transthoracic echocardiographic (TTE) parameters and global hemodynamic variables derived from TPTD and those derived from conventional measurements in infants and neonates undergoing corrective cardiac surgery. METHODS: After approval from the Ethics Committee of Gottsegen György Hungarian Institute of Cardiology and individual parental consent were obtained, patients were prospectively enrolled. In parallel with continuous postoperative conventional monitoring, TPTD was measured four times daily, and TTE was performed once per day. Conventional hemodynamic, TPTD and TTE parameters were compared with weighted linear regression statistics and a Pearson correlation. RESULTS: One hundred forty-five TPTD measurements and 35 TTE examinations of thirteen enrolled patients were analyzed. Global end-diastolic volume index (GEDVI) was correlated with the fractional shortening (SF, r=0.67, P=0.001) measured by TTE. Among the preload parameters, the percentage change of GEDVI between two consecutive time points showed a pertinent correlation with changes of cardiac index (r=0.67, P=0.001) and changes of stroke volume index (r=0.57, P=0.008). Percentage changes in SF demonstrated a strong negative correlation with changes of left ventricular end-systolic diameter (r=-0.86, P<0.001). There was no significant relationship between alterations in arterial or central venous pressure values with TTE or TPTD parameters. CONCLUSION: Both TPTD and TTE may be used in the estimating volumetric preload parameters. The time course of TPTD-derived parameters may have clinical relevance in pediatric critical care practice.

First isolation of Clostridium difficile PCR ribotype 027 from a patient with severe persistent diarrhoea in Hungary.

A recent Supplement to Clinical Microbiology and Infection entitled 'Infection control measures to limit the spread of C. difficile' pointed out that the incidence of C. difficile-associated diarrhoea (CDAD) has been increasing worldwide, and stressed the importance of research in the fields of epidemiology and infection control [1]. Since 2003, one of the main causes of the increasing prevalence of CDAD has been claimed to be the emergence of PCR ribotype 027/NAP1, which has caused epidemics in North America, the UK, the Netherlands, Belgium and France. The presence of PCR ribotype 027 in Austria, Japan, Ireland, Germany and Switzerland has also been reported recently [2,3]. The majority of publications have emphasized that the presence of this strain is usually associated with more severe symptoms and signs than those associated with the other more common toxin-positive strains [4,5]. Whereas PCR ribotype 027 was present in the population earlier, the majority of the historic strains were fluoroquinolone sensitive [6]. The overuse of antibiotics such as fluoroquinolones may lead to the selection and emergence of resistant strains, and may contribute to the spread of PCR ribotype 027, which is usually resistant to erythromycin. Here, the Eastern European spread of C. difficile PCR ribotype 027 is reported.

Real-time PCR-based pathotyping of Newcastle disease virus by use of TaqMan minor groove binder probes.

A real-time reverse-transcription PCR was developed to detect and pathotype Newcastle disease viruses (NDV) in clinical samples. Degenerate oligonucleotide primers and TaqMan probes with nonfluorescent minor groove binder (MGB) quencher amplified and hybridized to a region in the fusion protein (F) gene that corresponds to the cleavage site of the F0 precursor, which is a key determinant of NDV pathogenicity. The application of degenerate primers and TaqMan MGB probes provided high specificity to the assay, as was shown by the successful and rapid pathotype determination of 39 NDV strains representing all the known genotypes (I to VIII) and pathotypes (lentogens/mesogens/velogens). The PCR assays specific for lentogenic and velogenic/mesogenic strains had high analytical sensitivity, detecting approximately 10 and 20 copies of the target molecule per reaction, respectively. The detection limit was also determined in terms of 50% egg infective dose (EID(50)) by using dilution series of virus stock solutions to be approximately 10(1.0) and 10(-1.3) EID(50)/ml for lentogens and velogens/mesogens, respectively. Organ, swab, and stool specimens from experimentally infected animals were tested to prove the clinical suitability of the method. The results of this study suggest that the described real-time PCR assay has the potential to be used for the rapid detection/pathotyping of NDV isolates and qualitative/quantitative measurement of the virus load.

The effect of citrus flavonoids on the redox state of alimentary-induced fatty liver in rats.

Both chronic venous insufficiency (CVI) and fatty liver may develop at the same time. Hesperidin and diosmin are used for the treatment CVI. There is no information, however, on the effect of these flavonoids in the redox state of fatty liver. In this study, male Wistar albino rats were fed a lipid-rich diet with or without 450 mg diosmin-50 mg hesperidin-containing drug (60 mg kg(-1) body weight/day, per os) for 9 days to determine the impact of treatment on antioxidant defence system of the fatty liver. We detected free SH-group concentration (SHC), hydrogen-donating ability (HDA), and natural scavenger capacity were decreased and hepatic malonaldehyde content and dien conjugate (DC) content in rats with fatty liver were increased compared to the control. After treatment in fatty liver, these parameters (except DC) significantly improved and approached the control value. Our results indicate that diosmin-hesperidin-containing drug may be a useful agent in improving the antioxidant defensive system in alimentary-induced fatty liver disease.

Effects of vitamin E administration on the hemorheological status and redox homeostasis of patients with porphyria cutanea tarda treated with phlebotomy.

BACKGROUND: Conflicting results were reported about the efficacy of vitamin E (E) treatment in porphyria cutanea tarda (PCT). We conducted a study in PCT patients to investigate whether E treatment has any additional beneficial effects compared with phlebotomy (P) treatment alone on rheological and oxidative stress parameters. METHODS: Twenty three patients with sporadic PCT in clinical remission and 10 healthy control patients were studied. All patients were treated with P prior to the study until clinical remission was achieved. Baseline routine laboratory [blood glucose, serum lipids, C-reactive protein (CRP), iron metabolism indices, liver function tests], oxidative stress [serum thiobarbituric acid reactive substances (TBARS), plasma H-donor activity, plasma free SH-groups, erythrocyte glutathion peroxidase activity] and rheological parameters (whole blood and plasma viscosity, cell transit time, clogging rate) were measured in both groups. Then all PCT patients received E (tocopherol acetate) 200 mg/day for 8 weeks and at the end of treatment measurements identical to those performed at baseline were repeated. RESULTS: Increased urine uroporphyrin, serum CRP, TBARS concentrations, whole blood and plasma viscosity and decreased plasma H-donor activity, free SH-group level, erythrocyte glutathione peroxidase activity were detected in PCT patients treated with P alone compared with control group consistent with residual oxidative stress in PCT patients. E treatment decreased urine uroporphyrin and serum TBARS concentrations; increased plasma H-donor activity and did not influence whole blood and plasma viscosity compared with P treatment alone. CONCLUSIONS: E treatment reduced the residual oxidative stress and did not influence increased plasma and whole blood viscosity present in PCT patients receiving P treatment prior to clinical remission.

Hypercalcitoninemia in a patient with a recurrent goitre and insulinoma: a case report.

Serum calcitonin has become a very sensitive and specific marker for medullary thyroid carcinoma that should be determined in patients with nodular thyroid disease. However, a few earlier reports indicated that tumors other than medullary thyroid carcinoma including insulinomas arising from pancreatic islet cells may also produce calcitonin. Of the few cases of calcitonin-producing insulinomas previously reported, most had incomplete data or lack of documentation of the association between raised serum calcitonin concentration and immunohistochemical detection of calcitonin in pancreatic islet cell tumors. In this paper we are reporting a 54-year-old woman with a history of partial thyroidectomy for multinodular goitre at the age of 50 yrs, she was evaluated for a 2-months history of fasting hypoglycemia (plasma glucose 1.9 mmol/L during a supervised fast), raised serum insulin (at the time of hypoglycemia 88.8 microU/ml; normal, 5 - 35 microU/ml) and C-peptide levels (at the time of hypoglycemia 6.1 ng/ml; normal, 1.37 - 3.51 ng/ml), markedly increased serum calcitonin concentration (481 pg/ml; normal, < 9.9 pg/ml), and an enlarged residual thyroid gland. Aspiration biopsy of the thyroid was negative for parafollicular C-cell hyperplasia or medullary thyroid carcinoma. Abdominal ultrasound and CT scan revealed a tumor in the head of the pancreas, which was surgically removed. Histopathological evaluation of the pancreatic tumor showed typical features of a neuroendocrine neoplasm with strong immunostaining for both insulin and calcitonin. After removal of the pancreatic tumor, clinical symptoms resolved and biochemical markers normalized (serum insulin, 14.9 microU/ml; C-peptide, 3.0 ng/ml; calcitonin, 2.9 pg/ml) confirming the causal relationship between insulinoma and markedly increased serum calcitonin levels.

Major and trace elements in whole blood of phlebotomized patients with porphyria cutanea tarda.

Porphyria cutanea tarda (PCT) is a disorder of hem biosynthesis resulting from a decreased activity of the uroporphyrinogen decarboxylase enzyme. Hem precursors are accumulated in the blood, liver and skin. Inherited and acquired factors also contribute to the pathogenesis of PCT. Hem precursors and porphyrins are excreted with urine and faeces. Whole blood of 8 PCT patients and 6 volunteers of Caucasian origin were analysed. In addition to routine laboratory measurements, 19 elements (Al, B, Ba, Ca, Cd, Co, Cu, Fe, K, Li, Mg, Mn, Mo, Na, Ni, P, S, V, Zn) were determined by means of inductively coupled plasma optical emission spectrometry (ICP-OES). Mg, P and S concentrations in whole blood were decreased significantly (p<0.05), whereas Ba was increased in PCT patients compared to controls. Metabolic alterations are reflected in the correlation of parameters. Positive correlations were found between the element pairs of Zn-Al, Zn-Mg, Zn-Mn, B-S, Fe-Mg, K-P, Mg-Mn for PCT patients, whereas in the control group Al-Mn, Ca-Cu, Ca-Na, Cu-Mg, Fe-K, Mg-Na, Zn-P showed positive correlations.

[Dental avulsions and blood coagulation disorders]. / Avulsions dentaires et coagulophaties.

INTRODUCTION: We performed a retrospective study of tooth removal for patients with coagulation disorders. MATERIAL AND METHOD: The study included 67 patients divided into 3 groups according to their coagulation disorder. The first group included 31 patients with a congenital disorder, the second 19 patients receiving anticoagulant therapy, and the third 16 patients with an acquired disorder. The same surgical procedure was used for all patients: alveoli regulation, socket preparation with resorbable oxycellulose dressing, and sutures with separate stitches. Biological glue and celluloid splints were not used. Depending on the severity of the coagulation disorder, factor VIII or concentrated von Willebrand factor or Desmopressine was administered for patients in the first group. If possible, low-molecular-weight heparin replaced oral anticoagulation for patients in the second group. Platelet concentrates were administered for 2 of the patients in the third group. RESULTS: Postoperative bleeding was noted in 4 patients in the first group, 2 in the second and 2 in the third. DISCUSSION: We have abandoned the use of biological glue and celluloid splints. The rate of bleeding in the first and second group was similar to that reported in the literature. We were unable to find any comparable report for the third group.

Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation.

Bone marrow-derived mesenchymal stem cells (MSCs) are known to interact with hematopoietic stem cells (HSCs) and immune cells, and represent potential cellular therapy to enhance allogeneic hematopoietic engraftment and prevent graft-versus-host disease (GVHD). We investigated the role of human MSCs in NOD-SCID mice repopulation by unrelated human hematopoietic cells and studied the immune interactions between human MSCs and unrelated donor blood cells in vitro. When hematopoietic stem cell numbers were limited, human engraftment of NOD-SCID mice was observed only after coinfusion of unrelated human MSCs, but not with coinfusion of mouse mesenchymal cell line. Unrelated human MSCs did not elicit T-cell activation in vitro and suppressed T-cell activation by Tuberculin and unrelated allogeneic lymphocytes in a dose-dependent manner. Cell-free MSC culture supernatant, mouse stromal cells and human dermal fibroblasts did not elicit this effect. These preclinical data suggest that unrelated, human bone marrow-derived, culture-expanded MSCs may improve the outcome of allogeneic transplantation by promoting hematopoietic engraftment and limiting GVHD and their therapeutic potential should be tested in clinic.

[New possibilities and results in pediatric thoracic surgery]. / Uj lehetóségek és eredményeink a gyermek-mellkassebészetben.

In the last 5 years 104 thoracic operations were performed on children and adolescents in the 3rd Surgical Clinic of the Semmelweis University of Budapest and in the Heim Pál Children's Hospital by the authors. The number of the lung interventions was 47 and 57 operations were performed on the mediastinum, thoracic wall, pleura, trachea and on the diaphragm. Distribution ot the lung operations: 21 developmental malformations, 14 bronchiectasia, 9 tumours and 3 others. All the 16 mediastinal operations were performed because of tumours. The others were: 27 thoracic wall interventions, 11 pleural, and 3 other operations. All the operations were performed by the same surgeon. Authors introduced new techniques in the pediatric thoracic surgery in their country as the laser technique and the Video Assisted Thoracic Surgery. One reoperation was performed because of postoperative bleeding. No patients died in the postoperative period.

[Lymphoepithelial cyst of the pancreas]. / A pancreas lymphoepithelialis cystája.

Authors present a case of a retroperitoneal lymphoepithelial cyst, which occurs rarely in this localisation. The histological picture is reminiscent of a branchiogen cyst. Usually it is recognised accidentally, with US or CT examinations performed for other reasons. In case the general condition of the patient is satisfactory, the surgical removal of such a tumour is recommended, since it is almost impossible to differentiate from more harmful lesions by CT or US examination, and if there are no tumour cells on the smears obtained by fine needle aspiration, there is always the doubt of sampling error.

Optical resolution of 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline by supercritical fluid extraction.

6-Fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (FTHQ) enantiomers were separated by supercritical fluid extraction using carbon dioxide. Diastereoisomeric salts were formed from the racemic base with less than one equivalent of O,O'-di-(4-toluoyl)-(2R,3R)-tartaric acid (DPTTA). Further purification was achieved by partial salt formation of the enantiomeric mixture with an achiral acid (HCl) followed by the supercritical fluid extraction of the free enantiomers.

Six regimens for the eradication of Helicobacter pylori (Hp) in duodenal ulcer patients: three consecutive trials (1995-1999).

AIM: to present our experience in eradicating Hp in three consecutive trials performed between 1995 and 1999. METHODS: 320 duodenal ulcer outpatients have been enrolled in three open, prospective controlled trials. Hp infection was confirmed by Giemsa stain and Rut. In Trial I, 52 cases received 20 mg omeprazole + 2 x 250 mg clarithromycin + 2 x 500 mg tinidazole (OCT), 48 patients were given 20 mg omeprazole, 2 x 1000 mg amoxicillin + 2 x 500 mg metronidazole (OAM) for 7 days; in Trial II, 48 cases received 40 mg pantoprazole + 2 x 1000 mg amoxicillin + 2 x 500 mg clarithromycin (PAC) for 7 days and 5l cases 2 x 400 mg ranitidin bismuth citrate + 2 x 500 mg clarithromycin for 14 days (RBC-C); in Trial III, 60 cases were treated with 2 x 30 mg lansoprazole + 2 x 250 mg clarithromycin + 2 x 500 mg metronidazole and 6l patients received 2 x 400 mg ranitidin bismuth citrate+2 x 250 mg clarithromycin + 2 x 500 mg metronidazole (RBC-CM). The patients were controlled within 4-6 weeks by endoscopy in trials I-II and 13C-urea breath test in trial III. RESULTS: Eradication rates on ITT/PP basis were: OCT: 72.3/80.2% vs OAM 51.2/63.5% (P = 0.02/P = 0.03); PAC: 80.8/88.3% vs RBC-C 80.3/85.4% (P = 0.65/0.67) and LCM 78.3/92.1% vs RBC-CM 78.7/90.5% (P = 0.86/P = 0.93). Side effects occurred in 5.2, 8.6, 9.5, 14.5, 13.5 and 18.3% of the cases. CONCLUSION: Regimens using 2 x l PPI or RBC + 2 antibiotics for l week proved to be the most effective for Hp eradication in duodenal ulcer patients.