[Mental disorders in the dental practice. Patients with body dysmorphic disorder]. / Serie: Psychische stoornissen in de mondzorgpraktijk. Patiënten met een morfodysfore stoornis.

Oral healthcare professionals are frequently consulted by patients who are dissatisfied with their teeth and/or facial looks. Sometimes, this dissatisfaction takes a pathological form. When someone is preoccupied with a (supposed) abnormality barely or not visible to others, performs certain actions in response to the concerns about their appearance and experiences significant suffering, this may be a case of body dysmorphic disorder. Its prevalence is 0.7-2.4% in the general population, but significantly higher in clinics where cosmetic or orthognathic procedures are performed (10-15%). Procedures aimed at improving the abnormality experienced by the patient rarely lead to a reduction of the symptoms, but more often result in more dissatisfaction and complaints towards the practitioner. It is difficult for practitioners to recognise this condition. An overview of characteristics, co-morbidity and consequences of body dysmorphic disorder for oral health and treatment will result in increased awareness of this condition among oral care providers.

Evaluating the evidence for non-monotonic dose-response relationships: A systematic literature review and (re-)analysis of in vivo toxicity data in the area of food safety.

This study aims to evaluate the evidence for the existence of non-monotonic dose-responses (NMDRs) of substances in the area of food safety. This review was performed following the systematic review methodology with the aim to identify in vivo studies published between January 2002 and February 2015 containing evidence for potential NMDRs. Inclusion and reliability criteria were defined and used to select relevant and reliable studies. A set of six checkpoints was developed to establish the likelihood that the data retrieved contained evidence for NMDR. In this review, 49 in vivo studies were identified as relevant and reliable, of which 42 were used for dose-response analysis. These studies contained 179 in vivo dose-response datasets with at least five dose groups (and a control group) as fewer doses cannot provide evidence for NMDR. These datasets were extracted and analyzed using the PROAST software package. The resulting dose-response relationships were evaluated for possible evidence of NMDRs by applying the six checkpoints. In total, 10 out of the 179 in vivo datasets fulfilled all six checkpoints. While these datasets could be considered as providing evidence for NMDR, replicated studies would still be needed to check if the results can be reproduced to rule out that the non-monotonicity was caused by incidental anomalies in that specific study. This approach, combining a systematic review with a set of checkpoints, is new and appears useful for future evaluations of the dose response datasets regarding evidence of non-monotonicity.

Profiling of volatile organic compounds produced by clinical Aspergillus isolates using gas chromatography-mass spectrometry.

Volatile organic compounds (VOCs) in exhaled breath may identify the presence of invasive pulmonary aspergillosis. We aimed to detect VOC profiles emitted by in vitro cultured, clinical Aspergillus isolates using gas chromatography-mass spectrometry (GC-MS). Three clinical Aspergillus isolates and a reference strain were cultured while conidiation was prevented. Headspace samples were analyzed using a standardized method. Breath samples of patients from which the cultures were obtained were checked for the presence of the VOCs found in vitro. Each Aspergillus isolate produced a distinct VOC profile. These profiles could not be confirmed in exhaled breath in vivo.

The fragility of statistically significant findings in randomised controlled anaesthesiology trials: systematic review of the medical literature.

The fragility index (FI), the number of events the statistical significance a result depends on, and the number of patients lost to follow-up are important parameters for interpreting randomised clinical trial results. We evaluated these two parameters in randomised controlled trials in anaesthesiology. For this, we performed a systematic search of the medical literature, seeking articles reporting on anaesthesiology trials with a statistically significant difference in the primary outcome and published in the top five general medicine journals, or the top 15 anaesthesiology journals. We restricted the analysis to trials reporting clinically important primary outcome measures. The search identified 139 articles, 35 published in general medicine journals and 104 in anaesthesiology journals. The median (inter-quartile range) sample size was 150 (70-300) patients. The FI was 4 (2-17) and 3 (2-7), and the number of patients lost to follow-up was 0 (0-18) and 0 (0-6) patients in trials published in general medicine and anaesthesiology journals, respectively. The number of patients lost to follow-up exceeded the FI in 41 and 27% in trials in general medicine journals and anaesthesiology journals, respectively. The FI positively correlated with sample size and number of primary outcome events, and negatively correlated with the reported P-values. The results of this systematic review suggest that statistically significant differences in randomised controlled anaesthesiology trials are regularly fragile, implying that the primary outcome status of patients lost to follow-up could possibly have changed the reported effect.

Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis.

RATIONALE: We hypothesised that patients with acute respiratory distress syndrome (ARDS) can be clustered based on concentrations of plasma biomarkers and that the thereby identified biological phenotypes are associated with mortality. METHODS: Consecutive patients with ARDS were included in this prospective observational cohort study. Cluster analysis of 20 biomarkers of inflammation, coagulation and endothelial activation provided the phenotypes in a training cohort, not taking any outcome data into account. Logistic regression with backward selection was used to select the most predictive biomarkers, and these predicted phenotypes were validated in a separate cohort. Multivariable logistic regression was used to quantify the independent association with mortality. RESULTS: Two phenotypes were identified in 454 patients, which we named 'uninflamed' (N=218) and 'reactive' (N=236). A selection of four biomarkers (interleukin-6, interferon gamma, angiopoietin 1/2 and plasminogen activator inhibitor-1) could be used to accurately predict the phenotype in the training cohort (area under the receiver operating characteristics curve: 0.98, 95% CI 0.97 to 0.99). Mortality rates were 15.6% and 36.4% (p<0.001) in the training cohort and 13.6% and 37.5% (p<0.001) in the validation cohort (N=207). The 'reactive phenotype' was independent from confounders associated with intensive care unit mortality (training cohort: OR 1.13, 95% CI 1.04 to 1.23; validation cohort: OR 1.18, 95% CI 1.06 to 1.31). CONCLUSIONS: Patients with ARDS can be clustered into two biological phenotypes, with different mortality rates. Four biomarkers can be used to predict the phenotype with high accuracy. The phenotypes were very similar to those found in cohorts derived from randomised controlled trials, and these results may improve patient selection for future clinical trials targeting host response in patients with ARDS.

Exhaled breath profiles in the monitoring of loss of control and clinical recovery in asthma.

BACKGROUND: Asthma is a chronic inflammatory airway disease, associated with episodes of exacerbations. Therapy with inhaled corticosteroids (ICS) targets airway inflammation, which aims to maintain and restore asthma control. Clinical features are only modestly associated with airways inflammation. Therefore, we hypothesized that exhaled volatile metabolites identify longitudinal changes between clinically stable episodes and loss of asthma control. OBJECTIVES: To determine whether exhaled volatile organic compounds (VOCs) as measured by gas-chromatography/mass-spectrometry (GC/MS) and electronic nose (eNose) technology discriminate between clinically stable and unstable episodes of asthma. METHODS: Twenty-three patients with (partly) controlled mild to moderate persistent asthma using ICS were included in this prospective steroid withdrawal study. Exhaled metabolites were measured at baseline, during loss of control and after recovery. Standardized sampling of exhaled air was performed, after which samples were analysed by GC/MS and eNose. Univariate analysis of covariance (ANCOVA), followed by multivariate principal component analysis (PCA) was used to reduce data dimensionality. Next paired t tests were utilized to analyse within-subject breath profile differences at the different time-points. Finally, associations between exhaled metabolites and sputum inflammation markers were examined. RESULTS: Breath profiles by eNose showed 95% (21/22) correct classification for baseline vs loss of control and 86% (19/22) for loss of control vs recovery. Breath profiles using GC/MS showed accuracies of 68% (14/22) and 77% (17/22) for baseline vs loss of control and loss of control vs recovery, respectively. Significant associations between exhaled metabolites captured by GC/MS and sputum eosinophils were found (Pearson r≥.46, P<.01). CONCLUSIONS & CLINICAL RELEVANCE: Loss of asthma control can be discriminated from clinically stable episodes by longitudinal monitoring of exhaled metabolites measured by GC/MS and particularly eNose. Part of the uncovered biomarkers was associated with sputum eosinophils. These findings provide proof of principle for monitoring and identification of loss of asthma control by breathomics.

[Non Tuberculous Mycobacteria--a Short Review about Epidemiology, Diagnosis and Treatment]. / Nichttuberkulöse Mykobakterien--eine kurze Übersicht zur Epidemiologie, Diagnostik und Therapie.

Non tuberculous mycobacterial diseases are caused by mycobacteria other than M. tuberculosis complex. NTM are found in the environment and are not transmitted from humans to humans. Infection occurs by the inhalation of dust or aerosols. The finding of NTM is not equal to a diagnosis of active disease. For the diagnosis of active disease well defined clinical and microbiological criteria have to be fulfilled. Gold standard is the detection of NTM by culture, in the case of pulmonary NTM at least two times. There is no established susceptibility testing. Treatment mostly consists of three drugs, given for up to 24 months.

[Resistance to second-line drugs in migrants with multidrug-resistant tuberculosis in the Berlin region]. / Resistenzen gegen Zweitlinienmedikamente bei Migranten mit multiresistenter Tuberkulose in der Region Berlin.

The empiric therapy of multidrug-resistant (MDR) tuberculosis (TB) after rapid molecular testing is rendered difficult by an often several weeks-long period of uncertainty, because results of susceptibility testing for second-line TB drugs are pending. The analysis of regional resistance patterns could lead to a more targeted empiric treatment for migrants depending on their country of origin. The results of the susceptibility testing from 2008 to 2013 of all mycobacteria sent to the Institute of Microbiology, working with the department of Pneumology, Heckeshorn Lung Clinic, Berlin, were reanalysed and tested for regional differences. We found 39 multidrug-resistant Mycobacterium tuberculosis strains among the examined strains. More than half of these strains tested susceptible to the following second line drugs namely, linezolid (97%), clofazimine (95%), cycloserine (95%), capreomycin (90%), p-aminosalicylic acid (82%), moxifloxacin (79%) and amikacin (79%). The proportion of strains susceptible to pyrazinamide (44%), ethambutol (28%), prothionamide (15%), rifabutin (8%) and streptomycin (8%) was lower. The mycobacterial cultures of the Chechen patients (n = 14) showed significantly different susceptibilities to amikacin (57%) and prothionamide (36%) compared to the strains from migrants of other regions. In this study, the regional differences in mycobacterial susceptibility to second line drugs suggest that the initial MDR TB therapy of migrants should be tailored to their country of origin.

Prolonged preoperative hospital stay is a risk factor for complications after emergency colectomy for severe colitis.

AIM: Risk factors for postoperative complications in patients undergoing emergency colectomy for severe colitis in inflammatory bowel disease have hardly been studied. Therefore, this study aimed to define predictors of a complicated postoperative course in these patients. METHOD: A retrospective review was performed of 71 consecutive patients who underwent emergency colectomy for severe colitis between 1999 and 2012 at a tertiary referral centre. Complications were graded according to the Clavien-Dindo classification. Patients with a complication Grade II or higher were compared with those with no complications or a Grade I complication. RESULTS: Nineteen patients (26.7%) had at least one postoperative complication classified as Clavien-Dindo Grade II or higher. In the group with postoperative complications, patients had a higher age (mean 45 vs 35 years, P = 0.020) and a higher body mass index (BMI) (mean 25.9 vs 21.0 kg/m(2), P = 0.006). Length of preoperative hospital stay (median 15 vs 6 days, P = 0.032) was longer in the group with postoperative complications. During the study period, the preoperative hospital stay decreased by 0.8 days per study year (95% CI 0.2-1.5 days, P < 0.001). This did not influence the complication rate over time, however. CONCLUSION: Factors increasing the risk of complications after emergency colectomy for severe colitis were a higher age, a higher BMI and a longer preoperative hospital stay.

[Recommendations for diagnosis and treatment of nontuberculous mycobacterioses of the German Central Committee against tuberculosis and the German Respiratory Society]. / Empfehlungen zur Diagnostik und Therapie nichttuberkulöser Mykobakteriosen des Deutschen Zentralkomitees zur Bekämpfung der Tuberkulose (DZK) und der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP).

Nontuberculous mycobacterioses comprise a group of diseases caused by mycobacteria which do not belong to the Mycobacterium (M.) tuberculosis complex and are not ascribed to M. leprae. These mycobacteria are characterized by a broad variety as to environmental distribution and adaptation. Some of the species may cause specific diseases, especially in patients with underlying immunosuppressive diseases, chronic pulmonary diseases or genetic predisposition, respectively. Worldwide a rising prevalence and significance of nontuberculous mycobacterioses can be recognized. The present recommendations summarise actual aspects of epidemiology, pathogenesis, clinical aspects, diagnostics - especially microbiological methods including susceptibility testing -, and specific treatment for the most relevant species. Diagnosis and treatment of nontuberculous mycobacterioses during childhood and in HIV-infected individuals are described in separate chapters.

Bio-discrimination of alpha-tocopherol stereoisomers in rearing and veal calves fed milk replacer supplemented with all-rac-alpha-tocopheryl acetate.

This study evaluated the biological discrimination of different alpha-tocopherol stereoisomers (i. e. RRR-, RRS-, RSR-, RSS- and the four 2S-alpha-tocopherols) from all-rac-alpha-tocopheryl acetate supplementation in milk replacer for rearing and veal calves respectively, in practical farming conditions. Two experiments were conducted. In experiment 1, six rearing calves were fed milk replacer supplemented with 80 mg/kg all-rac-alpha-tocopheryl acetate for a period of 9 weeks. The calves were supplied calf starter concentrate from 1 to 12 weeks. In experiment 2, six veal calves were fed milk replacer supplemented with 80 mg/kg all-rac-alpha-tocopheryl acetate for a period of 24 weeks. Blood samples were taken at the start and every 4 weeks until 12 weeks for rearing calves in experiment 1, and until slaughter (24 weeks) for veal calves in experiment 2. Liver, adipose, muscle, and brain samples were taken at slaughter of the six veal calves in experiment 2. The distribution of different alpha-tocopherol stereoisomers in feed, plasma, and tissues was analyzed. In both experiments, it was observed that RRR-alpha-tocopherol was the dominant stereoisomer in plasma and tissues. The average percentage of the RRR-alpha-tocopherol stereoisomer was 64 %, and 39 % of the total alpha-tocopherol in plasma for rearing and veal calves, respectively. The higher RRR-alpha-tocopherol stereoisomer proportion as percentage of the total alpha-tocopherol in rearing calves was related to higher dietary natural vitamin E intake. Other 2R-alpha-tocopherol stereoisomers had lower utilization efficiency than RRR-alpha-tocopherol stereoisomer. 2S-alpha-tocopherol stereoisomers were basically not utilized by calves.

Resistance of surface-dried virus to common disinfection procedures.

It is believed that surface-dried viruses can remain infectious and may therefore pose a threat to public health. To help address this issue, we studied 0.1 N NaOH and 0.1% hypochlorite for their capacity to inactivate surface-dried lipid-enveloped (LE) [human immunodeficiency virus (HIV), bovine viral diarrhoea virus (BVDV) and pseudorabies virus (PRV)] and non-lipid-enveloped [NLE; canine parvovirus (CPV) and hepatitis A virus (HAV)] viruses in a background of either plasma or culture medium. In addition, 80% ethanol was tested on surface-dried LE viruses. Without treatment, surface-dried LE viruses remained infectious for at least one week and NLE viruses for more than one month. Irrespective of the disinfectant, inactivation decreased for viruses dried in plasma, which is more representative of viral contaminated blood than virus in culture medium. Inactivation by all disinfectants improved when preceded by rehydration, although the infectivity of CPV actually increased after rehydration and disinfection may thus be overestimated in the absence of rehydration. This is the first comprehensive study of five important (model) viruses in a surface-dried state showing persistence of infectivity, resistance to three commonly used disinfectants and restoration of susceptibility after rehydration. Our results may have implications for hygiene measurements in the prevention of virus transmission.

Toxicity of 6-thioguanine: no hepatotoxicity in a series of IBD patients treated with long-term, low dose 6-thioguanine. Some evidence for dose or metabolite level dependent effects?

BACKGROUND: 6-Thioguanine is used in inflammatory bowel disease since 2001, with promising short-term results. In 2003, liver histology of some 6-thioguanine treated patients showed nodular regenerative hyperplasia. Recently, magnetic resonance imaging revealed nodular regenerative hyperplasia in patients with normal histology. AIMS: Investigating the presence of nodular regenerative hyperplasia in long-term 6-thioguanine treated patients. PATIENTS AND METHODS: Inflammatory bowel disease patients, using 6-thioguanine minimally 24 months, were asked to undergo liver biopsy and magnetic resonance imaging. RESULTS: Fourteen patients used 6-thioguanine minimally 24 months, 13 participated. Mean 6-thioguanine therapy duration, daily dose and 6-thioguanine nucleotide levels were: 36 months, 18.8 mg (0.28 mg/kg) and 705 pmol/8x10(8) erythrocytes, respectively. Liver histology and magnetic resonance imaging showed no nodular regenerative hyperplasia. DISCUSSION: Liver biopsy and magnetic resonance imaging showed no nodular regenerative hyperplasia in these long-term 6-thioguanine treated inflammatory bowel disease patients. 6-thioguanine dose and metabolite levels were lower compared with previous nodular regenerative hyperplasia reports, suggesting dose or metabolite level-dependent effects. Otherwise, nodular regenerative hyperplasia is related with inflammatory bowel disease itself and immunosuppressives, including azathioprine and 6-mercaptopurine. CONCLUSION: 6-Thioguanine is debated due to nodular regenerative hyperplasia. We found no nodular regenerative hyperplasia in inflammatory bowel disease patients with long-term, low dosed 6-thioguanine, suggesting metabolite level-dependent effects. Therefore, 6-thioguanine still seems useful, but in selected patients, intolerant for other immunosuppressives, low dosed and under close surveillance of metabolite levels and hepatotoxity.

Concepts and terminology on plant/pest relationships: toward consensus in plant pathology and crop protection.

In plant pathology , terminological confusion still reigns despite national attempts at standardization. Terminological agreements reached within the crop protection community in The Netherlands are elaborated here and presented as an endeavor toward international consensus. Much of the on-going terminological disconcert derives from differences in outlook between academically oriented biologists (including biologically trained pathologists) and pathologists working in and for agricultural institutions where disease and harm have anthropocentric connotations. The name crop protection science more realistically covers and marks the field dealt with by most plant pathologists, and adoption of the FAO-defined term pest to encompass all biotic factors that are harmful to plants and their products is advocated. The effect of pests on plants and the interrelationships between pests and plants in dependence upon the environment, topical in resistance breeding, are especially dealt with. A diagrammatic model is used to better describe these relationships and to define the terms that denote the phenomena and mechanisms involved.

A case of extreme hypokalaemia.

Hypokalaemia is a common clinical problem. It can lead to severe disturbances in cardiac, neurological and muscle function. We present the case of a 45-year-old woman who was transported to our hospital with cardiac arrest following ventricular fibrillation. Blood sampling revealed severe acidosis (pH 7.02) and extreme hypokalaemia (0.9 mmol/l). The low serum potassium level was most likely caused by the combination of a very deficient diet and use of a thiazide diuretic. She never reported any symptoms. An acute intracellular shift of potassium due to epinephrine and perhaps also the cathecholamines in Red Bull may have further decreased the serum potassium concentration. To our knowledge, this is the lowest potassium level reported in literature. Longer-lasting hypokalaemia might be asymptomatic but when combined with even minor triggers of acute hypokalaemia, serious morbidity or mortality can suddenly occur. Patients on diuretic treatment with suspected malnutrition or chronic gastrointestinal losses require regular monitoring of electrolytes.

Point and trend accuracy of a continuous intravenous microdialysis-based glucose-monitoring device in critically ill patients: a prospective study.

BACKGROUND: Microdialysis is a well-established technology that can be used for continuous blood glucose monitoring. We determined point and trend accuracy, and reliability of a microdialysis-based continuous blood glucose-monitoring device (EIRUS(®)) in critically ill patients. METHODS: Prospective study involving patients with an expected intensive care unit stay of ≥48 h. Every 15 min, device readings were compared with blood glucose values measured in arterial blood during blocks of 8 h per day for a maximum of 3 days. The Clarke error grid, Bland-Altman plot, mean absolute relative difference and glucose prediction error analysis were used to express point accuracy and the rate error grid to express trend accuracy. Reliability testing included aspects of the device and the external sensor, and the special central venous catheter (CVC) with a semipermeable membrane for use with this device. RESULTS: We collected 594 paired values in 12 patients (65 [26-80; 8-97] (median [IQR; total range]) paired values per patient). Point accuracy: 93.6 % of paired values were in zone A of the Clarke error grid, 6.4 % were in zone B; bias was 4.1 mg/dL with an upper limit of agreement of 28.6 mg/dL and a lower level of agreement of -20.5 mg/dL in the Bland-Altman analysis; 93.6 % of the values ≥75 mg/dL were within 20 % of the reference values in the glucose prediction error analysis; the mean absolute relative difference was 7.5 %. Trend accuracy: 96.4 % of the paired values were in zone A, and 3.3 and 0.3 % were in zone B and zone C of the rate error grid. Reliability: out of 16 sensors, 4 had to be replaced prematurely; out of 12 CVCs, two malfunctioned (one after unintentional flushing by unsupervised nurses of the ports connected to the internal microdialysis chamber, causing rupture of the semipermeable membrane; one for an unknown reason). Device start-up time was 58 [56-67] min; availability of real-time data was 100 % of the connection time. CONCLUSIONS: In this study in critically ill patients who had no hypoglycemic episodes and a limited number of hyperglycemic excursions, point accuracy of the device was moderate to good. Trend accuracy was very good. The device had no downtimes, but 4 out of 16 external sensors and 2 out of 12 CVCs had practical problems.

100 years of virology: from vitalism via molecular biology to genetic engineering.

The identification of the causative agent of tobacco mosaic disease as a novel pathogen by the Dutch microbiologist Beijerinck is now acknowledged as being the foundation of virology as a discipline distinct from bacteriology. However, as this was contrary to the prevailing theories of the time, it took many years for virology to become firmly established as a separate discipline. The history of virology illustrates how accepted concepts in science evolve by trial and error and the need for a balanced approach when manipulating natural systems.

The pharmacokinetic effect of discontinuation of mesalazine on mercaptopurine metabolite levels in inflammatory bowel disease patients.

BACKGROUND: In vitro studies suggest interactions between mesalazine (mesalamine) and thiopurines by thiopurine S-methyltransferase (TPMT) inhibition, influencing the balance of hepatotoxic 6-methylmercaptopurine ribonucleotide and immunosuppressive tioguanine (thioguanine) metabolites. AIM: To examine the in vivo pharmacokinetic interaction between mesalazine and mercaptopurine. METHODS: A prospective study was performed in quiescent inflammatory bowel disease patients using the combination of mercaptopurine and mesalazine. Laboratory parameters, 6-methylmercaptopurine ribonucleotide and tioguanine levels and thiopurine S-methyltransferase activity in erythrocytes were measured at stable medication, after mesalazine discontinuation and mesalazine reintroduction, further mercaptopurine was continued. RESULTS: Seventeen patients were participated. Mean mercaptopurine dose was 0.78 mg/kg/day and median of mesalazine dose was 3000 mg/day. After mesalazine discontinuation, mean tioguanine levels changed significantly from 262 to 209 pmol/8 x 10(8) red blood cell, increasing to 270 after reintroduction. Mean 6-methylmercaptopurine ribonucleotide levels were 1422, 2149 and 1503 pmol/8 x 10(8) red blood cell respectively. Mean 6-methylmercaptopurine ribonucleotide/tioguanine ratio increased significantly from 6.3 at baseline to 11.2. Mean baseline thiopurine S-methyltransferase activity was 0.58 pmol/10(6) red blood cell/h and stable. All patients had wild-type thiopurine S-methyltransferase genotypes however, leucocyte counts were stable. DISCUSSION: A significantly higher tioguanine levels and improving 6-methylmercaptopurine ribonucleotide/tioguanine ratio were found during mesalazine/mercaptopurine combination. Theoretically, mesalazine inhibits thiopurine S-methyltransferase activity. In vivo thiopurine S-methyltransferase activity did not change, however. CONCLUSION: Mesalazine has synergistic effects on mercaptopurine therapy, but the mechanism is unclear. Combining these drugs may be further indication for mesalazine in inflammatory bowel disease treatment.

Cyclosporin A effects during primary and secondary activation of human umbilical cord blood T lymphocytes.

OBJECTIVE: Cyclosporin A (CsA), effective in prophylaxis and treatment of graft-vs-host disease (GVHD) after human allogeneic transplantation, blunts T-cell responses by inhibiting nuclear factor of activated T cells-1 (NFAT1) activation. This laboratory has shown that NFAT1 protein expression is severely reduced in human UCB (umbilical cord blood) T cells. Since UCB is increasingly used as a hematopoietic stem cell source in allogeneic transplantation, it is important to determine whether CsA sensitivity in UCB differs from that of adult T cells. METHODS: Surface flow cytometric analysis, intracellular cytokine staining, flow cytometric analysis of cell death, and thymidine incorporation were used in this study to determine T-cell activation and effector functions during primary and secondary stimulation in the presence of CsA. RESULTS: Although we observed differential CsA sensitivity of T-cell activation marker (CD69, CD45RO, CD25) upregulation comparing UCB and adult, we did not observe any significant difference in CsA sensitivity of T-cell effector functions. Importantly, we observed reduced IFN-gamma and TNF-alpha expression in UCB T cells both in primary and secondary stimulation, as well as increased rates of activation-induced cell death (AICD). CONCLUSION: Thus, our studies do not support the previous hypothesis that reduced GVHD observed after UCB transplantation is attributable to increased CsA sensitivity of UCB T cells. Rather, reduced UCB T-cell cytokine production and increased AICD may be important cellular mechanisms underlying these favorable rates of GVHD in UCB transplant recipients.

Role of Vascular Disease in the Evolution of Heart Transplant Patients.

BACKGROUND: The clinical profile of heart transplantation (HT) recipients has changed in recent years. Nowadays, we have to deal with a higher number of co-morbidities, including peripheral vascular disease (PVD). Previous studies suggest an increase in post-HT morbidity and mortality associated with PVD, especially when it is symptomatic. Our study aims were to analyze the prognostic implications of the presence of PVD before transplantation and to determine the factors associated with its development after it. METHODS: HT patients (n = 217) who survived the first year after surgery were included in the study. Mean follow-up was 9 ± 5 years. RESULTS: There were no statistically significant differences in mortality rates between patients with PVD (before or after HT) and those without. One third of patients with PVD required surgery in the post-HT monitoring, either revascularization or amputation. Furthermore, the prevalence of PVD was doubled. Dyslipidemia before HT (odds ratio [OR]: 2.9, 95% confidence interval [CI]: 1.3-6.4; P < .01) and older recipient age (OR: 1.05, 95% CI: 1.01-1.09; P < .05) were independently associated with development of PVD by means of multivariate analysis. CONCLUSIONS: The presence of PVD must be evaluated individually in candidates for heart transplantation despite being a relative contraindication to it at the present time.