HLA-inferred extended haplotype disparity level is more relevant than the level of HLA mismatch alone for the patients survival and GvHD in T cell-replate hematopoietic stem cell transplantation from unrelated donor

Serious risks in unrelated hematopoietic stem cell transplantation (HSCT) including graft versus host disease (GvHD) and mortality are associated with HLA disparity between donor and recipient. The increased risks might be dependent on disparity in not-routinely-tested multiple polymorphisms in genetically dense MHC region, being organized in combinations of two extended MHC haplotypes (Ehp). We assessed the clinical role of donor-recipient Ehp disparity levels in N?=?889 patients by the population-based detection of HLA allele phase mismatch. We found increased GvHD incidences and mortality rates with increasing Ehp mismatch level even with the same HLA mismatch level. In multivariate analysis HLA mismatch levels were excluded from models and Ehp disparity level remained independent prognostic factor for high grade acute GvHD (p?=?0.000037, HR?=?10.68, 95%CI 5.50–32.5) and extended chronic GvHD (p?<?0.000001, HR?=?15.51, CI95% 5.36–44.8). In group with single HLA mismatch, patients with double Ehp disparity had worse 5-year overall survival (45% vs. 56%, p?=?0.00065, HR?=?4.05, CI95% 1.69–9.71) and non-relapse mortality (40% vs. 31%, p?=?0.00037, HR?=?5.63, CI95% 2.04–15.5) than patients with single Ehp disparity. We conclude that Ehp-linked factors contribute to the high morbidity and mortality in recipients given HLA-mismatched unrelated transplant and Ehp matching should be considered in clinical HSCT.     

Evaluation of serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry for the detection of prostate cancer: I. Assessment of platform reproducibility

BACKGROUND: Protein expression profiling for differences indicative of early cancer has promise for improving diagnostics. This report describes the first stage of a National Cancer Institute/Early Detection Research Network-sponsored multiinstitutional evaluation and validation of this approach for detection of prostate cancer. METHODS: Two sequential experimental phases were conducted to establish interlaboratory calibration and standardization of the surface-enhanced laser desorption (SELDI) instrumental and assay platform output. We first established whether the output from multiple calibrated Protein Biosystem II SELDI-ionization time-of-flight mass spectrometry (TOF-MS) instruments demonstrated acceptable interlaboratory reproducibility. This was determined by measuring mass accuracy, resolution, signal-to-noise ratio, and normalized intensity of three m/z "peaks" present in a standard pooled serum sample. We next evaluated the ability of the calibrated and standardized instrumentation to accurately differentiate between selected cases of prostate cancer and control by use of an algorithm developed from data derived from a single site 2 years earlier. RESULTS: When the described standard operating procedures were established at all laboratory sites, the across-laboratory measurements revealed a CV for mass accuracy of 0.1%, signal-to-noise ratio of approximately 40%, and normalized intensity of 15-36% for the three pooled serum peaks. This was comparable to the intralaboratory measurements of the same peaks. The instrument systems were then challenged with sera from a selected group of 14 cases and 14 controls. The classification agreement between each site and the established decision algorithm were examined by use of both raw peak intensity boosting and ranked peak intensity boosting. All six sites achieved perfect blinded classification for all samples when boosted alignment of raw intensities was used. Four of six sites achieved perfect blinded classification with ranked intensities, with one site passing the criteria of 26 of 28 correct and one site failing with 19 of 28 correct. CONCLUSIONS: These results demonstrate that "between-laboratory" reproducibility of SELDI-TOF-MS serum profiling approaches that of "within-laboratory" reproducibility as determined by measuring discrete m/z peaks over time and across laboratories.     

Use of MAG1 recombinant antigen for diagnosis of Toxoplasma gondii infection in humans

This paper describes the cloning, purification, and serological applications of matrix antigen MAG1 of Toxoplasma gondii. The expression system used allows the production of a large amount of T. gondii recombinant protein, which was assessed for its potential use in an enzyme-linked immunosorbent assay (ELISA) for detection of T. gondii infection in humans. Serum samples from 117 patients with different stages of infection, along with 10 serum samples from seronegative patients obtained for routine diagnostic tests, were used. The results were compared with those of an ELISA that uses a native T. gondii antigen extract. The MAG1 antigen detected antibodies more frequently from the acute stage (97.3%) than from the chronic stage (7.5%) of toxoplasmosis. Hence, this antigen may be used as a tool for detection of T. gondii immunoglobulin G antibodies in persons with acute toxoplasmosis.     

A biological,fluorescence and computational examination of synthetic coumarin derivatives with antithrombotic potential

Background

Scientists still look for new drugs, which have anticoagulant properties. This is so important because existing anticoagulant drugs give many side effects, for example major bleeding. In this study we examined nine coumarin derivatives – candidates to be future antithrombotic drugs, which were synthetized and crystallized in our previous paper.

Acupuncture and bronchial asthma: a long-term randomized study of the effects of real versus sham acupuncture compared to controls in patients with bronchial asthma

BACKGROUND: Acupuncture has traditionally been used in China in the treatment of bronchial asthma and is being increasingly applied in Western countries. Although there are many published studies on acupuncture and asthma, few meet the scientific criteria necessary to prove the effectiveness of acupuncture. OBJECTIVE: To examine the short- and long-term effects of real versus sham or no acupuncture in patients with bronchial asthma. DESIGN: Randomized partially blinded study with three parallel groups. SUBJECTS: Sixty-six (66) patients of both genders (mean age, 39 years) with mild-to-moderate persistent bronchial asthma. INTERVENTIONS: After 2 weeks of run-in, the patients with asthma were randomized to receive either real (23 patients) or sham acupuncture (23 patients) or no acupuncture (20 patients). Two acupuncture periods (each 4 weeks) within the first 4 months were followed by a 6-month observation. MEASUREMENTS: Primary outcome was the change of peak expiratory flow (PEF) variability at the end of the two treatment periods. Secondary outcomes were changes in forced expiratory volume in 1 second (FEV1), airway responsiveness, symptoms of asthma, the use of asthma drugs, and patients' well-being. Moreover, the effect of the intervention on eosinophils and eosinophil cationic protein (ECP) in blood and sputum was assessed. RESULTS: PEF variability decreased in all groups. In a subgroup of patients whose asthma medication remained fairly unchanged, PEF variability decreased significantly after needling of real as well as sham points at month 4 and 5 compared to controls (p < or = 0.005). However, there was no difference in the decrease of PEF variability between patients who had the blinded treatment with real or sham acupuncture. Most of the other functional and clinical variables did not differ from those obtained in controls. Eosinophils and ECP in blood and sputum decreased in all groups, but the only significant differences were found in blood eosinophil count at 4 months between sham acupuncture and the control group (p < 0.05) and at 10 months between real and sham acupuncture (p < 0.05) suggesting a possible effect on eosinophilic inflammation. CONCLUSIONS: In view of the fact that the effects after real and sham acupuncture compared to controls who had no needling at all were small, in all likelihood clinically irrelevant, our data do not seem to support the use of acupuncture in the management of pharmacologically well-treated patients with mild-to-moderate persistent asthma.     

The progress in the rehabilitation of dysarthria in Parkinson disease using LSVT (Lee Silverman Voice Treatment)

Parkison's disease causes damage to the central nervous system resulting in bradykinesia, muscle rigidity, rest tremor and dysarthric speech. In clinical terms dysarthria denotes the dysfunction of articulation, phonation and respiration. It is brought about by the impairment of neural paths innervating the speech apparatus, thus causing a decreased ability to communicate. The study was conducted by the Center for Speech and Language Processing (CSLP), Adam Mickiewicz University, Poznań and the Chair and Department of Phoniatrics and Audiology, the Medical University, Poznań within the interdisciplinary research project grant called "Speech and Language Virtual Therapist for Individuals with Parkinson's Disease". Apart from traditional voice and speech therapies, one of the ways of treating speech disturbances accompanying Parkinson's disease is an innovative Lee Silverman Voice Treatment (LSVT). The purpose of this innovative method introduced by dr L. Ramig and colleagues in 1987-1988, is to teach the patient to speak loud. As a result of co-operation between CLSP and the Center for Spoken Language Research (CSLR) at the University of Colorado, Boulder, USA, a Polish version of LSVT Virtual Therapist computer programme was created (LSVTVT). The programme is based on the principles of LSVT. The positive outcomes of the therapy give hope to Parkinson's disease patients with dysarthria, as well as to speech therapists.     

Giant tumor of the orbit--a case of hidradenoma

Orbital tumors are very differential group of lesions. The most common symptoms are ophthalmology dysfunction as: exophthalmus, eye movement dysfunction and visual loss. More often a benign lesions is found than malignant. They are originated mostly from lacrimal glands. We present a case of 62 years old man with large expansion of benign tumor of the orbit with exophthalmus, eye movement disability and complete blindness. The authors performed radical surgery with removing of the orbit content. Histopathology described a very rare tumor of the orbit-hidradenoma.     

An immunohistochemical study of cyclin D1 protein expression in laryngeal squamous cell carcinoma

CONCLUSION: Contrary to most reports, our study shows that the expression of cyclin D1 is not an independent prognostic factor in patients with laryngeal cancer (LC). No correlation between cyclin D1 expression and survival rates in LC was found in a multivariate analysis. OBJECTIVES: The aim of this study was to determine the possible relevance of the expression of cyclin D1 protein in LC as prognostic criteria and to analyse correlation of the expression with clinicopathological features and survival rates. MATERIALS AND METHODS: Immunohistochemistry staining was used to detect the expression of cyclin D1 in 130 samples of laryngeal cancer and in 22 specimens of laryngeal nodules. RESULTS: Cyclin D1 expression was found in 52 (40%) LC samples and in 3 (13.6%) samples of laryngeal nodules. There was no significant correlation between cyclin D1 expression and clinicopathological features of LC. A multivariate analysis of survival confirmed that cyclin D1 expression was not an independent prognostic factor in LC.     

Retinal dysfunction in patients treated with vigabatrin

PURPOSE: To present the current knowledge of vigabatrin influence on the retinal function and to introduce a case report of toxic retinopathy diagnosed in our laboratory, in patient treated with vigabatrin. MATERIAL AND METHODS: A review study based on other authors', concerning the role of diagnostic tests like: perimetry, flash electroretinography (ERG), multifocal electroretinography (mfERG), electrooculography (EOG) in patients treated with vigabatrin and presentation of toxic retinopathy in drug-resistant epileptic patient treated with vigabatrin. RESULTS: In vigabatrin treated patients a functional or structural retinal changes may occur, what can be measured by electrophysiological and visual field testing. Irreversible abnormalities of visual field and ERG tests results prove the toxic character of retinopathy in presented vigabatrin treated patient. CONLUSIONS: ERG tests and visual field assessment should be performed in patients treated with vigabatrin. Initial abnormalities occurrence should be a signal for considering the change of therapy.