Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD.

CD4+CD25+ regulatory T cells (Tregs) control immune responses to self- and foreign antigens and play a pivotal role in autoimmune diseases, infectious and noninfectious inflammation, and graft rejection. Since recent experimental studies have indicated that Tregs were able to ameliorate graft-versus-host disease (GvHD), we analyzed the number of infiltrating Tregs in the intestinal mucosa as one site of GvH reactivity using immunoenzymatic labeling to enumerate FOXP3+ T cells in 95 intestinal biopsies from 49 allografted patients in comparison with healthy controls and patients with infectious inflammation. While patients with cytomegalovirus (CMV)-colitis or diverticulitis showed a concomitant increase of CD8+ effectors and Tregs, acute and chronic GvHD were characterized by the complete lack of a counter-regulation indicated by a FOXP3+/CD8+ T-cell ratio identical to healthy controls.

Arthroscopic treatment of anterior shoulder instability.

In the late 1980s and early 1990s, several advances in arthroscopic shoulder stabilization procedures were made. However, these early techniques were associated with higher failure rates compared with the traditional open procedures and therefore were not widely disseminated throughout the orthopaedic community. Because of improved understanding in anatomy and pathology in conjunction with dramatic technologic advances, the past decade has demonstrated significant improvement in the arthroscopic management of the unstable shoulder Evolution of arthroscopic techniques over the past 5 years to more closely resemble open procedures has led to clinical outcomes previously seen only with open procedures.

Mesenchymal stem cells remain of host origin even a long time after allogeneic peripheral blood stem cell or bone marrow transplantation.

Objective: Plasticity of hematopoietic stem cells (HSC) has gained major interest in stem cell research. In order to investigate whether HSC may differentiate into mesenchymal stem cells (MSC), we assessed chimerism in peripheral blood (PB), mononuclear cell fractions (MNC) of bone marrow, and MSC derived from bone marrow (BM) from 27 up to 4225 days after allogeneic transplantation.

Patients And Methods: We applied fluorescence in situ hybridization using X/Y gene probes in sex-mismatched and STR-PCR in sex-matched patients.

Remission induction using alemtuzumab can permit chemotherapy-refractory chronic lymphocytic leukemia (CLL) patients to undergo allogeneic stem cell transplantation.

The outcome of allogeneic stem cell transplantation depends upon the disease status before transplantation. Patients with refractory disease are at high risk for relapse. To improve the curative potential of the transplant procedure, we treated 3 chemotherapy-refractory CLL patients with alemtuzumab before allogeneic stem cell transplantation.

Stem cell mobilization in multiple myeloma patients: do we need an age-adjusted regimen for the elderly?

The upper age limit for autologous progenitor cell transplantation in multiple myeloma patients is increasing continuously. We examined whether this shift in the age of pretreated myeloma patients requires modification of mobilization regimen. We compared retrospectively 21 consecutive progenitor cell mobilizations in 15 pts < 60 years (median age 56, range 37-59) with 33 consecutive mobilizations in 23 pts > 60 years (median age 65, range 60-73) of age.

Simultaneous determination of hypericin and hyperforin in human plasma with liquid chromatography-tandem mass spectrometry.

A selective and sensitive method for the simultaneous determination of hypericin and hyperforin--the two main active ingredients of St. John's Wort (SJW) extract--in human plasma depending on liquid/liquid-extraction and LC/MS/MS detection has been developed, validated after specifying the stability of the photosensitive hypericin in plasma samples during light exposure and applied to samples of a patient. After extraction with ethyl acetate/n-hexane in the darkness, sample extracts were chromatographed isocratically within 6 min on a Kromasil RP-18 column.

Short- and long-term outcomes after large pulmonary resection for germ cell tumors after bleomycin-combination chemotherapy.

Background: Treatment of nonseminomatous germ cell tumors frequently requires bleomycin-combination chemotherapy followed by resection of residual disease. Bleomycin administration however raises concerns with respect to postoperative respiratory complications, particularly for patients undergoing large pulmonary resections. We undertook an institutional review to determine the outcome of large pulmonary resections after bleomycin-combination chemotherapy.

Undeclared exposure to St. John's Wort in hospitalized patients.

Aim: The herbal medicine St. John's Wort (SJW) causes substantial decreases in the plasma concentrations of a range of co-administered drugs. Therefore, we evaluated the extent of systemic exposure to hyperforin and hypericin, two of the main constituents of SJW, in patients on admission and during hospital stay, and compared the results with known use of SJW as documented in the drug chart and detected in additional interviews.

Portrait of transcriptional responses to ultraviolet and ionizing radiation in human cells.

To understand the human response to DNA damage, we used microarrays to measure transcriptional responses of 10 000 genes to ionizing radiation (IR) and ultraviolet radiation (UV). To identify bona fide responses, we used cell lines from 15 individuals and a rigorous statistical method, Significance Analysis of Microarrays (SAM). By exploring how sample number affects SAM, we rendered a portrait of the human damage response with a degree of accuracy unmatched by previous studies.

High prevalence of unknown co-medication in hospitalised patients.

Objective: Co-medication unknown to the treating physician, including self-medication, may compromise drug safety by increasing the risk of duplicate therapy, drug interactions and adverse drug reactions that are not recognised as such. The aim of the current study was to estimate exposure to unknown co-medication during hospitalisation by performing an analytical screening for a broad range of drugs and drug classes in urine of patients admitted to a general internal medicine ward.

Methods: Urine samples of 44 patients were analysed with REMEDiHS (high-performance liquid chromatography) and six different immunoassays.

Efficacy and tolerability of alemtuzumab (CAMPATH-1H) in the salvage treatment of B-cell chronic lymphocytic leukemia--change of regimen needed?

We report on the response rate and tolerability of Alemtuzumab (Campath-1H) in a series of heavily pretreated patients with B-CLL with a special focus on treatment-related problems. All patients tested positive for CD52 on B-lymphocytes before entering the trial. Thirteen patients with B-chronic lymphocytic leukemia (B-CLL), 1 prolymphocytic leukemia (PLL), 1 mantle cell lymphoma (MCL) and 1 leukemic immunocytoma (IC) transformed into a high-grade NHL were included.

Toxicity from radiation therapy associated with abnormal transcriptional responses to DNA damage.

Toxicity from radiation therapy is a grave problem for cancer patients. We hypothesized that some cases of toxicity are associated with abnormal transcriptional responses to radiation. We used microarrays to measure responses to ionizing and UV radiation in lymphoblastoid cells derived from 14 patients with acute radiation toxicity.

Thoracoscopy-assisted Heller myotomy for the treatment of achalasia: results of a minimally invasive technique.

Background: Several surgical methods have been described to treat achalasia with a recent trend toward utilizing minimally invasive techniques to perform a myotomy. Since 1998 our institution has utilized a minimally invasive thoracoscopy-assisted technique (ThAM) that allows a myotomy to be performed under direct visualization.

Methods: From 1992 to 2002, 57 patients underwent transthoracic Heller myotomy at our institution.

Progressive multifocal leukoencephalopathy with detection of JC virus in a patient with chronic lymphocytic leukemia parallel to onset of fludarabine therapy.

Along with the establishment of more intense chemotherapeutic regimens including fludarabine for the treatment of indolent lymphoproliferative diseases like chronic lymphocytic leukemia (CLL), an increasing amount of cases with progressive multifocal leukoencephalopathy (PML) due to JC virus have been observed. We report a patient with CLL who developed PML parallel to the onset of fludarabine therapy. Spinal fluid was tested positive for JC virus.

Functional characterization of CaCBF1, the Candida albicans homolog of centromere binding factor 1.

The centromere binding factor 1 (Cbf1) is necessary for proper chromosome segregation and transcriptional activation of methionine biosynthesis genes in the yeast Saccharomyces cerevisiae and is essential for viability in the related yeasts Kluyveromyces lactis and Candida glabrata. To study the function of Cbf1p in Candida albicans, the major human fungal pathogen, we constructed strains in which both alleles of the CaCBF1 gene were deleted. The Deltacbf1 mutants exhibited a slow growth phenotype and were temperature-sensitive at 42 degrees C.

The Mtr2-Mex67 NTF2-like domain complex. Structural insights into a dual role of Mtr2 for yeast nuclear export.

The formation of the Mtr2-Mex67 heterodimer is essential for yeast mRNA export as it constitutes a key nuclear component for shuttling mRNA between the nuclear and cytoplasm compartments through the nuclear pore complex. We report the crystal structures of apo-Mtr2 from the human pathogen Candida albicans and of its complex with the Mex67 NTF2-like domain. Compared with other members of the NTF2 fold family, Mtr2 displays novel structural features involved in the nuclear export of the large ribosomal subunit and consistent with a dual functional role of Mtr2 during yeast nuclear export events.

DMXB, an alpha7 nicotinic agonist, normalizes auditory gating in isolation-reared rats.

Rationale: Impaired auditory gating is common in schizophrenic patients. Evidence suggests that this deficit is related to a reduced number of alpha(7) nicotinic receptors and therefore treatment with alpha(7) nicotinic agonists may improve this condition. 3-(2,4)-Dimethoxybenzylidine anabaseine (DMXB; also known as GTS-21) is such an agonist and has shown efficacy in mice both orally and intraperitoneally.

Functional analysis of CaRAP1, encoding the Repressor/activator protein 1 of Candida albicans.

The RAP1 gene (repressor/activator protein 1) encodes a transcription factor and telomere binding protein that is essential for viability in the budding yeast Saccharomyces cerevisiae. The genome sequence of the opportunistic fungal pathogen Candida albicans contains a RAP1 homologue. We generated C.

Mediastinal metastases from testicular nonseminomatous germ cell tumors: patterns of dissemination and predictors of long-term survival with surgery.

Objectives: The purpose of this study was to determine the pattern of mediastinal dissemination of nonseminomatous germ cell tumors of testicular origin and evaluate variables that may influence survival with mediastinal dissection in patients with metastatic nonseminomatous germ cell tumors.

Methods: From 1981 to 2000, a total of 421 patients were seen at our institution for extirpation of residual lung or mediastinal disease after cisplatin-based chemotherapy for metastatic testicular nonseminomatous germ cell tumors. We reviewed 268 of these patients, with a mean age of 26.

Twenty years of progress in congenital diaphragmatic hernia at the University of Florida.

Over the past 20 years the clinical paradigms underlying the care of children with congenital diaphragmatic hernia (CDH) have undergone profound changes. The purpose of this work is to provide an historic review of research and clinical studies related to CDH at the University of Florida (UF) and Shands Children's Hospital during the chairmanship of Edward M. Copeland, III, M.

Left anterior descending coronary artery wall thickness measured by high-frequency transthoracic and epicardial echocardiography includes adventitia.

High-frequency, 2-dimensional transthoracic echocardiography (HR-2DTTE) measurements of the left anterior descending (LAD) coronary artery wall thickness are larger than measurements obtained by intravascular ultrasound. We hypothesize that this difference is due to inclusion of the third vascular layer, which may represent adventitia by HR-2DTTE, and that this layer must be increasing in thickness with the development of atherosclerosis. We evaluated the contribution of this third layer to the wall thickness of the normal and atherosclerotic LAD artery imaged by HR-2DTTE using high-frequency epicardial echocardiography (HFEE) as the reference standard.

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In Austria an index of 3 μg/kg of Ochratoxin A for coffee, 0,3 μg/kg for fruit juices and 0,2 μg/kg for beer is discussed. The laboratory of the food inspection authority of the state of Vorarlberg investigated the contribution of selected foodstuffs to the daily OTA intake and compared it with the recommendation of the scientific food committee of the EC. The focal point of this study was on beverages (coffee, coffee substitutes, beer and fruit juices) and their ingredients.

Sterilization of a new medical device using broad-spectrum pulsed light.

In the development of implantable medical devices, effective sterilization is an essential design element. This article outlines how broad-spectrum pulsed light (BSPL) has been implemented to sterilize a novel, implantable medical device. Components of the device have properties incompatible with most sterilization techniques.