Recommendations for probiotic use--2008

Recommendations for the clinical use of probiotics were published after a Yale University Workshop in 2005. A similar workshop was held in 2007, and the recommendations were updated and extended into other areas. The recommendations are graded into an "A," "B," "C" or no category based on the expert's opinion and review by the workshop participants. An "A" recommendation is made for acute childhood diarrhea, prevention of antibiotic-associated diarrhea, preventing and maintaining remission in pouchitis, and in an immune response for the treatment and prevention of atopic eczema associated with cow's milk allergy. The group maintained several "B" recommendations in other areas of treating inflammatory bowel disease and irritable bowel syndrome. Although there are significant studies in the "B" group, most "B" recommendations did not reach an "A" level because of some negative studies or a limited number of studies. Many reports in the "C" recommendations were significant but fell short of receiving stronger ratings because of the size of reported patient studies, and also the factors that limited categories to the "B" rating.     

Nitric oxide sera levels as an inflammatory marker in asthma.

BACKGROUND: Nitric oxide is an important regulator of various biological activities in human physiology, and it has been studied in the physiopathology of asthma, especially in exhaled air. OBJECTIVE: We studied the presence of NO in sera of patients with distinct degrees of asthma severity in order to determine a parameter of diagnosis and control of efficacious treatment. METHODS: We determined the presence of NO based upon the Griess reaction in the sera of 124 donors--34 controls and 90 asthmatic subjects. RESULTS: Asthmatic patients presented higher levels of nitric oxide in peripheral blood (56.54 +/- 33.37) compared to the control group (3.06 +/- 4.48). A statistically significant difference (p < 0.0001) between the nitric oxide sera levels from the two groups was demonstrated. CONCLUSION: This study demonstrates that nitric oxide sera levels can be used as an additional inflammatory marker in asthma, especially as an auxiliary diagnostic method in children where NO exhaled air analysis is difficult.     

Severity of multiple organ failure (MOF) but not of sepsis correlates with irreversible platelet degranulation

Summary Multiple hemostatic changes occur in sepsis and multiple organ failure (MOF). To evaluate the role of platelets in patients with sepsis and MOF, we examined changes in surface glycoproteins on circulating platelets of 14 patients with suspected sepsis and MOF. The severity of sepsis and MOF was assessed by the Elebute and APACHE II scoring systems, respectively. Using flow cytometric techniques and platelet specific monoclonal antibodies, platelet surface expression of fibrinogen receptor on GPIIb-IIIa, of von Willebrand Factor receptor GPIb, and of granule glycoproteins (thrombospondin (TSP), GMP-140, GP53) was measured. Plasma membrane expression of GPIIb-IIIa and GPIb on circulating platelets was not affected by sepsis or MOF. Septic patients, however, showed a significantly elevated fibrinogen receptor activity (LIBS1 expression) (p<0.05) that correlated with severity of disease (r=0.597, p=0.043). No significant change in surface expression of granule glycoproteins (TSP, GMP-140, GP53) was noted in septic patients. In contrast, degranulation of granule glycoproteins was significantly elevated in MOF (p<0.05) which correlated well with severity of MOF (GMP-140, r=0.611, p=0.013; TSP, r=0.643, p=0.026). We speculate that platelets in sepsis circulate in a hyperaggregable but still reversible state that results in increased risk of microthrombotic events. In the course of the disease, irreversible platelet degranulation of adhesion molecules occurs that may play an important role in the development of MOF.

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Schweregrad des Multiorganversagens (MOV) jedoch nicht der Sepsis korreliert mit irreversibler Degranulation zirkulierender Thrombozyten

Zusammenfassung Ziel der vorliegenden Pilotstudie war es, die Thrombozytenfunktion von 14 Intensivpatienten mit unterschiedlicher Ausprägung von Sepsis und Multiorganversagen (MOV) zu untersuchen. Schweregrad der Sepsis und des MOV wurde anhand intensivmedizinischer Scoresysteme (APACHE II, Elebute) beurteilt. Die Thrombozytenfunktion wurde durch durchflußzytometrische Bestimmung von membranständigen Glykoproteinen (GPIIb-IIIa, GPIb, Thrombospondin (TSP), GMP-140, GP53) untersucht. Weder Sepsis noch MOV beeinflußten die Oberflächen-expression von GPIIb-IIIa oder GPIb. Die Aktivierung des Fibrinogenrezeptors war jedoch bei Sepsis deutlich erhöht (p<0.05) und korrelierte signifikant mit dem Schweregrad der Erkrankung (r=0,597, p=0,043). Eine signifikant gesteigerte Degranulation der Thrombozyten bei Sepsis konnte jedoch nicht beobachtet werden. Im Gegensatz dazu war die thrombozytäre Freisetzung von Granula-Glykoproteinen (TSP, GMP-140, GP53) bei MOV deutlich erhöht (p<0,05) und korrelierte mit dem Schweregrad der Erkrankung (GMP-140, r=0,611, p=0,013; TSP, r=0,643, p=0,026). Die Ergebnisse dieser Arbeit zeigen, daß Blutplättchen in Patienten mit Sepsis in einem aktivierten jedoch noch reversiblen Aggregationszustand zirkulieren (Aktivierung des Fibrinogenrezeptors), einhergehend mit einem erhöhten Risiko von Mikrothrombosen. Im Laufe der Erkrankung kann es zur gesteigerten Freisetzung und Oberflächenexpression von thrombozytären Glykoproteinen kommen, die eine entscheidende pathophysiologische Rolle in der Entwicklung von Mikrozirkulationsstörungen und MOV spielen könnten.

     

Eisenmenger's syndrome: current management

Eisenmenger's syndrome describes the elevation of pulmonary arterial pressure to the systemic level caused by increased pulmonary vascular resistance with reversal or bi-directional shunting through a large intracardiac or extracardiac congenital heart defect. This article reviews the natural history and pathophysiology of Eisenmenger's syndrome untreated and medical and surgical treatment options presently available. Although there is no cure for this condition at present, recent advances in management have improved the quality of life for many patients with Eisenmenger's syndrome.     

K-RasG12D-induced T-cell lymphoblastic lymphoma/leukemias harbor Notch1 mutations and are sensitive to gamma-secretase inhibitors

To study the impact of oncogenic K-Ras on T-cell leukemia/lymphoma development and progression, we made use of a conditional K-Ras(G12D) murine knockin model, in which oncogenic K-Ras is expressed from its endogenous promoter. Transplantation of whole bone marrow cells that express oncogenic K-Ras into wild-type recipient mice resulted in a highly penetrant, aggressive T-cell leukemia/lymphoma. The lymphoblasts were composed of a CD4/CD8 double-positive population that aberrantly expressed CD44. Thymi of primary donor mice showed reduced cellularity, and immunophenotypic analysis demonstrated a block in differentiation at the double-negative 1 stage. With progression of disease, approximately 50% of mice acquired Notch1 mutations within the PEST domain. Of note, primary lymphoblasts were hypersensitive to gamma-secretase inhibitor treatment, which is known to impair Notch signaling. This inhibition was Notch-specific as assessed by down-regulation of Notch1 target genes and intracellular cleaved Notch. We also observed that the oncogenic K-Ras-induced T-cell disease was responsive to rapamycin and inhibitors of the RAS/MAPK pathway. These data indicate that patients with T-cell leukemia with K-Ras mutations may benefit from therapies that target the NOTCH pathway alone or in combination with inhibition of the PI3K/AKT/MTOR and RAS/MAPK pathways.     

Association between the TAP1 gene polymorphisms and recurrent respiratory papillomatosis in patients from Western Mexico: A pilot study

BackgroundRecurrent respiratory papillomatosis (RRP) is a respiratory tract disease that affects children and adults and is characterized by the recurrent proliferation of multiple papillomas. The etiologic agent is the human papillomavirus, mainly genotypes 6 and 11. Furthermore, polymorphisms in TAP1 appear to influence the selection of antigenic peptides and the transport process to the rough endoplasmic reticulum, for their subsequent presentation to T lymphocytes, an essential process against viral diseases and tumor processes. Previous studies have shown that individuals with those polymorphisms are susceptible to immune, infectious, and tumor‐related diseases. The present study aimed to determine the association between the TAP1 rs1057141 (c.1177A>G) and rs1135216 (c.2090A>G) single nucleotide polymorphisms (SNPs) and RRP.MethodsA case–control study was carried out on a group of 70 individuals (35 controls and 35 patients). RRP diagnosis, HPV genotyping, and viral load were determined through histology and PCR. SNPs rs1057141 and rs1135216 were identified through allelic discrimination, using real‐time PCR. The haplotypic analyses were performed using the Arlequin 3.5 program.ResultsHPV‐6 and HPV‐11 were the genotypes found in the samples. In the polymorphism analysis, rs1057141 showed no significant differences (p = 0.049, CI = 0.994–7.331). In contrast, a significant difference was found in rs1135216 (p = 0.039, OR = 2.4) in the allelic analysis, as well as in the dominant (p = 0.027, OR = 3.06), codominant (p = 0.033, OR = 3.06), and additive model (p = 0.043, OR = 2.505) in subjects with the G allele.ConclusionThe G allele in rs1135216 was associated with a genetic risk of susceptibility for RRP in a population in Western Mexico.     

Joint Trauma System,Defense Committee on Trauma,and Armed Services Blood Program consensus statement on whole blood

Hemorrhage is the most common mechanism of death in battlefield casualties with potentially survivable injuries. There is evidence that early blood product transfusion saves lives among combat casualties. When compared to component therapy, fresh whole blood transfusion improves outcomes in military settings. Cold-stored whole blood also improves outcomes in trauma patients. Whole blood has the advantage of providing red cells, plasma, and platelets together in a single unit, which simplifies and speeds the process of resuscitation, particularly in austere environments. The Joint Trauma System, the Defense Committee on Trauma, and the Armed Services Blood Program endorse the following: (1) whole blood should be used to treat hemorrhagic shock; (2) low-titer group O whole blood is the resuscitation product of choice for the treatment of hemorrhagic shock for all casualties at all roles of care; (3) whole blood should be available within 30 min of casualty wounding, on all medical evacuation platforms, and at all resuscitation and surgical team locations; (4) when whole blood is not available, component therapy should be available within 30 min of casualty wounding; (5) all prehospital medical providers should be trained and logistically supported to screen donors, collect fresh whole blood from designated donors, transfuse blood products, recognize and treat transfusion reactions, and complete the minimum documentation requirements; (6) all deploying military personnel should undergo walking blood bank prescreen laboratory testing for transfusion transmitted disease immediately prior to deployment. Those who are blood group O should undergo anti-A/anti-B antibody titer testing.     

Autologous canine immunotherapy: short-time generated dendritic cells loaded with canine transmissible venereal tumor-whole lysate

Abstract

Objective: The aim of the present study was to evaluate the therapeutic potential of autologous DCs loaded with whole tumor cell lysate of CTVT generated under a simplified and rapid procedure in vitro production process, in a vulvar submucosal model of CTVT in dogs.

Materials and methods: We generated a model of intravulvar CTVT in dogs. A CTVT lysate antigen was prepared according to the method of 1-butanol and after administered with complete Freund's adjuvant via subcutaneous in female healthy dogs and challenge with CTVT cells to corroborate the immunogenicity. Short-time generated dendritic cell pulsed with CTVT whole-lysate was performed, and analyzed by FITC-dextran uptake assay and characterized using anti-canine monoclonal antibodies CD14, CD80, CD83, and DLAII by flow cytometry. Dendritic cell therapy was administered in a frequency of three times every 2 weeks when the CTVT had 4 months of growth and 89?±?5 cm diameter. The CD3⁺, CD4⁺ and CD8⁺ lymphocytes were determined by flow cytometry, and IFN-γ by ELISA assay.

Results and discussion: The administration of CTVT whole-lysate resulted in tumor prevention. The short-time generated dendritic cell pulsed with CTVT whole-lysate administration resulted in an efficient reduction and elimination of CTVT, probably due to the increase in lymphocyte populations (CD3⁺, CD4⁺, and CD8⁺), IFN-γ production and tumor infiltrating lymphocytes.

Conclusion: In conclusion, this study demonstrates the efficacy of immunotherapy based in short-time generated dendritic cell pulsed with CTVT whole-lysate for the treatment of CTVT, and offer veterinary oncologists new alternative therapies to treat this and another malignancy.     

The variability of MR axon radii estimates in the human white matter

The noninvasive quantification of axonal morphology is an exciting avenue for gaining understanding of the function and structure of the central nervous system. Accurate non‐invasive mapping of micron‐sized axon radii using commonly applied neuroimaging techniques, that is, diffusion‐weighted MRI, has been bolstered by recent hardware developments, specifically MR gradient design. Here the whole brain characterization of the effective MR axon radius is presented and the inter‐ and intra‐scanner test–retest repeatability and reproducibility are evaluated to promote the further development of the effective MR axon radius as a neuroimaging biomarker. A coefficient‐of‐variability of approximately 10% in the voxelwise estimation of the effective MR radius is observed in the test–retest analysis, but it is shown that the performance can be improved fourfold using a customized along‐tract analysis.