Rotator cuff tears: preliminary application of high-resolution MR imaging with counter rotating current loop-gap resonators

A new class of radio frequency (RF) coils for magnetic resonance (MR) imaging and spectroscopy is introduced. The coils consist of two loop-gap resonators of equal diameters positioned along a common axis. They are tuned to the mode in which the current in the two loops flows in opposite directions. These coils are "decoupled" from a uniform excitation field of arbitrary orientation (including circularly polarized fields) by intrinsic decoupling and by means of back-to-back fast recovery diodes. Measurements made with the coils and a phantom saline tank indicate that the signal-to-noise ratio obtainable with these coils is almost identical to that obtained with single loops. Imaging of several anatomic areas, including knee, wrist, and shoulder, has been performed with a 1.5-T MR system that uses circularly polarized RF. A small series of patients with torn rotator cuffs underwent imaging. Difficulties in establishing the diagnosis with MR imaging because of anatomic complexity are illustrated. The value of pulse sequences with long repetition times to increase the signal intensity of fluid in the joint is shown.     

Congenital chylothorax in siblings

We describe two cases of congenital chylothorax in siblings with important differences from previously described familial cases. Our findings support the likelihood of an autosomal recessive inheritance in some cases of this condition, rather than X-linked recessive inheritance, which has also been suggested. Autopsy findings from one of these cases and others previously described suggest that the pathophysiological mechanisms involved may be variable.     

An approach to immunotherapy using antibody to IgE in mast cell leukemia.

Passive immunotherapy was attempted in a patient with mast cell leukemia using antibody against IgE. The results of both in vitro and in vivo studies indicate that although receptor sites for IgE were retained by the malignant mast cell, a secretory defect was present characterized by the spontaneous release of histamine and an impaired secretory response to anti-IgE antibody. Anti-IgE antibody selectively and reproducibly reduced the number of circulating mast cells probably by facilitating their permanent uptake by the reticuloendothelial system. Tolerance was not achieved with high dose deaggregated sheep IgG, nor were we able to confirm the effectivity of immunochemotherapy based on linking chlorambucil to antibody directed against the tumor-associated "antigen" IgE.     

The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement.

BACKGROUND: Heparins and warfarin are currently used as venous thromboembolism (VTE) prophylaxis in surgery. Inhibition of factor (F) Xa provides a specific mechanism of anticoagulation and the potential for an improved benefit-risk profile. OBJECTIVES: To evaluate the safety and efficacy of apixaban, a potent, direct, oral inhibitor of FXa, in patients following total knee replacement (TKR), and to investigate dose-response relationships. PATIENTS/METHODS: A total of 1238 patients were randomized to one of six double-blind apixaban doses [5, 10 or 20 mg day(-1) administered as a single (q.d.) or a twice-daily divided dose (b.i.d.)], enoxaparin (30 mg b.i.d.) or open-label warfarin (titrated to an International Normalized Ratio of 1.8-3.0). Treatment lasted 10-14 days, commencing 12-24 h after surgery with apixaban or enoxaparin, and on the evening of surgery with warfarin. The primary efficacy outcome was a composite of VTE (mandatory venography) and all-cause mortality during treatment. The primary safety outcome was major bleeding. RESULTS: A total of 1217 patients were eligible for safety and 856 patients for efficacy analysis. All apixaban groups had lower primary efficacy event rates than either comparator. The primary outcome rate decreased with increasing apixaban dose (P = 0.09 with q.d./b.i.d. regimens combined, P = 0.19 for q.d. and P = 0.13 for b.i.d. dosing).A significant dose-related increase in the incidence of total adjudicated bleeding events was noted in the q.d. (P = 0.01) and b.i.d. (P = 0.02) apixaban groups; there was no difference between q.d. and b.i.d. regimens. CONCLUSIONS: Apixaban in doses of 2.5 mg b.i.d. or 5 mg q.d. has a promising benefit-risk profile compared with the current standards of care following TKR.     

Immunoglobulin and T cell receptor gene configuration in acute lymphoblastic leukemia of infancy

We examined immunoglobulin (Ig) heavy chain, K light chain, and T cell receptor (TCR) gamma and beta gene configuration in the leukemic cells from a series of infants aged less than 1 year with acute lymphoblastic leukemia (ALL). Each of these 11 cases demonstrated leukemic cell surface antigens that have been correlated with a B cell precursor phenotype. Of the 11, lymphoblasts of 4 retained the germline configuration of both Ig and TCR loci, whereas 7 had rearranged the Ig heavy chain gene. Two of these seven showed light chain gene rearrangement. TCB beta chain rearrangement had occurred in only one of the 11 patients' tumors. No TCR gamma chain rearrangements were identified. These results are in contrast to earlier studies of B cell precursor ALL in children in which Ig heavy chain gene rearrangements were evident in every case and approximately 40% showed Ig light chain rearrangement as well. In addition, 45% of cases of B cell precursor ALL of children had rearranged their gamma TCR genes, and 20% had rearranged beta. These data suggest that ALL in infancy represents an earlier stage of B cell development than is found in B cell precursor ALL of children. ALL in the infant age group has been associated with the worst prognosis of all patients with ALL. This study suggests that the disease in infants differs not only clinically, but also at the molecular genetic level, from the disease in children.     

The beta-globin gene on the Chinese delta beta-thalassemia chromosome carries a promoter mutation

A new type of delta beta-thalassemia characterized by decreased expression of the beta-globin gene and increased expression of both G gamma and A gamma globin gene in the absence of a detectable deletion has recently been described in the Chinese population. In this study we characterize the mutant beta-globin gene from this delta beta- thalassemia chromosome. An A to G transversion is identified in the "ATA" sequence of the promoter region that leads to decreased expression of the beta-globin gene in vivo and in vitro. We also demonstrate the presence of this mutation in every individual with a high fetal hemoglobin phenotype in this family and its absence in every individual with a normal hemoglobin phenotype. This same promoter mutation has recently been detected in Chinese beta-thalassemia genes where it is present on chromosomes of the same haplotype as that of the delta beta-thalassemia chromosome we are studying. These data support the hypothesis that an as yet unidentified mutation occurred on the ancestral chromosome carrying the promoter mutation and subsequently gave rise to the delta beta-thalassemia phenotype.     

Comparison of assays for anti-HBc in blood donors

Testing for anti-HBc has been recommended for use as a paradoxical or surrogate marker of carriers of non-A, non-B hepatitis. Serial sampling on a pool of 35,600 donors was done and those donors found to be repeatedly reactive by EIA method were rested using RIA methodology. Of 1367 donors found to be repeatedly reactive by EIA method, only 984 were confirmed by RIA. Those found to be reactive by EIA only were allowed to donate blood again, with only three of them becoming positive by both EIA and RIA on subsequent donations. The majority of these donors (107 out of 151) reverted to EIA negative status. Therefore, the finding of a positive anti-HBc by EIA method that could not be repeated by RIA method is not an early reproducible sign of anti-HBc reactive status.     

Infection of Nippostrongylus brasiliensis induces normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit

All basophils, mucosal-type mast cells (MMC) and connective tissue-type mast cells (CTMC) are derived from the multipotential hematopoietic stem cell. Mutations at the c-kit locus resulted in deficiency of MMC and CTMC in both mice and rats. To investigate the role of the c-kit receptor tyrosine kinase for production of basophils, we used white spotting/white spotting (Ws/Ws) mutant rats that have a small deletion at the tyrosine kinase domain of the c-kit gene. When Ws/Ws, nude athymic, and normal (+/+) rats were infected with Nippostrongylus brasiliensis (NB), the number of basophils increased greater than 50- fold in the peripheral blood of Ws/Ws and +/+ rats but did not increase in that of nude rats. Blood histamine concentration increased significantly in Ws/Ws and +/+ rats but did not increase in nude rats. Immature basophils increased greater than 10-fold in the bone marrow of Ws/Ws and +/+ rats but did not increase in that of nude rats. Mature and immature basophils that developed after the NB infection were identified by electron microscopy. The present result confirms that T- cell-derived cytokines are indispensable for the augmented production of basophils and suggests that stimulation via the c-kit receptor may not be necessary for the augmented production.     

结直肠癌淋巴管生成与淋巴结转移相关检测的临床研究进展

结直肠癌是人类常见的可经淋巴道转移的恶性肿瘤,其淋巴管生成与转移过程中牵涉了多种生物标志物表达水平的改变,检测这些相关生物标志物可为结直肠癌的诊断、治疗和预后情况提供重大参考价值．本文主要综述近年来与结直肠癌淋巴管生成与淋巴结转移相关检测的临床研究进展．     

A bicistronic retrovirus vector containing a picornavirus internal ribosome entry site allows for correction of X-linked CGD by selection for MDR1 expression

Chronic granulomatous disease (CGD) is an inherited hematologic disorder involving failure of phagocytic cell oxidase to produce superoxide (O2-.), resulting in recurrent infections. The success of retrovirus gene therapy for hematopoietic diseases will be limited both by the efficiency of ex vivo transduction of target cells and by the ability of corrected cells to replace uncorrected cells in vivo. Using MFG-based retrovirus vectors containing oxidase genes, we have previously demonstrated in vitro correction of CGD, but transduction rates were low. In the present study we explore a strategy for providing a selective growth advantage to transduced cells, while retaining the single promoter feature of MFG responsible for high virus titer and enhanced protein production. We constructed a bicistronic retrovirus producing a single mRNA encoding both the therapeutic gene for the X-linked form of CGD (X-CGD), gp91phox, and the selectable human multidrug resistance gene, MDR1 linked together by the encephalomyocarditis virus internal ribosome entry site (IRES). As a control we constructed a bicistronic vector with the polio virus IRES element and using the bacterial neomycin resistance gene (neor) as the selective element. In Epstein-Barr virus transformed B (EBV-B) cells from an X-CGD patient, a tissue culture model of CGD, we show correction of the CGD defect and complete normalization of the cell population using either of these vectors and appropriate selection (vincristine for MDR1 and G418 for neor). Using a chemiluminescence assay of O2-. production, populations of cells transduced with either vector demonstrated initial correction levels of from less than 0.1% up to 2.7% of normal EBV-B cell oxidase activity. With either construct, cell growth under appropriate selection enriched the population of transduced cells, resulting in correction of X-CGD EBV-B cells to a level of O2-. production equalling or exceeding that of normal EBV-B cells. These studies show that a therapeutic gene can be linked to a resistance gene by an IRES element, allowing for selective enrichment of cells expressing the therapeutic gene. Furthermore, the use of MDR1 as a selective element in our studies validates an important approach to gene therapy that could allow in vivo selection and is generalizable to a number of therapeutic settings.