Severe Ehrlichia chaffeensis Infection in a Lung Transplant Recipient: A Review of Ehrlichiosis in the Immunocompromised Patient

We describe a case of human ehrlichiosis in a lung transplant recipient and review published reports on ehrlichiosis in immunocompromised patients. Despite early therapy with doxycycline, our patient had unusually severe illness with features of thrombotic thrombocytopenic purpura. Of 23 reported cases of ehrlichiosis in immunocompromised patients, organ failure occurred in all patients and 6 (25%) died

Randomization and Statistical Power: Paramount in Trial Reproducibility (Even for Rare Cancers)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139967/1/onco1129.pd

Ifosfamide May Be Safely Used in Patients with End Stage Renal Disease on Hemodialysis

Background. Pharmacokinetic data on clearance of ifosfamide in hemodialysis patients are limited. Consequently, these patients are excluded from therapy with this agent. We review the outcomes for patients at our institution with end stage renal disease on dialysis who received ifosfamide for metastatic sarcoma. Patients and Methods. We treated three patients with end stage renal disease on hemodialysis with escalating doses of ifosfamide. Data on radiographic response to therapy, WBC and platelet counts, signs or symptoms of infection, neuropathy and bladder toxicity are reported. Starting doses of ifosfamide were based on review of the literature available with subsequent modifications based on each patient's prior exposure to myelosuppressive agents and on symptoms of neurotoxicity and the degree of myelosuppression following each cycle of chemotherapy. Results. Myelosuppression was the most common side effect from therapy, but no patient developed a life threatening infection, neurotoxicity, or hematuria. One patient developed epistaxis in the setting of thrombocytopenia while on warfarin therapy. All patients had clinical evidence for therapeutic response and two had documented radiographic improvement following ifosfamide administration. Conclusion. Ifosfamide can be used safely in combination with hemodialysis in patients with end stage renal disease

EBV-Associated Smooth Muscle Neoplasms: Solid Tumors Arising in the Presence of Immunosuppression and Autoimmune Diseases

Background. Epstein-Barr virus (EBV)-related smooth muscle neoplasms (SMNs) have been associated with immune dysregulation, most notably in patients who have undergone solid organ transplantation or in patients with HIV/AIDS. Objective. to report our experience with EBV-related neoplasms as well as describing the first EBV-related SMN in the setting of administration of glucocorticoids and the tumor necrosis factor inhibitor etanercept. Design. We have case reports, of minimum 3-year follow-up, 2002–2005. Setting. It was held in an academic and tertiary referral cancer center. Patients. Patients are with dysregulated immunity after solid organ transplantation, HIV/AIDS, or with psoriasis after treatment with etanercept. Interventions. There were discontinuation of etanercept, right hepatic trisegmentectomy, and chemotherapy. Measurements. We use survival as a measurement here. Results. Patients who were able to withstand reduction in immunosuppression survived. Surgical resection or chemotherapy was successful in delaying progression of disease. Limitations. There was a relatively short follow-up for these slow-growing neoplasms. Conclusion. EBV-related SMNs have variable aggressiveness. While chemotherapy may slow disease progression, resection and improving the host immune status provide the best opportunity for primary tumor control

A Retrospective Analysis of Vinorelbine Chemotherapy for Patients With Previously Treated Soft-Tissue Sarcomas

Introduction. The role of vinorelbine in specific soft tissue sarcoma subtypes is unclear. We present retrospective single institution experience with single-agent vinorelbine in subjects with metastatic soft tissue malignancies. Methods. Fifty-eight patients were treated with single agent intravenous vinorelbine between April 1997 and December 2004. Doxorubicin had been administered previously to 53 subjects (91%), and the median number of lines of previous chemotherapy was 3 (range 0–7). Results. Patients received a median 6 doses of vinorelbine (range 1–65). The overall response rate was 6% (3 patients: 1 angiosarcoma, 1 epithelioid sarcoma, and 1 embryonal rhabdomyosarcoma). Fourteen patients (26%) experienced a best result of stable disease. Median time to progression was 1.8 months (95% confidence intervals 1.5–2.1 months, Kaplan-Meier estimate). Eight patients experienced grade 3 or 4 toxicity, most commonly febrile neutropenia. Conclusion. Vinorelbine demonstrates limited activity in a heavily pretreated group of soft-tissue sarcoma patients. Prospective investigation may be considered for selected sarcoma subtypes

Role of Interleukin 12 and Costimulators in T Cell Anergy In Vivo

The induction of T cell anergy in vivo is thought to result from antigen recognition in the absence of co-stimulation and inflammation, and is associated with a block in T cell proliferation and Th1 differentiation. Here we have examined the role of interleukin (IL)-12, a potent inducer of Th1 responses, in regulating this process. T cell tolerance was induced by the administration of protein antigen without adjuvant in normal mice, and in recipients of adoptively transferred T cells from T cell receptor transgenic mice. The administration of IL-12 at the time of tolerance induction stimulates Th1 differentiation, but does not promote antigen-specific T cell proliferation. Conversely, inhibiting CTLA-4 engagement during anergy induction reverses the block in T cell proliferation, but does not promote full Th1 differentiation. T cells exposed to tolerogenic antigen in the presence of both IL-12 and anti–CTLA-4 antibody are not anergized, and behave identically to T cells which have encountered immunogenic antigen. These results suggest that two processes contribute to the induction of anergy in vivo; CTLA-4 engagement, which leads to a block in the ability of T cells to proliferate to antigen, and the absence of a prototypic inflammatory cytokine, IL-12, which prevents the differentiation of T cells into Th1 effector cells. The combination of IL-12 and anti–CTLA-4 antibody is sufficient to convert a normally tolerogenic stimulus to an immunogenic one

SDSS J115517.35+634622.0: A Newly Discovered Gravitationally Lensed Quasar

We report the discovery of SDSSJ115517.35+634622.0, a previously unknown gravitationally lensed quasar. The lens system exhibits two images of a $z = 2.89$ quasar, with an image separation of 1{\farcs}832 \pm 0.007 . Near-IR imaging of the system reveals the presence of the lensing galaxy between the two quasar images. Based on absorption features seen in the Sloan Digital Sky Survey (SDSS) spectrum, we determine a lens galaxy redshift of $z = 0.1756$. The lens is rather unusual in that one of the quasar images is only 0{\farcs}22\pm0{\farcs}07 ($\sim 0.1 R_{\rm eff}$) from the center of the lens galaxy and photometric modeling indicates that this image is significantly brighter than predicted by a SIS model. This system was discovered in the course of an ongoing search for strongly lensed quasars in the dataset from the SDSS.Comment: 18 pages, 6 figures. Accepted for publication in A

Molecular structures of gas‐phase polyatomic molecules determined by spectroscopic methods

Spectroscopic data related to the structures of polyatomic molecules in the gas phase have been reviewed, critically evaluated, and compiled. All reported bond distances and angles have been classified as equilibrium (re), average (rz), substitution (rs), or effective (ro) parameters, and have been given a quality rating which is a measure of the parameter uncertainty. The surveyed literature includes work from all of the areas of gas‐phase spectroscopy from which precise quantitative structural information can be derived. Introductory material includes definitions of the various types of parameters and a description of the evaluation procedure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87746/2/619_1.pd

DNA Copy Number Analysis in Gastrointestinal Stromal Tumors Using Gene Expression Microarrays

We report a method, Expression-Microarray Copy Number Analysis (ECNA) for the detection of copy number changes using Affymetrix Human Genome U133 Plus 2.0 arrays, starting with as little as 5 ng input genomic DNA. An analytical approach was developed using DNA isolated from cell lines containing various X-chromosome numbers, and validated with DNA from cell lines with defined deletions and amplifications in other chromosomal locations. We applied this method to examine the copy number changes in DNA from 5 frozen gastrointestinal stromal tumors (GIST). We detected known copy number aberrations consistent with previously published results using conventional or BAC-array CGH, as well as novel changes in GIST tumors. These changes were concordant with results from Affymetrix 100K human SNP mapping arrays. Gene expression data for these GIST samples had previously been generated on U133A arrays, allowing us to explore correlations between chromosomal copy number and RNA expression levels. One of the novel aberrations identified in the GIST samples, a previously unreported gain on 1q21.1 containing the PEX11B gene, was confirmed in this study by FISH and was also shown to have significant differences in expression pattern when compared to a control sample. In summary, we have demonstrated the use of gene expression microarrays for the detection of genomic copy number aberrations in tumor samples. This method may be used to study copy number changes in other species for which RNA expression arrays are available, e.g. other mammals, plants, etc., and for which SNPs have not yet been mapped