Clonal karyotype evolution involving ring chromosome 1 with myelodysplastic syndrome subtype RAEB-t progressing into acute leukemia

s Karyotypic evolution is a well-known phenomenon in patients with malignant hernatological disorders during disease progression. We describe a 50-year-old male patient who had originally presented with pancytopenia in October 1992. The diagnosis of a myelodysplastic syndrome (MDS) FAB subtype RAEB-t was established in April 1993 by histological bone marrow (BM) examination, and therapy with low-dose cytosine arabinoside was initiated. In a phase of partial hernatological remission, cytogenetic assessment in August 1993 revealed a ring chromosome 1 in 13 of 21 metaphases beside BM cells with normal karyotypes {[}46,XY,r(1)(p35q31)/46,XY]. One month later, the patient progressed to an acute myeloid leukemia (AML), subtype M4 with 40% BM blasts and cytogenetic examination showed clonal evolution by the appearance of additional numerical aberrations in addition to the ring chromosome{[}46,XY,r(1),+8,-21/45,XY,r(1),+8,-21,-22/46, XY]. Intensive chemotherapy and radiotherapy was applied to induce remission in preparation for allogeneic bone marrow transplantation (BMT) from the patient's HLA-compatible son. After BMT, complete remission was clinically, hematologically and cytogenetically (normal male karyotype) confirmed. A complete hematopoietic chimerism was demonstrated. A relapse in January 1997 was successfully treated using donor lymphocyte infusion and donor peripheral blood stem cells (PB-SC) in combination with GM-CSF as immunostimulating agent in April 1997, and the patient's clinical condition remained stable as of January 2005. This is an interesting case of a patient with AML secondary to MDS. With the ring chromosome 1 we also describe a rare cytogenetic abnormality that predicted the poor prognosis of the patient, but the patient could be cured by adoptive immunotherapy and the application of donor's PB-SC. This case confirms the value of cytogenetic analysis in characterizing the malignant clone in hernatological neoplasias, the importance of controlling the quality of an induced remission and of the detection of a progress of the disease. Copyright (c) 2006 S. Karger AG, Basel

Lower respiratory tract infection and rapid expansion of an abdominal aortic aneurysm: a case report

<p>Abstract</p> <p>Introduction</p> <p>The rate of abdominal aortic aneurysm expansion is related to multiple factors. There is some evidence that inflammation can accelerate aneurysm expansion. However, the association between pulmonary sepsis and rapid abdominal aortic aneurysm expansion is rarely reported.</p> <p>Case presentation</p> <p>Here we present a case of a rapidly expanding abdominal aortic aneurysm in a 68-year-old Caucasian man with a concomitant lower respiratory tract infection and systemic sepsis requiring intensive monitoring and urgent endovascular intervention. Our patient had an uncomplicated post-operative recovery and a follow-up computed tomography scan at one month demonstrated no evidence of an endoleak.</p> <p>Conclusion</p> <p>This case highlights the potential association between pulmonary sepsis and rapid abdominal aortic aneurysm expansion. In such cases, a policy of frequent monitoring should be adopted to identify those patients requiring definitive management.</p

Cellular therapies for treating pain associated with spinal cord injury

Spinal cord injury leads to immense disability and loss of quality of life in human with no satisfactory clinical cure. Cell-based or cell-related therapies have emerged as promising therapeutic potentials both in regeneration of spinal cord and mitigation of neuropathic pain due to spinal cord injury. This article reviews the various options and their latest developments with an update on their therapeutic potentials and clinical trialing

Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients

Aging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to surgery. Patients were 75 years and older and admitted for surgical repair of an acute hip fracture. CSF samples were collected preoperatively. In an exploratory study, we measured 42 cytokines and chemokines by multiplex analysis. We compared CSF levels between patients with and without postoperative delirium and examined the association between CSF cytokine levels and delirium severity. Delirium was diagnosed with the Confusion Assessment Method; severity of delirium was measured with the Delirium Rating Scale Revised-98. Mann-Whitney U tests or Student t-tests were used for between-group comparisons and the Spearman correlation coefficient was used for correlation analyses. Sixty-one patients were included, of whom 23 patients (37.7%) developed postsurgical delirium. Concentrations of Fms-like tyrosine kinase-3 (P=0.021), Interleukin-1 receptor antagonist (P=0.032) and Interleukin-6 (P=0.005) were significantly lower in patients who developed delirium postoperatively. Our findings fit the hypothesis that delirium after surgery results from a dysfunctional neuroinflammatory response: stressing the role of reduced levels of anti-inflammatory mediators in this process. The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient.Registration number: NCT00497978. Local ethical protocol number: NL16222.094.0

Tyrosine kinase Flt3/Flt3-ligand signaling in the modulation of immune responses in experimental arthritis

Rheumatoid arthritis (RA) is an autoimmune, chronic systemic inflammatory disorder that primarily affects flexible joints resulting in severe joint destruction and disability if left untreated. Today, advances in treatment have significantly improved the outcome for patients, although the pathogenesis of RA remains relatively unknown. Signaling through the tyrosine kinase receptor fms-like tyrosine kinase 3 (Flt3) has been suggested to play a part in the RA pathogenesis. Flt3 is primarily expressed on hematopoietic stem cells and lymphoid progenitors in the bone marrow and has an important role in early B-cell development and formation of dendritic cells (DC). Furthermore, the ligand for Flt3 (Flt3L) serves as a regulator of regulatory T-cell (Treg) homeostasis and has been suggested to support differentiation of bone-resorbing osteoclasts. This thesis aimed to investigate the effect of Flt3/Flt3L signaling on the immune system during development of arthritis using an experimental animal model of human RA. Our study shows that Flt3 signaling supports formation of DCs and Treg cells during arthritis development. Treg expansion associated with Flt3L treatment resulted in a reduced production of inflammatory cytokines, reduced levels of antigen-specific antibodies and reduced bone destruction. On the contrary, lack of Flt3L was associated with reduced Treg formation resulting in loss of control over T-cell proliferation, and bone destruction during arthritis. Flt3L was found to positively influence the transcription of the osteoclast-regulating factor IRF8, and could by this mechanism influence osteoclast formation. Impaired signaling through Flt3 resulted in low IRF8 expression, accumulation of osteoclasts in the arthritic joint and an increased loss of femoral trabecular bone. Conversely, Flt3L treatment was associated with increased IRF8 expression, reduced osteoclast formation and restoration of trabecular bone formation in mice lacking Flt3L (Flt3LKO). Finally, we could identify a previously unacknowledged role for Flt3 in peripheral B-cell responses. We demonstrated that Flt3 was re-expressed on activated B-cells following LPS stimulation in vitro and on a population of germinal center B-cells in vivo. By using Flt3LKO mice we could identify an important role for Flt3L in class switch recombination (CSR) to IgG1. B-cells from Flt3LKO mice were found have reduced activation of Stat6 after IL-4 stimulation, resulting in impaired initiation of CSR to IgG1 and highly reduced formation of IgG1+ B-cells and IgG1 production. In summary this thesis shows that Flt3L has an important function in regulating DC and Treg homeostasis and function during arthritis. Furthermore, Flt3L has a regulatory role on osteoclast development and on trabecular bone formation. Finally, signaling through the Flt3 receptor on activated B-cells has an important role in the CSR process and deficiency of Flt3L leads to a skewed antibody response towards the more potent IgG subclasses IgG2b and IgG2c. Together, these results suggest that Flt3L might play a protective role during arthritis by reduction of bone destruction, induction of regulatory T-cells and regulation of antibody effector functions. The conclusion of this thesis is that signaling through the tyrosine kinase Flt3 plays an important role in modulating immune responses during experimental arthritis