Factors influencing the variations of ejection fraction during exercise in chronic aortic regurgitation

The influence of left ventricular volume variations and regurgitant fraction variations upon left ventricular ejection fraction, during exercise was examined using equilibrium radionuclide angiography in patients suffering from aortic regurgitation. Ejection fraction (EF), regurgitant fraction (RF), end diastolic volume (EDV) and end systolic volume (ESV) variations from rest to peak exercise were determined in 44 patients suffering from chronic aortic regurgitation (AR) and in 8 healthy volunteers (C). In C, EF increased (+0.10±0.03, P<0.01) and ESV decreased significantly (-23%±12%, P<0.01) RF and EDV did not vary significantly. In AR patients, EF, EDV and ESV did not vary significantly because of important scattering of individual values. Changes in EF and ESV were inversely correlated (r=-0.79, P<0.01) and RF decreased significantly (-0.12±0.10, P<0.01). Volumes and EF changes during exercise occurred in three different ways. In a 1st subgroup of 7 patients, EF increased (+0.09±0.03, P<0.05) in conjunction with a reduction of ESV (-24%±12%, P<0.05) without a significant change in EDV. In a 2nd group of 22 patients. EF decreased (-0.04±0.07, P<0.01) in association with an increase in ESV (+17%±16%, P<0.01) and no change in EDV. In a 3rd subgroup of 15 patients, EF decreased (-0.02±0.06, P<0.01) despite a reduction in ESV (-7%±6%, P<0.01) because of a dramatic EDV decrease (-10%±6%, P<0.05). In this subgroup, changes in EF were inversely correlated with changes in ESV (r=-0.55, P<0.01) and positively related to EDV variations (r=0.42, P=0.02). EDV related to EDV variations (r=0.42, P=0.02). EDV changes were weakly, but significantly, correlated to RF decrease (r=0.39, P<0.05). We conclude that changes in left ventricular ejection fraction during exercise in patients with chronic aortic regurgitation are significantly related in some patients to changes in ventricular loading conditions as well as contractile state. Therefore, a correct interpretation of EF changes during exercise requires the simultaneous determination of changes in LV volumes.Abbreviations EDV end diastolic volume - EF ejection fraction - ESV end systolic volume - LV left ventricle - RV right ventricle     

Interleukin-18 Affects Local Cytokine Expression But Does Not Impact on the Development of Kidney Allograft Rejection

Interleukin-18 is predominantly a macrophage-derived cytokine with a key role in inflammation and cell-mediated immunity. Having previously demonstrated IL-18 upregulation in a rat model of kidney rejection, here we examined IL-18 in a fully MHC-mismatched murine model of acute kidney rejection using IL-18-deficient recipients (IL-18-/-) and animals administered neutralizing IL-18 binding protein (IL-18BP). Gene expression of IL-18 and its receptor were significantly upregulated in allografts compared to isografts, as was the cellular infiltrate (T cells and macrophages) (p < 0.001). Allografts developed kidney dysfunction (p < 0.05) and tubulitis (p < 0.01) not observed in controls. There was a significant reduction in gene expression of IL-18 downstream pro-inflammatory molecules (iNOS, TNFalpha and IFNgamma) in IL-18-/- recipients (p < 0.01), and IL-18BP-treated animals. The CD4+ infiltrate and IL-4 mRNA expression was greater in the IL-18-/- recipients than wild-type (WT) allografts and IL-18BP-treated animals (p < 0.05), suggesting a Th2-bias which was supported by IFNgamma and IL-4 ELISPOT data and an increased eosinophil accumulation (p < 0.001). Neither IL-18 deficiency nor neutralization prevented renal dysfunction or tubulitis. This study demonstrates increased production of IL-18 in murine kidney allograft rejection and provides evidence that IL-18-induced pathways of inflammation are active. However, neither IL-18 deficiency nor neutralization was protective against the development of allograft rejection.     

Inflammatory malignant fibrous histiocytomas and dedifferentiated liposarcomas: histological review, genomic profile, and MDM2 and CDK4 status favour a single entity

Inflammatory malignant fibrous histiocytoma (inflammatory MFH) is a very rare tumour that occurs most often in the retroperitoneum. So far, it has been considered to be a special subtype of MFH. As it is now widely accepted that most retroperitoneal pleomorphic MFHs are dedifferentiated liposarcomas, the present study compared histological features, genomic profile (CGH analysis), and MDM2 and CDK4 status (immunohistochemistry, FISH, and quantitative PCR) in inflammatory MFHs from 12 patients and dedifferentiated liposarcomas that had an inflammatory MFH component from eight patients. Metaphase cytogenetic and FISH analyses were also performed on one inflammatory MFH. Histological review showed areas of well-differentiated liposarcoma in nine inflammatory MFHs. CGH analysis showed 12q13-15 amplification or gain in six of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Immunohistochemistry showed positivity of tumour cells for MDM2 in every tumour in both groups and for CDK4 in ten and seven inflammatory MFHs and dedifferentiated liposarcomas, respectively. Metaphase cytogenetic and FISH analysis performed on one inflammatory MFH showed the presence of a supernumerary large marker chromosome and ring chromosome with high-level amplification of both MDM2 and CDK4 genes. FISH analysis on paraffin wax-embedded sections showed amplifications of MDM2 and CDK4 in seven of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Quantitative PCR showed amplification of MDM2 in six and of CDK4 in seven of nine inflammatory MFHs. In conclusion, this study strongly suggests that most so-called inflammatory MFHs are dedifferentiated liposarcomas.     

Autosome and Sex Chromosome Diversity Among the African Pygmy Mice, Subgenus Nannomys (Murinae; Mus)

The African pygmy mice, subgenus Nannomys, constitute the most speciose lineage of the genus Mus with 19 recognized species. Although morphologically very similar, they exhibit considerable chromosomal diversity which is here confirmed and extended by the G-banding analysis of 65 mice from West and South Africa. On the basis of their karyotype and distribution area, the specimens were assigned to at least five species. Extensive differentiation both within and between species was observed that involved almost exclusively Robertsonian translocations, 23 of which are newly described. Two of the rearrangements were sex chromosome-autosome translocations, associated in some cases with partial deletions of the X or Y chromosomes. Several authors have predicted that the highly deleterious effect of this rearrangement would be reduced if the sex and autosomal segments were insulated by a block of centromeric heterochromatin. The C-banding analyses performed showed that among the species carrying X-autosome translocations, one followed the expected pattern, while the other did not. In this case, functional isolation of the sex and autosome compartments must involve other repetitive sequences or genomic traits that require further molecular characterization. Such studies will provide insight into the causes and consequences of the high diversity of sex chromosome rearrangements in this subgenus.     

Detection of Staphylococcal Superantigenic Toxins by a CD69-Specific Cytofluorimetric Assay Measuring T-Cell Activation

The presence of staphylococcal superantigenic toxins in the supernatants of liquid cultures was detected by an easy and rapid method assessing the activation of T lymphocytes by cytofluorimetric measurement of CD69 expression. Staphylococcus aureus cells were grown in Eagle’s minimum essential medium supplemented with 5% heat-inactivated fetal calf serum. Supernatant fluids from all S. aureus strains producing superantigen-related toxins, including enterotoxins A to E, toxic shock syndrome toxin, and exfoliative toxins A and B, induced CD69 expression in a significantly higher number of T cells than a cutoff of 2%. This CD69 assay might be used for initial detection of superantigens from S. aureus strains isolated in the context of staphylococcal toxemia or related chronic human diseases such as atopic dermatitis or Kawasaki syndrome.     

t(8;21) prior to acute leukemia

A t(8;21)(q22;q22) without blood and bone marrow invasion by immature myeloid precursor cells occurred in a patient previously treated for polycythemia vera. The presence of a molecular rearrangement confirmed that the chromosomal abnormality was identical to that observed in acute leukemia with t(8;21). This case shows that the translocation, t(8;21), may occur in myelodysplasia and suggests that it can precede the appearance of overt leukemia.     

Recurring bone epithelioid hemangioma

Bone vascular tumors are very rare. Epithelioid types are described according to their architecture, their degree of vascular differentiation, and their cytonuclear atypia. The include epithelioid hemangioma, epithelioid hemangioendothelioma, and angiosarcoma. We report a case of L4 corpus vertebral bone epithelioid hemangioma. The patient was a 25-year-old man with a tumor that recurred twice. The lesion was characterized by a vascular lumen lined by cells with regular nuclei and inflammatory infiltrates. Capillaries were lined by prominent epithelioid endothelial cells, associated with CD31+ and cytokeratin-.     

Building research administration applications for the academic health center: a case study.

The academic health center information environment is saturated with information of varying quality and overwhelming quantity. The most significant challenge is transforming data and information into knowledge. The University of Cincinnati Medical Center's (UCMC) focus is to develop an information architecture comprising data structures, Web services, and user interfaces that enable individuals to manage the information overload so that they can create new knowledge. UCMC has accomplished much of what is reported in this article with the help of a four-year Integrated Advanced Information Management Systems (IAIMS) operation grant awarded by the National Library of Medicine in 2003. In the UCMC vision for knowledge management, individuals have reliable, secure access to information that is filtered, organized, and highly relevant for specific tasks and personal needs. Current applications and tool sets will evolve to become the next generation knowledge management applications or smart digital services. When smart digital services are implemented, silo applications will disappear. A major focus of UCMC's IAIMS grant is research administration. Testing and building out existing and new research administration applications and digital services is underway. The authors review UCMC's progress and results in developing a software architecture, tools, and services for research administration. Included are sections on the evolution to full integration, the impact of the work at UCMC to date, lessons learned during this research and development process, and future plans and needs.     

Early brain lesions and face-processing development

Studies of functional plasticity after pre- or perinatal brain damage can tell us whether the neural substrate normally involved in the development of a given ability is specific and, if so, when it becomes functionally specified and unique. Development of face processing was investigated in 5- to 17-year-old children who had a unilateral brain injury in the pre-, peri-, or postnatal period. In Studies 1 and 2, patients with a posterior injury involving the temporal regions exhibited a face-processing deficit that was independent of their age at test time. Even though differences were observed between the two hemispheres in face processing during infancy as well as in adults in cases of normal development, no clear differences between right and left injury were observed here in face-processing deficit. Poor postlesional face-processing plasticity seems to contrast with results of several studies on speech development after early unilateral injury. If the difference in the time window for postlesional plasticity between these two areas of competency is confirmed, it would suggest that the two kinds of abilities rely on neural cells which are sensitive to different plasticity factors.     

Inflammatory myofibroblastic tumour (inflammatory pseudotumour) of the breast. Clinicopathological and genetic analysis of a case with evidence for clonality.

Inflammatory myofibroblastic tumours (IMTs) were initially considered to be benign reactive processes, but cases with an unfavourable outcome have been reported. Moreover, clonal genetic alterations have recently been published in some cases, suggesting that IMT may represent a malignant neoplastic entity. This paper reports a case of IMT that developed in the mammary gland, an unusual site. The histological picture was characterized by a proliferation of spindle cells with little cellular atypia and rare mitoses, associated with a polymorphous inflammatory infiltrate. Their immunophenotype, characterized by the expression of vimentin, smooth muscle actin, and cytokeratins, corresponded to that of myofibroblasts. Cytogenetic analysis revealed the clonal nature of the lesion. The modal karyotype was 48, X, ins(2;X)(q34;p21.2p22.2), +7, del(9)(p23), +19. Including the present observation, a 9p deletion has now been found in three cases of IMT. These observations show that IMT may be a clonal neoplasm, even in sites different from deep soft tissues.