Reproducibilidad de la prueba de sobrecarga oral de glucosa en pacientes con glucosa alterada en ayunas / Reproducibility of the glucose tolerance test in patients with impaired fasting glucose

Fundamento y objetivos. La glucemia alterada en ayunas (GAA) se define por una glucemia basal comprendida entre 5,6 y 6,9 mmol/l en sujetos sin diabetes conocida. Los objetivos del presente estudio fueron: a) analizar la reproducibilidad de la glucemia post-sobrecarga oral de glucosa (SOG) y b) evaluar la concordancia entre los diagnósticos basados en dicha prueba. Sujetos y método. Estudio transversal en adultos diagnosticados de GAA. El estudio consistió en la repetición de una SOG (75 g). Resultados. Se estudiaron 59 pacientes. La SOG se repitió con un intervalo de 37 ± 26 días. Los coeficientes de variación intraindividual de la glucemia basal y postSOG fueron 6,9% y 31,0%, respectivamente. Se evaluó el grado de acuerdo entre los diagnósticos basados en la primera y segunda prueba de SOG (tolerancia normal frente a tolerancia alterada), obteniendo un índice kappa de 0,62 (intervalo de confianza [IC] 95% 0,42-0,82). La concordancia diagnóstica osciló entre un 80% (IC 95%, 70-90%) y un 83% (IC 95%, 73-93%), en función de que el resultado de la SOG inicial fuera patológico o normal, respectivamente. Conclusiones. En pacientes con GAA la reproducibilidad de la SOG es moderada. Por este motivo parece conveniente repetir la prueba antes de tomar decisiones clínicas (AU)

Background and objectives. Impaired fasting glucose (IFG) is defined by a fasting glucose between 5.6 and 6.9 mmol/l in subjects with no known diabetes. The present study objectives were: a) to analyze the glucose tolerance test (GTT) reproducibility and b) to assess this test's diagnostic classification agreement. Patients and method. Cross-sectional study in adult patients diagnosed with IFG. Study subjects underwent a 75 g GTT in two occasions. Results. Fifty-nine patients were studied. The interval between GTT tests was 37 ± 26 days. Fasting and post-GTT plasma glucose intra-individual variation coefficients were 6.9 and 31.0%, respectively. Diagnostic agreement between the two tests (normal tolerance vs. abnormal tolerance) was measured using the kappa index: 0.62 (95% CI 0.42-0.82). Agreement ranged from 80% (95% CI, 70-90%) to 83% (95% CI, 73-93%) depending on whether the first GGT results were abnormal or normal, respectively. Conclusions. GTT reproducibility is moderate in patients diagnosed with IFG. Considering this fact, perhaps this test should be repeated before therapeutic decisions are made (AU)

Intestinal parasitic infection among five interior communities at upper Rejang River, Sarawak, Malaysia.

Intestinal parasitic infection among five interior communities at Bakun Valley, upper Rejang River, Sarawak, Malaysia, was investigated as part of a public health impact assessment of the proposed US$ 3 billion Bakun Hydroelectric Project. Coproparasitological examination of 355 stool samples from 7 of 16 villages representing 5 of 7 tribes in the area revealed infection rate of 41%. A higher infection rate was found among the settled Kayans (56%) than the seminomadic Penans (29%). Infection rate was high (68%) among children less than 14 years old. Trichuris trichiura accounted for more than 90% of all infections; less common were Ascaris lumbricoides, hookworms and Strongyloides stercoralis. Polyparasitism was found in 8% of the individuals surveyed with dual infection due to T. trichiura and A. lumbricoides being more common than dual infection with T. trichiura and hookworm. Women had higher infection rates (57%) than men (33%).

Separation of Notch1 promoted lineage commitment and expansion/transformation in developing T cells.

Notch1 signaling is required for T cell development. We have previously demonstrated that expression of a dominant active Notch1 (ICN1) transgene in hematopoietic stem cells (HSCs) leads to thymic-independent development of CD4(+)CD8(+) double-positive (DP) T cells in the bone marrow (BM). To understand the function of Notch1 in early stages of T cell development, we assessed the ability of ICN1 to induce extrathymic T lineage commitment in BM progenitors from mice that varied in their capacity to form a functional pre-T cell receptor (TCR). Whereas mice repopulated with ICN1 transduced HSCs from either recombinase deficient (Rag-2(-/)-) or Src homology 2 domain--containing leukocyte protein of 76 kD (SLP-76)(-/)- mice failed to develop DP BM cells, recipients of ICN1-transduced Rag-2(-/)- progenitors contained two novel BM cell populations indicative of pre-DP T cell development. These novel BM populations are characterized by their expression of CD3 epsilon and pre-T alpha mRNA and the surface proteins CD44 and CD25. In contrast, complementation of Rag-2(-/)- mice with a TCR beta transgene restored ICN1-induced DP development in the BM within 3 wk after BM transfer (BMT). At later time points, this population selectively and consistently gave rise to T cell leukemia. These findings demonstrate that Notch signaling directs T lineage commitment from multipotent progenitor cells; however, both expansion and leukemic transformation of this population are dependent on T cell-specific signals associated with development of DP thymocytes.

Demonstration of varicella-zoster virus infection in the muscularis propria and myenteric plexi of the colon in an HIV-positive patient with herpes zoster and small bowel pseudo-obstruction (Ogilvie's syndrome).

Gastrointestinal symptomatology as a complication of herpes zoster (HZ) is extremely rare, with the majority of reported cases showing only temporal or radiological evidence of GI tract involvement by varicella zoster virus (VZV) infection. We present the first case of documented direct VZV infection in the muscularis propria of the gut presenting as intestinal pseudo-obstruction (Ogilvie's syndrome). The patient was a 34-yr-old HIV+ man who developed small bowel pseudo-obstruction in association with disseminated cutaneous HZ. A partial ileocolectomy specimen demonstrated a focal ulcer in the terminal ileum. Immunohistochemistry against VZV gpI demonstrated diffuse staining of the muscularis propria and myenteric plexi throughout the length of the specimen. Viral particles consistent with Herpesviridae were shown to be present ultrastructurally. We postulate that the viral infection in the neuronal plexi and muscularis propria caused muscle injury leading to pseudo-obstruction.

Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength.

Notch signaling regulates cell fate decisions in multiple lineages. We demonstrate in this report that retroviral expression of activated Notch1 in mouse thymocytes abrogates differentiation of immature CD4+CD8+ thymocytes into both CD4 and CD8 mature single-positive T cells. The ability of Notch1 to inhibit T cell development was observed in vitro and in vivo with both normal and TCR transgenic thymocytes. Notch1-mediated developmental arrest was dose dependent and was associated with impaired thymocyte responses to TCR stimulation. Notch1 also inhibited TCR-mediated signaling in Jurkat T cells. These data indicate that constitutively active Notch1 abrogates CD4+ and CD8+ maturation by interfering with TCR signal strength and provide an explanation for the physiological regulation of Notch expression during thymocyte development.

Fludeoxyglucose positron emission tomography in the diagnosis of giant cell arteritis.

We describe a case in which fludeoxyglucose F 18 positron emission tomography (PET) led directly to the diagnosis of giant cell arteritis in an elderly woman with a fever of unknown origin. The patient presented with a 3-month history of fatigue, fever, headache, visual disturbance, jaw claudication, and anemia. A computed tomographic scan showed an anterior mediastinal mass that was suspected of being malignant. A fludeoxyglucose F 18 PET scan performed for preoperative evaluation identified striking uptake of fludeoxyglucose F 18 in the walls of the entire aorta, left main coronary artery, and subclavian, carotid, and common iliac arteries bilaterally, suggestive of an arteritis, a diagnosis subsequently confirmed by the findings of an arterial biopsy. Her erythrocyte sedimentation rate was 129 mm/h. There was normalizaton of the PET scan 2 weeks following treatment with prednisolone. This case suggests that fludeoxyglucose F 18 PET contributes to the noninvasive diagnosis of giant cell arteritis, as well as to the evaluation of the extent of disease, response to therapy, and disease recurrence.

Essential roles for ankyrin repeat and transactivation domains in induction of T-cell leukemia by notch1.

Notch receptors participate in a conserved signaling pathway that controls the development of diverse tissues and cell types, including lymphoid cells. Signaling is normally initiated through one or more ligand-mediated proteolytic cleavages that permit nuclear translocation of the intracellular portion of the Notch receptor (ICN), which then binds and activates transcription factors of the Su(H)/CBF1 family. Several mammalian Notch receptors are oncogenic when constitutively active, including Notch1, a gene initially identified based on its involvement in a (7;9) chromosomal translocation found in sporadic T-cell lymphoblastic leukemias and lymphomas (T-ALL). To investigate which portions of ICN1 contribute to transformation, we performed a structure-transformation analysis using a robust murine bone marrow reconstitution assay. Both the ankyrin repeat and C-terminal transactivation domains were required for T-cell leukemogenesis, whereas the N-terminal RAM domain and a C-terminal domain that includes a PEST sequence were nonessential. Induction of T-ALL correlated with the transactivation activity of each Notch1 polypeptide when fused to the DNA-binding domain of GAL4, with the exception of polypeptides deleted of the ankyrin repeats, which lacked transforming activity while retaining strong transactivation activity. Transforming polypeptides also demonstrated moderate to strong activation of the Su(H)/CBF1-sensitive HES-1 promoter, while polypeptides with weak or absent activity on this promoter failed to cause leukemia. These experiments define a minimal transforming region for Notch1 in T-cell progenitors and suggest that leukemogenic signaling involves recruitment of transcriptional coactivators to ICN1 nuclear complexes.

Notch1 expression in early lymphopoiesis influences B versus T lineage determination.

Notch receptors regulate fate decisions in many cells. One outcome of Notch signaling is differentiation of bipotential precursors into one cell type versus another. To investigate consequences of Notch1 expression in hematolymphoid progenitors, mice were reconstituted with bone marrow (BM) transduced with retroviruses encoding a constitutively active form of Notch1. Although neither granulocyte or monocyte differentiation were appreciably affected, lymphopoiesis was dramatically altered. As early as 3 weeks following transplantation, mice receiving activated Notch1-transduced BM contained immature CD4+ CD8+ T cells in the BM and exhibited a simultaneous block in early B cell lymphopoiesis. These results suggest that Notch1 provides a key regulatory signal in determining T lymphoid versus B lymphoid lineage decisions, possibly by influencing lineage commitment from a common lymphoid progenitor cell.

Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow.

Expression of the 210-kD bcr/abl fusion oncoprotein can cause a chronic myelogenous leukemia (CML)-like disease in mice receiving bone marrow cells transduced by bcr/abl-encoding retroviruses. However, previous methods failed to yield this disease at a frequency sufficient enough to allow for its use in the study of CML pathogenesis. To overcome this limitation, we have developed an efficient and reproducible method for inducing a CML-like disease in mice receiving P210 bcr/abl-transduced bone marrow cells. All mice receiving P210 bcr/abl-transduced bone marrow cells succumb to a myeloproliferative disease between 3 and 5 weeks after bone marrow transplantation. The myeloproliferative disease recapitulates many of the hallmarks of human CML and is characterized by high white blood cell counts and extensive extramedullary hematopoiesis in the spleen, liver, bone marrow, and lungs. Use of a retroviral vector coexpressing P210 bcr/abl and green fluorescent protein shows that the vast majority of bcr/abl-expressing cells are myeloid. Analysis of the proviral integration pattern shows that, in some mice, the myeloproliferative disease is clonal. In multiple mice, the CML-like disease has been transplantable, inducing a similar myeloproliferative syndrome within 1 month of transfer to sublethally irradiated syngeneic recipients. The disease in many of these mice has progressed to the development of acute lymphoma/leukemia resembling blast crisis. These results demonstrate that murine CML recapitulates important features of human CML. As such, it should be an excellent model for addressing specific issues relating to the pathogenesis and treatment of this disease.

Myofibroblastoma associated with bilateral gynecomastia: a case report and literature review.

Myofibroblastoma of the breast is a recently recognized benign mesenchymal mammary tumor that typically occurs as a unilateral, solitary lesion. Myofibroblastomas are well-circumscribed, unencapsulated tumors characterized by spindle cells in fascicles which exhibit varying degrees of myogenic and fibroblastic differentiation. Our case reports a mammary myofibroblastoma occurring in an 82-year-old male with gynecomastia and reviews the reported incidence of this benign spindle cell tumor in the world literature.