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1.
Rev Med Liege ; 74(7-8): 431-435, 2019 Jul.
Artículo en Francés | MEDLINE | ID: mdl-31373460

RESUMEN

We report the case of a 67 years old patient with a history of gastric adenocarcinoma who died in a context of severe dyspnea and whose autopsy will confirm the diagnosis of a Pulmonary Tumor Thrombotic Microangiopathy (PTTM). PTTM is a fatal pulmonary complication associated to multiple cancers. It starts with an acute or subacute respiratory failure quickly evolving towards fatal thrombo-embolic pulmonary hypertension and right heart failure. Pre-mortem diagnosis is difficult and not frequent because the pathology is rare, the underlying neoplastic disease is not always known, clinical and radiological signs are not specific and progression is fast. When made soon enough, PTTM diagnosis avoids useless and sometimes harmful medication. In some cases, an improvement of patient's symptoms and comfort is observed. Some studies described several months of extended survival.


Nous rapportons le cas d'un patient de 67 ans avec un antécédent d'adénocarcinome gastrique décédé dans un contexte de dyspnée majeure et dont l'autopsie confirmera la présence d'une microangiopathie thrombotique tumorale pulmonaire (Pulmonary Tumor Thrombotic Microangiopathy - PTTM). La PTTM est une complication pulmonaire fatale associée à de multiples cancers. Elle se présente par une insuffisance respiratoire d'installation aiguë ou subaiguë, évoluant rapidement vers une hypertension thrombo-embolique pulmonaire et une insuffisance cardiaque droite fatales. Le diagnostic ante-mortem est difficile et rarement posé car la pathologie est rare. L'affection néoplasique sous-jacente n'est pas toujours connue, les signes cliniques et radiologiques sont peu spécifiques et son évolution est rapide. Réalisé à temps, le diagnostic permet, néanmoins, d'éviter une médication inefficace et parfois délétère. Dans certains cas, on observe une amélioration des symptômes et de l'inconfort du patient et, parfois, une survie prolongée de quelques mois.


Asunto(s)
Adenocarcinoma , Neoplasias Pulmonares , Neoplasias Gástricas , Microangiopatías Trombóticas , Adenocarcinoma/complicaciones , Anciano , Humanos , Neoplasias Pulmonares/complicaciones , Células Neoplásicas Circulantes , Neoplasias Gástricas/complicaciones , Microangiopatías Trombóticas/complicaciones
2.
Opt Express ; 19(4): 3304-15, 2011 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-21369153

RESUMEN

We have developed an efficient iterative algorithm for electromagnetic scattering of arbitrary but relatively smooth dielectric objects. The algorithm iteratively adapts the equivalent surface currents until the electromagnetic fields inside and outside the dielectric objects match the boundary conditions. Theoretical convergence is analyzed for two examples that solve scattering of plane waves incident upon air/dielectric slabs of semi-infinite and finite thicknesses. We applied the iterative algorithm for simulation of sinusoidally-perturbed dielectric slab on one side and the method converged for such unsmooth surfaces. We next simulated the shift in radiation pattern of a 6-inch dielectric lens for different offsets of the feed antenna on the focal plane. The result is compared to that of the Geometrical Optics (GO).

3.
J Clin Invest ; 91(4): 1481-9, 1993 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8473495

RESUMEN

IL-2 gene transcription is affected by several nuclear proteins. We asked whether dexamethasone (Dex) and cyclosporin A (CsA) inhibit IL-2 gene transcription by interfering with the activity of nuclear proteins that bind to the IL-2 promoter. Nuclear extracts from primary human T lymphocytes were analyzed by electrophoretic DNA mobility shift assays. Both Dex and CsA inhibited the binding of transcription factors AP-1 and NF-AT, but not of NF-kB and OCT-1/OAF, to their corresponding sites on the IL-2 gene promoter. To correlate changes in nuclear factor binding in vitro with transcriptional activity in vivo and define the structural requirements for IL-2 promoter repression, we used transient DNA transfections. Jurkat cells were transfected with plasmids containing either the intact IL-2 promoter or its AP-1, NF-AT, and NF-kB motifs. Dex inhibited the IL-2 promoter and the AP-1, but not the NF-AT and NF-kB plasmids. In contrast, CsA inhibited the IL-2 promoter and the NF-AT, but not the AP-1 and NF-kB plasmids. These results suggest that in human T lymphocytes both Dex and CsA inhibited IL-2 gene transcription through interference with transcription factors AP-1 and NF-AT. We propose that, while maximum inhibition may involve interaction with both transcription factors, AP-1 is the primary target of Dex.


Asunto(s)
Proteínas de Unión al ADN/farmacología , Glucocorticoides/farmacología , Interleucina-2/genética , Proteínas Nucleares , Proteínas Proto-Oncogénicas c-jun/farmacología , Factores de Transcripción/farmacología , Ciclosporina/farmacología , Proteínas de Unión al ADN/efectos de los fármacos , Dexametasona/farmacología , Humanos , Factores de Transcripción NFATC , Regiones Promotoras Genéticas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-jun/efectos de los fármacos , Linfocitos T/fisiología , Factores de Transcripción/efectos de los fármacos , Transcripción Genética/efectos de los fármacos
4.
J Diabetes Complications ; 20(5): 302-7, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16949517

RESUMEN

AIMS: This study is an investigation of the impact of Type 1 diabetes on bone mineral density (BMD) with regard to bone composition. MATERIAL AND METHODS: Thirty male and 30 premenopausal female patients with Type 1 diabetes (IDD) were retrospectively compared with an equal number of healthy individuals, matched on a person-to-person basis and to the reference population mean. BMD was measured at the L2-L4 vertebrae and femoral neck (FN) by dual energy X-ray absorptiometry (DXA). RESULTS: BMD absolute values were significantly lower in the diabetic than in the healthy males at vertebrae and FN (P<.05). The vertebral BMD values of diabetic women did not significantly differ, whereas those of FN were significantly lower compared with those of the healthy participants. FN age-adjusted BMD values (Z scores) were significantly lower than those of the healthy persons and the population reference mean in both genders (P=.01, <.001 for males and <.01 for females), whereas regarding the vertebrae, only in the diabetic males (P<.05 and <.01 respectively). The percentages of osteopenia and osteoporosis were significantly higher in the male compared to the female diabetic patients (P<.001). No significant correlations existed between the BMD values and diabetes duration, glycosylated hemoglobin (HbA1c) concentration, or age of diabetes onset. Similar results were obtained when applying stepwise multiple regression analysis to explain the BMD value variance. CONCLUSIONS: Young males with Type 1 diabetes exhibit significantly lower BMD values of trabecular and mixed cortical-trabecular bone, compared with matched healthy persons. Premenopausal females with Type 1 diabetes present significantly lower BMD values of mixed bone only. Blood glucose control and diabetes duration do not appear to influence BMD behavior.


Asunto(s)
Densidad Ósea/fisiología , Enfermedades Óseas Metabólicas/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Osteoporosis/complicaciones , Absorciometría de Fotón , Adulto , Índice de Masa Corporal , Enfermedades Óseas Metabólicas/diagnóstico , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Cuello Femoral/anatomía & histología , Cuello Femoral/fisiología , Humanos , Masculino , Análisis por Apareamiento , Osteoporosis/diagnóstico , Valores de Referencia , Factores Sexuales , Columna Vertebral/anatomía & histología , Columna Vertebral/fisiología
5.
Biochim Biophys Acta ; 971(1): 63-71, 1988 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-2900655

RESUMEN

The effect of exogenously added adenylate cyclase from Bordetella pertussis (strain 114) has been investigated in Y-1 mouse adrenal tumor, chinese hamster ovary (CHO) and several other cells. A partially purified adenylate cyclase was found not to enter cells but, nevertheless, produced large amounts of cAMP in the medium. We could show that this resulted from release of ATP (and not larger molecules). The ATP released by the cells could be (1) directly measured and was replenished after each change of medium; (2) was reciprocally related to the cAMP produced; and (3) was competed for by ATPases present in added serum or by hexokinase and, less effectively, by exoenzymes on the cell surface. The extent of ATP leakage varied widely between different cell lines, being marked in CHO and Y-1 adrenal cells but negligible in transformed lymphocyte lines. The uncertainty of the origin of cAMP found in media of cultured cells requires separate analysis of cell and medium cAMP and an assessment of ATP leakage.


Asunto(s)
Adenosina Trifosfato/metabolismo , Adenilil Ciclasas/fisiología , Bordetella pertussis/enzimología , Matriz Extracelular/metabolismo , Animales , Línea Celular , Cricetinae , Cricetulus , Medios de Cultivo/análisis , AMP Cíclico/metabolismo , Femenino , Humanos , Cinética , Ratones , Ovario , Células Tumorales Cultivadas
6.
Eur J Endocrinol ; 152(3): 437-42, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15757861

RESUMEN

OBJECTIVE: Premature menopause is a known risk factor for osteoporosis, whilst the influence of type 2 diabetes on bone mineral density (BMD) is still controversial. DESIGN AND METHODS: BMD values assessed by dual-energy X-ray absorptiometry (DXA) in L2-L4 vertebrae and the femoral neck (FN) of 40 diabetic women with premature menopause (D-EMP) were compared with those of 60 non-diabetic, prematurely menopausal women (EMP) and 60 diabetic women with normal menopause (D-NMP) who had been matched by age and body mass index (BMI). In all women, the time elapsed since menopause ranged between 10 and 25 years and the duration of diabetes exceeded 75% of the postmenopausal time period. The age of D-EMP women was 58.7+/-5 years (mean+/-1 s.d.), age at menopause 39.5+/-2.7, years since menopause 18.6+/-4.9, BMI 27.8+/-4.3 kg/m(2) and duration of diabetes 13.9+/-3.9 years. RESULTS: Vertebral BMD values of D-EMP women were significantly higher than those of EMP women (0.908+/-0.135 vs. 0.817+/-0.14 g/cm(2), P = 0.002), although there was no significant difference between D-EMP and D-NMP women (0.886+/-0.15 g/cm(2)). No significant differences were observed in FN BMD values between all groups. Age-adjusted BMD values (Z scores) of D-EMP women were higher than EMP women in both anatomic sites (P < 0.01), but did not differ from D-NMP women. In contrast to the other two groups, no statistically significant correlation was observed in D-EMP women between the BMD values of either anatomic area and the time elapsed since menopause. HbA(1c) values were positively correlated only to vertebral BMD values of the D-EMP group (P < 0.05). No correlation was observed between the BMD values and the duration of diabetes either in D-EMP or in D-NMP women. CONCLUSIONS: Type 2 diabetes seems to positively affect the mineral density of the trabecular bone in women with premature menopause. The duration of diabetes does not appear to influence bone mass.


Asunto(s)
Densidad Ósea , Diabetes Mellitus Tipo 2/fisiopatología , Menopausia Prematura/metabolismo , Absorciometría de Fotón , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Cuello Femoral/diagnóstico por imagen , Hemoglobina Glucada/metabolismo , Humanos , Vértebras Lumbares/diagnóstico por imagen , Menopausia Prematura/sangre , Persona de Mediana Edad , Factores de Tiempo
7.
Diabetes Care ; 5 Suppl 2: 93-101, 1982.
Artículo en Inglés | MEDLINE | ID: mdl-6765550

RESUMEN

This study investigates and compares human insulin (recombinant DNA) and purified porcine insulin (PPI) in healthy volunteers and in type II diabetic patients, in terms of whether both these insulins were capable of influencing in a different manner pancreatic glucagon, C-peptide, and free fatty acids (FFA) concentrations. The findings reveal that the beta-cell of human pancreas apparently recognizes human insulin more readily than PPI, as assessed by the inhibition of C-peptide, and a similar conclusion follows for the alpha-cell; this conclusion is underscored by the inhibited glucagon values. The delayed increments of glucagon under human insulin following arginine stimulation may be the result of a more rapid insulin absorption from subcutaneous tissue and a greater biologic action of this insulin in comparison with the PPI. Finally, human insulin has additional properties as demonstrated by its stronger antilipolytic effects.


Asunto(s)
Arginina/farmacología , Diabetes Mellitus Tipo 2/fisiopatología , Glucagón/metabolismo , Insulina/farmacología , Absorción , Adulto , Animales , Glucemia , Diabetes Mellitus Tipo 2/sangre , Humanos , Islotes Pancreáticos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/farmacología , Porcinos
8.
J Diabetes Res ; 2015: 354923, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25722989

RESUMEN

OBJECTIVE: This study investigates the association of homocysteine and cortisol with psychological factors in type 2 diabetic patients. METHOD: Homocysteine, cortisol, and psychological variables were analyzed from 131 diabetic patients. Psychological factors were assessed with the Eysenck Personality Questionnaire (EPQ), Hostility and Direction of Hostility Questionnaire (HDHQ), the Symptom Checklist 90-R (SCL 90-R), the Zung Self-Rating Depression Scale (ZDRS), and the Maudsley O-C Inventory Questionnaire (MOCI). Blood samples were taken by measuring homocysteine and cortisol in both subgroups during the initial phase of the study (T0). One year later (T1), the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments and with an identical blood analysis. RESULTS: The relation of psychoticism and homocysteine is positive among controlled diabetic patients (P value = 0.006 < 0.05) and negative among uncontrolled ones (P value = 0.137). Higher values of cortisol correspond to lower scores on extraversion subscale (r(p) = -0.223, P value = 0.010). Controlled diabetic patients showed a statistically significant negative relationship between homocysteine and the act-out hostility subscale (r(sp) = -0.247, P = 0.023). There is a statistically significant relationship between homocysteine and somatization (r(sp) = -0.220, P = 0.043). CONCLUSIONS: These findings support the notion that homocysteine and cortisol are related to trait and state psychological factors in patients with diabetes mellitus type 2.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/psicología , Homocisteína/sangre , Hidrocortisona/sangre , Trastornos Psicóticos/sangre , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Escalas de Valoración Psiquiátrica , Psicometría , Psicopatología , Trastornos Psicóticos/complicaciones , Encuestas y Cuestionarios
9.
Lung Cancer ; 34(1): 133-9, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11557123

RESUMEN

PURPOSE: To define the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) of topotecan in combination with epirubicin in pretreated patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Twenty-seven SCLC patients with performance status (WHO) of 0-2 and adequate renal, hepatic, and bone marrow function who had failed EP-containing front-line chemotherapy entered the study. Patients received escalated doses of topotecan (starting dose 0.5 mg/m(2)) for 5 days and epirubicin (starting dose 40 mg/m(2)) on day 8, every 28 days. RESULTS: All patients were assessable for toxicity and 20 for response. The MTD was topotecan 0.90 mg/m(2) and epirubicin 40 mg/m(2) with neutropenia being the most common dose-limiting event. Seventy-three courses were administered. Grade 3-4 neutropenia occurred in 22 (30%) courses, grade 3-4 anemia in 7 (10%), and grade 3-4 thrombocytopenia in 11 (15%). Seven courses were complicated with fever and one patient died of neutropenic sepsis. Grade 3-4 non-hematologic toxicity was mild and infrequent with only grade 2-3 asthenia occurring in 16 (22%) courses. Among 20 patients who were evaluable for response, 16 (80%) were refractory to prior treatment. One patient with refractory disease (5%) achieved a complete response of 14 weeks duration and four experienced stabilization of the disease. CONCLUSIONS: The combination of topotecan 0.90 mg/m(2) on days 1-5, with epirubicin 40 mg/m(2) on day 8, administered every 28 days is a feasible outpatient regimen which merits further evaluation in patients with chemosensitive disease.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anemia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Pequeñas/patología , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Femenino , Humanos , Infusiones Intravenosas , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Topotecan/administración & dosificación , Topotecan/efectos adversos
10.
Bone Marrow Transplant ; 34(5): 419-23, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15286696

RESUMEN

In an attempt to induce a graft-versus-myeloma effect, we administered donor lymphocyte infusions (DLI) after high-dose therapy with autologous stem cell transplant rescue to seven patients with refractory or relapsed multiple myeloma. High-dose therapy consisted of melphalan, idarubicin and etoposide (days -9 to -6) followed by autologous stem cell infusion on day 0. DLI (five of seven donors with two or three HLA antigens mismatched) were administered on days +1, +5 and +10 along with IL-2 (from day +1 through +12). Six of the seven patients developed acute graft-versus-host disease (GVHD), which resolved spontaneously, coincidentally with autologous hematopoietic reconstitution. One patient failed to engraft and received a second autologous graft. One patient died from complications of a pulmonary hemorrhage after experiencing GVHD. With a minimum follow-up of 38 months, five patients remain without disease progression in complete remission or with minimal residual disease. In this setting, DLI/IL-2 is biologically active resulting in GVHD. A graft-versus-myeloma effect is suggested by the improved outcome of our small cohort of high-risk patients. The use of partially mismatched related donors makes this approach potentially available to nearly all patients.


Asunto(s)
Traslado Adoptivo , Trasplante de Células Madre Hematopoyéticas , Interleucina-2/administración & dosificación , Mieloma Múltiple/terapia , Adulto , Terapia Combinada , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Factores de Riesgo , Donantes de Tejidos
11.
Bone Marrow Transplant ; 24(11): 1259-60, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10642819

RESUMEN

Hemorrhagic cystitis (HC) is a known complication of allogenic BMT. We report a case of a 28-year-old female with CML in chronic phase, which was treated with a matched unrelated donor (MUD) transplant, complicated by hemorrhagic cystitis on day +42 after the transplant. Adenovirus was isolated from the urine and she was treated with ribavirin, 1 g twice a day for 8 days. We report the use of Amicar (E-aminocaproic acid), 2.5 g solution as bladder instillation to treat the intractable hematuria.


Asunto(s)
Infecciones por Adenoviridae , Ácido Aminocaproico/administración & dosificación , Cistitis/tratamiento farmacológico , Hematuria/tratamiento farmacológico , Adulto , Antifibrinolíticos/uso terapéutico , Trasplante de Médula Ósea/efectos adversos , Cistitis/virología , Femenino , Hematuria/virología , Humanos
12.
Bone Marrow Transplant ; 24(8): 879-83, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10516700

RESUMEN

In a series of 74 patients with hematological malignancies undergoing allogeneic bone marrow or peri- pheral blood stem cell transplants from an HLA-identical sibling donor, four developed diffuse alveolar hemorrhage (DAH) between days 0 and 23 post transplant. Diagnosis was made by the radiographic finding of diffuse bilateral lung opacities, and bloody lavage fluid on bronchoscopy. Two patients required mechanical ventilatory support. They were treated with methylprednisolone 0.25-1.5 g/day for at least 4 days with slow tapering thereafter. All patients showed an immediate response and two became long-term survivors with normal respiratory function. Two had a relapse of DAH, developed acute respiratory distress syndrome (ARDS) and died with multi-organ failure. Risk factors for DAH were one or more courses of intensive chemotherapy pretransplant vs no treatment or low-dose chemotherapy (4/4 DAH vs 23/70 no DAH; P = 0.015), and second transplants (2/2 DAH vs 1/70 with no DAH; P = 0.006). These results indicate that DAH is life-threatening but is potentially reversible by prompt treatment with high doses of steroids.


Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Neoplasias Hematológicas/terapia , Hemorragia/tratamiento farmacológico , Enfermedades Pulmonares/tratamiento farmacológico , Adulto , Femenino , Hemorragia/etiología , Humanos , Enfermedades Pulmonares/etiología , Masculino , Trasplante Homólogo
13.
Bone Marrow Transplant ; 21(5): 431-40, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9535034

RESUMEN

To increase the stem cell content of T cell-depleted bone marrow transplants (BMT), we treated 12 patients with hematological malignancies with BMT from HLA-identical sibling donors given G-CSF 10 microg/kg/day for 5 days before marrow harvest. After CD34+ cell selection, patients received a median of 1.7 (range, 0.82-3.1) x 10(6) CD34+ cells/kg and 2.3 (range, 0.25-4.0) x 10(5) CD3+ cells/kg. All patients had initial engraftment but four developed pancytopenia between days 55-130 post-BMT. In two patients, this required a second infusion of G-CSF-mobilized donor peripheral blood progenitor cells. We observed no delayed pancytopenia in a matched historical group of 24 patients receiving T cell-depleted BMT without prior G-CSF stimulation. Compared to this control group, G-CSF-stimulated marrow recipients showed a significant decline in neutrophil and monocyte counts after 8 weeks. However, outcome after BMT was otherwise comparable, with a similar incidence of acute graft-versus-host disease and transplant-related mortality. Disease-free survival was 63 vs 67% for controls matched for CD34+ cell dose (P = NS). These results indicate that G-CSF stimulation can increase the CD34+ cell content of T cell-depleted marrow but carries a risk of late graft failure.


Asunto(s)
Antígenos CD34 , Trasplante de Médula Ósea/métodos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias Hematológicas/terapia , Células Madre Hematopoyéticas , Pancitopenia/etiología , Linfocitos T , Acondicionamiento Pretrasplante , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Citomegalovirus/crecimiento & desarrollo , Supervivencia sin Enfermedad , Transfusión de Eritrocitos , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/terapia , Transfusión de Plaquetas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Activación Viral
14.
Clin Breast Cancer ; 2(1): 52-8, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11899383

RESUMEN

The anti-idiotype monoclonal antibody breast cancer vaccine 11D10 (TriAb) was administered before and after autologous stem cell transplantation (ASCT) in 45 patients with metastatic breast cancer whose disease was responsive to conventional chemotherapy. Evidence of a positive anti-anti-idiotype antibody (Ab3) humoral response was noted at a median of 1.76 months post-ASCT (range, before ASCT-6 months) with this strategy. Maximal Ab3 levels and idiotype-specific T-cell proliferative responses were observed at a median of 3 and 4 months, respectively, after ASCT. The achievement of rapid immune responses after ASCT, during a known period of decreased immunoresponsiveness, opens the possibility of an additional antitumor effect at a time when the tumor burden is relatively small. Moreover, in this interim analysis, patients with the most vigorous humoral and cellular immune responses had a significant improvement in progression-free survival. Further follow-up and evaluation of this approach is warranted.


Asunto(s)
Anticuerpos Antiidiotipos/inmunología , Neoplasias de la Mama/terapia , Vacunas contra el Cáncer/uso terapéutico , Glucolípidos/inmunología , Glicoproteínas/inmunología , Trasplante de Células Madre Hematopoyéticas , Adulto , Anciano , Anticuerpos Monoclonales , Neoplasias de la Mama/inmunología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunidad Celular , Gotas Lipídicas , Activación de Linfocitos , Persona de Mediana Edad , Tasa de Supervivencia , Linfocitos T/inmunología , Trasplante Autólogo , Resultado del Tratamiento
15.
Exp Clin Endocrinol Diabetes ; 109 Suppl 2: S424-37, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11460589

RESUMEN

Diabetic Nephropathy (DN) is the commonest cause of end-stage renal failure (ESRF) in the Western world. Diabetic nephropathy follows a well outline clinical course, starting with microalbuminuria through proteinuria, azotaemia and culminating in ESRF. Before the onset of overt proteinuria, there are various renal functional changes including renal hyperfiltration, hyperperfusion, and increasing capillary permeability to macromolecules. Basement-membrane thickening and mesangial expansion have long been recognized as pathological hallmark of diabetes. It has been postulated that DN occurs as a result of the interplay of metabolic and hemodynamic factors in the renal microcirculation. There is no doubt that there is a positive relationship between hyperglycaemia, which is necessary but not sufficient, and microvascular complications. The accumulation of advanced glycosylated end-products (AGEs), the activation of isoform(s) of protein kinase C (PKC) and the acceleration of the aldose reductase pathway may explain how hyperglycemia damages tissue. PKC is one of the key signaling molecules in the induction of the vascular pathology of diabetes. The balance between extracellular matrix production and degradation is important in this context. Transforming growth factor-beta (TGF-beta) appears to play a pivotal role in accumulation in the diabetic kidney. Hemodynamic disturbances are believed to be directly responsible for the development of glomerulosclerosis and its attendant proteinuria. There is familial clustering of diabetic kidney disease. A number of gene loci have been investigated to try to explain the genetic susceptibility to diabetic nephropathy. The genes coding for components of renin-angiotensin system have drawn special attention, due to the central role that this system plays in the regulation of blood pressure, sodium metabolism, and renal hemodynamics. Endothelial dysfunction is closely associated with the development of diabetic retinopathy, nephropathy and atherosclerosis, both in IDDM and in NIDDM. The pathogenesis of diabetic nephropathy is not clarified completely yet.


Asunto(s)
Nefropatías Diabéticas/etiología , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/genética , Endotelio Vascular/fisiopatología , Hemodinámica , Humanos
16.
Exp Clin Endocrinol Diabetes ; 107(6): 350-5, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10543411

RESUMEN

A single-center, randomised, placebo- controlled, cross-over study was conducted to characterize the new sulfonylurea glimepiride and to compare its profile of action with the second generation sulfonylurea glibenclamide. The total duration of each experiment was 5 hours. At zero time an i.v. injection of 2 and 4 mg glimepiride, 1 mg glibenclamide or placebo was given i.v. to 24 healthy volunteers. Blood samples were collected for three hours after the injection (0-3 hours, preprandial experiment). At 3 hours, a standard mixed meal was given (20%, of a 30 Kcal/Kg Body Weight diet) and blood samples were collected for 2 more hours (postprandial experiment). Pre-prandially (0-3 hrs) blood glucose (expressed as the area under the curve divided by the time) was significantly lower (p < 0.0001) after the administration of 2 and 4 mg glimepiride (3.8 +/- 0.22 and 3.5 +/- 0.3 mM respectively) compared to placebo (4.63 +/- 0.31 mM), but not compared to glibenclamide. Insulin and C-peptide were not different after glimepiride or glibenclamide. Both glimepiride and glibenclamide had similar effects on insulin secretion. Post-prandially (3-5 hrs) blood glucose was significantly higher after glibenclamide (6.54 +/- 0.8 mM) (p < 0.0001) than after 2 mg glimepiride (5.75 +/- 0.5 mM). Despite this C-peptide was significantly higher (p < 0.002) glibenclamide (5.7 +/- 1.5 ng/ml) compared to glimepiride (5.1 +/- 1.3 ng/ml); the trend was the same for insulin but the results were not significantly different (p = 0.06) In conclusion, in the fasting state, glimepiride and glibenclamide had similar effects on the changes in blood glucose levels after i.v. administration. After the meal, less pronounced hyperglycemia and lower insulin and C-peptide levels following glimepiride (2 mg) suggests either that glimepiride induces insulin secretion through a pathway which is different from that of glibenclamide or that glimepiride facilitates insulin action through extrapancreatic effects.


Asunto(s)
Gliburida/farmacología , Hipoglucemiantes/farmacología , Compuestos de Sulfonilurea/farmacología , Adolescente , Adulto , Glucemia/metabolismo , Péptido C/sangre , Estudios Cruzados , Método Doble Ciego , Ayuno , Alimentos , Humanos , Insulina/sangre , Cinética , Masculino , Persona de Mediana Edad , Placebos
17.
Curr Diabetes Rev ; 9(6): 450-61, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24111620

RESUMEN

Oxytocin (OXT) is a neurohypophysial hormone which is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. OXT is currently attracting considerable attention because it has been discovered that it regulates various functions of behavior especially in the context of social interactions. OXT is a key component in bone formation, glycemia, male sexuality, cardiac differentiation and pregnancy and thus it is important to be further explored. The authors review various aspects of gestational diabetes, including definition, screening, diagnostic procedures, complications, clinical evaluation, indications of delivery and neonatal aspects. Not only the relation among diabetes mellitus, oxytocin and neurophysiology concerning erectile dysfunction, but also the role of OXT in the activity of arginine and vasopressin is investigated. It is imperative to develop technological and experimental methods that will be able to reveal the oxytocin and its potential.


Asunto(s)
Arginina Vasopresina/metabolismo , Química Encefálica/efectos de los fármacos , Diabetes Mellitus/metabolismo , Hipotálamo/metabolismo , Oxitócicos/metabolismo , Oxitocina/metabolismo , Animales , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/fisiopatología , Femenino , Vaciamiento Gástrico/efectos de los fármacos , Humanos , Trabajo de Parto/metabolismo , Lactancia/efectos de los fármacos , Masculino , Oxitócicos/administración & dosificación , Oxitocina/administración & dosificación , Embarazo , Ratas , Receptores de Superficie Celular/efectos de los fármacos , Receptores de Superficie Celular/metabolismo , Receptores de Oxitocina/metabolismo , Conducta Social
18.
Exp Clin Endocrinol Diabetes ; 120(7): 416-9, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22441720

RESUMEN

Therapy with either angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB) or thiazolidinediones (TZD) is associated with dose-dependent decrements in hematocrit and hemoglobin levels. We aimed to investigate the impact of the coadministration of TZD and ACEI/ARB on hematocrit and hemoglobin values in uncomplicated patients with type 2 diabetes mellitus and normal serum creatinine.Data from patients with type 2 diabetes currently followed, were reviewed and patients treated with ACEI/ARB and/or TZD were identified. For the purpose of this study the following 4 groups of 30 stable non-anemic diabetic patients each matched for age, gender, and BMI were formed. Group ACEI/ARB included patients on ACEI/ARB without TZD, group TZD included patients on TZD and antihypertensive agents other than ACEI/ARB, group ACEI/ARB/TZD consisted of patients on combined therapy with ACEI/ARB and TZD and the control group C included patients never exposed to ACEI/ARB or TZD. Clinical and laboratory data were collected prior to initiation of treatment and after 6 months.Neither hematocrit nor hemoglobin showed any significant change from baseline at the end of the study in group C. In both group ACEI/ARB and group TZD a small, but statistically significant reduction in hematocrit (~ 1% point) and hemoglobin levels (~ 0.3 g/dl) was seen. A greater statistically and clinically important reduction in hematocrit (~ 3% points) and hemoglobin (~ 1 g/dl) levels was observed in group ACEI/ARB/TZD. Furthermore, incident anemia at the end reached 7% in group TZD and 23% in group ACEI/ARB/TZD.Coadministration of RAS inhibitors and PPAR-γ agonists should be considered in the differential diagnosis of hematocrit lowering and anemia in uncomplicated type 2 diabetic patients with normal serum creatinine. Further studies are required to clarify the mechanism(s), the cardiovascular consequences and the cost utility of anemia workup in such patients.


Asunto(s)
Anemia/inducido químicamente , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , PPAR gamma/agonistas , Tiazoles/efectos adversos , Anciano , Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Índice de Masa Corporal , Quimioterapia Combinada/efectos adversos , Femenino , Hematócrito , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Sistema Renina-Angiotensina/efectos de los fármacos , Tiazoles/administración & dosificación
19.
Exp Diabetes Res ; 2012: 560864, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22997507

RESUMEN

BACKGROUND: The aim of this study was to investigate the association of oxytocin with trait and state psychological factors in type 2 diabetic patients. METHODS: OXT and psychological variables were analyzed from 86 controlled diabetic patients (glycosylated haemoglobin A1c (HbA1c) < 7%) from 45 uncontrolled diabetic patients (HbA1c ≥ 7). Psychological characteristics were assessed with the Eysenck Personality Questionnaire (EPQ), while state psychological characteristics were measured with the Symptom Checklist 90-R (SCL 90-R). Blood samples were taken for measuring oxytocin in both subgroups during the initial phase of the study. One year later, the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments. RESULTS: During the first evaluation of the uncontrolled diabetic patients, a statistically significant positive relationship between the levels of OXT and psychoticism in EPQ rating scale (P < 0.013) was observed. For controlled diabetic patients, a statistically significant negative relationship between oxytocin and somatization (P < 0.030), as well as obsessive-compulsive scores (P < 0.047) in SCL-90 rating scale, was observed. During the second assessment, the values of OXT decreased when the patients managed to control their metabolic profile. CONCLUSIONS: The OXT is in association with psychoticism, somatization, and obsessionality may be implicated in T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Hiperglucemia/prevención & control , Trastorno Obsesivo Compulsivo/complicaciones , Oxitocina/sangre , Trastornos Psicóticos/complicaciones , Trastornos Somatomorfos/complicaciones , Anciano , Estudios Transversales , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/terapia , Regulación hacia Abajo , Femenino , Hemoglobina Glucada/análisis , Grecia , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/etiología , Servicio Ambulatorio en Hospital , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/etiología , Trastornos Somatomorfos/etiología
20.
IEEE Trans Biomed Eng ; 58(6): 1839-45, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21382761

RESUMEN

This paper analyzes heart rate (HR) information from physiological tracings collected with a remote millimeter wave (mmW) I-Q sensor for biometric monitoring applications. A parameter optimization method based on the nonlinear Levenberg-Marquardt algorithm is used. The mmW sensor works at 94 GHz and can detect the vital signs of a human subject from a few to tens of meters away. The reflected mmW signal is typically affected by respiration, body movement, background noise, and electronic system noise. Processing of the mmW radar signal is, thus, necessary to obtain the true HR. The down-converted received signal in this case consists of both the real part (I-branch) and the imaginary part (Q-branch), which can be considered as the cosine and sine of the received phase of the HR signal. Instead of fitting the converted phase angle signal, the method directly fits the real and imaginary parts of the HR signal, which circumvents the need for phase unwrapping. This is particularly useful when the SNR is low. Also, the method identifies both beat-to-beat HR and individual heartbeat magnitude, which is valuable for some medical diagnosis applications. The mean HR here is compared to that obtained using the discrete Fourier transform.


Asunto(s)
Análisis de Fourier , Frecuencia Cardíaca/fisiología , Monitoreo Fisiológico/métodos , Algoritmos , Biometría , Distribución de Chi-Cuadrado , Humanos , Dinámicas no Lineales , Radar , Frecuencia Respiratoria
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