Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 67
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
B-ENT ; 9(2): 122-31, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23909119

RESUMEN

OBJECTIVE: The purpose of this study is to describe the results of universal newborn hearing screening (UNHS) in 2229 newborns and to assess the effectiveness of a two-stage automated transient evoked otoacoustic emission (a-TEOAE) test protocol. MATERIALS AND METHODS: Between May 2007 and January 2008, a universal newborn hearing screening program, instituting two-stage a-TEOAE, was evaluated. The hearing status of the newborns who failed the two-stage screening tests were evaluated with the auditory brainstem response (ABR) test during the diagnostic stage. The risk factors for hearing loss determined by the Joint Committee on Infant Hearing Loss (JCIH) and prematurity, consanguineous marriage, and birth type as presumptive risk factors were recorded. RESULTS: During the study period, 2229 newborns were screened. Sensorineural hearing loss (SNHL) was identified in 8 newborns. Fourteen newborns were lost to follow-up. One hundred thirty six newborns were high-risk neonatal intensive care unit (NICU) patients. The prevalence of SNHL was 2.9% (4/136) in NICU newborns, and 0.19% (4/2079) in the well-baby nursery. SNHL prevalence in the study group overall was found to be 0.36% (8/2215). Craniofacial anomalies and family history of hearing loss were found to be significantly related to SNHL in newborns. Prematurity and consanguinity that are not listed among JCIH risk factors were also found to be statistically significantly related with SNHL. CONCLUSIONS: This is the first report of a universal hearing screening program in the Eastern Black Sea region of Turkey. Two-stage a-TEOAE is an efficient and feasible hospital-based screening protocol in newborns.


Asunto(s)
Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/epidemiología , Tamizaje Neonatal , Emisiones Otoacústicas Espontáneas , Humanos , Recién Nacido , Prevalencia , Factores de Riesgo , Turquía/epidemiología
2.
Turk J Haematol ; 30(3): 256-62, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24385804

RESUMEN

OBJECTIVE: Graft-versus-host disease (GVHD) is a major obstacle to successful allogeneic bone marrow transplantation (allo-BMT). While multipotent mesenchymal stromal cells (MSCs) demonstrate alloresponse in vitro and in vivo, they also have clinical applications toward prevention or treatment of GVHD. The aim of this study was to investigate the ability of MSCs to prevent or treat GVHD in a rat BMT model. MATERIALS AND METHODS: The GVHD model was established by transplantation of Sprague Dawley rats' bone marrow and spleen cells into lethally irradiated (950 cGy) SDxWistar rat recipients. A total of 49 rats were randomly assigned to 4 study and 3 control groups administered different GVHD prophylactic regimens including MSCs. After transplantation, clinical GVHD scores and survival status were monitored. RESULTS: All irradiated and untreated control mice with GVHD died. MSCs inhibited lethal GVHD as efficiently as the standard GVHD prophylactic regimen. The gross and histopathological findings of GVHD and the ratio of CD4/CD8 expression decreased. The subgroup given MSCs displayed higher in vivo proportions of CD25+ T cells and plasma interleukin-2 levels as compared to conventional GVHD treatment after allo-BMT. CONCLUSION: Our results suggest that clinical use of MSCs in both prophylaxis against and treatment of established GVHD is effective. This study supports the use of MSCs in the prophylaxis and treatment of GVHD after allo-BMT; however, large scale studies are needed. CONFLICT OF INTEREST: None declared.

3.
Cytokine ; 57(1): 61-7, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22082804

RESUMEN

BACKGROUND: Leptin and adiponectin receptors mediate the role of leptin in stimulating the growth of leukemic cells and the protective function of adiponectin undertaken in several malignancies such as leukemia. In this study, we investigated the involvement of the expression of leptin and adiponectin receptors in chronic myeloid leukemia (CML) pathogenesis. METHODS: The expression of leptin receptor isoforms, OB-Rt, OB-Ra, and OB-Rb, and the expression of adiponectin receptors, AdipoR1 and AdipoR2, were measured as mRNA levels in two CML cell lines (K562 and Meg-01) and 20 CML patients and 24 healthy controls by using RT-PCR. RESULTS: OB-Rt and OB-Ra isoforms expression of the leptin receptors were found to be significantly lower in Meg-01 cell lines than K562 cells. All leptin receptors were downregulated in CML patients and more particularly OB-Rb level was found to be undetectably low in normal PBMC as well as in CML patients. AdipoR1 expression level was higher in Meg-01 than in K562, whereas AdipoR2 level was found to be unchanged in both cell lines. Interestingly, while AdipoR1 expression increased in CML patients, AdipoR2 decreased. Moreover, imatinib therapy did not affect both leptin and adiponectin isoform expressions. CONCLUSION: While the decrease in leptin receptor levels in CML patients was confirmed, the increase in AdipoR1 levels and relevant decrease in AdipoR2 levels depicted their possible involvement in CML pathogenesis. This suggests different functions of adiponectin receptors in CML development.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Receptores de Adiponectina/genética , Receptores de Leptina/genética , Adulto , Estudios de Casos y Controles , Línea Celular Tumoral , Femenino , Regulación Leucémica de la Expresión Génica , Humanos , Masculino , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Adiponectina/metabolismo , Receptores de Leptina/metabolismo
4.
Cell Biol Int ; 35(7): 721-5, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21241250

RESUMEN

Emergence of resistance to chemotherapy and radiotherapy is a major obstacle for the successful treatment of MM (multiple myeloma). Prednisone, vincristine and melphalan are commonly used chemotherapeutic agents for the treatment of MM. In the current study, we examined the presence of possible cross-resistance between these drugs and gamma (γ) radiation. Prednisone, vincristine and melphalan resistant RPMI-8226 and U-266 MM cells were generated by stepwise increasing concentrations of the drugs. The sensitive and resistant cells were exposed to 200- and 800 cGy γ radiation, and proliferation was examined by XTT {2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide} assay. The results showed that Prednisone- and melphalan-resistant RPMI-8226 cells were also cross-resistant to 200 and 800 cGy γ radiation application, while vincristine-resistant cells did not show resistance. On the other hand, Prednisone-, vincristine- and melphalan-resistant U-266 cells showed cross-resistance to 200- and 800 cGy γ radiation application. These results demonstrated that MM cells resistant to anticancer agents respond to radiation in different levels. These findings may be important in the clinical applications of radiation therapy in the treatment of vincristine resistant MM.


Asunto(s)
Antineoplásicos/farmacología , Proliferación Celular , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Mieloma Múltiple , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Radioisótopos de Cobalto , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Múltiples Medicamentos/efectos de la radiación , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de la radiación , Rayos gamma , Humanos , Melfalán/farmacología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Mieloma Múltiple/radioterapia , Prednisona/farmacología , Sales de Tetrazolio/análisis , Vincristina/farmacología
5.
B-ENT ; 7(1): 65-8, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21563561

RESUMEN

OBJECTIVE: Mucoceles of the sphenoid sinus are rare and may remain undiagnosed until symptoms arise due to the compression of surrounding structures. Because of its close proximity to the sphenoid sinus, the optic nerve may be compressed and visual impairment may result. CASE REPORT: We report on a case of sphenoid sinus mucocele presenting with unilateral visual loss as the only symptom in a 72-year-old patient. Physical examination, computerised tomography, magnetic resonance imaging, bacteriological cultures and histopathological evaluation were used to make the diagnosis. The patient underwent endoscopic sinus surgery for drainage and marsupialisation of the mucocele. Intravenous ceftriaxone was administered over the following three days, and the patient was discharged on the third post-operative day. In the post-operative period, a slight improvement in vision was observed. CONCLUSION: Early diagnosis and prompt surgical intervention are imperative in patients with sphenoid sinus mucoceles presenting with acute visual loss.


Asunto(s)
Mucocele/complicaciones , Mucocele/diagnóstico , Enfermedades de los Senos Paranasales/complicaciones , Enfermedades de los Senos Paranasales/diagnóstico , Seno Esfenoidal , Trastornos de la Visión/etiología , Anciano , Femenino , Humanos , Enfermedades de los Senos Paranasales/diagnóstico por imagen , Seno Esfenoidal/diagnóstico por imagen , Tomografía Computarizada por Rayos X
6.
Thromb Res ; 121(4): 567-71, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-17910980

RESUMEN

INTRODUCTION: Proteasome inhibitor bortezomib (PS-341) has been the first proteasome inhibitor that has entered clinical trials with its antiproliferative and proapoptotic effects in patients with multiple myeloma. Recent studies indicate that proteasome inhibitors can be useful in prevention of experimental arterial thrombosis in renovascular hypertensive rat models. The aim of the present study is to investigate the effect of bortezomib on in vitro platelet aggregation and adenosine triphosphate (ATP) release of human platelets. MATERIALS AND METHODS: For this purpose, platelet aggregation was induced in the platelet-rich plasma (PRP) using 3 microg ml(-1) collagen, 5 microM adenosine diphosphate (ADP), 10 microM epinephrine and 1 U ml(-1) thrombin and ATP release was induced by collagen. RESULTS AND CONCLUSIONS: Bortezomib showed an inhibitory effect on platelet aggregation induced by ADP in human PRP in a dose- and time-dependent manner, whereas it had no effect on collagen-, epinephrin and thrombin-induced aggregation. ATP-release reaction induced by collagen was inhibited dose- and time-dependently by bortezomib, even though collagen-induced platelet aggregation was apparently not affected in human PRP. These findings indicate that bortezomib may be an antiaggregating agent and its' effects may be related to adenine nucleotide receptor dependent regulatory proteins which are important for physiological and pathophysiological cellular processes. However, our in vitro studies suggest that this hypothesis is inadequate to explain the observations completely. This phenomenon and its clinical implication justify further clinical investigations.


Asunto(s)
Adenosina Trifosfato/metabolismo , Plaquetas/efectos de los fármacos , Ácidos Borónicos/farmacología , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasoma , Pirazinas/farmacología , Plaquetas/metabolismo , Bortezomib , Humanos , Óxido Nítrico/biosíntesis
7.
Med Oncol ; 25(3): 350-5, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18202925

RESUMEN

Patients with advanced breast cancer frequently develop metastasis to bone. Bone metastasis results in intractable pain and high risk of pathologic fractures due to osteolysis. The treatment of breast cancer patients with bone metastases requires a multidisciplinary approach. Radiotherapy is an established treatment for metastatic bone pain. It may be delivered either as a localized low dose treatment for localized bone pain or systemically for more widespread symptoms. Bisphosphonates have been shown to reduce morbidity and bone pain from bone metastases when given to patients with metastatic bone disease. In vivo studies indicate that early bisphosphonates administration in combination with radiotherapy improves remineralization and restabilization of osteolytic bone metastases in animal tumor models. This review focused on a brief discussion about biology of bone metastases, the effects of radiotherapy and bisphosphonate therapy, and possible mechanisms of combination therapy in metastatic breast cancer patients.


Asunto(s)
Neoplasias Óseas/secundario , Neoplasias Óseas/terapia , Neoplasias de la Mama/patología , Difosfonatos/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/radioterapia , Terapia Combinada , Femenino , Humanos
8.
B-ENT ; 3(2): 73-8, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17685048

RESUMEN

OBJECTIVE: To demonstrate the functional long-term results after reconstruction of the lower lip with the tongue flap. METHODS: We describe the surgical technique and long-term results of lower lip reconstruction with the tongue flap and review five cases in which this technique was used to reconstruct defects of the lower lip, particularly the lip vermilion. RESULTS: Between 1993 and 2003 we performed reconstruction of the lower lip using the tongue flap in five patients. All patients were followed for 2 to 10 years (mean 3.4 years). The procedure achieved good functional and aesthetic results, with no major complications, in particular no flap necrosis. One patient complained of paresthesias of the tongue which resolved within 24 months. Speech was unaffected by use of the tongue flap, although eating and drinking were temporarily impaired prior to the flap separation at the second and final stage of surgery. CONCLUSION: The tongue flap is a simple and reliable technique for reconstruction of part or all of the lip vermilion. The technique is easy to perform and provides good aesthetic and functional results.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Neoplasias de los Labios/cirugía , Labio/cirugía , Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos , Lengua/trasplante , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Satisfacción del Paciente , Estudios Retrospectivos , Factores de Tiempo
9.
Breast Cancer Res ; 8(4): R52, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16925824

RESUMEN

INTRODUCTION: Bisphosphonates are mostly used in the treatment of bone metastases. They have been shown to act synergistically with other chemotherapeutic agents. It is not known, however, whether similar synergistic effects exist with radiation on breast cancer cells. METHODS: Human MCF-7 breast cancer cells were treated with up to 100 microM zoledronic acid, were irradiated with up to 800 cGy or were exposed to combinations of both treatments to determine the antiproliferative effects of zoledronic acid and radiation. RESULTS: Zoledronic acid and radiation caused a dose-dependent and time-dependent decrease in cell viability (approximate 50% growth inhibition values were 48 microM and 20 microM for 24 hours and 72 hours, respectively, for zoledronic acid and 500 cGy for radiation). A synergistic cytotoxic effect of the combination of zoledronic acid and radiation was confirmed by isobologram analysis. CONCLUSION: These data constitute the first in vitro evidence for synergistic effects between zoledronic acid and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with metastatic breast carcinoma.


Asunto(s)
Neoplasias de la Mama/terapia , Fenómenos Fisiológicos Celulares/efectos de los fármacos , Fenómenos Fisiológicos Celulares/efectos de la radiación , Difosfonatos/farmacología , Imidazoles/farmacología , Radioterapia , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Terapia Combinada , Femenino , Humanos , Ácido Zoledrónico
10.
Int J Hematol ; 83(3): 254-8, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16720558

RESUMEN

Adiponectin, an adipocyte-secreted hormone, is an important negative regulator in the immune system and hematopoiesis. In this study, we investigated the association of adiponectin levels with chronic lymphocytic leukemia (CLL) and myeloproliferative diseases (MPDs). We measured adiponectin levels in 19 patients with CLL and 30 patients with MPD (chronic myelogenous leukemia, 15; polycythemia vera, 9; myelofibrosis, 4; essential thrombocythemia, 2). The data were (chronic myelogenous leukemia, 15; polycythemia vera, 9; myelofibrosis, 4; essential thrombocythemia, 2). The data were compared with results from a control group of healthy volunteers who were matched according to age, sex, and body mass index. The adiponectin levels in patients with CLL were lower than in the controls (4.71 +/- 1.33 microg/mL versus 16.61 +/- 3.91 microg/mL; P <.001). They were also significantly lower in patients with MPD than in the controls (8.95 +/- 1.33 microg/mL versus 16.16 +/- 4.77 microg/mL; P <.001). In addition, we compared the adiponectin levels of MPD patients who were treated with interferon (IFN) to the levels of patients who were not treated with IFN. Adipnectin levels were significantly higher in IFN-treated patients (11.03 +/- 1.39 microg/mL versus 6.87 +/- 1.79 microg/mL; P <.001). These results suggest that lymphopoiesis and myelopoiesis negatively influence adiponectin levels. Adiponectin may be related to inflammatory cytokine release. IFN therapy appears to have a positive influence on adiponectin secretion by suppressing inflammatory cytokines. Future studies are needed to prove causality and to provide insight about this hormone's mechanism of action and its potential role regarding the etiology and progression of CLL and MPD.


Asunto(s)
Adiponectina/sangre , Leucemia Linfocítica Crónica de Células B/sangre , Linfopoyesis , Trastornos Mieloproliferativos/sangre , Adiponectina/inmunología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inflamación/sangre , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Interferones/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/inmunología , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/inmunología
11.
J Int Med Res ; 34(5): 520-4, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17133781

RESUMEN

Intranasal polyposis is a chronic inflammatory upper airway disease with unknown aetiology. Interleukin (IL)-4 and IL-8 play very significant roles in allergic events and infectious inflammation, respectively. In contrast, E-selectin is important in the initiation and organization of inflammation. In this study, levels of IL-4, IL-8 and E-selectin were measured in nasal mucosa specimens of intranasal polyposis patients with and without allergic rhinitis, and healthy controls. Healthy controls had significantly higher IL-4 levels than allergic patients and non-allergic patients; IL-4 levels were similar in allergic and non-allergic patients. Allergic and non-allergic patients had significantly higher IL-8 levels than healthy controls; IL-8 levels were comparable in allergic and non-allergic patients. E-selectin levels were similar in all groups. The infection-based theory, represented by IL-8, seems to be more likely than the allergy-based theory, represented by IL-4, for the pathogenesis of nasal polyposis.


Asunto(s)
Pólipos Nasales/etiología , Rinitis/complicaciones , Estudios de Casos y Controles , Selectina E/análisis , Humanos , Infecciones/complicaciones , Interleucina-4/análisis , Interleucina-8/análisis , Mucosa Nasal/patología
12.
Arch Intern Med ; 160(9): 1349-53, 2000 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-10809040

RESUMEN

BACKGROUND: Evidence for vitamin B12 deficiency usually involves combinations of low serum vitamin B12 levels, clinical and metabolic abnormalities, and therapeutic response. Identification of the underlying cause is important in the diagnosis of vitamin B12 deficiency that is usually attributed to malabsorption. Helicobacter pylori is one of the most common causes of peptic ulcer disease worldwide and a major cause of chronic superficial gastritis leading to atrophy of gastric glands. It is suggested that there may be a casual relationship between H. pylori and food-cobalamin malabsorption. OBJECTIVES: To evaluate the H. pylori incidence in patients with vitamin B12 deficiency prospectively and to assess whether treatment for H pylori infection could correct this deficiency over time. PATIENTS AND METHODS: We performed a prospective cohort study involving 138 patients who had anemia and vitamin B12 deficiency. An upper gastrointestinal endoscopy was performed to assess the severity of atrophic gastritis and biopsy specimens for Campylobacter-like organisms tests and histological examination for H pylori were obtained at the time of diagnosis. The diagnosis of H. pylori prompted a combination treatment. RESULTS: Helicobacter pylori was detected in 77 (56%) of 138 patients with vitamin B12 deficiency and eradication of H pylori infection successfully improved anemia and serum vitamin B12 levels in 31 (40 %) of 77 infected patients. CONCLUSIONS: Helicobacter pylori seems to be a causative agent in the development of adult vitamin B12 deficiency. Eradication of H. pylori infection alone may correct vitamin B12 levels and improve anemia in this subgroup of patients.


Asunto(s)
Anemia Perniciosa/etiología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Deficiencia de Vitamina B 12/microbiología , Adulto , Anciano , Causalidad , Endoscopía Gastrointestinal , Femenino , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Deficiencia de Vitamina B 12/complicaciones
13.
J Laryngol Otol ; 129(12): 1224-7, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26654640

RESUMEN

OBJECTIVE: This study aimed to describe the results of a retrospective analysis of a specific cohort of patients with benign lip lesions encountered in the last 15 years in the School of Medicine at Karadeniz Technical University. METHOD: A total of 312 patients were managed for lip lesions during the period 2000-2014. Data from 160 samples of benign lip biopsies were retrieved from the pathology laboratory records. RESULTS: The study group included 20 different histopathological types of lesions, with mucocele being the most frequent lesion (43.13 per cent). The other frequent lesions were chronic inflammatory infiltrate (11.25 per cent), intradermal naevus (5.63 per cent), pyogenic granuloma (5.63 per cent), fibroma (5 per cent) and papilloma (5 per cent). Mucocele was significantly more common in younger patients (p < 0.001). CONCLUSION: Knowledge of the epidemiology and distribution of oral mucosal lesions is essential to promote early diagnosis and treatment. Further epidemiological studies exploring the causal relationships and risk factors for lip lesions are necessary for a better understanding of lip diseases.


Asunto(s)
Neoplasias de los Labios/epidemiología , Neoplasias de los Labios/patología , Labio/patología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Inmunohistoquímica , Incidencia , Enfermedades de los Labios/epidemiología , Enfermedades de los Labios/patología , Enfermedades de los Labios/fisiopatología , Masculino , Persona de Mediana Edad , Mucosa Bucal/patología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Distribución por Sexo , Factores de Tiempo , Turquía/epidemiología
14.
Cancer Gene Ther ; 8(12): 966-73, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11781659

RESUMEN

Severe 5-fluorouracil (5-FU) toxicity has been reported among patients lacking dihydropyrimidine dehydrogenase (DPD) enzymatic activity. DPD is the principal enzyme involved in the degradation of 5-FU to 5'-6'-dihydrofluorouracil, which is further metabolized to fluoro-beta-alanine. We demonstrate here that overexpression of human DPD confers resistance to 5-FU in NIH3T3 cells, mouse bone marrow cells, and in human CD34+-enriched hematopoietic progenitor cells. An SFG-based dicistronic retroviral vector containing human DPD cDNA, an internal ribosomal entry site (IRES), and the neomycin phosphotransferase (Neo) gene was constructed (SFG-DPD-IRES-Neo). Transduced NIH3T3 cells demonstrated a 2-fold (ED50) increase in resistance to a 4-hour exposure of 5-FU in comparison to nontransduced cells. Expression of DPD was confirmed by Northern and Western blot analyses, and DPD enzyme activity was detectable only in transduced cells. Infection of mouse bone marrow cells with this retroviral construct resulted in an increased number of 5-FU-resistant CFU-GM colonies, compared to mock-transduced bone marrow in both 4-hour and 12- to 14-day exposures. Infection of human CD34+-enriched cells with this construct and incubation with 5-FU (10(-6) M) for 14 days also resulted in an increased number of 5-FU-resistant colonies. Retroviral transduction of human hematopoietic progenitor cells with a cDNA-expressing human DPD conferred resistance to 5-FU in NIH3T3 cells, mouse bone marrow cells, and human CD34+-enriched cells. These results encourage the use of this gene as a method to protect patients from 5-FU myelotoxicity.


Asunto(s)
Resistencia a Medicamentos/genética , Células Madre Hematopoyéticas/fisiología , Oxidorreductasas/genética , Células 3T3 , Animales , Antimetabolitos Antineoplásicos/toxicidad , ADN Complementario/biosíntesis , ADN Complementario/genética , Dihidrouracilo Deshidrogenasa (NADP) , Fluorouracilo/toxicidad , Vectores Genéticos , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Inmunosupresores/toxicidad , Ratones , Oxidorreductasas/biosíntesis , Retroviridae , Transfección
15.
Cancer Gene Ther ; 7(6): 910-9, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10880023

RESUMEN

We previously reported the protection of hematopoietic cells from methotrexate (MTX) toxicity using an N2-based double copy vector containing serine 31 (S31)-mutated dihydrofolate reductase (DHFR) (DC/SV6S31). To examine whether the use of SFG-based dicistronic vectors will lead to improvement in gene transfer over the DC/SV6 vector, we compared the protection provided by MTX to NIH3T3 cells and hematopoietic progenitor cells infected with these retroviral constructs containing the S31 variant DHFR cDNA. In NIH3T3 cells, the 50% effective dose values of MTX conferred by the SFG vector were 8-fold higher than those obtained with the DC/SV6 vector. DHFR mRNA levels were 22-fold and 38-fold higher than that seen for the DC/SV6 vector according to Northern blot and real-time polymerase chain reaction analysis, respectively. However, DHFR protein expression and DHFR enzyme activity were only 1.5-fold and 2-fold higher in the SFG vector, respectively, indicating that the mRNA from the SFG vector is translated less efficiently than the mRNA generated from the DC/SV6 vector. Furthermore, the degree of MTX protection conferred by each vector in both mouse and human hematopoietic cells was the same. These results indicate that the in vitro transduction efficiency and transgene expression of human DHFR in hematopoietic progenitor cells is equally conferred by both vectors.


Asunto(s)
Células 3T3/efectos de los fármacos , Médula Ósea/metabolismo , ADN Complementario/genética , Resistencia a Medicamentos/genética , Células Madre Hematopoyéticas/metabolismo , Metotrexato/farmacología , Virus de la Leucemia Murina de Moloney/genética , Tetrahidrofolato Deshidrogenasa/genética , Animales , Northern Blotting , Southern Blotting , Western Blotting , Médula Ósea/efectos de los fármacos , Cartilla de ADN/química , Regulación Enzimológica de la Expresión Génica , Vectores Genéticos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/análisis , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Leucemia/patología , Masculino , Ratones , Regiones Promotoras Genéticas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tetrahidrofolato Deshidrogenasa/metabolismo , Transducción Genética , Células Tumorales Cultivadas
16.
Int J Hematol ; 76(3): 279-83, 2002 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12416740

RESUMEN

Platelet activation, impairment of fibrinolysis, activation of the coagulation pathway, and dyslipidemia are important factors in the pathogenesis and progression of ischemic heart disease, and patients generally need to use an antiplatelet agent. Lipid-lowering cerivastatin, a novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, was administered to 20 patients with primary mixed hyperlipidemia for the assessment of the effect of cerivastatin on lipid levels, plasma fibrinogen concentration, factor VII, VIII, and X levels, plasminogen and antiplasmin concentrations, platelet count, and aggregation (adenosine diphosphate [ADP], collagen, and epinephrine induced). Assessments were made immediately after 2 months of a standard lipid-lowering diet, 4 weeks of placebo administration, and 4 weeks of cerivastatin treatment. Cerivastatin achieved significant reductions in triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels. The significant improvement of the lipid profile was associated with platelet aggregation reduction in vitro stimulated by ADP, collagen, and epinephrine (P < .05, P = .05, P < .005, respectively). Significantly lower levels of factor VII and fibrinogen were observed (P = .001, P < .0001) immediately after cerivastatin treatment. No significant differences were detected in factor VIII level, plasminogen and antiplasmin concentrations, and platelet count after cerivastatin treatment. It was concluded that cerivastatin in mixed hyperlipidemia can exert beneficial changes on specific hemostatic variables and platelet aggregation in addition to its positive effects on plasma lipid values.


Asunto(s)
Coagulación Sanguínea/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hiperlipidemias/tratamiento farmacológico , Agregación Plaquetaria/efectos de los fármacos , Piridinas/farmacología , Administración Oral , Factores de Coagulación Sanguínea/análisis , Colágeno/análisis , Femenino , Fibrinógeno/análisis , Humanos , Hiperlipidemias/patología , Lípidos/sangre , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/tratamiento farmacológico , Recuento de Plaquetas , Resultado del Tratamiento
17.
Int J Hematol ; 78(5): 443-9, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14704038

RESUMEN

Bisphosphonates have recently been introduced in the therapeutic armamentarium for long-term treatment of patients with multiple myeloma. These pyrophosphate analogs not only reduce the occurrence of skeletal events but also provide clinical benefit to patients and improve the survival of some of them. The existence of these capabilities raises the possibility that these compounds may have a direct antiproliferative effect on tumor cells. To investigate whether these drugs exert a direct antitumor effect, we exposed human myeloma cell lines ARH-77 and RPMI-8226 to increasing concentrations of zoledronic acid (ZOL) in vitro. A concentration- but not time-dependent cytotoxic effect was detected with drug treatment of ARH-77 and RPMI-8226 cell lines (30% and 60% at 48 hours and 38% and 62% at 72 hours, respectively, for 50 microM of ZOL). Cytotoxicity was not due to ZOL-induced chelation of extracellular calcium as shown by control experiments with the calcium chelator ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid. Addition of the competitive inhibitor of the nitric oxide synthase N omega-nitro-L-arginine methyl ester did not modulate ZOL-induced cytotoxicity. However, a decrease in the number of apoptotic cells was detected when protein kinase C was inhibited by addition of staurosporine to ZOL-containing cultures. Cytotoxicity also was increased by addition of dexamethasone (Dex) and thalidomide (Thal) to ARH-77 and RPMI-8226 cultures. We demonstrated that exposing myeloma cell lines ARH-77 and RPMI-8226 to ZOL inhibits cell growth in a dose-dependent but not a time-dependent manner and that combination of Dex and Thal with ZOL induces apoptotic cell death, providing a rationale for potential applications in vivo.


Asunto(s)
Antineoplásicos/farmacología , Dexametasona/farmacología , Difosfonatos/farmacología , Imidazoles/farmacología , Leucemia de Células Plasmáticas/patología , Mieloma Múltiple/patología , Talidomida/farmacología , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Ácido Egtácico/farmacología , Inhibidores Enzimáticos/farmacología , Humanos , NG-Nitroarginina Metil Éster/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Óxido Nítrico Sintasa/antagonistas & inhibidores , Proteína Quinasa C/antagonistas & inhibidores , Estaurosporina/farmacología , Células Tumorales Cultivadas/efectos de los fármacos , Ácido Zoledrónico
18.
Artículo en Inglés | MEDLINE | ID: mdl-11505263

RESUMEN

OBJECTIVE: The aim of this study was to determine whether a relationship exists between gastric and oral Helicobacter pylori and oral hygiene in patients with vitamin B12 deficiency. STUDY DESIGN: One hundred eight patients with vitamin B12 deficiency who were H pylori -positive in their gastric mucosa were enrolled in the study. These patients were divided into 3 groups determined by Oral Hygiene Index (OHI) scores of good, fair, or poor. H pylori was detected in the dental plaque with camphylobacter-like organism test gels. All patients were treated with a combination regimen to eradicate H pylori. RESULTS: H pylori positivity in dental plaque was correlated with OHI scores; the positivity was 28.5%, 90.2%, or 100% in patients with good, fair, or poor OHI scores, respectively. The eradication of H pylori was associated with recovery from anemia and increased serum vitamin B12 level (P <.0001 and P <.0001). The patients with poor OHI scores had the most frequent gastric recurrence of H pylori (58.3%) compared with those with fair OHI scores (41.2%) and good OHI scores (4.8%). CONCLUSIONS: H pylori seems to be an etiologic factor in vitamin B12 deficiency, since anemia was cured and the level of vitamin B12 in the serum increased as a result of its eradication. However, eradication of H pylori from gastric mucosa alone is not enough to prevent gastric recurrence of the bacteria. Proper oral hygiene must be established to eliminate H pylori in dental plaque. Therefore, we suggest that control of H pylori in dental plaque is necessary to control recurrence of H pylori.


Asunto(s)
Anemia Perniciosa/microbiología , Placa Dental/microbiología , Mucosa Gástrica/microbiología , Helicobacter pylori/fisiología , Higiene Bucal , Deficiencia de Vitamina B 12/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Amoxicilina/uso terapéutico , Anemia Perniciosa/terapia , Antibacterianos/uso terapéutico , Antiulcerosos/uso terapéutico , Campylobacter/clasificación , Distribución de Chi-Cuadrado , Claritromicina/uso terapéutico , Cálculos Dentales/clasificación , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/uso terapéutico , Índice de Higiene Oral , Penicilinas/uso terapéutico , Recurrencia , Estadística como Asunto , Gastropatías/tratamiento farmacológico , Gastropatías/microbiología , Vitamina B 12/sangre , Deficiencia de Vitamina B 12/terapia
19.
Mikrobiyol Bul ; 26(1): 70-6, 1992 Jan.
Artículo en Turco | MEDLINE | ID: mdl-1574023

RESUMEN

Botulism is an acute form of poisoning that results from ingestion of a toxin produced by Clostridium botulinum. Botulism toxin causes their major effect by blocking neuromuscular transmission in autonomic and motor nerve terminals. Guillain Barre Syndrome, Myasthenia Graves, Lambert Eaton Myasthenic Syndrome, acute poliomyelitis and diphtheria must be considered in the differential diagnosis. Electrodiagnostic studies have been shown to be of value in differentiating botulism from other paralytic diseases. Identification of the toxin in the patients serum is diagnostic. The treatment of botulism is mainly supportive. In this study we have discussed a patient who was treated in our clinic as a botulism from unknown source, the differential diagnosis from other paralytic diseases.


Asunto(s)
Botulismo/diagnóstico , Parálisis/diagnóstico , Diagnóstico Diferencial , Electrocardiografía , Electromiografía , Femenino , Humanos , Persona de Mediana Edad
20.
Turk J Haematol ; 16(4): 181-4, 1999 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-27265592

RESUMEN

A case of Schistosoma mansoni infection in a 28 year old male after allogeneic bone marrow transplantation presenting with portal hypertension and gross hematuria is described. Schistosomiasis was confirmed by the discovery of parasites in the feces, together with the failure the patient to respond to multiple antimicrobial and antifungal treatment. After praziquantel administration, toxic or septic shock syndrome evolved and the patients died of acute renal failure on day 39 post-transplant. In this report, we would like to emphasize the importance of pre-transplant stool and urine cultures, and appropriate serologic tests in patients coming from endemic areas. Patients diagnosed with schistosomiasis must be treated at least 3 to 7 weeks before transplantation.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA