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3.
Eur J Med Res ; 16(5): 237-42, 2011 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-21719398

RESUMEN

OBJECTIVES: Outbreaks of sexually transmitted acute HCV infection have been described recently in several cities in the western world. The epidemic affects mainly MSM who are coinfected with HIV and is supposably linked to certain sexual risk practices. Here, we compared our findings with current knowledge and recommendations. METHODS: HIV-positive patients with the diagnosis of acute HCV infection were included in the retrospective analysis. The patients came from outpatient infectious disease centers in northern German cities. We looked at markers of HIV and HCV infection and compared patients who received treatment and those who did not. Treated patients were followed up to 72 weeks. RESULTS: Three hundred nineteen HIV-positive patients with the diagnosis of acute hepatitis C between 2001 and 2008 and were included in the analysis. All patients were male, 315 (99%) patients were of caucasian origin, 296 (93%) declared homosexual contacts as a risk factor for HCV infection, intravenous drug use was declared in 3 (1%) cases. Median age at HCV diagnosis was 40 years (range 20-69 years). Median HCV viral load was 1.2 x 106 IU/mL, 222 patients (70%) had HCV genotype 1, 59 (18%) genotype 4. The median time of HIV infection was 5.5 years (range 0 to 22.4 years). Median HIV viral load was 110 copies/mL (range 25 to 10x106 copies/mL). The median CD 4 count was 461 cells/mm3 (range 55-1331 cells/mm3). Two hundred and fourty-six patients (77%) received anti-HCV treatment, and 175 (55%) had completed therapy by the time of the analysis. Median treatment duration was 33 weeks (IQR 24.1-49.9). 93 of the 175 treated patients (53%) reached a sustained virological response (SVR). In the multivariate analysis, ART at diagnosis, HCV RNA drop at week 12, hemoglobin levels and higher platelets were associated with SVR. Treatment duration was significantly higher in the SVR group (40.6 weeks vs 26.6 weeks, p<0.0001). Seventy-three patients (23%) did not receive anti-HCV treatment. In 19 of the untreated patients (26%) the hepatitis C virus was cleared spontaneously. CONCLUSIONS: Our findings confirm that acute hepatitis C in HIV infected patients affects mainly MSM who acquire HCV sexually. Patients had a short duration of HIV infection and a stable immunological situation. In this real-life setting from urban regions in northern Germany, treatment rates appear to be high and effective.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Enfermedad Aguda , Adulto , Anciano , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Hepatitis C/complicaciones , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
4.
Eur J Med Res ; 16(3): 93-100, 2011 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-21486721

RESUMEN

OBJECTIVE: We have previously reported data from the German cohort of the multinational observational prospective RAINBOW survey which assessed the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r)-containing regimens over 48 weeks in routine clinical practice. This analysis presents data from antiretroviral (ART)-naive and pretreated but protease inhibitor (PI)-naive patients treated in a long-term one line (96 weeks) follow-up of the initial study. METHODS: All ART- and PI-naive patients from the initial RAINBOW cohort who had recorded data to one line 96 weeks of treatment were eligible for inclusion in the current analysis. Efficacy assessments included the proportion of patients with HIV-1 RNA <50 and <400 copies/mL and changes in CD4 cell count from baseline to week 96. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 96. For evaluation of efficacy, intent-to-treat analysis, in which missing values were recorded as failure (ITT), and last-observation-carried-forward (LOCF) analysis were used. Metabolic parameters were assessed using LOCF analysis. RESULTS: The analysis included 175 ART-naive and 109 pretreated but PI-naive patients. After 96 weeks, a similar proportion of patients in the ART-naive and in the pretreated but PI-naive group had HIV-1 RNA levels <400 copies/mL (68.0% and 70.6% [ITT], respectively; 96.6% and 90.8% [LOCF], respectively). The proportion of patients with HIV RNA <50 copies/mL was higher in the ART-naive group compared with the pretreated but PI-naive group (61.1% and 56.9% [ITT], respectively; 84.0% and 75.2% [LOCF], respectively). Median change in CD4 cell count from baseline to week 96 was +263 cells/mm3 (IQR 170; 384. LOCF; p<0.0001) in the ART-naive group, and one line +181 cells/mm3 (IQR 60; 309. LOCF; p<0.0001) in the pretreated but PI-naive group. Treatment was well tolerated, with only 2.5% of patients withdrawing from treatment due to side effects. There were no clinically relevant changes in liver enzyme levels. Overall total cholesterol, triglyceride, and low- and high-density lipoprotein levels increased to week 96, although levels remained within normal ranges in the majority of ART-naive and pretreated patients. CONCLUSIONS: This follow-up analysis confirms the long term efficacy and tolerability of SQV/r in ART-naive and pretreated but PI- naive patients in the real-life clinical setting.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Saquinavir/uso terapéutico , Adulto , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Carga Viral
5.
Infection ; 38(2): 108-16, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20352287

RESUMEN

BACKGROUND: The RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500-mg film-coated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of antiretroviral therapy (ART)-naïve and pretreated but protease inhibitor (PI)-naïve patients. METHODS: This was a multicenter, prospective, open-label, 48-week observational cohort study. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48. Efficacy assessments included changes in the proportion of patients with HIV-1 RNA <50 and <400 copies/ml, and changes in CD4 cell count from baseline to week 48. RESULTS: The analysis included 275 ART-naïve and 179 pretreated but PI-naïve patients. The proportion of ART-naïve patients achieving <50 copies/ml by 48 weeks was 53.1% by intent-to-treat (ITT) analysis and 67.3% using last observation carried forward (LOCF) analysis. In pretreated but PI-naïve patients, the proportions achieving <50 copies/ml by 48 weeks were 53.1% (ITT) and 70.4% (LOCF). The median increase in CD4 count at week 48 was +174 cells/mm3 (interquartile range [IQR] 86, 265) in the ART-naïve group and +100 cells/mm3 (IQR 0, 209) in the pretreated but PI-naïve group (p < 0.01 for both; LOCF). Drug-related adverse events were reported in 7.6% of ART-naïve and 2.8% of pretreated but PI-naïve patients. Treatment with SQV/r was stopped in 21.5% of ART-naïve and 17.9% of pretreated but PI-naïve patients (due to side effects in 3.3% and 2.8%, respectively). There were no clinically relevant changes in liver enzyme levels. Overall, the total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein levels increased to week 48, although the levels remained within normal ranges in the majority of patients. CONCLUSIONS: The results of this observational cohort study of treatment with the 500-mg tablet formulation of SQV are consistent with high efficacy and tolerability results seen in controlled studies of SQV/r. This analysis confirms that SQV/r is effective and well tolerated in ART-naïve and pretreated but PI-naïve patients in 'real-world' clinical settings.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Saquinavir/administración & dosificación , Saquinavir/efectos adversos , Administración Oral , Adulto , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , VIH-1/efectos de los fármacos , VIH-1/aislamiento & purificación , Humanos , Lípidos/sangre , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Resultado del Tratamiento , Carga Viral
6.
Eur J Med Res ; 15(9): 369-76, 2010 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-20952345

RESUMEN

OBJECTIVE: the RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500 mg film-coated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of protease inhibitor (PI)-pretreated, but SQV-naive patients. METHODS: multicenter, prospective, open-label, 48 week cohort study. Efficacy assessments included the proportion of patients with HIV-1 RNA <50 and <400 copies/mL and changes in CD4 cell count from baseline to week 48. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48. RESULTS: a total of 426 patients were included in the analysis. The proportion of patients with HIV RNA levels <50 copies/mL at week 48 was 60.3 % (compared with 31.7% at switch to SQV/r) (intent-to-treat, last observation carried forward analysis). After 48 weeks, median CD4 count increased by +61 cells/mm3 from baseline (p<0.01) and 60.3% of patients achieved HIV-1 RNA <50 copies/mL. Median changes in fasting triglyceride levels (stratified according to baseline level) at week 48 were: +14 mg/dL (IQR -8; 57) for patients with baseline triglyceride <200 mg/dL; -50 mg/dL (IQR -139; 0) for baseline triglyceride 200-750 mg/dL, and -656 mg/dL (IQR -1024; 0) for baseline triglyceride >750 mg/dL (p<0.01 for all). Median changes in fasting total cholesterol (TC) levels (stratified according to baseline) were +16 mg/dL (IQR -3; 43) for patients with baseline TC <200 mg/dL (p<0.01), -3 mg/dL (IQR -25; 25) for baseline TC 200-300 mg/dL (p = 0.4), and -47 mg/dL (IQR -87; -4) for baseline TC >300 mg/dL (p<0.01). No significant changes in liver enzymes or bilirubin were observed. SQV treatment was discontinued in 22% of patients, 6% due to side effects. CONCLUSIONS: these data confirm the efficacy and tolerability of SQV/r in PI-experienced, SQV-naive patients treated in a real-life clinical setting. Of particular relevance are the improvements in triglycerides and TC levels observed in patients with baseline grade III-IV elevations.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/efectos adversos , Encuestas Epidemiológicas/métodos , Saquinavir/administración & dosificación , Saquinavir/efectos adversos , Adulto , Química Farmacéutica/métodos , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios de Cohortes , Femenino , Alemania , Infecciones por VIH/metabolismo , Humanos , Lipasa/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos
7.
Eur J Med Res ; 15(3): 102-11, 2010 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-20452894

RESUMEN

OBJECTIVE: This study was performed to investigate the impact of HAART versus no HAART and nucleoside free versus nucleoside containing HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV/HCV co-infected patients. In addition a control group of HCV mono-infected patients undergoing anti-HCV therapy was evaluated. METHODS: Multicenter, partially randomized, controlled clinical trial. HIV-negative and -positive patients with chronic HCV infection were treated with pegylated interferon alfa-2a and ribavirin (800 - 1200 mg/day) for 24 - 48 weeks in one of four treatment arms: HIV-negative (A), HIV-positive without HAART (B) and HIV-positive on HAART (C). Patients within arm C were randomized to receive open label either a nucleoside containing (C1) or a nucleoside free HAART (C2). RESULTS: 168 patients were available for analysis. By intent-to-treat analysis similar sustained virological response rates (SVR, negative HCV-RNA 24 weeks after the end of therapy) were observed comparing HIV-negative and -positive patients (54% vs. 54%, p = 1.000). Among HIV-positive patients SVR rates were similar between patients off and on HAART (57% vs. 52%, p = 0.708). Higher SVR rates were observed in patients on a nucleoside free HAART compared to patients on a nucleoside containing HAART, though confounding could not be ruled out and in the intent-to-treat analysis the difference was not statistically significant (64% vs. 46%, p = 0.209). CONCLUSIONS: Similar response rates for HCV therapy can be achieved in HIV-positive and -negative patients. Patients on nucleoside free HAART reached at least equal rates of sustained virological response compared to patients on standard HAART.


Asunto(s)
Terapia Antirretroviral Altamente Activa , Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Estudios de Casos y Controles , Portadores de Fármacos , Quimioterapia Combinada , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Hepacivirus/fisiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes , Adulto Joven
8.
Eur J Med Res ; 12(3): 93-102, 2007 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-17507306

RESUMEN

BACKGROUND: The EU approval of enfuvirtide (Fuzeon) was granted in May 2003 on the basis of the 48-week data from the TORO 1 and TORO 2 studies. Enfuvirtide is licensed for use in pretreated HIV patients experienced with three classes of drugs who exhibited treatment failure or who have shown intolerance to previous antiretroviral treatment regimens. Recent studies with the new protease inhibitors tipranavir and darunavir (RESIST and POWER studies) showed that a high proportion of heavily pretreated HIV patients achieve a viral load reduction to below the limit of detection when treated with enfuvirtide plus one of these new ritonavir-boosted protease inhibitors and an optimised background treatment regimen. The International AIDS Society (IAS-USA Panel) has recently updated its treatment guidelines in view of these new data and recommends the use of an antiretroviral treatment regimen containing at least two active drugs, one of which that has a new mechanism of action, for HIV patients who have been heavily pretreated. A new treatment goal has also emerged for heavily pretreated patients with advanced HIV disease: reduction of the viral load to below the detection limit of 50 copies/ml. The IAS concluded that the likelihood of achieving this treatment goal is higher when enfuvirtide is selected as one of the two active drugs. OBJECTIVE: A panel of German experts convened to discuss the currently available data and to incorporate them into the updated German consensus recommendations for the use of enfuvirtide when switching treatment in heavily pretreated HIV patients. METHODS: The consensus recommendations are based on published data from controlled, randomised clinical studies and on the expert opinions of the discussants. RESULTS AND CONCLUSIONS: The consensus recommendations were developed to provide practice-relevant standardised recommendations for selecting suitable candidates for enfuvirtide therapy and for their management. Aspects including predictive prognostic factors, disease stage, selection of the optimised background regimen, early indicators of a response to enfuvirtide, as well as accompanying educational measures treatment were considered. New protease inhibitors or other remaining active drugs should be used together with enfuvirtide in heavily pretreated patients in order to enable at least two active drugs to be included in such a salvage regimen.


Asunto(s)
Proteína gp41 de Envoltorio del VIH/uso terapéutico , Inhibidores de Fusión de VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Fragmentos de Péptidos/uso terapéutico , Algoritmos , Ensayos Clínicos Fase III como Asunto , Farmacorresistencia Viral , Enfuvirtida , Alemania , Proteína gp41 de Envoltorio del VIH/administración & dosificación , Proteína gp41 de Envoltorio del VIH/efectos adversos , Inhibidores de Fusión de VIH/administración & dosificación , Inhibidores de Fusión de VIH/efectos adversos , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Educación del Paciente como Asunto , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Carga Viral
9.
IEEE Trans Neural Netw ; 18(3): 955-9, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17526366

RESUMEN

In this letter, we present an implementation of a neural microcircuit for image processing employing Hebbian-adaptive learning. The neuronal circuit utilizes only excitatory synapses to correlate action potentials, extracting the uncorrelated ones, which contain significant image information. This circuit is capable of approximating Gabor-like image filtering and other image processing functions.


Asunto(s)
Algoritmos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/instrumentación , Almacenamiento y Recuperación de la Información/métodos , Redes Neurales de la Computación , Procesamiento de Señales Asistido por Computador/instrumentación , Inteligencia Artificial , Electrónica , Diseño de Equipo , Análisis de Falla de Equipo , Aumento de la Imagen/instrumentación , Interpretación de Imagen Asistida por Computador/métodos , Miniaturización
10.
Eur J Cancer ; 85: 15-22, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28881247

RESUMEN

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006-2015. MATERIALS AND METHODS: Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006-2015. RESULTS: On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor-negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015. CONCLUSION: The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time.


Asunto(s)
Neoplasias de la Mama/terapia , Prestación Integrada de Atención de Salud/tendencias , Evaluación de Procesos, Atención de Salud/tendencias , Indicadores de Calidad de la Atención de Salud/tendencias , Benchmarking/tendencias , Neoplasias de la Mama/patología , Certificación/tendencias , Bases de Datos Factuales , Europa (Continente) , Femenino , Adhesión a Directriz/tendencias , Humanos , Auditoría Médica , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/tendencias , Nivel de Atención/tendencias , Factores de Tiempo , Resultado del Tratamiento
11.
Clin Res Hepatol Gastroenterol ; 40(3): e23-e25, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27055386

RESUMEN

Chronic hepatitis E has been described several times in strongly immunosuppressed HIV-patients. We describe the persistence of HEV-infection in an HIV-patient despite a restored immune response. This case demonstrates that HEV-infection can persist in formerly immunosuppressed individuals irrespective of the current immune status. Persisting HEV-infection can lead to chronic inflammation and liver cirrhosis. Physicians should be aware of the possibility of chronic hepatitis E even in patients that are not any longer immunocompromised. However, ribavirin is an efficient treatment option.


Asunto(s)
Infecciones por VIH/complicaciones , Hepatitis E/tratamiento farmacológico , Cirrosis Hepática/virología , Antivirales/uso terapéutico , ADN Viral/sangre , Virus de la Hepatitis E/genética , Humanos , Masculino , Persona de Mediana Edad , Ribavirina/uso terapéutico
12.
Eur J Surg Oncol ; 41(10): 1423-9, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26278019

RESUMEN

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast units to establish minimum standards and ensure specialist multidisciplinary care. In the present study we assess the impact of EUSOMA certification for all breast units for which sufficient information was available before and after certification. MATERIALS AND METHODS: For 22 EUSOMA certified breast units data of 30,444 patients could be extracted from the EUSOMA database on the evolution of QI's before and after certification. RESULTS: On the average of all units, the minimum standard of care was achieved for 12/13 QI's before and after EUSOMA certification (not met for DCIS receiving just one operation). There was a significant improvement of 5 QI's after certification. The proportion of patients with invasive cancer undergoing an axillary clearance containing >9 lymph nodes (91.5% vs 89.4%, p 0.003) and patients with invasive cancer having just 1 operation (83.1% vs 80.4%, p < 0.001) dropped, but remained above the minimum standard. The targeted standard of breast care was reached for the same 4/13 QI's before and after EUSOMA certification. CONCLUSION: Although the absolute effect of EUSOMA certification was modest it further increases standards of care and should be regarded as part of a process aiming for excellence. Dedicated units already provide a high level of care before certification, but continuous monitoring and audit remains of paramount importance as complete adherence to guidelines is difficult to achieve.


Asunto(s)
Benchmarking , Neoplasias de la Mama/terapia , Instituciones Oncológicas/normas , Carcinoma Intraductal no Infiltrante/terapia , Carcinoma/terapia , Certificación , Sociedades Médicas , Nivel de Atención , Quimioterapia Adyuvante/normas , Estudios de Cohortes , Europa (Continente) , Femenino , Humanos , Mastectomía/normas , Estudios Prospectivos , Calidad de la Atención de Salud , Radioterapia Adyuvante/normas , Estudios Retrospectivos
13.
Arch Surg ; 115(11): 1384-6, 1980 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-7436732

RESUMEN

Poor cardiopulmonary reserve was demonstrated in a group of 75 elderly patients undergoing elective vascular reconstruction when cardiovascular hemodynamics were analyzed with the automated physiologic profile (APP) preoperatively. Only 25 patients (33.3%) had normal left ventricular function (LVF) and did not need any corrective therapy before surgery. Increment in preload was necessary in 20 patients (26.7%) to improve myocardial function; 30 patients (40%) revealed abnormal LVF and hence required pharmacologic modulation and preload adjustment, inotropic support, and afterload reduction to enhance the ventricular performance. Conventional methods of clinical evaluation did not reveal the degree of compromised ventricular function and potential high risk of surgical morbidity and mortality in many of these patients. The APP disclosed subtle and important physiologic aberrations indicating modification of anesthetic and operative procedures and precise modulation of physiologic factors. Optimization was achieved in all except two patients, and only one was denied the benefits of vascular reconstruction.


Asunto(s)
Hemodinámica , Monitoreo Fisiológico , Cuidados Preoperatorios , Enfermedades Vasculares/cirugía , Anciano , Femenino , Pruebas de Función Cardíaca , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Monitoreo Fisiológico/métodos , Pruebas de Función Respiratoria , Riesgo , Enfermedades Vasculares/fisiopatología
14.
Peptides ; 19(2): 253-8, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9493857

RESUMEN

The formation and processing of neurotensin (NT) by three prostate cancer cell lines was investigated. Neurotensin (NT) immunoreactivity was detected in conditioned media and extracts of LNCaP cells. Using HPLC techniques, the immunoreactivity extracted from LNCaP cells coeluted with synthetic NT standard. Metalloendopeptidase 3.4.24.15 activity was detected in PC-3, DU-145 and LNCaP cells, whereas high levels of neutral endopeptidase 3.4.24.1 1 activity was detected only in LNCaP cells. NT was relatively stable when incubated with PC-3 or D-145 cells but was rapidly degraded by LNCaP cells to NT1-11 and NT1-10. Phosphoramidon inhibited the metabolism of NT by LNCaP cells. These data suggest that NT is present in and metabolized by LNCaP cellular enzymes.


Asunto(s)
Endopeptidasas/metabolismo , Neoplasias Hormono-Dependientes/metabolismo , Neurotensina/metabolismo , Neoplasias de la Próstata/metabolismo , Cromatografía Líquida de Alta Presión , Glicopéptidos/farmacología , Humanos , Inmunohistoquímica , Masculino , Metaloendopeptidasas/metabolismo , Neprilisina/metabolismo , Neurotensina/aislamiento & purificación , Inhibidores de Proteasas/farmacología , Células Tumorales Cultivadas/metabolismo
15.
Leuk Lymphoma ; 45(5): 897-904, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15291346

RESUMEN

Despite recent advances, chronic lymphocytic leukemia (CLL) as the most common leukemia remains a largely incurable disease. Modern treatment options include novel drugs like purine analogues, monoclonal antibodies and transplantation strategies. Moreover, gene transfer of immunostimulatory molecules is another, but still experimental approach that can be used to potentiate immune responses against leukemic cells. CD40 ligand (CD40L) was shown to be a promising molecule for immunotherapy of B-CLL playing a critical role in immune activation. However, CLL B cells are resistant to transduction with most currently available vector systems. Improving the efficiency and specificity of gene vectors is critical for the success of gene therapy in this area. Using replication defective adenovirus encoding CD40L (Ad-CD40L), immunologic and clinical responses were seen in CLL patients after infusion of autologous Ad-CD40L-CLL cells in a recent phase I trial. Due to the immunogenic nature of adenovirus vectors, alternative vector systems are currently explored. Recombinant adeno-associated virus (rAAV) was shown to enable efficient transduction of primary B-CLL cells. By use of a library of AAV clones with randomly modified capsids, receptor-targeting mutants with a tropism for CLL cells can be selected. Furthermore, helper-virus free Epstein-Barr virus (EBV)-based gene transfer vectors hold promise for development of CLL-targeted vaccines after remaining safety issues will be resolved. Herpes simplex virus (HSV)-based vectors, especially HSV amplicons, have favorable features for B-CLL gene transfer including high transduction efficiency, ability to infect postmitotic cells and a large packaging capacity. The challenge for the future will be to transfer these alternative vector systems into clinic and allow the detection of a CLL-specific immune response by use of defined tumor antigens. This will make it possible to establish the potential clinical role of gene therapy for CLL patients.


Asunto(s)
Vectores Genéticos , Leucemia Linfocítica Crónica de Células B/patología , Leucemia Linfocítica Crónica de Células B/terapia , Transducción Genética , Ligando de CD40/administración & dosificación , Terapia Genética , Humanos , Inmunoterapia , Leucemia Linfocítica Crónica de Células B/inmunología , Virus/genética
16.
Fertil Steril ; 75(2): 252-9, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11172823

RESUMEN

OBJECTIVE: To measure folate levels in seminal plasma from smokers and nonsmokers and to evaluate relationships between seminal plasma folate levels and both folate nutriture and semen quality measures. DESIGN: Observational study. SETTING: United States Department of Agriculture, Western Human Nutrition Research Center, Presidio of San Francisco, San Francisco, California. PATIENT(S): Healthy male smokers (n=24) and nonsmokers (n=24). MAIN OUTCOME MEASURE(S): Blood levels of plasma folate and homocysteine, seminal plasma total, non-methyl- and 5-methyltetrahydrofolate concentrations, and total sperm count and density. RESULTS: Total seminal plasma folate concentrations were on average 1.5 times higher than blood plasma folate concentrations in all men. Seminal plasma folates contained 5-methyltetrahyrdofolate (74% of total) and non-methyltetrahydrofolates (26% of total); all samples had less than four glutamyl residues. Total and 5-methyltetrahydrofolate concentrations correlated significantly with blood plasma folate and homocysteine concentrations. Seminal plasma non-methyltetrahydrofolate levels correlated significantly with sperm density and total sperm count. Seminal plasma of smokers contained a proportionally lower concentration of non-methyltetrahydrofolates compared with nonsmokers. CONCLUSION(S): Seminal plasma total folate and 5-methyltetrahydrofolate concentrations reflect folate nutriture. The non-methyltetrahydrofolate fraction of seminal plasma may be important for male reproductive function.


Asunto(s)
Ácido Fólico/análisis , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Semen/química , Fumar , Recuento de Espermatozoides , Adulto , Dieta , Ácido Fólico/sangre , Genotipo , Homocisteína/sangre , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Mutación , Espermatozoides/química , Tetrahidrofolatos/sangre , Vitamina B 12/sangre , Vitaminas/administración & dosificación
17.
J Microbiol Methods ; 36(1-2): 35-43, 1999 May.
Artículo en Inglés | MEDLINE | ID: mdl-10353798

RESUMEN

Plots of an alpine grassland in the Swiss Alps were treated with elevated (680 microl l(-1)) and ambient CO2 (355 microl l(-1)) in open top chambers (OTC). Several plots were also treated with NPK-fertilizer. Community level physiological profiles (CLPPs) of the soil bacteria were examined by Biolog GN microplates and enzyme activities were determined through the release of methylumbelliferyl (MUF) and methylcoumarin (MC) from MUF- or MC-labelled substrates. A canonical discriminant analysis (CDA) followed by multivariate analysis of variance showed a significant effect of elevated CO2 on the CLPPs both under fertilized and unfertilized conditions. Further, the installation of the OTCs caused significant shifts in the CLPPs (chamber effect). Of the four enzyme activities tested, the beta-D-cellobiohydrolase (CELase) and N-acetyl-beta-D-glucosaminidase (NAGase) activity were enhanced under elevated CO2. L-Leucin-7-aminopeptidase (APEase) activity decreased, when the plots received fertilizer. Beta-D-glucosidase (GLUase) remained unaffected. The results suggest effects of elevated CO2 on specific microbial activities even under low mineral nutrient conditions and when bulk parameters like microbial biomass or respiration, which have been investigated on the same site, remain unaffected. The observed medium-term changes point at possible long-term consequences for the ecosystem that may not be specified yet.


Asunto(s)
Dióxido de Carbono/metabolismo , Microbiología del Suelo , Acetilglucosaminidasa/metabolismo , Aminopeptidasas/metabolismo , Celulasa/metabolismo , Celulosa 1,4-beta-Celobiosidasa , Cumarinas/metabolismo , Ecosistema , Fertilizantes , Poaceae , Suiza , beta-Glucosidasa/metabolismo
18.
J Microbiol Methods ; 36(1-2): 29-33, 1999 May.
Artículo en Inglés | MEDLINE | ID: mdl-10353797

RESUMEN

Extraction and purification of bacteria from soil by the Nycodenz gradient centrifugation procedure described by Bakken and Lindahl (1995; Recovery of bacterial cells from soil. In: van Elsas, J.D., Trevors, J.T. (Eds.), Nucleic Acids in the Environment: Methods and Applications. Springer Verlag, Berlin, pp. 9-27) were compared to soil slurry extractions. Bacterial communities from four different soils were described by the bacterial abundance, CTC-reducing capacity, culturability and the community level physiological profiles (CLPP) in BIOLOG GN plates. A significant loss of both total and culturable number of bacteria g(-1) soil dry weight were found after extraction and purification of cells. The origin of soil influenced the yield of cells and a difference between the four soils and an interaction between the soils and extraction procedure were found. The culturability and the CLPP were different between the four soils but were unaffected by the extraction procedure. The bacterial community obtained after extraction and purification thus represented the same fraction of the indigenous bacterial community.


Asunto(s)
Bacterias/crecimiento & desarrollo , Bacterias/aislamiento & purificación , Ecosistema , Microbiología del Suelo , Centrifugación por Gradiente de Densidad , Medios de Cultivo
19.
Adv Exp Med Biol ; 477: 197-204, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10849747

RESUMEN

The notion that patients with eating disorders maintain a functional immunosurveillance in spite of severe malnutrition has attracted researchers for years. Dipeptidyl Peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, operates in the cascade of immune responses. Membrane-bound DPP IV expressed on lymphocytes, also known as the leukocyte antigen CD26, is considered to participate in T cell activation. We hypothesized that the activity of DPP IV in serum and expression of CD26 in lymphocytes may be altered in patients with eating disorders. Serum DPP IV activity and the number of CD26 (DPP IV)-positive peripheral blood lymphocytes were measured in 44 patients (anorexia nervosa (AN): n = 21, bulimia (B): n = 23) in four consecutive weekly analyses. The analysis of CD26-positive cells included the characterization of CD26-bright and CD26-dim positive subsets. Additionally, the expression of CD25 (IL-2 Receptor alpha chain) was evaluated to estimate the degree of T cell activation. The same analyses were carried out in healthy female volunteers (HC, n = 20). CD26-positive cells were reduced in patients as compared to healthy controls (mean 40.2% (AN) and 41.1% (B) vs. 47.4% (HC), p < 0.01), while the DPP IV activity in serum was elevated (mean 108.4 U/l (AN) and 91.1 U/l (B) vs. 80.3 U/l (HC), p < 0.01). The potential implications of changes in DPP IV expression and serum activity on--and beyond--immune function are discussed.


Asunto(s)
Anorexia Nerviosa/enzimología , Bulimia/enzimología , Dipeptidil Peptidasa 4/sangre , Subgrupos Linfocitarios/enzimología , Adulto , Anorexia Nerviosa/inmunología , Índice de Masa Corporal , Bulimia/inmunología , Estudios Transversales , Femenino , Humanos , Inmunocompetencia , Inmunofenotipificación , Recuento de Linfocitos , Receptores de Interleucina-2/biosíntesis , Receptores de Interleucina-2/genética
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