RESUMEN
Surgical aortic valve replacement in the elderly is now being supplanted by transcatheter aortic valve implantation (TAVI). Scoring systems to predict survival after catheter-based procedures are understudied. Both diabetes (DM) and underlying inflammatory conditions are common in patients undergoing TAVI, but their impact remains understudied in this patient group. We examined 560 consecutive TAVI procedures and identified eight pre-procedural factors: age, body mass index (BMI), DM, fasting blood glucose (BG), left-ventricular ejection fraction (EF), aortic valve (AV) mean gradient, C-reactive protein levels, and serum creatinine levels and studied their impact on survival. The overall mortality rate at 30 days, 1 year and 2 years were 5.2%, 16.6%, and 34.3%, respectively. All-cause mortality was higher in patients with DM (at 30 days: 8.9% vs. 3.1%, p = 0.008; at 1 year: 19.7% vs. 14.9%, p = 0.323; at 2 years: 37.9% vs. 32.2%, p = 0.304). The presence of DM was independently associated with increased 30-day mortality (hazard ratio [HR] 5.38, 95% confidence interval [CI], 1.24-23.25, p = 0.024). BG levels within 7-11, 1 mmol/L portended an increased risk for 30-day and 2-year mortality compared to normal BG (p = 0.001 and p = 0.027). For each 1 mmol/L increase in BG 30-day mortality increased (HR 1.21, 95% CI, 1.04-1.41, p = 0.015). Reduced EF and elevated CRP were each associated with increased 2-year mortality (p = 0.042 and p = 0.003). DM, elevated BG, reduced EF, and elevated baseline CRP levels each are independent predictors of short- and long-term mortality following TAVI. These easily accessible screening parameters should be integrated into risk-assessment tools for catheter-based aortic valve replacement candidates.
RESUMEN
The authors review current advances in the therapy of diabetic neuropathy. The role of glycemic control and management of cardiovascular risk factors in the prevention and treatment of neuropathic complications are discussed. As further options of pathogenetically oriented treatment, recent knowledge on benfotiamine and alpha-lipoic acid is comprehensively reviewed. Alpha-lipoic acid is a powerful antioxidant and clinical trials have proven its efficacy in ameliorating neuropathic signs and symptoms. Benfotiamine acts via the activation of transketolase and thereby inhibits alternative pathways triggered by uncontrolled glucose influx in the cells comprising polyol, hexosamine, protein-kinase-C pathways and formation of advanced glycation end products. Beyond additional forms of causal treatment, choices of symptomatic treatment will be summarized. The latter is mostly represented by the anticonvulsive agents pregabalin and gabapentin as well as duloxetine widely acknowledged as antidepressant. Finally, non-pharmacological therapeutic alternatives are summarized. The authors conclude that combination therapy should be more often suggested to our patients; especially the combination of pathogenetic and symptomatic agents.
Asunto(s)
Antioxidantes/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Neuropatías Diabéticas/tratamiento farmacológico , Ácido Tióctico/uso terapéutico , Adyuvantes Inmunológicos/administración & dosificación , Aminas/administración & dosificación , Anticonvulsivantes/administración & dosificación , Antidepresivos/administración & dosificación , Ensayos Clínicos como Asunto , Ácidos Ciclohexanocarboxílicos/administración & dosificación , Quimioterapia Combinada , Clorhidrato de Duloxetina/administración & dosificación , Medicina Basada en la Evidencia , Gabapentina , Humanos , Pregabalina/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Tiamina/administración & dosificación , Tiamina/análogos & derivados , Resultado del Tratamiento , Ácido gamma-Aminobutírico/administración & dosificaciónRESUMEN
OBJECTIVE: Historically, a set of 5 Cardiovascular Autonomic Reflex Tests (CARTs) were considered to be the gold standard in the assessment of Cardiovascular Autonomic Neuropathy (CAN). However, measuring diastolic Blood Pressure (BP) response to sustained handgrip is omitted in recent guidelines. We aimed to assess the association between the handgrip and the other 4 tests as well as to identify determinants of the handgrip test results in diabetic patients. PATIENTS AND METHODS: 353 patients with diabetes (DM) were recruited (age: 60.2±7.4 years; female: 57.2%; BMI: 29.3±2.1 kg/m2; DM duration: 15.6±9.9 years; HbA1c: 7.8±1.4% (66 mmol/mol); with type 1 DM: 18.1%). CAN was assessed by 5 CARTs: the deep breathing test, Valsalva ratio, 30/15 ratio, handgrip and orthostatic hypotension test. RESULTS: Sensitivity and specificity of the handgrip test in the diagnosis of definite CAN were 24.6% (95%CI 17.7-33.1%) and 79.4% (95%CI 73.3-84.4%), respectively. Results of the handgrip test did not show any association with those of the deep-breathing test (y=0.004, p=0.563), 30/15 ratio (y=0.282, p=0.357), Valsalva ratio (y=-0.058, p=0.436) and orthostatic hypotension (y=-0.026, p=0.833). Handgrip test abnormality showed an independent association with higher initial diastolic BP (OR 1.05, p=0.0009) and an independent inverse association with the presence of hypertension (OR=0.42, p=0.006). CONCLUSION: Our data confirm that the handgrip test should no longer be part of the cardiovascular autonomic testing being highly dependent on hypertensive status and baseline diastolic BP. Exaggerated exercise pressor response is proposed as putative mechanism for the inverse association between abnormal results of the handgrip test and hypertension. Adequate CARTs are important to allow their use in clinical trials and for the prevention of DM-associated complications by initiating early treatment.
Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Presión Sanguínea , Sistema Cardiovascular/inervación , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/diagnóstico , Fuerza de la Mano , Hipertensión/fisiopatología , Examen Neurológico/métodos , Anciano , Biomarcadores/sangre , Estudios Transversales , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/fisiopatología , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipertensión/diagnóstico , Hipotensión Ortostática/fisiopatología , Masculino , Persona de Mediana Edad , Posicionamiento del Paciente , Valor Predictivo de las Pruebas , Reflejo , Reproducibilidad de los Resultados , Mecánica Respiratoria , Maniobra de ValsalvaRESUMEN
INTRODUCTION: The aim of our study was to evaluate the relative effect of diabetes and hypertension on heart rate variability. RESEARCH DESIGN AND METHODS: Four age-matched groups including type 2 diabetic patients with and without hypertension, non-diabetic patients with essential hypertension and healthy control subjects were studied. Autonomic function was evaluated by the standard cardiovascular reflex tests and 24-hour heart rate variability measurement. Heart rate variability was characterized by the triangular index value and by the spectral components of the frequency domain analysis. RESULTS: According to the two-way analysis of variance on ranks, all parameters were influenced negatively by diabetes (heart rate variability triangular index: p < 0.001; low-frequency component: p < 0.0001; high-frequency component: p < 0.001; and total power: p < 0.0001), whereas hypertension had a negative effect only on the low-frequency component (p < 0.05). The interaction between hypertension and diabetes was not significant, indicating that their effects on the heart rate variability parameters are additive. Beat-to-beat variation upon deep breathing, the most sensitive cardiovascular reflex test was also negatively influenced by both diabetes (p < 0.001) and hypertension, (p < 0.05), and their effects were additive. CONCLUSIONS: Diabetes appears to have a greater effect on autonomic dysfunction compared with hypertension. Patients suffering from both diabetes and hypertension are at the highest risk of reduced heart rate variability. Early assessment of the autonomic nerve function is suggested in diabetic patients with hypertension.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/complicaciones , Cardiomiopatías Diabéticas/complicaciones , Neuropatías Diabéticas/complicaciones , Hipertensión/complicaciones , Disfunción Ventricular/complicaciones , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Vías Autónomas/fisiopatología , Presión Sanguínea , Estudios Transversales , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Cardiomiopatías Diabéticas/epidemiología , Neuropatías Diabéticas/epidemiología , Femenino , Frecuencia Cardíaca , Ventrículos Cardíacos/inervación , Ventrículos Cardíacos/fisiopatología , Humanos , Hungría/epidemiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio , Reproducibilidad de los Resultados , Riesgo , Disfunción Ventricular/epidemiologíaRESUMEN
BACKGROUND: Obstructive sleep apnea (OSA) is often accompanied by the metabolic syndrome. Because both conditions are associated with depressed heart rate variability (HRV) separately, our aim was to study whether co-morbid OSA is associated with more reduced HRV in male patients with the metabolic syndrome. METHODS: In this cross-sectional study, 35 men (age, 57±11 years) with the metabolic syndrome (according to International Diabetes Federation criteria) were included. OSA severity was defined by the apnea-hypopnea index (AHI). HRV was assessed by 24-hr ambulatory electrocardiographic monitoring. Standard deviation of all normal-to-normal RR intervals (SDNN), the high frequency power (HFP), and the ratio of low- to high-frequency power (LF/HF) were measured. RESULTS: There were 14, 6, and 8 cases of severe (AHI ≥30/hr), moderate (15/hr≤AHI <30/hr), and mild (5/hr ≤AHI <15/hr) OSA, respectively. Seven patients had no OSA. Patients with mild-moderate or severe OSA had reduced SDNN and HFP values compared to those without OSA. Increasing OSA severity was associated significantly with lower daytime LF/HF ratio [standardized ß regression coefficient (ß)=-0.362, P=0.043] and higher night/day LF/HF ratio (ß=0.377, P=0.023) after controlling for age, duration of diabetes, and severity of metabolic syndrome. CONCLUSIONS: Co-morbid OSA is associated with decreased overall HRV, parasympathetic loss, and impaired diurnal pattern of sympathovagal balance that may further increase the cardiovascular vulnerability of male patients with the metabolic syndrome. The role of the HRV analysis in the risk assessment of these patients warrants further studies.
Asunto(s)
Frecuencia Cardíaca/fisiología , Síndrome Metabólico/epidemiología , Síndrome Metabólico/fisiopatología , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Electrocardiografía Ambulatoria , Humanos , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Polisomnografía , Apnea Obstructiva del Sueño/complicaciones , Adulto JovenRESUMEN
We aimed to summarise recent advances in the therapy of diabetic neuropathy. Although all therapeutic choices in the treatment of diabetes mellitus itself are based on clear pathophysiological basis, this approach is less present in the treatment of the "forgotten complication", diabetic neuropathy. As part of pathogenetic oriented treatment, the role of glycemic control and cardiovascular risk factors are reviewed. The mode of action of benfotiamine is based on inhibition of key alternative pathways, including the polyol, hexosamine, protein-kinase-C pathways, and inhibition of advanced glycation end products formation, just as on activation of transketolase. Alpha- lipoic-acid is considered as the most potent antioxidant. Other forms of pathogenetic oriented treatment, including actovegin, will be summarised. The anticonvulsants gabapentin and pregabalin, as well as the antidepressant duloxetine represent the most important new drugs among agents for symptomatic relief. Most likely, we should offer combination treatment to our patients much more often, first of all combination of pathogenetic and symptomatic drugs. Finally, the broad spectrum of non-pharmacological treatment will be reviewed.
Asunto(s)
Neuropatías Diabéticas/tratamiento farmacológico , Medicina Basada en la Evidencia , Terapia Molecular Dirigida , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Fármacos del Sistema Nervioso Central/farmacología , Fármacos del Sistema Nervioso Central/uso terapéutico , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/fisiopatología , Quimioterapia Combinada , Humanos , Hiperglucemia/prevención & control , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Factores de RiesgoRESUMEN
Among the 300 peripheral T-cell lymphomas (PTCL) searched for EBV positive non-resting B-cells by EBER in situ hybridization 12 have been identified with various forms of EBV-driven B-cell proliferation. This could be categorized into three major forms. i. In the first form scattered immature, mononuclear B-cells of immuno-, centroblastic type with CD20+. CD30+ CD45+, LMP1+ phenotype, reactive appearance and polyclonal immunoglobulin heavy chains gene rearrangement (IgH-R) were admixed to the PTCL cells. ii. The second form mimicked diffuse large B-cell lymphoma as homogenous sheets, largely demarcated from the PTCL, of mononuclear, immature B-cell of CD20+, CD30+, CD45+, LMP1+, EBNA-2+ phenotype but with lack of monoclonal IgH-R were present. iii. In the third form scattered Hodgkin-Reed-Sternberg (HRS) type of cells were noticed which exhibited the CD15+/-, CD20-/+, CD30+, CD45-, LMP1+, EBNA-2- phenotype and in 50% showed clonal IgH gene rearrangement in whole tissue DNA extract. The IgH associated transcription factors' (OCT2, BOB.1/OBF.1, PU.1) expression patterns in these cells corresponded to those of HRS cells in cHL. Based on analysis of 65 PTCLs, we have identified in the positive cases a highly significant increase of EBV+ small, reactive, resting B-cell compartment (75.9 / 100 HPF in PTCL vs. 1.5 / 100 HPF in control lymph nodes) likely to be due to the decreased immune surveillance. This progressive accumulation of EBV+ by-stander B-cell population in PTCLs might be the source of various B-cell proliferations, which in any form represent major diagnostic pitfalls and require a careful differential diagnostic procedure.
Asunto(s)
Linfocitos B/patología , Linfocitos B/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Linfoma de Células T Periférico/inmunología , Linfoma de Células T Periférico/patología , Diagnóstico Diferencial , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/patología , Reordenamiento Génico de Linfocito B/inmunología , Reordenamiento Génico de Linfocito T/inmunología , Genotipo , Humanos , Cadenas Pesadas de Inmunoglobulina/inmunología , Inmunohistoquímica , Hibridación in Situ , Linfoma de Células B/patología , Linfoma de Células T Periférico/virología , Fenotipo , Reacción en Cadena de la Polimerasa , ARN Viral/aislamiento & purificación , Receptores de Antígenos de Linfocitos T gamma-delta/inmunologíaRESUMEN
OBJECTIVE: To evaluate neural dysfunction in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: For this study, 46 subjects with IGT and 45 healthy volunteers underwent detailed neurological assessment. Cardiovascular autonomic function was assessed by standard cardiovascular reflex tests, and heart rate variability was characterized by the triangle index. Sensory nerve function was assessed using Neurometer (for current perception threshold) and Medoc devices. Peak plantar pressure was measured by dynamic pedobarography, and symptoms were graded using the neuropathy total symptom score. RESULTS: Subjects with IGT had significantly greater abnormalities detected by four of five cardiovascular reflex tests and greater heart rate variability characterized by the triangle index. They had a higher frequency of both hyperesthesia and hypoesthesia as detected by current perception threshold testing at 5 Hz, as well as increased heat detection thresholds. CONCLUSIONS: This study provides evidence that subclinical neural dysfunction is present in subjects with IGT and can be detected noninvasively. Cardiovascular autonomic neuropathy may contribute to increased cardiovascular risk in IGT subjects.
Asunto(s)
Intolerancia a la Glucosa/fisiopatología , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/fisiopatología , Adulto , Sistema Nervioso Autónomo/fisiología , Sistema Nervioso Autónomo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Presión Sanguínea , Índice de Masa Corporal , Femenino , Intolerancia a la Glucosa/complicaciones , Prueba de Tolerancia a la Glucosa , Frecuencia Cardíaca , Humanos , Masculino , Fibras Nerviosas/fisiología , Valores de Referencia , Células Receptoras Sensoriales/fisiología , Adulto JovenRESUMEN
UNLABELLED: Adolescent patients with Hodgkin's lymphoma (HL) are treated either in pediatric, or in adult oncological wards. AIM: The aim of our work was to compare the treatment modalities and the survival rates in adolescents with HL treated in adult (A) or pediatric (P) institutes. METHODS: From January 1990 to December 2004, 138 patients (14-21 years) with HL were treated in two adult institutes (A) and 107 in the 10 centres of the Hungarian Pediatric Oncology Network (P). RESULTS: Male:female ratio was 1:1.15 (A) and 1:1.38 (P). The mean age was 18.6 (A) and 15.7 (P) years. There was no difference between the distribution of the stages in the two patient groups. The distribution of histological subtypes (A and P): nodular sclerosing 47% and 59%, mixed cellularity 45% and 25%, lymphocyte rich 1.5% and 10%, lymphocyte depleted 4% and 1%, nodular lymphocyte predominant 1.5% and 3% and unknown 1% and 2%. The majority of the patients were treated with ABVD (A) and OPPA/OEPA +/- COPP (P). One hundred and fifteen (A) and 97 (P) adolescents received irradiation therapy. 80% (A) and 91% (A) of the patients got radiotherapy. In group A 14%, in group P 13% of the patients had relapse. In group A 16 patients died and in group P 7. There was no significant difference in the overall survival (OS) rates at 5 and 10 years in the two patient groups. The event-free survival (EFS) was 76.5 +/- 4% and 72.5 +/- 4% at 5 and 10 years in group A, and 85.3 +/- 4% at both times in group P ( p = 0.0452). CONCLUSION: Survival rates in HL are quite high, 80-90% of the patients can be cured. Event-free survival was higher in pediatric than in adult institutes. In case of patients younger than 18 years, the survival rates were much better in pediatric institutes, so these patients should be treated in pediatric institutes or with protocols used by the pediatricians.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Instituciones Oncológicas/estadística & datos numéricos , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Dacarbazina/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/radioterapia , Humanos , Hungría/epidemiología , Masculino , Estadificación de Neoplasias , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Vinblastina/administración & dosificación , Vincristina/administración & dosificación , Adulto JovenRESUMEN
The composition of reactive cell populations, which constitute the majority of tumor load in Hodgkin's lymphoma (HL), can influence the prognosis of the disease. Besides widely accepted and applied prognostic scores, the authors evaluate biological factors that may have a prognostic impact. Previous data indicate that the rate of eosinophils and mast cells in the reactive cell population, determined already at diagnosis, can be used for this purpose. Histological samples from 104 patients with HL with an average follow-up period of 110 (24-214) months were retrospectively analyzed. Mast cell positivity was associated with better overall survival, although this difference was only of borderline statistical significance (p=0.092). No significant difference was found in parameters like overall survival (OS, p=0.906) or event-free survival (EFS, p=0.307) of eosinophil-positive vs. -negative cases or in EFS (p=0.742) of mast cell-positive vs. -negative individuals (criterion for a positive specimen was more than 5% of appropriate cells in the reactive cell population). Looking at the effect of eosinophilia and mastocytosis together, there was no significant difference between the subgroups categorized according to the combined presence of the two cell types. It seems that tissue eosinophil and mast cell predominance have no prognostic value that could be used in clinical practice, although a tendency for correlation of mast cell positivity with overall survival could be seen. For a definitive statement, multicenter studies should be performed involving a higher number of patients suffering from HL.
Asunto(s)
Eosinófilos/patología , Enfermedad de Hodgkin/patología , Mastocitos/patología , Adolescente , Adulto , Anciano , Niño , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios RetrospectivosRESUMEN
INTRODUCTION: Recently, in the diagnostics and treatment of Hodgkin's disease significant developments have occurred. AIM: To summarize the clinical and histological data of patients with Hodgkin's disease, treated at the 3rd Department of Internal Medicine, University of Debrecen between 1995-2004. In 2006 January, the mean follow-up was 69 (12-132) months. METHODS: Patients data was analyzed by using SPSS statistical software. RESULTS: The mean age of the 163 patients at the diagnosis was 36 years (14-75), with bimodal age distribution, the most frequent disease subtype was mixed-cell Hodgkin's disease (48.5%). 41.1% of the patients was at early stage, 15.7% had the worst prognosis, while 28.8% had bulky tumor. 7 patients had radiotherapy, 63 had chemotherapy, while at 92 patients combined modality treatment was used. 61.6% of radiotherapies were involved field, 61 patients received cyclophosphamide, vincristine, procarbazine, prednisolone, adriamycine, bleomycin, vinblastine, 87 adriamycine, bleomycin, vinblastine, 7 had other chemotherapies. As the response to the primary treatment 146 complete, 10 partial remission occurred, while 6 patients showed no response. 10 patients with partial remission and 5 non-responders were continually treated. 27 patients with complete remission had relapse, while 15 had high dose treatment with autologous peripheral stem cell transplantation. During the follow-up 18 patients died, 11 due to the lymphoma progression, or as the result of treatment, 6 had secondary malignancies, 1 due to other reasons. The 10-year prognosed overall survival was 83% (in details: early, advanced, favourable vs. unfavourable: 100% vs. 87.8%, 88.9% vs. 41.6%), the event free survival was 70% (82.6% vs. 70.8%, 64.5% vs. 0%). CONCLUSION: The treatment results of our Hodgkin's disease patients improved, additionally we showed that patients with early stage favourable disease the treatment toxicity should be reduced, while patients with advanced, unfavourable prognosis (10% of all patients) aggressive primary treatment should be used even with more severe side effects and complications.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Dacarbazina/administración & dosificación , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Humanos , Hungría , Masculino , Mecloretamina/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Pronóstico , Radioterapia Adyuvante , Inducción de Remisión , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
INTRODUCTION: Epstein-Barr virus is a ubiquitous human herpes virus in the Hungarian population. The virus is associated with an increasing number of lymphoid malignancies, such as Hodgkin and non-Hodgkin lymphomas. The ability of the virus to establish life-long persistent infection and induce growth transformation is related to the viral proteins that are variously expressed in both normal and malignant cells. Although the presence of ZEBRA protein induces lytic cycle, some lymphoma cases show this protein expression. AIM: In our present study we investigated the frequency of expression of ZEBRA protein in Hungarian patients with Hodgkin lymphoma associated with Epstein-Barr virus infection. The authors wanted to clarify whether this expression is specific to latency type II or occurs in some non-Hodgkin lymphoma cases with latency type III as well. Does the expression of ZEBRA protein have any effect on therapeutic response and survival rate of the patients? METHOD: 109 HL and 59 NHL were studied for the presence of the virus in the tumor and for expression of the latency proteins and ZEBRA by immunohistochemistry. RESULTS: 25 samples were evaluated successfully for ZEBRA of the 47 LMP1 positive HL samples. We detected the weak expression of ZEBRA protein in 13 of the 25 LMP1 positive Hodgkin lymphoma cases and in 6 of the 18 LMP1 positive non-Hodgkin lymphoma samples. The authors could not find correlation between the expression of ZEBRA protein and the type of latency. During the followed 120 months the total survival of patients with ZEBRA positivity proved to be significantly shorter as compared to that of ZEBRA negative cases. The authors could not find significant difference in the uneventful survival of these two groups. CONCLUSION: In the examined group of patients the ZEBRA positivity associated with a poor prognosis of the disease. Besides this relatively small number of cases, additional extensive studies are needed to conclude our observation. Elucidation of the switching mechanisms by which Epstein-Barr virus induces lytic cycle may provide an efficacious therapeutic approach to the EBV-related malignancies.
Asunto(s)
Proteínas de Unión al ADN/análisis , Infecciones por Virus de Epstein-Barr/metabolismo , Herpesvirus Humano 4/metabolismo , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/virología , Transactivadores/análisis , Proteínas Virales/análisis , Adulto , Anciano , Infecciones por Virus de Epstein-Barr/complicaciones , Antígenos Nucleares del Virus de Epstein-Barr/análisis , Femenino , Regulación Neoplásica de la Expresión Génica , Regulación Viral de la Expresión Génica , Enfermedad de Hodgkin/terapia , Humanos , Hungría , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento , Proteínas de la Matriz Viral/análisisRESUMEN
We aimed at investigating the distribution of various types of immunoregulatory T cells in the peripheral blood of patients with Hodgkin's lymphoma (HL) (n = 94) being in the state of long-lasting complete remission using flow cytometry. Healthy patients (n = 41) as 'negative' and patients in complete remission with breast cancer (n = 47) as 'positive' controls were investigated in the study. We found significant elevations in the number of CD4+ CD25high naturally occurring regulatory T cells, CD4+/intracellular IL-10+ (Tr1) and CD8+/intracellular IL-10+ T cells in HL compared to the healthy controls. In carcinoma patients, however, the number of Tr1 and CD8+/IL-10+ T cells was higher than that in the other two groups. The increase in the number of CD4+ CD25high T cells seems to be characteristic of HL compared to the two other types of regulatory T cells. This change exists for a long time and it seems to be a characteristic of HL and independent of the types of therapy and the duration of time since therapy.
Asunto(s)
Enfermedad de Hodgkin/inmunología , Subgrupos Linfocitarios/citología , Linfocitos T Reguladores/citología , Adulto , Anciano , Recuento de Linfocito CD4 , Antígenos CD8/análisis , Femenino , Enfermedad de Hodgkin/sangre , Humanos , Interleucina-10/sangre , Masculino , Persona de Mediana Edad , Receptores de Interleucina-2/análisisRESUMEN
This retrospective study included 109 patients with Hodgkin's lymphoma (HL; 45 females, 64 males). In 47 of the 109 HL patients (43%), immunohistochemical analysis of their formalin-fixed, paraffin-embedded histologic samples revealed Epstein-Barr virus (EBV) by latent membrane protein (LMP) 1. The highest virus association (50%) was found with the mixed cellularity histologic subtype, especially in patients aged 11-20 and >50 years. Virus positivity in nodular sclerosis was 35% (negative cases accumulated in patients aged 15-30 years). Regarding clinical stages, histologic subtypes, general symptoms, treatments employed and response to treatment, the EBV-positive group was not significantly different from the virus-negative group. During the mean follow-up time of 83 months (9-300 months), the overall or event-free survival of EBV-negative patients was more favorable than that of EBV-positive patients, although the difference was not significant (p = 0.16 and p = 0.24, respectively). EBV infection may be involved in the pathogenesis of HL in our Hungarian study cohort, but it does not significantly affect clinical symptoms, therapeutic results or complete and event-free survival of HL patients.
Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Enfermedad de Hodgkin/complicaciones , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/mortalidad , Infecciones por Virus de Epstein-Barr/patología , Infecciones por Virus de Epstein-Barr/terapia , Femenino , Herpesvirus Humano 4/aislamiento & purificación , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Humanos , Hungría , Lactante , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
INTRODUCTION: Removal of the colon polyps is a routine approach. Polyps larger than 2 cm can not be removed in one piece, the piecemeal technique is to be applied for these cases. The risk for the complications (bleeding, perforation) and the malignancy are higher, than in conventional cases. PATIENTS AND METHOD: At the 1st Surgical Department of Semmelweis University the piecemeal technique have been used at 13 patients, among others at five patients who were declared for operation because of the size of the polyps in other institutions. The average size of the polyps was 3,5 cm. Ten polyps in the rectum, three in the sigmoid colon were found. RESULTS: The executing procedure required two sections in two cases. Massive bleeding started after the procedure in one patient, which was successfully stopped by infiltration the basement of the polyps with adrenalin. The histology showed in situ carcinoma in two patients. CONCLUSION: The risk of removal of large colon polyps could be undertaken at those endoscopic units where anesthesiologic and surgical background are present, and the patient--in case of unsuccessful removal--could be treated with other minimal invasive therapy (laparoscopic colon resection).
Asunto(s)
Colon Sigmoide/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Pólipos Intestinales/cirugía , Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Colon Sigmoide/patología , Pólipos del Colon/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Femenino , Humanos , Pólipos Intestinales/patología , Masculino , Persona de Mediana Edad , Recto/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: The occurrence of Epstein-Barr virus associated Hodgkin's lymphoma shows considerable variation from continent to continent and from country to country but in Hungary no such investigations have been performed so far. AIM: The authors analyse the presence of Epstein-Barr virus and the type of latency in histologic samples taken from Hodgkin's disease patients. METHOD: They have analyzed the presence of virus using PCR, in situ hybridisation and immunohistochemistry. RESULTS: Out of 109 cases, 61 patients (56%) showed virus positivity by PCR while latent membrane protein 1 positivity was found in 47 cases (43%). As regards to gender ratio, 53% female and 58% male patients were virus positive by PCR. Epstein-Barr virus association did not show any alteration in children (1-14 years) when compared to that of adults (out of the 10 children 6 were positive by PCR). As regards to the lifestyle of Epstein-Barr virus positive patients, the incidence of smoking and the ratio of poor social conditions were significantly higher. Mixed cell type was the most frequent (65%) in these patients and Epstein-Barr PCR virus positivity was highest in this type (60%), primarily in age groups 11-20 and over 51 years. Epstein-Barr virus PCR positivity was 52% in nodular sclerosis (negative cases cumulated in the age group 15-30 years), other histologic subtypes could not be evaluated due to the small number of cases. On examining Hodgkin's lymphoma and Epstein-Barr virus association disease models, they could not categorize their patients into any of them though characteristic patient groups could be more or less observed also in their material. This may be explained by the socioeconomic differences of the population living under different economic conditions. CONCLUSION: These results indicate that Epstein-Barr infection may play an important role in the development of Hodgkin's lymphoma in Hungary, too.
Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/aislamiento & purificación , Enfermedad de Hodgkin/virología , Adolescente , Adulto , Anciano , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/epidemiología , Femenino , Herpesvirus Humano 4/genética , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/patología , Humanos , Hungría/epidemiología , Inmunohistoquímica , Hibridación in Situ , Lactante , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
The authors are presenting a rare paraneoplastic syndrome in Hodgkin's disease. Young female patient presented with symptoms of nephrotic syndrome. Renal biopsy showed mesangiocapillary glomerulonephritis. Remission was achieved with combined therapy. Four months later, when the nephrosis syndrome relapsed, Hodgkin's disease was diagnosed (nodular sclerosing subtype). Hodgkin's disease was staged as III/BS. Polychemotherapy resulted complete remission of both Hodgkin's disease and nephrotic syndrome. Causes of nephrotic syndrome in Hodgkin's disease can include renal vein thrombosis, amyloidosis or paraneoplastic syndrome. Nephrotic syndrome in Hodgkin's disease may relate to dysfunction of T-cells or altered cytokine balance, but the exact pathogenesis is not known. This case attracts attention that a rare cause of nephrotic syndrome can be Hodgkin's disease.
Asunto(s)
Enfermedad de Hodgkin/complicaciones , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/etiología , Síndromes Paraneoplásicos/diagnóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Femenino , Glomerulonefritis/diagnóstico , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Humanos , Estadificación de Neoplasias , Síndrome Nefrótico/sangre , Síndrome Nefrótico/patología , Síndromes Paraneoplásicos/sangre , Síndromes Paraneoplásicos/patología , Resultado del TratamientoRESUMEN
Radiotherapy increases the risk of cardiovascular morbidity. We examined arteria carotis atherosclerosis and stenosis in Hodgkin's lymphoma patients. We examined arteria carotis of 120 Hodgkin's lymphoma patients who have been in complete remission for at least 5 years. 70 patients received neck irradiation (mean age at the time of the examination was 44.6 years). Twenty-four (34.3%) of them had carotis sclerosis or stenosis, and it was significantly more than in the control group [8 out of 60 patients 13.3%)]. Twelve patients of the 50 who did not receive radiotherapy had carotis lesions, and there was no significant difference compared to the control group. Significant stenosis (>50%) was detected in only 3 patients (in the irradiated group). TIA, stroke or amaurosis fugax did not occur. Carotis stenosis does not seem to play a role in late mortality in Hodgkin's lymphoma, but if the patient has an increased risk for atherosclerotic changes, then regular examinations are necessary, and other risk factors (smoking, hypertension, diabetes mellitus, hypothyroidism, early menopause) need to be treated.
Asunto(s)
Arterias Carótidas/patología , Estenosis Carotídea/patología , Enfermedad de Hodgkin/radioterapia , Adulto , Anciano , Arterias Carótidas/diagnóstico por imagen , Estenosis Carotídea/diagnóstico por imagen , Estudios de Casos y Controles , Femenino , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Radioterapia/efectos adversos , Factores de Riesgo , UltrasonografíaRESUMEN
Among the 193 patients (82 female, 111 male) treated primarily for Hodgkin's disease at our clinic between 1990 and 2001 and followed up until 2003, 42 (22%) had mediastinal bulky tumours (MBTs) by the Cotswolds criteria. The rate of MBT diagnosis was significantly greater in the early stage of the disease, these patients were younger and--in contrast to the other group--they all received combined therapy. No significant differences were found in the overall and relapse-free survival rate in the two groups, but relapse and death rates were lower in the patients with bulky tumours. Of the total number of patients, 27 underwent a total of 31 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) examinations, mainly for the evaluation of post-treatment residual mass viability. In the 12 positive cases, the majority of patients received further therapy. During the mean follow-up time of 58 months (range 5-98 months) after obtaining negative results, progression of the disease was found in 2 cases 14 and 23 months later, respectively. Based on our results, we conclude that FDG-PET examinations show a good correlation with clinical follow-up results.
Asunto(s)
Enfermedad de Hodgkin/diagnóstico , Tomografía de Emisión de Positrones , Niño , Preescolar , Errores Diagnósticos , Supervivencia sin Enfermedad , Femenino , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/terapia , Humanos , Lactante , Masculino , Neoplasia Residual/diagnóstico , Pronóstico , Recurrencia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
AIM: Cardiovascular autonomic and peripheral sensory neuropathy is a known complication of chronic alcoholic and non-alcoholic liver diseases. We aimed to assess the prevalence and risk factors for peripheral sensory nerve and autonomic dysfunction using sensitive methods in patients with primary biliary cirrhosis (PBC). METHODS: Twenty-four AMA M2 positive female patients with clinical, biochemical and histological evidence of PBC and 20 age matched healthy female subjects were studied. Five standard cardiovascular reflex tests and 24-h heart rate variability (HRV) analysis were performed to define autonomic function. Peripheral sensory nerve function on median and peroneal nerves was characterized by current perception threshold (CPT), measured by a neuroselective diagnostic stimulator (Neurotron, Baltimore, MD). RESULTS: Fourteen of 24 patients (58%) had at least one abnormal cardiovascular reflex test and thirteen (54%) had peripheral sensory neuropathy. Lower heart rate response to deep breathing (P = 0.001), standing (P = 0.03) and Valsalva manoeuvre (P = 0.01), and more profound decrease of blood pressure after standing (P = 0.03) was found in PBC patients than in controls. As a novel finding we proved that both time domain and frequency domain parameters of 24-h HRV were significantly reduced in PBC patients compared to controls. Each patient had at least one abnormal parameter of HRV. Lower CPT values indicated hyperaesthesia as a characteristic feature at peroneal nerve testing at three frequencies (2000 Hz: P = 0.005; 250 Hz: P = 0.002; 5 Hz: P = 0.004) in PBC compared to controls. Correlation of autonomic dysfunction with the severity and duration of the disease was observed. Lower total power of HRV correlated with lower CPT values at median nerve testing at 250 Hz (P = 0.0001) and at 5 Hz (P = 0.002), as well as with those at peroneal nerve testing at 2000 Hz (P = 0.01). CONCLUSION: Autonomic and sensory nerve dysfunctions are frequent in PBC. Twenty-four-hour HRV analysis is more sensitive than standard cardiovascular tests for detecting of both parasympathetic and sympathetic impairments. Our novel data suggest that hyperaesthesia is a characteristic feature of peripheral sensory neuropathy and might contribute to itching in PBC. Autonomic dysfunction is related to the duration and severity of PBC.