RESUMEN
This paper presents the largest study in Cyprus evaluating the frequency and distribution of BRCA1/2 mutations in a high risk patient cohort. Deleterious mutations in the BRCA1/2 genes were identified in 68 of the 527 patients tested (13%). It is of interest that a quarter of those tested positive, did not have an extensive family history of breast/ovarian cancer but were diagnosed with early onset breast cancer, ovarian cancer under the age of 60 or triple negative breast cancer. The spectrum of mutations identified in our patient cohort is different compared to other Mediterranean countries. Furthermore, several of the mutations detected are novel and have not been identified in other ethnic populations. This highlights the importance of operating a national reference center for cancer genetic diagnosis which offers services tailored to the needs of the Cypriot population.
Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ováricas/genética , Neoplasias de la Mama Triple Negativas/genética , Adulto , Anciano , Chipre/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Genética de Población , Humanos , Persona de Mediana Edad , Epidemiología Molecular , Mutación , Neoplasias Ováricas/epidemiología , Neoplasias de la Mama Triple Negativas/epidemiologíaRESUMEN
Relative reaction rates for hole transfer between G radical cations and GGG triplets in DNA, through different bridges of varying lengths, are numerically calculated and the obtained results are compared with corresponding experimental observations [Giese et al., 2001, Nature, 412, 318; Angew. Chem., Int. Ed., 1999, 38, 996]. Hole donors and acceptors are separated either by (T-A)n bridges or by N repeated barriers consisting of (T-A,T-A) double base-pairs which are connected through single G-C base-pairs. In the former case, hole transfer rates show a strong exponential decrease with the length of the bridge for short bridges, while a switching to weak distance dependence has been observed for longer bridges. In the latter case, a power law seems to better describe the distance dependence of charge transfer rates. All these experimental observations are qualitatively reproduced by our simulations without any adjustable parameter, considering only tunneling as the charge transfer mechanism. Physical insights into the mechanism providing the switching behavior in the case of (T-A)n bridges are presented through an analysis of the eigenfunctions of the system.
Asunto(s)
ADN/química , Guanina/química , Emparejamiento Base , Secuencia de Bases , Cationes/químicaRESUMEN
AIM: Cytotoxic drugs have reduced the mortality in patients with ANCA-associated vasculitis (AASV) but their use carries a substantial risk of toxicity. Efforts are made to switch from cytotoxic drugs to less toxic maintenance regimens. In this study we aimed to assess the efficacy of mycophenolate mofetil (MMF) as maintenance therapy in patients with AASV and renal involvement. METHODS: 22 patients with newly diagnosed AASV, microscopic polyangiitis (MPA) (n = 16), Wegener's granulomatosis (WG, n = 4), renal limited vasculitis (RLV, n = 1) and Churg-Strauss syndrome (CSS, n = 1) and renal involvement were followed for a median of 42 months (range 24 - 101). After 6 months of standard induction therapy, patients were switched to MMF monotherapy for 18 months. Renal parameters i.e. serum creatinine, proteinuria and urine sediment, BVAS scores and ANCA titers were assessed at baseline, after induction and after 18 months with MMF. RESULTS: After the end of induction, 3 of the 4 patients who were initially hemodialysis (HD) dependent, remained on HD and were withdrawn from further analysis. In the remaining 19 patients, the improvement in renal function (p < 0.001), hematuria (p = 0.011), proteinuria (p = 0.007) and BVAS scores (p < 0.001) after induction was sustained after 18 months maintenance with MMF and no patient relapsing during this period. Until the end of the follow up, 31.58% of patients relapsed, at a median of 21.5 months (range: 18 - 60). Side effects were transient and infrequent. CONCLUSION: In patients with AASV and renal involvement, MMF seems to be an effective and well tolerated option in sustaining short- and medium-term remission.
Asunto(s)
Inmunosupresores/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Ácido Micofenólico/análogos & derivados , Vasculitis/tratamiento farmacológico , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Distribución de Chi-Cuadrado , Ciclofosfamida/uso terapéutico , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Enfermedades Renales/etiología , Pruebas de Función Renal , Ácido Micofenólico/uso terapéutico , Estadísticas no Paramétricas , Resultado del Tratamiento , Vasculitis/complicaciones , Vasculitis/inmunologíaRESUMEN
The current management of early stage Hodgkin's disease (HD) is usually based on clinical staging, combined modality therapy and the use of less toxic chemotherapy regimens. This approach entails high cure rates, while ensures less long term toxicity with avoidance of laparotomy. The aim of this study was to assess the efficacy of a brief course of Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by limited field radiotherapy (RT) in favorable clinical stage (CS) I and IIA HD. Forty patients, aged 17-68 (median 34) years, with favorable CS I and IIA HD, without bulky mediastinal disease, have been treated with 4-6 (median 4) cycles of ABVD plus limited field RT. Twenty seven (67%) patients received 4 cycles of chemotherapy, while 13 received 5-6 cycles. Thirty five (87%) patients received limited field RT with dose 24-36 Gy and five (13%) received extended field with 36-46 Gy. All patients responded completely to chemotherapy. One patient experienced a relapse two months after the end of therapy. All patients are alive; 39 in continuous complete remission. With a median follow-up period of 44 months (range 18-101) the actuarial overall and progress free survival was 100 and 97% at 5 years. We did not observe any case of secondary leukemia or solid tumor. Pulmonary toxicity was mild in cases of mediastinal irradiation. Considering the short follow-up time and the small number of patients, the combination of a brief course of ABVD plus regional RT is a very efficacious treatment of favorable CS I and IIA HD with mild toxicity. However, long term survival data are needed, which could give confident answers regarding the risk of late therapy related complications, particularly second malignancies.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/terapia , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Terapia Combinada , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Dosificación Radioterapéutica , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/efectos adversosRESUMEN
BACKGROUND: Metabolic syndrome (MetSyn) is associated with a marked increase in the risk of cardiovascular disease, especially in patients with type 2 diabetes mellitus (DM). AIM: To investigate the effect of orlistat plus hypocaloric diet (HCD) vs HCD alone on the cardiovascular risk profile in patients with both MetSyn (National Cholesterol Educational Program--NCEP--Adult Treatment Panel III definition) and type 2 DM. METHODS: This was a prospective, multicentre, open-label, randomized, controlled study. One hundred and twenty-six patients, free of cardiovascular disease at baseline, were included in the final analysis. Ninety-four (73%) patients were treated with orlistat (360 mg/day) and HCD for a 6-month period, while 34 (27%) were on HCD alone. Analysis of covariance was used to assess differences between the treatment groups over time. MAIN OUTCOME MEASURES: Components of the MetSyn criteria assessed were: waist circumference; systolic and diastolic blood pressure; fasting glucose, triglycerides; high-density lipoprotein cholesterol (HDL-C) plus body mass index; glycosylated haemoglobin (HbA1C); homeostasis model for assessment of insulin resistance (HOMA) index; and total and low-density lipoprotein cholesterol (LDL-C). RESULTS: By protocol, all patients had MetSyn at baseline. After a 6 month treatment period there were significant differences between the orlistat plus HCD vs the HCD-alone groups in body weight (p = 0.0001), waist circumference (p < 0.0001), fasting glucose (p < 0.0001), HbA(1C) (p < 0.0001), systolic blood pressure (p = 0.024), total cholesterol (p < 0.0001), LDL-C (p = 0.034), and HOMA index (p = 0.022), while there were no significant differences in triglycerides and HDL-C. Orlistat was well tolerated. By the end of the study, 65% of the patients on orlistat plus HCD were still meeting the MetSyn criteria and 41% had four to five MetSyn components vs 91% (p < 0.0001) and 53% (p = 0.017), respectively, of those on HCD alone. CONCLUSIONS: Orlistat plus HCD favourably modified several cardiovascular risk factors in patients with both MetSyn and type 2 DM. These effects might partly offset the excess cardiovascular risk and improve outcome in this patient population.
Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Lactonas/uso terapéutico , Síndrome Metabólico/complicaciones , Obesidad/tratamiento farmacológico , Glucemia , Diabetes Mellitus Tipo 2/sangre , Dieta Reductora , Femenino , Humanos , Lipasa/antagonistas & inhibidores , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/dietoterapia , Orlistat , Factores de RiesgoRESUMEN
A great number of publications in the international literature have revealed the possible part of biological factors in eating disorders and as well as characteristics of the patients' personality that favour or contribute in the development of these disorders. The research in etiology, however, includes the examination of family and socio-cultural factors. The aim of the present paper was to concentrate bibliographic data related to the family and socio-cultural factors that form the conditions under which anorexia nervosa and bulimia nervosa develop, excluding articles about binge-eating disorder. Articles from 1995 to 2005 were included through search in the files of the electronic database Medline (PubMed) on terms of inventory (MESH) for both disorders. About the role of the family environment, it was found that the factors studied more were family dysfunction, overprotection and sexual or physical abuse. As for the socio-cultural factors it is not perfectly clear whether the western standards of life are linked to the development of these disorders or if there is simply a lack of culturally sensitive instruments to detect these disorders in their different possible forms in the non-western world. An important finding is that there are not enough researches to show clearly any negative part played by the mass media.
RESUMEN
AIMS: In patients with diabetes and microalbuminuria, small changes of GFR could have been missed, due to the lack of sensitive methodology for GFR determination in clinical practice (creatinine based calculations). Therefore we explored the relation of the degree of albumin excretion with Cystatin C, which has been recently proved to be a better marker of GFR, compared to serum creatinine. METHODS: We studied 179 patients with type 2 diabetes, in whom renal function and microalbuminuria were evaluated. RESULTS: In patients with normal renal function, GFR/MDRD>or=60 ml/min/1.73 m(2), (n=79), urinary albumin concentration (UAC) was significantly correlated with Cystatin C, both in patients with normoalbuminuria (r=0.547, p<0.023) or microalbuminuria (r=0.305, p<0.035), while it was not correlated either with serum creatinine or calculated creatinine clearance. In patients with GFR/MDRD<60 ml/min/1.73 m(2), (n=100), UAC was significantly correlated with Cystatin C, also both in patients with normoalbuminuria (r=0.536, p<0.032) or microalbuminuria (r=0.340, p<0.016), while it was significantly correlated with serum creatinine and calculated creatinine clearance only in those with microalbuminuria. CONCLUSIONS: Subtle changes in renal function, as judged by Cystatin C concentration, may parallel the degree of albuminuria, even in the normoalbuminuric stage. This finding needs further confirmation by more appropriate methodology in prospective follow up studies.
Asunto(s)
Albuminuria/sangre , Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Anciano , Creatinina/sangre , Creatinina/orina , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/orina , Femenino , Tasa de Filtración Glomerular , Hemoglobina Glucada/metabolismo , Humanos , Insulina/sangre , Pruebas de Función Renal , Masculino , Valores de Referencia , Análisis de RegresiónRESUMEN
OBJECTIVE: To investigate the smoking habits and associated risk factors among Greek physicians. STUDY DESIGN: Cross-sectional survey of a randomly selected sample of Greek physicians. METHODS: A national sample of 1284 physicians (718 men, 566 women) participated in the study, which was conducted between September 2003 and June 2005. Data were collected through an anonymous self-completed questionnaire. Logistic regression was used to analyse the influence of different factors on the probability of a physician being a current or former smoker. RESULTS: Overall, 38.6% of the physicians (40% of men; 37% of women) currently smoked, 13.8% were former smokers, and 47.6% had never smoked. Eighty-three per cent of smokers reported starting smoking before the age of 25 years, with half of them during medical school (aged 19-24 years). Multivariate analyses revealed that physicians who were male, unmarried, divorced or widowed, surgeons or anaesthetists, and residents were more likely to be current smokers. Former smokers were more likely to be older, male and born in a rural area. Moreover, the odds of being a current or former smoker were significantly higher among physicians with a history of parents who smoked. The proportion of physicians who reported counselling patients (often or always) to stop smoking was lower among current smokers compared with those who never smoked or those who were former smokers (74.4% vs. 85.3% vs. 84.7%, P<0.0001). CONCLUSIONS: The prevalence of smoking among Greek physicians is exceedingly high and similar to that of the general population. More effective interventions that reduce smoking in the medical community should be implemented immediately so that physicians will be better able to fulfil their function as role models for the general population.
Asunto(s)
Actitud del Personal de Salud , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Médicos/psicología , Fumar/epidemiología , Adulto , Anciano , Estudios Transversales , Femenino , Grecia/epidemiología , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Médicos/estadística & datos numéricos , Prevalencia , Encuestas y CuestionariosRESUMEN
Junctional epidermolysis bullosa with congenital pyloric or duodenal atresia is a distinct variant within this group of autosomal recessive blistering skin diseases. In this study we demonstrate, for the first time, a homozygous mutation in the alpha6 integrin gene (ITGA6) in a family with three affected individuals. For this purpose, we first determined the genomic organization of ITGA6, and placed the gene on chromosome 2q by high resolution radiation hybrid mapping. Heteroduplex analysis of PCR products containing the individual exons of ITGA6, followed by direct nucleotide sequencing, revealed that the proband was homozygous for a G-to-T transversion in the +1 position of intron 12. This mutation, 1856+1G-->T, affects an invariant base of the 5' donor splice site predicting aberrant splicing involving exon 12. The mutation was verified in the proband's DNA by restriction enzyme digestion which also confirmed that the parents were heterozygous carriers of this mutation. Altered expression of alpha6 integrin, which forms a heterodimer with the beta4 subunit at the dermal-epidermal junction, would explain fragility and blistering as a result of minor trauma to the skin.