Impact of chemotherapy on telomere length in sporadic and familial breast cancer patients.

Recently, we observed that telomeres of BRCA1/2 mutation carriers were shorter than those of controls or sporadic breast cancer patients, suggesting that mutations in these genes might be responsible for this event. Given the contradictory results reported in the literature, we tested whether other parameters, such as chemotherapy, could be modifying telomere length (TL). We performed a cross-sectional study measuring leukocyte TL of 266 sporadic breasts cancer patients treated with first-line chemotherapy, with a median follow-up of 240 days. Additionally, we performed both cross-sectional and longitudinal studies in a series of 236 familial breast cancer patients that included affected and non-affected BRCA1/2 mutation carriers. We have measured in leukocytes from peripheral blood: the TL, percentage of short telomeres (<3 kb), telomerase activity levels and the annual telomere shortening speed. In sporadic cases we found that chemotherapy exerts a transient telomere shortening effect (around 2 years) that varies depending on the drug combination. In familial cases, only patients receiving treatment were associated with telomere shortening but they recovered normal TL after a period of 2 years. Chemotherapy affects TL and should be considered in the studies that correlate TL with disease susceptibility.

A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study.

Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) for 4 cycles) followed either by D (docetaxel 100 mg/m(2) × 4 cycles; EC-D) or DCb (docetaxel 75 mg/m(2) plus carboplatin AUC 6 × 4 cycles; EC-DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC-D, 48 EC-DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC-D and 14 patients (30 %) with EC-DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56-83) in the EC-D arm and 77 % (95 % CI 65-87) in the EC-DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC-D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.

Targeted screening and health education for Chagas disease tailored to at-risk migrants in Spain, 2007 to 2010.

Chagas disease is endemic in Latin America, but migration has expanded the disease's geographical limits. Spain is the most affected country in Europe. From 2007, a specific Chagas disease programme aimed at at-risk migrants was developed in three Spanish cities (Madrid, Jerez de la Frontera and Alicante). The objectives of the programme were to increase participants' knowledge and decrease their fears about the disease and to encourage them to undergo screening for Trypanosoma cruzi infection. The programme was specially focused on migrants from Bolivia and Latin American women of childbearing age. Culturally tailored interventions were carried out in non-clinical settings. A total of 276 migrants were screened using a rapid immunochromatographic test following talks on the disease: the results were then later confirmed by standard serological tests. Of those tested, 44 (15.9%) were confirmed cases of Chagas disease. All of them came from Bolivia and a quarter were pregnant women. Of the 44 cases, 31 were later followed up at a specialised Chagas disease clinic. We consider that the adaptation of the programme to the target population's needs and collaboration with non-governmental organisations and migrants' associations contributed to the acceptance of the programme and the increasing number of patients seen at a specialised clinic.

Clinical and laboratorial findings in pregnant ewes and their progeny infected with Border disease virus (BDV-4 genotype).

To evaluate the pathogenicity of local isolates of ovine pestiviruses (BDV-4 genotype), 13 virus- and antibody-negative, artificially inseminated pregnant ewes were challenged on days 108 (5 ewes), 76 (5 ewes) and 55 of pregnancy (3 ewes) with 2 ml of ovine pestivirus containing 10(6) TCID(50). Viraemia was detected by RT-PCR from 2 to 15 days pi in most ewes. No abortion due to the infection was observed but the number of stillbirths was high (32%), and bodyweight at lambing was significantly reduced compared to the experimental flock of origin used as control. Clinical symptoms in live lambs consisted on tremors, gait anomalies and inability to stand unaided. Skeletal abnormalities (brachygnathia, prognathia, arthrogryposis) were present in 44% of the lambs. Only 20% of the lambs were clinically normal. RT-PCR was a very sensitive technique compared to antigen ELISA in detecting viral presence in experimentally infected ewes and their progeny.

Doxorubicin and cyclophosphamide followed by weekly docetaxel as neoadjuvant treatment of early breast cancer: analysis of biological markers in a GEICAM phase II study.

INTRODUCTION: To evaluate the sequential administration of doxorubicin (A) and cyclophosphamide (C) followed by weekly docetaxel in women with stage II to IIIA breast cancer. PATIENTS AND METHODS: Patients received 60 mg/m(2) of A and 600 mg/m(2) of C every three weeks for four cycles followed by 12 infusions of weekly docetaxel at a dose of 36 mg/m(2) and with a 2-week resting period. RESULTS: Sixty-three women were included. On an intention-to- treat basis, clinical response rate was 90% (95% CI: 83-98), with 46% complete responses. Breast-conserving surgery could be performed in 43 patients (68%). Complete pathological responses in the breast were confirmed in 17% of patients. No correlations between levels of expression of topoisomerase II alpha, survivin or p27 and the pathological response were detected. The study treatment was generally well tolerated. CONCLUSION: Neoadjuvant AC followed by weekly docetaxel is a feasible regimen for patients with early-stage breast cancer.

Dramatic photoluminescence quenching in carbon dots induced by cyclic voltammetry.

This study focuses on the structural rearrangements and the photoluminescent behavior of pyrolytically derived carbon dots when subjected to a series of cyclic voltammetry sweeps. Although the electrical signals involved are not pronounced, multiple electrochemical cycling results in a progressive suppression of the photoluminescence, so that after 42 sweeps the intensity is reduced by one order of magnitude. At the same time, the fluorescence component stemming from the organic fluorophores is blue-shifted, while the contribution of the carbogenic cores is red-shifted. XPS and FTIR spectra reveal that the voltammetric field induces an extensive formation of C-O and C[double bond, length as m-dash]O at the expense of the C[double bond, length as m-dash]C bonds. Our findings indicate a close relationship between the electrochemical response and the structure of C-dots and, thus, have direct implications on the development of C-dot based electroluminescent materials, electrochemical sensors and solar cells.

Current controversies in the management of early breast cancer.

Medical professionals in general, and medical oncologists in particular, have highly stressful practices because they are under constant pressure to have the highest-quality, up-to-date evidence available in order to make the right decision for each individual patient. From a practical point of view, being updated on oncological and other medical specialties may seem an insurmountable task because the number of scientific publications has increased dramatically. The use of systematic reviews of randomised controlled trials or the application of results obtained from high-quality randomised controlled trials are some of the most common ways to address this need. Unfortunately, they do not cover all complex clinical situations that the majority of medical oncologists face in their outpatient consultations. In this review, we report the conclusions achieved in a multiexpert meeting where five important controversies in the treatment of breast cancer were analysed. Five highly experienced medical oncologists were required to defend an affirmative answer and another five were required to defend a negative answer for each of the clinical questions. After that, a one-day meeting was organised to debate each clinical question and to reach a consensus. We report here the content of this multi-expert meeting along with the conclusions drawn.

Biweekly docetaxel and gemcitabine as neoadjuvant chemotherapy followed by adjuvant doxorubicin and cyclophosphamide therapy in stage II and III breast cancer patients: results of a phase II study.

INTRODUCTION: The purpose of this phase II study was to evaluate the efficacy and safety of neoadjuvant docetaxel/gemcitabine treatment in a biweekly regimen. MATERIALS AND METHODS: Patients with stage II/III breast cancer were treated with docetaxel (65 mg/m(2)) followed by gemcitabine (2500 mg/m(2)) every 2 weeks for 6 cycles. Patients with a clinical response or stable disease underwent mastectomy or breast-conserving surgery plus axillary dissection. After surgery, patients received 4 cycles of standard doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 21 days. RESULTS: Thirty-five patients were included in the trial. The overall response rate was 71.4% (95% CI: 53.7-85.4), with 8 complete and 17 partial responses. Breast conservation was possible in 59% of the patients. Toxicity was manageable. CONCLUSIONS: We consider biweekly docetaxel and gemcitabine could be an active and tolerable regimen option in the neoadjuvant setting sequentially with standard adjuvant doxorubicin-cyclophosphamide in patients with stage II or III breast cancer.

Flock-prevalence of border disease virus infection in Basque dairy-sheep estimated by bulk-tank milk analysis.

Bulk-tank milk (BTM) samples from 154 sheep flocks were used to estimate BDV prevalence in the Basque Country in Spain using an ELISA and a RT-PCR test. The proportion of antibody-positive flocks was 68% but varied significantly between provinces and was 93% in Araba and 54-55% in Bizkaia and Gipuzkoa. Most ELISA-positive flocks had very low antibody inhibition percentage (AIP) indicating high seroprevalence and recent BDV exposure. However, only 9% flocks were PCR-positive suggesting few infected ewes were being milked at the time of sampling. Phylogenetic analysis of the 5' NCR sequences of BDV from seven infected flocks showed that all except one clustered within the group formed by BDV type C strains from a previous study in the region, whereas the remaining isolate was closest to BDV type A. These results suggest that BDV strains in most Basque flocks have a common origin and differences in prevalence between provinces are associated to recent events affecting BDV spread such as use of communal pastures and sheep trading. The widespread distribution of BDV in the region, advocates for the implementation of BDV control strategies and highlights the potential risk of sheep as a pestivirus reservoir for other species.

Inhibiting the PI3K signaling pathway: buparlisib as a new targeted option in breast carcinoma.

Aberrations in the PI3K signaling pathway are frequently observed in patients with breast cancer. Because of that, PI3K inhibitors are attractive options for the treatment of breast cancer because PI3K is the most proximal component of the pathway other than receptor tyrosine kinases. Buparlisib is a potent and highly specific oral pan-class I PI3K inhibitor, which is currently under investigation in patients with breast cancer. In this article, we describe the PI3K signaling pathway, the prognostic value of PI3K pathway mutations, as well as the mechanism of action of buparlisib. Lastly, we discuss preliminary results of preclinical and clinical studies showing the efficacy and safety profile of this agent in breast cancer patients.

The presence of CFH, HTRA1, ARMS2, VEGF-A and VEGF-R and the appearance of age-related macular degeneration sub-types.

OBJECTIVE: To demonstrate the genetic influence in the onset of the different age-related macular disease (AMD) subtypes by analysing the genotype distribution of CFH, ARMS2, HTRA1, VEGF-A and VEGF-R polymorphisms in patients with neovascular and atrophic AMD. MATERIALS AND METHODS: The study was conducted on 101 consecutive patients with AMD diagnosis (74 exudative, 27 atrophic) following Wisconsin international classification criteria. The CFH rs1410996, ARMS2 rs10940923, VEGF-A rs833061, rs699947, and VEGF-R rs2071559 polymorphisms were analysed using real time PCR with taqman probes, and HTRA1 rs112000638 using restriction endonucleases digestion. A study was made of the genotype distribution of the different polymorphisms in our group of patients with neovascular AMD and those with the atrophic type, and a comparison was made of the results for each one of the genes studied. RESULTS: No statistically significant differences (P>.05) were found in the genotype distribution of the different polymorphisms between patients with neovascular AMD and patients with atrophic AMD in our population, although the "risk" genotypes tended to appear more frequently in patients with neovascular AMD, despite the lack of statistical significance. CONCLUSIONS: Allelic variants of CFH, ARMS2, HTRA1, VEGF-A or VEGF-R genes are not associated with the different AMD subtypes. This suggests that, although the polymorphisms seem to be associated with the disease susceptibility, they are not involved in the onset of the different clinical variants of AMD. Further studies in different populations, and with a larger cohort of patients, are needed to confirm these results.

SEOM clinical guidelines in early-stage breast cancer 2015.

Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.

[Questionnaire to evaluate the importance of the family in nursing care. Validation of the Spanish version (FINC-NA)]. / Cuestionario para evaluar la importancia de la familia en los cuidados de enfermería. Validación de la versión española (FINC-NA).

BACKGROUND: The nursing profession is focused on patient care, without forgetting that patients are part of a social group, the family. The aim of this study was the adaptation of the "Families' Importance in Nursing Care-Nurses' Attitudes" (FINC-NA) scale to the Spanish language and its validation. METHODS: A descriptive cross-sectional study was carried out, using the bidirectional translation method for linguistic-cultural adaptation. It was applied to the nursing staff in the Paediatric Department of a University Hospital in Madrid. To evaluate the psychometric properties of the Spanish version, reliability, internal consistence and construct validity were calculated. RESULTS: The sample consisted of 274 professionals. Cronbach´s Alpha coefficient for the total scale was 0.864, oscillating between 0.888 and 0.769 in the subscales. The principal components factor analysis identified 4 factors, which explained 54.22% of total variance. CONCLUSIONS: The new instrument makes it possible to determine the importance nurses give to participation by family members and their attitude to involving the latter in patient care, and the possibility of involving them in planning. It has been adapted to the Spanish population with good psychometrics results and enough evidence for its use in this context.

Carbamyl-phosphate synthetase domain of the yeast multifunctional protein Ura2 is necessary for aspartate transcarbamylase inhibition by UTP.

In Saccharomyces cerevisiae, the first two reactions of pyrimidine biosynthesis are catalyzed by the multifunctional protein Ura2 carrying both carbamyl-phosphate synthetase (CPSase) and aspartate transcarbamylase (ATCase) enzyme activities. In order to study how UTP regulates both of these activities mutant strains were constructed: one strain which expressed the Ura2 protein fused to the green fluorescent protein, and two strains expressed truncated Ura2 proteins. These strains exhibited a phenotype associated with a modified regulation of the pyrimidine pathway. Results presented in this report provide arguments in favor of a single UTP binding site located on the CPSase domain, and support a model in which ATCase activity is inhibited by UTP only when it can interact with the CPSase domain.

Gemcitabine and carboplatin for patients with advanced non-small cell lung cancer.

The survival of patients with advanced non-small cell lung cancer remains poor. Cisplatin-based chemotherapy produces a modest benefit in survival compared with that observed with best supportive care. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a novel nucleoside antimetabolite, is active and well tolerated. The combination of gemcitabine/cisplatin has shown a significant improvement in response rate and survival over cisplatin alone. Phase III trials comparing gemcitabine/cisplatin with older combinations such as cisplatin/etoposide or mitomycin/ifosfamide/cisplatin have shown a higher activity for gemcitabine/cisplatin; however, the best way to combine these drugs remains unclear. In addition, the 3-week schedule has obtained a higher dose intensity with less toxicity and similar efficacy as the 4-week schedule. The role of carboplatin in combination with new drugs is still under evaluation. Gemcitabine/carboplatin seems to be a good alternative, with the advantage of ambulatory administration and lower nonhematologic toxicity. The 4-week schedule has produced frequent grade 3/4 neutropenia and thrombocytopenia in some studies. The 3-week schedule, using gemcitabine on days 1 and 8 and carboplatin on day 1, is a convenient and well-tolerated regimen. The toxicity profile is acceptable without serious symptoms. This schedule could be considered a good option as a standard regimen. Semin Oncol 28 (suppl 10):4-9.

Gemcitabine/vinorelbine in metastatic breast cancer patients previously treated with anthracyclines: results of a phase II trial.

This phase II study was designed to evaluate the response rate (RR) and toxicity of gemcitabine/vinorelbine in patients with metastatic breast cancer. All patients had previously received anthracyclines. Treatment consisted of gemcitabine 1200 mg/m2 and vinorelbine 30 mg/m2 on days 1 and 8, every 3 weeks. Twenty-five patients were enrolled. Median age was 59 years (range, 33-73 years). Ten patients had received only adjuvant therapy with anthracyclines. The remaining 15 patients had received chemotherapy for metastatic disease, including taxanes in 11 cases. Four patients could not be evaluated for response. By intent-to-treat analysis, the overall RR was 44% (95% CI, 24.4%-65%). Median duration of response and median time to treatment failure were 21 and 17 weeks, respectively. The main toxicity was hematologic, with grade 3/4 neutropenia occurring in 13 patients and 1 patient developing febrile neutropenia. Two deaths from pneumonia occurred. These results reveal an encouraging activity with a reasonable toxicity profile in a patient population with an unfavorable prognosis. Our group is conducting a randomized study to compare this combination with vinorelbine alone in patients with metastatic breast cancer after failure to respond to anthracyclines and taxanes

Phase II study of ifosfamide plus vinorelbine in metastatic breast cancer patients previously treated with combination chemotherapy.

Forty-six patients were included in a phase II study to evaluate the response rate and toxicity of a combination of ifosfamide and vinorelbine in metastatic breast cancer patients previously treated with one or more regimens of chemotherapy. Treatment consisted of ifosfamide 1.6 g/m(2) IV days 1-3 (with mesna) and vinorelbine 25 mg/m(2) IV days 1 and 8, every 3 weeks up to 6 cycles. The median age was 55 years (range 40-76), the World Health Organization (WHO) performance status was 0-1 in 93% of the patients and 2 in the remaining 7%. In all, 43% had received two or more previous lines of chemotherapy, and 91% had been treated with anthracyclines. Forty-four patients were evaluable for response, and all patients for toxicity. The overall response rate was 36.4% [95% confidence interval (CI) 22.4-52.2]. Stabilization was observed in 20.4% and progression in 43.2%. The median time to progression was 25 weeks (95% CI 14-36). Median relative dose intensity (=actual received dose intensity/planned dose intensity) was 0.99 for ifosfamide and 0. 80 for vinorelbine. The main toxicity was hematological, with 63% of the patients experiencing grade 3-4 neutropenia. With a moderate toxicity, this is an active regimen that may be taken into consideration in pretreated metastatic breast cancer patients when further chemotherapy is indicated.

Pathologic-clinical characterization of leptospirosis in a golden Syrian hamster model.

Experimental leptospirosis was reproduced in golden Syrian hamsters (Mesocricetus aureatus). Evaluation of three Leptospira serogroups (canicola, icterohaemorrhagiae and pomona) was carried out regarding their virulence, production of symptoms and lethal activity. Macroscopic and microscopic studies of tissue lesions were also made. Animals were inoculated with 3.75 x 10(6) to 6 x 10(7) bacteria through the intraperitoneal (IP) route. The clinical development of the disease in Syrian hamsters was characterized by the presence of general symptoms between the third and fifth day after inoculation. With highly virulent strains, the distinctive clinical picture occurred and death followed before the seventh day. The strain of the pomona serogroup proved to be more virulent than those of the other serogroups and produced the most florid picture of the disease. Pathogenic aspects of this process were also studied.

[Bilateral hemifacial spasm: eight personal case reports]. / Espasmo hemifacial bilateral. A propósito de ocho casos.

INTRODUCTION: Hemifacial spasms consist in tonic clonic, involuntary, asymmetrical and asynchronous contractions in the territory innerved by the facial nerve. Several different causes may give rise to this disorder, the most frequent of which are vascular abnormalities in the cerebellopontine angle. Its clinical features and electrophysiological studies are commonly used in diagnosis and its etiological diagnosis is most frequently performed by means of magnetic resonance imaging. Symptoms are treated using local injections of Botulinum toxin Type A in the affected muscles. AIMS: To review our experience in the handling of this pathological condition and to determine the results of employing Botulinum toxin. PATIENTS AND METHODS: We describe the cases of bilateral hemifacial spasms that have been diagnosed in the Virgen Macarena Hospital in Seville and La Fe in Valencia since 1980, as well as the follow up after treatment with Botulinum toxin. RESULTS: We describe eight cases of this pathological condition in which patients were treated with Botulinum toxin, and in all cases there was an improvement in the symptoms. CONCLUSIONS: Treatment with Botulinum toxin is considered to be satisfactory and provides a marked improvement in the patients quality of life.

[Vesico-acetabular fistula following prosthesis migration]. / Fístula vésico-acetabular tras migración protésica.

A rare case is described of vesico-acetabular fistula following acetabulum displacement of a hip replacement towards the inner bladder, fourteen years after the original insertion of the prosthesis. In all the reviewed literature of we have not found a single described case of vesico-acetabular fistula associated with displacement towards the bladder interior of a hip prosthesis, which leads us to consider this complication an exceptional one.