DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 ovarian carcinomas.

BACKGROUND: Few studies have attempted to characterise genomic changes occurring in hereditary epithelial ovarian carcinomas (EOCs) and inconsistent results have been obtained. Given the relevance of DNA copy number alterations in ovarian oncogenesis and growing clinical implications of the BRCA-gene status, we aimed to characterise the genomic profiles of hereditary and sporadic ovarian tumours. METHODS: High-resolution array Comparative Genomic Hybridisation profiling of 53 familial (21 BRCA1, 6 BRCA2 and 26 non-BRCA1/2) and 15 sporadic tumours in combination with supervised and unsupervised analysis was used to define common and/or specific copy number features. RESULTS: Unsupervised hierarchical clustering did not stratify tumours according to their familial or sporadic condition or to their BRCA1/2 mutation status. Common recurrent changes, spanning genes potentially fundamental for ovarian carcinogenesis, regardless of BRCA mutations, and several candidate subtype-specific events were defined. Despite similarities, greater contribution of losses was revealed to be a hallmark of BRCA1 and BRCA2 tumours. CONCLUSION: Somatic alterations occurring in the development of familial EOCs do not differ substantially from the ones occurring in sporadic carcinomas. However, some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify BRCA-related patients likely to respond to PARP inhibitors.

Enhancement of confocal microscopy images using Mueller-matrix polarimetry.

A simplified procedure based on Mueller-matrix polarimetry has recently been reported as a method of retinal image improvement in a confocal ophthalmoscope [J. M. Bueno et al., J. Opt. Soc. Am. A 24, 1337 (2007)]. Here, we have applied the technique to imaging static samples providing well-defined reflection properties. The method uses a generator of polarization states in the illumination pathway of a confocal scanning laser system. From the calculated four elements of the Mueller matrix of any sample and instrument combination, the best images defined by different metrics were constructed. For samples with specular, diffuse and mixed reflections, the best-constructed images showed an enhancement in both objective and subjective image quality compared to the original images and those obtained from frame averaging. This technique could improve microscopic imaging in many diverse fields, particularly in biomedical imaging.

Pegfilgrastim and daily granulocyte colony-stimulating factor: patterns of use and neutropenia-related outcomes in cancer patients in Spain--results of the LEARN Study.

Daily granulocyte colony-stimulating factors [(G-CSFs); e.g. filgrastim, lenograstim] are frequently used to reduce the duration of chemotherapy-induced neutropenia (CIN) and the incidence of febrile neutropenia (FN) in cancer patients. A pegylated formulation of filgrastim, pegfilgrastim, which is administered once per cycle, was introduced in Spain in 2003. LEARN was a multi-centre, retrospective, observational study in Spain comparing patterns of use of daily G-CSF and pegfilgrastim, and CIN-related outcomes in adults with non-myeloid malignancies receiving myelosuppressive chemotherapy. Outcome measures were the percentage of patients receiving G-CSF for primary prophylaxis versus secondary prophylaxis/treatment, duration of treatment with G-CSF and incidence of CIN-related complications. Medical records from consecutive patients with documented pegfilgrastim (n = 75) or daily G-CSF (n = 111) use during 2003 were included. The proportion of patients receiving primary or secondary prophylaxis was comparable between the pegfilgrastim (39 and 48% respectively) and daily G-CSF (40 and 48% respectively) groups. However, there was a trend towards less frequent use to treat a neutropenic event such as FN or neutropenia in the pegfilgrastim group (17 versus 30% with daily G-CSF). Chemotherapy-induced neutropenia-related complications were less frequent in patients receiving pegfilgrastim (e.g. FN 11 versus 24% with daily G-CSF). This is the first study to show the potential benefits of pegfilgrastim over daily G-CSF in Spanish clinical practice.

Main information requests of family members of patients in Intensive Care Units. / Principales demandas informativas de los familiares de pacientes ingresados en Unidades de Cuidados Intensivos.

OBJECTIVE: To compile an inventory of information requests prioritized by the family members, to find out which professionals them consider able to respond these requests, and to explore the differences in perception between family members and professionals. DESIGN: Qualitative analysis of content validation and descriptive cross-sectional study. SCOPE: 41 Spanish ICU. PARTICIPANTS: Relatives, physicians and nurses of critical patients. INTERVENTION: From an initial list of questions extracted from literature review, physicians, nurses, and relatives of critical patients incorporated issues that they considered not included. After analyzing content validity, a new list was obtained, which was again submitted to the participants' assessment to evaluate the level of importance that they assigned to each question and which professional they considered appropriate to answer it. RESULTS: most important questions for the relatives: concern about the clinical situation, measures to be taken, prognosis and information. There was a coincidence between relatives and professionals in the priority issues for families. There were significant differences in the importance given to each question: between doctors and relatives (72/82 questions), and between nurses and relatives (66/82 questions) (P<.05). For the relatives, 63% of the questions could be answered by doctors or nurses, 27% preferably by doctors and 10% by nurses. CONCLUSIONS: The most relevant issues for families were prognosis and severity, but also the need for information. Healthcare professionals tend to underestimate the importance of many of the questions that concern families. Relatives feel that most of their concerns can be resolved either by doctors or nurses.

Prevalence of agenesis of frontal sinus in human skulls with metopism.

BACKGROUND: The frontal bone is an anatomical structure of the skull separated by the metopic suture in the childhood. The scientific literature indicates that metopic suture consolidates with closure in the early stages of life. Metopism is the term used to describe a metopic suture that persists up to the adulthood. Persistent metopic suture is associated potentially with the agenesis of the frontal sinus. AIM: To investigate the prevalence of absent frontal sinuses in dry skulls with metopism. MATERIALS AND METHODS: The present study was performed after the approval of the local Committee of Ethics in Research. The sample consisted of dry skulls (n=245), aging between 17 and 50 years old, of the Forensic Medical Institute of Goiânia, Brazil. The skulls underwent anthropological exam in the search for metopism. Radiographic exam was performed in the skulls with metopism to verify the presence or absence of the frontal sinus. The radiographic assessment was performed with a Mobile DaRt Evolution device (Shimadzu, Kyoto, Japan) with protocol set in 64 kV and 16 mA). RESULTS: From the 245 dry skulls, 17 presented metopism. The length of the metopic suture in the skulls, considering the distances between nasio and bregma craniometric landmarks, ranged between 114 mm and 137 mm. Radiographic exams were performed on 16 skulls (one skull was not analysed radiographically because of extensive destruction). Only one skull (6.25%) had the frontal sinus absent. Besides the agenesis, the present study also found four (12.5%) skulls with aplasia and eight (25.0%) hyperplasia of the frontal sinus in dry skulls with metopism. CONCLUSION: The present study found a low prevalence rate of the agenesis of frontal sinuses in dry skulls with metopism.

GEINOFOTE: efficacy and safety of fotemustine in patients with high-grade recurrent gliomas and poor performance status.

PURPOSE: The treatment of recurrent high-grade gliomas (HGG) is controversial. There are different therapeutic schedules but without a clear orientation about which of them should be used in each clinical situation. In addition, when patients suffer a second recurrence or they have poor performance status, they are excluded from clinical trials, although second recurrences and poor performance status are indeed more and more real and common situations in the clinical setting. In this study, we assessed the efficacy and safety of fotemustine (FTM) in HGG [fundamentally, glioblastomas (GB)], independent of time of recurrence or performance status. METHODS/PATIENTS: Retrospective study in HGG patients treated with FTM in second or further line according to standard, the Addeo or any other scheme, starting treatment prior to 30 November 2012. Included patients reflect the regular situation in which the drug is used in terms of comorbidities and analytic situation (hematologic, renal and hepatic functions). Response assessment was performed by MRI and according to the clinical protocols of each center (every 8-12 weeks). Clinical situation and supportive care drugs were evaluated in each medical consultation. Clinical end-points analyzed, among others, were: PFS-6, PFS, OS, response rates, toxicity, quality of life and neurocognitive impact. RESULTS: In terms of activity, an overall response rate of 8 % was observed: partial response 6 % (7 patients) and complete response 2 % (2 patients). The median time to achieve the greater response with FTM was 73 days (4-841 days). Patients treated according to the Addeo schedule had a shorter time to greater response in comparison with other schedules (85.9 vs 114 days), although without statistical significance. There were no significant differences in progression-free survival (PFS) when comparing different FTM schedules or using FTM in first or second recurrence. Median PFS: 3 months. PFS-6: 30.3 %. Overall survival (OS): although without significant differences, a tendency to better survival when using the Addeo schedule versus other schedules was observed (at 6 months, 44.6 vs 34.5 %; at 12 months, 25 vs 23.6 %; at 18 months, 11.5 vs 7.9 %), as well as if earlier use (second vs third line) concerning OS-12 (33.7 vs 18.2 %). Median OS: 5.2 months. Grades 3-4 toxicity was 28 % (31 patients), being neutropenia (4 %) and thrombocytopenia (17 %) the most frequent adverse reactions. From quality of life and neuro-cognitive function perspectives, 11 patients (10 %) and 16 (14 %) improved the Karnofsky Index and neurological impairment, respectively, after FTM treatment. CONCLUSION: This study has shown that FTM is safe and has a comparable activity with other available therapeutic options of use in the treatment of recurrent HGG.

Human breast cancer cell metastasis to long bone and soft organs of nude mice: a quantitative assay.

Bone is a common metastatic site in human breast cancer (HBC). Since bone metastasis occurs very rarely from current spontaneous or experimental metastasis models of HBC cells in nude mice, an arterial seeding model involving the direct injection of the cells into the left ventricle has been developed to better understand the mechanisms involved in this process. We present here a sensitive polymerase chain reaction (PCR) method to detect and quantitate bone and soft organ metastasis in nude mice which have been intracardially inoculated with Lac Z transduced HBC cells. Amplification of genomically incorporated Lac Z sequences in MDA-MB-231-BAG HBC cells enables us to specifically detect these cells in mouse organs and bones. We have also created a competitive template to use as an internal standard in the PCR reactions, allowing us to better quantitate levels of HBC metastasis. The results of this PCR detection method correlate well with cell culture detection from alternate long bones from the same mice, and are more sensitive than gross Lac Z staining with X-gal or routine histology. Comparable qualitative results were obtained with PCR and culture in a titration experiment in which mice were inoculated with increasing numbers of cells, but PCR is more quantifiable, less time consuming, and less expensive. This assay can be employed to study the molecular and cellular aspects of bone metastasis, and could easily be used in conjunction with RT-PCR-based analyses of gene products which may be involved with HBC metastasis.

Measurement of parameters of polarization in the living human eye using imaging polarimetry.

An imaging polarimeter using liquid-crystal variable retarders (Bueno, J. M., Artal, P. (1999). Double-pass imaging polarimetry in the human eye. Optics Letters, 24, 64-66) has been used to study the parameters of polarization in the living human eye. Retardation introduced by birefringent structures of the eye has been calculated by using a spatially resolved collection of Mueller matrices obtained from series of 16 double-pass retinal images. Results for images with a 2-mm pupil diameter show that although the retardation introduced by the eye in a double-pass varies among individuals, at the central cornea the slow axis is directed along the upper-temporal to lower-nasal line and the ellipticity is close to zero, which indicates the presence of linear birefringence. As pupil size increased, the measured retardation also increased, while ocular birefringence remained linear and azimuthal angle changed without a clear tendency.

Depolarization effects in the human eye.

We have studied the effects of depolarization in the living human eye by using a spatially resolved Mueller-matrix polarimeter [Opt. Lett. 24 (1999) 64]. Results show that the degree of polarization for the central part of double-pass images is about 0.85 and 0.70 for 2 mm and 5 mm of pupil, respectively. This parameter decreases towards the tails of the image. In the plane of the pupil, the degree of polarization also depends on the analyzed area, and it has been related to the different components of the light coming back from the retina. Values of polarizance suggest that the eye presents a slight polarizing power mainly due to the existence of both circular birefringence and dichroic properties. Polarizance is also larger at the central part of double-pass images (about 0.25 on average) and decreases along the radius. In addition, it has been shown that the major retinal layer where the light is reflected does not depend on the state of polarization of the incident light.

Teaching veterinary parasitology throughout the world.

In order to understand how the teaching of parasitology in veterinary schools and faculties in the world is carried out, a questionnaire was sent to all centres listed in the W.H.O. World Directory. A total of 91 replies were received. Additional information was obtained from the report of a symposium held in Hannover, Germany in 1978 and from the Education Committee of the American Association of Veterinary Parasitologists in 1981. The academic level, the place of parasitology in the veterinary curriculum, textbooks and practical instruction, evaluation techniques, teaching staff, institute organization and publications are discussed.

[Thrombolysis of thrombosed heart valve prostheses: presentation of 2 cases and review of the literature]. / Trombólisis de prótesis valvulares cardíacas trombosadas: presentación de 2 casos y revisión de la literatura.

Two women aged 38 and 51 years with thrombosed prosthetic heart valves (TPHV) in both tricuspid and mitral positions have been successfully treated with recombinant tissue plasminogen activator (rt-PA), 70 mg over 5 hours, and streptokinase (SK) 2,000,000 U over 10 hours without important complications. Cardiac surgery is the most commonly used therapy for combating this serious complication with a high mortality rate in general. There is controversy over the use of thrombolytics in TPHV. We reviewed the literature concerning treatment in 90 patients with this complication involving the different valve positions. We found an 80% therapeutical success rate, 8% partially successful, and 7% mortality rate. The main complications were of an embolic nature in 17% of cases, although the majority of these were transitory; haemorrhage occurred in 11% but there was only one case needing a transfusion. We conclude that thrombolytics are an efficient therapy in cases of TPHV in any position and should be started as soon as possible after the diagnosis has been confirmed.

An infrared study of CO adsorption on silica-supported Ru-Sn catalysts.

CO adsorption on Ru-Sn/SiO(2) catalysts of various Sn/(Ru+Sn) ratios was examined by Diffuse Reflectance Infrared Fourier-Transform Spectroscopy (DRIFTS). The catalysts were prepared by the incipient wetness impregnation method. Catalysts were activated by H(2) reduction at 773 K. CO adsorbed on the catalysts shows spectra whose band frequencies are divided into three groups: (i) High Frequency Region (HFR), containing a band at 2065 cm(-1), (ii) Low Frequency Region 1 (LFR(1)), containing bands at 2040-2015 cm(-1), (iii) Low Frequency Region 2 (LFR(2)), containing bands at 1990 and 1945 cm(-1). The types of adsorbed CO species formed strongly depend on the ratio Sn/(Ru+Sn) in the catalyst, CO pressure and temperature of adsorption. Adsorption of CO on Ru sites in the Ru/SiO(2) catalyst results in LFR(1) bands at 2040-2015 cm(-1), which are independent of the CO pressure but the adsorption complexes are easily destroyed by raising the temperature. The addition of Sn to the catalyst creates new sites for CO adsorption. After adsorption at 298 K, the HFR band at 2065 cm(-1) and LFR(2) bands at 1990-1950 cm(-1) are observed. The relative intensities of these bands increase with increasing Sn-content in the samples. The LFR bands are thermally stable while the HFR band is not. The formation of the corresponding species is favored by increasing the CO pressure. Adsorbed CO species giving LFR(1) bands are assigned to linearly-adsorbed CO on the Ru(0) and/or on the Ru-Sn alloy sites. Adsorbed CO species giving HFR bands are assigned to CO adsorption on Ru(delta+)-O-Sn sites. After low temperature CO adsorption on samples with high Sn-content, only species that show bands at 1990 and 1945 cm(-1) in LFR(2) are observed.

[Immunotherapeutic treatment for metastatic renal carcinoma]. / Tratamiento inmunoterápico para el carcinoma renal metastásico.

Immunotherapy management for advanced renal carcinoma has awaken a growing interest over the last few years. Based on Atzpodien's studies, in December 1994 a protocol was initiated in our centre for the treatment of metastatic renal carcinoma, using subcutaneous alpha interferon, subcutaneous Interleukin-2 and endovenous 5-Fluorouracil. The present report analyzes all six cases included in the protocol and their results.

[Fastrach intubation in patients with cervical disease]. / Intubación con Fastrach en pacientes con enfermedad cervical.

The Fastrach laryngeal mask for intubation is a new device designed for blind orotracheal intubation in patients with criteria predictive of difficult airway control. The new device looks like the conventional laryngeal mask but offers a series of design changes that allow orotracheal intubation to be accomplished without visualization of the glottis. The rigid metal tube is bent and incorporates a metal handle; the two fixed bars that prevent the epiglottis from falling and blocking the opening have been replaced by a moveable bar that rises with the passage of the endotracheal tube and the exit of the V-shaped metal tube guides the endotracheal tube that was specially designed for this use. We describe three patients with cervical disease, one with advanced ankylosing spondylitis, one with traumatic luxation of the C6-C7 articulation and one diagnosed of two cervical disk hernias. All their tracheas were intubated without difficulty through the Fastrach mask with the patients' heads in neutral position. Although fiberoptic bronchoscopy is the method of choice in patients with cervical problems, the non-availability of the technique and the need for training in its use make the Fastrach mask an alternative worth considering for such patients.

Should we continue temozolomide beyond six cycles in the adjuvant treatment of glioblastoma without an evidence of clinical benefit? A cost analysis based on prescribing patterns in Spain.

PURPOSE: The standard adjuvant treatment for glioblastoma is temozolomide concomitant with radiotherapy, followed by a further six cycles of temozolomide. However, due to the lack of empirical evidence and international consensus regarding the optimal duration of temozolomide treatment, it is often extended to 12 or more cycles, even in the absence of residual disease. No clinical trial has shown clear evidence of clinical benefit of this extended treatment. We have explored the economic impact of this practice in Spain. MATERIALS AND METHODS: Spanish neuro-oncologists completed a questionnaire on the clinical management of glioblastomas in their centers. Based on their responses and on available clinical and demographic data, we estimated the number of patients who receive more than six cycles of temozolomide and calculated the cost of this extended treatment. RESULTS: Temozolomide treatment is continued for more than six cycles by 80.5 % of neuro-oncologists: 44.4 % only if there is residual disease; 27.8 % for 12 cycles even in the absence of residual disease; and 8.3 % until progression. Thus, 292 patients annually will continue treatment beyond six cycles in spite of a lack of clear evidence of clinical benefit. Temozolomide is covered by the National Health Insurance System, and the additional economic burden to society of this extended treatment is nearly 1.5 million euros a year. CONCLUSIONS: The optimal duration of adjuvant temozolomide treatment merits investigation in a clinical trial due to the economic consequences of prolonged treatment without evidence of greater patient benefit.