Pax8 has a critical role in epithelial cell survival and proliferation.

The transcription factor Pax8, a member of the Paired-box gene family, is a critical regulator required for proper development and differentiation of thyroid follicular cells. Despite being Pax8 well characterized with respect to its role in regulating genes responsible for thyroid differentiation, its involvement in cell survival and proliferation has been hypothesized but remains unclear. Here, we show that Pax8 overexpression significantly increases proliferation and colony-forming efficiency of Fischer rat thyroid line 5 epithelial cells, although it is not sufficient to overcome their hormone dependence. More interestingly, we show that Pax8-specific silencing induces apoptosis through a p53-dependent pathway that involves caspase-3 activation and cleavage of poly(ADP)ribose polymerase. Our data indicate that tumor protein 53 induced nuclear protein 1 (tp53inp1), a positive regulator of p53-dependent cell cycle arrest and apoptosis, is a transcriptional target of Pax8 and is upregulated by Pax8 knockdown. Remarkably, tp53inp1 silencing significantly abolishes Pax8-induced apoptosis thus suggesting that tp53inp1 may be the mediator of the observed effects. In conclusion, our data highlight that Pax8 is required for the survival of differentiated epithelial cells and its expression levels are able to modulate the proliferation rate of such cells.

Qué síntomas presentan los niños con cáncer avanzado en cuidados paliativos? / Symptoms in childrens with advanced cancer who were attended by the palliative care

El dolor es el síntoma más frecuente y que genera más temor en los pacientes y sus cuidadores en la etapa avanzada de la enfermedad oncológica. Estos niños también presentan otros síntomas que pueden provocar importante malestar y empeorar la sensación dolorosa. En nuestro medio no contamos con información en este ámbito, que permita optimizar el tratamiento de estos pacientes. Objetivo. Caracterizar síntomas distintos del dolor en pacientes con cáncer avanzado, controlados por el equipo de cuidado paliativo (CP) del Hospital Roberto del Río. Pacientes y método. Se revisaron 71 fichas clínicas de pacientes ingresados a CP entre abril de 2002 y diciembre de 2010. Se registraron las características demográficas y los diagnósticos fueron clasificados en leucemia aguda, tumores sólidos y tumores del sistema nervioso central (SNC). Se evaluó un listado de síntomas y sus frecuencias. Resultados. El síntoma más frecuente en los pacientes con leucemia aguda fue fiebre (15 por ciento), al igual que los pacientes con tumores sólidos (16 por ciento). En los pacientes con tumores SNC la alteración de conciencia fue el más frecuente (19 por ciento). Sobre el 70 por ciento de los pacientes tuvieron hasta cuatro síntomas y la evaluación de intensidad en la mayoría fue cualitativa. Conclusiones. Síntomas distintos del dolor son frecuentes y pueden producir gran incomodidad. Evaluarlos objetivamente permitiría un mejor manejo, favoreciendo con esto el control del dolor.

Pain is the most common symptom which generates most fear in patients and their caregivers in the advanced stage of cancer. These children also have other symptoms that can cause significant discomfort and exacerbate the sensation of pain. In Chile, there has been no evaluation of the intensity of these symptoms and their effect on pain, and relevant knowledge could improve patient treatment. Objective: Describe symptoms other than pain in patients with advanced cancer who were attended by the palliative care (PC) team at the Roberto del Rio Hospital. Patients and methods: We reviewed medical records of 71 patients admitted to PC between April 2002 and December 2010. We recorded demographic characteristics and diagnoses were classified into acute leukemia, solid tumors and tumors of the central nervous system (CNS). We evaluated a list of symptoms and their frequencies. Results: The most common symptom in patients with acute leukemia was fever (15 percent) as well as in patients with solid tumors (16 percent). In patients with CNS tumors alteration of consciousness was the most frequent (19 percent). Over 70 percent of patients had four or more symptoms and intensity assessment was mostly qualitative. Conclusions: Besides pain, other symptoms are common and can cause great discomfort. Objective assessment of these symptoms would allow better management of children and also optimize pain control.

Unusual endotracheal and breast metastasis from renal clear cell carcinoma: a case report.

We report a case of a woman affected by a metastatic renal clear cell carcinoma who showed unusual metastasis into the trachea and in the right breast 17 years and 21 years after nephrectomy respectively. Two endotracheal metastasis were identified during rigid bronchoscophy and were treated with endotracheal electro-surgery. Solitary metastasis in the right breast was identified by a mammography that revealed a dense mass of 1.5 cm at lower outer quadrant and she underwent to a right breast quadrantectomy. Histological examination showed a clear cell renal carcinoma metastasis as for the trachea as for the breast mass.

[A new experimental model for inducing interstitial cystitis by oxidative stress using bladder instillation of a nitric oxide donor gel]. / Un nuevo modelo experimental de inducción de cistitis intersticial mediante estrés oxidativo empleando instilación vesical de un gel donante de óxido nítrico.

PURPOSE: The aim of this study is to develop a new experimental model of inducing interstitial cystitis (IC) through vesical instillation of a polymeric solution containing the NO donor S-nitrousglutathione (GSNO) and to compare it to the experimental interstitial cystitis induced by vesical instillation of protamine and potassium chloride. MATERIAL AND METHOD: For that purpose 40 female Wistar rats were used, divided in four groups: 1. saline solution + GSNO; 2. saline solution + polymeric solution (without GNSO); 3. protamine sulphate + KCl; 4. protamine sulphate + GSNO. The rats received one application (5 animals) or 3 applications (5 animals) of the corresponding substance through intravesical instillation, and after 6 days (5 animals) or 9 days (5 animals) they were euthanized and their bladders were removed for macroscopic evaluation and histological study. RESULTS: In the macroscopic evaluation we observed edema and hyperemia of the mucosa in 2 (22%) of the animals in group 1, in 0 (0%) of the animals in group 2, in 10 (100%) of the animals in group 3, and in 5 (50%) of the animals in group 4. In the protamine + KCl group and in saline + GSNO similar effects were observed on the bladder wall. The animals in group 2 (saline + polymeric) showed vascular congestion, significantly smaller than the rest after 9 days instillations (p=0.0035). Significant increased fibrosis was observed after instillations in groups 3 and 4, after 6 days (p=0.3781) and 9 days (p=0.0459) respectively, when compared to control (group 2). All groups presented neutrophilic infiltrate of variable intensity 6 days after instillations (p=0.7277). After 9 days, there was a regression of the infiltrate, with no evidence of accentuated neutrophilic reaction in all the groups (p=0.2301). CONCLUSION: The inflammatory response to bladder instillation of an aqueous solution of S-nitrousglutathione was very similar to that induced by bladder instillation of protamine and KCl. Instillation of an aqueous solution of GSNO can be considered a new model for experimental induction of interstitial cystitis.

[NPT (near patient test) in the pharmacy: document and practice guidelines 2008]. / Screening nelle farmacia: documento e linee guida 2008.

NPT tests in the pharmacy. Blood testing can be made with NPT (near patient testing) directly in the pharmacy. Most tests can be made with a single drop of blood (i.e. from a finger) and results are comparable with results from blood test obtained with standard vein blood samples. NPT is basically used for: 1 - evaluating the risk of a disease. 2 evaluating or confirming the presence of a disease. 3 to manage and monitor treatments. The social role of the pharmacy in NPT (particularly in cardiovascular screening) is very important as the pharmacy is an institution with capillary diffusion in the territory. The pharmacy often constitutes an important, first-level consultancy point for the population, particularly where health institutions are far away (small villages) or not easily accessible. Rules for NPT. Guidelines for NPT testing in the pharmacy have been proposed and discussed in a consensus meeting (Spoleto, 2007). NPT guidelines suggest operating management and technical procedures and indicate prospective lines of action defining new roles for the pharmacy. Coagulation tests can be now made in the pharmacy at a very low cost and with an efficacy comparable to blood tests obtained with a vein sample. Results can be read in seconds. This test is also available for personal use and home testing. NPT: The Clinical Study. The evaluation of the results of a clinical study (patients with venous thrombosis/pulmonary embolisation, patients with fibrillation and patients with artificial cardiac valves) indicates that costing is very favourable for NPT which may reduce costs and improve management of many clinical conditions and their monitoring. Training and control systems help NPT testing to be reliable and useful to screen and manage most clinical and risk conditions. The clinical study also shows the positive correlation between NPT tests and standard' tests. In conclusion NPT tests are now very reliable and cost-effective and can be used for screening, diagnosis and to monitor treatments.

[Headache in patient with neurofibromatosis type 1]. / Cefalea en paciente con neurofibromatosis tipo I.

INTRODUCTION: Neurofibromatosis type 1 (NF-1) is an autosomal dominant neurocutaneous syndrome due to a mutation in chromosome 17 (at 17q11.2). The association of NF-1 with Arnold-Chiari I malformation has been previously described. CASE REPORT: A 23 year-old woman diagnosed of NF-1 based on the presence of cutaneous lesions and a familiar background consistent with this was referred to the neurologist due to oppressive frontooccipital bilateral headache that irradiated to both shoulders. It worsened on physical effort and Valsalva maneuver and had more than one year of evolution. Physical examination showed multiple café au lait spots in the trunk and cutaneous neurofibromas in the cervico-dorsal region, as well as short height and mild dorsal scoliosis. Neurological examination showed hyperreflexia in both legs and slight light touch and pinprick hyposthesia in the left arm. The magnetic resonance findings suggested Arnold - Chiari I malformation with associated cervical syrinx, without any other abnormalities in the central nervous system. She underwent surgery, with partial improvement of the symptoms. CONCLUSION: The association between NF-1 and Arnold- Chiari I malformation seems to be more than coincidental. The abnormalities of the embrionary development secondary to NF-1 would be responsible for the posterior fossa hypoplasia found in Arnold-Chiari malformation. Our case focuses on the idea that Arnold- Chiari malformation should be included in the list of abnormalities reported in NF-1.

A novel biweekly pancreatic cancer treatment schedule with gemcitabine, 5-fluorouracil and folinic acid.

Pancreatic adenocarcinoma is a common disease considered to be poorly responsive to antiblastic treatment. Recent clinical and preclinical results suggest that a combined treatment of gemcitabine (GEM), 5-flurouracil (5-FU) and folinic acid (FA) offers a clinical benefit in patients with advanced pancreas adenocarcinoma. The aim of this phase II clinical trial was to evaluate the antitumour activity and toxicity of a novel biweekly schedule of this combination in patients with pancreatic adenocarcinoma. A total of 42 patients received a 30 min infusion of FA (100 mg m(-2)) and 5-FU (400 mg m(-2)) (FUFA) on days 1-3, and GEM 1000 mg m(-2) on day 1 every 15 days. We observed 13 objective responses (two complete, 11 partial) and 23 stable diseases. The median time to progression was 9.75 months (95% Confidence Interval (CI), 6.88-12.62) and the median overall survival was 13.10 months (95% CI 9.64-16.56). There were seven cases of each grade III gastroenteric and haematological toxicity. The GEM plus FUFA combination appears to be well tolerated and very active in patients with pancreatic carcinoma.

[Spontaneous intracranial hypotension]. / Hipotensão intracraniana espontânea.

The authors consider some clinical and radiological aspects of spontaneous intracranial hypotension syndrome, based on the knowledge obtained from three clinical situations. Postural headache was a constant complaint. In all cases, magnetic resonance imaging data obtained was diffuse dural enhancement and, in two cases, bilateral subdural fluid collections. The increasing recognition of this syndrome led to its distinction from meningeal inflammatory or neoplasic conditions, sparing the patient from unnecessary investigation.

[Preoperative applications of cortical mapping with functional magnetic resonance]. / Aplicações pré-cirúrgicas do mapeamento cortical por Ressonância Magnética Funcional.

The authors describe a clinical experience in cortical brain mapping by Functional Magnetic Resonance Imaging (FMRI) with a 1.0 T MR scanner with BOLD technique and echo-planar imaging (EPI). A brief review is made of the theoretical basis of the BOLD technique and of the different functional tasks used. The main clinical applications of FMRI cortical mapping regarding the sensorimotor cortex of the hand and of language are mentioned. The experiment involves 29 patients, 16 with gliomas (G), 7 with mesial temporal sclerosis (MT S) and 6 with arteriovenous malformations (AVM) The most frequent clinical applications were the determination of the topographic relationship of the cerebral lesions with these eloquent cortices as well as the presurgical lateralization of language in medically intractable epileptic patients. The results are discussed in order to assess the FMRI cortical mapping role as a noninvasive method for presurgical planning, regarding the evaluation of the potential neurosurgical risks and the identification of viable cortex regions displaced or reorganized as a consequence of disease. Additionally, FMRI cortical mapping can also assess the atypical speech representations and the language lateralization of the patients.

[Three-dimensional magnetic resonance reconstruction. Significance of neurosurgical planning]. / Reconstruções tridimensionais cerebrais por Ressonância Magnética. Importância no planeamento neurocirúrgico.

The authors describe their experience with three-dimensional (3D) MRI reconstructions of the cerebral cortex in neurosurgical planning of cortical and subcortical lesions. The majority of the lesions were located on the cerebral hemispheres; there were also few cases of posterior fossa lesions. The authors selected three clinical cases to demonstrate the interest of 3D MRI. The authors describe another image processing method based on the three dimensional models obtained by using Curvilinear Multiplanar Reformatting (CMR) for the identification of subtle focal dysplastic lesions in patients with epilepsy. The advantages and disadvantages of those 3D MRI reconstructions methods are discussed and a comparison with conventional cross-sectional images is mentioned. The main disadvantages are the raw data relative to long acquisition time and the difficulty in sometimes establishing the cleavage plane between the cortex and extra-axial structures (e.g. young patients; lesions with great mass effect; lesions ventrally located in the cerebral lobes). In conclusion, the 3D MRI reconstructions of the cerebral cortex reveal additional information to conventional cross-sectional images and permit a precise location of the lesions. This is essential in some circumstances for neurosurgical planning and strategy, improving neurosurgical performance and patient outcome.

Automated screening for quality control using PAPNET: a study of 638 negative Pap smears.

To determine if the PAPNET screening system can be used for quality control to lower false-negative rates for Pap smears 638 manually screened, "negative" Pap smears were subjected retrospectively to the PAPNET screening system. Twenty-nine of the smears came from 18 patients who subsequently had biopsyproven high-grade squamous intraepithelial lesions (SIL). The remaining 609 negative smears were arbitrarily selected as controls. One hundred twenty-eight (128) of the retrospectively reviewed smears (20%) were selected by PAPNET for microscopic referral because of potential abnormalities. Abnormalities were confirmed on 14 of these smears upon microscopic evaluation. Five of these 14 smears were from smears obtained from four of the 18 women with high-grade SIL. The incidence of manually screened false-negatives detected by PAPNET rescreening was 14/638 or 2.2% for the entire patient population in this study and 5/29 or 17.24% for the targeted patients known to have subsequently developed highgrade lesions. The 2.2% decrease in the false-negative rate in this experiment may be partly artificial as this study group was seeded with false-negative cases at high risk for containing missed abnormalities. The implementation of the PAPNET system for quality control may lower false-negative rates for Pap smears.

[Infection in severe neutropenia: analysis of 140 episodes]. / Infecciones en neutropenias severas: analisis de 140 episodios.

We analyzed infections complicating 140 episodes of severe neutropenia in 86 patients. The underlying diagnosis was acute leukemia in 64, lymphoma in 12 and isolated cases of bone marrow aplasia, agranulocytosis, dysmyelopoiesis and solid tumors. No fever developed in 35 (25%) episodes. No cause for the fever was identified in 40% of the remaining episodes. Clinical evidence of an infection was present in 20%, with positive bacteriologic findings in 27%. Respiratory infection (16%), pneumonia (11%) and sepsis (10%) were the most common infectious processes. Infectious agents isolated were gram negative bacilli (72%), gram positive cocci (19%) and fungi (9%). The association of amikacin and carbenicillin or cephalosporins proved to be superior to gentamycin-penicillin (p less than 0.01). 16 patients died for an overall mortality of 11%. Pneumonia and infection by K pneumoniae or C albicans were associated to a poorer prognosis.

[Sheehan syndrome and spontaneous pregnancy: report of 2 cases]. / Sindrome de Sheehan y embarazo espontáneo: comunicación de dos casos.

Two patients receiving substitution therapy for Sheehan syndrome became pregnant. No pituitary trophins, except LH responded to stimulation with the hypothalamic hormones TRH and Gn-Rh, or insulin induced hypoglycemia. Computed tomography showed a normal size sella with arachnoid cyst.

Correlacion entre la excrecion de estriol en orinas de 12 y 24 horas en embarazadas sanas. / Correlation between the urinary estriol excretion of 12 and 24 hours in healthy pregnant women

En 16 mujeres embarazadas sanas con edad de gestacion entre 35 y 41 semanas se efectuaron 3 mediciones de estriol urinario por radioinmunoanalisis, correspondientes a orina recolectada en las primeras y segundas doce horas, y la cantidad de estriol excretado en orina de 24 hrs.Se comprueba que existe una relacion directa entre el estriol excretado en las primeras 12 horas, con el estriol excretado en las doce horas siguientes. Esto, a su vez, prueba la alta asociacion entre el estriol excretado en 12 o en 24 horas

Carencia de fierro en mujeres jovenes supuestamente normales, incidencia en un grupo de 100 alumnas de la Facultad de Medicina sede occidente. / Iron deficiency in normal young women. Incidence in a group of 100 students of the Faculty of Medicine, occidental branch

Se estudio la carencia de fierro en 100 mujeres jovenes sin antecedentes de embarazos, hemorragias y otra patologia reciente. Se efectuaron tests hematologicos habituales (hemoglobina y hematocrito) que mostraron no reflejar la totalidad del problema ya que solo indicaron 3 a 1% de carencia, en cambio de medicion de ferritina muestra un 50% de carencia probable (bajo 20 mg/ml) y un 26% seguro (-10% mg/ ml). Se recomienda el suplemento de hierro a la dieta

Hemobilia traumatica. Presentacion de tres casos. / Traumatic hemobilia. Report of three cases

Se presentaron tres casos de hemobilia traumatica, el tratamiento quirurgico realizado y las consideraciones practicas sobre la ligadura de la arteria hepatica. Se revisa la literatura principalmente la relacionada a la hemobilia traumatica por heridas contusas o penetrantes al higado y se destaca el papel de la angiografia en el diagnostico y orientacion de la tactica operatoria a ser ejecutada en cada caso en particular