Determining personalized treatment by gene expression profiling in metastatic breast carcinoma patients: a pilot study.

PURPOSE: The present study evaluates the massive study of gene expression in metastatic breast carcinoma (MBC) patients using microarray gene expression profiling (MAGE) complemented with conventional sequencing, immunohistochemistry (IHC) and fluorescent "in situ" hybridization (FISH), seeking to optimize the treatment in a subset of heavily pretreated patients and with limited life expectancy. PATIENTS, MATERIAL AND METHODS: MBC patients in hormone therapy progression with survival expectancy of at least 3 months (m) have been included. The MAGE contains gene probes representing genes known to potentially interact with available drugs as cited in the literature. RESULTS: Thirty-nine procedures were performed from October 2010 to April 2016. Within the 30 evaluable procedures, considering all hormonal manipulations as a single line, the patients had received a median of 4 treatment lines prior to MAGE (range 1-7). Progression was observed in 6 cases, stable disease (SD) in 7 cases and partial response (PR) in 16 cases, which implies a clinical benefit rate (SD + PR) of 76%. Actuarial median progression-free survival (PFS) was 6 m (95% CI 2.5-9.5) in patients with clinical benefit. The median overall survival (OS) for the entire series was 11 m (95% CI 2.2-19.8). CONCLUSION: Data presented here indicate that the use of MAGE provides relevant information to establish personalized treatment in frail patients with limited life expectancy in which therapeutic futility is a particularly difficult burden to assume.

Phonoarticulation in spinocerebellar ataxia type 3.

Phonoarticulation is characterized by changes in resonance, diadochokinesis, prosody, sound frequency, vocal quality, and intraoral pressure. The main aim of this study was to characterize the phonoarticulation in spinocerebellar ataxia type 3 (SCA3) and correlate it with clinical and genetic factors. Thirty-one patients with SCA3 who were subjected to spontaneous speech recordings and phonoarticulatory diadochokinesis (DDK) participated in the study. Speech analyses were performed starting after 10 s of spontaneous speech, by three experienced speech therapists, using a protocol for dysarthria adapted from the Mayo Clinic. The intra-evaluator reliability was analyzed. The lower the patient's age at disease onset was, the more frequent the occurrences of monofrequency and altered speech rhythm were. Articulation, DDK, resonance, and prosody showed a moderate correlation with the number of "CAG" triplet repeats. We conclude that the phonoarticulation of patients with Machado-Joseph disease (MJD) is characterized by mixed dysarthrophonia with cerebellar and hypokinetic components, and that there is a tendency toward higher frequency of dysarthrophonia symptoms with lower age of disease onset, longer time since onset and higher number of "CAG" triplet repeats.

Value of sentinel lymph node biopsy in papillary thyroid cancer: initial results of a prospective trial.

The objectives of the study were to evaluate the performance of sentinel lymph node biopsy (SLNB) in detecting occult metastases in papillary thyroid carcinoma (PTC) and to correlate their presence to tumor and patient characteristics. Twenty-three clinically node-negative PTC patients (21 females, mean age 48.4 years) were prospectively enrolled. Patients were submitted to sentinel lymph node (SLN) lymphoscintigraphy prior to total thyroidectomy. Ultrasound-guided peritumoral injections of (99m)Tc-phytate (7.4 MBq) were performed. Cervical single-photon emission computed tomography and computed tomography (SPECT/CT) images were acquired 15 min after radiotracer injection and 2 h prior to surgery. Intra-operatively, SLNs were located with a gamma probe and removed along with non-SLNs located in the same neck compartment. Papillary thyroid carcinoma, SLNs and non-SLNs were submitted to histopathology analysis. Sentinel lymph nodes were located in levels: II in 34.7 % of patients; III in 26 %; IV in 30.4 %; V in 4.3 %; VI in 82.6 % and VII in 4.3 %. Metastases in the SLN were noted in seven patients (30.4 %), in non-SLN in three patients (13.1 %), and in the lateral compartments in 20 % of patients. There were significant associations between lymph node (LN) metastases and the presence of angio-lymphatic invasion (p = 0.04), extra-thyroid extension (p = 0.03) and tumor size (p = 0.003). No correlations were noted among LN metastases and patient age, gender, stimulated thyroglobulin levels, positive surgical margins, aggressive histology and multifocal lesions. Sentinel lymph node biopsy can detect occult metastases in PTC. The risk of a metastatic SLN was associated with extra-thyroid extension, larger tumors and angio-lymphatic invasion. This may help guide future neck dissection, patient surveillance and radioiodine therapy doses.

A prospective study of long-term dysphagia following total laryngectomy.

OBJECTIVE: To evaluate the degree of dysphagia in patients before and after total laryngectomy using the Performance Status Scale for Head and Neck Cancer Patients (PSS) and to determine the effects of post-operative radiation therapy, neck dissection, and pharyngoesophageal spasm on PSS scores. METHODS: We performed a controlled, prospective study at a tertiary referral university hospital. Twenty consecutive patients undergoing laryngectomy were included. Patients were followed for at least two years post-operative, without evidence of local, regional, or distant disease. Only patients with squamous cell carcinoma limited to the endolarynx requiring total laryngectomy with or without elective neck dissection for surgical management of cancer and with no pre-operative treatment were included. Dysphagia was evaluated by PSS prior to surgery and again two years postoperatively with an emphasis on eating in public and normalcy of diet domains. Video fluoroscopic evaluation of swallowing was performed one year after treatment. RESULTS: The relative number of patients with low mean scores in PSS (i.e. usually swallow paste of fluid food in presence of some selected persons or alone; < or = 50) increased after total laryngectomy (p = 0.04). Patients with lower scores reported more frequent spasm of the pharyngoesophageal segment (p = 0.005). Mean scores of both domains decreased after surgery (p < 0.05). CONCLUSION: Eating in public and normalcy of diet scores decreased in 50% of patients after total laryngectomy.

Allelic polymorphism of human FcγRIIA-H/R131 receptor in American tegumentary leishmaniasis.

FcγRIIA binding to IgG subclasses with different levels of affinity is influenced by the polymorphism in the gene that encodes this receptor. The substitution of arginine (R) for histidine (H) in the 131 position defines three allelic patterns, H/H, R/R, and H/R, resulting in FcγRIIA-H/H131 affinity for IgG2 and higher affinity for IgG3 subclasses. Studies have shown the importance of genetic host factors in leishmaniasis and participation of FcγRs on the macrophage infection by amastigote forms and in the immune response to Leishmania sp. We analysed the influence of allelic diversity patterns of the receptor FcγRIIA on American tegumentary leishmaniasis (ATL). FcγRIIA-H/R131 polymorphism was determined by PCR followed by an allele-specific enzymatic digestion in 88 individuals with ATL and 98 healthy volunteer blood donors (control group). The genotypic and allelic distributions of FcγRIIA-H/R131 were similar among the studied groups as well in mild and severe clinical forms of ATL. Our results suggest no association between this allelic polymorphism and susceptibility or resistance to ATL, neither influencing the development of different clinical forms of this illness.

Seasonal mortality factors of the coffee leafminer, Leucoptera coffeella.

Seasonal population fluctuation of the coffee leafminer, Leucoptera coffeella (Guérin-Méneville & Perrottet) (Lepidoptera: Lyonetiidae), led to an investigation of its natural mortality factors during the rainy season when the population level is low and during the dry season when population peaks occur. Life-table data were collected from insecticide-free plots within a 3 ha coffee plantation on the upper, medium and lower canopy. Leafminer mortality was similar among the canopy parts but varied in the two seasons studied. During the rainy season, the generational mortality averaged 94.3%, with 50.2, 33.7 and 10.4% occurring during egg, larval and pupal stages, respectively. During the dry season, total mortality was 89%, with 13.2, 61.0 and 14.8% occurring during egg, larval and pupal stages, respectively. Marginal mortality rates during the rainy season were highest for physiological disturbances, rainfall and egg inviability; but, in the dry season, they were highest for predaceous wasps, physiological disturbances and parasitoids. Egg and larval stages accounted for most of the mortality variation in the rainy season, while the combination of larval and pupal mortality better described the generational mortality in the dry season. Variation in mortality during the rainy season was primarily associated with egg inviability, rainfall and parasitoids. In contrast, predatory wasps and physiological disturbances were the main factors associated with mortality variation during the dry season. These results suggest that weather conditions, natural enemies and plant quality attributes are the main determinants of the population dynamics of L. coffeella.

Laryngeal electromyography: contribution to vocal fold immobility diagnosis.

Laryngeal Electromyography (LEMG) is a diagnostic test commonly used in patients with vocal fold movement disorder. The aim of this study is to describe LEMG in patients with vocal fold immobility. A total of 55 dysphonic patients with vocal fold immobility diagnosed by laryngeal endoscopy were grouped according to probable clinical cause: 1) unknown; 2) traumatic; or 3) tumoral compression. They were submitted to LEMG by percutaneous insertion of concentric needle electrode. LEMG was conclusive in all patients and showed a majority with peripheral nerve injury. LEMG diagnosed peripheral nerve damage in 25 group 1, 12 group 2, and 11 group 3 patients. LEMG was normal in 4 patients, suggesting cricoarytenoid joint fixation. Central nervous system disorders was suggested in 2 and myopathic pattern in 1. As the major cause of vocal fold immobility is peripheral nerve damage, LEMG is an important test to confirm diagnosis.

Laryngeal electromyography in normal Brazilian population.

Quantitative analysis of normal values of motor unit action potentials duration and amplitude of muscles tireoaritenoideus (TA), cricotireoideus (CT), cricoaritenoideus lateralis (CAL), and cricoaritenoideus posterioris (CAP) was performed in 14 adult normal Brazilian volunteers. The recordings were obtained by percutaneously inserted concentric needle electrode. Different motor unit action potentials were manually selected in each muscle for quantitative computerized analysis of duration and amplitude. The mean values for duration and amplitude were respectively 3.8 ms and 413 microV for TA, 4.9 ms and 585 microV for CT 4.1 ms and 388 microV for CAL and 4.5 ms and 475 microV in CAP. There were no similar reports of normal values of motor unit action potentials in Brazilian subjects.

Laryngeal electromyography: technical features.

Laryngeal Electromyography (LEMG) is an auxiliary diagnostic method used for the comprehension and diagnosis of different neurological diseases that compromise laryngeal function. The most common LEMG technique is the percutaneous insertion of needle electrodes guided by surface anatomical references. We describe techniques for inserting needle electrodes into the tireoaritenoideus (TA), cricotireoideus (CT), cricoaritenoideus lateralis (CAL) and cricoaritenoideus posterioris (CAP) muscles; these are used at UNICAMP laryngology ambulatory, we discuss difficulties found and their proposed solutions. All patients were submitted to otorhinolaryngological, phonoaudiological and laryngeal endoscopy before LEMG. The CAP approach, by digital rotation of the thyroid cartilage was found to be the most difficult, followed by the CAL approach. TA and CT approaches gave no major problems, except with some older and obese patients. A significant complication of the TA approach via thyroid cartilage was a hematoma in one patient which partially obstructed the laryngeal lumen.

[Detection of phospholipidolytic Candida albicans isolated from saliva of children with Down's syndrome]. / Detecção de Candida albicans fosfolipidolíticas isoladas da saliva de crianças com síndrome de Down.

The childhood is one of the most propitious period of the life to the occurrence of infection by yeasts of the genus Candida. In children with Down's syndrome, besides the predispose factors to bucal candidiasis; macroglossia, bucal muscular incompetence, frequent respiratory diseases, motor difficulty and immunologic deficit are mentioned as additional elements for this fungus disease. It was verified that the children attacked by this syndrome have much more strains of Candida than other children. The aim of this study was to detect the prevalence of phospholipase producer, Candida on the saliva of children with Down's syndrome. Candida albicans was the only identified specie of Candida. The phospholipase production was found in isolated strains from both of study and control. However, the isolated strains of the group of children with Down's syndrome have strongly present phospholipidolitic.

Mitochondrial DNA analysis reveals substantial Native American ancestry in Puerto Rico.

To estimate the maternal contribution of Native Americans to the human gene pool of Puerto Ricans--a population of mixed African, European, and Amerindian ancestry--the mtDNAs of two sample sets were screened for restriction fragment length polymorphisms (RFLPs) defining the four major Native American haplogroups. The sample set collected from people who claimed to have a maternal ancestor with Native American physiognomic traits had a statistically significant higher frequency of Native American mtDNAs (69.6%) than did the unbiased sample set (52.6%). This higher frequency suggests that, despite the fact that the native Taíno culture has been extinct for centuries, the Taíno contribution to the current population is considerable and some of the Taíno physiognomic traits are still present. Native American haplogroup frequency analysis shows a highly structured distribution, suggesting that the contribution of Native Americans foreign to Puerto Rico is minimal. Haplogroups A and C cover 56.0% and 35.6% of the Native American mtDNAs, respectively. No haplogroup D mtDNAs were found. Most of the linguistic, biological, and cultural evidence suggests that the Ceramic culture of the Taínos originated in or close to the Yanomama territory in the Amazon. However, the absence of haplogroup A in the Yanomami suggests that the Yanomami are not the only Taíno ancestors.

Effect of dopamine on platelet activating factor induced-pulmonary edema in isolated and perfused rabbit lungs.

The effect of dopamine over pulmonary edema induced by PAF was studied. Thirty preparations of rabbit lungs were used: six control preparations (CP), six PAF preparations (PP) in which we injected a dose of 1 microg/kg of rabbit weight and eighteen dopamine preparations (DAP) divided in three groups of six pretreated with a dose of 1-5 (dopaminergic range), 10-20 (Beta range) and 20-30 ug/kg/min (Alpha range) of dopamine, respectively for 30 min, followed by an injection of PAF as in the PP. DAP at Beta and Alpha-adrenergic range decreased pulmonary artery pressure (Pap) as compared to CP, with values of 11.66 (CI 95%: 10.83-12.48), 11.66 (CI 95%: 9.87-13.44) versus 17.12 (CI 95%: 16.12-18.11) cm of water, respectively. DAP in Beta and Alpha-adrenergic range prevented Pap increment as compared to PP, with values of 17.16 (CI 95%: 16.37-17.94), 17.5 (CI 95%: 14.93-20.06) versus 84 cm of water (CI 95%: 71.41-96.58), respectively. Dopamine, at its three ranges inhibited the augmentation of the fluid filtration rate observed in PP with values of 1.01 (CI 95%: 0.77-1.24), 0.03 (CI 95%: 0.01-0.04) and 0.02 g/min (CI 95%: -0.0004-0.03) versus 2.13 g/min (CI 95%: 1.56-2.69), respectively. We concluded that dopamine has a vasodilator effect on Pap and exerts an inhibiting action over PAF effects in pulmonary circulation. Such effects seem to be mainly mediated by Beta-receptors, rather than by dopaminergic receptors.

Ewing's sarcoma of the head and neck.

CONTEXT: Ewing's sarcoma is a rare neoplasm, which usually arises in long bones of the limbs and in flat bones of the pelvis, with the involvement of head and neck bones being very unusual. CASE REPORT: a case of Ewing's sarcoma occurring in the mandible of a 35-year-old female. Pain and swelling of the tumor were the main complaints. The early hypothesis was an undifferentiated malignant neoplasm, possibly a sarcoma. The CT scan depicted an expansive lesion, encapsulated, with septa and characteristics of soft tissue, involving the left side of the mandible and extending to the surrounding tissues. The patient underwent surgical excision of the lesion, the definitive diagnosis of Ewing's sarcoma was established, and the patient commenced on radiotherapy.

Nucleolar organizer region (NORs) in pseudocarcinomatous hyperplasia and squamous cell carcinoma of the oral mucosa.

Counts of nucleolar regions (NORs) demonstrated by a silver staining technique in paraffin sections, have been used to distinguish benign from malignant lesions. AgNORs were studied in 24 biopsies from oral cavity (5 cases of normal oral mucosa, 5 of pseudocarcinomatous hyperplasia and 14 of squamous cell carcinoma, subdivided according to degree of differentiation: 5 grade 1, 5 grade 2 and 4 grade 3) to find whether they were helpful in distinguishing pseudocarcinomatous hyperplasia due to chronic parasitic infections from squamous cell carcinoma. Two methods of counting AgNORs were used: (A) a simpler one which counts nucleolar clusters (AgNU) and satellite AgNORs and the other (B) counting all individual AgNORs, including those within AgNUs. In both methods the lowest mean values were observed for grade 3 carcinoma, while the highest belonged to grade 2 carcinoma. The simpler method (A) was the most useful because AgNU counts showed significant difference when pseudocarcinomatous hyperplasia was compared with grade 1 and 2 carcinomas, which are the most difficult to discriminate from it. However the overlapping of values render the technique of limited use in individual cases.

Timoma y anemia hemolítica: presentación de un caso / Thymoma and hemolytic anemia: presentation of a case

Presentamos un paciente masculino, blanco, de 53 años, conocido diabético. Consultó a nuestro hospital por anemia, ictericia, hepato-esplenomegalia y pérdida de 10 kgrs. en los últimos 2 meses. Las radiografías de tórax mostraron una masa en mediastino anterior e inferior de 8x11 cms. Las pruebas de laboratorio rebelaron reticulocitosis, elevada sedimentación globular, hiperbilirrubinemia indirecta, Coombs fuertemente positivo, complemento C3 y C4 normales y ANA negativo. El tratamiento inicial con prednisona mejoró sus cifras hematológicas y se practicó toracotomía. Después de la remoción del tumor que resultó ser un timoma lifo-epitelial, el paciente se recuperó totalmente desde el punto de vista hematológico, con negativización del Coombs. Hacemos enfásis en la rara asociación de timoma con anemia hemolítica, (menos del 1// en las grandes series) y que el tratamiento definitivo de esta condición es la cirugía

Hiperplasia angiolinfoide con eosinofilia / Angiolymphoid hyperplasia with eosinophia

Se presenta un caso de Hiperplasia Angiolinfoide con Eosinofilia en una paciente de 37 años de edad con caracteres clínicos e histopatológicos típicos. Se describe el tratamiento realizado y se destacan los ragos más importantes de esta entidad nosológica

Hiperplasia angiolinfoide con eosinofilia / Angiolymphoid hyperplasia with eosinophia

Se presenta un caso de Hiperplasia Angiolinfoide con Eosinofilia en una paciente de 37 años de edad con caracteres clínicos e histopatológicos típicos. Se describe el tratamiento realizado y se destacan los ragos más importantes de esta entidad nosológica (AU)