DNA repair pathways to regulate response to chemoradiotherapy in patients with locally advanced head and neck cancer.

Platinum-based chemoradiotherapy (CRT) is a preferred standard of care for locally advanced head and neck cancer (HNC). However, survival benefit is small, with substantial toxicity and biomarkers of CRT resistance that could guide treatment selection and spare morbidity. Increased DNA repair in solid tumors may contribute to cancer cells' ability to survive in genotoxic stress environments afforded by therapy. We assessed mRNA expression levels of DNA repair-related genes BRCA1, RAP80, 53 binding protein 1 (53BP1), mediator of DNA damage checkpoint 1 (MDC1), and RNF8. We correlated our findings with response and overall survival in 72 head and neck patients treated with weekly carboplatin AUC 2 and radiotherapy. Complete response (CR) to CRT was 50 % in patients with low levels of 53BP1 compared to 6.3 % in patients with high levels (p = 0.0059). Of high BRCA1 mRNA expressors, 41.2 % had CR compared to 29.4 % of low expressors (p = 0.72). For a small group of patients with low 53BP1 and either high BRCA1 or RAP80, CRs were 66.7 and 71.4 %, respectively. A trend for better overall survival (OS) was found for patients with low 53BP1 (15 vs 8 m; p = 0.056). Our findings highlight the potential usefulness of 53BP1 mRNA as a predictive biomarker of response and overall survival in HNC patients treated with chemoradiotherapy. Those with high 53BP1 expression could derive only a meager benefit from treatment. Analysis of BRCA1 and RAP80 could further reinforce the predictive value of 53BP1. Although this was a retrospective study with small sample size, it could inform larger translational studies in HNC.

Aberrant gene methylation and bronchial dysplasia in high risk lung cancer patients.

INTRODUCTION: The risk for lung cancer is incremented in high degree dysplasia (HGD) and in subjects with hypermethylation of multiple genes. We sought to establish the association between them, as well as to analyze the DNA aberrant methylation in sputum and in bronchial washings (BW). METHODS: Cross sectional study of high risk patients for lung cancer in whom induced sputum and autofluorescence bronchoscopy were performed. The molecular analysis was determined on DAPK1, RASSF1A and p16 genes using Methylation-specific PCR. RESULTS: A total of 128 patients were enrolled in the study. Dysplasia lesions were found in 79 patients (61.7%) and high grade dysplasia in 20 (15.6%). Ninety eight patients out of 128 underwent molecular analysis. Methylation was observed in bronchial secretions (sputum or BW) in 60 patients (61.2%), 51 of them (52%) for DAPK1, in 20 (20.4%) for p16 and in three (3.1%) for RASSF1A. Methylated genes only found in sputum accounted for 38.3% and only in BW in 41.7%, and in both 20.0%. In the 11.2% of the patients studied, HGD and a hypermethylated gene were present, while for the 55.1% of the sample only one of both was detected and for the rest of the subjects (33.6%), none of the risk factors were observed. CONCLUSIONS: Our data determines DNA aberrant methylation panel in bronchial secretions is present in a 61.2% and HGD is found in 15.6%. Although both parameters have previously been identified as risk factors for lung cancer, the current study does not find a significative association between them. The study also highlights the importance of BW as a complementary sample to induced sputum when analyzing gene aberrant methylation.

5-HT Receptor Antagonism Attenuates the Ischemia-Reperfusion Injury After Rabbit Lung Preservation.

The success of lung transplantation is threatened by the appearance of ischemia-reperfusion injury, which is characterized by increased vascular permeability. 5-Hydroxytryptamine (5-HT; serotonin) is known to produce microvascular leakage in the systemic circulation, but its possible role in ischemia-reperfusion injury after lung preservation has not been reported. In this work we measured the release of 5-HT during a 24-hour rabbit lung preservation, and the effect of methiothepin (antagonist of the majority of 5-HT receptors) and SB204741 (antagonist of 5-HT2B/2C receptors) on the modified capillary filtration coefficient (mKf,c) was evaluated at the end of this period. Our results showed that the highest release rate of 5-HT occurred during the first 15 minutes after the lung harvesting and progressively decreased in the following time intervals. The baseline mKf,c greatly increased after 24 hours of lung preservation, and this increment was partially reduced by methiothepin and even more by SB204741. We concluded that 5-HT may play an important role in the ischemia-reperfusion process after lung preservation.

Feedlot performance and carcass traits of hairbreed ewe lambs in response to zilpaterol hydrochloride and soybean oil supplementation.

The aim of the present study was to evaluate the impact of zilpaterol hydrochloride (ZH; 0 or 10 mg/lamb daily) and soybean oil (SBO; 0 or 6%) supplementation on feedlot performance, carcass traits, and wholesale cut yield of 32 Dorper × Pelibuey ewe lambs (30.55 ± 2. 57 kg of initial BW). Lambs were blocked by BW and randomly assigned to treatments under a randomized complete block design with a 2 × 2 factorial arrangement. After a 34-d feeding period, all ewes were slaughtered. No ZH × SBO interactions were detected (P ≥ 0.11) for the variables evaluated. In the overall feeding period and first 17 d of experiment, feedlot performance was not affected (P ≥ 0.26) by ZH supplementation, but from d 18 to 34, ZH increased (P ≤ 0.03) total gain, ADG, and G:F without affecting DMI (P = 0.58). Also, ZH increased (P ≤ 0.02) HCW, cold carcass weight, dressing percentage, LM area, and leg perimeter. Lung weight as percentage of final BW decreased (P = 0.05) whereas other noncarcass components and wholesale cut yields were not affected (P ≥ 0.06) by ZH supplementation. Inclusion of SBO did not affect (P ≥ 0.08) feedlot performance or wholesale cut yields. The LM pH at 24 h postmortem as well as liver and peritoneum percentages were decreased (P ≤ 0.05) by SBO supplementation, but no other carcass characteristics or noncarcass components were affected (P ≥ 0.08) by SBO. In conclusion, feedlot performance and carcass characteristics were not altered by the interaction of ZH × SBO. However, ZH alone increased the growth of ewes during the last 17 d of the feeding period. Likewise, carcass characteristics of economic importance (i.e., HCW, dressing percentage, LM area, and leg perimeter) increased with ZH supplementation. In general, feedlot performance, carcass traits, and wholesale cut yields were not altered by including 6% of SBO in the finishing diet of ewe lambs.

Effects of zilpaterol hydrochloride and soybean oil supplementation on feedlot performance and carcass characteristics of hair-breed ram lambs under heat stress conditions.

Forty Dorper × Pelibuey ram lambs initially weighing 31.7 ± 2.30 kg were stratified by BW and randomly assigned to treatments under a completely randomized design with a 2 × 2 factorial arrangement of treatments to evaluate effects of zilpaterol hydrochloride (ZH; 0 or 10 mg/lamb daily) and soybean oil (SBO; 0 or 6%) on feedlot performance, carcass characteristics, and wholesale cut yield of ram lambs under heat stress conditions. After a 34-d feeding period, all lambs were harvested. Climatic conditions were of moderate heat stress (average temperature 35.7°C) for lambs during the study. Interactions ZH × SBO were not observed (P ≥ 0.11) for any of the variables evaluated. During the first 17 d of experiment, ZH increased (P ≤ 0.05) BW, ADG, and G:F without affecting feed intake (P = 0.40), but from d 18 to 34 and the entire 34-d feeding period, feedlot performance was not affected (P = 0.18) by ZH. Also, ZH decreased KPH, dressing percent, LM area, LM pH at 24 h postmortem, and leg perimeter (P ≤ 0.04). Renal fat (P = 0.03) decreased with ZH while other noncarcass components were not affected (P ≥ 0.06) by ZH supplementation. Leg yield (P = 0.01) and plain loin (P = 0.04) decreased with ZH and yields of other wholesale cuts were not affected (P ≥ 0.10) by ZH. Feedlot performance (P ≥ 0.20) and wholesale cut yield (P ≥ 0.21) were not affected by SBO. Additionally, dressing percentage decreased (P < 0.01) with SBO while other carcass characteristics (P ≥ 0.12) were not affected by SBO. In conclusion, inclusion of both ZH and SBO in feedlot finishing diets did not improve feedlot performance, carcass characteristics, or wholesale cut yield of hair-breed ram lambs under moderate heat stress. Feedlot performance responded only to ZH and only during the first 17 d of the feeding period. In addition, some carcass characteristics of economic importance, such as dressing, LM area, and leg yield, were improved by ZH.

Prospective assessment of XRCC3, XPD and Aurora kinase A single-nucleotide polymorphisms in advanced lung cancer.

PURPOSE: New therapeutic approaches are being developed based on findings that several genetic abnormalities underlying non-small-cell lung cancer (NSCLC) can influence chemosensitivity. The identification of molecular markers, useful for therapeutic decisions in lung cancer, is thus crucial for disease management. The present study evaluated single-nucleotide polymorphisms (SNPs) in XRCC3, XPD and Aurora kinase A in NSCLC patients in order to assess whether these biomarkers were able to predict the outcomes of the patients. METHODS: The Spanish Lung Cancer Group prospectively assessed this clinical study. Eligible patients had histologically confirmed stage IV or IIIB (with malignant pleural effusion) NSCLC, which had not previously been treated with chemotherapy, and a World Health Organization performance status (PS) of 0-1. Patients received intravenous doses of vinorelbine 25 mg/m(2) on days 1 and 8, and cisplatin 75 mg/m(2) on day 1, every 21 days for a maximum of 6 cycles. Venous blood was collected from each, and genomic DNA was isolated. SNPs in XRCC3 T241M, XPD K751Q, XPD D312N, AURORA 91, AURORA 169 were assessed. RESULTS: The study included 180 patients. Median age was 62 years; 87 % were male; 34 % had PS 0; and 83 % had stage IV disease. The median number of cycles was 4. Time to progression was 5.1 months (95 % CI, 4.2-5.9). Overall median survival was 8.6 months (95 % CI, 7.1-10.1). There was no significant association between SNPs in XRCC3 T241M, XPD K751Q, XPD D312N, AURORA 91, AURORA 169 in outcome or toxicity. CONCLUSIONS: Our findings indicate that SNPs in XRCC3, XPD or Aurora kinase A cannot predict outcomes in advanced NSCLC patients treated with platinum-based chemotherapy.

Diferencia en la población de células cebadas de glándulas apocrinas de sacos anales de perros adultos y seniles / Difference in the population of mast cells of anal sac apocrine glands of adult and senile dogs

Se estudió la población de células cebadas (CC) presentes en sacos anales de perros adultos y seniles mediante su conteo en cortes de tejido procesado con la técnica de inclusión en parafina y teñidos con azul de toluidina. El promedio de CC obtenido para el grupo de perros adultos jóvenes fue de 18,16 +/- 7,58 (n=12 perros) y para el grupos de adultos maduros fue de 73,75 +/- 16,29 (n=12 perros). Al comparar el número de células de ambos grupos con la prueba de U Mann-Withney se encontró que son significativamente diferentes (P< 0,0001), siendo mayor en el grupo de perros seniles. Esta mayor población de CC puede estar relacionada con una mayor susceptibilidad de los perros seniles a reacciones inflamatorias del tejido de los sacos anales causadas por cambios en la dieta, obesidad y diarrea crónica.

We studied the population of mast cells (CC) present in anal sacs of adult and senile dogs by its count in tissue processed with the technique of embedding in paraffin and stained with toluidine blue. The average CC obtained for the group of adult dogs (n=12) was 18.16 +/- 7.58 and for group of senile dogs (n=12) was 73.75 +/- 16.29. When comparing the number of cells in both groups with Mann-Whitney U test were found to be significantly different (P0.0001), being higher in the group of senile dogs. The largest population of CC may be related to an increased susceptibility of senile dogs to inflammatory reactions in the tissue of the anal sacs caused by changes in diet, obesity and chronic diarrhea.

[Prevalence of neutropenic enterocolitis in adults with severe neutropenia and associated mortality.]. / Prevalencia de enterocolitis neutropénica en adultos con neutropenia grave y mortalidad asociada.

BACKGROUND: Neutropenic enterocolitis (NEC) is characterized by inflammatory damage and necrosis of the intestinal mucosa, mainly of the terminal ileum and the cecum. It is more frequent in patients with leukemia and/or undergoing antineoplastic chemotherapy, and the main risk factor is neutropenia <1000/mm3. OBJECTIVE: To know the prevalence of NEC and the mortality associated with it in adults with hematologic conditions and neutropenia <1000/mm3. MATERIAL AND METHODS: All adult patients who were hospitalized for malignant hematologic conditions with neutropenia <1000/mm3 were enrolled in the study; those with neutropenia >1000/mm3 were excluded. The diagnosis of NEC was based on the clinical data and imaging tests (abdominal plain X-rays and CT scan). Demographics of all patients were collected, as well as the data related with the course and treatment of the underlying hematologic condition and the NEC. RESULTS: 117 patients were enrolled in the study; 75.2% of them with some type of acute leukemia. The diagnosis of NEC was made in 8 patients (6.8%). NEC occurred in 10.5% of the patients with acute myeloid leukemia and in 8.0% of those with acute lymphocytic leukemia. Three patients died, which resulted in a 37.5% mortality rate. No association was found between the severity of neutropenia and the onset of NEC or NEC-related mortality. CONCLUSIONS: The prevalence of NEC in patients with hematologic conditions admitted for severe neutropenia is 6.8% and the mortality rate associated with this complication is 37.5%.

[Colonic poliposis and acromegaly. Colonoscopy prevalence and detection]. / Pólipos colónicos y acromegalia. Prevalencia y detección por colonoscopia.

BACKGROUND: The prevalence of colorectal polyps in the general population is 10%. Hormonal alterations in acromegaly stimulates adenomatose polyps development making that increase it prevalence. Colonoscopy has elevated sensibility and specificity in detection of colorectal adenomas. OBJECTIVE: Identify colonic polyps in patients with acromegaly and establish the importance of colonoscopy as a detection method. MATERIAL AND METHODS: Retrospective, observational and descriptive study made in Colon and Rectum Surgery Department from March 2000 to March 2007 in patients with acromegaly and colonoscopy. Analyzed variables were: gender,age, endoscopy findings and histopathological results. Descriptive statistics were used to analysis of results. RESULTS: Thirty-two patients were included: 14 (44%) men, 18 (56%) women. The mean age was 48 (range 22 to 75 years old). In 9 (28%) patients were detected colorectal polyps, predominately in the sigmoid. Fifteen polyps lesion were found: 7 (46.6%) adenomas: 5 (33.3%) tubular and 2 (13.3) villous, 6 (40%) hyperplasic, 1 (6.6%) inflammatory and 1 (6.6%) carcinoma. Colonoscopy was complete in 30 (93.7%) patients. CONCLUSIONS: The prevalence of colonic polyps inpatients with acromegaly undergoing colonoscopy,was 28%, higher than expected in the general population. Colonoscopy constitutes an important diagnosis technique in early neoplasia detection.

[Non Hodgkin lymphoma of the sigmoid colon: case report]. / Linfoma no Hodgkin de sigmoides: reporte de un caso.

Non-Hodgkin lymphoma (NHL) occurs in extranodal location in approximately 20% of patients with limited stage, high-grade disease. Colon is infrequently involved as a primary location, accounting for 4% of all extranodal NHL and far less than 1% of all colonic malignancies. Colonic NHL differs significantly in terms of presentation, therapy and outcome relative to other more common gastrointestinal sites, like stomach or small bowel. The most common location is the cecum (60-74% of cases), while the sigmoid is involved in 2.5-14%. Largely related to the lack of specific signs and symptoms, patients frequently present advanced locoregional disease. Moreover, more than half of patients require an emergent surgery, usually due to pain, bleeding, or obstruction. Therapy usually involves resection of the affected colon and regional lymph nodes followed by adjuvant chemotherapy or/and radiotherapy. Utilizing this approach 5 years survival rates range between 27-55%. We present a 59 years old man with weight loss,abdominal pain, palpable mass and intestinal obstruction. A sigmoidectomy was realized with histopathologic report of NHL. Systemic adjuvant chemotherapy and abdominal radiation were administered. After a 6 month follow-up from initial procedure he is now asymptomatic with Karnofsky of 90. Therefore a surgeon should consider the possibility of NHL when evaluating such patients.

The place of targeted therapies in the management of non-small cell bronchial carcinoma. Molecular markers as predictors of tumor response and survival in lung cancer.

This review highlights the numerous molecular biology findings in the field of lung cancer with potential therapeutic impact in both the near and distant future. Abundant pre-clinical and clinical data indicate that BRCA1 mRNA expression is a differential modulator of chemotherapy sensitivity. Low levels predict cisplatin sensitivity and antimicrotubule drug resistance, and the opposite occurs with high levels. The main core of recent research has centered on epidermal growth factor receptor (EGFR) mutations and gene copy numbers. For the first time, EGFR mutations have been shown to predict dramatic responses in metastatic lung adenocarcinomas, with a threefold increase in time to progression and survival in patients receiving EGFR tyrosine-kinase inhibitors. Evidence has also been accumulated on the crosstalk between estrogen and EGFR receptor pathways, paving the way for clinical trials of EGFR tyrosine-kinase inhibitors plus aromatase inhibitors. Understanding the relevance of these findings can help to change the clinical practice in oncology towards customizing chemotherapy and targeted therapies, leading to improvement both in survival and in cost-effectiveness.

Link between primary and secondary metabolism in the biotransformation of trimethylammonium compounds by escherichia coli.

The aim of this work was to understand the steps controlling the process of biotransformation of trimethylamonium compounds into L(-)-carnitine by Escherichia coli and the link between the central carbon or primary and the secondary metabolism expressed. Thus, the enzyme activities involved in the biotransformation process of crotonobetaine into L(-)-carnitine (crotonobetaine hydration reaction and crotonobetaine reduction reaction), in the synthesis of acetyl-CoA (pyruvate dehydrogenase, acetyl-CoA synthetase, and ATP:acetate phosphotransferase) and in the distribution of metabolites for the tricarboxylic acid (isocitrate dehydrogenase) and glyoxylate (isocitrate lyase) cycles, were followed in batch with both growing and resting cells and during continuous cell growth in stirred-tank and high-cell-density membrane reactors. In addition, the levels of carnitine, crotonobetaine, gamma-butyrobetaine, ATP, NADH/NAD(+), and acetyl-CoA/CoA ratios were measured to determine how metabolic fluxes were distributed in the catabolic system. The results provide the first experimental evidence demonstrating the important role of the glyoxylate shunt during biotransformation of resting cells and the need for high levels of ATP to maintain metabolite transport and biotransformation (2.1 to 16.0 mmol L cellular/mmol ATP L reactor h). Moreover, the results obtained for the pool of acetyl-CoA/CoA indicate that it also correlated with the biotransformation process. The main metabolic pathway operating during cell growth in the high cell-density membrane reactor was that related to isocitrate dehydrogenase (during start-up) and isocitrate lyase (during steady-state operation), together with phosphotransacetylase and acetyl-CoA synthetase. More importantly, the link between central carbon and L(-)-carnitine metabolism at the level of the ATP pool was also confirmed.

Serum DNA as a tool for cancer patient management.

PURPOSE: Genetic analysis has shown that cell-free circulating DNA in plasma or serum of cancer patients shares similar genetic alterations to those described in the corresponding tumor. One of the most important alterations involved in carcinogenesis is aberrant promoter methylation. The interest in this field has grown due to the implementation of the methylation-specific PCR (MSP) assay. The main objective of this study is to analyze the methylation status of different genes in tumor and serum DNA obtained at the time of surgery in two different tumor models (glioblastoma [GBM] and non-small-cell lung cancer [NSCLC]) and their relationship to clinico-pathological characteristics and response to chemotherapy. MATERIAL AND METHODS: Using MSP assay, we assessed the methylation status of MGMT, RASSF1A, p16, DAPK, TMS-1 in tumor and serum DNA obtained at time of surgery or stereotactic biopsy from 28 GBM patients and from 51 NSCLC patients. RESULTS: In GBM patients, the prevalence of MGMT, p16, DAPK, and RASSF1A promoter methylation was 38.1%, 66.7%, 52.4%, 57.1%, respectively, in glioma tissue, and 39.3%, 53.6%, 34.3%, 50%, respectively, in serum. A high correlation between methylation in tumor and serum (Spearman test p = 0.0001) was observed. In NSCLC patients, RASSF1A, DAPK and TMS-1 were methylated in 34%, 45% and 35% tumors, respectively, and in 34%, 40% and 34% serum, respectively. A good correlation was found between alterations found in tumor and serum (Spearman test p = 0.0001). CONCLUSIONS: The study of serum or plasma DNA has opened new roads for translational research and new strategies for molecular diagnosis. Due to the similarities of alterations found in serum DNA and primary tumor, we can use this tool to calculate the risk of local or distant recurrence and its relationship with survival and its value in patient follow-up to evaluate response to therapy.

Comportamiento del cáncer colorrectal en pacientes menores de cuarenta años deñ Hospital Universitario Hernando Moncaleano Perdomo de Neiva (HUHMP) y el Hospital Universitario San Vicente de Paul de Medellín (HUSVP) entre 1980 y 2000 / Clinical behavior of colorectal cancer in patients less than 40 years of age in Neiva and Medellín, Colombia, in 1980-2000

Objetivo: Determinar el comportamiento del cancer colorectal (CCR) en pacientes menores de 40 años diagnosticados en el HUHMP y el HUSVP entre los años 1980 y 2000. Metodologia: Estudio de tipo descriptivo retrospectivo. La recoleccion de datos se realizó a partir de las historias clinicas, previa revision de los informes de patologia en cada una de las instituciones. Resultados: La frecuencia del CCR en el HUHMP fue del 20.9 vs 21.9 por ciento en el HUSVP, con un promedio de edad de 28 y 30 años respectivamente, confirmando la alta incidencia de la enfermedad en menores de 40 años en nuestro pais con respecto a lo informado mundialmente (21 por ciento vs 5 por ciento). Las lesiones se localizaron principalmente en el recto. Los sintomas más frecuentes fueron dolor abdominal, sangrado rectal y perdida de peso; el diagnostico fue realizado en los estadios Dukes C y D, indicando que en personas jovenes el diagnostico se realiza generalmente en forma tardia. Conclusion: En nuestra poblacion, la frecuencia de CCR en personas jovenes es la mas altas informada en el mundo.

Correlation between serum levels of 17 beta-estradiol, progesterone and beta-human chorionic gonadotropin and the karyotype of first trimester anembryonic and embryonic pregnancies.

We aimed at establishing the correlation between karyotype of anembryonic and embryonic first trimester pregnancies and serum levels of beta-hCG, 17beta-estradiol and progesterone. Chromosomal analyses were performed on products of conceptions lower than 12 weeks, using standard-banding protocols. Measurements of 17beta-estradiol and progesterone were carried out by immunoenzymatic assays and beta-hCG by radioimmunoanalysis (RIA). Chromosomal analyses among 11 spontaneous abortions revealed 6 (54,5%) to be normal and 5 (45,5%) abnormal; of these latter, 4 were anembryonic pregnancies (44,4% total frequency). Serum beta hCG and beta-estradiol average levels were lower in the anembryonic pregnancies but did not reveal significant differences with normal levels. Hormonal levels were correlated with karyotype results and it was found that average beta-hCG value was 3.8 times higher in cases with abnormal karyotype than in those in whom it was normal (p <0.05). Linear correlation analyses between hormonal measurements in anembryonic pregnancies were statistically significant (p <0.05). Correlations between beta-hCG and progesterone, beta-hCG and 17-beta estradiol, and the latter with progesterone, proved to be significant in the group with abnormal karyotype (p < 0.05). Anembryonic pregnancies present high frequency of chromosomal anomalies; such pregnancies with abnormal karyotype have a high serum level of beta-hCG; this condition increased the rate of abortion.

Detection of Leishmania causing visceral leishmaniasis in the Old and New Worlds by a polymerase chain reaction assay based on telomeric sequences.

We present a new polymerase chain reaction assay based on telomeric sequences of Leishmania donovani. When this assay was used in dilutions of purified L. donovani DNA, a strong amplification signal was observed with 1 fg of DNA. In a specificity test that used purified DNA from Old World and New World Leishmania, the assay recognized all parasites isolated from patients with visceral leishmaniasis, except for 2 isolates of Leishmania colombiensis from Venezuela and 1 isolate from Brazil. All Leishmania major and Leishmania tropica isolates tested were negative, except for one isolate in each species. We also used the assay on fresh and archive bone marrow samples recovered from Giemsa-stained slides and from dried blood stains.

High risk human papillomavirus in oral squamous carcinoma: evidence of risk factors in a Venezuelan rural population. Preliminary report.

In a search for the presence of human papillomavirus (HPV) and some etiologic cofactors in oral squamous cell carcinoma (OSCC), 50 women diagnosed as OSCC were analyzed by a multiplex polymerase chain reaction (PCR) assay specific for HPV types 6, 11, 16, and 18. This study revealed that 60% (30/50) of the OSCC patients were positive for HPV-DNA sequences. This group was analyzed according to smoking, alcohol consumption, number of pregnancies, poor oral health and low social economic status. The current results indicate an increased incidence of HPV malignant types in the oral cavity in women with OSCC. Also, they support a multifactorial model of oral cancer causation.

Stability and interactions of recombinant human nerve growth factor in different biological matrices: in vitro and in vivo studies.

The purpose of this investigation was to characterize the stability, activity, and interactions of recombinant human nerve growth factor (rhNGF) in various biological matrices in vitro and in vivo. rhNGF (10 microg/ml) remained stable in human plasma for up to 4 days at 37 degrees C. There was a decrease in the recovery of rhNGF after incubation at lower concentrations (20 ng/ml) and for longer time periods (3 and 5 days at 37 degrees C). Size exclusion HPLC analysis indicated that rhNGF forms high molecular weight (HMW) complexes after long incubation periods. We confirmed that alpha(2)-macroglobulin (alpha(2)M) is the major plasma component that binds to rhNGF. Furthermore, this interaction was considerably increased by treatment of plasma with primary amines such as CH(3)NH(2). Changes in the pH environment did not affect the interaction of rhNGF with alpha(2)M. We also determined that the binding of rhNGF to CH(3)NH(2)-treated pure alpha(2)M or alpha(2)M present in human plasma substantially diminished its immunoreactivity and bioactivity detection. The interaction of rhNGF with activated alpha(2)M was reversed and inhibited by coincubation with dimethyl sulfoxide. Released rhNGF under these conditions was fully bioactive. (125)I-rhNGF also binds to alpha(2)M by forming similar (125)I-rhNGF/HMW complexes in plasma after i.v. administration in rats and mice. Sixty minutes after dosing in rats, most of the labeled material was in the form of a (125)I-rhNGF/HMW complex. These studies have provided a better understanding of the nature of the interactions of rhNGF with plasma components as well as methods to enhance, reverse, and inhibit these interactions.

[Colonoscopy. Analysis of 2,000 procedures]. / La colonoscopia. Análisis de 2,000 procedimientos.

BACKGROUND: During the last 3 decades, colonoscopy has become the diagnostic study with greatest sensitivity and acuity in colonic pathology. AIMS: To know the most frequent diagnostic and colonoscopic disorders, and the pathology found, to establish certainty of the colonoscopic procedure. METHOD: Between 1987 and 1997, a descriptive, transversal, retrospective and observational study of the 2,000 colonoscopies that were carried out at on service was done, making a registry of the endoscopic search in colorectal pathology and their characteristics in on patients. RESULTS: Colonoscopies were done in 967 men (47.3%) and 1,053 women (52.6%) with a median age of 55.8 years (10 range (-) 93 years). In 1,780 of them (89.%), it was possible to arrive to cecum; 1,150 (57.5%) were pathologic. The most frequent finding was hemorrhage of the lower digestive tube in 525 (26.2%) patients; in addition cancer in 402 (20.1%), suspicion of intestinal inflammatory disease 292 (14.6%) and colorectal polyps 199 (10%) were found. The most frequent endoscopic diagnosis was colorectal polyps in 405 (35.7%) patients; in additions diverticular disease was found in 404 (35.1%) patients intestinal inflammatory disease in 185 (16%), colorectal cancer in 85 (7.4%), and vascular ectasias in 52 (4.5%) patients. There were four complicated cases (0.25%), three by resolved therapeutic colonoscopy and one diagnostically. CONCLUSION: The most frequent colonoscopic were findings hemorrhage of the lower digestive tube and the finding of cancer. The most frequent diagnoses were colorectal polyps and diverticular disease. Colonoscopy is a safe diagnostic and therapeutic procedure.

[Malignant stromal tumor of the transverse colon. Case report]. / Tumor estromal maligno de colon transverso. Informe de un caso.

OBJECTIVE: Case report of a malignant stromal tumor of the transverse colon. BACKGROUND: Colon sarcomas are rare; the most frequent presentation is the leiomyosarcoma. Forty five cases of malignant stromal tumor have been reported in the international literature. The histogenesis of these mesenchymatous neoplasms is determined by ultrastructural analysis and immunohistochemical stains, nevertheless when special techniques are negative and there is uncertainty related to the cellular differentiation line (smooth muscle, neural or undifferentiated) it is preferable to call them stromal tumors of gastrointestinal tract. METHOD: A 46 year old patient with the diagnosis of malignant stromal tumor of transverse colon and the prescribed treatment was reported. RESULTS: A case of a patient with the diagnosis of malignant stromal tumor in transverse colon is presented, who had as the main clinical features abdominal pain, transanal hemorrhage and finally intestinal occlusion. He was submitted to exploratory laparotomy finding a transverse colon intussusception, which was treated with an extended right hemicolectomy and a post surgical satisfactory recovery. Follow-up to three years hasn't found tumoral activity. CONCLUSIONS: Stromal tumors are rare in colon, treatment is a wide surgical resection with curative or palliative purposes.