Adjuvant chemotherapy for stage II colod cancer

The use of adjuvant chemotherapy following resection for all patients with stage III colon cancer is now part of the standard of care around the world. Recent trials have led to changes in the standard regimens, which now include the use of oxaliplatin (Eloxatin) for most patients with stage III colon cancer. The addition of oxaliplatin has resulted in a 23% reduction in the risk of recurrence compared with fluorouracil/leucovorin alone, with a small but statistically significant survival benefit. Unfortunately, no adequately powered trial has determined whether adjuvant chemotherapy is beneficial for stage II patients, and its use is much more controversial. Most investigators agree that adjuvant chemotherapy has some activity against stage H disease. However, its impact on progression-free and overall survival remains highly controversial. Despite the lack of data, there is growing acceptance of an informal classification system, which stratifies stage II patients by risk on the basis of clinical data, as a guide for deciding whether to use adjuvant therapy. The only phase III clinical trial for stage H patients currently ongoing in the United States uses molecular classification as the basis for patient randomization.

Hipertensão em segmentos sociais pauperizados da região do Vale do Paraíba São Paulo

O objetivo deste trabalho foi verificar as relações entre fatores socioeconômicos, ambientais e biológicos com a hipertensão, segundo gênero. A população estudada foi formada por adultos residentes em dois municípios do Vale do Paraíba (SP), uma das regiões mais pobres do estado de São Paulo. Foi composta por 274 (39,8%) homens e 415 (60,2 %) mulheres. O estudo foi realizado por meio de um modelo de regressão logística hierarquizada, aplicado separadamente para homens e mulheres. Foram estimados os odds ratios ajustados (ORaj), com intervalo de confiança de 95% e a = 0,05. Para os homens, os seguintes fatores de risco estiveram associados à hipertensão: viver na zona rural (ORaj=2,00; p=0,01); etilismo (ORaj= 1,90; p=0,03) e idade acima de 40 anos (ORaj=3,10; p<0,0001). Famílias numerosas, com mais de seis pessoas exerceram efeito protetor (ORaj=0,46; p=0,02). Para mulheres, os fatores de risco associados foram: ausência de escolaridade (ORaj= 2,37; p=0,0003); sedentarismo (ORaj=1,71; p=0,04); obesidade acompanhada de baixa estatura (ORaj= 4,66; p <0,0001) e idade acima de 40 anos ( ORaj=5,29; p=0,01). A obesidade isolada não se associou à hipertensão, nos níveis pressóricos iguais ou maiores do que os correspondentes ao estágio II do padrão de referência.

Incidence of Pressure Ulcers in the Institutionalized Elderly

PURPOSE: The aim of this study was to analyze the incidence of pressure ulcers (PUs) in elderly people living in long-term care facilities (LTCFs). DESIGN: We completed a prospective, comparison cohort study. SUBJECTS AND SETTING: Ninety-four persons, 60 years or older, participated in the study. Participants resided in 4 not-for-profit LTCFs in 3 cities in the southern region of the Brazilian state of Minas Gerais. METHODS: Participants underwent complete skin examination and Braden Scale rating every 2 days for 3 months. When a PU was detected, a careful examination was done to assess its stage, location, and size. From this moment on, the patient was included in the incidence rate and was excluded from the study. RESULTS: The incidence rate of PUs was 39.4%; 37 (77.1%) developed a single ulcer. The most common locations were the malleolus (27.1%) and the ischium (25.0%). Stage I PU were most frequent (66.7%). Females (62.8%) and whites (68.19%) prevailed, with an average age of 79.06 +/- 9.6 years. Body mass index was 20.93 +/- 4.9, with a predominance of urinary diseases (58.5%) and use of neuroleptics/psychotropics (52.1%); 28.7% had had a previous ulcer. Gender and the occurrence of a previous ulcer were found to predict the development of PU, based on logistic regression analysis (r(2) = 0.311). CONCLUSIONS: The overall incidence of PU was significant, but the incidence of stage II and higher PUs was less than 12% and no elders had stage III or IV ulcers. Factors associated with PU development include female gender, regular use of neuroleptic or psychotropic medications, and a history of pressure ulceration.

The Role of Carcinoembriogenic Antigen in Predicting Response and Survival to Neoadjuvant Chemoradiotherapy for Distal Rectal Cancer

PURPOSE: Carcinoembriogenic antigen (CEA) is the most frequently used tumor marker in rectal cancer. A decrease in carcinoembriogenic antigen after radical surgery is associated with survival in these patients. Neoadjuvant chemoradiotherapy may lead to significant primary tumor downstaging, including complete tumor regression in selected patients. Therefore, we hypothesized that a decrease in CEA after neoadjuvant chemoradiotherapy could reflect tumor response to chemoradiotherapy, affecting final disease stage and ultimately survival. METHODS: Patients with distal rectal cancer managed by neoadjuvant chemoradiotherapy and available pretreatment and postchemoradiotherapy levels of CEA were eligible for the study. Outcomes studied included final disease stage, relapse, and survival, and these were compared according to initial CEA level, postchemoradiotherapy CEA level, and the reduction in CEA. RESULTS: Overall 170 patients were included. Postchemoradiotherapy CEA levels < 5 ng/ml were associated with increased rates of complete clinical response and pathologic response. Additionally, postchemoradiotherapy CEA levels < 5 ng/ml were associated with increased overall and disease-free survival (P = 0.01 and P = 0.03). There was no correlation between initial CEA level or reduction in CEA and complete response or survival. CONCLUSION: A postchemoradiotherapy CEA level < 5 ng/ml is a favorable prognostic factor for rectal cancer and is associated with increased rates of earlier disease staging and complete tumor regression. Postchemoradiotherapy CEA levels may be useful in decision making for patients who may be candidates for alterative treatment strategies.

Vascular endothelial growth factor and beta-human chorionic gonadotropin are associated with trophoblastic invasion into the tubal wall in ectopic pregnancy

Objective: To assess the association between the depth of trophoblastic penetration into the tubal wall with serum concentrations of vascular endothelial growth factor (VEGF) and beta-hCG and to assess its predictive value. Design: Prospective study. Setting: Tertiary care university hospital. Patient(s): Thirty patients with ampullary pregnancy undergoing salpingectomy were analyzed. Intervention(s): Trophoblastic invasion was histologically classified as stage I when limited to the tubal mucosa, stage II when extending to the muscle layer, and stage III in the case of complete tubal wall infiltration. Main Outcome Measure(s): The relation between depth of trophoblastic infiltration into the tubal wall with VEGF and beta-hCG serum concentrations on the day of surgery. Result(s): An association between the depth of trophoblastic invasion and maternal serum concentrations of VEGF and beta-hCG was observed. VEGF levels of 297.2 pg/mL showed 100.0% sensitivity and 90.0% specificity for stage I, and levels of 440.1 pg/mL showed 81.8% sensitivity and 88.8% specificity for stage III. Beta-hCG levels of 2590.0 mIU/mL showed 88.9% sensitivity and 80.0% specificity for stage I, and levels of 10,827.0 mUI/mL showed 72.7% sensitivity and 88.9% specificity for stage III. Conclusion(s): Maternal serum VEGF and beta-hCG concentrations are associated with depth of trophoblastic penetration into the tubal wall. (Fertil Steril (R) 2010;94:1595-600. (C) 2010 by American Society for Reproductive Medicine.)

Association between ultrasound findings and extent of trophoblastic invasion into the tubal wall in ampullary pregnancy

Objective Predictive factors of damage to the Fallopian tube may guide the treatment of Patients with tubal pregnancy. The aim of the present study was to investigate the association between the depth of trophoblastic invasion into the tubal wall, assessed on postoperative histological examination, with the findings obtained on transvaginal sonograpby (TVS) in women with ampullary Methods Women with ampullary pregnancy undergoing salpingectomy were enrolled into the study. Only women with a finding of either an embryo with cardiac activity or a tubal ring on TVS were included in the analysis, a total of 8.5 patients. Trophoblastic invasion was assessed postoperatively and was histologically classified as Stage I when limited to the tubal mucosa, Stage II when extending to the muscle layer and Stage III in the case of complete tubal wall infiltration. The association between findings on TVS and the stage of trophoblastic invasion was evaluated. Results There was a significant association between the findings on TVS and the depth of trophoblastic invasion (P < 0.001). All patients in whom an embryo with cardiac activity bad been identified were found to have Stage II (17.9%) or Stage III (82.1%) invasion, whereas in those patients who showed a tubal ring on TVS, Stage I invasion was the most frequent finding (41.3%). Conclusions In ampullary pregnancy, the finding on TVS of an embryo with cardiac activity is associated with deeper penetration of trophoblastic tissue into the tubal wall than is the finding of a tubal ring. Copyright (C) 2009 ISUOG, Published by John Wiley & Sons, Ltd.

Kidney Function and 24-Hour Proteinuria in Patients with Fabry Disease during 36 Months of Agalsidase Alfa Enzyme Replacement Therapy: A Brazilian Experience

Background. Prior to the introduction of enzyme replacement therapy (ERT), management of Fabry disease (FD) consisted of symptomatic and palliative measures. ERT has been available for several years using recombinant human agalsidase alfa, an analogue of alpha-galactosidase A (GALA). However, the limitations of ERT in improving kidney function have not been established. This study evaluates the safety and therapeutic effect of agalsidase alfa replacement in terms of kidney function and reduction in 24-hour proteinuria. Methods. During the period between January 1, 2002, and August 1, 2005, nine Fabry patients (7 male, 2 female) were treated according to protocol, receiving 0.2 mg/kg agalsidase alfa IV every two weeks. Kidney function was evaluated by measuring the glomerular filtration rate (GFR) using chromium ethylene diamine tetra-acetate clearance ((51)Cr-EDTA mL/min/1.73 m(2)) at baseline, 12, 24, and 36 months. 24-hour proteinuria was measured at baseline, 3, 6, 12, 18, 24, and 36 months of ERT. Kidney disease was classified according to National Kidney Foundation Disease Outcome Quality Initiative (NKF/DOQI) Advisory Board criteria, which define stage I chronic kidney disease (CKD) as GFR >= 90mL/min/1.73 m(2), stage II as 60-89 mL/min/1.73m(2), stage III as 30-59 mL/min/1.73 m(2), stage IV as 15-29 mL/min/1.73m(2), and stage V as < 15 mL/min/1.73m(2). Results. Six patients completed 36 months of therapy, 2 patients completed 18 months, and 1 patient completed 12 months. Mean patient age at baseline was 34.6 +/- 11.3 years. During the study period, kidney function remained stable in patients with stages I, II, or III CKD. One patient, who entered the study with stage IV CKD, progressed to end-stage chronic kidney disease, beginning hemodialysis after 7 months and receiving a kidney transplant after 12 months of ERT. Proteinuria also remained stable in the group of patients with pathologic proteinuria. The use of agalsidase alfa was well tolerated in 99.5% of the infusions administered. Conclusion. Over the course of 36 months of ERT, there was no change in kidney function and 24-hour proteinuria. This suggests thatagalsidase alfa may slow or halt the progression of kidney disease when used before extensive kidney damage occurs. No significant side effects were observed with ERT during the course of the study.

Expression of fibroblast growth factor receptors during development and regression of the bovine corpus luteum

There is evidence that fibroblast growth factors (FGFs) are involved in the regulation of growth and regression of the corpus luteum (CL). However, the expression pattern of most FGF receptors (FGFRs) during CL lifespan is still unknown. The objective of the present study was to determine the pattern of expression of `B` and `C` splice variants of FGFRs in the bovine CL. Bovine CL were collected from an abattoir and classed as corpora hemorrhagica (Stage I), developing (Stage II), developed (Stage III) or regressed (Stage IV) CL. Expression of FGFR mRNA was measured by semiquantitative reverse transcription-polymerase chain reaction and FGFR protein was localised by immunohistochemistry. Expression of mRNA encoding the `B` and `C` spliced forms of FGFR1 and FGFR2 was readily detectable in the bovine CL and was accompanied by protein localisation. FGFR1C and FGFR2C mRNA expression did not vary throughout CL lifespan, whereas FGFR1B was upregulated in the developed (Stage III) CL. FGFR3B, FGFR3C and FGFR4 expression was inconsistent in the bovine CL. The present data indicate that FGFR1 and FGFR2 splice variants are the main receptors for FGF action in the bovine CL.

A retrospective model of oocyte competence: global mRNA and housekeeping transcripts are not associated with in vitro developmental outcome

Oocyte developmental competence depends on maternal stores that support development throughout a transcriptionally silent period during early embryogenesis. Previous attempts to investigate transcripts associated with oocyte competence have relied on prospective models, which are mostly based on morphological. criteria. Using a retrospective model, we quantitatively compared mRNA among oocytes with different embryo development competence. A cytoplasm biopsy was removed from in vitro matured oocytes to perform comparative analysis of amounts of global polyadenylated (polyA) mRNA and housekeeping gene transcripts. After parthenogenetic activation of biopsied oocytes, presumptive zygotes were cultured individually in vitro and oocytes were classified according to embryo development: (i) blocked before the 8-cell stage; (ii) blocked between the 8-cell and morulae stages; or (iii) developed to the blastocyst stage. Sham-manipulated controls confirmed that biopsies did not alter development outcome. Total polyA mRNA amounts correlate with oocyte diameter but not with the ability to develop to the 8-cell and blastocyst stages. The last was also confirmed by relative quantification of GAPDH, H2A and Hprt1 transcripts. In conclusion, we describe a novel retrospective model to identify putative markers of development competence in single oocytes and demonstrate that global mRNA amounts at the metaphase II stage do not correlate with embryo development in vitro.

Evolution of a rift basin dominated by subaerial deposits: The Guaritas Rift, Early Cambrian, Southern Brazil

Most existing models for the evolution of rift basins predict the development of deep-water depositional systems during the stage of greatest tectonic subsidence, when accommodation generation potentially outpaces sedimentation. Despite this, some rift basins do not present deep-water systems, instead being dominated by subaerial deposits. This paper focuses on one of these particular rift basins, the Cambrian Guaritas Rift, Southern Brazil, characterized by more than 1500 m of alluvial and aeolian strata deposited in a 50-km-wide basin. The deposits of the Guaritas Rift can be ascribed to four depositional systems: basin-border alluvial fans, bedload-dominated ephemeral rivers, mixed-load ephemeral rivers and aeolian dune fields. These four systems are in part coeval and in part succeed each other, forming three stages of basin evolution: (i) Rift Initiation to Early Rift Climax stage, (ii) Mid to Late Rift Climax stage, and (iii) Early Post-Rift stage. The first stage comprises most of the Guaritas Group and is characterized by homogeneous bed-load-dominated river deposits, which do not clearly record the evolution of subsidence rates. The onset of sedimentation of finer-grained deposits occurred as a consequence of a reactivation event that changed the outline of the basin and the distribution of the nearby highlands. This strongly suggests that the capture of the main river system to another depression decreased the sediment supply to the basin. The study of the Guaritas Rift indicates that rift basins in which the sediment supply exceeds the accommodation generation occur as a consequence of moderate subsidence combined with the capture of a major river system to the basin during the initial stages of basin evolution. In these basins, changes in the average discharge of the river system or tectonic modification of the drainage network may be the major control on the stratigraphic architecture. (c) 2009 Published by Elsevier B.V.

Effects of Raloxifene on Ki-67 and CD34 Antigen Expression in Breast Cancer

Background: The aim of this study was to evaluate the effect of raloxifene on CD34 and Ki-67 antigen expression in breast cancer specimens from postmenopausal women. Methods: Sixteen postmenopausal patients with operable, stage II (>= 3 cm), estrogen receptor-positive breast cancer, who took 60 mg of raloxifene daily for 28 days, participated in this study. Immunohistochemistry was carried out in tumor samples prior to and following raloxifene treatment to evaluate CD34 and Ki-67 protein expression. Angiogenesis was quantified in 10 randomly selected fields per slide, and Ki-67-stained nuclei were counted in 1,000 cells per slide using an image capture and analysis system with 400 ! magnification. Student`s t test for paired samples was used for the statistical analysis of data. Statistical significance was established at p < 0.05. Results: The mean number of microvessels was 44.44 +/- 3.54 prior to raloxifene therapy and 22.63 +/- 1.61 following therapy (p < 0.001), and the mean percentage of Ki-67-stained nuclei was 19.28 +/- 8 1.61 and 12.13 +/- 8 1.48 prior to and following raloxifene treatment, respectively (p < 0.001). Conclusion: Raloxifene significantly reduces CD34 and Ki-67 protein expression in breast carcinoma in postmenopausal women. Copyright (C) 2008 S. Karger AG, Basel

Comparison of three vascular endothelial markers in the evaluation of microvessel density in breast cancer

Purpose: To evaluate the microvessel density by comparing the performance of anti-factor VIII-related antigen, anti-CD31 and, anti-CD34 monoclonal antibodies in breast cancer. Methods: Twenty-three postmenopausal women diagnosed with Stage II breast cancer submitted to definitive surgical treatment were evaluated. The monoclonal antibodies used were anti-factor VIII, anti-CD31 and anti-CD34. Microvessels were counted in the areas of highest microvessel density in ten random fields (200 x). The data were analyzed using the Kruskal-Wallis nonparametric test (p < 0.05). Results: Mean microvessel densities with anti-factor VIII, anti-CD31 and anti-CD34 were 4.16 +/- 0.38, 4.09 +/- 0.23 and 6.59 +/- 0.42, respectively. Microvessel density as assessed by anti-CD34 was significantly greater than that detected by anti-CD31 or anti-factor VIII (p < 0.0001). There was no statistically significant difference between anti-CD31 and anti-factor VIII (p = 0.4889). Conclusion: The density of stained microvessels was greater and staining was more intense with anti-CD34 compared to anti-CD31 and anti-factor VII-related antigen.

P-Glycoprotein Expression, Tumor Weight, Age, and Relapse in Patients with Stage I and II Favorable-Histology Wilms` Tumor

Fifteen percent of patients with Wilms`` tumor (WT) experience relapse. It has been suggested that weight and age may affect the chances of relapse. Few studies have investigated the role, if any, between P-glycoprotein (P-gp) and relapse. The authors assessed the prognostic value of tumor weight and age at diagnosis and asked whether some other potential biological markers, specifically P-gp protein expression, had a prognostic value in favorable-histology WT. No association between age and relapse could be found. Patients with tumor weight >= a parts per thousand yen550 g were 6 times more likely to relapse, whereas P-gp expression was positive in 18/40 (45%%) of the patients, of which 10/12 (83.3%%) relapsed and 8/28 (28.6%%) did not. Further studies are necessary to elucidate whether or not P-gp is related to relapse in patients with histologically favorable Wilms`` tumor. If confirmed, the protein may be used in the future as a target for new drugs and treatments for this group of patients.

Vertical alveolar crest bone maintenance around implants in two-stage surgery: an in situ study in dogs

The aim of this study was to evaluate in situ changes in the alveolar crest bone height around immediate implant-supported crowns in comparison to tooth-supported crowns (control) with the cervical margins located at the bone crest level, without occlusal load. In Group I, after extraction of 12 mandibular premolars from 4 adult dogs, implants from Branemark System (MK III TiU RP 4.0 x 11.5 mm) were placed to retain complete acrylic crowns. In Group II, premolars were prepared to receive complete metal crowns. Sixteen weeks after placement of the crowns (38 weeks after tooth extraction), the height of the alveolar bone crest was measured with a digital caliper. Data were analyzed statistically by the Mann-Whitney test at 5% significance level. The in situ analysis showed no statistically significant difference (p=0.880) between the implant-supported and the tooth-supported groups (1.528 + 0.459 mm and 1.570 + 0.263 mm, respectively). Based on the findings of the present study, it may be concluded that initial peri-implant bone loss may result from the remodeling process necessary to establish the biological space, similar to which occurs with tooth-supported crowns.

PKC beta II inhibition attenuates myocardial infarction induced heart failure and is associated with a reduction of fibrosis and pro-inflammatory responses

Protein kinase C beta II (PKC beta II) levels increase in the myocardium of patients with end-stage heart failure (HF). Also targeted overexpression of PKC beta II in the myocardium of mice leads to dilated cardiomyopathy associated with inflammation, fibrosis and myocardial dysfunction. These reports suggest a deleterious role of PKC beta II in HF development. Using a post-myocardial infarction (MI) model of HF in rats, we determined the benefit of chronic inhibition of PKC beta II on the progression of HF over a period of 6 weeks after the onset of symptoms and the cellular basis for these effects. Four weeks after MI, rats with HF signs that were treated for 6 weeks with the PKC beta II selective inhibitor (beta IIV5-3 conjugated to TAT(47-57) carrier peptide) (3 mg/kg/day) showed improved fractional shortening (from 21% to 35%) compared to control (TAT(47-57) carrier peptide alone). Formalin-fixed mid-ventricle tissue sections stained with picrosirius red, haematoxylin and eosin and toluidine blue dyes exhibited a 150% decrease in collagen deposition, a two-fold decrease in inflammation and a 30% reduction in mast cell degranulation, respectively, in rat hearts treated with the selective PKC beta II inhibitor. Further, a 90% decrease in active TGF beta 1 and a significant reduction in SMAD2/3 phosphorylation indicated that the selective inhibition of PKC beta II attenuates cardiac remodelling mediated by the TGF-SMAD signalling pathway. Therefore, sustained selective inhibition of PKC beta II in a post-MI HF rat model improves cardiac function and is associated with inhibition of pathological myocardial remodelling.