Timing of adjuvant chemotherapy in colorectal cancer.

AIM: Delay in commencing adjuvant therapy for colorectal cancer seems to impair survival in some retrospective studies. This study was planned to evaluate its impact on survival. METHODS: This was a retrospective study enrolling patients registered from 2000 to 2012 in two large cancer-dedicated institutions in Brazil. The primary outcome was overall survival according to early vs late chemotherapy initiation. The interval between the primary surgery and the start of adjuvant chemotherapy was calculated. Survival was estimated using the Kaplan-Meier method and the impact of multiple prognostic factors on survival by Cox regression analysis. RESULTS: By the end of 2012, a total of 1963 Stage II and III colorectal patients were identified and 1318 patients received adjuvant chemotherapy, with 22% and 46% of those starting adjuvant chemotherapy within 6 weeks and 8 weeks of surgery. The median period of follow-up was 41 months. Patients starting chemotherapy within 6-8 weeks of surgery had longer overall survival compared with those who started after (6 weeks vs later, hazard ratio 0.76, 95% CI 0.57-0.99, P = 0.046; 8 weeks vs later, hazard ratio 0.74, 95% CI 0.59-0.93, P = 0.011). In the multivariate analysis, age, stage, histological grade, angiolymphatic invasion, emergency surgery and preoperative therapy were independent prognostic factors, but the interval between surgery and start of adjuvant therapy was not. CONCLUSION: In this large retrospective study, the standard prognostic factors impacted on survival whereas the timing of adjuvant therapy did not. Patients with delayed adjuvant chemotherapy may have worse prognostic factors which could play a major role in their poor outcome.

In vitro effect of children's toothpaste on brushing abrasion of eroded primary enamel.

PURPOSE: Emerging data have suggested that acid erosion has become an increasing clinical problem in pediatric dentistry. This study aimed to investigate the abrasive effects of two commercial toothpastes on primary enamel eroded by orange juice using an in vitro model. METHODS: Thirty enamel slabs were obtained from primary teeth and then randomly assigned to three groups (n = 8) comprising two different toothpastes: G1-control-distilled water; G2-Dentifrice A (containing no fluoride); and G3-Dentifrice B (1.100 ppmF-NaF). Each slab had one half protected to provide a control side, and the other one was subjected to treatments. The slabs were submitted to daily erosive challenges (3×/day, 2 min) in concentrated orange juice (pH 3.38) associated with abrasive challenges using a tooth-brushing machine (150 brush movements for each cycle). During the experimental period, the slabs were kept in 37 °C artificial saliva, and the experiment was carried out for 5 days. The depths of the resulting eroded areas were measured by stylus profilometry. The data were analyzed using ANOVA and the Tukey-Kramer test (α = 5%). RESULTS: Tooth loss (µm, mean ± SD) was 2.46 ± 1.18 for G1, 3.32 ± 2.12 for G2 and 2.14 ± 1.03 for G3. Therefore, the NaF dentifrice (Dentifrice B) produced significantly less mineral loss (p = 0.04) than dentifrice A. CONCLUSIONS: The findings suggest that fluoride toothpaste could protect primary enamel against erosion.

Exploring human porphobilinogen synthase metalloprotein by quantum biochemistry and evolutionary methods.

Previous studies have shown the porphobilinogen synthase (PBGS) zinc-binding mechanism and its conservation among the living cells. However, the precise molecular interaction of zinc with the active center of the enzyme is unknown. In particular, quantum chemistry techniques within the density functional theory (DFT) framework have been the key methodology to describe metalloproteins, when one is looking for a compromise between accuracy and computational feasibility. Considering this, we used DFT-based models within the molecular fractionation with conjugate caps scheme to evaluate the binding energy features of zinc interacting with the human PBGS. Besides, phylogenetic and clustering analyses were successfully employed in extracting useful information from protein sequences to identify groups of conserved residues that build the ions-binding site. Our results also report a conservative assessment of the relevant amino acids, as well as the benchmark analysis of the calculation models used. The most relevant intermolecular interactions in Zn2+-PBGS are due to the amino acids CYS0122, CYS0124, CYS0132, ASP0169, SER0168, ARG0221, HIS0131, ASP0120, GLY0133, VAL0121, ARG0209, and ARG0174. Among these residues, we highlighted ASP0120, GLY0133, HIS0131, SER0168, and ARG0209 by co-occurring in all clusters generated by unsupervised clustering analysis. On the other hand, the triple cysteines at 2.5 Å from zinc (CYS0122, CYS0124, and CYS0132) have the highest energy attraction and are absent in the taxa Viridiplantae, Sar, Rhodophyta, and some Bacteria. Additionally, the performance of the DFT-based models shows that the processing time-dependence is more associated with the choice of the basis set than the exchange-correlation functional.

In situ effects of restorative materials on dental biofilm and enamel demineralisation.

OBJECTIVES: Since secondary caries is one of the main reasons for replacing restorations, this study assessed the effects of different restorative materials on the microbiological composition of dental biofilm and on enamel demineralisation around the restoration. METHODS: A randomized, double-blind, split-mouth in situ design was conducted in one phase of 14 days, during which, 20 volunteers wore palatal devices containing five human dental enamel slabs. Each slab was randomly restored with one of the following materials: Filtek-Z-250/Single Bond, control group (composite resin), Permite (amalgam), Fuji II (encapsulated resin-modified glass ionomer), Vitremer (resin-modified glass ionomer) and Ketac Molar (conventional glass ionomer). The volunteers used fluoride dentifrice, 3x/day and a 20% sucrose solution was dripped onto the slabs 8x/day. The biofilm formed on the slabs was analyzed to determine the counts of total streptococci, mutans streptococci and lactobacilli. Enamel demineralisation was determined by cross-sectional microhardness (CSMH) at 20 and 70 microm from the margin of the restoration. Kruskal-Wallis and analysis of variance, followed by least mean squares (LMS) test, were used to evaluate microbiota and CSMH among the groups. The significance level used was 5%. RESULTS: No statistically significant differences were found in the cariogenic microbiota grown on the slabs. At a 20-mum distance, only Fuji II statistically differed from the other groups, showing the lowest demineralisation. At 70 microm, Fuji II significantly inhibited demineralisation when compared to Permite, Filtek-Z-250 and Ketac Molar. CONCLUSIONS: In the context of fluoride dentifrice and under the cariogenic exposure conditions of this study, only the encapsulated resin-modified glass ionomer material provided additional protection against secondary caries.

The value of quantitative analysis in 18F-NaF PET/CT.

AIM: To evaluate the ability of SUVmax to differentiate bone metastases from degenerative lesions, blastic from lytic metastases, as well as to determine the correlation between SUVmax with 18F-NaF and with 18F-FDG. MATERIAL AND METHODS: A review was performed on 115 18F-NaF PET/CT studies. Of the 64 patients with bone metastases, 49 (39 women, 10 men, 61±12 years (16-81)), in whom the PET/CT supported the diagnosis of bone metastases, were selected for analysis. A record was made of the SUVmax of a maximum of ten metastases in each patient (total 172: 141 blastic, 31 lytic), as well as four degenerative lesions (total 188) with the greatest 18F-NaF uptake intensity. Of the 49 patients analyzed, 43 also had a 18F-FDG PET/CT performed in which a record was made of the SUVmax values for 18F-FDG calculated in the locations corresponding to the bone metastases observed in the 18F-NaF PET/CT: 128 metastases (106 blastic, 22 lytic). RESULTS: The mean of the SUVmax values was significantly higher in metastases than in degenerative lesions, 26.8±17.3 vs. 15.3±6.3 (P<0.001) and in blastic than in lytic metastases, 27.9±18.3 vs. 22.1±11.3 (P=0.03). A SUVmax value above 42 always represented metastases, with all values above 49 representing blastic metastases. Using the SUVmax values, it was possible to predict the occurrence of metastases (AUC=0.723; P<0.001; 95% CI=0.671-0.776). The mean of the SUVmax with 18F-NaF was significantly higher in blastic metastases (27.9±18.3 vs. 22.1±11.3, P=0.03), whereas with 18F-FDG it was significantly higher in lytic ones (3.9±3.4 vs. 9.6±3.3; P<0.01). CONCLUSIONS: SUVmax can contribute to the differentiation of metastases from degenerative lesions, and blastic from lytic metastases.

18F-FDG PET/CT in lung cancer. The added value of quantification.

OBJECTIVE: To test a software application for the quantification of metabolic heterogeneity and to evaluate its superiority in relation to visual interpretation. To investigate if a quantitative analysis adds information to the interpretation of 18F-FDG-PET/CT. MATERIAL AND METHODS: The study analyzed 215 patients with a 18F-FDG-PET/CT done for the initial staging of lung cancer between March 2011 and December 2015. The study included 57 (26.5%) women and 158 (73.5%) men, with ages ranging from 34 to 88 years (mean±SD: 67.23±10.04). There were 82 surgical stages (I, II, IIIA), and 133 non-surgical stages (IIIB, IV). The primary tumour was analyzed quantitatively by obtaining the following parameters: SUVmax, metabolic active tumour volume (MATV), total lesion glycolysis (TLG), and the entropy heterogeneity index (ET). Heterogeneity was assessed visually. Death dates and/or the follow-up time were registered, ranging from 0.70 to 67.60 months (mean±SD: 23.20±17.68). RESULTS: In multivariate analysis, ET emerged as a better predictor of survival than visual analysis of heterogeneity that was not statistically significant. The C-index determination demonstrated that all quantitative parameters were statistically-significant predictors of survival. Cut-offs were obtained in order to compare survival times. A multivariate analysis was performed. In the total population, the best predictor was the TNM stage, but MATV, ET, and male gender were statistically significant and independent predictors of survival. In stages without surgical indication, the best predictor was the TNM stage, but the MATV and male gender were statistically significant and independent predictors of survival. In the surgical stages, ET was the only statistically significant and independent predictor of survival. CONCLUSIONS: Quantification adds prognostic information to the visual analysis of 18F-FDG-PET/CT.

Comparative analyses of whole genome sequences of Leishmania infantum isolates from humans and dogs in northeastern Brazil.

The genomic sequences of 20 Leishmania infantum isolates collected in northeastern Brazil were compared with each other and with the available genomic sequences of 29 L. infantum/donovani isolates from Nepal and Turkey. The Brazilian isolates were obtained in the early 1990s or since 2009 from patients with visceral or non-ulcerating cutaneous leishmaniasis, asymptomatic humans, or dogs with visceral leishmaniasis. Two isolates were from the blood and bone marrow of the same visceral leishmaniasis patient. All 20 genomic sequences display 99.95% identity with each other and slightly less identity with a reference L. infantum genome from a Spanish isolate. Despite the high identity, analysis of individual differences among the 32 million base pair genomes showed sufficient variation to allow the isolates to be clustered based on the primary sequence. A major source of variation detected was in chromosome somy, with only four of the 36 chromosomes being predominantly disomic in all 49 isolates examined. In contrast, chromosome 31 was predominantly tetrasomic/pentasomic, consistent with its regions of synteny on two different disomic chromosomes of Trypanosoma brucei. In the Brazilian isolates, evidence for recombination was detected in 27 of the 36 chromosomes. Clustering analyses suggested two populations, in which two of the five older isolates from the 1990s clustered with a majority of recent isolates. Overall the analyses do not suggest individual sequence variants account for differences in clinical outcome or adaptation to different hosts. For the first known time, DNA of isolates from asymptomatic subjects were sequenced. Of interest, these displayed lower diversity than isolates from symptomatic subjects, an observation that deserves further investigation with additional isolates from asymptomatic subjects.

Caroli's disease: report of 10 cases in children and adolescents in southern Brazil.

PURPOSE: The aim of this study was to describe the authors' experience with Caroli's disease in children and adolescents. METHODS: The authors reviewed the hospital charts of 10 children and adolescents with Caroli's disease diagnosed between 1968 and 1996. RESULTS: The median age at the onset of symptoms was 5.5 months and the median age at diagnosis was 12 months, both much lower than those reported in the literature. Clinical symptoms were compatible with the classical findings of Caroli's disease, but jaundice and hepatosplenomegaly occurred more frequently. There was an association with congenital renal malformation in eight cases (80%), congenital hepatic fibrosis in five cases, and choledochal cyst in two cases. One case presented the pure form of the disease.

Articular lymphoscintigraphy in human knees using radiolabeled dextran.

Whereas joint lymphatics are inaccessible to conventional (oil-contrast) lymphography, articular lymphatic dysfunction can be assessed by lymphoscintigraphy (isotope lymphography). Using 99mTc-labeled dextran (molecular weight-70,000 daltons), we performed dynamic lymphoscintigraphy in 38 patients with degenerative osteoarthropathy of the knee. Comparison with the normal (contralateral knee) in 25 patients demonstrated that tracer disappeared at 24 hours more slowly from the abnormal side (86.5 +/- 3.3% retention in the abnormal joint compared with 77.1 +/- 4.6%; p less than 0.01), but accumulated more intensely in regional lymph nodes on the pathologic side (3.8 +/- 2.4% vs 1.9 +/- 0.3%; p less than 0.01). The findings suggest deranged macromolecular transport and lymphatic dysfunction in degenerative knee joint disease.

[Anatomy and physiology of the liver secretory apparatus]. / Anatomia e fisiologia do aparelho excretor do fígado.

Bile secretion by the liver is thoroughly reviewed on its histologic and functional aspects. Regarding biliary flux, it is quantified as dependent or independent from bile acids. The mechanisms of excretion of other compounds like organic anions, cholesterol and phospholipids, are described. Such aspects allow the classification of intrahepatic cholestasis, based on their mechanisms, which can encompass the following: 1) decreased bile acid synthesis; 2) qualitative changes of bile acids; 3) enzymatic changes of the canalicular membrane; 4) changes in the permeability of the canalicular membrane; 5) dysfunction of the contractile microfilaments of the hepatocyte.

[Cimetidine in the prevention of upper digestive hemorrhage in fulminating hepatitis]. / A cimethidina na profilaxia da hemorragia digestiva superior na hepatite fulminante.

The value of cimetidine on the prevention of gastric hemorrhage in 8 patients with fulminant hepatic failure was appreciated. The frequency of hemorrhage in this series was about 25% which is significant different from his past experience (52%) or from that of the literature (54%).

[Abnormalities of the cystic duct diagnosed by oral cholecystography. Report of a case]. / Anomalias do ducto cístico através da colecistografia oral. Registro de um caso.

A rare case of septal gallbladder with a long spiral cystic duct crossing the common hepatic duct and joining it at the papilla of Vater is described. These anomalies wer observed by oral cholecystography after a fatty meal.

[Budd-Chiari syndrome and oral contraceptives. Report of a case and review of the literature]. / Síndrome de Budd-Chiari e anticoncepcional oral. Relato de um caso e revisão da literatura.

One case of Budd-Chiari syndrome is described in a woman taking for 10 months oral contraceptive. The diagnosis was established by liver biopsy and inferior cavography. A review of the pertinent literature was made and the causal relationship between Budd-Chiari syndrome and oral contraceptive was considered.

Identification, characterisation and molecular modelling of two AP endonucleases from base excision repair pathway in sugarcane provide insights on the early evolution of green plants.

Unlike bacteria and mammals, plant DNA repair pathways are not well characterised, especially in monocots. The understanding of these processes in the plant cell is of major importance, since they may be directly involved in plant acclimation and adaptation to stressful environments. Hence, two sugarcane ESTs were identified as homologues of AP endonuclease from the base-excision repair pathway: ScARP1 and ScARP3. In order to understand their probable function and evolutionary origin, structural and phylogenetic studies were performed using bioinformatics approaches. The two predicted proteins present a considerable amino acid sequence similarity, and molecular modelling procedures indicate that both are functional, since the main structural motifs remain conserved. However, inspection of the sort signal regions on the full-length cDNAs indicated that these proteins have a distinct organelle target. Furthermore, variances in their promoter cis-element motifs were also found. Although the mRNA expression pattern was similar, there were significant differences in their expression levels. Taken together, these data raise the hypothesis that the ScARP is an example of a probable gene duplication event that occurred before monocotyledon/dicotyledon segregation, followed by a sub-functionalisation event in the Poaceae, leading to new intracellular targeting and different expression levels.

Effect of the ketamine/xylazine anesthetic on the auditory brainstem response of adult gerbils.

The auditory brainstem response (ABR) is a test widely used to assess the integrity of the brain stem. Although it is considered to be an auditory-evoked potential that is influenced by the physical characteristics of the stimulus, such as rate, polarity and type of stimulus, it may also be influenced by the change in several parameters. The use of anesthetics may adversely influence the value of the ABR wave latency. One of the anesthetics used for e ABR assessment, especially in animal research, is the ketamine/xylazine combination. Our objective was to determine the influence of the ketamine/xylazine anesthetic on the ABR latency values in adult gerbils. The ABRs of 12 adult gerbils injected with the anesthetic were collected on three consecutive days, or a total of six collections, namely: pre-collection and A, B, C, D, and E collections. Before each collection the gerbil was injected with a dose of ketamine (100 mg/kg)/xylazine (4 mg/kg). For the capture of the ABR, 2000 click stimuli were used with rarefaction polarity and 13 stimuli per second, 80 dBnHL intensity and in-ear phones. A statistically significant difference was observed in the latency of the V wave in the ABR of gerbils in the C and D collections compared to the pre-, A and E collections, and no difference was observed between the pre-, A, B, and E collections. We conclude that the use of ketamine/xylazine increases the latency of the V wave of the ABR after several doses injected into adult gerbils; thus clinicians should consider the use of this substance in the assessment of ABR.