Search

Aim: MERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC)., Methods: In this double-blind placebo-controlled randomised phase III trial, eligible patients had HER2-negative mBC previously untreated with chemotherapy. pVEGF-A was measured before randomisation to paclitaxel 90 mg/m 2 on days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal. Stratification factors were baseline pVEGF-A, prior adjuvant chemotherapy, hormone receptor status and geographic region. Co-primary end-points were investigator-assessed progression-free survival (PFS) in the intent-to-treat and pVEGF-A high populations., Results: Of 481 patients randomised (242 placebo-paclitaxel; 239 bevacizumab-paclitaxel), 471 received study treatment. The stratified PFS hazard ratio was 0.68 (99% confidence interval, 0.51-0.91; log-rank p = 0.0007) in the intent-to-treat population (median 8.8 months with placebo-paclitaxel versus 11.0 months with bevacizumab-paclitaxel) and 0.64 (96% confidence interval, 0.47-0.88; log-rank p = 0.0038) in the pVEGF-A high subgroup. The PFS treatment-by-VEGF-A interaction p value (secondary end-point) was 0.4619. Bevacizumab was associated with increased incidences of bleeding (all grades: 45% versus 27% with placebo), neutropenia (all grades: 39% versus 29%; grade ≥3: 25% versus 13%) and hypertension (all grades: 31% versus 13%; grade ≥3: 11% versus 4%)., Conclusion: The significant PFS improvement with bevacizumab is consistent with previous placebo-controlled first-line trials in mBC. Results do not support using baseline pVEGF-A to identify patients benefitting most from bevacizumab., Clinical Trials Registration: ClinicalTrials.gov NCT01663727., (Copyright © 2016. Published by Elsevier Ltd.)

Phenolic compounds are ubiquitous in plant-based foods. High dietary intake of fruits, vegetables and cereals are related to a decreased rate in chronic diseases. Phenolic compounds are thought to be responsible, at least in part, for those health effects. No-netheless, the bioaccessibility of phenolic compounds is not often considered in these studies; thus, a precise mechanism of action of phenolic compounds is not known. In this review, we aim to present a comprehensive knowledge of the potential health promotion effects of polyphenols and the importance of considering the factors that affect their bioavailability on research projects.

Aims: Trastuzumab, in combination with chemotherapy, is the standard of care for patients with early and metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The Retreatment after HErceptin Adjuvant trial assessed the efficacy and safety of trastuzumab plus a taxane as first-line treatment for patients with metastatic breast cancer (MBC) who had relapsed after adjuvant trastuzumab for HER2-positive early breast cancer., Materials and Methods: In total, 43 patients with HER2-positive MBC who had received previous adjuvant trastuzumab for ≥10 months, with a relapse-free interval of ≥6 months after the last adjuvant trastuzumab dose, were recruited. Eligible patients (n = 41) were assigned to receive trastuzumab, either weekly or every 3 weeks, in combination with docetaxel or paclitaxel until disease progression., Results: At the final analysis, with a median follow-up time of 40 months, a positive response was observed in 25/41 patients (61%; 95% confidence interval: 48.7-80.4%), stable disease in 7/41 (17.1%) and progressive disease in 6/41 (14.6%). Three patients had missing response assessments (one had no measurable lesions at baseline and two had no post-baseline tumour assessments). The median progression-free survival (PFS) was 8.0 months (95% confidence interval: 6-11 months) and the median overall survival was 25.0 months (16-33 months). No correlation was found between response rate, PFS or overall survival and the duration of adjuvant trastuzumab treatment, trastuzumab-free interval, relapse-free interval, hormone receptor status or type of pre-metastatic treatment. The most common adverse events (all grades) were alopecia (32%) and diarrhoea (32%). Six patients (14.6%) developed at least one serious adverse event. No congestive heart failure or any unexpected adverse events were reported., Conclusion: Trastuzumab, in combination with a taxane, is an effective and well-tolerated first-line treatment for MBC in patients who relapse after trastuzumab-based adjuvant therapy., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Several randomised trials have confirmed the benefit of adjuvant trastuzumab for patients with HER2-positive early breast cancer. However, concern has been expressed that adjuvant trastuzumab might be associated with an increased frequency of CNS relapses. We assessed the frequency and course of CNS relapses, either as first event or at any time, using data from the HERA trial., Methods: We estimated the cumulative incidence of first disease-free survival (DFS) events in the CNS versus other sites by competing risks analysis in patients with HER2-positive early breast cancer who had been randomly assigned to receive 1 year of trastuzumab or to observation in the HERA trial after a median follow-up of 4 years (IQR 3·5-4·8). To obtain further information about CNS relapse at any time before death, we circulated a data collection form to investigators to obtain standardised information about CNS events that occurred in all patients who had died before July, 2009. We estimated the cumulative incidence of CNS relapse at any time with a competing risks analysis., Results: Of 3401 patients who had been assigned to receive 1 year of trastuzumab or to observation, 69 (2%) had a CNS relapse as first DFS event and 747 (22%) had a first DFS event not in the CNS. The frequency of CNS relapses as first DFS event did not differ between the group given 1 year of trastuzumab (37 [2%] of 1703 patients) and the observation group (32 [2%] of 1698; p=0·55 [Gray's test]). 481 data collection forms were distributed, of which 413 (86%) were returned. The proportion of patients who had died and experienced a CNS relapse was numerically higher in the observation group (129 [57%] of 227) than in the group given trastuzumab for 1 year (88 [47%] of 186; p=0·06 [Gray's test]). Most CNS relapses were symptomatic (189 [87%] of 217)., Conclusion: Adjuvant trastuzumab does not increase the risk of CNS relapse in patients with HER2-positive early breast cancer., Funding: None., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Hibiscus sabdariffa L. is used as a refreshing beverage and as a traditional medicine. The objective of this study was to determine the in vitro effect of phenolic compounds present in aqueous, ethyl acetate, and chloroform extracts of H. sabdariffa against mutagenicity of 1-nitropyrene (1-NP), and also the antiproliferative effect of these extracts. Inhibition of cell proliferation and DNA fragmentation were tested on transformed human HeLa cells. The hot aqueous extract (HAE) contained 22.27 +/- 2.52 mg of protocatechuic acid (PCA) per gram of lyophilized dried extract, and was not statistically different from the cold aqueous or chloroform extracts; the ethyl acetate extract produced the least amount of PCA. The H. sabdariffa extracts inhibited mutagenicity of 1-NP in a dose-response manner. The inhibition rate on HeLa cells of HAE was also dose-dependent. The HAE did not induce DNA fragmentation. The results suggest that H. sabdariffa L. extracts have antimutagenic activity against 1-NP and decrease the proliferation of HeLa cells, probably due to phenolic acid composition.

Background: Trastuzumab--a humanised monoclonal antibody against HER2--has been shown to improve disease-free survival after chemotherapy in women with HER2-positive early breast cancer. We investigated the drug's effect on overall survival after a median follow-up of 2 years in the Herceptin Adjuvant (HERA) study., Methods: HERA is an international multicentre randomised trial that compared 1 or 2 years of trastuzumab treatment with observation alone after standard neoadjuvant or adjuvant chemotherapy in women with HER2-positive node positive or high-risk node negative breast cancer. 5102 women participated in the trial; we analysed data from 1703 women who had been randomised for treatment with trastuzumab for 1 year and 1698 women from the control group, with median follow-up of 23.5 months (range 0-48 months). The primary endpoint of the trial was disease-free survival. Here, we assess overall survival, a secondary endpoint. Analyses were done on an intent-to-treat basis. This trial is registered with the European Clinical Trials Database, number 2005-002385-11., Findings: 97 (5.7%) patients randomised to observation alone and 58 (3.4%) patients randomised to 1 year of treatment with trastuzumab were lost to follow-up. 172 women stopped trastuzumab prematurely. 59 deaths were reported for trastuzumab and 90 in the control group. The unadjusted hazard ratio (HR) for the risk of death with trastuzumab compared with observation alone was 0.66 (95% CI 0.47-0.91; p=0.0115). 218 disease-free survival events were reported with trastuzumab compared with 321 in the control group. The unadjusted HR for the risk of an event with trastuzumab compared with observation alone was 0.64 (0.54-0.76; p<0.0001)., Interpretation: Our results show that 1 year of treatment with trastuzumab after adjuvant chemotherapy has a significant overall survival benefit after a median follow-up of 2 years. The emergence of this benefit after only 2 years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer.

The genotype of single-nucleotide polymorphism type 3, CTC, at positions 14676, 164275, and 2935685, along with four copies of 6 bp repeats in the rpoT gene, was predominant for isolates originating in the Japanese mainland. Type 1, CGA, type 2, CTA, and type 3 were detected from Korea, Indonesia, and Myanmar. No isolates with four copies of 6 bp were detected from Myanmar, Okinawa, and Japanese Brazilian patients. Type 4, TTC, with three copies of 6 bp, was detected only from Japanese Brazilians. The results indicate that infection occurred in Brazil and the disease developed later in Japan.

Background: House-dust mites contain components that are allergenic in mite-sensitive patients, and a number of these have been produced in recombinant form., Methods: In the present study, we evaluated by skin prick testing the positivity to native Der p 2 and recombinant Der p 2, Der p 5, and Der p 7 allergens of Dermatophagoides pteronyssinus in patients with rhinitis, asthma, or a combination of these diseases, who were positive to whole-mite extract., Results: In all patients, the positivity to both native and recombinant Der p 2 was high. In patients with either rhinitis or asthma, the reactivity to Der p 5 and 7 was significantly lower than to Der p 2. However, in patients with combined disease, the positivity to the minor allergens was almost as high as that to Der p 2., Conclusions: These results raise the question of whether patients with combined allergic rhinitis and asthma, when compared to those with either of these diseases alone, are predisposed to react to a wider range of mite allergens, or, inversely, whether patients who respond to the minor allergens are more susceptible to suffering the combined disease.

Widely variable prevalences of allergic diseases have been reported in tropical populations, and this has been suggested to be due to effects of the nonspecific polyclonal stimulation of IgE synthesis caused by the helminthic infections that are endemic in these areas. Since 1980, we have been evaluating the allergic reactivity of different socioeconomic sectors of the population of tropical Venezuela (lat. 2-12 degrees N), and in the present study analyze the overall results obtained in the laboratory evaluation of children (5-15 years of age) belonging to these groups. Children of medium-high socioeconomic level (M-HSEL), who experience occasional helminthic infections, have moderately high total serum IgE levels, and have elevated skin test positivities and specific IgE levels against environmental allergens. Persons of low socioeconomic level, in the urban, and particularly rural situation experience frequent helminthic infection, and have highly elevated total serum IgE levels. In contrast to the M-HSEL, the majority of these children have detectable specific IgE antibody against a variety of inhalant allergens, but relatively few have high levels, and their skin test positivity is also low. In these frequently parasitized persons, evidence of saturation of mast cell Fc epsilon receptors was found by tests of passive sensitization. We propose, therefore, that helminthic parasites have a biphasic effect on allergic reactivity; occasional infections are stimulatory, via their nonspecific potentiation of IgE synthesis against environmental allergens, and frequent infections are suppressive due to the widely polyclonal stimulation that they cause, resulting in both diminished specific antibody production against any given allergen and mast cell Fc epsilon receptor saturation.

The author believes that the pediatrician is in a position to counsel adolescents and parents. Some pediatricians are uncomfortable with the idea of offering separate office hours to counsel adolescents, but once the interest is there and the physician is well versed in dealing with adolescent care, the counseling aspect of patient care becomes a natural consequence. Common areas of adolescent turmoil are addressed, including the depressed adolescent, the adolescent who is failing in school, the adolescent who is not functioning well at home, the adolescent who is using drugs, and the adolescent who is having a sexual problem.

This article discusses economic issues that are relevant to a medical practice that deals with teenagers. The economic obstacles are divided into four major categories: (1) attitude toward physician; (2) sources of referrals and recruitment of patients; (3) overhead; and (4) billing procedures and accounts receivable.

Since some previous studies have reported elevated total serum IgE levels in leprosy, that may be associated with the existence of a state of generalized T cell anergy, we undertook a carefully controlled study of this immunoglobulin in such patients before and after treatment with a Mycobacterium leprae-BCG vaccine. We found, firstly, that lepromatous leprosy patients suffering active disease had only a moderate elevation of IgE levels that was not statistically significant when compared to appropriate controls. In addition, multiple injections of the vaccine did not cause alterations in the concentration of this immunoglobulin. We were, therefore, unable to confirm the possible existence of a generalized immunodeficiency in lepromatous leprosy that could cause hyper-production of IgE.

An enzyme-linked immunosorbent assay (ELISA) was used to determine the seroprevalence of Toxocara canis infection in different socio-economic groups of the tropical population of Venezuela. The lack of definitive independent diagnostic criteria for toxocariasis required the establishment of operational upper limits of normality for Toxocara ELISA values, based upon their log-normalized distribution in a presumptive "non-toxocariasis" sub-population. Only 1.8% of urban subjects of medium-high socio-economic level were considered to be clearly positive in Toxocara ELISA, compared to 20.0% of urban slum dwellers, 25.6% rural subsistence farmers and 34.9% Amazon Indians. As the test was performed using excretory-secretory antigen, and under conditions of competitive inhibition by soluble extracts of non-homologous parasites, co-infection by common intestinal helminths, protozoa or other organisms did not give rise to false positive results. However, strong cross-reactivity with Onchocerca volvulus may have influenced the prevalence figure obtained for the Amazon Indians. These results indicate that T. canis is yet another parasite that is widely distributed in economically underprivileged tropical populations.

The mutual correlations between immediate, intermediate, and delayed cutaneous reactions, IgE, IgG, or combined IgG, A, and M antibody levels, and antigen- or mitogen-induced lymphocyte transformation were evaluated in a mixed group of allergic or non-allergic individuals. As might be expected, immediate and delayed reactions correlated significantly with IgE antibody levels and lymphocyte transformation, respectively. Intermediate time-course reactions did not correlate with IgG or IgG, A, and M antibody levels, but did so with immediate reactions, thus suggesting their "late phase" nature. Of particular interest was the finding of correlations that do not conform to the classical concept of the mechanisms involved in the generation of the different cutaneous reactions. Significant correlations were found between immediate or intermediate reactions and antigen-induced lymphocyte transformation, and between immediate and delayed reactions. These results are discussed in relation to recent suggestions that factors released from sensitized T cells can mediate early time-course reactions, and that such reactions may contribute to the manifestation of delayed-type hypersensitivity.

As some factors associated with the tropical environment can modify the expression of atopic disease, various indicators of allergic reactivity were compared between allergic and non-allergic subjects of different socio-economic level in Caracas, Venezuela (Lat. 10 degrees N). The socio-economic levels considered were high (HSEL), medium-high (MSEL) or low (LSEL). As generally found in temperature climates, in the HSEL the total serum IgE levels of allergic patients were significantly greater than those of non-allergic individuals (geometric means of 274 vs 126 IU/ml, respectively), as were also the specific serum IgE antibody levels (55.6 vs 23.8% positive, respectively, for house dust). These results correlated closely with the skin-test reactivity of these subjects (60.3 vs 17.5% positive for house dust). In this group, the degree of intestinal helminthic infection was low (5.6% positive for Ascaris). In contrast, for the MSEL where the degree of parasitic infection was higher (13.0%), the total serum IgE levels were elevated in both allergic and non-allergic subjects (602 vs 363 IU/ml). Similarly, positivity for specific IgE antibody was high, and comparable between allergics and non-allergics of this group (61.5 vs 54.2%), as was also the case for skin-test reactivity (71.9 vs 60.4%). In the LSEL, parasitic infection was prevalent (47.6%), and the total serum IgE levels were markedly elevated, with little difference occurring between allergic and non-allergic individuals (2269 vs 1981 IU/ml). The positivity for specific IgE antibody was high, and effectively independent of the allergic state (75.6 vs 53.7%), but in contrast the skin test reactivity was relatively low (22.0 vs 9.8%).(ABSTRACT TRUNCATED AT 250 WORDS)