The frequency of twinning among women who have already borne twins, the 'repeat frequency', is significantly higher than in the general population. Individual propensity is not necessarily genetic in origin, but pedigree studies (for reviews see refs 1, 2) confirm that twinning is a family trait. Studies based on archives restrict this conclusion to dizygotic (DZ) twinning and the maternal side, while studies based on interviews of relatives of twins find monozygotic (MZ) twinning and the paternal side also to be involved. However, interview studies can overestimate, while archive studies can underestimate, the real frequency of twinning. We have now analysed the incidence of twinning in the families of 950 zygosity-determined, unselected twin pairs under complete ascertainment. Our results indicate that a propensity to MZ twinning, as well as one to DZ twinning, can be inherited through the maternal line, and that the two mechanisms of twinning might be related. We have also found a paternal role in DZ, but not in MZ twinning.

In a previous study we applied a three-step avidin -biotin pretargeting approach to target 90 Y-biotin to the tumour in patients with recurrent high grade glioma. The encouraging results obtained in this phase I -II study prompted us to apply the same approach in an adjuvant setting, to evaluate (i) time to relapse and (ii) overall survival. We enrolled 37 high grade glioma patients, 17 with grade III glioma and 20 with glioblastoma, in a controlled open non-randomized study. All patients received surgery and radiotherapy and were disease-free by neuroradiological examinations. Nineteen patients (treated) received adjuvant treatment with radioimmunotherapy. In the treated glioblastoma patients, median disease-free interval was 28 months (range=9 -59); median survival was 33.5 months and one patient is still without evidence of disease. All 12 control glioblastoma patients died after a median survival from diagnosis of 8 months. In the treated grade III glioma patients median disease-free interval was 56 months (range=15 -60) and survival cannot be calculated as only two, within this group, died. Three-step radioimmunotherapy promises to have an important role as adjuvant treatment in high grade gliomas, particularly in glioblastoma where it impedes progression, prolonging time to relapse and overall survival. A further randomized trial is justified.

The aim of this study was to determine the maximum-tolerated dose, of a pre-targeting three-step (3-S) method employing 90Y-biotin in the locoregional radioimmunotherapy (RIT) of recurrent high grade glioma, and to investigate the antitumor efficacy of this new treatment. Twenty-four patients with recurrent glioma underwent second surgical debulking and implantation of a catheter into the surgical resection cavity (SRC), in order to introduce the radioimmunotherapeutic agents [biotinylated monoclonal antibody (MoAb), avidin and 90Y-biotin]. Eight patients with anaplastic astrocytoma (AA) and 16 patients with glioblastoma (GBM) were injected with biotinylated anti-tenascin MoAb (2 mg), then with avidin (10 mg; 24 h later) and finally 90Y-biotin (18 h later). Each patient received two of these treatments 8-10 weeks apart. The injected activity ranged from 0.555 to 1.110 GBq (15-30 mCi). Dosage was escalated by 0.185 GBq (5 mCi) in four consecutive groups. The treatment was well tolerated without acute side effects up to 0.740 GBq (20 mCi). The maximum tolerated activity was 1.110 GBq (30 mCi) limited by neurological toxicity. None of the patients developed hematologic toxicity. In three patients infection occurred around the catheter. The average absorbed dose to the normal brain was minimal compared with that received at the SRC interface. At first control (after 2 months), partial (PR) and minor (MR) responses were observed in three GBM (1 PR; 2 MR) and three AA patients (1 PR; 2 MR) with an overall objective response rate of 25%. Stable disease (SD) was achieved in seven GBM and five AA patients (50%). There was disease progression in six GBM patients (25%), but in none of the AA patients. At the dosage of 0.7-0.9 GBq per cycle, locoregional 3-S-RIT was safe and produced an objective response in 25% of patients. Based on these encouraging results, phase II studies employing 3-S-RIT soon after first debulking are justified.

Somatostatin receptors type 2 (sst(2)) are expressed in high concentration on numerous neudoendocrine tumors. The successful use of radiolabeled somatostatin analogs in imaging promoted further studies in utilizing them in radiopeptide therapy. The somatostatin analog [(90)Y-DOTA-D-Phe(1)-Try3]octreotide (DOTATOC) (DOTA: 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) possesses favorable characteristic for its therapeutic use; shows high affinity for sst(2), moderately high affinity for sst(5), and intermediate affinity for sst(3); high hydrophilicity; stable and facile labeling with (111) In and (90) Y. In this article we report our experience with (90)Y-DOTATOC in neuroendocrine tumors. Eighty-seven patients with neuroendocrine tumors were treated with a cumulated activity ranging from 7.4 to 20.2 GBq. Most patients responded with stabilization of disease (48%); however, objective responses were observed in 28% of patients (5% complete response). No major acute reactions were observed up to the activity of 5.55 GBq per cycle. The dose limiting was bone marrow toxicity and the maximal tolerated dose was defined as 5.18 GBq.

BackgroundHeterologous fibrin sealant (HFS) consists of a fibrinogen-rich cryoprecipitate extracted from Bubalus bubalis buffalo blood and a thrombin-like enzyme purified from Crotalus durissus terrificus snake venom. This study evaluated the safety and immunogenicity of HFS, estimated the best dose, and assessed its preliminary efficacy in the treatment of chronic venous ulcers (CVU).MethodsA phase I/II non-randomized, single-arm clinical trial was performed on 31 participants, accounting for a total of 69 active CVUs. All ulcers were treated with HFS, essential fatty acid, and Unna boot for 12 weeks. The outcomes assessed were: (1) primary safety, immunogenicity analyses, and confirmation of the lowest safe dose; (2) secondary promising efficacy by analyzing the healing process. Immunogenicity was evaluated using the serum-neutralizing (IgM and IgG) and non-neutralizing (IgA and IgE) antibody techniques against the product. The immuno-detection of IgE class antibodies was assessed using dot-blot assay before and at the end of treatment. Positive samples on dot-blot assays were subsequently analyzed by western blotting to verify the results.ResultsNo severe systemic adverse events related to the use of HFS were observed. Local adverse events potentially related to treatment include ulcer pain (52%), peri-ulcer maceration (16%), peri-ulcer pruritus (12%), critical colonization (8%), peri-ulcer eczema (4%), the opening of new ulcers (4%), and increased ulcerated area 4%). Neutralizing and non-neutralizing antibodies did not show significant deviations at any of the evaluated time points. Blot assays showed that all patients presented negative immunological reactions, either before or after treatment, with the thrombin-like enzyme component. In addition, two participants showed a positive immunological reaction to the cryoprecipitate component, while another two were positive before and during treatment. Regarding the secondary outcomes of preliminary efficacy, a total healing and significant reduction of the area was observed in 47.5 and 22%, respectively. A qualitative improvement was observed in the wound beds of unhealed ulcers.ConclusionsThe investigational HFS bioproduct proved to be safe and non-immunogenic with a good preliminary efficacy for the treatment of CVU, according to the protocol and doses proposed. A multicentric phase III clinical trial will be necessary to verify these findings.

This study sought to investigate the quality of life of women who suffer from breast cancer and are part of a support group, comparing the data gathered from mastectomized women who had breast reconstruction and women who had not had surgery. It also compared data of women who had quadrantectomy surgery but did not need reconstruction and those who had not had reconstruction surgery. It is a quantitative transversal study, and data was collected by application of a questionnaire to the respondents and by the SF-36 of the WHO. Fifty women with average age of 57.2 years participated in the survey. The groups were compared against each other - two by two - considering types of surgery, using the Mann-Whitney Test at a 5% level of significance. The results showed that women who had quadrantectomy surgery and did not need reconstruction are those who had the highest average scores in all fields and therefore have the best quality of life. They are followed by the group of women who had a mastectomy and reconstruction. The mastectomized group of women who had not had reconstruction surgery were seen to have a very low level of quality of life. They are followed by the group of women who had quadrantectomy surgery and also had not had reconstruction.

Objetivou-se mensurar o nível de capacidade funcional de idosos e suas associações, por meio de um estudo transversal com 516 residentes nas áreas circunscritas à Estratégia Saúde da Família no distrito de Grande Santos Reis, Montes Claros-MG. Foram aplicados dois questionários: um de características sociodemográficas, condições de moradia e percepção da própria situação econômica, e outro para a avaliação da capacidade funcional. Foram realizadas abordagens descritiva (frequências absoluta e relativa para variáveis categóricas, média e desvio-padrão para as contínuas) e analítica (teste de associação do qui-quadrado e regressão logística binária hierarquizada). Do total de idosos, 39,5% eram homens (70,4±7,1 anos) e 60,5% mulheres (69,1±6,9 anos); 63,4% com escolaridade de zero a dois anos; 85,7% tinham renda de até dois salários mínimos; 73,1% moravam com seus familiares; 33,9% apresentaram capacidade funcional não adequada, sendo 38,5% mulheres e 27,0% homens. A capacidade funcional não adequada foi associada às mulheres, ter mais que 70 anos de idade, renda de até dois salários mínimos e menor tempo de escolaridade. Há necessidade de direcionar a atenção à saúde do idoso, aliando o incentivo à pesquisa e às ações planejadas e direcionadas para melhorar as condições de saúde e qualidade de vida desse grupo.

Venous ulcers of the lower limbs complicated by infection or chronicity represent a serious public health problem. The elevated number of those afflicted burdens the health services, interferes in quality of life and causes absenteeism. Although there are 2,500 items on the market, ranging from the simplest dressing up to the most complex types of dressing, treatment remains a challenge. Among the substances used, fibrin sealant is the one that promotes diminution of bacterial colonization and of edema, controls hemorrhaging, alters the pain threshold by protecting the nerve endings, hydrates the wound bed and forms granulation tissue that favors healing. Its disadvantages include higher cost and utilization of human fibrinogen that can transmit infectious diseases. The Center for the Study of Venoms and Venomous Animals (CEVAP) at São Paulo State University (UNESP) developed a new sealant made up of fibrinogen extracted from large animals and from an enzyme obtained from snake venom. The present study, developed in the Health Education Clinic (CEPS) of Sacred Heart University (USC) aimed to evaluate the effect of the new sealant on the healing process of venous ulcers in 24 adult patients, seven of whom were male and 17 female. Two study groups were formed as follows: Group 1 (G1) -control group of 11 patients treated with essential fatty acid (EFA) and Unna's boot, and Group 2 (G2) -13 patients treated with essential fatty acid (EFA), fibrin sealant and Unna's boot. The follow-up lasted eight weeks and the sealant was applied at only the first and fourth weeks. The results showed that Group 2 presented worse lesion conditions as to healing, but, when comparing the two groups, it was noteworthy that the the sealant was effective in healing venous ulcers. There is evidence that the new sealant is recommended for leg ulcers with the following advantages: ease of application, preparation of the wound bed, diminution of pain and a higher number of discharges in the eighth week. More important, other positive characteristics are non-transmission of infectious diseases, absence of adverse reactions, and economic advantage of being produced by Brazilian technology. Finally, it is suggested that the weekly application of sealant, for at least eight weeks, could improve the healing process and consequently life quality.