Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive/HER2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood. Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed. Study Design: Multicenter retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer. Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%). Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.

Utilização de hormônios e antibióticos em produtos alimentícios de origem animal: aspectos gerais e toxicológicos / Use of hormones and antibiotics in animal food products: general and toxicological aspects

OBJECTIVE: To approach the use of hormones and antibiotics in the production of animal origin food, mechanisms of action, toxicity, regulations in Brazil and worldwide and methods for residues detection in food. Data source: For this review, articles were searched using databases indexed in MEDLINE, LILACS, PUBMED and SciELO, using the key words: residues, antibiotics, hormones, meat, milk, eggs, in addition to their translations in Portuguese and Spanish. Data synthesis: We considered publications in the last 10 years, including 28 articles. CONCLUSIONS: The consumption of foods containing antibiotics and hormones residues is a problem to be considered, therefore, it is necessary to develop better methods of compounds detection and invest in food inspection

OBJETIVO: Abordar o uso de hormônios e antibióticos na produção de alimentos de origem animal, mecanismos de ação, toxicidade, regulamentação no Brasil e no mundo e os métodos para detecção dos resíduos nos alimentos. FONTE DE DADOS: Para essa revisão, artigos foram pesquisados usando bancos de dados indexados no MEDLINE, LILACS, PubMed e SciELO, utilizando as palavras-chave: resíduos, antibióticos, hormônios, carne, leite, ovos, além das respectivas traduções em inglês e espanhol. SÍNTESE DOS DADOS: Foram consideradas publicações dos últimos 10 anos, sendo incluídos 28 artigos. CONCLUSÕES: O consumo de alimentos contendo resíduos de hormônios e antibióticos constitui um problema a ser considerado, entretanto há necessidade de desenvolver melhores metodologias de detecção dos compostos e investir em fiscalização de alimentos

Confirmation of hormones in animal serum by liquid chromatography/tandem mass spectrometry according to European Commission Decision 2002/657.

A novel and rapid method was developed and validated for the confirmation of endogenous and synthetic hormones in animal serum using LC/MS/MS. Detection of 17 beta-estradiol and beta-testosterone below the respective European Union-recommended levels of 0.1 and 0.5 microg/L was achieved, as was a required performance level of 0.1 microg/L for 17 alpha-estradiol and 0.5 microg/L for 17 alpha-testosterone, medroxyprogesterone-17-acetate, and progesterone. The method was established with dilution of serum followed by ion-exchange SPE, LC separation and MS detection with electrospray ionization, selected reaction monitoring, and positivelnegative switching. Two characteristic transitions were monitored for each analyte. The method was applied to bovine, ovine, porcine, equine, and avian samples and validated according to European Commission Decision 2002/657/EC and accepted for ISO/IEC 17025:2005 accreditation. An extended calibration curve allows naturally occurring levels of endogenous hormones to be quantified. Recoveries ranged from 97.3% for 17 alpha-testosterone to 102.0% for 17 alpha-estradiol. The decision limit CCalpha ranged from 0.02 microg/L for 17 alpha- and beta-estradiol to 0.12 microg/L for progesterone. Detection capability CCbeta ranged from 0.03 microg/L for 17 a-estradiol to 0.20 microg/L for progesterone.

Urinary steroid profiling.

Urinary steroid profiling provides quantitative information on the steroid biosynthetic and catabolic pathways. It is essential for identification of inborn errors of steroid metabolism, and useful in other disorders with altered steroid secretion. A general method is detailed. Steroids, mostly in the form of glucuronide and sulphate conjugates, are extracted using solid-phase cartridges, followed by enzymatic hydrolysis, re-extraction of freed steroids, formation of methoxime trimethylsilyl derivatives and analysis by sas chromatography and gas chromatography-mass spectrometry. Newborns excrete large quantities of sulphates, so conjugate separation by liquid gel chromatography is used prior to hyrolysis. Normal ranges for adults and children are given, together with advice on chromatogram evaluation and a summary of the profile findings in steroid disorders.

Evaluation of tests based on individual versus population modeling to compare dissolution curves.

This study is aimed at comparing dissolution curves obtained for several batches of sustained release formulations of octreotide, a somatostatin analog used in acromegaly. We evaluated four tests to compare the parameters of two series of curves: a Mann-Whitney-Wilcoxon test comparing individual estimates; a likelihood ratio test after population analysis (NONMEM), and two Wald tests using population parameters estimated by two-stage methods. The four approaches were evaluated by simulations. The Mann-Whitney-Wilcoxon test and the population approach had adequate type-I error, and the latter provided the highest power under the alternatives simulated. The two-stage method including the uncertainty on individual estimates was disappointing.

Laparoscopia e histerectomía / Laparoscopy and hysterectomy

No disponible

H.H. Dale and the London Centre for WHO standards--some milestones of the early years.

Henry Dale, a Nobel laureate and statesman of science, helped to organize the meetings in 1923 and 1925 to set up international standards for insulin and other biologicals. He made the National Institute for Medical Research one of the two world centres for standards. Some milestones in the work of the London centre are described: (i) the first standards; (ii) vitamins and hormones; (iii) WHO standards for many antibiotics; (iv) the provision of an international working standard for ACTH; (v) the old and new methods of ampouling; (vi) the impact of research and immunoassay on the need for standards; and (vii) the special ECBS sessions for endocrinology and haematology. Dale tells how he had to preserve the first batch of insulin for use as the standard instead of for treatment.

Efficacy, cycle control, and side effects of low- and lower-dose oral contraceptives: a randomized trial of 20 micrograms and 35 micrograms estrogen preparations.

Estrogen content represents a tradeoff between cycle control and side effects, but few direct comparisons of 20 and 30/35 micrograms preparations are available. To address this issue, we conducted a randomized, open-label multicenter clinical trial comparing Alesse (20 micrograms ethinyl estradiol [EE]), Mircette (20 micrograms EE), and Ortho Tri-Cyclen (35 micrograms EE) among 463 OC starters or switchers. Bloating, breast tenderness, and nausea were approximately 50% more common in women using 35 micrograms EE as compared to 20 micrograms EE preparations. Cycle control was similar in all products, although during the first two cycles among starters; users of Mircette and Ortho Tri-Cyclen (Tri-Cyclen) exhibited better cycle control than Alesse users. Discontinuation and pregnancy rates were not significantly higher in 35 micrograms EE users.

PIP: Estrogen content represents a tradeoff between cycle control and side effects, but few direct comparisons of 20 and 30/35 mcg preparations are available. To address this issue, researchers conducted a randomized, open-label multicenter clinical trial comparing Alesse (20 mcg ethinyl estradiol [EE]), Mircette (20 mcg EE), and Ortho Tri-Cyclen (35 mcg EE) among 463 oral contraceptive starters or switchers. Bloating, breast tenderness, and nausea were approximately 50% more common in women using 35 mcg EE as in those using 20 mcg EE preparations. Cycle control was similar in all products, although during the first two cycles among starters, users of Mircette and Ortho Tri-Cyclen (Tri-Cyclen) exhibited better cycle control than Alesse users. Discontinuation and pregnancy rates were not significantly higher in 35 mcg EE users.

WHO Expert Committee on Biological Standardization. Forty-sixth Report.

This report presents the recommendations of a WHO Expert Committee commissioned to coordinate activities leading to the adoption of international requirements for the production and control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the Committee's attention and provides information on the status and development of reference materials for various antibiotics, antibodies, antigens, blood products, cytokines, endocrinological and related substances and toxins. The second part of the report, of particular relevance to manufacturers and national control authorities, contains the revised list of laboratories approved by WHO for the production of yellow fever vaccine, revised requirements for yellow fever vaccine, an amendment to the General Requirements for the Sterility of Biological Substances, and a summary protocol for the batch release of virus vaccines.

Endocrine manipulation--toxicological frontiers.

A variety of hormonal products has been developed for use in food animal production. Applications include therapy, particularly for fertility problems, zootechnical purposes comprising mainly the management of reproduction, for example the synchronization of oestrus, and the improvement of performance such as increased growth rate or increased milk yield. Although there is well established legislation both domestically and internationally for the registration of veterinary pharmaceutical products, hormones have become a special case at least to the public. This is particularly true when hormones are used to improve animal performance. The two notable issues to date have been the use of anabolic steroids as growth promoters and of bovine somatotrophin (BST) to increase milk yield in dairy cows. The high public profiles of these two issues have separately forced the introduction of new legislation in the EC, which will continue to have far-reaching implications for research and development in animal health and production for many years. This paper interprets recent developments in legislation concerning veterinary products and hormonal products in particular, giving examples of the toxicological assessment of four specific molecules and speculating upon the likely implications for the future practical exploitation of endocrine mechanisms in food animal production.

Immunoassay standardization.

Assays employed in the biological sciences fall into two categories, which may be respectively termed "comparative" (or "functionally-specific") and "analytical" (or "structurally-specific"). The former are intended to compare the relative effects of substances, or mixtures of substances--not necessarily of identical chemical structure--on a biological system (e.g. whole animal, tissue, cell, etc). Results are represented by units of effect (i.e. they are not units of "amount" of the substance(s) measured), and differ depending on the biological system used. Such assays cannot be "standardised" by the use of a calibrant. In contrast, analytical assays are intended to measure the number of molecules (or mass) of a single substance of unique chemical structure in a test sample, and cannot legitimately be employed to measure mixtures of substances of different structure. Results are represented by units of molecular number or mass, and should be identical for any test sample irrespective of the assay system used. Immunoassays generally fall into this category. Insofar as the antigenic substances present in standards or test samples are dissimilar and/or molecularly heterogeneous, an immunoassay is invalid, and the results it yields have no universal significance. Attempts to standardize "analytically-invalid" immunoassays inevitably fail. Many substances of biological interest (e.g. TSH)--initially defined in terms of their biological function--have subsequently been shown to be molecularly heterogenous. Problems thus arise in the standardization of immunoassays used for their measurement, reflecting the fact that the measurement of a mixture of substances of differing molecular structure (and function) is a meaningless concept. It is thus impossible to "measure TSH"; it is only possible to measure the effect TSH exerts in a particularly assay system. The only long-term solution to this problem is the development of assay systems measuring individual components of such heterogenous mixtures.

The stability of synthetic gonadotropin-releasing hormone in solution.

The stability of GnRH stored in solution under different conditions was assessed employing both immunoassay and bioassay techniques. No appreciable loss of activity was encountered after 4 weeks of storage at either 4 degrees C or room temperature.

Reduction of animal usage: British Pharmacopoeia Commission policy.

The British Pharmacopoeia Commission is committed to working towards the replacement or modification, wherever possible, of those assays and tests of the Pharmacopoeia that are performed in vivo and which may involve pain. An alternative or modified method is adopted by the Commission once it has been clearly demonstrated that it offers satisfactory control for pharmacopoeial purposes of the potency or other specific property of the preparation concerned. The relevant monographs of the British Pharmacopoeia and of the British Pharmacopoeia (Veterinary) are kept under active review and number of lines of investigation are being pursued by the appropriate advisory committees in furtherance of the Commission's objective. In vivo techniques are currently required for two main purposes, safety and potency testing of a range of biological materials. The progress being made towards a reduction in animal usage for safety purposes is exemplified by work being carried out with the aim of reducing reliance on rabbit testing for pyrogens. It is expected that the use of HPLC for the assay of peptide hormones may permit the phasing out of certain bioassays. With respect to immunological products several lines of enquiry are being followed. While in vitro alternatives remain the long term objective, the modification of existing in vivo methods to permit non-lethal end-points and the possibility of using analgesics are also considered. In pursuing this policy the Commission actively encourages those associated with its work to seek alternative procedures but it must be understood that the Commission itself has no source of funds to finance the necessary research.(ABSTRACT TRUNCATED AT 250 WORDS)