Assessment of lung deposition and analysis of the effect of fluticasone/salmeterol hydrofluoroalkane (HFA) pressurized metered dose inhaler (pMDI) in stable persistent asthma patients using functional respiratory imaging.

BACKGROUND: Unambiguously for inhaled products, PK measures are best suited for ensuring that the total systemic exposure is equivalent for two products but cannot provide regional information about lung deposition and structural changes. Functional respiratory imaging (FRI) has been demonstrated to be sensitive for distinguishing small but imperative differences related to a single treatment. METHODS: In this study FRI is used in 16 asthmatic patients to assess equivalence in regional deposition for two products (fluticasone/salmeterol, test and reference) by directly measuring regional functional and structural changes within the lungs following its administration. RESULTS: No differences were observed between the lung deposition patterns and the effects on lung structure and function of two products, having the same formulation and manufactured by different organizations using FRI. CONCLUSIONS: Results using FRI complement PK assessments. The added value of this approach to the conventional clinical methods could be significant.

Analysis of disease-free survival and overall survival in patients with luminal a breast cancer stratified according to TNM.

BACKGROUND AND AIM: The TNM classification of malignant tumours is the most commonly used system to assess the stage as well as the prognosis of cancer. However, one of the biggest challenges in treatment of breast cancer is the understanding of tumour heterogeneity typical of these carcinomas. The aim of this study was to analyse the disease-free survival and overall survival in patients with luminal A subtype of breast cancer, stratified by TNM staging system. METHODS AND STUDY DESIGN: A total of 363 medical records from January 2001 to May 2006 were evaluated for data collection. There were 136 patients with luminal A breast cancer, selected for the cohort. The main objective was the analysis of disease-free survival (DFS) and overall survival (OS) in patients with luminal A breast cancer, stratified according to the TNM classification. RESULTS: The group of 136 patients with immunohistochemically defined luminal A subtype represented 53% of the 253 patients with breast cancer. There was no significant difference in the number and type of patients as for TNM stage and histological grading among patients treated with chemotherapy and HT in comparison to patients treated with HT alone. CONCLUSION: Our analysis did not prove any significant difference in survival of patients treated with chemotherapy followed by hormone therapy in comparison to patients treated with HT alone. We suggest that the IHC luminal A subtype of breast cancer generally warrants a good prognosis independently on other prognostic factors such as TNM stage. We conclude that patients might not benefit of adding a chemotherapy to hormonal therapy in adjuvant settings.

Adjuvant! Online: mind the gap!

The objective of this study was to compare the actual outcome and prognosis estimated by the program Adjuvant! Online for breast cancer in Itajaí (Brazil). It is a retrospective cohort study, post-hoc analysis, in which 214 patients of three institutions were compared in real overall survival (OS) and disease-free survival (DFS) during a 3-year follow-up, and estimated OS and DFS with the program for 10 years by Adjuvant! Online, using the following variables: age, clinical stage, histological grade, lymph node involvement, immunohistochemical subtype and type of adjuvant therapy. The DFS and OS rates in the sample observed and estimated by the program demonstrated correspondence, with the curves trailing beneath the same pattern, due to shorter "real" follow-up (3 versus 10 years). The only group that demonstrated a marked decline in DFS in relation to the real prognosis was that of patients younger than 40 years.

The use of ultrasonic guided waves and wavelets analysis in pipe inspection.

One of the main applications of guided waves is for pipe inspection, since its one-dimensional geometry allows inspecting long distances in a short time. As with most configurations (frequency, thickness) ultrasonic waves with many modes of propagation are generated, recent research focuses mostly on the generation and reception of specific modes, mainly by means of sophisticated arrays of transducers. In this paper this problem is addressed with a different approach, by processing ultrasonic signals with a low signal/noise ratio acquired with a single transducer in an pulse-echo configuration. In order to improve the evaluation of results, frequency bandpass filters and wavelet analysis were tested. Results showed that even when very noisy signals are utilized, signal processing improve the signal/noise (S/N) ratio up to 12 dB approximately and enhance the analysis of the results, thus demonstrating its usefulness.

Crystal structures of CheY mutants Y106W and T87I/Y106W. CheY activation correlates with movement of residue 106.

Position 106 in CheY is highly conserved as an aromatic residue in the response regulator superfamily. In the structure of the wild-type, apo-CheY, Tyr106 is a rotamer whose electron density is observed in both the inside and the outside positions. In the structure of the T87I mutant of CheY, the threonine to isoleucine change at position 87 causes the side chain of Tyr106 to be exclusively restricted to the outside position. In this report we demonstrate that the T87I mutation causes cells to be smooth swimming and non-chemotactic. We also show that another CheY mutant, Y106W, causes cells to be more tumbly than wild-type CheY, and impairs chemotaxis. In the structure of Y106W, the side chain of Trp106 stays exclusively in the inside position. Furthermore, a T87I/Y106W double mutant, which confers the same phenotype as T87I, restricts the side chain of Trp106 to the outside position. The results from these behavioral and structural studies indicate that the rotameric nature of the Tyr106 residue is involved in activation of the CheY molecule. Specifically, CheY's signaling ability correlates with the conformational heterogeneity of the Tyr106 side chain. Our data also suggest that these mutations affect the signal at an event subsequent to phosphorylation.

Klebocin typing of Klebsiella species isolated from nosocomial infection in intensive care unit.

Klebocin typing and antibiotic resistance have been studied for 518 strains of Klebsiella pneumoniae, [106 from intensive care unit (ICU) sites, 182 from ICU staff flora, 192 from patient flora and 38 from clinical specimens]. The overall typability was 71.62%. The most common mnemonic types among various sources were 111, 211, and 112. Of the total strains tested, 28.37% strains were found to be untypable. These strains are labelled as "444". When klebocin typing was used in association with antibiogram, in 86.84% cases of clinical infection probable source of infection could be detected. Thus a combination of two typing methods poses a significant contribution in epidemiological studies.

Regulation of synthesis of glutamine synthase in Bacillus subtilis.

A study of the regulation of the synthesis of the enzyme glutamine synthase in Bacillus subtilis was initiated. An assay, based on the measurement of glutamo-hydroxamate, was used to characterize the enzyme in crude preparations and in toluene-treated cells. Determinations were made of the Michaelis constants for adenosine triphosphate, hydroxylamine, and glutamate (9 x 10(-3), 4 x 10(-3), and 2.2 x 10(-2)m, respectively), the pH optimum (7.6 to 7.7), and the stability. The differential rate of synthesis was determined under various growth conditions. The enzyme was found to be relatively insensitive to regulation. Partial repression was caused by glutamine, arginine, asparagine, and glutamate, or by carbon limitation in a chemostat. Derepression was caused by exhaustion of externally added amino acids or by nitrogen limitation in a chemostat.