Analysis of the molecular mobility of collagen and elastin in safe, atheromatous and aneurysmal aortas.

AIM OF THE STUDY: In this study, we propose to use a thermal technique, Differential Scanning Calorimetry (DSC) to follow the evolution of elastin and collagen in safe and pathological cardiovascular tissues. PATIENTS AND METHODS: The first part of this study deals with the analysis of the elastin network and associated proteins during ageing (from children to old persons) in aortic walls. The second part is devoted to the characterization of the collagenic phase in aneurysms. In both cases, physical data are correlated with biochemical analyses. RESULTS AND CONCLUSION: For old persons aortas with atheromatous stades, elastin and associated proteins are found to interpenetrate to form a homogenous phase. Abdominal aortic aneurysms (AAA) are characterized by structural alterations of the aortic wall resulting from the degradation of elastic fibers and an increase of collagen/elastin ratio. Notable modifications are evidenced between collagen from control tissue and collagen from AAA, particularly concerning the thermal denaturation. Biochemical and thermal results are compatible with the increase of new collagen deposition and/or impairment of the collagen phase stability in the extracellular matrix of AAAs.

Interventions to enhance medication adherence.

BACKGROUND: People who are prescribed self-administered medications typically take less than half the prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications, but also might increase their adverse effects. OBJECTIVES: To update a review summarizing the results of randomized controlled trials (RCTs) of interventions to help patients follow prescriptions for medications for medical problems, including mental disorders but not addictions. SEARCH STRATEGY: Computerized searches were updated to September 2004 without language restriction in MEDLINE, EMBASE, CINAHL, The Cochrane Library, International Pharmaceutical Abstracts (IPA), PsycINFO and SOCIOFILE. We also reviewed bibliographies in articles on patient adherence and articles in our personal collections, and contacted authors of original and review articles on the topic. SELECTION CRITERIA: Articles were selected if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications, measuring both medication adherence and treatment outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive initial findings. DATA COLLECTION AND ANALYSIS: Study design features, interventions and controls, and results were extracted by one reviewer and confirmed by at least one other reviewer. We extracted adherence rates and their measures of variance for all methods of measuring adherence in each study, and all outcome rates and their measures of variance for each study group, as well as levels of statistical significance for differences between study groups, consulting authors and verifying or correcting analyses as needed. MAIN RESULTS: For short-term treatments, four of nine interventions reported in eight RCTs showed an effect on both adherence and at least one clinical outcome, while one intervention reported in one RCT significantly improved patient compliance, but did not enhance the clinical outcome. For long-term treatments, 26 of 58 interventions reported in 49 RCTs were associated with improvements in adherence, but only 18 interventions led to improvement in at least one treatment outcome. Almost all of the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, reminders, self-monitoring, reinforcement, counseling, family therapy, psychological therapy, crisis intervention, manual telephone follow-up, and supportive care. Even the most effective interventions did not lead to large improvements in adherence and treatment outcomes. Six studies showed that telling patients about adverse effects of treatment did not affect their adherence. AUTHORS' CONCLUSIONS: Improving short-term adherence is relatively successful with a variety of simple interventions. Current methods of improving adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. High priority should be given to fundamental and applied research concerning innovations to assist patients to follow medication prescriptions for long-term medical disorders.

Enantiomeric determination of the plasma levels of omeprazole by direct plasma injection using high-performance liquid chromatography with achiral-chiral column-switching.

A direct injection high-performance liquid chromatographic (HPLC) method, with column-switching, for the determination of omeprazole enantiomers in human plasma is described. A restricted access media (RAM) of bovine serum albumin (BSA) octyl column has been used in the first dimension for separation of the analyte from the biological matrix. The omeprazole enantiomers were eluted from the RAM column onto an amylose tris(3,5-dimethylphenylcarbamate) chiral column by the use of a column-switching valve and the enantioseparation was performed using acetonitrile-water (60:40 v/v) as eluent. The analytes were detected by their UV absorbance at 302 nm. The validated method was applied to the analysis of the plasma samples obtained from 10 Brazilian volunteers who received a 40 mg oral dose of racemic omeprazole and was able to quantify the enantiomers of omeprazole in the clinical samples analyzed. The assay was able to determine the cytochrome P450 2C19 phenotype of the subjects participating in this study.

Enantiomeric determination of pantoprazole in human plasma by multidimensional high-performance liquid chromatography.

Multidimensional HPLC is a powerful tool for the analysis of samples of a high degree of complexity. This work reports the use of multidimensional HPLC by coupling a RAM column with a chiral polysaccharide column to the analysis of Pantoprazole in human plasma by direct injection. The enantiomers from the plasma samples were separated with high resolution on a tris(3,5-dimethoxyphenylcarbamate) of amylose phase after clean-up by a RAM BSA octyl column. Water was used as solvent for the first 5 min in a flow-rate of 1.0 ml/min for the elution of the plasmatic proteins and then acetonitrile-water (35:65 v/v) for the transfer and analysis of pantoprazole enantiomers, which were detected by UV at 285 nm. Analysis time was 28 min with no time spent on sample preparation. A good linear relationship was obtained in the concentration range of 0.20 to 1.5 microg/ml for each enantiomer. Inter and intra-day precision and accuracy were determined by one low (0.24 microg/ml), one medium (0.70 microg/ml) and one high (1.3 microg/ml) plasma concentration and gave a C.V. varying from 1.80 to 8.43% and accuracy from 86 to 92%. Recoveries of pantoprazole enantiomers were in the range of 93.7-101.2%. The validated method was applied to the analysis of the plasma samples obtained from ten Brazilian volunteers who received an 80 mg oral dose of racemic pantoprazole and was able to quantify the enantiomers of pantoprazole in all clinical samples analyzed.

Separation and NMR studies on lignans of Raulinoa echinata.

Investigation of the leaves of Raulinoa echinata Cowan (Rutaceae) has led to the isolation of several furofuran (2,6-diaryl-3,7-dioxabicyclo[3.3.0]-octane) lignan derivatives, namely (+)-sesamin, (+)-eudesmin, (+)-methylpiperitol (= kobusin), (+)-piperitol-gamma,gamma-dimethylallylether and the corresponding epi compounds: (+)-asarinin, (+)-epieudesmin, (+)-methylxanthoxylol, (+)-methylpluviatilol, (+)-xanthoxylol-gamma,gamma-dimethylallylether and (+)-pluviatilol-gamma,gamma-dimethylallylether. This is the first report of the chromatographic separation of the epimers (+)-methylxanthoxylol/(+)-methylpluviatilol and (+)-xanthoxylol-gamma,gamma-dimethylallylether/(+)-pluviatilol-gamma,gamma- dimethylallylether and of their NMR nOe difference studies.

Monitoring aspects during port-access cardiac surgery.

OBJECTIVE: To report the experience gained at our Cardiosurgical Centre with the recently introduced port-access technique. EXPERIMENTAL DESIGN: Prospective collection of data from the month of October 1997. SETTING: Regional University HospitaL Patients: Adult patients undergoing coronary bypass graft or mitral valve surgery. INTERVENTIONS: Port-access technique makes it possible to carry out open-heart procedures through a minithoracotomy and extrathoracic cardiopulmonary bypass with a set of properly designed catheters (Heartport EndoCPB system) for cardioplegia delivery and heart venting. MEASURES: Transesophageal echography and pressure traces are the main monitoring tools used for the correct placement of these catheters and for the clinical management of the patient. RESULTS: Sixty-two cases have been performed so far. A complete description of the procedure, with monitoring aspects and problems encountered is thoroughly presented. CONCLUSIONS: The major differences with traditional cardiac surgery are that interruption of myocardial perfusion is not achieved through a transversal clamp but through an endovascular occlusive balloon and that thoracic access is by minithoracotomy. Unlike traditional open surgery, the surgeon has no direct vision of the position of the clamp and the anesthesiologist can not visually inspect the contractile state of the heart. The operative team has to cope with a multifaceted system of monitored variables that must be continuously integrated and interpreted. Tight cooperation and continuous communication between anaesthesiologist, surgeons and perfusionist appear to be more important than in any other cardiac operation.

Procedures in complex systems: the airline cockpit.

In complex human-machine systems, successful operations depend on an elaborate set of procedures which are specified by the operational management of the organization. These procedures indicate to the human operator (in this case the pilot) the manner in which operational management intends to have various tasks done. The intent is to provide guidance to the pilots and to ensure a safe, logical, efficient, and predictable (standardized) means of carrying out the objectives of the job. However, procedures can become a hodge-podge. Inconsistent or illogical procedures may lead to noncompliance by operators. Based on a field study with three major airlines, the authors propose a model for procedure development called the "Four P's": philosophy, policies, procedures, and practices. Using this model as a framework, the authors discuss the intricate issue of designing flight-deck procedures, and propose a conceptual approach for designing any set of procedures. The various factors, both external and internal to the cockpit, that must be considered for procedure design are presented. In particular, the paper addresses the development of procedures for automated cockpits--a decade-long, and highly controversial issue in commercial aviation. Although this paper is based on airline operations, we assume that the principles discussed here are also applicable to other high-risk supervisory control systems, such as space flight, manufacturing process control, nuclear power production, and military operations.

ECMO and inhaled nitric oxide for cardiopulmonary failure after heart retransplantation.

Cardiopulmonary failure occurred in a 62-year-old patient a few hours after emergency cardiac retransplantation. Venoarterial extracorporeal membrane oxygenation was required to support biventricular dysfunction; thereafter, inhaled nitric oxide was given for residual hypoxemia and pulmonary hypertension. We report survival after venoarterial extracorporeal membrane oxygenation and inhaled nitric oxide treatment for both heart and lung failure in a heart recipient.

Enantiomeric resolution by HPLC of axial chiral amides using amylose tris[(S)-1-phenylethylcarbamate].

The enantiomeric resolution of a series of N-arylamides was examined on amylose tris[(S)-1-phenylethylcarbamate] coated onto aminopropylated 7 microns silica with 500 A diameter pores and on naked silica 5 microns particle size with 500 A diameter pores. The enantiomeric resolution obtained for this series was excellent on both columns. The enantioselectivity of cellulose and amylose tris(3,5-dimethylphenylcarbamate) coated onto APS-Hypersil (120 A pore size, 5 microns particle size) was also investigated for this series of compounds.

The morphology of elastin in non-specific and inflammatory abdominal aortic aneurysms. A comparative transmission, scanning and immunoelectronmicroscopy study.

The maintenance of the mechanical properties of the vessels results from the correct arrangement of smooth muscle cells and extracellular fibrous proteins (elastin and collagen) in their wall. The morphology of extracellular matrix modifications, particularly of elastin, was investigated in inflammatory (IA) and non specific (NSA) abdominal aortic aneurysms by scanning (SEM), transmission (TEM) and immunoelectron microscopy. Both NSAs and IAs were significantly characterized by extensive extracellular matrix remodelling, including different patterns of elastin degradation. Elastic and collagen fibres distribution appeared to be extensively altered in IAs, while it conformed more to a normal pattern in NSAs. With respect to NSAs, the morphology of elastic fibres in IAs was modified to such an extent that their identification by TEM had a rely on immunocytochemical methods and by SEM on back-scattered electron analysis. The observed ultrastructural changes are indicative of the central role of extracellular matrix modifications in the pathogenesis of IAs and NSAs.

A comparative study of two shovel designs.

In the present study a modified shovel design with two perpendicular shafts is presented. This modified, two-shaft shovel was compared with a regular shovel. The modified shovel was evaluated and tested in a controlled laboratory environment using surface electromyography recorded from the lumbar paraspinal muscles. The new shovel design was also tested in a field study using ratings of perceived exertion. The results indicate that there was a significant reduction in EMG values of the lumbar paraspinal muscles and a consistent reduction in perceived exertion ratings while the modified shovel was being used for removing dirt in digging trenches up to 90 cm in depth.

Content and turnover of extracellular matrix protein in human "nonspecific" and inflammatory abdominal aortic aneurysms.

Inflammatory aneurysms (IAs) have peculiar macroscopic and histological aspects which make them very different from nonspecific aneurysms (NSAs). These morphological differences seem to be determined by significant modifications of the extracellular matrix. Extracellular matrix protein component concentrations were determined biochemically in infrarenal aortic biopsies from 10 NSAs, five IAs and five non-aneurysmal aortic controls. The concentration of each wall component was expressed in % w/w (relative concentration) and in mg/wall longitudinal cm (absolute concentration) with reference to total protein recovered after hydrolysis and amino acid analysis. The biochemical results were correlated with the histological and ultrastructural features of the specimens. A significant increase in total collagen was observed in the two groups of aneurysms, with respect to the controls (NSA = 285%, IA = 382%). In contrast the 80-90% decrease in the relative concentration of elastin observed in both types of aneurysm was less marked (NSA = 55%, IA = 39%). This fall was not significant when expressed in mg/cm, although elastin derived peptide (EDP) levels in the plasma of these patients was significantly higher than in age-matched controls. The concentration of the soluble collagen fraction appeared significantly higher (Mann-Whitney, p < 0.05) in the IAs with respect to the NSAs, whilst no differences were observed between the two groups regarding the concentration of insoluble elastin and of wall and plasma EDPs. As well as providing evidence of increased elastin turnover, this study emphasises the conspicuous modifications of collagen deposition in the wall of abdominal aortic aneurysms which appeared more marked in the inflammatory group.(ABSTRACT TRUNCATED AT 250 WORDS)