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Biomedical subjects

I Martin

Publications and source records attributed to I Martin.

At least 37 records · Page 2Linked to original sources

Interventions for relieving the pain and discomfort of screening mammography.

BACKGROUND: Pain of mammography is recognised as a significant deterrent to breast screening and therefore may effect the success or failure of any screening programme. OBJECTIVES: To review research of interventions related to any aspect of breast screening to reduce or relieve the pain and discomfort of screening mammography. SEARCH STRATEGY: The Cochrane Breast Cancer Group conducted a search of their specialised register in the Cochrane Library. In addition a wide variety of databases and websites were searched using keywords 'mammography' and 'pain', along with handsearching selected journals. Information was requested from a wide range of interested people and organisations. SELECTION CRITERIA: Randomised controlled trials and non-randomised trials with a comparison group were considered. Studies had to include assessment of both pain and quality of mammograms. DATA COLLECTION AND ANALYSIS: Identified studies were independently reviewed by two reviewers to determine if they met the inclusion criteria. Additional information was sought from investigators as necessary. Each study was reviewed for quality, including concealment of the allocation sequence, generation of the allocation sequence, comparability between groups at the baseline, inclusion of all randomised participants in the analysis and blinding after allocation. MAIN RESULTS: Three RCTs were identified for inclusion. A well designed study found that patient controlled breast compression gave a significant reduction in discomfort. However, the quality of mammograms was only maintained if the technologist controlled the first compression. Another study involved the technologist reducing compression force for one view. This study was poorly designed and showed no significant differences. The result was the same in a well designed study of the use of acetoaminophen as a premedication. The differences in interventions, and the inconsistency in measures and validation of pain scales and assessment of quality of mammograms, mean that the results of the studies cannot be combined. REVIEWER'S CONCLUSIONS: The only intervention suggesting significant reduction in the pain and discomfort was of patient controlled compression. Further research is required to determine if these findings can be replicated. Reducing technologist applied compression force did not result in significant reduction in pain suggesting that more than actual compression force is involved in pain and discomfort. However, the poor design of this study could have influenced the results. Premedication with acetoaminophen has no effect on the pain of mammography. More research into interventions to reduce the pain of mammography is needed if this is to continue as the preferred screening method in the detection of breast cancer.

Acetaminophen↗

Remediation of contaminated land and groundwater: experience in England and Wales.

Remediation of contaminated land and groundwater is of common international concern. The context and approach taken to the problem are, however, country-specific. A survey of remedial activity occurring within England and Wales over the period 1996-1999 was commissioned by the Environment Agency (for England and Wales) to establish a baseline against which future trends in remedial activity could be judged. This paper: explains the context of contaminated land and groundwater remediation in England and Wales (Britain); provides an overview of the 1996-1999 survey of remedial activity, discussing its findings within its legislative and institutional context; and, discusses the survey results of significance to the management of contaminated land and groundwater internationally. The survey obtained specific data from 367 remediated sites supplemented by general data from a further 1189 contaminated (not necessarily remediated) sites. The survey aimed to be, and was indicative of remediation practice, and did not seek to identify every remediation scheme operating. Previous anecdotal evidences were generally confirmed. Civil engineering-based techniques dominated and were used at 94% of sites with in situ techniques (predominantly vapour extraction-based) on 16% and ex situ on just 5%. Although disposal to landfill was dominant and occurred at over 80% of sites, integrated use of multiple techniques was common. Remediation was predominantly of soil (rather than water), development-based, designed to protect human health and reflected national development-led and 'suitable for use' policies. Lessons of international relevance from the survey and general British experience are drawn concerning remediation technique selection, regulatory and financial support of innovative remediation techniques and demonstration sites, competent use of risk-based approaches to allow pragmatic remediation and effective use of quality guidelines, need for effective guidance to highlight water quality issues, the necessity of post remediation monitoring to prove remediation effectiveness and the keeping of remediation databases.

Conservation of Natural Resources↗

Early reoperation for acute dysphagia following laparoscopic fundoplication.

BACKGROUND: A small number of patients develop acute severe dysphagia for which reoperation is necessary within 10 days of laparoscopic fundoplication. The aim of this study was to identify clinical variables that might predict the likelihood of this condition occurring, such that it could be avoided in the future. METHODS: This was a prospective cohort study from three tertiary referral centres, using reoperation for acute dysphagia as the main outcome variable. Gastrointestinal symptom rating scale, and psychological well-being index questionnaires were undertaken before laparoscopic fundoplication, and dysphagia scores were determined before operation and 1 year later. Standard preoperative assessment included gastroscopy, oesophageal manometry and pH studies. RESULTS: Twelve (1.9 per cent) of the 617 patients suffered acute dysphagia, which was predicted by older age and female sex, and resulted in a longer duration of hospital stay. This condition was not predicted by any other demographic, clinical, investigative or operative variables. CONCLUSION: The study did not identify useful criteria by which severe acute dysphagia could be anticipated and thereby avoided following laparoscopic fundoplication.

Acute Disease↗

Plasminogen activation by blood monocytes and alveolar macrophages in primary pulmonary hypertension.

The pathophysiology of primary pulmonary hypertension (PPH) remains poorly understood. Vascular wall remodeling and endothelial dysfunction reflected by modifications in plasma fibrinolytic proteins and von Willebrand factor have been well documented in PPH. We hypothesize that endothelial mediators, produced in excess in PPH patients, may stimulate migrating mononuclear cells and thereby modulate alveolar macrophage function; in particular, the plasminogen activation system. Components of the fibrinolytic system were therefore studied in plasma, blood monocytes and alveolar macrophages obtained from bronchoalveolar lavage in 10 patients with PPH and in four controls. Compared with controls, PPH patients had elevated plasma levels of tissue-type plasminogen activator (15.6 +/- 9.9 versus 5.5 +/- 3 ng/ml) and plasminogen activator inhibitor-1 (27.8 +/- 23 versus 16.4 +/- 12 ng/ml). In contrast, binding and activation of plasminogen by single-chain urokinase-type plasminogen activator (scu-PA) at the surface of blood monocytes and alveolar macrophages were not different from those of control values. Dissociation constants (K(d)) for binding of scu-PA and plasminogen to alveolar macrophages were similar in both PPH (4.7 +/- 1.5 and 0.88 +/- 0.3 micromol/l, respectively) and control (6.7 +/- 0.1 and 1.02 +/- 0.12 micromol/l, respectively) groups. These results indicate that in PPH patients the fibrinolytic activity of alveolar macrophages is normal, whereas endothelial fibrinolytic proteins are abnormally elevated in plasma.

Adult↗

Bioreactor studies of native and tissue engineered cartilage.

Functional tissue engineering of cartilage involves the use of bioreactors designed to provide a controlled in vitro environment that embodies some of the biochemical and physical signals known to regulate chondrogenesis. Hydrodynamic conditions can affect in vitro tissue formation in at least two ways: by direct effects of hydrodynamic forces on cell morphology and function, and by indirect flow-induced changes in mass transfer of nutrients and metabolites. In the present work, we discuss the effects of three different in vitro environments: static flasks (tissues fixed in place, static medium), mixed flasks (tissues fixed in place, unidirectional turbulent flow) and rotating bioreactors (tissues dynamically suspended in laminar flow) on engineered cartilage constructs and native cartilage explants. As compared to static and mixed flasks, dynamic laminar flow in rotating bioreactors resulted in the most rapid tissue growth and the highest final fractions of glycosaminoglycans and total collagen in both tissues. Mechanical properties (equilibrium modulus, dynamic stiffness, hydraulic permeability) of engineered constructs and explanted cartilage correlated with the wet weight fractions of glycosaminoglycans and collagen. Current research needs in the area of cartilage tissue engineering include the utilization of additional physiologically relevant regulatory signals, and the development of predictive mathematical models that enable optimization of the conditions and duration of tissue culture.

Animals↗

Membrane interactions of mutated forms of the influenza fusion peptide.

We have studied a group of fusion peptides of influenza hemagglutinin in which the N-terminal amino acid, Gly (found in the wild-type peptide), has been systematically substituted with Ala, Ser, Val, or Glu. The activity of the intact hemagglutinin protein with these same substitutions has already been reported. As a measure of the extent of modulation of intrinsic membrane curvature by these peptides, we determined their effects on the polymorphic phase transition of dipalmitoleoylphosphatidylethanolamine. The wild-type peptide is the only one that, at pH 5, can substantially decrease the temperature of this transition. This is also the only form in which the intact protein promotes contents mixing in cells. The Ala and Ser mutant hemagglutinins exhibit a hemifusion phenotype, and their fusion peptides have little effect on lipid polymorphism at low pH. The two mutant proteins that are completely fusion inactive are the Val and Glu mutant hemagglutinins. The fusion peptides from these forms significantly increase the polymorphic phase transition temperature at low pH. We find that the effect of the fusion peptides on membrane curvature, as monitored by a shift in the temperature of this polymorphic phase transition, correlates better with the fusogenic activities of the corresponding protein than do measurements of the isotropic (31)P NMR signals or the ability to induce the fusion of liposomes. The inactivity of the hemagglutinin protein with the hydrophobic Val mutation can be explained by the change in the angle of membrane insertion of the helical fusion peptide as measured by polarized FTIR. Thus, the nature of the interactions of the fusion peptides with membranes can, in large part, explain the differences in the fusogenic activity of the intact protein.

Alanine↗

Specific growth factors during the expansion and redifferentiation of adult human articular chondrocytes enhance chondrogenesis and cartilaginous tissue formation in vitro.

Adult human articular chondrocytes were expanded in a medium with 10% serum (CTR) or further supplemented with different mitogens (i.e., EGF, PDGFbb, FGF-2, TGF beta 1, or FGF-2/TGF beta 1). Cells were then induced to redifferentiate in 3D pellets using serum-supplemented medium (SSM), serum-free medium (SFM), or SFM supplemented with factors inducing differentiation of chondroprogenitor cells (i.e., TGF beta 1 and/or dexamethasone). All factors tested during expansion enhanced chondrocyte proliferation and dedifferentiation, as assessed by the mRNA ratios of collagen type II to type I (CII/CI) and aggrecan to versican (Agg/Ver), using real-time PCR. FGF-2/TGF beta 1-expanded chondrocytes displayed the lowest doubling times, CII/CI and Agg/Ver ratios, averaging, respectively, 50, 0.2 and 15% of CTR-expanded cells. Redifferentiation in pellets was more efficient in SFM than SSM only for EGF-, PDGFbb- or FGF-2-expanded chondrocytes. Upon supplementation of SFM with TGF beta and dexamethasone (SFM TD), CII/CI ratios decreased 4.4-fold for EGF- and PDGFbb-expanded chondrocytes, but increased 96-fold for FGF-2/TGF beta 1-expanded cells. Chondrocytes expanded with FGF-2/TGF beta 1 and redifferentiated in SFM TD expressed the largest mRNA amounts of CII and aggrecan and generated cartilaginous tissues with the highest accumulation of glycosaminoglycans and collagen type II. Our results provide evidence that growth factors during chondrocyte expansion not only influence cell proliferation and differentiation, but also the cell potential to redifferentiate and respond to regulatory molecules upon transfer into a 3D environment.

Adult↗

The fusion domain of HIV gp41 interacts specifically with heparan sulfate on the T-lymphocyte cell surface.

Studies of the interaction of the 16 residue fusion peptide domain of human immunodeficiency virus glycoprotein gp41 (gp41(FD)) with T lymphocytes are outlined. Fluorescence measurements of changes in the electrostatic surface and dipole potentials of the plasma membrane following the interaction with gp41(FD) are described. The results show that gp41(FD) interacts with heparan sulfate located on the cell surface. This interaction is blocked by interleukin-8 and abolished by pre-treating the cells with heparitinase. The specificity of the reaction was also assessed by observations that soluble heparan sulfate competes with the cell membrane interaction whereas soluble heparin (at the levels utilized) does not. Following binding to heparan sulfate, the interaction with the membrane seems to take place in a cooperative manner with the formation of gp41(FD) trimers. In simpler phospholipid membranes, however, a trimeric complex does not appear to be the dominant mode of interaction. Finally, by repeating some of these studies within an imaging regime, it appears that the gp41(FD)-T-cell interaction takes place within specific domains on the cell surface to similarly localized heparan sulfate moieties.

Binding Sites↗

Selective differentiation of mammalian bone marrow stromal cells cultured on three-dimensional polymer foams.

Bone marrow stromal cells (BMSC) are pluripotent progenitor cells that can regenerate different skeletal tissues in response to environmental signals. In this study, we used highly porous, structurally stable three-dimensional polymer foams in conjunction with specific regulatory molecules to selectively differentiate mammalian BMSC into either cartilaginous or bone-like tissues. Bovine BMSC were expanded in monolayers and cultured on 5-mm-diameter, 2-mm-thick foams made of poly(lactic-co-glycolic acid) and poly(ethylene glycol). Constructs maintained their original size and shape for up to 4 weeks of culture and supported BMSC growth and production of extracellular matrix (ECM). By proper use of chondrogenic (dexamethasone, insulin, transforming growth factor-beta1) or osteogenic (dexamethasone, beta-glycerophosphate) medium supplements, we could control whether the generated ECM was cartilaginous (containing collagen type II and sulfated glycosaminoglycans) or bone-like (containing osteocalcin, osteonectin, and mineralized foci). After 4 weeks of cultivation, cartilaginous and bone-like ECM were uniformly distributed throughout the construct volume and respectively represented 34.2 +/- 9.3% and 12.6 +/- 3.2% of the total available area. BMSC culture on poly(lactic-co-glycolic acid)/poly(ethylene glycol) foams provides a three-dimensional model system to study the development of mesenchymal tissues in vitro and has potential applications in engineering autologous grafts for skeletal tissue repair.

Animals↗

Multiplex PCR for the detection of tetracycline resistant genes.

Specific primer pairs were selected for the PCR amplification of 14 tetracycline resistant genes commonly found in Gram positive and Gram negative organisms. Combinations of primer pairs were used in multiplex PCR reactions to detect specific groups of tet genes as follows; Group I tet (B), tet (C), tet (D); Group II tet (A), tet (E), tet (G); Group III tet (K), tet (L), tet (M), tet (O), tet (S); Group IV tetA (P), tet (Q), tet (X). To test the multiplex PCR, Groups I and II were used on 25 clinical isolates of Salmonella enterica serovar Typhimurium DT104. Group III primers were used to investigate 19 clinical isolates of methicillin-resistant Staphylococcus aureus. Multiplex PCR should result in significant savings in terms of labour and cost in analysis of a large number of strains when compared with using an individual PCR for targeting each gene. It may also be a useful method to differentiate the types of tetracycline resistance when used as an additional marker for the purpose of outbreak investigation and surveillance.

DNA Fingerprinting↗

Thoracoscopic mobilization of the esophagus. A 6 year experience.

BACKGROUND: Traditionally, esophageal resection has been performed using a thoracotomy to access the intrathoracic esophagus. With the aim to avoid the potential morbidity of the open thoracic approach, mobilization of the esophagus under direct vision recently has been described. We report our experience at attempting thoracoscopic mobilization of the esophagus in 162 patients during a 6-year period. METHODS: Patients with malignancy or end-stage benign disease of the esophagus considered suitable for a three-stage esophagectomy underwent a thoracoscopy with a view to endoscopic mobilization of the esophagus. Of the 162 patients in whom the procedure was attempted, it was abandoned in 9 patients (6%), and the procedure was converted to open surgery in 11 patients (7%). RESULTS: In the patients whose esophagus was mobilized, the average blood loss was 165 ml, and the average time for the thoracoscopic segment of the surgery was 104 min. In the 133 patients who underwent a resection for invasive malignancy, a limited mediastinal nodal dissection retrieved an average of 11 nodes, and the median survival was 29 months. The 30-day mortality was 3.3% and the in-hospital mortality 5.3%. CONCLUSIONS: Thoracoscopic mobilization can be performed safely with satisfactory outcomes in a center performing a large volume of esophageal surgery and possessing advanced endoscopic surgery skills. Further assessment of this technique and comparisons with traditional open procedures are needed to assess this approach further as an appropriate oncologic procedure.

Adult↗

Integration of engineered cartilage.

The structure and function of cartilaginous constructs, engineered in vitro using bovine articular chondrocytes, biodegradable scaffolds and bioreactors, can be modulated by the conditions and duration of tissue cultivation. We hypothesized that the integrative properties of engineered cartilage depend on developmental stage of the construct and the extracellular matrix content of adjacent cartilage, and that some aspects of integration can be studied under controlled in vitro conditions. Disc-shaped constructs (cultured for 5+/-1 days or 5+/-1 weeks) or explants (untreated or trypsin treated cartilage) were sutured into ring-shaped explants (untreated or trypsin treated cartilage) to form composites that were cultured for an additional 1-8 weeks in bioreactors and evaluated biochemically, histologically and mechanically (compressive stiffness of the central disk, adhesive strength of the integration interface). Immature constructs had poorer mechanical properties but integrated better than either more mature constructs or cartilage explants. Integration of immature constructs involved cell proliferation and the progressive formation of cartilaginous tissue, in contrast to the integration of more mature constructs or native cartilage which involved only the secretion of extracellular matrix components. Integration patterns correlated with the adhesive strength of the disc-ring interface, which was markedly higher for immature constructs than for either more mature constructs or cartilage explants. Trypsin treatment of the adjacent cartilage further enhanced the integration of immature constructs.

Animals↗

An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic-pituitary disease.

OBJECTIVE: The insulin tolerance test (ITT) is usually regarded as the 'gold standard' for the assessment of the hypothalamic-pituitary axis (growth hormone (GH) and ACTH) but must be used with caution and is contra-indicated in certain groups of patients. The glucagon stimulation test (GST) has previously been shown to be a good alternative when the ITT is contra-indicated and like the ITT stimulates both GH and ACTH secretion. There is however limited data on the use of the GST in patients with hypothalamic-pituitary disease. DESIGN AND PATIENTS: An audit of 500 GST was performed in 374 patients with hypothalamic-pituitary disease. Glucagon was administered via the subcutaneous route and bloods were taken at times 0 90 120 150 180 210 and 240 minutes. RESULTS: In the vast majority peak GH (84.4%) and cortisol (93%) responses occurred between 120 and 180 minutes Little information was obtained from the 240 minute sample. The medical supervision required was minimal and the side-effects encountered during this test were mild; 20% of the tests were associated with nausea occasionally with vomiting sweating or headaches. Four patients fainted but recovered quickly. CONCLUSIONS: This large audit has shown that the glucose stimulation test is well tolerated and can easily be performed in an out-patient setting with minimal medical supervision. The 240 minute sample added little additional information and could be omitted.

Acromegaly↗

Quantitative analysis of gene expression in human articular cartilage from normal and osteoarthritic joints.

OBJECTIVE: To quantify the expression of genes encoding extracellular matrix (ECM) proteins in human cartilage from normal and osteoarthritic (OA) joints. DESIGN: Human cartilage samples were classified as control (CTR) or OA according to clinical evaluation and assessed histologically and biochemically to confirm the diagnosis. mRNAs encoding collagen types I, II and X, aggrecan, versican, osteopontin and osteocalcin were quantified by real-time reverse transcription-PCR assays and normalized to a reference mRNA (GAPDH). RESULTS: RNA from native cartilage could be reproducibly and efficiently amplified by real-time PCR only if isolated using purification membranes. Primers and fluorescent probes for real-time PCR, endowed with comparable (<6% difference from GAPDH) and high (>91%) amplification efficiencies, were designed and validated for the selected ECM genes. The expression of most genes under investigation displayed large variations and was not significantly different in CTR and OA cartilage. Only osteopontin mRNA levels were significantly higher in OA than CTR specimens. mRNA ratios of collagen type II to I and of aggrecan to versican, defined as indexes of chondrocyte differentiation, were less variable within each population than the single genes and markedly higher (27.0 and 7.6-fold, respectively) in CTR than OA cartilage, with high statistical significance (P = 0.00013 and P = 0.00007, respectively). CONCLUSIONS: Our results provide evidence that gene patterns related to chondrocyte differentiation discriminate between CTR and OA human cartilage with higher sensitivity than single ECM genes. The method described here has the potential to improve understanding of the progression of OA and could become a valuable diagnostic tool.

Adult↗