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Biomedical subjects

T Lang

Publications and source records attributed to T Lang.

At least 127 records · Page 7Linked to original sources

The biogenesis and properties of the parasitophorous vacuoles that harbour Leishmania in murine macrophages.

Leishmania are protozoan parasites that, as amastigotes, live in the macrophages of mammalian hosts within compartments called parasitophorous vacuoles. These organelles share features with late endosomes/lysosomes and are also involved in the trafficking of several major histocompatibility complex (MHC)-encoded molecules. Improved knowledge of the parasitophorous vacuoles may help clarify how these protozoa persist in their hosts.

Adaptation, Biological↗

Noninvasive assessment of bone density and structure using computed tomography and magnetic resonance.

For several reasons, including low cost and radiation dose, simplicity, and the ability to image several skeletal sites, dual X-ray absoptiometry (DXA) is the most widely employed technique for diagnostic and serial assessment of integral bone mass in osteoporosis and other metabolic bone diseases. However, three-dimensional imaging modalities such as quantitative computed tomography (QCT) and magnetic resonance (MR) imaging offer the ability to separately examine different factors that may play independent and important roles in osteoporosis. These factors include the density of the trabecular and cortical compartments as well as the pattern of trabecular microarchitecture. New developments in QCT include volumetric approaches for precise compartmental assessment of the spine and proximal femur as well as thin-slice tomography of the vertebral body for assessment of trabecular texture. In addition, ultrahigh resolution CT scanners (spatial resolution ë50-150(i)i) have been developed for imaging of trabecular structure in specimens and in some cases for the peripheral skeleton (distal radius and phalanges). High resolution MR measurements may be employed for assessment of the trabecular texture at a range of peripheral sites, including the calcaneus, distal radius, and phalanges.

Adult↗

High-resolution magnetic resonance imaging: three-dimensional trabecular bone architecture and biomechanical properties.

The purpose of this study was to use high-resolution magnetic resonance (MR) imaging combined with image analysis to investigate the three-dimensional (3D) trabecular structure, anisotropy, and connectivity of human vertebral, femoral, and calcaneal specimens. The goal was to determine whether: (a) MR-derived measures depict known skeletal-site-specific differences in architecture and orientation of trabeculae; (b) 3D architectural parameters combined with bone mineral density (BMD) improve the prediction of the elastic modulus using a fabric tensor formulation; (c) MR-derived 3D architectural parameters combined with BMD improve the prediction of strength using a multiple regression model, and whether these results corresponded to the results obtained using higher resolution depictions of trabecular architecture. A total of 94 specimens (12 x 12 x 12 mm cubes) consisting of trabecular bone only were obtained, of which there were 7 from the calcaneus, 15 from distal femur, 47 from the proximal femur, and 25 from the vertebral bodies. MR images were obtained using a 1.5 Tesla MR scanner at a spatial resolution of 117 x 117 x 300 microm. Additionally, BMD was determined using quantitative computed tomography (QCT), and the specimens were nondestructively tested and the elastic modulus (YM) was measured along three orthogonal axes corresponding to the anatomic superior-inferior (axial), medial-lateral (sagittal), and anterior-posterior (coronal) directions. A subset of the specimens (n=67) was then destructively tested in the superior-inferior (axial) direction to measure the ultimate compressive strength. The MR images were segmented into bone and marrow phases and then analyzed in 3D. Ellipsoids were fitted to the mean intercept lengths, using single value decomposition and the primary orientation of the trabeculae and used to calculate the anisotropy of trabecular architecture. Stereological measures were derived using a previously developed model and measures such as mean trabecular width, spacing, and number were derived. Because the spatial resolution of MR images is comparable to trabecular bone dimensions, these measures may be subject to partial volume effects and were thus treated as apparent measures, such as BV/TV, Tb.Sp, Tb.N, and Tb.Th rather than absolute measures, as would be derived from histomorphometry. In addition, in a subset of specimens, the Euler number per unit volume was determined to characterize the connectivity of the trabecular network. There were significant differences in the BMD, trabecular architectural measures, elastic modulus, and strength at the different skeletal sites. The primary orientation axes for most of the specimens was the anatomic superior-inferior (axial) direction. Using the fabric tensor formulation, in addition to BMD, improved the prediction of YM (SI), while including some of the architectural parameters significantly improved the prediction of strength. In comparing MR-derived 3D measures with those obtained from 20 microm optical images (n=18; 9 vertebrae, 9 femur specimens), good correlations were found for the apparent Tb.Sp and Tb.N, moderate correlation was seen for the apparent BV/TV, and poor correlation was found for the apparent Tb.Th. Using these higher resolution images, the fabric tensor formulation for predicting the elastic modulus also showed improved correlation between the measured and calculated modulus in the axial (SI) direction. In summary, high-resolution MR images may be used to assess 3D architecture of trabecular bone, and the inclusion of some of the 3D architectural measures provides an improved assessment of biomechanical properties. Further studies are clearly warranted to establish the role of architecture in predicting overall bone quality, and the role of trabecular architecture measures in clinical practice. (ABSTRACT TRUNCATED)

Anatomy, Cross-Sectional↗

Down-regulation of MHC class II molecules and inability to up-regulate class I molecules in murine macrophages after infection with Toxoplasma gondii.

Toxoplasma gondii is able to invade phagocytic cells of the monocyte-macrophage lineage and replicates within a parasitophorous vacuole. Since macrophages may activate specific T lymphocytes by presenting pathogen-derived antigens in association with molecules of the MHC, we investigated the in vitro expression of host cell molecules involved in antigen processing and presentation before and during infection of murine bone marrow-derived macrophages (BMM) with T. gondii. Fifty-one hours after addition of T. gondii tachyzoites at different parasite-to-host ratios, up-regulation of total MHC class II molecules by interferon-gamma (IFN-gamma) was dose-dependently abrogated in up to 50% of macrophages compared with uninfected control cultures. Quantitative analyses by flow cytometry revealed that the IFN-gamma-induced surface expression of class II antigens as well as the IFN-gamma-induced upregulation of class I molecules was significantly decreased in T. gondii-infected macrophage cultures compared with uninfected controls. However, the constitutive expression of MHC class I antigens was not altered after parasitic infection, and infected BMM remained clearly positive for these molecules. After infection of macrophages preactivated with IFN-gamma for 48 h, T. gondii also actively down-regulated an already established expression of MHC class II molecules. Furthermore, kinetic analysis revealed that the reduction in intracellular and plasma membrane-bound class II molecules started approximately 20 h after infection. While MHC class II antigens were most prominently reduced in parasite-positive host cells, culture supernatant from T. gondii-infected BMM cultures also significantly inhibited expression of these molecules in uninfected macrophages. However, down-regulation of MHC class II molecules was not mediated by an increased production of prostaglandin E2, IL-10, transforming growth factor-beta or nitric oxide by infected BMM compared with uninfected controls. Our data indicate that intracellular T. gondii interferes with the MHC class I and class II antigen presentation pathway of murine macrophages and this may be an important strategy for evasion from the host's immune response and for intracellular survival of the parasite.

Animals↗

Is hospital care involved in inequalities in coronary heart disease mortality? Results from the French WHO-MONICA Project in men aged 30-64.

OBJECTIVES: The goal of the study was to assess whether possible disparities in coronary heart disease (CHD) management between occupational categories (OC) in men might be observed and contribute to the increasing inequalities in CHD morbidity and mortality reported in France. METHODS: The data from the three registers of the French MONICA Collaborative Centres (MCC-Lille, MCC-Strasbourg, and MCC-Toulouse) were analysed during two period: 1985-87 and 1989-91. Acute myocardial infarctions and coronary deaths concerning men, aged 30-64 years, were included. Non-professionally active and retired men were excluded. Results were adjusted for age and MCC, using a logistic regression analysis. RESULTS: 605 and 695 events were analysed for 1985-87 and 1989-91, respectively. Out of hospital cardiac arrests, with or without cardiac resuscitation, and 28 day case fatality rates were lower among upper executives in both periods. A coronarography before the acute event had been performed more frequently in men of this category and the proportion of events that could be hospitalised was higher among them. In both periods, the management of acute myocardial infarctions in hospital and prescriptions on discharge were similar among occupational categories. CONCLUSIONS: For patients who could be admitted to hospital, the management was found to be similar among OCs, as was the 28 day case fatality rate among the hospitalised patients. In contrast, lower prognosis and higher probability of being hospitalised after the event among some categories suggest that pre-hospital care and the patient's conditions before the event are the primary factors involved.

Adult↗

A cross sectional analysis of 5 different markers of collagen degradation in rheumatoid arthritis.

OBJECTIVE: To compare 5 different assays measuring collagen degradation in rheumatoid arthritis (RA). METHODS: Daily serum samples and 3 consecutive 24 h urine samples were obtained from 25 patients with RA and 20 control subjects. Levels of pyridinoline (PYD), deoxypyridinoline (DPYD), n-telopeptide (NTx), CrossLaps (XL), and carboxy-terminal peptide of type I collagen (ICTP) were determined by ELISA or radioimmunoassay. PYD, DPYD, NTx, and XL were measured in urine and expressed as a ratio of the amount of crosslink to mmoles of creatinine (Cr). ICTP was determined in serum. The day-to-day variability of urinary collagen crosslink levels and serum ICTP was assessed over 3 day hospitalization. RESULTS: Four of the 5 markers were significantly elevated in the RA cohort compared to controls: PYD (nmol)/Cr (median 33.8 vs 19.3; p = 0.0001), NTx (nmol)/Cr (median 22.5 vs 13.8; p = 0.01), XL (microg)/Cr (median 191.4 vs 126.1; p = 0.01), and ICTP (microg/l) (median 5.8 vs 3.7; p = 0.001). In the RA group, higher levels of the markers were associated with concomitant prednisone therapy. The levels of the 4 urine markers and of ICTP in serum exhibited little day-to-day variability. CONCLUSION: Biochemical evidence of increased collagen degradation can be readily observed in RA using simple quantitative assays. These measures have minimal short term, day-to-day variability and hence may be useful to assess the effect of potentially disease modifying therapies.

Amino Acids↗

Outpatient care in emergency departments: feasibility and comparison of three strategies for follow-up.

The outpatient population using the emergency department (ED) is increasing and so is the risk of not admitting people who need it. There is, thus, one important question: are the services delivered appropriate to the needs of these ED outpatients? Follow-up of non-admitted patients after a visit to the ED is a prerequisite for the evaluation of these health services. A multicentric follow-up study was thus performed in order to assess the possibility of contacting outpatients after a visit to the ED. Three randomized follow-up methods were compared: (1) telephone call 1 week after the emergency department visit; (2) telephone call 2 weeks after the visit; (3) telephone call 4 weeks after the visit. The follow-up rate did not change depending on whether patients were contacted at 1, 2 or 4 weeks after the visit. The success rate was 78.6%, 85.6% and 74% respectively (NS). In each strategy, 50% of patients were contacted at the first telephone call, 20% at the second telephone call and 10% by mail. Thus, in a group of outpatients who gave their consent to be called, the follow-up was found to be feasible with a high success rate whatever the time between the visit and the phone recall.

Adolescent↗

[Appropriateness of medical procedures: measurements and relations with needs and access to health care].

Efforts to reduce cost expenditures and improve quality of care have raised some concern over the recent years as to the appropriateness of medical procedures. However, the relationships between the appropriateness of medical procedures, the need for such procedures and access to health care have not been described in detail. The appropriateness of medical procedures is usually measured on the basis of procedures actually performed. We present a critical appraisal of this type of measurement. From a population point of view, measurement of appropriateness does not actually reflect simply those procedures which have been performed, but rather involves three parameters: needs for a particular procedure, access to the procedure by those who need it, and non performance of the procedure among those who do not need it. This analysis revealed three consequences. First, there is an inverse relationship between access to a procedure among subjects who need the procedure and the appropriateness of such a procedure among those who do not need it. Secondly, comparisons of appropriateness rates between individual facilities or between regions must take into account the need for this procedure in the general population. Finally, it is possible to observe similar rates of procedure performance between regions or social groups despite major regional or social differences in appropriateness and access to health care.

Ambulatory Care↗

Cholic acid synthesis is reduced in pediatric liver recipients during graft dysfunction due to ischemic injury and allograft rejection.

BACKGROUND: Bile acids are synthesized and secreted by the liver. During liver failure and hepatic dysfunction, a marked reduction of bile acid synthesis has been shown. The purpose of this study was to determine whether the biliary bile acid pattern was affected by preservation injury and rejection and whether it was a reliable marker for graft function in pediatric liver recipients after liver transplantation. METHODS: We prospectively measured the biliary bile acid pattern in 126 serial bile samples obtained from 15 consecutive pediatric liver recipients by reversed phase high pressure liquid chromatography and correlated our results with clinical findings: preservation injury, no rejection, rejection, or infection. RESULTS: There was a significant change of the bile acid pattern during the first 3 days after transplant. Total biliary bile acids, cholic acid (CA), and CA/chenodeoxycholic acid (CDCA) ratio increased in 12 of 15 patients with mild preservation injury. These changes of the bile acid pattern were markedly delayed in patients with severe preservation injury. During 16 rejection episodes, total biliary bile acid, CA, and CA/CDCA ratio decreased significantly, but returned to normal after successful treatment of rejection. Bacterial infection, observed in nine children, and cyclosporine toxicity, observed in three children, seemed to have no affect on the biliary bile acids. CONCLUSIONS: Liver cell damage as a result of preservation injury or rejection leads to a reduction of biliary CA, resulting in a decrease of total biliary bile acids and the CA/CDCA ratio in pediatric liver recipients. This might be caused by a diminished secretion of bile acids and by a decreased synthesis of bile acids.

Adolescent↗

[Psychiatric comorbidity and psychosocial markers in patients before heart, liver or lung transplantation].

Organ transplant operations are regularly carried out in Switzerland at 6 transplantation centres. Between January 1995 and October 1996, 119 patients at Zurich University Hospital completed a semistructured psychiatric interview and the Transplant Evaluation Rating Scale (TERS). Inclusion criteria comprised all indications for organ transplant. Diagnostic evaluation was according to ICD-10. Of the 44 women and 75 men (mean age 40.2 years), 48 required a heart transplantation (HTPL), 37 a liver transplantation (LETPL), and 34 lung transplantation (LUTPL). 39 patients (32.8%) had one, and 15 (12.6%) 2 current psychiatric disorders. 65 of the 119 patients (54.6%) were without a current psychiatric disorder. The candidates for lung transplantation were the most psychologically healthy (68% had no psychiatric disorder). Approximately half of the heart and liver patients had at least one psychiatric disorder. The LETPL group had the highest prevalence of psychiatric comorbidity, with organic brain disorders present in a third of the patients. A quarter of all patients had stress disorders, panic disorder or a somatoform disorder. Full criteria for an affective disorder were not met by any patient. 61% enjoyed good to excellent family and social support, 29% had an unresolved conflict, and 11% had strong conflicts. Earlier coping behaviour appeared to be good to excellent in 57%, sufficient in 37%, and poor in 6%. Estimated compliance rate was found to be complete in 87%, partial or involving problems in 12% and unsatisfactory in 1%. We conclude that in transplant candidates psychiatric disorders and psychosocial problems are frequent and must be considered regularly during evaluation and the transplantation process. The results of this analysis and 3 case examples and the results of the study show the clinical importance of a detailed psychiatric and psychosocial examination as part of the evaluation of patients about to undergo life-saving organ transplant operations.

Adaptation, Psychological↗

Information theoretical concepts in clinical chemistry: the use of spreadsheet programs for convenient calculation of information theoretical quantities.

Information theoretical concepts can be used as most valuable tools for evaluating clinical chemical tests. They offer several advantages over the conventional test evaluation by Bayesian concepts. Although long known, information theory has failed to gain widespread acceptance among clinical chemists, probably due to the rather laborious computation of the necessary quantities. To resolve this technical problem, this paper demonstrates how commonly available computer spreadsheet programs can assist in the computation of information theoretical quantities such as the diverse entropies and the information content. Two spreadsheet versions are presented: firstly, a working sheet is developed for information theoretical evaluation of a two-by-two contingency table corresponding to a dichotomous diagnostic problem (e.g., diseased versus non-diseased) and a dichotomous diagnostic test outcome (e.g., normal versus abnormal), and secondly, a working sheet is shown for a more general situation with up to ten diagnostic alternatives and up to ten possible test outcomes. Typical examples for application of these tools are demonstrated.

Chemistry, Clinical↗

Ca2+-triggered peptide secretion in single cells imaged with green fluorescent protein and evanescent-wave microscopy.

Green fluorescent protein fused to human chromogranin B or neuropeptide Y was expressed in PC12 cells and caused bright, punctate fluorescence. The fluorescent points colocalized with the endogenous secretory granule marker dopamine beta-hydroxylase. Stimulation of live PC12 cells with elevated [K+], or of permeabilized PC12 cells with Ca2+, led to Ca2+-dependent loss of fluorescence from neurites. Ca2+ stimulated secretion of both fusion proteins equally well. In living cells, single fluorescent granules were imaged by evanescent-wave fluorescence microscopy. Granules were seen to migrate; to stop, as if trapped by plasmalemmal docking sites; and then to disappear abruptly, as if through exocytosis. Evidently, GFP fused to secreted peptides is a fluorescent marker for dense-core secretory granules and may be used for time-resolved microscopy of single granules.

Animals↗

How can we measure bone quality?

Osteoporosis is a systematic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue. This leads to diminished biomechanical competence of the skeleton and is associated with low-trauma or atraumatic fractures. In the past decade, considerable progress has been made in the development of methods for assessing the skeleton non-invasively, so that osteoporosis can be better managed. While dual X-ray absorptiometry (DXA) is still the preferred methodology, several limitations will be addressed. Another densitometric technique which is widely accepted for diagnosis of spinal osteoporosis is single energy QCT. Measurements of vertebral trabecular bone mineral density (BMD) demonstrate larger percentage decrements between vertebrally-fractured subjects and normal controls, and confer higher relative risks for vertebral fracture than either anteroposterior or lateral DXA measurements. As an emerging alternative to photon absorptiometry techniques, there is a growing interest in the use of quantitative ultrasound (QUS) measurements for the non-invasive assessment of osteoporotic fracture risk in the management of osteoporosis. The attractiveness of QUS lies in the fact that indirect and in vitro experience has suggested that ultrasound may give information not only about BMD but also about architecture and elasticity. Whether or not combining QUS and DXA improve fracture prediction is still unclear and needs further analysis. Due to the growing evidence supporting the use of QUS in osteoporosis and the large number of QUS devices already on the market, a general clinical consensus on the application of QUS is urgently needed. Other techniques that are less widely used for the management of osteoporosis. For example, peripheral quantitative computed tomography, quantitative magnetic resonance (QMR) and magnetic resonance microscopy are promising tools for the evaluation of the skeleton. For example, the ability of QMR and high resolution magnetic resonance imaging has been explored and shows promise as a technique for assessing trabecular bone structure in osteoporosis.

Absorptiometry, Photon↗

Using the hospital emergency department as a regular source of care.

OBJECTIVES: to evaluate the proportion of the patients who report the emergency department as their regular source of care and to describe the demographics and health status of this population. DESIGN: A cross-sectional study was performed at the emergency department in two hospitals (around 12,000 visits per year each). Subjects were interviewed using a standardised questionnaire, before and after the emergency department visit. SETTING: The medical emergency department of two university hospitals, one in Paris and one in Besançon (France). SUBJECTS: Each patient aged 15 and more attending the emergency department for a visit during forty randomly selected periods of 12 hours was included. MAIN OUTCOME MEASURES: Self report of the utilization of the emergency department as a regular source of care. RESULTS: Fourteen percent of the patients cited the emergency department as a regular source of care in Paris, and 3.3% in Besançon. In Paris, young age, being born outside of France, homelessness or precarious housing, lack of social support in case of illness and lack of health insurance were independently associated with this health care utilization behavior. CONCLUSIONS: From a public health point of view, the patients reported to use the emergency department as a primary health care structure should not be considered as 'inappropriate' or 'abusers'. Specific health needs have been found, which would require some continuity of care, a task for which the emergency department is not organised nowadays.

Adolescent↗

Perioperative myocardial cell injury: the role of troponins.

Early recognition of minor myocardial cell injury and appropriate treatment may prevent development of myocardial infarction as one of the most severe postoperative cardiac complications. Troponins have been shown to be sensitive biochemical markers for the assessment of myocardial cell injury. We investigated prospectively 67 cardiac risk patients undergoing elective non-cardiac surgery. Troponin T (TNT) concentrations were measured during the perioperative period, and in those patients with increased TNT (cut-off 0.2 ng ml-1), troponin I (TNI) concentrations were measured additionally (cut-off 0.6 ng ml-1). Patients were allocated to one of three groups: group I, all patients with normal TNT concentrations had a good cardiac outcome (80.5%). In those patients with increased TNT concentrations (19.5%) TNI was also positive; group II, patients (8.8%) with only slightly increased TNT concentrations (0.32-0.99 ng ml-1) also had a good outcome, indicating minor myocardial cell injury, whereas patients with cardiac complications (11.9%) had higher TNT concentrations (0.47-9.8 ng ml-1) (P < 0.05) (group III). With a TNT cut-off at 0.2 ng ml-1, the positive predictive value for adverse outcome was 61.5%; the negative predictive value was 100%. With a TNT cut-off at 0.6 ng ml-1, the positive predictive value for adverse outcome increased to 87.5%, but the negative predictive value was still high (98%). Most of the patients showed an increase in TNT content from the day of surgery until the third postoperative day. We conclude that serial troponin measurements during the perioperative period identify pre-, intra- and postoperative myocardial cell injury. The concentration of troponin T may reflect the degree of injury and help categorize the subsequent risk.

Aged↗