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Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 19 recordsLinked to original sources

The Attitudes to Ageing Questionnaire (AAQ): development and psychometric properties.

OBJECTIVE: This paper describes the development of the Attitudes to Ageing Questionnaire (AAQ) which is a self-report measure with which older people themselves can express their attitudes to the process of ageing. METHOD: The development of the AAQ followed a coherent, logical and empirical process taking full account of relevant gerontological knowledge and modern and classical psychometric analytical methods. Pilot testing with 1,356 participants from 15 centres worldwide refined the scale and provided the basis for a field test. A total of 5,566 participants from 20 centres worldwide contributed to the further development of this new scale with the derivation involving both classical and modern psychometric methods. RESULTS: The result is a 24-item cross-cultural attitudes to ageing questionnaire consisting of a three-factor model encompassing psychological growth, psychosocial loss, and physical change. The three-factor model suggests a way of conceptualizing and measuring successful ageing in individuals. CONCLUSIONS: The AAQ provides researchers, clinicians and policy makers with a unique scale to measure the impact of successful ageing interventions. It also provides a vehicle for the measurement of how individuals age across cultures and under different economic, political and social circumstances.

Aged↗

Double inversion recovery brain imaging at 3T: diagnostic value in the detection of multiple sclerosis lesions.

BACKGROUND AND PURPOSE: To prospectively determine the sensitivity in the detection of multiple sclerosis (MS) lesions by using double inversion recovery (DIR), fluid-attenuated inversion recovery (FLAIR), and T2-weighted turbo spin-echo (T2 TSE) MR imaging at 3T. METHODS: Seventeen patients presenting with a clinically isolated syndrome (CIS) suggestive of MS, 9 patients with definite MS, and 6 healthy control subjects were included. Imaging was performed on a 3T MR system using DIR, FLAIR, and T2 TSE sequences. Lesions were counted and classified according to 5 anatomic regions: infratentorial, periventricular, deep white matter, juxtacortical, and mixed white matter-gray matter. The sensitivity at DIR was compared with the corresponding sensitivity at FLAIR and T2 TSE sequence. The contrast between lesions and normal-appearing gray matter, normal-appearing white matter, and CSF was determined for all sequences. RESULTS: Because of higher lesion-white matter contrast, the DIR showed a higher number of lesions compared with the FLAIR (7% gain, P = 0.04) and the T2 TSE (15% gain, P = 0.01). The higher sensitivity was also significant for the infratentorial region compared with the FLAIR (56% gain, P = 0.02) and the T2 TSE (44% gain, P = 0.02). Compared with the FLAIR, no significant changes of the lesion load measurements were observed in the supratentorial brain: slightly higher numbers of periventricular and mixed gray matter-white matter lesions on the DIR were counterbalanced by a slightly reduced sensitivity regarding juxtacortical lesions. CONCLUSION: DIR brain imaging at 3T provides the highest sensitivity in the detection of MS lesions especially in the infratentorial region.

Adult↗

The major population of PHA-stimulated PBMC infected by R5 or X4 HIV variants after a single cycle of infection is predominantly composed of CD45RO+CD4+ T lymphocytes.

PHA-stimulated peripheral blood mononuclear cells (PBMCs) are widely used for investigating replication and neutralization of HIV primary isolates in vitro. The objective of this study was to identify the T lymphocyte subset(s) that are found infected after one replication cycle by either R5- or X4-HIV-1 variants in PHA-stimulated PBMCs from healthy donors. Infected T lymphocytes were detected by intracellular p24 staining and characterized by cell surface immunophenotyping using flow cytometry. The predominant lymphocyte subset expressing p24 after 24 h of infection with either R5 or X4 HIV-1 strains was found to exhibit mainly the memory CD45RO phenotype, a greater percentage of CD62L(+)CD45RO(+) central memory T lymphocytes was infected with X4 HIV strains. Although some CD45RA(+) lymphocytes were also infected, these cells co-expressed CD45RO(+). The proportion of lymphocytes expressing CD4 and CD4/CD45RO decreased by 20% after 24 h of infection. A 2-fold decrease of CD4(+)CD8(+) T lymphocytes could also be recorded, even though this subset accounted for less than 5% of total lymphocytes in control cultures. Moreover, CD4(+)CD8(+) T cells further decreased by 90% after 4 days of infection, a time at which they scored p24(+). Therefore, our results indicate that the in vitro infection system of PHA-stimulated PBMC utilized in neutralization assays provides an appropriate model for the study of infected CD45RO(+) lymphocytes but not CD45RA(+) lymphocytes.

CD4-Positive T-Lymphocytes↗

Telemetric monitoring of tracheal pressure after tracheal occlusion for treatment of severe congenital diaphragmatic hernia.

INTRODUCTION: Prenatal tracheal occlusion using endoscopic techniques obstructs the normal egress of lung fluid during pulmonary development and stimulates lung growth in cases of congenital diaphragmatic hernia (CDH). Although FETO might be an effective strategy for treatment of CDH, the mechanism especially due to the supposed increasing transpulmonary pressure is unknown. OBJECTIVE: The purpose of this study was to monitor the pressure below the attached balloon in the fetal lamb telemetrically. METHODS: Four time-dated pregnant Merino ewes underwent fetal and maternal surgery. A special prepared silicone catheter was placed below the epiglottis by laryngoscopy on day 110 or 140 of gestation. The tracheal pressure below the fixed catheter could be monitored telemetrically using the Data Sciences TA11-PA-C40 pressure device. Hundred and twenty measurement points were recorded over a period of 2 min. RESULTS: A maximum of lung pressure rate was found immediately after implantation (23.7 +/- 4.6 mm Hg). During the first hour, the pressure decreased to an average value of 16.9 mmHg. About 70 h after the block, this value decreased to a minimum level of 8.3 +/- 0.4 mmHg. CONCLUSION: Decreasing pressure variation might indicate that lung growth has stopped and that the ideal point of time to remove the balloon is achieved. Increasing pressure has to be related to the morphometric analysis of the lung's structural development and maturation, comparing the efficacy of FETO in preventing or reversing pulmonary hypoplasia. Further investigation of continuous telemetric monitoring of tracheal pressure in the fetal lamb is required.

Animals↗

Choledocholithiasis: repetitive thick-slab single-shot projection magnetic resonance cholangiopancreaticography versus endoscopic ultrasonography.

This prospective study compares repetitive thick-slab single-shot projection magnetic resonance cholangiopancreatography (MRCP) with endoscopic ultrasonography (EUS) for the detection of choledocholithiasis. Fifty-seven consecutive patients (36 women, mean age 61) referred for suspected choledocholithiasis underwent MRCP, followed by EUS. Each procedure was performed by different operators blinded to the results of the other investigation. MR technique included a turbo spin-echo T2-weighted axial sequence with selective fat saturation (SPIR/TSE, TE=70 ms, TR=1,600 ms), followed by coronal dynamic MRCP. The same thick-slab slice was sequentially acquired 12 times as breath-hold single-shot projection imaging (SSh, TE=900 ms, TE=8,000 ms) centred on the common bile duct (CBD). Two experienced radiologists independently and blindly evaluated MR images for the detection of CBD stones. Their inter-observer agreement kappa was determined. Secondly, the two observers read MR images in consensus again. CBD stones were demonstrated in 18 out of 57 patients (31.6 %) and confirmed by endoscopic retrograde cholangiography (ERCP, n=17) or intraoperative cholangiography (n=1). Clinical follow-up served as the "gold standard" in patients with negative results without following invasive procedure (n=28). Sensitivity, specificity, accuracy, positive and negative predictive value for MRCP resulting from consensus reading were 94.9%, 94.4%, 94.7%, 97.4% and 89.5%, respectively. Corresponding values of EUS were 97.4%, 94.4%, 96.5%, 97.4% and 94.4%. Inter-observer agreement kappa was 0.81. Repetitive thick-slab single-shot projection MRCP is an accurate non-invasive imaging modality for suspected choledocholithiasis and should be increasingly used to select those patients who require a subsequent therapeutic procedure, namely ERCP.

Adult↗

[CT-enteroclysis].

Computed tomography enteroclysis (CTE) has become a well-defined imaging modality for the evaluation of various small bowel disorders. The large volume (2 l) of enteral contrast agent administrated via a nasojejunal catheter ensures small bowel distension. Following helical CT acquisition is completed by multiplanar views. CTE is of particular value in intermediate or advanced Crohn's disease. It has become the method of choice for small bowel tumours. The cause and degree of low-grade small bowel obstruction is more readily analyzed with the technique of CTE than conventional CT. CTE should be selectively used to answer specific questions of the small bowel. It essentially contributes to the diagnostic quality of modern small bowel imaging, and therefore deserves an established, well-defined place among the other available techniques.

Humans↗

Studies on the progress of third-molar mineralisation in a Black African population.

The forensic determination of the age of living people has become increasingly important in recent years. With regard to the relevant age group, the radiographic assessment of third-molar mineralisation is of particular importance. So far, the influence of geographic origin on the mineralisation rate has been insufficiently analysed. The paper is based on a total of 595 conventional orthopantomograms of 474 male and 121 female Black Africans aged between 10 and 26 years for whom dates of birth were known. The mineralisation status of third molars was evaluated based on Demirjian's classification of stages [Demirjian et al., 1973. A new system of dental age assessment. Hum. Biol. 45, 221-227]. This study presents the means and standard deviations, median values and the lower and upper quartiles separately for both sexes for the mineralisation stages D-H. Statistically significant differences between the upper and lower jaws were observed in males examined with regard to their attaining the stage F. Mandibular teeth developed 0.8 years earlier than maxillary teeth. Significant sex-specific differences were found with regard to the age at which tooth 38 reached the stage G. In females, tooth 38 reached stage G 1.5 years earlier than in males. In comparison to White probands, the Black African sample showed a tendency to achieve the mineralisation stages earlier. We would recommend using population-specific standards for age determination purposes.

Adolescent↗

Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis.

Discrepant findings have been reported regarding an association of the apolipoprotein E (APOE) gene with the clinical course of multiple sclerosis (MS). To resolve these discrepancies, we examined common sequence variation in six candidate genes residing in a 380-kb genomic region surrounding and including the APOE locus for an association with MS severity. We genotyped at least three polymorphisms in each of six candidate genes in 1,540 Caucasian MS families (729 single-case and multiple-case families from the United States, 811 single-case families from the UK). By applying the quantitative transmission/disequilibrium test to a recently proposed MS severity score, the only statistically significant (P=0.003) association with MS severity was found for an intronic variant in the Herpes Virus Entry Mediator-B Gene PVRL2. Additional genotyping extended the association to a 16.6 kb block spanning intron 1 to intron 2 of the gene. Sequencing of PVRL2 failed to identify variants with an obvious functional role. In conclusion, the analysis of a very large data set suggests that genetic polymorphisms in PVRL2 may influence MS severity and supports the possibility that viral factors may contribute to the clinical course of MS, consistent with previous reports.

3' Untranslated Regions↗

APOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers.

BACKGROUND: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. METHODS: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. RESULTS: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of epsilon2 or epsilon4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. CONCLUSION: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.

Alleles↗

A genetic model to investigate drug-target interactions at the ribosomal decoding site.

Recent advances in X-ray crystallography have greatly contributed to the understanding of the structural interactions between aminoglycosides and the ribosomal decoding site. Efforts to genetically probe the functional relevance of proposed drug-nucleotide contacts have in part been hampered by the presence of multiple rRNA operons in most bacteria. A derivative of the Gram-positive Mycobacterium smegmatis was rendered single rRNA operon allelic by means of gene inactivation techniques. In this system, genetic manipulation of the single chromosomal rRNA operon results in cells carrying homogeneous populations of mutant ribosomes. An exhaustive mutagenesis study of the ribosomal A site has been performed to define the importance of individual drug-nucleotide contacts. Mutational alterations in the M. smegmatis decoding site are discussed here, comparing the results with those obtained in other organisms. Implications for the selectivity of antimicrobial agents and for the fitness cost of resistance mutations are addressed.

Anti-Bacterial Agents↗

Multifactor dimensionality reduction reveals gene-gene interactions associated with multiple sclerosis susceptibility in African Americans.

Multiple sclerosis (MS) is a common disease of the central nervous system characterized by inflammation, myelin loss, gliosis, varying degrees of axonal pathology, and progressive neurological dysfunction. Multiple sclerosis exhibits many of the characteristics that distinguish complex genetic disorders including polygenic inheritance and environmental exposure risks. Here, we used a highly efficient multilocus genotyping assay representing variation in 34 genes associated with inflammatory pathways to explore gene-gene interactions and disease susceptibility in a well-characterized African-American case-control MS data set. We applied the multifactor dimensionality reduction (MDR) test to detect epistasis, and identified single-IL4R(Q576R)- and three-IL4R(Q576R), IL5RA(-80), CD14(-260)- locus association models that predict MS risk with 75-76% accuracy (P<0.01). These results demonstrate the importance of exploring both main effects and gene-gene interactions in the study of complex diseases.

Black or African American↗

Methionine metabolism and phenotypic variability in X-linked adrenoleukodystrophy.

A combined genotype of polymorphisms of methionine metabolism has been associated with CNS demyelination in methotrexate-treated patients. Within a sample of 86 patients with X-linked adrenoleukodystrophy, this genotype was overrepresented in a subgroup of 15 patients with adrenomyeloneuropathy (AMN) with CNS demyelination (adrenoleukomyeloneuropathy) in comparison to 49 AMN patients without CNS demyelination ("pure" AMN; p = 0.002), suggesting that methionine metabolism might contribute to the phenotypic variability in adrenoleukodystrophy.

Adolescent↗

Examination of seven candidate regions for multiple sclerosis: strong evidence of linkage to chromosome 1q44.

Multiple sclerosis (MS) is a debilitating neuroimmunological and neurodegenerative disease with a strong genetic component. Numerous studies have failed to consistently identify genes that confer disease susceptibility except for association with HLA-DR. Seven non-HLA regions (1q, 2q, 9q, 13q, 16q, 18p and 19q) identified in a recent genomic screen were investigated by genotyping approximately 20 single-nucleotide polymorphisms (SNPs) at approximately 1 Mb intervals. Non-parametric multipoint analyses identified a peak LOD* score of 2.99 for the 1q44 region and substantially narrowed the linkage peak to approximately 7 Mb. Ordered subset analyses (OSA) identified significant LOD score increases for 2q35 and 18p11 when ranking families by HLA-DR status and identified a significant LOD score increase in region 2q35 when ranking families by linkage to chromosome 1q44. 1q44 is particularly interesting because of linkage evidence for this region in studies of both rheumatoid arthritis and systemic lupus erythematosus.

Chromosomes, Human, Pair 1↗

[Quality of data transfer in perinatal data -- experience of a centre].

BACKGROUND: A sufficient quality of data transfer from written patient records to electronic data processing is a precondition for a reasonable usage of perinatal data. However the quality of data transfer of the almost 200 characteristics routinely recorded at each delivery is largely unknown. MATERIALS AND METHODS: The quality of data transfer of 33 characteristics in 350 randomly selected singleton deliveries of the women's clinic of the University of Marburg from 2002 and 2003 has been checked by comparing electronically recorded data with the original written documents. RESULTS: The quality of data transfer of the tested characteristics turned out to be heterogeneous. Characteristics necessary to calculate quality indicators show a very high data quality when excluding the characteristic attendance of a paediatrician. The quality of data transfer of characteristics denoting time as well as blood gas analysis are heterogeneous. Characteristics with a low quality of data transfer are associated with ambiguous instructions, the fact that the coding obstetrician is not dealing in the first instance with the item being encoded and the characteristics are of no immediate relevance for delivery, as well as difficult application of the software. CONCLUSION: The quality of data transfer of the characteristics collected in perinatal surveys needs to be validated. The type and amount of data being collected should be reassessed considering improvements of data quality.

Documentation↗

Biochemical markers of bone turnover during pregnancy: a longitudinal study.

OBJECTIVE: The objective of this study was to prospectively investigate the effect of pregnancy on biochemical markers of bone turnover in healthy pregnant women. METHODS: During the course of our longitudinal study, biochemical markers of bone remodeling were measured in all three trimester of pregnancy (first trimester: 12.5+/-1.8 SD, second trimester: 21.6+/-1 SD, third trimester: 34.8+/-1.6 SD weeks of gestation). Serum type I collagen C-telopeptides (CTX) and a crosslinked peptide of the carboxy-terminal telopeptide of type I collagen (ICTP) were used as markers of bone resorption. Bone alkaline phosphatase (BAP) and the N-terminal propeptides of type I collagen (PINP) were used as biochemical markers of bone formation. Blood samples for the analysis of all 4 biochemical markers according to each trimester of pregnancy were available in 49 patients. RESULTS: The main changes for all biochemical markers were seen between the second and the third trimester. According to the markers of bone resorption, both serum CTX and ICTP showed a significant increase from the first to the third and from the second to the third trimester (p<0.001; median percentage change: CTX=101.5% and ICTP=40%). Concerning markers of bone formation, PINP showed a significant decrease from the first to the second trimester (p=0.001) followed by a significant increase from the second to the third trimester (p<0.001, 63.8%) and an overall increase from the first to the third trimester (p<0.001). BAP also showed a significant increase from the second to the third trimester (p<0.001; 51.7%) and an overall increase from the first to the third trimester (p<0.001). CONCLUSION: Markers of bone resorption were significantly increased during pregnancy. In contrast to bone resorption, markers of bone formation showed an increase as well as a decrease during pregnancy indicating a state of high bone turnover. This might coincide with the change in bone mineral density that was observed in some, but not all, studies using "dual-energy x-ray absorptiometry" (DXA) as well as "quantitative ultrasonometry" (QUS).

Alkaline Phosphatase↗

[Evaluation of quantitative ultrasonometry of bone in singleton and multiple pregnancies].

OBJECTIVE: During pregnancy about 30 grams of calcium are transferred to a full-term neonate. The enormous demand for calcium can be regulated by compensatory mechanisms in the maternal metabolism such as elevated steroid hormone levels, increased intestinal absorption of dietary calcium, and renal conservation, but also by mobilization of calcium from the maternal skeleton. Therefore we have investigated whether a decrease in maternal bone mineral density (BMD) can be observed during pregnancy and whether it differs between singleton and twin pregnancies. METHODS: Quantitative ultrasonometry (QUS) was performed at the distal metaphysis of the phalanges (digits II - V). 54 singleton pregnancies and 6 twin pregnancies were longitudinally followed throughout pregnancy. In each trimester the amplitude-dependent speed of sound (AD-SOS) and the bone transmission time (BTT) were measured. RESULTS: In 54 singleton pregnancies significant decreases in AD-SOS of 1.9 % (p </= 0.001) and in BTT of 7.2 % (p < or = 0.001) were observed. In the corresponding twin pregnancies no significant decreases in AD-SOS (1.6 %) or BTT (6.6 %) could be detected. CONCLUSIONS: The results show that the compensatory mechanisms in maternal metabolism are not able to cover the fetal calcium demand and lead to a decrease in QUS parameters. In our pilot study due to the small number of twin pregnancies the decrease in QUS parameters did not reach statistical significance although the results seemed comparable to those of singleton pregnancies.

Bone Density↗

[Origin and significance of leptin and neuropeptide Y (NPY) in amniotic fluid between the 14th and 18th weeks of gestation].

INTRODUCTION: Leptin and neuropeptide Y (NPY) play important roles in the regulation of food intake, energy expenditure, hematopoesis and reproduction. The biological functions of leptin and NPY in fetal development, and their regulation during pregnancy by fetal and maternal factors remain poorly understood. PATIENTS AND METHODS: From 55 women undergoing diagnostic amniocentesis between the 14th and 18th weeks of gestation samples of amniotic fluid were collected. In accord with the circadian rhythm of leptin secretion all amniocenteses were performed between 8.00 and 12.00 a. m. The concentrations of leptin and NPY in amniotic fluid were analysed using commercially available RIA's. RESULTS: The amniotic fluid samples of 32 male and 23 female fetuses were determined and demonstrated no gender-dependent differences in leptin and NPY levels. No correlation was found between leptin/NPY and the maternal body mass index. NPY concentrations are lower in advanced gestational age pregnancies. Leptin levels revealed no differences with respect to gestational age. CONCLUSION: Leptin and NPY levels were independent of fetal gender and maternal BMI. This provides clues for alternative regulatory mechanisms in leptin and NPY secretion. Compared to the data of adults, our findings show high leptin concentrations in the amniotic fluid in the presence of only minor amounts of white adipose tissues which might include the placenta. Our data including the observation of lower levels of NPY in more advanced gestational age support the idea of specific factors regulating leptin and NPY secretion into the amniotic fluid.

Adult↗