Search PubMed⌕ Search

Biomedical subjects

S Hahn

Publications and source records attributed to S Hahn.

At least 19 recordsLinked to original sources
PubMed2002

Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study.

OBJECTIVES: The National Institute of Child Health and Human Development Fetal Cell Isolation Study (NIFTY) is a prospective, multicenter clinical project to develop non-invasive methods of prenatal diagnosis. The initial objective was to assess the utility of fetal cells in the peripheral blood of pregnant women to diagnose or screen for fetal chromosome abnormalities. METHODS: Results of fluorescence in situ hybridization (FISH) analysis on interphase nuclei of fetal cells recovered from maternal blood were compared to metaphase karyotypes of fetal cells obtained by amniocentesis or chorionic villus sampling (CVS). After the first 5 years of the study we performed a planned analysis of the data. We report here the data from 2744 fully processed pre-procedural blood samples; 1292 samples were from women carrying singleton male fetuses. RESULTS: Target cell recovery and fetal cell detection were better using magnetic-based separation systems (MACS) than with flow-sorting (FACS). Blinded FISH assessment of samples from women carrying singleton male fetuses found at least one cell with an X and Y signal in 41.4% of cases (95% CI: 37.4%, 45.5%). The false-positive rate of gender detection was 11.1% (95% CI: 6.1,16.1%). This was higher than expected due to the use of indirectly labeled FISH probes in one center. The detection rate of finding at least one aneuploid cell in cases of fetal aneuploidy was 74.4% (95% CI: 76.0%, 99.0%), with a false-positive rate estimated to be between 0.6% and 4.1%. CONCLUSIONS: The sensitivity of aneuploidy detection using fetal cell analysis from maternal blood is comparable to single marker prenatal serum screening, but technological advances are needed before fetal cell analysis has clinical application as part of a multiple marker method for non-invasive prenatal screening. The limitations of the present study, i.e. multiple processing protocols, are being addressed in the ongoing study.

Adult↗
PubMed2002

[Cerebral MRI and evoked potentials in Wilson disease. Comparison of findings in patients with neurological follow-up].

Wilson's disease is caused by toxic copper accumulation, which leads predominantly to hepatic and basal ganglia damage. Characteristic findings in MRI and electrophysiologic examinations are described according to the occurrence of neurological symptoms. In the present study, 28 patients suffering from Wilson's disease (neurological type) were investigated. The results of MRI are compared with abnormalities of evoked potentials (BAEP, MSEP, T-VEP, MEP). All patients show hypodensities in the basal ganglial area (putamen and GI. pallidus) regularly combined with atrophy of the cerebrum and cerebellum in MRI. Signal abnormalities in the mesencephalic region (46% occurrence) and Nc. dentatus (36% occurrence) are combined with the other findings in variable patterns. Only slight changes are found in the pontine region. BAEP are disturbed in 71% of all cases and MSEP in 46%. Combined abnormalities of BAEP and MSEP were found in 39%. Pathological values occurred with a lower frequency in T-VEP (36%) and MEP (39%). The comparison of MRI findings with electrophysiological data done separately for each patient reveals no strong correlation between both methods. Individual MRI findings do not correspond with the patterns of disturbed evoked potentials and vice versa. Therefore we conclude that these methods, MRI and electrophysiological evaluation, supplement each other. Magnetic resonance imaging and electrophysiological evaluation should be performed simultaneously for therapy monitoring.

Adult↗
PubMed2002

[Basic principles of successful implantation of the SB Charité model LINK intervertebral disk endoprosthesis].

The scope of the LINK SB Charité Artificial Disc is to replace degeneratively changed, symptomatic intervertebral discs and to restitute the fundamental functions of the lumbar mobile segment. Biomechanical static- and dynamic test results as well as postoperative controls of a patient-group with uniform indications are presented. The options of an intervertebral disc replacement with the SB Charité Artificial Disc are discussed. For the evaluation of segmental stability, comparative static examinations of the range of motion of cadaveric lumbar segments prior to and after the implantation of the artificial disc were carried out. The stress-dependent mechanical response to directional static load on implanted SB Charité Discs in neutral position, extension and flexion was examined under different testing-conditions in order to gain results on changes of surfaces, durability and sustain of functionality. Restitutable changes to the UHMWPE sliding core, prognosed definite deformations of the sliding core after 5 and 10 years, and the functionality of the UHMWPE sliding cores after stress were examined using dynamic compression tests. Our clinical results refer to 20 patients, who received a mono- (n = 14) or bisegmental (n = 6) implantation of a SB Charité Artificial Disc following a postnucleotomy-syndrome. Comparison of the ranges of motion in cadaveric segments with and without a SB Charité Artificial Disc reflected a significantly higher mobility in cases with an implanted prosthesis only in axial rotation. Other movements showed similar ranges of motion in native segments and in segments with prosthesis. The UHMWPE sliding cores showed tolerable changes during maximal static compression in neutral position and extension. The 7.5 mm sliding cores showed changes beyond normal deformations on compression in maximal flexion. None the less it may be concluded that in vivo these sliding cores also retain their mechanical integrity. Most of the 7.5 mm and 9.5 mm high sliding cores showed a regeneration of 50% compared to maximal deformation. All the tested UHMWPE sliding cores reflected continued articulation despite plastic deformation. Predictions for a period of 5 and 10 years state that extreme loads of 4.5 kN would lead to a reduction in the height of the sliding cores of less than 8%. There was no failure of the sliding cores due to delamination or extreme coldflow. The Oswestry-Score amounted to 24% (0-56) in the postoperative controls 46 months (6 months-13 years) postoperatively. In pain analysis 5 patients (25%) were pain free, 14 patients (70%) reported a pain reduction and 1 patient (5%) had no pain relief compared to preoperatively. 15 (83%) of 18 patients had no leg pain anymore after implantation of the SB Charité Artificial Disc. 14 (93%) of 15 patients had a negative leg raising test. 2 of 5 patients recovered from their motor symptoms. The segmental saggital total range of motion was 6.8 degrees (0-20) and in cases of bisegmental implantation 5.8 degrees (0-14) in the second disc segment. Those neighboring segments with the best function showed a range of motion of 6.8 degrees (2-15). The stated general and specific complications (n = 9) had a definite influence on the results of the postoperative control in one patient and a questionable influence in another patient. Based on biomechanical static and dynamic testing, the SB Charité Artificial Disc is suited to replace the fundamental functions of the lumbar intervertebral disc. Patients suffering from a postnucleotomy-syndrome can be rendered pain free with the implantation of this prosthesis.

Adult↗
PubMed2002

Investigation of within-study selective reporting in clinical research: follow-up of applications submitted to a local research ethics committee.

RATIONALE, AIMS AND OBJECTIVES: Within-study selective reporting is widely believed to exist, although to date there have been no empirical studies to assess the extent of the problem in clinical research. The present study aimed to examine this process. METHODS: We undertook a pilot study, involving a single local research ethics committee (LREC), in which we compared the outcomes, analysis and sample size proposed in the original approved study protocol with the results presented in the subsequent study report. RESULTS: We received 41 (73%) replies from lead researchers of 56 projects, which were a complete cohort of clinical research applications approved in a particular time period by the LREC. Fifteen of these projects, which were completed and published at the time of our study, were further investigated. Only six (40%) stated which outcome variables were of primary interest and four (67%) of these showed consistency in the reports. Eight (53%) of the 15 studies mentioned an analysis plan. However, seven (88%) of these eight studies did not follow their prescribed analysis plan: the analysis of outcome variables or associations between certain variables were found to be missing from the report. CONCLUSIONS: Our pilot study has shown that within-study selective reporting may be examined qualitatively by comparing the study report with the study protocol. Our results suggest that it might well be substantial; however, the bias can only be broadly identified as protocols are not sufficiently precise.

Data Interpretation, Statistical↗
PubMed2001

Transvenous biventricular defibrillation halves energy requirements in patients.

BACKGROUND: Defibrillation thresholds (DFT) with standard implantable cardioverter-defibrillator leads in the right ventricle (RV) may be determined by weak shock field intensity in the myocardium of the left ventricle (LV). Adding a shocking electrode in a coronary vein on the middle of the LV free wall, thereby establishing biventricular defibrillation, substantially reduced defibrillation requirements in animals. We investigated the feasibility of this approach in 24 patients receiving an implantable cardioverter-defibrillator using a prototype over-the-wire temporary LV defibrillation lead. METHODS AND RESULTS: The LV lead was inserted through the coronary sinus, using a guide catheter and guidewire, into a posterior or lateral coronary vein whose location was determined by retrograde venography. Paired DFT testing compared a standard system (RV to superior vena cava plus can emulator [SVC+Can], 60% tilt biphasic shock) to a system including the LV lead. The biventricular system was tested with a dual-shock waveform (20% tilt monophasic shock from LV-->SVC+Can, then 60% tilt biphasic shock from RV-->SVC+Can). Twenty patients completed DFT testing. Venography and LV lead insertion time was 46+/-40 minutes. The biventricular system reduced mean DFT by 45% (8.9+/-1.1 J versus 4.9+/-0.5 J, P<0.001). Twelve patients (60%) had a standard system DFT >/=8 J, and the biventricular system gave a lower DFT in all patients. There were no adverse events related to the use of the LV lead, which was removed after testing. CONCLUSIONS: Internal defibrillation using a transvenously inserted LV lead is feasible, produces significantly lower DFTs, and seems safe under the conditions tested. Biventricular defibrillation may be a useful option for reducing DFTs or could be added to an LV pacing lead for heart failure.

Coronary Angiography↗
PubMed2001

Investigation of coronary venous anatomy by retrograde venography in patients with malignant ventricular tachycardia.

BACKGROUND: The coronary venous system is increasingly used for left ventricular or biventricular pacing in patients with severe heart failure. The present study investigated the structure of the coronary veins in patients presenting with structural heart disease and malignant ventricular tachyarrhythmias. The availability of veins for possible lead placement was assessed. METHODS AND RESULTS: The number, relative size, and location of coronary veins were evaluated by retrograde venography in 129 patients undergoing cardioverter-defibrillator implantation. Detailed x-ray image analysis was performed in 86 patients, for whom optimal coronary sinus occlusion and vein visualization was achieved. The anterior interventricular vein and the middle cardiac vein were visible in 85 (99%) of 86 patients and in 86 (100%) of 86 patients, respectively. Between these 2 veins, at least 1 additional prominent vein was visible in 85 (99%) of 86 patients. Just 1 vein was present in 44 (51%) of 86 patients. Two veins were observed in 40 (46%) of 86 patients, and >2 veins were visualized in 2 (2%) of 86 patients. Venous anatomy allowed positioning of a 0.014-in guidewire in a coronary vein in 115 (93%) of 124 patients. CONCLUSIONS: The presence, diameter, angulation, and tortuosity of veins as visualized by retrograde venography determine their acceptability for the placement of a lead in a predetermined location. Despite the considerable variability of the coronary venous system among patients, a lateral vessel for lead introduction was available in 82%, and a posterior or lateral vessel was available in 99% of individuals within a patient population that could potentially benefit from a lead on the left ventricle.

Aged↗
PubMed2001

Reduced osmolarity oral rehydration solution for treating dehydration due to diarrhoea in children: systematic review.

OBJECTIVES: To compare reduced osmolarity oral rehydration solution with standard World Health Organization oral rehydration solution in children with acute diarrhoea. DESIGN: Systematic review of randomised controlled trials. STUDIES: 15 randomised controlled trials including 2397 randomised patients. OUTCOMES: The primary outcome was unscheduled intravenous infusion; secondary outcomes were stool output, vomiting, and hyponatraemia. RESULTS: In a meta-analysis of nine trials for the primary outcome, reduced osmolarity rehydration solution was associated with fewer unscheduled intravenous infusions compared with standard WHO rehydration solution (odds ratio 0.61, 95% confidence interval 0.47 to 0.81). Three trials reported that no patients required unscheduled intravenous infusion. Trials reporting secondary outcomes suggested that in the reduced osmolarity rehydration solution group, stool output was lower (standardised mean difference in the log scale -0.214 (95% confidence interval -0.305 to -0.123; 13 trials) and vomiting was less frequent (odds ratio 0.71, 0.55 to 0.92; six trials). Six trials sought presence of hyponatraemia, with events in three studies, but no significant difference between the two arms. CONCLUSION: In children admitted to hospital with dehydration associated with diarrhoea, reduced osmolarity rehydration solution is associated with reduced need for unscheduled intravenous infusions, lower stool volume, and less vomiting compared with standard WHO rehydration solution.

Administration, Oral↗
PubMed2001

The neural correlates of driving.

We studied 12 healthy subjects with fMRI while they performed a driving simulation task. In the active condition they steered the car themselves (driving), in the passive condition a person from outside the scanner was steering the car (passive driving). Common activations in both conditions were found in occipital and parietal regions bilaterally. Activity specifically associated with driving was found only in the sensorimotor cortex and the cerebellum. Compared to passive driving, activity during driving was reduced in numerous brain regions including MT/MST. It is concluded that simulated driving requires mainly perceptual-motor integration and that the limited cognitive capacity model of driving has to be revised.

Adult↗
PubMed2001

Yeast nuclear extract contains two major forms of RNA polymerase II mediator complexes.

The yeast Mediator complex is required for transcription by RNA polymerase II (pol II) in vivo and in vitro. This complex of over 20 polypeptides associates with pol II and is recruited to transcription complexes at promoters. Previous isolations of yeast Mediator-containing complexes in different laboratories have identified several distinct complexes. To identify the major forms of Mediator in yeast, Mediator was isolated from nuclear extracts using a two-step chromatographic procedure, avoiding ion exchange chromatography and high salt conditions to prevent dissociation of subunits during purification. Components of the Mediator complexes were identified by mass spectrometry and Western analysis. The major form of Mediator, termed pol II x Med, contained pol II and Mediator, including the Srb8-11 module. A second lower molecular size complex was also identified, termed Mediator core (Medc), which lacked pol II, Srb8-11, Rox3, Nut1, and the Rgrl module. Both of these complexes were active in transcription in vitro, although the Medc complex had significantly lower activity and could compete with the activity of the pol II x Med complex in vitro.

Animals↗
PubMed2001

Correlation between genotype and phenotype in Korean patients with spinal muscular atrophy.

The goal of this study was to define the correlation between genotype and phenotype in Korean patients with spinal muscular atrophy (SMA). The SMA can be classified into three groups based on the age of onset and the clinical course. The candidate genes, survival motor neuron (SMN) gene, neuronal apoptosis inhibitory protein (NAIP) gene, and p44 gene were mapped and duplicated with telomeric and centromeric. The loss of the telomeric SMN occurs by a different mechanism. That is the deletion or conversion of telomeric SMN to centromeric SMN, in which case the conversion could produce a mild phenotype and deletion could produce a severe one. It has been known that there may be a balance between the numbers of copies expressed by the centromeric and telomeric SMN genes. In our study, ten patients with type I SMA and two type II patients were identified by their clinical findings and DNA studies. The major deletion of SMA candidate genes, deletion of the SMN gene, NAIP gene, and p44 gene were identified in six patients with type I SMA, while the rest of type I and all the type II patients showed the deletion of the SMN gene only. Allele numbers of the C212 marker were compared in patients and normal controls in order to find the correlation between the copy numbers and the clinical severity. The result was that type I patients had 2-5 alleles and the normal controls had 4-6. This suggests that the deletion is a major determining factor in the clinical phenotype. However, two type I patients with telomeric NAIP gene deletion notably had 4-5 alleles, as in the normal controls. This result implies that the correlation between the copy numbers and the severity is uncertain as opposed to the previous hypothesis. One type I patient showed the conversion of the centromeric SMN gene to the telomeric, which supports the conclusion that gene conversion is an important molecular mechanism for SMA. In the study of one hundred normal newborns, two physically normal newborns showed deletion of the centromeric SMN gene, suggesting frequent rearrangement in the locus.

Child↗
PubMed2001

Risk free simultaneous prenatal identification of fetal Rhesus D status and sex by multiplex real-time PCR using cell free fetal DNA in maternal plasma.

QUESTIONS UNDER STUDY: Pregnancies with a Rhesus constellation still present a considerable obstetric problem. In addition, pregnancies with male Rhesus D fetuses are more severely affected by haemolytic disease of the newborn, requiring more transfusions in utero and having a three fold higher mortality than female Rhesus D fetuses. Furthermore, almost 150 X-linked genetic deficiencies have now been characterised, increasing the need for prenatal sex determination in pregnancies at risk for such a disorder. In order examine these two important fetal loci in a risk free manner, we have developed a novel multiplex real-time PCR assay for the analysis of extracellular fetal DNA in maternal plasma. METHODS: Cell free DNA was isolated from 34 maternal plasma samples and examined by a multiplex real-time PCR assay for the Rhesus D gene and the SRY locus on the Y chromosome. RESULTS: Our study showed that we were able to genotype 12/13 Rhesus D males correctly. All 5 Rhesus d males were correctly identified. In addition a 100% concordance was found in the 16 samples obtained from pregnancies with female Rhesus D or Rhesus d fetuses. CONCLUSIONS: By developing a novel multiplex real-time PCR assay we present the first report describing the determination of multiple fetal loci from cell free DNA in maternal plasma by these means. As this assay is suitable for automation, our data, therefore, suggest that such assays provide a good basis for the clinical examination of multiple fetal loci, in particular Rhesus D status or fetal sex, and can be performed effectively using real-time multiplex PCR assays.

DNA↗
PubMed2001

Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children.

BACKGROUND: Oral rehydration solution (ORS) has reduced childhood deaths from diarrhoea in many countries. Recent studies suggest that the currently recommended formulation of ORS recommended by the World Health Organization (WHO) may not be optimal, and solutions that contain lower concentrations of sodium and glucose may be more effective. OBJECTIVES: In children with acute diarrhoea, to compare reduced osmolarity glucose-based oral rehydration salt solution with international WHO formulation. SEARCH STRATEGY: The Cochrane Collaboration Trials Register, MEDLINE, and EMBASE were searched. Additional trials were identified by hand searching. Content experts were contacted. SELECTION CRITERIA: Randomised controlled trials comparing reduced osmolarity ORS solution with the WHO formulation. Outcomes sought were unscheduled intravenous fluid infusion therapy and measures of clinical illness. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers. We tested for heterogeneity using the chi-square statistic, conducted sensitivity analysis by allocation concealment, and the regression approach to assess funnel plot asymmetry from selective trial publication. MAIN RESULTS: The primary outcome was reported in 12 trials. In a meta-analysis of nine trials, reduced osmolarity ORS was associated with fewer unscheduled infusions compared with standard WHO ORS (Mantel Haenzel odds ratio 0.61, 95% confidence interval 0.47 to 0.81) with no evidence for heterogeneity between trials. No unscheduled intravenous fluid infusion therapy was required in any participant in three trials. Thirteen trials reported stool output, and data suggested less stool output in the reduced osmolarity ORS group. Vomiting was less frequent in the reduced osmolarity group in the six trials reporting this. Six trials sought hyponatraemia, with events in three studies, but no obvious difference between the two arms. REVIEWER'S CONCLUSIONS: In children admitted to hospital with diarrhoea, reduced osmolarity ORS when compared to WHO ORS is associated with fewer unscheduled intravenous infusions, smaller stool volume post randomisation, and less vomiting. No additional risk of developing hyponatraemia when compared with WHO ORS was detected.

Bicarbonates↗
PubMed2001

Changing clinical course of patients with malignant mesothelioma: implications for FNA cytology and utility of immunocytochemical staining.

The diagnosis of both local recurrences and distant metastases of mesothelioma can be accomplished by fine-needle aspiration (FNA) biopsy. Although the previous history of mesothelioma provides strong support for recurrent/metastatic mesothelioma, other diagnostic possibilities (particularly adenocarcinoma) may require exclusion via special stains in some cases. In this study, we report on the morphologic findings in 13 cases of mesothelioma which underwent FNA (7 metastatic lesions, 6 local recurrences). In addition, immunohistochemical staining results for 7 cases with available material using antibodies directed against cytokeratin AE 1/3 and two antibodies reported to show consistently positive results in mesothelioma (calretinin and cytokeratin 5/6) are reported and compared to results seen for 10 cases of adenocarcinoma. All cases of mesothelioma and adenocarcinoma showed strong staining with cytokeratin AE 1/3. Three of 7 cases of mesothelioma showed strong staining with calretinin, while only focal staining was detected in 3 additional cases; only one case showed positive staining with cytokeratin 5/6. One of 10 cases of adenocarcinoma showed calretinin positivity; however, at least focal staining with cytokeratin 5/6 was seen in 4 cases. These results suggest that cytokeratin 5/6 is neither a sensitive nor specific stain for the diagnosis of mesothelioma in cytology material. Calretinin appears to be more specific for mesothelioma but showed disappointing sensitivity for this tumor, potentially limiting its diagnostic utility in FNA material.

Aged↗
PubMed2001

Identification of four novel mutations in classical Menkes disease and successful prenatal DNA diagnosis.

Menkes disease is an X-linked recessive disorder of the copper metabolism and affected males suffer a systemic copper deficiency due to malabsorption and defective distribution of dietary copper. It is caused by a defect in the Menkes (ATP7A) gene, which encodes a transmembrane copper-transporting P-type ATPase. A variety of mutations were reported; however, only a few mutations were reported in Asian patients. We identified four novel mutations and one known mutation in five Korean patients. Arg646Ter in exon 8, a novel mutation transmitted from his carrier mother, was identified in one patient. Prenatal DNA diagnosis on an unaffected fetus in this carrier mother was successfully accomplished. An additional three novel mutations, Leu706Arg in exon 9, Gly1118Asp in exon 17, and Gly1255Arg in exon 19, were identified. Splicing mutation was not identified. Menkes disease in Korean patients appears to be caused by heterogeneous mutations with different spectrums from Caucasian patients.

Adenosine Triphosphatases↗