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Biomedical subjects

C Kessler

Publications and source records attributed to C Kessler.

At least 19 recordsLinked to original sources
PubMed2006

Differential regulation of transport proteins in the periinfarct region following reversible middle cerebral artery occlusion in rats.

Members of various transport protein families including ATP-binding cassette transporters and solute carriers were shown to be expressed in brain capillaries, choroid plexus, astrocytes or neurons, controlling drug and metabolite distribution to and from the brain. However, data are currently very limited on how the expression of these transport systems is affected by damage to the brain such as stroke. Therefore we studied the expression of four selected transporters, P-glycoprotein (Mdr1a/b; Abcb1a/b), Mrp5 (Abcc5), Bcrp (Abcg2), and Oatp2 (Slc21a5) in a rat model for stroke. Transporter expression was analyzed by real-time polymerase chain reaction in the periinfarcted region and protein localization and cellular phenotyping were done by immunohistochemistry and confocal immunofluorescence microscopy. After stroke, P-glycoprotein staining was detected in endothelial cells of disintegrated capillaries and by day 14 in newly generated blood vessels. There was no significant difference, however, in the Mdr1a mRNA amount in the periinfarcted region compared with the contralateral site. For Bcrp, a significant mRNA up-regulation was observed from days 3-14. This up-regulation was followed by the protein as confirmed by quantitative immunohistochemistry. Oatp2, located in the vascular endothelium, was also up-regulated at day 14. For Mrp5, an up-regulation was observed in neurons in the periinfarcted region (day 14). In conclusion, after stroke the transport proteins were up-regulated with a maximum at day 14, a time point that coincides with behavioral recuperation. The study further suggests Bcrp as a pronounced marker for the regenerative process and a possible functional role of Mrp5 in surviving neurons.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Evaluation of single nucleotide polymorphisms in the phosphodiesterase 4D gene (PDE4D) and their association with ischaemic stroke in a large German cohort.

Genetic fine mapping of the first locus identified for genetically complex forms of stroke, STRK1 (which has been mapped to chromosome 5q12 in Icelandic families), has identified the phosphodiesterase 4D gene (PDE4D) gene as a good candidate gene. Association analysis of single nucleotide polymorphisms (SNPs) in the PDE4D gene in an Icelandic stroke cohort demonstrated genetic association between six SNPs in the 5' region of PDE4D and ischaemic stroke. The present study aimed to test whether the same six SNPs in PDE4D were also associated with stroke in a large stroke cohort from northern Germany (stroke patients with acute completed ischaemic stroke: n = 1181; population based controls: n = 1569). None of the six SNPs showed significant association with ischaemic stroke in the whole stroke sample before and after adjustment for conventional stroke risk factors (age, sex, hypertension, diabetes, and hypercholesterolaemia). Haplotype analysis did also not reveal any significant association. Marginally positive statistical measures of association in the subgroup with cardioembolic stroke did not remain significant after correction for multiple testing. In conclusion, this study was unable to demonstrate an association between the six SNPs which had showed significant single marker association with stroke in the Icelandic stroke cohort and ischaemic stroke in a large German cohort.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Forkhead transcription factor FOXO1A is critical for induction of human decidualization.

Experiments utilizing RNA interference technology were performed to determine whether the forkhead transcription factor FOXO1A, a member of the FOXO family of proteins, plays a critical role in the induction of human uterine decidualization. Human decidual fibroblast cells were decidualized in vitro for 6 days with medroxyprogester-one, estradiol, and dibutyryl cAMP in the presence or absence of a highly specific FOXO1A small interfering RNA (siRNA) that inhibits FOXO1A mRNA and protein expression by more than 80%. RNA and proteins were extracted from the cells at 0, 2, 4, and 6 days. FOXO1A and IGFBP-1 proteins were determined by immunoblotting; and intracellular mRNA levels for several decidualization marker genes were determined by real-time PCR. Exposure of the cells to FOXO1A siRNA in five separate experiments resulted in a 40-75% inhibition of prolactin, IGFBP-1, tissue inhibitor of metalloproteinase 3 (TIMP3), somatostatin and endometrial bleeding-associated factor (EBAF) mRNAs, all of which are markedly induced during the decidualization process. In contrast, actin and GAPDH mRNA levels did not change during decidualization. The inhibition of mRNA levels was first noted at day 2 and persisted for the remainder of each experiment. Western blot analysis indicated that the FOXO1A siRNA inhibited IGFBP-1 protein expression by 60-80%. Decidual fibroblast cells exposed in an identical manner to a control RNA that had no effect on FOXO1A expression caused only a 0-15% inhibition of the marker genes and IGFBP-1 protein. Taken together, these findings strongly suggest a critical role for FOXO1A in the induction of human decidualization.

Actins↗
PubMed2005

Relation between psychological strain and carotid atherosclerosis in a general population.

OBJECTIVE: To investigate the hypothesis that psychological strain is related to carotid atherosclerosis in a large general population sample. METHODS: Intima-media thickness and the prevalence of atherosclerotic plaques in the carotid arteries were quantitatively assessed by high resolution ultrasound among 2164 participants (1112 women and 1052 men, aged 45 to 75 years) of the SHIP (study of health in Pomerania), an epidemiological survey of a random sample of the population of north eastern Germany. Psychological strain was measured by 13 items reflecting typical psychological complaints. Each item was graded by the study participants on a four point scale (from 0, absent, to 3, severe) and a psychological strain score was generated by summing these 13 items. RESULTS: Mean psychological strain score was 10.8 (7.0) (median score 10) among women and 8.5 (6.2) (median score 8) among men. Psychological strain did not predict carotid intima-media thickness among either men or women. However, after adjustment for covariates, high psychological strain and carotid plaques were independently and linearly related, with plaque prevalence odds of 1.03 (95% confidence interval (CI) 1.01 to 1.05, p = 0.009) per increment of the psychological strain score among women and 1.04 (95% CI 1.01 to 1.07, p = 0.003) among men. CONCLUSIONS: This study identified a relation between general psychological strain and carotid atherosclerosis.

Aged↗
PubMed2004

A multicenter clinical evaluation of the Clot Signature Analyzer.

BACKGROUND: The Clot Signature Analyzer (CSA) was designed to assess global hemostasis as a screening assay using non-anticoagulated whole blood. Three different measurements are produced by the instrument: platelet hemostasis time (PHT), clot time (CT), and collagen-induced thrombus formation (CITF). OBJECTIVES: The purpose of the present study was to determine normal ranges for these measurements and assess the performance of the CSA in patients with well-characterized hemostatic disorders and in normal subjects. PATIENTS AND METHODS: Four institutions participated in the study. Each established their own normal reference ranges. Patients with well-characterized hemostatic disorders and concurrent normal controls were subsequently examined. RESULTS: Normal ranges between institutions were similar although statistically different. One hundred and eight patients were examined: 46 individuals with von Willebrand disease (VWD) (type 1, 26; type 2A, 11; type 2B, six; type 3, three); 38 patients with a coagulation factor deficiency; 13 individuals with platelet function defects; 10 patients taking warfarin; and one individual on low-molecular-weight heparin. Of these patients, 89% had at least one abnormality by CSA: 42/46 VWD patients, 35/38 coagulation protein defect patients, 9/13 patients with platelet function defects, 9/10 patients on warfarin and 1/1 patient on low-molecular-weight heparin. Of 116 normal subjects, 103 (89%) fell within the centers' normal range. These data suggest that the CSA has a good sensitivity for bleeding disorders.

Adult↗
PubMed2004

[Fertility, maternal mortality and survival of the children in the medical district of Kolda (Senegal)].

Maternal mortality and lethality in childhood constitute a major problem in Senegal. These two rates are often hight in areas off hight birth rate. In the medical district of Kolda (Senegal) no reliable data on reproductive health exists. We report the results of a preliminary investigation of a community based reproductive project. We've used the sisterhood methods reproductive health's indicators. This cross-sectional study was carried out in a sample of 1287 women in age of procreating. An "aggregative" fertility index of 6.59 was found in the "intervention" area as compare to 5,53 in the control area. The maternal death rate was estimated at 1285 per 100.000 alive births [998-1576]. The infant mortality rate was 83 per 1000. These results justify impremantation of a "vigorous" reproductive health policy in this area.

Adolescent↗
PubMed2002

Volumetric assessment of plaque progression with 3-dimensional ultrasonography under statin therapy.

BACKGROUND AND PURPOSE: Lowering of serum cholesterol levels with HMG-CoA reductase inhibitors (statins) slowed the progression of atherosclerosis in the carotid arteries in several clinical trials using carotid artery intima media thickness as primary outcome measure. Whereas conventional ultrasonography is limited to thin 2-dimensional image planes, 3-dimensional (3D) ultrasonography provides quantitative measurement of the entire carotid artery plaque volume. This study aims to assess the feasibility of 3D ultrasonography to monitor plaque progression in hypercholesterolemic patients. METHODS: The authors prospectively assessed the progression of 31 carotid artery plaques over 15.1 +/- 4.5 months in a study of 23 patients (6 women, 17 men; mean age = 61.7 +/- 7.5 years) with hypercholesterolemia under therapy with HMG-CoA reductase inhibitors. All patients were maintained on a lipid-lowering diet. Sixteen patients were additionally treated with statins. Quantitative measurements of carotid artery plaque volumes were performed after 3D reconstruction of exactly parallel transverse duplex ultrasound scans (slice distance = 0.1 mm) into volumetric 3D data sets and segmentation of voxels representing the carotid artery plaque. RESULTS: Within the treatment group, plaques were significantly less frequently progressive if they had a hypoechoic echogenicity (11%, n = 9 vs 64%, n = 14; P = .016) or if baseline serum cholesterol levels were above 8.0 mmol/L (9%, n = 11 vs 75%, n = 12; P = .002). CONCLUSION: Three-dimensional ultrasonography extends the measurement of the arterial wall thickness to the 3D volume of an entire atherosclerotic plaque including analysis of its morphology and configuration. However, further clinical trials with an adequate sample size to achieve sufficient statistical power are necessary to assess the effect of statin therapy on plaque progression.

Carotid Artery Diseases↗
PubMed2001

[Diagnosis of space-occupying lesions of the liver. What is the value of diagnostic imaging?].

Ultrasound in B-mode or tissue harmonic imaging is the procedure of first choice for investigating the liver. If US is employed to screen for metastatic disease, B-mode contrast harmonic imaging should be used in addition to conventional ultrasound. For the diagnosis "space-consuming liver lesion", the echogenicity and clinical aspects determine the further diagnostic procedure. Echogenic liver lesions in patients with known malignant disease, and echo-poor or "echo-complex" lesions always indicate a need for further spiral CT or MRT investigations. In tumour patients, spiral CT offers the advantage of enabling simultaneous evaluation of the parenchyma, and abdominal staging. Primary SPIO-amplified MRT is indicated whenever the primary interest is the detection of space-consuming liver lesions. In the case of echogenic lesions in the absence of underlying malignant disease, US follow-up suffices. Here, differential diagnostic information can be gained from the vascular distribution patterns of a lesion obtained with color-coded duplex US. Hepatic lesions that, after exhausting all diagnostic imaging procedures remain suspicious, require biopsy.

Diagnosis, Differential↗
PubMed2001

Characterization of high-risk HIV-1 seronegative hemophiliacs.

Mechanisms that protect most high-risk HIV-1 seronegative (HRSN) persons are not well understood. Among hemophiliacs from the Multicenter Hemophilia Cohort Study who remained HIV-1 seronegative despite a high (94%) risk for acquisition of HIV-1 infection, only 7/43 were homozygous for the protective CCR5 Delta32 polymorphism. Among the remainder, neither CCR5 density nor beta-chemokine production, nor in vitro susceptibility to infection with the HIV-1 isolate JR-FL could distinguish HRSN hemophiliacs from healthy controls. When compared to lymphocytes of healthy controls not at risk for HIV-1 infection, diminished spontaneous lymphocyte proliferation was seen in lymphocytes of HRSN hemophiliacs as well as in lymphocytes of hemophiliacs not at risk for HIV-1 infection. Surprisingly sera/plasmas obtained from high-risk HIV-1 seropositve hemophiliacs prior to seroconversion more often contained alloreactive antibodies than date-matched sera/plasmas obtained from HRSN hemophiliacs. Thus alloreactivity may predispose to acquisition of HIV-1 infection after parenteral exposure.

Adolescent↗
PubMed2001

Study of Health In Pomerania (SHIP): a health examination survey in an east German region: objectives and design.

OBJECTIVES: The reason for the Study of Health in Pomerania (SHIP) is the lack of epidemiological studies with a broad range of health indicators. Furthermore, in Germany there is a need for studies that take into account the particular situation of life after the reunification. One objective of SHIP is to provide prevalence estimates on a broad range of diseases, risk and health factors for a defined region in the former GDR. METHODS: A sample of 7008 women and men aged 20 to 79 years in a north-east region of Germany, 4900 expected participants. The sample was drawn in two steps: First, 32 communities in the region were selected. Second, within the communities a simple random sample was drawn from residence registries, stratified by gender and age. The data collection and instruments include four parts: oral health examination, medical examination, health-related interview, and a health- and risk-factor-related questionnaire. The oral health examination includes the teeth, periodontium, oral mucosa, craniomandibular system, and prosthodontics. The medical examination includes blood pressure measurements, electrocardiography, echocardiography, carotid, thyroid and liver ultrasounds, neurological screening, blood and urine sampling. The computer-aided health-related interview includes cardiovascular symptoms, utilisation of medical services, health-related behaviours, and socioeconomic variables. The self-administered questionnaire comprises housing conditions, social network, work conditions, subjective well-being and individual consequences from the German reunification.

Adult↗
PubMed2001

Naftidrofuryl in the treatment of vascular dementia.

The design of this study was based on the European guidelines for the treatment of Alzheimer's disease. After a placebo run-in period of 4 weeks, patients with a diagnosis of vascular dementia (VaD) were randomised to receive either 400 mg naftidrofuryl/day, 600 mg naftidrofuryl/day or placebo for 6 months. The patients were assessed using the ADAS-cog, the SCAG, the NOSGER and the CGI item 2 scale. The primary analysis was undertaken on the ITT population. At the end of the study, significantly more patients in the treatment groups showed no deterioration on both ADAS-cog and SCAG scales compared with placebo (400 mg p = 0.005, 600mg p = 0.015). There were also significant differences between the active and placebo groups for the individual scales. This study has demonstrated that treatment with naftidrofuryl can slow the rate of deterioration of patients with vascular dementia.

Aged↗
PubMed2001

Continuous administration of contrast medium for transcranial colour-coded sonography.

Since the introduction of contrast media, transcranial colour-coded sonography (TCCS) has become increasingly important for examination of the intracranial vessels. However, the widely practised bolus injection of these agents leads to initial blooming artefacts and thereafter the level of contrast enhancement decreases rapidly, reducing the effective time of enhancement. It was our aim to investigate the effect of continuous administration of contrast medium at a defined infusion rate. We performed 28 TCCS examinations of the intracranial vessels in 26 patients using a 2.25 MHz phased-array transducer during administration of 4 g Levovist (Schering, Berlin, Germany) 300 mg/ml with a constant infusion rate of 60 ml/h into an antecubital vein. The degree of enhancement was graded over time in a subjective analysis by two independent observers. During continuous administration, a constant level of contrast enhancement was reached after 60.1+/-26.2 s and this lasted 663.4+/-55.8 s as assessed by the first observer (66.6+/-26.2 s and 664.3+/-55.9 s according to the second observer). The limits of inter-observer agreement ranged from -10.1% to 9.9%. No major blooming effect was seen in the initial phase of the examination.

Artifacts↗
PubMed2001

[Comparison of 3D power doppler ultrasound, color doppler ultrasound and digital subtraction angiography in carotid stenosis].

PURPOSE: To compare easy-to-perform three-dimensional power Doppler ultrasound (3D PDUS) to color Doppler ultrasound (CDUS) and digital subtraction angiography (DSA) in the assessment of internal carotid artery (ICA) stenoses in patients with severe atherosclerosis. METHODS: 26 ICA's (7 without stenosis, 4 low-, 4 middle-, and 11 high-grade stenoses) in 13 patients were examined with DSA, CDUS, and 3D PDUS. CDUS and 3D PDUS were performed with a 7.5 MHz standard transducer and a Sonoline Elegra ultrasound machine. The three methods were performed and interpreted by different persons who were not aware of the diagnoses. RESULTS: Regarding the degree of stenosis correlations between DSA and 3D PDUS were r = 0.98 (p < 0.001), between DSA and CDUS r = 0.97 (p < 0.001), and between CDUS and 3D PDUS r = 0.95 (p < 0.001). Sensitivity and specificity regarding the detection of a high-degree stenosis was 90% and 100% for 3D PDUS, and 100% and 93.3% for CDUS. CONCLUSION: Even in cases with severe atherosclerosis, both sonographic methods reveal similar results comparable to DSA. 3D PDUS does not result in a diagnostic improvement on CDUS, however, it does give the new opportunity for complete data storage, reconstruction, and survey presentations.

Aged↗
PubMed2001

Bilateral cerebellar infarctions caused by a stenosis of a congenitally unpaired posterior inferior cerebellar artery.

Bilateral symmetrical cerebellar infarcts in the territory supplied by the medial posterior inferior cerebellar artery (PICA) branches are extremely rare. In the few cases published, it has not been possible to clearly pinpoint the cause of this infarct pattern. The authors present the case history of a 58-year-old man who had acute headaches accompanied by pronounced rotatory vertigo with nausea and vomiting. The neurological examination revealed bilateral cerebellar signs. Cranial magnetic resonance imaging showed bilateral, nearly symmetrical infarcts in the territory of the medial branches of both PICAs. These bilateral PICA infarctions were caused by a stenosis of an unpaired PICA originating from the left vertebral artery supplying both cerebellar hemispheres.

Arterial Occlusive Diseases↗