Biomedical subjects

T Hagen

Publications and source records attributed to T Hagen.

At least 19 recordsLinked to original sources

PubMed2006

Screening for diabetes using HbA1c in elderly subjects.

The objective of the study was to determine the prevalence of known diabetes among elderly subjects receiving nursing care in a north Norwegian population, to screen for new cases using HbA1c measurement and to evaluate the quality of care for those with diabetes. Men and women, with and without known diabetes, above 69 years and receiving nursing care either in an institution or in their own home in the municipality of Tromsø, were included. A health questionnaire was administered and HbA1c measured. An oral glucose tolerance test (OGTT) was performed in those with HbA1c > 6.5% (upper reference limit). A total of 788 subjects were evaluated for participation and 228 completed the study. Forty-six subjects (20.2%) had a previous diagnosis of diabetes. Their age was 80.1+/-5.9 years (mean+/-SD) and HbA1c level 7.6+/-1.4%. Most patients had their blood glucose measured weekly and 65% used blood pressure medication; on average they were seen by their private doctor four times a year and annually by an ophthalmologist. Six subjects with undiagnosed diabetes had HbA1c > 6.5%. Diabetes was confirmed in one, excluded in two and further testing declined in three. None of these six subjects had HbA1c > 7.0%. In conclusion, there is a high prevalence of diabetes among elderly subjects needing nursing care. The prevalence of undiagnosed diabetes in need of treatment, as evaluated by the HbA1c level, was low, indicating that the focus on diabetes and quality of care for the elderly in our area is fairly good.

Aged↗

PubMed2006

[Personal contextual factors, part I].

The International Classification of Functioning, Disability and Health (ICF) does not yet classify personal contextual factors. To determine the interaction of these factors on activities and participation of a person as well as their influence on the probable outcome of interventions, they must be taken into account in individual sociomedical expertises. Therefore, a group of medical experts working for the social health insurance medical advisory boards in Germany compiled a proposal for a systematic classification of personal contextual factors into domains, categories and items with respect to the ethical guidelines of the ICF. In a second step the main issues were transferred into the preliminary draft for a short version which will be published later to give support for practical daily use in health insurance matters.

Persons with Disabilities↗

PubMed2004

[Aspects of expertise which are jointly valid for German sociomedicine and statutory health care].

A project group of the Medical Advisory Board of the German Federal Rehabilitation Council (BAR) developed fundamental joint principles on experts' opinions according to the social law code no. IX (SGB IX). The principles aim at medical experts working in different social organisations and statutory health care insurance. It was intended to create a "sociomedical language" which should be used as jointly as possible by experts in rehabilitation and social medicine and which is based on the ICF (International Classification of Functioning, Disability and Health, WHO 2001). Its stringent application will increase the utility of medical expertise across different institutions. The authors recommend to evaluate whether this model could provide a tool in the communication and cooperation between different sectors of the health system. Part I describes the theoretical model, Part II its application to a virtual individual case history.

Delivery of Health Care↗

PubMed2003

Three-dimensional true FISP for high-resolution imaging of the whole brain.

While high-resolution T1-weighted sequences, such as three-dimensional magnetization-prepared rapid gradient-echo imaging, are widely available, there is a lack of an equivalent fast high-resolution sequence providing T2 contrast. Using fast high-performance gradient systems we show the feasibility of three-dimensional true fast imaging with steady-state precession (FISP) to fill this gap. We applied a three-dimensional true-FISP protocol with voxel sizes down to 0.5 x 0.5 x 0.5 mm and acquisition times of approximately 8 min on a 1.5-T Sonata (Siemens, Erlangen, Germany) magnetic resonance scanner. The sequence was included into routine brain imaging protocols for patients with cerebrospinal-fluid-related intracranial pathology. Images from 20 patients and 20 healthy volunteers were evaluated by two neuroradiologists with respect to diagnostic image quality and artifacts. All true-FISP scans showed excellent imaging quality free of artifacts in patients and volunteers. They were valuable for the assessment of anatomical and pathologic aspects of the included patients. High-resolution true-FISP imaging is a valuable adjunct for the exploration and neuronavigation of intracranial pathologies especially if cerebrospinal fluid is involved.

Adult↗

PubMed2003

[Aspects of expertising which are jointly valid for German sociomedicine and statutory health care].

A project group of the Medical Advisory Board of the German Federal Rehabilitation Council (BAR) developed fundamental joint principles on experts' opinions according to the social law code no. IX (SGB IX). The principles aim at medical experts working in different social organisations and statutory health care insurances. It was intended to create a "sociomedical language" which should be used as jointly as possible by experts in rehabilitation and social medicine and which is based on the ICF (International Classification of Functioning, Disability and Health, WHO 2001). Its stringent application will increase the utility of medical expertise across different institutions. The authors recommend to evaluate whether this model could provide a tool in the communication and cooperation between different sectors of the health system. Part I describes the theoretical model, Part II its application to a virtual individual case history.

Delivery of Health Care↗

PubMed2002

Time course of the apparent diffusion coefficient after cerebral infarction.

The purpose of this study was to evaluate quantitative apparent diffusion changes in the center of infarction by measurement of the apparent diffusion coefficient (ADC), and to investigate the influence of ischemia on the contralateral hemisphere. By diffusion echo-planar imaging (EPI) 52 patients showing cerebral infarction were studied within 5 h to >12 months after onset of clinical symptoms. Using three diffusion gradient strengths (b1=30 s/mm(2); b2=300 s/mm(2), b3=1100 s/mm(2)) ADC maps were generated. After onset of ischemia, ADC in the center of infarction was lower than in the contralateral regions of human brain. At first ADC declined for approximately 28 h to a minimum of approximately 150x10(-8) cm(2)/s. Then the ADC reincreased and reached a "pseudonormalization" after approximately 5 days. Chronic infarctions did show much higher ADC values (2000x10(-8) cm(2)/s) than unaffected areas. Neither localization nor size of infarctions showed a significant influence on this time course. In the center of infarction diffusion is isotropic. Even brain regions of the contralateral hemisphere are influenced by cerebral ischemia. In these regions ADC is higher than for physiological conditions. The ADC also declines especially for the first 2-3 days after onset of symptoms, also followed by reincrease. The ADC calculation enables determination of the onset of infarction more exactly than is possible using only diffusion-weighted imaging. Diffusion in the center of infarction is isotropic; hence, orientation of the diffusion gradients has no significant influence on sensitivity of measurements. The calculation of the ADC ratio based on data derived from the center of infarction and the contralateral hemisphere seems to be critical because the ADC in the unaffected contralateral hemisphere also changes.

Brain↗

PubMed2002

Pathophysiological changes after traumatic brain injury: comparison of two experimental animal models by means of MRI.

In an experimental study MRI was used to compare the pathophysiological changes of brain tissue after lateral fluid percussion injury (FPI) versus cold injury (CI) as models of traumatic brain injury (TBI). Two groups of Sprague-Dawley rats (n=23) were subjected to mild FPI, respectively, CI localized over the right parietal cortex. MRI was performed at different time points including T1w, T2w and T1w-CE (Gd-DTPA 0.2 mmol/kg BW) sequences as well as perfusion-weighted imaging with calculation of regional cerebral blood volume (rCBV) and regional cerebral blood flow (rCBF). T2w and T1w-CE images showed hyperintense areas in the traumatised cortex demonstrating brain edema and blood-brain barrier (BBB)-breakdown increasing up to 12 h. Perfusion-weighted imaging demonstrated a significant decrease of rCBV and rCBF in the ipsilateral cortex of CI animals compared with the contralateral hemisphere. In contrast, rats of the FPI group showed only slight differences in rCBF and rCBV comparing the left and right cortex. The results of our study confirm that both mild FPI and CI produced focal brain edema with concomitant breakdown of the BBB as a model of TBI. Since differences regarding perfusion are much more pronounced in CI our results suggest that, this model more likely seems to reflect pathophysiological changes of brain ischemia, whereas FPI seems to be better suited to model the pathophysiological characteristics of TBI.

Animals↗

PubMed2002

Mitochondrial uncoupling proteins in human physiology and disease.

Uncoupling proteins are mitochondrial carrier proteins that catalyse a regulated proton leak across the inner mitochondrial membrane, diverting free energy from ATP synthesis by the mitochondrial F0F1-ATP synthase to the production of heat. Uncoupling protein 1 (UCP1), which is exclusively expressed in brown adipose tissue, is the mediator of thermogenesis in response to beta-adrenergic stimulation. Using gene a knockout mouse model, UCP1 has been shown to be required for cold acclimation. Two homologues of UCP1, UCP2 and UCP3, have been identified recently and show a much wider tissue distribution. UCP2 and UCP3 have been postulated to play a role in the regulation of cold acclimation, energy expenditure and diet-induced thermogenesis in humans, who, in contrast to rodents, have very little brown fat in adult life. However, evidence is accumulating that thermogenesis and regulation of body weight may not be the physiological functions of UCP2 and UCP3. For instance, mice deficient for UCP2 or UCP3 are not cold-intolerant and do not develop obesity. Alternative functions were suggested, primarily based on findings in UCP2 and UCP3 gene knockout mice. Both UCP2- and UCP3-deficient mice were found to overproduce reactive oxygen species and UCP2-deficient mice to hypersecrete insulin. Thus, the UCP1 homologues may play a role in regulating mitochondrial production of reactive oxygen species and b-cell function. In this review, we discuss the role of UCP1, UCP2 and UCP3 in human physiology and disease, primarily based on findings from the various animal models that have been generated.

Carrier Proteins↗

PubMed2001

Immunodetection of 3-nitrotyrosine in the liver of zymosan-treated rats with a new monoclonal antibody: comparison to analysis by HPLC.

Zymosan-induced peritonitis is associated with an increased production of reactive nitrogen oxides that may contribute to the often-observed failure of multiple organ systems in this model of acute inflammation. Quantitative biochemical evidence is provided for a marked 13-fold increase in protein-bound 3-nitrotyrosine (NTyr), a biomarker of reactive nitrogen oxides, in liver tissue of zymosan-treated rats. In order to investigate the localization of NTyr in this affected tissue, a monoclonal antibody, designated 39B6, was raised against 3-(4-hydroxy-3-nitrophenylacetamido) propionic acid-bovine serum albumin conjugate and its performance characterized. 39B6 was judged by competition ELISA to be approximately 2 orders of magnitude more sensitive than a commercial anti-NTyr monoclonal antibody. Binding characteristics of 39B6 were similar, but not identical, to that of a commercial affinity-purified polyclonal antibody in ELISA and immunohistochemical analyses. Western blot experiments revealed high specificity of 39B6 against NTyr and increased immunoreactivity of specific proteins from liver tissue homogenates of zymosan-treated rats. Immunohistochemical analysis of liver sections indicated a marked zymosan-induced increase in immunofluorescent staining, which was particularly intense in or adjacent to nonparenchymal cells, but not in the parenchymal cells of this tissue. Quantitative analysis of fractions enriched in these cell populations corroborated the immunofluorescent data, although the relative amounts detected in response to zymosan treatment was greatly reduced compared to whole liver tissue. These results demonstrate the high specificity of the newly developed antibody and its usefulness in Western blot and immunohistochemical analysis for NTyr, confirm the presence of NTyr by complementary methods, and suggest the possible involvement of reactive nitrogen oxides in hepatic vascular dysfunction.

Animals↗

PubMed2001

GSK-3 inhibition by adenoviral FRAT1 overexpression is neuroprotective and induces Tau dephosphorylation and beta-catenin stabilisation without elevation of glycogen synthase activity.

Glycogen synthase kinase 3 (GSK-3) has previously been shown to play an important role in the regulation of apoptosis. However, the nature of GSK-3 effector pathways that are relevant to neuroprotection remains poorly defined. Here, we have compared neuroprotection resulting from modulation of GSK-3 activity in PC12 cells using either selective small molecule ATP-competitive GSK-3 inhibitors (SB-216763 and SB-415286), or adenovirus overexpressing frequently rearranged in advanced T-cell lymphomas 1 (FRAT1), a protein proposed as a negative regulator of GSK-3 activity towards Axin and beta-catenin. Our data demonstrate that cellular overexpression of FRAT1 is sufficient to confer neuroprotection and correlates with inhibition of GSK-3 activity towards Tau and beta-catenin, but not modulation of glycogen synthase (GS) activity. By comparison, treatment with SB-216763 and SB-415286 proved more potent in terms of neuroprotection, and correlated with inhibition of GSK-3 activity towards GS in addition to Tau and beta-catenin.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes.

beta cells sense glucose through its metabolism and the resulting increase in ATP, which subsequently stimulates insulin secretion. Uncoupling protein-2 (UCP2) mediates mitochondrial proton leak, decreasing ATP production. In the present study, we assessed UCP2's role in regulating insulin secretion. UCP2-deficient mice had higher islet ATP levels and increased glucose-stimulated insulin secretion, establishing that UCP2 negatively regulates insulin secretion. Of pathophysiologic significance, UCP2 was markedly upregulated in islets of ob/ob mice, a model of obesity-induced diabetes. Importantly, ob/ob mice lacking UCP2 had restored first-phase insulin secretion, increased serum insulin levels, and greatly decreased levels of glycemia. These results establish UCP2 as a key component of beta cell glucose sensing, and as a critical link between obesity, beta cell dysfunction, and type 2 diabetes.

Adenosine Triphosphate↗

PubMed2001

Cloning and functional characterization of an uncoupling protein homolog in hummingbirds.

The cDNA of an uncoupling protein (UCP) homolog has been cloned from the swallow-tailed hummingbird, Eupetomena macroura. The hummingbird uncoupling protein (HmUCP) cDNA was amplified from pectoral muscle (flight muscle) using RT-PCR and primers for conserved domains of various known UCP homologs. The rapid amplification of cDNA ends (RACE) method was used to complete the cloning of the 5' and 3' ends of the open reading frame. The HmUCP coding region contains 915 nucleotides, and the deduced protein sequence consists of 304 amino acids, being approximately 72, 70, and 55% identical to human UCP3, UCP2, and UCP1, respectively. The uncoupling activity of this novel protein was characterized in yeast. In this expression system, the 12CA5-tagged HmUCP fusion protein was detected by Western blot in the enriched mitochondrial fraction. Similarly to rat UCP1, HmUCP decreased the mitochondrial membrane potential as measured in whole yeast by uptake of the fluorescent potential-sensitive dye 3',3-dihexyloxacarbocyanine iodide. The HmUCP mRNA is primarily expressed in skeletal muscle, but high levels can also be detected in heart and liver, as assessed by Northern blot analysis. Lowering the room's temperature to 12-14 degrees C triggered the cycle torpor/rewarming, typical of hummingbirds. Both in the pectoral muscle and heart, HmUCP mRNA levels were 1.5- to 3.4-fold higher during torpor. In conclusion, this is the first report of an UCP homolog in birds. The data indicate that HmUCP has the potential to function as an UCP and could play a thermogenic role during rewarming.

Amino Acid Sequence↗

PubMed2001

[Juxta-facet cysts: magnetic resonance tomography diagnosis].

The term juxta-facet cyst summarizes synovial cysts, arising from degenerated facet joints and ganglion cysts, developing from mucinous degeneration of periarticular connective tissue. Most juxta-facet cysts are observed at the L4/5 level, which generally has the most motion within the lumbar spine. In this retrospective study 31 juxta-facet cysts in 28 patients were detected within 2898 lumbar MRI studies over a 2-year period (frequency 1%). 24 patients complained of back and lower extremity pain, the other 4 patients had unilateral back pain. In 7 cases radicular symptoms were observed, in 6 patients a neurogenic claudication. In 78% of the patients juxta-facet cysts were responsible for clinical symptoms. MRI is the diagnostic imaging technique of choice due to a high sensitivity. The juxta-facet cysts were located extradural, laterally to the thecal sack and adjacent to a degenerated facet joint. In all but one cases the cysts showed a signal intensity equivalent to cerebrospinal fluid. T2-weighted pulse sequences in sagittal orientation were very useful in delineating the hypointense cyst wall. In 1 patient with acute radicular pain MRI demonstrated a subacute hemorrhage within a juxta-facet cyst. Calcifications and gas-filled cysts can be missed with MRI, but will be demonstrated by computed tomography. 45% of the juxta-facet cysts showed an enhancement of the cyst wall after injection of Gd-DTPA. Spontaneous reduction or resolution of the cyst may occur during rest. Injection of corticosteroids into the corresponding facet joint may reduce the inflammatory process and resolve the symptoms in up to 70%. Surgical resection of the cyst is indicated in case of intractable pain and significant neurologic deficit and generally produces good relief from radicular symptoms.

Aged↗

PubMed2001

Comparison of color-flow Doppler scanning, power Doppler scanning, and frequency shift for assessment of carotid artery stenosis.

OBJECTIVE: We investigated the accuracy of color-flow Doppler (CD) scanning, power Doppler (PD) scanning, and peak systolic Doppler frequency shift (PSF) in assessment of carotid artery stenosis with angiography used as gold standard, including the measurement techniques used in the North American Symptomatic Carotid Surgery Trial (NASCET) and the European Carotid Surgery Trial (ECST). METHODS: Fifty-eight consecutive patients diagnosed for carotid artery surgery underwent color-coded duplex sonography and angiography. The duplex examination included the assessment of PSF and the videotaping of sagittal images in CD and PD mode from the proximal common carotid artery to the distal internal carotid artery. Two experienced examiners performed the studies, but once one examiner had done the taping, the other examiner was allowed only to review the tape. Separately, each examiner reviewed the tapes and determined by cursor settings each stenosis according to NASCET and ECST. For interobserver agreement kappa statistic was used. To compare with angiography (degree of stenosis 40%, 50%, 60%, 70%, and 80%) sensitivity, specificity, positive and negative predictive values, and overall accuracy were calculated. PSF cut-off frequencies were based on receiver operator curve analysis. RESULTS: Because interobserver agreement in CD and PD was good (chance-corrected kappa > 0.6), further analysis used the between-observer mean value for each stenosis. With the NASCET measurement technique, accuracy of Doppler techniques to distinguish a 50% stenosis was 89% for PSF, 91% for CD, and 93% for PD; for a 70% stenosis it was 83% for PSF, 84% for CD, and 81% for PD. With the ECST measurement technique, accuracy to distinguish a 70% stenosis was 86% for PSF, 88% for CD, and 86% for PD; for an 80% stenosis it was 87% for PSF, 87% for CD, and 77% for PD. CONCLUSION: CD and PD carotid artery stenosis measurements are highly reproducible, and in our hands provided accuracy equal to PSF.

Aged↗

PubMed2000

Chimeric proteins between UCP1 and UCP3: the middle third of UCP1 is necessary and sufficient for activation by fatty acids.

Uncoupling protein (UCP) 1 and UCP3 are mitochondrial inner membrane proteins which both mediate proton leak and thus decrease the mitochondrial transmembrane proton gradient. However, UCP1 and UCP3 differ in their biochemical regulation. UCP1 is activated by free fatty acids and inhibited by purine nucleotides. Using heterologous expression studies in yeast, UCP3 was found to lack both fatty acid activation and purine nucleotide inhibition. To assess which domains are responsible for the regulation of UCP1 by free fatty acids and by purine nucleotides and the absence of such regulation in UCP3, chimeric proteins were generated. Given that uncoupling proteins, like all members of the mitochondrial carrier family, possess a tripartite structure and consist of three repeated domains of approximately 100 residues, swaps in the three repeated domains were made between UCP1 and UCP3. Regulation of the resulting six different chimeric proteins by free fatty acids and purine nucleotides was studied after heterologous expression in yeast mitochondria. In this study, it is shown that activation of UCP1 by free fatty acids is mediated by the second repeated domain, since substitution of the second repeat of UCP1 by the equivalent repeat of UCP3 abolishes fatty acid activation. In contrast, replacing the second repeat of UCP3 by the corresponding repeated domain of UCP1 results in fatty acid activation similar to wild type UCP1. The lack of free fatty acid activation of UCP3 is not due to the absence of the histidine pair H145 and H147 found in the second repeated domain of UCP1. Furthermore, the findings with respect to purine nucleotide inhibition are consistent with a significant role of the C-terminal repeated domain of UCP1 in mediating purine nucleotide inhibition.

Animals↗

PubMed2000

Energy metabolism in uncoupling protein 3 gene knockout mice.

Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily. Based upon its high homology with UCP1 and its restricted tissue distribution to skeletal muscle and brown adipose tissue, UCP3 has been suggested to play important roles in regulating energy expenditure, body weight, and thermoregulation. Other postulated roles for UCP3 include regulation of fatty acid metabolism, adaptive responses to acute exercise and starvation, and prevention of reactive oxygen species (ROS) formation. To address these questions, we have generated mice lacking UCP3 (UCP3 knockout (KO) mice). Here, we provide evidence that skeletal muscle mitochondria lacking UCP3 are more coupled (i.e. increased state 3/state 4 ratio), indicating that UCP3 has uncoupling activity. In addition, production of ROS is increased in mitochondria lacking UCP3. This study demonstrates that UCP3 has uncoupling activity and that its absence may lead to increased production of ROS. Despite these effects on mitochondrial function, UCP3 does not seem to be required for body weight regulation, exercise tolerance, fatty acid oxidation, or cold-induced thermogenesis. The absence of such phenotypes in UCP3 KO mice could not be attributed to up-regulation of other UCP mRNAs. However, alternative compensatory mechanisms cannot be excluded. The consequence of increased mitochondrial coupling in UCP3 KO mice on metabolism and the possible role of yet unidentified compensatory mechanisms, remains to be determined.

Animals↗

PubMed2000

Uncoupling proteins 1 and 3 are regulated differently.

Using a heterologous yeast expression system, we have previously found a marked discordance between the effects of uncoupling protein (UCP) 1 and UCP3L on basal O(2) consumption in whole yeast versus isolated mitochondria. In whole yeast, UCP3L produces a greater stimulation of basal O(2) consumption, while in isolated mitochondria, UCP1 produces a much greater effect. As shown previously and in this report, UCP3L, in contrast to UCP1, is not inhibited by purine nucleotides. In the present study, we addressed two hypothetical mechanisms that could account for the observed discordance: (i) in whole yeast, purine nucleotides inhibit UCP1 but not UCP3L and (ii) preparations of isolated mitochondria lack an activator of UCP3L that is normally present in vivo. By use of a mutant of UCP1 that lacks purine nucleotide inhibition, it is demonstrated that cytosolic concentrations of purine nucleotides present in yeast effectively inhibit UCP1 activity. This suggests that the lower activity of UCP1 compared to UCP3L in whole yeast is due to purine nucleotide inhibition of UCP1 but not UCP3L. As potential activators of UCP3L we tested free fatty acids in whole yeast and isolated mitochondria. While UCP1 was strongly activated by free fatty acids, no stimulatory effect on UCP3L was observed. In summary, this study indicates that UCP1 and UCP3L differ in their regulation by purine nucleotides and free fatty acids. This different regulation may be related to different physiological functions of the two proteins.

Animals↗

PubMed2000

Urinary lactate excretion to monitor the efficacy of treatment of type I glycogen storage disease.

The purpose of this study was to investigate the usefulness of urinary lactate measurements to assess the adequacy of dietary treatment in patients with type I glycogen storage disease (GSD-I). We determined the correlation of urine and blood lactate concentrations in 21 GSD-I patients during 24-h admissions to the General Clinical Research Center (GCRC) during which hourly blood samples and aliquots of every void were obtained. In all but 1 patient, we found a good correlation between blood lactate concentrations and urinary lactate excretion. One patient did not excrete lactate in significant amounts despite elevated blood lactate concentrations. In 17 patients, the highest blood lactate concentrations occurred during the night. Markedly elevated nighttime average blood lactate concentrations above 3.5 mmol/l resulted in a urinary lactate concentration above the normal limit of 0.067 mmol/mmol creatinine in the first morning urine specimen. Mildly elevated nighttime blood lactate concentrations (between 2.2 and 3.5 mmol/l) led to urinary lactate concentrations that were either normal or moderately elevated. All patients with normal blood lactate concentrations during the night also had normal first morning urinary lactate concentrations. The degree of urinary lactate excretion in relation to blood lactate concentrations varied by individual. Urinary filter paper specimens, collected at home during the night and in the morning and mailed to the laboratory, were used to monitor the dietary compliance of 5 GSD-I patients at home over a period of 6 to 9 weeks prior to their GCRC admissions. These data suggested variable degrees of dietary control. In conclusion, the urinary lactate concentration is a useful parameter to monitor therapy of GSD-I patients at home. To be interpretable, the baseline urinary lactate concentration in relation to the blood lactate concentration has to be determined.

Adolescent↗