| 1. |
- Holmer, Helene, et al.
(författare)
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Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:9, s. 3560-3567
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Tidskriftsartikel (refereegranskat)abstract
- Context: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown. Objective: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus ( T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls. Design and Participants: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively. Results: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication. Conclusions: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.
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| 2. |
- Nilsson, Christer, et al.
(författare)
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Tracking the neurodegeneration of parkinsonian disorders - A pilot study
- 2007
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Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 1432-1920 .- 0028-3940. ; 49:2, s. 111-119
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to explore the possibilities of using diffusion tensor imaging (DTI) and tractography (DTT) for the differential diagnosis and monitoring of disease progression in idiopathic Parkinson's disease (IPD), compared with the atypical parkinsonian disorders multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). A 3.0-T MR scanner was used. DTI was acquired using a single-shot EPI sequence with diffusion encoding in 32 directions and a voxel size of 2×2×2 mm3. DTI data were analysed and DTT was performed using the PRIDE fibre tracking tool supplied by the manufacturer. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) within each tract were determined. DTI and DTT images in patients with moderate to advanced MSA demonstrated degeneration of the middle cerebellar peduncles and pontine crossing tracts, with decreased FA and increased ADC. This accounted for most of the pontine and cerebellar atrophy characteristic of this disease. In contrast, patients with PSP showed a selective degeneration of the superior cerebellar peduncle. Three-dimensional images of whole-brain white matter tracts demonstrated a reduction of cortical projection fibres in all patients with PSP. Visualization of the selective degeneration of individual fibre tracts, using DTI and DTT, adds qualitative data facilitating the differential diagnosis of parkinsonian disorders. Repeated measurements of FA and ADC values in a whole fibre tract might be used for monitoring disease progression and studying the effect of treatment in neuroprotective trials. The results are preliminary considering the small number of subjects in the study. © Springer-Verlag 2007.
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| 3. |
- Borgquist, Rasmus, et al.
(författare)
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Coronary flow velocity reserve reduction is comparable in patients with erectile dysfunction and in patients with impaired fasting glucose or well-regulated diabetes mellitus
- 2007
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8275. ; 14:2, s. 258-264
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Tidskriftsartikel (refereegranskat)abstract
- Background There is growing evidence that erectile dysfunction is a sentinel for future coronary artery disease. Recently published studies have shown signs of impaired coronary endothelial function in patients with erectile dysfunction, without clinical cardiovascular disease and diabetes. We evaluated the magnitude of coronary vasodilatory dysfunction in men with erectile dysfunction, as compared with men with impaired glucose metabolism (impaired fasting glucose or diabetes) and healthy controls. Methods We investigated men aged 68-73 years with erectile dysfunction (n=12), age-matched men with impaired glucose metabolism, who all proved to have erectile dysfunction (n=15), and age-matched male controls (n=12). Erectile dysfunction was evaluated using the International Index of Erectile Function (IIEF)-5 questionnaire. Coronary flow velocity reserve in the left anterior descending artery was examined using Doppler ultrasound and intravenous adenosine provocation. Results Coronary flow velocities at rest did not differ between the three groups, but maximum coronary flow velocity was significantly lower in the erectile dysfunction group (P= 0.004) and in the impaired glucose metabolism group (P= 0.019), as compared with controls. There was no difference between the erectile dysfunction and impaired glucose metabolism groups. Coronary flow velocity reserve was reduced in the erectile dysfunction group (P=0.026) compared to controls, but was similar compared to the impaired glucose metabolism group. In multivariate analysis including all groups, erectile dysfunction score was the only independent predictor of reduced coronary flow velocity reserve (P=0.020). Conclusions The magnitude of early coronary endothelial and smooth muscle cell dysfunction in otherwise healthy men with erectile dysfunction was comparable to that of patients with impaired glucose metabolism: a well known risk factor for coronary artery disease.
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| 4. |
- Pasupuleti, Mukesh, et al.
(författare)
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Preservation of Antimicrobial Properties of Complement Peptide C3a, from Invertebrates to Humans
- 2007
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 282:4, s. 2520-2528
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Tidskriftsartikel (refereegranskat)abstract
- The human anaphylatoxin peptide C3a, generated during complement activation, exerts antimicrobial effects. Phylogenetic analysis, sequence analyses, and structural modeling studies paired with antimicrobial assays of peptides from known C3a sequences showed that, in particular in vertebrate C3a, crucial structural determinants governing antimicrobial activity have been conserved during the evolution of C3a. Thus, regions of the ancient C3a from Carcinoscorpius rotundicauda as well as corresponding parts of human C3a exhibited helical structures upon binding to bacterial lipopolysaccharide permeabilized liposomes and were antimicrobial against Gram-negative and Gram-positive bacteria. Human C3a and C4a (but not C5a) were antimicrobial, in concert with the separate evolutionary development of the chemotactic C5a. Thus, the results demonstrate that, notwithstanding a significant sequence variation, functional and structural constraints imposed on C3a during evolution have preserved critical properties governing antimicrobial activity.
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| 5. |
- Ahrén, Bo
(författare)
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Insulin secretion and insulin sensitivity in relation to fasting glucose in healthy subjects.
- 2007
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 30:3, s. 644-648
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - This study evaluated insulin secretion and insulin sensitivity in healthy subjects with normal fasting glucose. RESEARCH DESIGN AND METHODS - A total of 148 healthy women (aged 53-70 years) underwent a glucose-dependent arginine stimulation test and a 2-h euglycemic-hyperinsulinemic clamp. In the arginine test, arginine (5 g) was injected intravenously under baseline (fasting) conditions and after raising the glucose levels to 15 and > 28 mmol/l. From this test, the acute insulin response (AIR) to arginine during the three glucose levels (AIR(1), AIR(2), and AIR,) were estimated. The subjects were divided into quartiles of fasting glucose (n = 37 in each group [range < 432; 4.33-4.84; 4.85-5.22; and 5:23-6.1 mmol/l, respectively). RESULTS - The results show that 1) AIR(1) was higher in subjects in the two highest quartiles (P = 0.004), 2) AIR(3) was higher in the quartile with the highest fasting glucose (P = 0.012), and 3) insulin sensitivity was reduced in subjects in the highest quartile (P = 0.026) compared with the lower quartiles. The results also show, in contrast, that AIR(2) did not show a similar trend to be increased at higher fasting glucose. CONCLUSIONS - it is concluded that 1) raised fasting glucose (albeit still within normal values) augments baseline and maximal arginine-induced insulin secretion in healthy subjects, and 2) this is associated with reduced insulin sensitivity. This suggests that high, but still normal, fasting glucose may contribute to the augmented insulin secretion in subjects with low insulin sensitivity.
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| 6. |
- Bendsoe, Niels, et al.
(författare)
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Fluorescence monitoring of a topically applied liposomal temoporfin formulation and photodynamic therapy of nonpigmented skin malignancies.
- 2007
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Ingår i: Journal of Environmental Pathology and Toxicology. - 2162-6537. ; 26:2, s. 117-126
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Tidskriftsartikel (refereegranskat)abstract
- Meso-tetra(hydroxyphenyl)chlorin (mTHPC) (INN: Temoporfin) is a potent photodynamically active substance in clinical use today. Usually, the substance is given systemically and a known drawback with this administration route is a prolonged skin light sensitization. For the first time to our knowledge, a liposomal Temoporfin gel formulation for topical application was studied in connection with photodynamic therapy (PDT) of nonpigmented skin malignancies in humans. Intervals of 4 hr between drug administration and light irradiation were used. Sensitizer distribution within tumor and surrounding normal skin was investigated by means of point monitoring and imaging fluorescence spectroscopy before, during, and after PDT, showing high tumor selectivity. Furthermore, the bleaching of Temoporfin was studied during the PDT procedure by monitoring the fluorescence following excitation by using a therapeutic light. A 30−35% light-induced photometabolization was shown. No pain occurred during or after treatment. It was also observed that the treated area did not show any swollen tissue or reddening, as is often seen in PDT using topical δ-aminolevulinic acid. On controlling the patients one week after treatment, healing progress was observed in several patients and no complications were registered.
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| 7. |
- Hesselgard, Karin, et al.
(författare)
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Selective dorsal rhizotomy and postoperative pain management. A worldwide survey.
- 2007
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Ingår i: Pediatric Neurosurgery. - : S. Karger AG. - 1016-2291 .- 1423-0305. ; 43:2, s. 107-112
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Tidskriftsartikel (refereegranskat)abstract
- Background: Selective dorsal rhizotomy (SDR) is an operation method that decreases the degree of spasticity with long-lasting beneficial effects for children with spastic diplegia. Children undergoing SDR are postoperatively in severe pain, a pain related to both the extensive surgical exposure with multilevel laminectomy and the nerve root manipulation. Various pain management strategies for children undergoing SDR have been published. The postoperative pain treatment is a vital part of the management. The aim of this study was to estimate the number of centers performing SDR, the frequency of SDR surgery and to investigate pain management of the different centers. Methods: A questionnaire comprising 7 questions was sent by mail and/or e-mail to a total of 59 potential centers performing SDR, centers that have published material concerning SDR or centers that have been recommended. Forty-seven (80%) centers responded to the questionnaire; 11 of them do not presently perform SDR surgery, and the remaining 36 centers constitute the material of the present study. Results: 23 of the 36 centers use Peacock's operation technique and 8 centers use Park's technique. Continuous intravenous infusion of opioids for postoperative pain treatment is used by 17 (47%) of the centers. Seven (19%) centers use the epidural (ED) approach for treating postoperative pain and 6 (17%) centers use intrathecal (IT) pain treatment. The duration of intravenous ED or IT pain relief ranged from 24 h up to 7 days. To evaluate pain relief, 25 (70%) centers used some form of pain scale. Conclusion: The most common operation techniques in use today are described by Peacock or by Park, with an estimated number of procedures of more than 487/year in 36 centers. The majority of the centers seem to have a satisfactory pain management strategy. These centers administer continuous infusions of opioids, with an intravenous, ED or IT approach, and incorporate the use of a pain assessment tool to evaluate pain relief. Copyright (c) 2007 S. Karger AG, Basel
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| 8. |
- Lindgärde, Folke, et al.
(författare)
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Improved metabolic risk markers following two 6-month physical activity programs among socioeconomic marginalized women of native American ancestry in Lima, Peru
- 2007
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 30:9, s. 2230-2232
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Tidskriftsartikel (refereegranskat)abstract
- It is known that ethnicity is a risk factor for diabetes. Thus, individuals of African, Latin American, and Asian descent are particularly susceptible (1). As an example, a health survey in six urban areas in Peru found a diabetes prevalence of 17% among women (2,3). It was also found that low socioeconomic status was associated with a high burden of noncommunicable diseases and appeared as an independent risk factor for diabetes. In several populations, it is known that increased physical activity reduces the risk for diabetes (4,5). Whether this applies for all populations is, however, not known. The aim of the present study was to explore if supervised endurance training is feasible among socioeconomically marginalized women of a poor urban area in Lima, Peru.
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| 9. |
- Oldberg, Åke, et al.
(författare)
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Collagen-binding proteoglycan fibromodulin can determine stroma matrix structure and fluid balance in experimental carcinoma.
- 2007
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 104:35, s. 13966-13971
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Tidskriftsartikel (refereegranskat)abstract
- Research on the biology of the tumor stroma has the potential to lead to development of more effective treatment regimes enhancing the efficacy of drug-based treatment of solid malignancies. Tumor stroma is characterized by distorted blood vessels and activated connective tissue cells producing a collagen-rich matrix, which is accompanied by elevated interstitial fluid pressure (IFP), indicating a transport barrier between tumor tissue and blood. Here, we show that the collagen-binding proteoglycan fibromodulin controls stroma structure and fluid balance in experimental carcinoma. Gene ablation or inhibition of expression by anti-inflammatory agents showed that fibromodulin promoted the formation of a dense stroma and an elevated IFP. Fibromodulin-deficiency did not affect vasculature but increased the extracellular fluid volume and lowered IFP. Our data suggest that fibromodulin controls stroma matrix structure that in turn modulates fluid convection inside and out of the stroma. This finding is particularly important in relation to the demonstration that targeted modulations of the fluid balance in carcinoma can increase the response to cancer therapeutic agents.
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| 10. |
- Persson, Oscar, et al.
(författare)
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Microarray analysis of gliomas reveals chromosomal position-associated gene expression patterns and identifies potential immunotherapy targets.
- 2007
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 85:J1, s. 11-24
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Tidskriftsartikel (refereegranskat)abstract
- Gliomas are among the most aggressive malignant tumors and the most refractory to therapy, in part due to the propensity for malignant cells to disseminate diffusely throughout the brain. Here, we have used 27 K cDNA microarrays to investigate global gene expression changes between normal brain and high-grade glioma (glioblastoma multiforme) to try and better understand gliomagenesis and to identify new therapeutic targets. We have also included smaller groups of grade II and grade III tumors of mixed astrocytic and oligodendroglial origin as comparison. We found that the expression of hundreds of genes was significantly correlated to each group, and employed a naive Bayesian classifier with leave-one-out cross-validation to accurately classify the samples. We developed a novel algorithm to analyze the gene expression data from the perspective of chromosomal position, and identified distinct regions of the genome that displayed coordinated expression patterns that correlated significantly to tumor grade. The regions identified corresponded to previously known genetic copy number changes in glioma (e.g. 10q23, 10q25, 7q, 7p) as well as regions not previously associated significantly with glioma (e.g. 1p13, 6p22). Furthermore, to enrich for more suitable targets for therapy, we took a bioinformatics approach and annotated our signatures with two published datasets that identified membrane/secreted genes from cytosolic genes. The resulting focused list of 31 genes included interesting novel potential targets as well as several proteins already being investigated for immunotherapy (e.g. CD44 and tenascin-C). Software for the chromosome analysis was developed and is freely available at http://base.thep.lu.se.
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