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Biomedical subjects

G Andersen

Publications and source records attributed to G Andersen.

At least 37 records · Page 2Linked to original sources

Concentrations and patterns of organochlorine contaminants in white whales (Delphinapterus leucas) from Svalbard, Norway.

Blubber was collected from live-captured, adult male white whales (Delphinapterus leucas) from Svalbard, Norway, and analysed for levels and patterns of organochlorine (OC) contaminants. The OC compounds analysed were HCB, dieldrin, sigmaHCH (alpha-HCH, beta-HCH and gamma-HCH), sigmaChl (heptachlor epoxide, oxychlordane, cis-chlordane, trans-nonachlor, and cis-nonachlor), sigmaDDT (pp'-DDT, pp'-DDE and pp'-DDD) and sigmaPCB (27 PCB congeners). The major OC compounds detected in the blubber were sigmaPCB (5103+/-1874 ng/g l.w.) and sigmaDDT (5108+/-1089 ng/g l.w.), which made up 70% of the sigmaOC. These compounds were followed in prevalence by sigmaChl (2872+/-1177 ng/g l.w.), which contributed 20% of the sigmaOC burden. SigmaHCH, HCB and dieldrin were present, but at low concentrations. This OC pattern is typical of top predators in Arctic marine food chains. OC levels in white whales from Svalbard are lower than white whales from the St Lawrence River in Canada and are generally similar to values reported previously for other Arctic white whale stocks. Some geographic patterns in relative prevalence of various OC compounds appear to be quite consistent among various marine mammal species in the Arctic. PCB and DDT concentrations in Svalbard's white whales are below the levels that are thought to have negative effects on reproduction or the immune system.

Adipose Tissue↗

Mutation analysis of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus.

AIM/HYPOTHESIS: This study aimed to investigate if variability in the peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) gene is associated with Type II (non-insulin-dependent) diabetes mellitus. METHODS: The PGC-1 gene was examined in 53 Type II diabetic patients applying single strand conformational polymorphism analysis followed by nucleotide sequencing. Identified variants were genotyped in an association study comprising 483 Type II diabetic patients and 216 glucose-tolerant control subjects. A replication study was done in an additional 201 Type II diabetic patients and 293 glucose-tolerant subjects. Furthermore, a potential interaction between the Pro12Ala polymorphism of PPAR-gamma2 and the PGC-1 Gly482Ser variant on risk of Type II diabetes was investigated. RESULTS: A total of seven variants (Ser74Leu, IVS2 + 52C-->A, Thr394Thr, Asp475Asp, Gly482Ser, Thr528Thr, and Thr612Met) were identified and investigated in an association study. Six of the variants showed no association with Type II diabetes in the initial study. However, the Gly482Ser polymorphism, was more frequent among Type II diabetic patients (37.0 %) than among glucose-tolerant subjects (30.8 %) (p = 0.032). In a replication study the difference in allele frequencies of the Gly482Ser variant remained significant (p = 0.0135). The combined study yielded an allele frequency of 37.3 % (34.7-39.9) for Type II diabetic patients and 30.5 % (27.7-33.4) for glucose-tolerant subjects (p = 0.0007). No interaction between this variant and the Pro12Ala polymorphism of PPAR-gamma2 was observed. CONCLUSION/INTERPRETATION: A widespread Gly482Ser polymorphism of PGC-1 is associated with a 1.34 genotype relative risk of Type II diabetes.

Aged↗

Studies of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene in relation to insulin sensitivity among glucose tolerant caucasians.

AIMS/HYPOTHESIS: We examined whether the Pro12-Ala polymorphism of the human peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene was related to altered insulin sensitivity among glucose-tolerant subjects or a lower accumulated incidence or prevalence of IGT and Type II (non-insulin-dependent) diabetes mellitus among Scandinavian Caucasians. METHODS: The Pro12Ala polymorphism was examined using PCR-RFLP Whole-body insulin sensitivity measured under hyperinsulinaemic-euglycaemic conditions was estimated in a population-based sample of 616 glucose tolerant Swedish Caucasian men at age 70. In addition, insulin sensitivity index was measured using IVGTT and Bergman minimal modelling in a population-based sample of 364 young healthy Danish Caucasians. Finally, we evaluated whether the polymorphism predicted Type II diabetes and IGT in 841 seventy-year-old Swedish men. A case-control study was carried out in 654 unrelated Danish Type II diabetic patients and 742 Danish glucose tolerant subjects matched for age and sex. RESULTS: Whole-body insulin sensitivity was significantly improved in carriers compared with non-carriers of the Ala-allele of the codon 12 polymorphism in Swedish Caucasian men (6.0+/-2.5 vs 5.6+/-2.5 mg kg(-1) x min(-1) x mU/l](-1) x 100, p = 0.044). The same tendency, but not significant, was observed in the insulin sensitivity index among the group of young healthy Danish Caucasians. The incidence of Type II diabetes and IGT among the Swedish subjects at the age of 70 was similar in the three genotype-groups of the Pro12Ala variant and the Ala-allele was not related to a lower prevalence of Type II diabetes in Danish Caucasians. CONCLUSION/INTERPRETATION: The Ala-allele of the PPAR-gamma2 polymorphism is associated with improved whole body insulin sensitivity among Swedish Caucasians.

Aged↗

Myocardial distribution and regulation of GRK and beta-arrestin isoforms in congestive heart failure in rats.

Myocardial G protein-coupled receptor kinase 2 (GRK2) has been shown to be involved in the pathophysiology of congestive heart failure (CHF). However, the cellular distribution of this isoform, as well as the other isoforms of the GRK-arrestin system, has not been studied in myocardial tissue. Thus myocardial expression and cellular distribution of the different GRK and arrestin isoforms were investigated in a rat model of CHF. Rats subjected to ligation of the left coronary artery or sham operation were euthanized 2, 7, or 42 days after the surgical procedure. Myocardial GRK2, GRK5, beta-arrestin-1, and beta-arrestin-2 mRNA levels, but not that of GRK3, were induced in the failing hearts. Consistently, Western blot analysis of tissue extracts from the nonischemic region of the left ventricle revealed 3.0-, 2.6-, and 1.5-fold elevations of GRK2, GRK5, and beta-arrestin-1, respectively, 7 days after induction of myocardial infarction compared with the sham-operated rats (P < 0.05). Immunohistochemical analysis of myocardial tissue sections and Western blot analysis of isolated cells revealed localization of GRK2 and beta-arrestin-1 predominantly in endothelial cells. Conversely, GRK3 was confined to cardiac myocytes. GRK5 immunostaining appeared to be homogeneously distributed in the cellular elements of the myocardium. In conclusion, myocardial mRNA and protein levels of GRK2, GRK5, and beta-arrestin-1 are induced in postinfarction failure in rats. The immunohistochemical analysis suggests that GRK2 and beta-arrestin-1 may act as primary regulators of endothelial function. Conversely, the cellular distribution of GRK3 and GRK5 implicates these isoforms as putative regulators of cardiac myocyte function.

Animals↗

Correlation between diffusion- and perfusion-weighted MRI and neurological deficit measured by the Scandinavian Stroke Scale and Barthel Index in hyperacute subcortical stroke (< or = 6 hours).

OBJECTIVE: We used combined diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI to characterize hyperacute infarctions within 6 h of symptom onset with special reference to subcortical infarctions, and investigated the relation between perfusion-diffusion mismatch volume and functional outcome. MATERIAL AND METHODS: Twenty-two patients presenting with symptoms of acute stroke underwent DWI and PWI within 6 h of symptom onset, and follow-up MRI 30 days later. Twelve of these had a subcortical infarction on acute DWI. Lesion volumes were measured by acute DWI and PWI as well as chronic T(2)-weighted MRI (T2WI). Clinical severity was measured by the Scandinavian Stroke Scale (SSS) and the Barthel Index (BI). RESULTS: In the 12 patients with subcortical infarctions, PWI and especially DWI correlated strongly with acute and chronic neurological SSS score, as well as with final infarct volume. Furthermore, a hyperacute PWI/DWI mismatch in this subgroup predicted lesion growth. There was a weaker correlation between acute DWI/PWI and neurological score among all 22 patients, and patients with a PWI/DWI mismatch larger than 100 ml had a significantly larger lesion growth and a poorer outcome than patients with a smaller mismatch. CONCLUSIONS: Subcortical infarctions may represent a sizeable subgroup of acute stroke patients. Also subcortical infarctions may have a PWI/DWI mismatch and therefore may respond to neuroprotective/thrombolytic therapy. Hyperacute DWI may reflect the acute clinical status and predict the outcome in patients with subcortical infarction.

Adult↗

Viability thresholds of ischemic penumbra of hyperacute stroke defined by perfusion-weighted MRI and apparent diffusion coefficient.

BACKGROUND AND PURPOSE: The penumbra of ischemic stroke consists of hypoperfused, but not irreversibly damaged, tissue surrounding the ischemic core. The purpose of this study was to determine viability thresholds in the ischemic penumbra, defined as the perfusion/diffusion mismatch in hyperacute stroke, by the use of diffusion- and perfusion-weighted MRI (DWI and PWI, respectively). METHODS: DWI and PWI were performed in 11 patients </=6 hours after the onset of symptoms of acute ischemic stroke. Regions of interest (ROIs) were placed covering the ischemic core (ROI 1), the penumbra that progressed to infarction on the basis of follow-up scans (ROI 2), and the penumbra that recovered (ROI 3). The ratios of relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT), and apparent diffusion coefficient were calculated as lesion ROIs relative to the contralateral mirror ROIS: RESULTS: The post hoc analysis showed that the penumbra progressed to infarction at the following cutoff values: rCBF <0.59 and MTT >1.63. Higher sensitivity and accuracy in predicting outcome of the penumbra were obtained from the rCBF maps compared with the rCBV and MTT maps. The initial rCBV and apparent diffusion coefficient ratios did not differentiate between the part of the penumbra that recovered and the part that progressed to infarction. The mean rCBF ratio was optimal in distinguishing the parts of the penumbra recovering or progressing to infarction. CONCLUSIONS: The thresholds found in this study by combined DWI/PWI might aid in the selection of patients suitable for therapeutic intervention within 6 hours. However, these hypothesized thresholds need to be prospectively tested at the voxel level on a larger patient sample before they can be applied clinically.

Acute Disease↗

[Neutralization of lidocaine-adrenaline. A simple method for less painful application of local anesthesia].

The amount of sodium bicarbonate necessary to neutralise commercially available lignocaine-epinephrine (pH 4.7) to physiologically neutral pH (7.4) was established. The analysis showed that neutral pH could be accomplished by adding 1.0 ml sodium bicarbonate (8.4 g/l) to 10 ml lignocaine-epinephrine (1%, 5 microgram/ml). Chemical analysis also established that the neutralised lignocaine-epinephrine was stable for 24 hours after adding sodium bicarbonate. A double-blinded randomised clinical trial with crossover design done on volunteers from hospital staff proved that injection of neutralised lignocaine-epinephrine is less painful than commercially available lignocaine-epinephrine (p < 0.001).

Anesthetics, Local↗

Postoperative pain control by epidural analgesia after transabdominal surgery. Efficacy and problems encountered in daily routine.

BACKGROUND: The efficacy of postoperative epidural pain treatment has been well documented in controlled studies. However, the literature concerning results of daily routine use of this method often only emphasises certain aspects of it. METHODS: A prospective study of 168 patients scheduled for major surgery with transabdominal access was performed in order to evaluate efficacy, side effects, complications and rate of acceptance of postoperative epidural pain treatment. The epidural catheter was placed before surgery and the patients received epidural analgesia by a bupivacaine/morphine mixture for 3 days postoperatively, continued by another 3 days with bolus injections of morphine only. RESULTS: Only few complications followed the insertion of the epidural catheter, but in about 16% of the patients the epidural catheter or the drugs administered by it made reinsertion or change in the type of analgesia necessary during the first 3 post-operative days. Despite the possibility for individualising the treatment and p.r.n. analgesics, pain relief when coughing and moving during day 1-3 was insufficient in 30-50% of the patients. Serious side effects were rare, but pruritus was frequent, as were the symptoms of nausea and vomiting. The patients were generally satisfied with the treatment; however, a small group had unacceptable pain when the epidural catheter was inserted. CONCLUSION: Analgesia was insufficient when coughing and moving in an unacceptably large number of the patients. Also the number of epidural catheter related problems was high. In order to make early intervention possible, the patients and epidural catheters should be observed daily and systematically by members of the staff competent to detect possible problems.

Abdomen↗

Magnetic, microplate-format plasmid isolation protocol for high-yield, sequencing-grade DNA.

We have developed a rapid, microplate-format plasmid isolation procedure to purify sequencing-grade DNA templates for high-throughput DNA sequencing operations. A modified lysozyme/boiling method is used to produce a plasmid-containing supernatant that is then purified by iron bead capture. After binding, the beads are pelleted in a magnetic field, washed and the DNA eluted in water. The method yields up to 10 micrograms plasmid DNA from a 1-mL overnight culture in a deep-well microplate. The procedure is suitable for large-scale experiments, amenable to automation and does not require expensive reagents or equipment. The entire protocol can be completed in as little as 2 h, and one technician with a 96-well pipetting station can process up to 48 plates per day. This protocol is ideal for any high-throughput operation in which template quantity, quality and reproducibility are of primary importance.

DNA↗

Tramadol relieves pain and allodynia in polyneuropathy: a randomised, double-blind, controlled trial.

It is generally believed that opioids relieve neuropathic pain less effectively than nociceptive pain and that they have no effect on some of the key characteristics of neuropathic pain such as touch-evoked pain (allodynia). Tramadol is an analgesic drug acting directly on opioid receptors and indirectly on monoaminergic receptor systems. The aim of this trial was to determine whether tramadol relieved painful polyneuropathy and reduced allodynia. The study design was randomised, double-blind, placebo-controlled and cross-over. After baseline observations, 45 patients were assigned to one of the two treatment sequences. The dose of tramadol slow-release tablets was titrated to at least 200 mg/day and at highest 400 mg/day. During the two treatment periods of 4 weeks duration, patients rated pain, paraesthesia and touch-evoked pain by use of 0-10 point numeric rating scales. Mechanical allodynia induced by stimulation with an electronic toothbrush was rated at the end of each treatment period with a similar scale. Thirty-four patients completed the study. Their ratings for pain (median 4 vs. 6, P=0.001), paraesthesia (4 vs. 6, P=0.001) and touch-evoked pain (3 vs. 5, P<0.001) were lower on tramadol than on placebo, as were their ratings of allodynia (0 vs. 4, P=0.012). The number needed to treat to obtain one patient with >/=50% pain relief was 4.3 (95% confidence interval 2.4-20). It is concluded that tramadol appears to relieve both ongoing pain symptoms and the key neuropathic pain feature allodynia in polyneuropathy.

Adult↗

Citalopram treatment of traumatic brain damage in a 6-year-old boy.

Traumatic brain damage may cause acute emotional symptoms such as uncontrolled crying, apathy, and sleep problems. Rehabilitation may be less effective in patients afflicted by these symptoms. Citalopram, a selective serotonin reuptake inhibitor (SSRI), has a documented immediate and dramatic effect on pathological crying in stroke patients. The present case history of a 6-year-old boy with a traumatic right-sided hemorrhage in the basal ganglia indicates that early SSRI treatment has a dramatic effect on pathological crying and in addition may have a concomitant beneficial effect on motor paresis, sleep disturbance, and neurobehavioral problems.

Basal Ganglia↗

[Epidemiology of cancer pain].

The prevalence of pain in cancer patients is influenced by several factors, for example the cancer disease, stage of disease, metastases present and treatment. However, only very few studies take all these factors in account when presenting the prevalence of pain in cancer patients. Pain may be caused by direct tumour infiltration, but may also be indirectly related to the cancer disease, caused by the cancer treatment or unrelated to the cancer. The most frequent pain quality is somatic pain followed by visceral and neuropathic pain. Pain with certain qualities or characteristics, such as incident pain, tenesmi in the gastrointestinal tract or cramps located to the bladder or rectum are more difficult to relieve than other pains. Other factors, such as major psychological distress, fast increasing doses of opioids and a past history of addictive behaviour may also be predictive of a poor treatment outcome. Besides pain cancer patients may also suffer from other troublesome symptoms such as asthenia, anorexia, constipation, nausea and vomiting and poor quality of sleep. These symptoms have great impact on the patients' well-being and should be treated contemporarily.

Humans↗

Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty--the Danish Prolonged Prophylaxis (DaPP) Study.

The aim of this study was to compare the efficacy and safety of prolonged (35 days) thromboprophylaxis with a standard length (7 days) regimen of a low molecular weight heparin in patients undergoing total hip arthroplasty. The study was multicentre, randomised, double-blind, and prospective with two groups. Following seven days on a standard length regimen of dalteparin (5000 antifactor Xa units subcutaneously once daily starting 12 h before surgery), patients were randomized to continue the prophylaxis with either subcutaneous injections of dalteparin or placebo injections for a further 28 days. Efficacy was evaluated at the end of the study (day 35) in all patients with bilateral ascending phlebography to detect deep vein thrombosis. Bleeding complications and other adverse events were registered throughout the study period. Three hundred consecutive patients agreed to participate before the operation: 281 were finally randomised and 215 completed the study; two patients died before randomisation; 17 developed deep vein thrombosis; none developed pulmonary embolism; and five of 113 patients (4.4%, 95% CI 1-10%) developed deep vein thrombosis in the dalteparin group, compared with 12 of 102 (11.8%; 95% CI 6-20%) in the placebo group (p=0.039). Deep vein thrombosis in the proximal veins was diagnosed in one patient (0.9%; 95% CI 0-5%) in the dalteparin group, and in five (5.0%; 95% CI 2-11%) in the placebo group (p=0.076). Major bleeding was observed in one patient in the placebo group; minor bleeding complications and adverse events were equally distributed between the groups. We concluded that prolonged (35 days) thrombo prophylaxis with dalteparin is more effective than a standard length (7 days) regimen without increased risk of bleeding complications or other adverse events.

Adult↗

Risks associated with removal of ventricular epicardial pacing wires after cardiac surgery.

BACKGROUND: Epicardial pacing wires are routinely used for the diagnosis and treatment of bradyarrhythmias after cardiac surgery. The frequency of arrhythmias during removal of the wires is unknown, and methods of removal vary among institutions. OBJECTIVES: To describe the frequency of ventricular arrhythmias during removal of epicardial pacing wires from the right ventricle, to determine variables that are predictive of ventricular arrhythmias during wire removal, and to describe patients' perceptions of wire removal. METHODS: A convenience sample of 145 patients who had undergone cardiac surgery was studied during the course of 1 year. Electrocardiographic and vital signs were recorded throughout wire removal. Patients' records were reviewed for variables that could predict the occurrence of arrhythmias during wire removal: laboratory values, history of arrhythmias, medications, medical history, postoperative course, and pain reported by the patient. RESULTS: Sixty-six percent of patients had one premature ventricular contraction or more while the ventricular wires were being removed. Seven percent of patients had nonsustained ventricular tachycardia during wire removal. Patients who had repeat cardiac surgery had significantly more nonsustained ventricular tachycardia than did all other patients (P < .01). Only a history of heart failure (P < .02) was a significant predictor of premature ventricular contractions during wire removal. On a scale of 0 (no pain) to 10 (worst pain), the mean rating of pain intensity reported by patients was 2.39 (SD = 2.77). CONCLUSION: Patients may be at risk for ventricular arrhythmias during removal of epicardial pacing wires. Findings support the need for electrocardiographic monitoring while pacing wires are being removed.

Adult↗

[Morphine metabolism--pharmacokinetics and pharmacodynamics].

With the increasing use of morphine, growing interest for the clinical implications of its metabolites, morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) has emerged in the literature. M-6-G binds to the opioid receptor and has analgesic properties in man. Clinical studies have not delivered strong evidence of significant correlation between the concentration of morphine and its glucuronides in plasma and cerebrospinal fluid and pharmacodynamics such as analgesia. There is no clinical evidence to indicate that M-6-G has a pronounced respiratory depressing effect in man, while the literature contains conflicting reports with regard to other side-effects. M-3-G does not bind to the m-opioid receptor and consequently has no antinociceptive effects. Studies in rodents have shown that morphine, M-6-G and especially M-3-G may induce hyperalgesia, allodynia and myoclonus. It is assumed that these side effects are caused by a spinal antiglycinergic mechanism. The role of M-3-G in morphine antagonism and development of tolerance has not yet been settled. As M-3-G and M-6-G are eliminated by the kidneys, renal insufficiency will lead to accumulation of these. Accordingly dosage should be reduced or other opioids be considered in such cases.

Humans↗

The structure of cyclin H: common mode of kinase activation and specific features.

The crystal structure of human cyclin H refined at 2.6 A resolution is compared with that of cyclin A. The core of the molecule consists of two repeats containing five helices each and forming the canonical cyclin fold also observed in TFIIB. One hundred and thirty-two out of the 217 C alpha atoms from the cyclin fold can be superposed with a root-mean-square difference of 1.8 A. The structural homology is even higher for the residues at the interface with the kinase, which is of functional significance, as shown by our observation that cyclin H binds to cyclin-dependent kinase 2 (cdk2) and that cyclin A is able to activate cdk7 in the presence of MAT1. Based on this superposition, a new signature sequence for cyclins was found. The specificity of the cyclin H molecule is provided mainly by two long helices which extend the cyclin fold at its N- and C-termini and pack together against the first repeat on the side opposite to the kinase. Deletion mutants show that the terminal helices are required for a functionally active cyclin H.

Amino Acid Sequence↗