Search PubMed⌕ Search

Biomedical subjects

H Andersen

Publications and source records attributed to H Andersen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Volume of ankle dorsiflexors and plantar flexors determined with stereological techniques.

The validity of the methods used for determination of muscle mass has not been evaluated previously. We determined muscle mass by estimating muscle volume with assumption-free stereological techniques applied to magnetic resonance imaging (MRI) in 18 healthy untrained subjects (6 women, 12 men) aged 41 yr (29-64 yr; median, range). Muscle mass was also estimated by measuring leg circumference and cross-sectional muscle areas (CSA) from MRIs at three predetermined levels. Power [peak torque (PT)] of the ankle dorsiflexors and plantar flexors was estimated by using isokinetic dynamometry. Dorsiflexor volume (r2 = 0.76, P < 5 x 10(-6)) and CSA (r2 = 0.73, P < 5 x 10(-5)) were related to PT, whereas circumference was not (r2 = 0.17, not significant). Correspondingly, a relationship to plantar PT was established for plantar flexor volume (r2 = 0.69, P < 5 x 10(-5)) and CSA (r2 = 0.46, P < 5 x 10(-3)) but not leg circumference (r2 = 0.15, not significant). SDs of the residuals were smaller for the relationship between dorsiflexor PT and volume than between PT and CSA (0.42 vs. 0.45) for plantar flexors (1.5 vs. 2.0). By using the Cavalieri method, six MRI sections and 15 min of point counting are sufficient to obtain a valid estimate of the volume of the muscles of the lower leg.

Adult↗
PubMed1998

Cloning and characterization of human protease-activated receptor 4.

Protease-activated receptors 1-3 (PAR1, PAR2, and PAR3) are members of a unique G protein-coupled receptor family. They are characterized by a tethered peptide ligand at the extracellular amino terminus that is generated by minor proteolysis. A partial cDNA sequence of a fourth member of this family (PAR4) was identified in an expressed sequence tag database, and the full-length cDNA clone has been isolated from a lymphoma Daudi cell cDNA library. The ORF codes for a seven transmembrane domain protein of 385 amino acids with 33% amino acid sequence identity with PAR1, PAR2, and PAR3. A putative protease cleavage site (Arg-47/Gly-48) was identified within the extracellular amino terminus. COS cells transiently transfected with PAR4 resulted in the formation of intracellular inositol triphosphate when treated with either thrombin or trypsin. A PAR4 mutant in which the Arg-47 was replaced with Ala did not respond to thrombin or trypsin. A hexapeptide (GYPGQV) representing the newly exposed tethered ligand from the amino terminus of PAR4 after proteolysis by thrombin activated COS cells transfected with either wild-type or the mutant PAR4. Northern blot showed that PAR4 mRNA was expressed in a number of human tissues, with high levels being present in lung, pancreas, thyroid, testis, and small intestine. By fluorescence in situ hybridization, the human PAR4 gene was mapped to chromosome 19p12.

Amino Acid Sequence↗
PubMed1998

[Frequency of admissions to neonatal care units of 1994 birth cohorts in Funen and Frederiksborg Counties].

The frequency of admission to neonatal intensive care units is higher in Denmark than in the UK. The organization of the paediatric departments varies from county to county in Denmark. To investigate possible differences due to the organization, the records for all hospitalized newborns in a one year period in two counties (FR and FU) were studied. The rate of prematurity was higher in county FU than in FR, but, surprisingly, the admission rate was lowest in county FU. For full term infants the highest admission rate was found in county FR, where more infants were treated with nasal continuous positive airway pressure compared to FU. Short admissions were more common in FR. The on-call paediatrician is a senior doctor in FU, whereas it is a junior doctor in FR, and this could be a possible explanation for the differences between the two counties.

Denmark↗
PubMed1998

Association of muscle strength and electrophysiological measures of reinnervation in diabetic neuropathy.

Motor function was assessed in 34 non-insulin-dependent and 19 insulin-dependent diabetic patients with macroelectromyography and isokinetic dynamometry. Fiber density (FD) and the amplitude of the macro motor unit potential (macro MUP) of the anterior tibial and lateral vastus muscles were obtained and maximal isokinetic strength of the ankle and knee extensors were determined. All patients underwent standardized clinical examination including a neurological disability score (NDS), quantitative sensory examination, and conventional motor nerve conduction studies. The amplitude of the macro MUP and FD of the anterior tibial muscle were increased in neuropathic patients without weakness (P < 0.05) and further increased in neuropathic patients with weakness (P < 0.05). The NDS was related to the FD and the amplitude of the macro MUP for the anterior tibial and lateral vastus muscle [r=0.55-0.75 (P < 0.005)]. Muscle strength of ankle and knee extensors correlated with the FD [r=-0.69 (P < 0.0001) and r=-0.58 (P< 0.001), respectively] and with the amplitude of the macro MUP of the two muscles [r=-0.63 (P < 0.0001) and r=-0.37 (P < 0.05), respectively]. Our findings support the hypothesis that loss of muscle strength in diabetic patients is due to incomplete reinnervation following axonal loss.

Adult↗
PubMed1998

Association of IgM type anti-GM1 antibodies and muscle strength in chronic acquired demyelinating polyneuropathy.

The pathogenetic role of anti-GM1 in chronic acquired demyelinating polyneuropathy (CADP) is uncertain. An association between antibodies and disease activity has not yet been established. In 8 patients with CADP followed longitudinally, anti-GM1 antibodies were monitored with a standardized enzyme-linked immunosorbent assay technique and muscle performance with isokinetic dynamometry. During a mean observation period of 24 months, strength improved in 6 of 8 patients by a median value of 54.5%, and anti-GM1 fell in all 6 patients; the reduction being 43%. In 2 patients, muscle performance deteriorated by 30 and 8%, whereas anti-GM1 titers increased by 10 and 9%, respectively. The relative change in anti-GM1 was inversely related to muscle performance. Clinical scoring of muscle performance according to the Medical Research Council scale failed to show an association with anti-GM1. It is concluded that anti-GM1 antibodies are closely related to disease activity, and that the close association indicates a role of anti-GM1 in the pathogenesis of CADP.

Adult↗
PubMed1998

Decreased muscle strength in patients with alcoholic liver cirrhosis in relation to nutritional status, alcohol abstinence, liver function, and neuropathy.

To study motor function quantitatively in alcoholic liver cirrhosis muscle strength, liver function, peripheral nerve function, and nutrition were assessed in 24 patients. Isokinetic strength of flexion and extension at elbow, wrist, hip, knee, and ankle and of shoulder abduction and adduction was evaluated and compared with findings in 24 matched healthy subjects. Degree of liver disease was assessed with the Child-Pugh score and the galactose elimination capacity (GEC). Nutritional status was evaluated with an estimation of lean body mass (LBM) from 24-hour urinary creatinine excretions. Peripheral nerve function was evaluated with neurological symptom and disability scores, nerve conduction studies, and quantitative sensory tests summed to obtain a neuropathy rank-sum score (NRSS) for each patient. Combined muscle strength at hip, knee, ankle, shoulder, elbow, and wrist were weakened with 34% (P < .005), 35% (P < .001), 35% (P < .01), 34% (P < .01), 29% (P < .01), and 29% (P < .02), respectively. The median Child-Pugh score was 7 (range, 5-12), and the median duration of alcohol abstinence was 90 days (range, 5-960 days). After multiple linear regression analysis including LBM, Child-Pugh score, GEC, duration of alcohol abstinence, and NRSS, only LBM was correlated to the strength at the knee (r=.79; P < .0001) and at the ankle (r=.63; P < .01). It is concluded that muscle strength is weakened substantially in alcoholic patients with liver cirrhosis and that weakness is related to the severity of malnutrition but not to the severity of liver disease, duration of alcohol abstinence, or neuropathy.

Adult↗
PubMed1998

Muscular endurance in long-term IDDM patients.

OBJECTIVE: To determine the short-term muscular endurance and working capacity of leg muscles in long-term IDDM patients in relation to neuropathic complications, muscle strength, and metabolic control. RESEARCH DESIGN AND METHODS: The muscular endurance of extensors and flexors at the ankle and knee was assessed in 44 IDDM patients and in 44 matched control subjects during 30 maximal isokinetic movements. The endurance index was the work performance of the last 5 movements relative to the first 5 movements. Total work was the summated work of all movements. All patients underwent a neurological evaluation, nerve conduction studies, and quantitative sensory tests. RESULTS: The combined endurance index of the ankle extensors and flexors was 70% (51-88) (median [range]) in the diabetic group and 65% (55-82) in the control group (P < 0.01). For knee extensors and flexors the combined endurance index was 65% (55-103) for the diabetic patients and 63% (48-75) in the control subjects (P < 0.01). The endurance index related neither to the severity of neuropathy nor to the metabolic control (blood glucose and HbA1c) for any of the muscle groups. Diabetic patients had reduced strength of all muscle groups (14-24%, P < 0.02) and impaired total work performance (15-20%, P < 0.01) for ankle movements. CONCLUSIONS: Long-term IDDM patients have increased endurance but reduced strength and work performance of leg muscles. The combined effect of the motor abnormalities is suggested to give rise to functional impairment, including an increased risk of falls and injuries.

Adult↗
PubMed1997

High-affinity binding sites for 125I-labelled pancreatic secretory phospholipase A2 in rat brain.

Porcine pancreatic secretory phospholipase A2 (ppsPLA2) has been shown to modulate agonist and antagonist binding to alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) receptors and to effect neurotransmission in the central nervous system (CNS). To further elucidate the mechanism of action of ppsPLA2 in the CNS, the binding profile of 125I-labelled ppsPLA2 to rat whole-brain membranes was assessed. Two classes of calcium-dependent binding sites were detected using unlabelled ppsPLA2 as a displacer with IC50 values of 3 and 217 nM. Similar values were obtained for [125I]ppsPLA2 binding to membranes prepared from isolated cortical and hippocampal rat brain regions. [125I]ppsPLA2 binding displayed bell-shaped concentration-dependence curves to Ca2+, Zn2 + and pH. Binding was not inhibited by AMPA, the false substrate, oleoyloxyethyl phosphocholine (OOPC), or by BSA-galactose or wheat germ agglutinin. [125I]ppsPLA2 binding was reduced by treatment of the rat brain membranes with mercaptoethanol and proteinase K treatment or by their pre-incubation at 95 degrees C. These results show a different binding profile to the previously characterised snake venom sPLA2 N-type receptors and suggest the existence of novel class of sPLA2 N-type binding sites.

Animals↗
PubMed1997

Disordered mobility of large joints in association with neuropathy in patients with long-standing insulin-dependent diabetes mellitus.

Movement performance was studied in 29 long-term patients with insulin-dependent diabetes mellitus (IDDM) and 29 matched control subjects. Velocity, range of motion, reaction time, and strength of ankle dorsal and plantar flexion and knee extension were measured. The neuropathic condition was assessed from clinical examination, nerve conduction studies, and quantitative sensory examination, and summed to obtain a neuropathy rank-sum score. Reaction time for the diabetic patients was increased by 29%, 23%, and 22% for ankle dorsal, ankle plantar, and knee extension movements respectively (p < 0.001). Range of motion was slightly decreased at ankle dorsal flexion (12%, p < 0.05). There was an inverse relationship between range of motion and neuropathy rank-sum score for ankle dorsal (r = -0.68, p < 0.001) and plantar flexion (r = -0.61, p < 0.001). Peak velocity was significantly decreased at ankle dorsal (21%, p < 0.001) and plantar flexion (23%, p < 0.001) and was related to the isokinetic muscle strength. Peak velocity was also related to the neuropathy rank-sum score at ankle dorsal flexion (r = 0.57, p < 0.002). We conclude that maximal movements at the ankle are delayed and slowed in long-term IDDM patients. The decreased peak velocity and the range of motion are related to the severity of neuropathy.

Adult↗
PubMed1997

F-wave latency, the most sensitive nerve conduction parameter in patients with diabetes mellitus.

In this study we examined the diagnostic sensitivity of minimal F-wave latency, F-wave persistence, motor nerve conduction velocity (MCV), and amplitude of the compound motor action potential (CMAP) of the median, ulnar, tibial, and peroneal nerves, and of sensory conduction velocity (SCV) and sensory nerve action potential (SNAP) amplitude of the sural nerve in 82 diabetic patients. For the median, ulnar, and tibial nerves the Z scores of the minimal F-wave latency were significantly larger than those of the MCV, and for all four motor nerves the Z scores of the minimal F-wave latency were significantly larger than those of the amplitude of the CMAP. The Z scores of the peroneal minimal F-wave latency exceeded those of peroneal MCV, sural SCV, and sural SNAP. F-wave persistence did not differ significantly from the reference values. In conclusion, minimal F-wave latency is the most sensitive measure for detection of nerve pathology and should be considered in electrophysiological studies of diabetic patients.

Action Potentials↗
PubMed1997

Muscular atrophy in diabetic neuropathy: a stereological magnetic resonance imaging study.

Diabetic patients with polyneuropathy develop motor dysfunction. To establish whether motor dysfunction is associated with muscular atrophy the ankle dorsal and plantar flexors of the non-dominant leg were evaluated with magnetic resonance imaging in 8 patients with symptomatic neuropathy, in 8 non-neuropathic patients and in 16 individually matched control subjects. In the neuropathic patients the muscle strength of the ankle dorsal and plantar flexors was reduced by 41% as compared to the non-neuropathic patients (p < 0.005). Volume of the ankle dorsal and plantar flexors was estimated with stereological techniques from consecutive cross-sectional images of the lower leg. The neuropathic patients had a 32% reduction in volume as compared with the non-neuropathic patients (p < 0.005). To determine the regional distribution of atrophy cross-sectional magnetic resonance images were performed at predetermined levels of the lower leg in relation to bone landmarks. In the neuropathic patients there was an insignificant increase of 3% of muscle area at the proximal lower leg level, whereas the atrophy was 43% (p < 0.002) at the mid lower leg level and 65% (p < 0.002) distally. Analysis of individual muscles confirmed that the atrophy predominated distally. We conclude that muscular atrophy underlies motor weakness at the ankle in diabetic patients with polyneuropathy and that the atrophy is most pronounced in distal muscles of the lower leg indicating that a length dependent neuropathic process explains the motor dysfunction.

Adult↗
PubMed1997

Early clinical investigation of sulofenur with a daily schedule in advanced solid tumours.

Sulofenur, a sulfonylurea, has demonstrated antitumour effect in preclinical studies. A phase I trial was initiated to study the clinical aspects. Sulofenur was given p.o. daily for a period of 28 days in 5-week courses. The initial dosage was 250 mg/m2 escalating to 700 mg/m2 daily with no dose modification for the individual patient at any given dose level; 38 patients with advanced solid malignant tumours were enrolled. Haemolytic anaemia was the main side effect. The toxicity was marked at dose levels of 600 and 700 mg/m2. Moderate methaemoglobinaemia also occurred. One case of reversible toxic hepatitis was observed. Generally was ALAT, and more moderately basic phosphatases, and LDH elevated. Tumour regression was not observed but one patient had stable disease throughout nine courses. The maximal detected plasma concentration of Sulofenur in this study was 348 x 10(-6) g/ml. In the present study the maximum tolerated dose (MTD) of Sulofenur was defined to 600 mg/m2. One conclusion from this study is that even at doses above that recommended for future studies-5-600 mg/m2-with this schedule, the suggested effective plasma level from preclinical studies could not be reached. The overall conclusion is that this schedule should not be recommended at all for future studies and the recommendation should be to try to find a schedule in which higher plasma levels can be achieved at a clinically tolerated dose.

Adult↗
PubMed1997

Detection of irregular red cell antibodies: more than 3 years of experience with a gel technique and pooled screening cells.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate more than 3 years of experience with a gel technique in combination with pooled screening cells for the detection of irregular red cell antibodies. MATERIALS AND METHODS: Conventional serologic methods were used for blood typing, antibody screening and cross-matching until the end of 1992. We introduced the gel technique as a routine assay for antibody detection and identification in 1993. RESULTS: After the tube technique had been abandoned, the number of false-positive antibody screening tests was reduced by 71%, positive antibody screening tests by 33%, enzyme agglutination by 100% and rouleaux reactions and cold-reacting antibodies by more than 50%. There was a 40% increase in first-time detection of clinically relevant antibodies. We saw no increase in delayed haemolytic transfusion reactions. CONCLUSIONS: For the detection of irregular red cell antibodies, pooled screening cells in combination with a gel technique are at least as efficient and safe as a conventional tube technique with unpooled test cells.

Blood Grouping and Crossmatching↗
PubMed1997

Diabetes mellitus.

Epidemiological studies have documented a high prevalence of diabetic neuropathy. The risk of lower leg amputation is increased three to four times in patients with clinical signs of neuropathy and ankle weakness is more common than hitherto recognized. Increased nerve hydration and increased expression of low affinity p75 receptor for neurotrophins suggest new therapeutic potentials for the prevention of diabetic neuropathy.

Diabetes Mellitus, Type 1↗
PubMed1997

A comparative study of isokinetic dynamometry and manual muscle testing of ankle dorsal and plantar flexors and knee extensors and flexors.

Muscle strength in neuropathic patients is usually evaluated clinically using manual muscle testing (MMT). Detection and grading of mild symmetrical muscle weakness using MMT is difficult partly because the examiner must take into consideration the normal variation in strength in relation to age, weight, height, and gender. In the present study assessment of the strength of ankle dorsal and plantar flexors and knee flexors and extensors with MMT and isokinetic dynamometry were compared in 108 patients, of whom 86 had diabetes mellitus and 22 had alcoholic liver cirrhosis. The isokinetic muscle strength of the patients was compared with the strength of 90 healthy control subjects, adjusted for the influence of age, weight, and height for both genders. MMT resulted in a significant underestimation of the frequency and severity of muscle weakness in both the ankle and the knee. In 28-41% of the comparisons, MMT misclassified the strength performance with one category or more (> 25%). Misclassifications were most frequent for the ankle plantar flexors.

Adult↗
PubMed1997

A clinical quality management support system.

In the CONQUEST Quality Management System, assessment and improvement of the quality of treatment process and outcome is done by introducing a Clinical Quality Management Support System. Initially the treatment of breast cancer was chosen to illustrate the potential benefits of introducing quality management in the treatment process. The main objective of the CONQUEST Quality Management System is to provide a flexible framework for supplying quality management of the treatment process and enable comparison of clinical results, despite differences in the local best clinical practice guidelines used in the participating treatment centres.

Breast Neoplasms↗
PubMed1996

Peptide, disulfide, and glycosylation mapping of recombinant human thrombopoietin from ser1 to Arg246.

Thrombopoietin (TPO) is a hematopoietic factor involved in the regulation of megakaryocytopoiesis. Full length recombinant human TPO (332 residues) has been expressed in BHK cells and purified to homogeneity using conventional means. Peptide, disulfide, and glycosylation mapping of human TPO from residues 1 to 246 has been carried out using liquid chromatography-electrospray mass spectrometry (LC-ESMS). A modification of the ramped orifice method of Carr and co-workers [Carr et al. (1993) Protein Sci. 2, 183-196] is employed, providing additional information for assignment of the LC-ESMS chromatograms. With the modification, b- and y-series peptide ions are produced via front-end CID which confirms the mass-based assignments. The results of our analysis of TPO indicate that the amino acid sequence of TPO 1-246 is as expected from the transfected cDNA with complete cleavage of the signal peptide. Two unique disulfides are formed between the four cysteines in the cytokine domain of TPO: Cys7-Cys151 and Cys29-Cys85. The glycosylation map indicates the position, occupancy, and structures of the N- and O-glycans in TPO 1-246. In addition, site specific structural characterization of the PNGase F-liberated N-glycans has been performed following purification by high-pH anionic exchange chromatography with pulsed amperometric detection (HPAEC-PAD); the results corroborate the LC-ESMS data. The N-glycans are of the complex type with the core-fucosylated disialylated biantennary and trisialylated triantennary structures predominating. The O-glycans are of the mucin type with the monosialylated and disialylated GalGalNAc-S/T structures predominating. Furthermore, we propose that the C-terminal domain of TPO be further divided into two domains on the basis of sequence homology among the cloned sequences and glycosylation/structural features: an N-glycan domain (154-246) and an O-glycan domain (247-332).

Amino Acid Sequence↗