Search PubMed⌕ Search

Biomedical subjects

M Hansen

Publications and source records attributed to M Hansen.

At least 145 records · Page 8Linked to original sources
PubMed1996

Procollagen type I N-terminal propeptide (PINP) as an indicator of type I collagen metabolism: ELISA development, reference interval, and hypovitaminosis D induced hyperparathyroidism.

A sandwich enzyme-linked immunosorbent assay (ELISA) for quantification of the N-terminal propeptide of human procollagen type I (PINP) utilizing purified alpha 1-chain specific rabbit antibodies is described. The ELISA measured the content of the alpha 1-chain of PINP independent of the molecular form of the molecule. A parallelism was found between amniotic fluid (calibrator), normal and patient serum, and purified PINP (alpha 1), as well as the high and low molecular weight forms of PINP (alpha 1). The concentration of PINP in the calibrator (second trimester amniotic fluid) was determined to 25 micrograms/mL and the detection limit was 62 pg/mL measured in amniotic fluid, and 41 pg/mL measured in serum. The interassay coefficients of variation were 4.6% (low control) and 5.3% (high control), and the corresponding intraassay parameters were 2.9% and 4.9%. Recovery studies revealed an accuracy between 93% and 105%. The normal range (n = 57) for PINP was 56 ng/mL (median) the 10th and 90th centiles being 30 and 82 ng/mL, respectively. Patients with hyperparathyroidism due to hypovitaminosis D had median serum level of 168 ng/mL with a 10th centile of 44 ng/mL and a 90th centile of 450 ng/mL, these values being significantly different from the normal range (p < 0.001). The PINP-ELISA was superior to commercially available assays for PICP and osteocalcin in separation between healthy controls and patients with osteomalaci.

Adult↗
PubMed1996

Incidence of extramural venous invasion in colorectal carcinoma: findings with a new technique.

In reported studies of extramural venous invasion (EVI) by colorectal carcinoma (CRC) in which conventional preparations involving a sectioning plane perpendicular to the tumor were used, an incidence as high as 36% has been found for unselected surgical material from patients operated on for cure. However, with this preparation technique, not all of the veins that exit the bowel wall roughly at right angles can be examined adequately. We investigated whether preparation of the adjacent vascular connective tissue with tangential sectioning might not result in different EVI rates. A total of 100 unselected surgical specimens of the bowel bearing 103 CRCs were prepared using a previously undescribed method, and EVI was found in 54.1% of the cases considered to have been treated curatively. To assess EVI fully, a complete study of all the vessels draining the tumor would be required yet the conventional preparation technique is associated with the distinct possibility of sampling error, because only a few vessels in each block are sectioned in the longitudinal axis. This sampling error might well be the explanation for the considerably higher incidence of EVI in our cases than in the reports in the literature. In all patients with EVI, the possibility of hematogenous metastases exists, and this has a significant bearing on the question of selecting patients for adjuvant chemotherapy.

Carcinoma↗
PubMed1996

Superiority of cisplatin or carboplatin in combination with teniposide and vincristine in the induction chemotherapy of small-cell lung cancer. A randomized trial with 5 years follow up.

PURPOSE: The introduction of platinum compounds and epipodophyllotoxins in combination with vincristine as induction chemotherapy in small-cell lung cancer (SCLC) was investigated in order to: (1) compare the efficacy of cisplatin with that of carboplatin in combination with teniposide and vincristine as inducers of remission over three cycles; (2) compare the toxicity pattern of carboplatin and of cisplatin when given in combination regimens; and (3) compare a chemotherapeutic regimen consisting of three alternating combinations with that of regimens consisting of four alternating combinations. PATIENTS AND METHODS: From November 1985 to September 1991, 484 consecutive, previously untreated patients with SCLC, performance status 0-4, entered a three armed randomized trial with three cycles of cisplatin (arm I) or carboplatin (arm II) in combination with teniposide and vincristine alternating with three treatment blocks of cyclophosphamide, etoposide, lomustine and vincristine (block A), doxorubicin and vincristine (block B) and cisplatin, hexamethylmelamine and vindesine (block C) versus alternating treatment with block A, B and C (arm III). RESULTS: No difference in efficacy or toxicity was found between cisplatin and carboplatin at the present dosages. Induction chemotherapy with teniposide plus cisplatin or carboplatin did not result in higher complete response rates (objective response rates 63%, 72% and 65%, respectively) or in significantly greater toxicity, but overall survival was superior compared with the arm III (log-rank test, P = 0.02). The median survival difference was 7 weeks, and two year survival 15% versus 9%. The Cox regression analysis identified the arm III, poor performance status and elevated LDH as factors with statistically significant negative impact on survival. CONCLUSION: Cisplatin and carboplatin produced similar response and survival rates and similar toxicity. Induction with platinum and epipodophyllotoxins did not improve objective response rates, but significantly improved survival without increasing the toxicity.

Adult↗
PubMed1996

Quantitative assessment of the synovial membrane in the rheumatoid wrist: an easily obtained MRI score reflects the synovial volume.

Determination of the synovial membrane volume in the rheumatoid arthritis (RA) wrist by gadolinium-DTPA-enhanced MRI is introduced. Moreover, dynamic imaging and an MRI score of synovial hypertrophy, based on gradings in six regions, are evaluated as substitutes of the time-consuming volume calculations. Twenty-six RA wrists were examined. Synovial membrane volumes ranged from 1 to 20 ml (median 9 ml). Synovial hypertrophy scores were highly correlated to synovial volumes (Spearman r = 0.88; P < 10(-8) for uncorrelated values). The volumes and scores were significantly higher in wrists with joint swelling and/or joint tenderness than in wrists without these signs (Mann-Whitney, both P < 0.05). Suboptimal slice selection made dynamic imaging uninformative. MRI allows quantification of the synovial volume in the rheumatoid wrist. The volume is related to clinical signs of inflammation, but may also give information about the cumulated synovial proliferation in the joint. An easily obtained score of synovial hypertrophy reflects the synovial volume and may thus be a useful marker of synovial involvement.

Adult↗
PubMed1996

Serum YKL-40 levels in healthy children and adults. Comparison with serum and synovial fluid levels of YKL-40 in patients with osteoarthritis or trauma of the knee joint.

YKL-40 is a recently discovered human glycoprotein which is related in amino acid sequence to the chitinase protein family. YKL-40 is a major secretory protein of human chondrocytes and synoviocytes, and could play a role in tissue remodelling. The aim of the study was to establish the serum YKL-40 level in normal subjects and to evaluate serum YKL-40 as a marker for osteoarthritis. Serum YKL-40 was 80 micrograms/l in healthy children (n = 476) and 102 micrograms/l in healthy adults (n = 260). No age or sex differences were found in serum YKL-40 in subjects younger than 70 yr, but thereafter serum YKL-40 increased significantly. Patients with late-stage osteoarthritis of the knee (n = 37) had significantly higher serum YKL-40 (1.5-fold; P < 0.01) compared to healthy age-matched subjects, whereas patients with early-stage osteoarthritis of the knee or recent torn cruciate ligaments or menisci did not have elevated serum YKL-40. The level of YKL-40 in serum and synovial fluid correlated significantly, and 10-fold higher values were found in synovial fluid. YKL-40 levels in serum and synovial fluid of patients with acute severe synovial inflammation were significantly higher (P < 0.05-P < 0.001) than those in patients with no, light or moderate synovitis of the knee joint. Furthermore, YKL-40 correlated significantly (P < 0.01) with the amino-terminal propeptide of type III procollagen, but not with serum C-reactive protein. Our data indicate that YKL-40 in synovial fluid and serum may reflect human articular cartilage degradation and the degree of synovial inflammation in the knee joint.

Adipokines↗
PubMed1996

Effects of a short-chain phospholipid on ion transport pathways in rabbit nasal airway epithelium.

We investigated the mechanism of interference of mucosal application of the short-chain phospholipid didecanoyl-L-alpha-phosphatidylcholine (DDPC; 0.1-0.5%) with ion transport pathways in isolated rabbit nasal airway epithelium (RNAE). Transports of Na+ and Cl- were evaluated from tracer ion fluxes, short-circuit current (Isc), and epithelial conductance (Gt) under short-circuit conditions in Ussing chambers. DDPC rapidly and reversibly abolished net Na+ absorption, reduced control Isc (approximately 110 microA/cm2) by approximately 80%, and induced a small Cl secretion. Intracellular Ca2+ concentration ([Ca2+]i) increased dose dependently and transiently (measured by fura 2 in cultured rabbit airway epithelium), but ionomycin failed to mimic the decrease in Isc. The rise in [Ca2+]i may explain a Ba(2+)-sensitive transient activation of a basolateral K+ conductance. Indomethacin-sensitive prostaglandin E2 production in RNAE increased severalfold, but cyclooxygenase and lipoxygenase inhibitors did not prevent DDPC-induced changes in Isc. DDPC initially decreased control Gt (approximately 13 mS/cm2) by approximately 25% due to inhibition of amiloride-sensitive Na+ channels, and then reversibly increased Gt to approximately 45% above control values. Passive Na+ fluxes increased more than Cl fluxes, suggesting that the increase in Gt is due to formation of a paracellular shunt conductance in parallel with unaffected, anion-selective tight junction channels. The results suggest that DDPC inhibits apical membrane Na+ channels and causes structural changes in tight junctions after incorporation in apical cell membranes.

Animals↗
PubMed1996

The effect of casein phosphopeptides on zinc and calcium absorption from high phytate infant diets assessed in rat pups and Caco-2 cells.

Milk and other foods of animal origin have been shown to improve zinc absorption from phytate-rich diets. The ability of milk proteins and casein phosphopeptides (CPP), the latter formed during digestion of casein, to overcome the inhibitory effect of phytate on zinc and calcium absorption was investigated. Suckling rat pups were given aqueous phytate-containing solutions, oat diet, or soy formula alone or with milk proteins or CPP added. Diets labeled extrinsically with 65Zn and 47Ca were given by gastric intubation. Absorption was determined from measurement of radioisotope activity in intestine, organs, and carcass. Addition of CPP improved zinc and calcium absorption from aqueous phytate-containing solutions and from oat diet. The effect of CPP on calcium absorption from soy formula was less pronounced. The influence of CPP on zinc absorption from aqueous phytate-containing solutions was also examined using a human colon carcinoma-derived cell line, Caco-2. Binding + uptake of 65Zn was determined after incubation with these solutions. Phytate reduced zinc binding + uptake to 79% of the control value. Addition of 14 mumol of CPP/L increased zinc binding + uptake to 94%, whereas 36 and 72 mumol of CPP/L depressed zinc binding + uptake (75 and 39%). In conclusion, CPP improved zinc and calcium bioavailability from high phytate meals in the rat pup model. In the Caco-2 cell system, addition of 14 mumol of CPP/L showed a positive effect on zinc binding + uptake from phytate-containing solutions, whereas higher levels of CPP inhibited zinc binding + uptake.

Animals↗
PubMed1996

Bone loss in rheumatoid arthritis. Influence of disease activity, duration of the disease, functional capacity, and corticosteroid treatment.

Axial and appendicular bone mass were studied in 95 patients with rheumatoid arthritis. The aims were to quantify bone mineral density (BMD) and to evaluate the importance of disease activity, duration of disease, functional capacity, and corticosteroid treatment for bone loss in patients with rheumatoid arthritis. The BMD in the lumbar spine (BMDSPINE) did not differ from age-matched healthy controls, but distal forearm BMD (BMDARM) and metacarpal BMD (BMDMCB) were significantly lower in the patients (p < 0.01 and p < 0.001, respectively). Neither BMDSPINE nor BMDMCB were related to the disease activity at the time of investigation. By contrast, BMDARM was decreased in patients with active disease. BMD in any of the three measured locations was not directly correlated to duration of the disease. However, the bone mass in the appendicular skeleton was already decreased within the first two years after the start of the disease. The overall functional capacity in terms of physical activity increased BMD in the axial skeleton. The local functional capacity in terms of grip strength was positively related to BMD in the appendicular skeleton. Patients with severe functional impairment had the lowest BMDARM. The decreased BMD in patients with rheumatoid arthritis seems primarily to be caused by an impaired physical activity which may be related to disease activity. Corticosteroids did not decrease BMD in neither the axial nor the appendicular skeleton. The antiinflammatory effect of steroids lead to clinical improvement, which may counteract the expected negative effect of these drugs on bone in rheumatoid arthritis.

Absorptiometry, Photon↗
PubMed1996

Randomized, placebo controlled trial of withdrawal of slow-acting antirheumatic drugs and of observer bias in rheumatoid arthritis.

Patients with rheumatoid arthritis, in stable treatment with methotrexate, penicillamine, or sulfasalazine, were randomized in a double-blind fashion either to continuation of their usual treatment or to placebo. 112 patients were included; 52 patients who refused participation had no more severe disease than the others. The patients felt worse on placebo than on active drug (p = 0.002). The mean differences in number of tender, painful and swollen joints after one month were 2.4 (p = 0.08), 3.0 (p = 0.12) and 2.2 (p = 0.03), respectively. Treatment failure occurred for 42 patients of whom 33 received placebo (p = 0.000,001). There was no difference in the severity of side effects (p = 0.91). The patients guessed their treatment correctly more often than expected (p = 0.02) because of the perceived effect. None of the two observers guessed better than chance, and there were no differences between the observers' evaluations of the joints. The effect of slow-acting antirheumatic drugs was unequivocal and no observer bias occurred.

Aged↗
PubMed1996

The indoor microfungus Trichoderma viride potentiates histamine release from human bronchoalveolar cells.

Trichoderma viride (Tv) is often found in damp and mouldy buildings where people complain of adverse health effects including mucosal/respiratory symptoms. Inhaled spores can reach the alveoli and may interact with the airway epithelium. An interaction with the mucosal mast cells was studied in cells obtained by bronchoalveolar lavage (BAL) from 18 individuals. The fungal spores were found to trigger histamine release from the BAL cells, but relatively high concentrations (0.1-2 mg/ml) were needed. A similar dose response was obtained in basophil histamine release. The Tv-induced mediator release was caused by non-immunological (non-IgE-dependent) mechanisms since the histamine release was not changed by removal of IgE from the basophils before exposure of the cells to the spores. However, in very low concentrations (0.1 ng/ml) the fungal spores were found to potentiate IgE-mediated histamine release triggered by anti-IgE antibody in suspensions of BAL cells. Potentiation was also obtained in basophil histamine release, but relatively high concentrations of Tv (10(-2) mg/ ml) were needed. Our in vitro experiments show that mucosal mast cells from the airways are highly sensitive to the potentiating effect of Tv. Although inhalation studies are needed to determine the in vivo effect of the spores, the results suggest reinforcement of mediator release to be a mechanism in the adverse health implications observed in mouldy buildings.

Adult↗
PubMed1996

[Costs and time savings by dilatation tracheotomy with bronchoscopic control].

Forty-seven patients underwent dilatational tracheostomy with bronchoscopic support. Bronchoscopic support during the procedure prevents perforation of the dorsal wall of the trachea and reveals any bleeding into the trachea. Complications intra- and postoperatively have not been seen as yet (follow-up up to 1 year). Duration of the procedure was 8 min versus 30 min for the conventional tracheostomy (mean values).

Bronchoscopy↗
PubMed1996

[Acute renal failure in critically ill elderly patients--a reason to dispense with therapy?].

846 patients on a surgical intensive care unit (436 patients over 70 years old = group I, 410 patients up to 70 years old = group II) were included in a prospective study of incidence, mortality and reversibility of acute renal failure (ARV). APACHE II-Score showed no differences (17.5 in group I and 15 in group II), but a preexisting renal insufficiency was seen in 18.1% in group I and in 7% in group II (p < 0.05). Incidence of acute renal failure (group I 7.3%, group II 8.3%) and mortality of patients with ARV (group I 18.7%, group II 17.6%) was comparable in both groups.

APACHE↗
PubMed1995

Determination of the structural role of the internal guanine-cytosine base pair in recognition of a seven-base-pair sequence cross-linked by bizelesin.

Bizelesin (formerly U77,779, The Upjohn Co.) is a bifunctional DNA cross-linking antitumor antibiotic consisting of two open-ring homologs of the (+)-CC-1065 cyclopropa[c]pyrrolo[3,2-e]indol-4(5H)-one (CPI) subunits connected by a rigid linking moiety. Previous studies have shown that Bizelesin most often forms an interstrand cross-link through the N3 of two adenines 6 base pairs (bp) apart (inclusive of the modified adenines). However, gel electrophoresis studies have also indicated that Bizelesin forms 7-bp cross-links in specific sequences. In most of these sequences the cross-linked adenines represent the only possible cross-link site (i.e., no 6-bp site is available); however, in several sequences, a 7-bp sequence is selected in overwhelming preference to a possible 6-bp sequence. In this study, we demonstrate the unique requirement for a G.C base pair within this sequence and the critical presence of the exocyclic 2-amino group of guanine. In a subsequent two-dimensional 1H-NMR study that concentrates on the 7-bp cross-link formed with the sequence 5'-TTAGTTA-3', the role of the central G.C base pairs in the formation of a 7-bp cross-link is probed. 1H-NMR analysis coupled with restrained molecular dynamics (rMD) provides evidence for distortion around the covalently modified adenines. Because of this distortion, the modified bases are twisted toward the center of the duplex adduct, effectively reducing the cross-linked distance. The rMD study also indicates that a hydrogen bond is formed between the exocyclic amine of the central guanine and the carbonyl of the ureylene linker. On the basis of the observation of the distortion in the duplex and the hydrogen bonding between the drug and DNA, it is possible to speculate on the role of the central G.C bases in this sequence preference and propose a mechanism by which Bizelesin forms a 7-bp rather than a 6-bp cross-link with this sequence.

Alkylation↗
PubMed1995

[Pressure and flow-profile of different spinal needles].

The flow characteristics of four different types of spinal needles were investigated by measuring the infusion pressure during steady state infusion of either saline or an X-ray contrast agent. Two pencilpoint needles, a Whitacre 22Gauge and a Sprotte 24Gauge, possessed flow characteristics similar to a 22Gauge Quincke point needle. Use of pencilpoint needles for spinal anaesthesia results in a lower incidence of postdural puncture headache compared to the Quincke point needle. We therefore recommended the use of pencilpoint needles for myelography.

Anesthesia, Spinal↗
PubMed1995

Upper gastrointestinal symptoms in the third trimester of the normal pregnancy.

OBJECTIVES: To report on the prevalence of well-being, heartburn, nausea, and vomiting related to gestational week, parity, and age in the third trimester of the normal pregnancy. STUDY DESIGN: Self-administered questionnaire filled in daily by 180 women from 31st gestational week to delivery. RESULTS: The study was completed by 120 women. The weekly prevalence of well-being decreased from 50% at the 31st gestational week to 24% at the 42nd gestational week (P = 0.00001). The weekly prevalence of heart-burn (approximately 60%), nausea (approximately 16%) and vomiting (approximately 7%) was nearly constant throughout the study period. Well-being was inversely related to parity, (P = 0.006), heartburn positively related to age (P = 0.016), and nausea and vomiting inversely related to age (P = 0.003 and P = 0.044). CONCLUSION: Discomforts are customary in the third trimester of normal pregnancy. However, heartburn and especially nausea and vomiting appeared occasionally and were not present for longer periods. The findings that heartburn, nausea and vomiting had different relations to age may suggest different etiologies.

Adult↗
PubMed1995

Hedamycin intercalates the DNA helix and, through carbohydrate-mediated recognition in the minor groove, directs N7-alkylation of guanine in the major groove in a sequence-specific manner.

BACKGROUND: The pluramycins are a class of antitumor antibiotics that exert their biological activity through interaction with DNA. Recent studies with the analog altromycin B have determined that these agents intercalate into the DNA molecule, position carbohydrate substituents into both major and minor grooves, and alkylate the DNA molecule by epoxide-mediated electrophilic attack on N7 of guanine located to the 3' side of the drug molecule. Alkylation is sequence dependent and appears to be modulated by glycoside substituents attached at the corners of a planar chromophore. The altromycin B-like analogs preferentially alkylate 5'AG sequences; hedamycin-like analogs prefer 5'TG and 5'CG sequences. Although the mechanism of guanine modification by altromycin B has been extensively studied, the mechanism of action of hedamycin has not been previously determined. RESULTS: Using high-field NMR, we have shown that hedamycin stacks to the 5' side of the guanine nucleotide at the site of intercalation in a DNA decamer, positioning both aminosaccharides into the minor groove to direct alkylation by the epoxide moiety on N7 of guanine. The C10 linked N,N-dimethylvancosamine sugar moiety interacts to the 5' side of the intercalation site, while the C8 linked anglosamine moiety interacts to the 3' side. The binding interactions of the two aminosugars steer the C2 double epoxide located in the major groove into the proximity of N7 of guanine. Unexpectedly, it is not the first epoxide that undergoes electrophilic addition to N7 of guanine, which would correspond to altromycin B, but the second, terminal epoxide. CONCLUSIONS: We have used two-dimensional NMR to elucidate the sequence-selective recognition of DNA by hedamycin and the mechanism of covalent modification of guanine by this antibiotic. Characterization of the intermolecular interactions between both hedamycin and altromycin B and their targeted DNA sequences has yielded a better understanding of the reasons for variations in sequence selectivity and alkylation reactivity among the pluramycin compounds.

Alkylation↗