Search PubMed⌕ Search

Biomedical subjects

M Hansen

Publications and source records attributed to M Hansen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of chronic ethanol on reproductive and growth hormones in the peripubertal male rat.

Ethanol (EtOH) has previously been shown to have profound effects on various endocrine systems. The present study further investigates the action of EtOH on testosterone and on the GH-IGF-I axis. Since these hormones are particularly important in male rats progressing through puberty, we examined the effect of 10 days of EtOH treatment at three different ages (35, 50 and 65 days old) as male rats progressed through puberty into adulthood. After 10 days of feeding a 6% EtOH liquid diet, serum testosterone levels were markedly decreased in all three ages (P < 0.02 at 35 days, P < 0.01 at 50 days and P < 0.03 at 65 days). IGF-I was assessed and was differentially affected at each age. At 35 days IGF-I levels were suppressed by EtOH (P < 0.0002), at 50 days no change was apparent, and at 65 days levels were significantly higher in EtOH-treated (P < 0.01) compared with liquid-fed controls. The levels of IGF-I in the EtOH-treated animals paralleled pituitary GH mRNA levels with a significant fall in the expression of GH mRNA levels noted at 35 days (P < 0.04), no change at 50 days and a significant rise observed at 65 days (P < 0.03). At the hypothalamic level, GH-releasing hormone (GRF) mRNA was significantly reduced in the two younger EtOH-treated age groups compared with controls (P < 0.04 at 35 days; P < 0.02 at 50 days). At 65 days of age, EtOH did not alter GRF mRNA levels. No EtOH-induced changes were seen in GRF content at any age. These observations indicate definite age-related alterations in hormonal gene expression and circulating serum hormone levels and emphasize the importance of studying these critical peripubertal ages after chronic EtOH exposure.

Animals↗
PubMed1997

Paclitaxel (175 mg/m2 over 3 hours) with cisplatin or carboplatin in previously untreated ovarian cancer: an interim analysis.

The side effects of cisplatin (75 mg/m2) in combination with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (175 mg/m2 over 3 hours) are expected to be more severe and frequent than those of carboplatin (area under the concentration-time curve of 5) in combination with the same dose of paclitaxel, but the combinations are expected to be equally effective. A disadvantage of the cisplatin-based regimen is that patients need to be admitted to the hospital. The carboplatin regimen can be administered to outpatients. We tested both combinations administered every 3 weeks in a randomized phase III study in patients with previously untreated epithelial ovarian cancer. An interim analysis for toxicity was performed in 145 patients shortly after study closure. We observed a difference in the incidence of nausea, vomiting, and neurotoxicity favoring the women treated with the carboplatin regimen, but this regimen caused more myelotoxicity. Maturation of the study is awaited before survival data can be analyzed and final conclusions can be drawn.

Adult↗
PubMed1996

[Headache, fatigue and edema of the lower limbs during the third trimester of normal pregnancy].

A series of 180 pregnant women with normal pregnancies participated in the study. A questionnaire concerning the presence of headache, fatigue and oedema of the lower limbs was filled out daily from the 30th gestational week to delivery. After the study period 120 questionnaires, of whom eight were excluded, were available for analysis. The weekly prevalences of headache and fatigue during the observation-period were nearly constant with values of 20% and 50%, respectively. The weekly prevalence of oedema increased significantly from 20% in the 31st week to 60% in the 42nd gestational week. Thirty-five percent had not suffered from headache, 22% did not report fatigue, and 42% did not describe oedema at all during the third trimester. The prevalence of headache and fatigue correlated significantly to increasing parity whereas headache was significantly correlated to decreasing age. Headache, fatigue, and oedema are common symptoms in the third trimester of normal pregnancy, and as such their presence alone should not usually give cause for suspicion of disease.

Edema↗
PubMed1996

SV40-like sequences in human bone tumors.

Simian virus 40 (SV40) is a monkey virus that induces ependymomas, choroid plexus tumors, mesotheliomas, osteosarcomas, sarcomas and true histiocytic lymphomas when injected in hamsters. Recently, approximately 60% of human ependymomas, choroid plexus tumors and mesotheliomas were reported to contain and express SV40-like sequences (N. Engl. J. Med., 1992, 36, 988-993; Oncogene, 1994, 9, 1781-1790). In this study the presence of SV40-like sequences was investigated in additional types of human tumors. Initially, 200 tumor and normal tissue DNA samples were analysed by polymerase chain reaction (PCR) with primers that amplify a 574 base pair region of SV40 large T antigen (Tag), which includes the Rb-pocket binding domain and the intron of Tag. PCR amplification and Southern blot hybridization with a probe specific for SV40 Tag revealed that 18/200 samples contained SV40-like sequences and, unexpectedly, 11/18 were from patients with osteosarcomas. Additional DNA samples from bone tumors were then analysed. In 40/126 osteosarcomas, and 14/34 other bone-related tumors, Tag sequences could be amplified. Sequence analysis of the DNA amplified from seven different tumors confirmed that the amplified sequences corresponded to SV40 Tag, with some demonstrating deletions in the intron region but not in the Rb-pocket binding domain. The extent of SV40 genome sequences present in the DNA samples was further analysed in two osteosarcomas. PCR amplification, Southern blot hybridization, and sequence analysis revealed that these samples also contained sequences for the carboxy-terminal domain of Tag, the viral regulatory region, and the VP1 capsid protein. These results indicate that SV40-like sequences are present in human bone tumors.

Base Sequence↗
PubMed1996

Treacher Collins syndrome: phenotypic variability in a family including an infant with arhinia and uveal colobomas.

We report extreme expression of Treacher Collins syndrome in an infant with arhinia, anotia, absent zygomatic bones, hypoplastic mandibular rami, and bilateral coloboma of iris, choroid plexus, and optic nerves. The Treacher Collins phenotype was mildly expressed in the mother and moderately in the sister. The father had no signs and was not ruled out as the father by DNA fingerprinting, thus making homozygosity by descent in the severely affected son very unlikely.

Adult↗
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↗