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Biomedical subjects

M Hansen

Publications and source records attributed to M Hansen.

At least 91 records · Page 5Linked to original sources

Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress.

Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts/10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96 nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative correlations were observed between bulky carcinogen-DNA adduct and PAH-albumin levels (p = 0.005), and between DNA adduct and [gamma]-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly significant correlations were found between PAH-albumin adducts and AAS in plasma (p = 0.001) and GGS in hemoglobin (p = 0.001). Significant correlations were also observed between urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and AAS in plasma (p = 0.001) and PAH-albumin adducts (p = 0.002). The influence of the glutatione S-transferase (GST) M1 deletion on the correlation between the biomarkers was studied in the combined group. A significant negative correlation was only observed between bulky carcinogen-DNA adducts and PAH-albumin adducts (p = 0.02) and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1 null group, but not in the workers who were homozygotes or heterozygotes for GSTM1. Our results indicate that some of the selected biomarkers can be used to distinguish between high and low exposure to environmental genotoxins.

Adult↗

Mink enteritis parvovirus. Stability of virus kept under outdoor conditions.

Feces from mink with acute mink enteritis were pooled and then allowed to dry out in open tubes kept under a roof in an open shed for one year starting in January. Samples of feces were harvested approximately once a month. These were reconstituted to their original volume and tested for antigen content and infectivity both in in vitro cell cultures and - on selected samples - in vivo. During the first 8 months, the antigen level in the feces samples decreased slowly. At this time point, a plateau was reached at 30-40% of the original viral antigen contents. The infectivity in vitro was unchanged for the first 5 months, but after mid-summer it decreased abruptly to below the detection level. Based on the in vitro infectivity, 10 samples were selected for inoculation into mink to measure the in vivo infectivity. The transmission of the infection to the experimental animals was successful for all samples showing infective virus by cultivation. In addition, it was possible to infect mink using material harvested one month after the cell culture test had turned negative. One mink inoculated with material collected in October excreted virus. We conclude that parvovirus can survive for at least 5-10 months (or during the winter period) under natural conditions, but complete drying out seems to lead to its inactivation. Mechanical cleaning of the premises is thus as critical as disinfection since virus can only survive the dry summer period if protected by protein or buried in moist soil on the premises.

Animals↗

Elimination of meropenem by continuous hemo(dia) filtration: an in vitro one-compartment model.

Meropenem is a carbapenem antibiotic with a wide spectrum of activity against most gram positive and gram negative bacteria including anaerobes. Dose adjustments are necessary during continuous renal replacement therapies of acute renal failure. This in vitro study was conducted to investigate the influence of different filter materials, surface areas (AN-69 0.6 m2 and 0.9 m2, polysulfone 0.75 m2, polyamide 0.6 m2), and increasing flow rates (from 3.3 - 26.7 ml/min) on the elimination of meropenem in an in vitro continuous hemo(dia)filtration model. Meropenem was measured using HPLC with UV-detection. While the clearance increased proportionally to increasing dialysate flow rates in filters with a surface area of 0.9 m2, a peak clearance was reached in the small filters at flow rates of 10.0 ml/min (polyamide 0.6 m2) and 18.3 ml/min (AN-69 0.6 m2), when tested under the same conditions. This indicated incomplete dialysate saturation due to the diminished time available for meropenem to equilibrate with the dialysate solution. No adsorption to either of the tested membranes was detected. Dosage recommendations derived from clinical studies might be appropriate when different filter materials, but similar operational settings of the continuous replacement therapy, are applied. Reduction of the recommended dose might be necessary, when renal replacement therapies with lower flow rates and/or filters with smaller surface areas are carried out.

Anti-Bacterial Agents↗

Simplified and more robust EBA processes by elution in expanded bed mode.

This paper illustrates the feasibility of eluting EBA columns in the expanded bed mode as an alternative to the generally used method of packed bed elution. It is shown that at linear flow rates of 1-3 cm/min the difference in total elution volume between expanded bed elution and packed bed elution is less than 20%. It is suggested that expanded bed elution offers a range of significant advantages, while the drawbacks will be insignificant in most applications. The key to the success of this method seems to be the use of EBA matrices with a relatively low degree of expansion (i.e. a high density) at the linear flow rates employed for elution of bound product.

Adsorption↗

Retroviral vector-modified bone marrow stromal cells secrete biologically active factor IX in vitro and transiently deliver therapeutic levels of human factor IX to the plasma of dogs after reinfusion.

Canine bone marrow stromal cells (BMSCs), transduced ex vivo with retroviral vectors, expressed and secreted biologically active human and canine coagulation factor IX (hFIX and cFIX) in vitro, and on autologous reinfusion expressed hFIX into the circulation of normal (nonhemophiliac) dogs. Human FIX, when expressed in vitro by BMSCs of two dogs at 1.22 and 1.39 microg/10(6) cells/24 hr in medium supplemented with vitamin K, respectively, exhibited 28.1 and 27.3% normal biological activity as determined on the basis of a one-stage clotting assay. BMSCs of two additional dogs expressed 1.54 and 4.81 microg of cFIX/10(6) cells/24 hr in vitamin K-supplemented medium and the expressed cFIX possessed 58.4 and 32.9% normal activity, respectively. Between 2.33 and 3.35 x 10(8) transduced BMSCs, expressing 1.22 and 2.61 microg of hFIX/10(6) cells/24 hr or 3.24 and 7.82 microg of cFIX/10(6) cells/24 hr were reintroduced into the four donor dogs by intravenous infusion. Human FIX was detected in plasma for 7 or 12 days after BMSC reinfusion, with peak levels of 85.8 and 233.0 ng/ml observed at 2 days. Canine anti-hFIX antibodies, which were detected as early as 2-4 days after reinfusion of BMSCs expressing hFIX, may have masked potentially longer duration expression in vivo. Peak plasma levels of hFIX represented 2.1 and 5.8% normal human hFIX levels. When adjusted for percent normal one-stage clotting activity determined in vitro, these levels represented 0.6 and 1.6% normal human hFIX activity levels. Thus, we have demonstrated that retroviral vector-modified BMSCs can deliver human therapeutic levels of hFIX to the circulation of dogs.

Animals↗

Quantification of the N-terminal propeptide of human procollagen type I (PINP): comparison of ELISA and RIA with respect to different molecular forms.

This paper compares the results of procollagen type I N-terminal propeptide (PINP) quantification by radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA). PINP in serum from a patient with uremic hyperparathyroidism was measured in RIA and ELISA to 20 micrograms l-1 and 116 micrograms l-1 and the corresponding concentrations in dialysis fluid were 94.5 micrograms l-1 and 140 micrograms l-1, respectively. PINP antigen appears in two distinct peaks following size chromatography and the two peak fractions display immunological identity and identical M(r)'s (27 kDa: SDS-PAGE). Analysis of fractions from size separated amniotic fluid, serum and dialysis fluid demonstrated that the RIA failed to measure the low molecular weight form of PINP. However, the anti-PINP supplied with the RIA-kit and the anti-PINP applied in the ELISA reacted equally well with both molecular forms of PINP when analysed in a direct ELISA. It is concluded that the major difference in the ELISA and RIA results is due to assay efficacy with respect to the low molecular weight form of PINP.

Amniotic Fluid↗

Follow-up evaluation of open intra-articular fractures of the calcaneus.

The results of a follow-up evaluation of open intra-articular calcaneal fractures are presented. A modified Merle d'Aubigné functional score and Zwipp radiographic score were used. A retrospective analysis of 35 patients with 36 open intra-articular fractures represents the basis of the study. At the time of follow-up examination (on average 44 months after the injury), 5 amputations of the affected extremity and 4 ankle arthrodeses had been carried out. The 23 patients still able to bear weight on the affected hindfoot and possessing a functional ankle joint were radiographically and functionally evaluated. No excellent results were documented. Only 6 good functional and 2 good radiographic outcomes were noted. In 17 instances, a poor functional or radiographic score was given. Devastating results were seen in the course of treatment of third-degree open joint depression or comminuted intra-articular fractures (n = 15): 9 cases of osteomyelitis, 5 amputations, 1 partial calcanectomy, 1 arthrodesis. An open reduction as part of the primary treatment (n = 6) led to local complications in all instances. The most favorable results were seen after nonoperative fracture management: complication-free course of treatment in 4 of 11 patients. All workmen's injuries led to a permanent disability, and these patients received compensation. The treatment and salvage of the soft-tissue envelope should be paramount in all therapeutic decisions. The fracture treatment must not further jeopardize these tissues. An aggressive operative treatment of local complications, including arthrodesis or amputation, is recommended.

Adolescent↗

Relationship between keratinocyte adhesion and death: anoikis in acantholytic diseases.

Loss of attachment to the substratum may trigger apoptosis in epithelial cells (anoikis). It is less clear whether apoptosis may be triggered by disruption of cell-cell contacts, as happens in acantholytic diseases. Biopsy specimens were obtained from the border of skin lesions from four patients with pemphigus vulgaris (PV), four patients with pemphigus foliaceus (PF), three patients with Darier's disease (DD), two patients with Darier's-type Grover's disease (GD), and two patients with benign familial pemphigus Hailey-Hailey disease (HH). Control skin was obtained from five healthy volunteers. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) and confocal laser scanning microscopy was employed to detect the nuclei containing fragmented DNA in apoptotic cells. In PV and PF, TUNEL-stained apoptotic keratinocytes were abundantly present in the regions of acantholysis and in the cohesive epidermis below the blisters. Apoptotic keratinocytes had pyknotic, condensed nuclei. In DD, GD and HH, the number of TUNEL-stained keratinocytes was lower, apoptotic keratinocytes were confined to the regions of dyskeratosis and acantholysis, and pyknosis was absent. In conclusion, disruption of cell-cell contacts in acantholytic skin disorders may in some cases cause apoptosis of keratinocytes. Further studies are needed to determine whether the observed differences in the pattern of apoptosis are due to targeting of different junctional elements (adherens junctions in PV and PF versus desmosomes in DD, GD and HH).

Apoptosis↗

Adverse effects of inhaled budesonide (800 micrograms) on growth and collagen turnover in children with asthma: a double-blind comparison of once-daily versus twice-daily administration.

BACKGROUND: Twice-daily administration of inhaled budesonide (400 micrograms) suppresses short-term growth in children with asthma. OBJECTIVE: To compare short-term growth and markers of collagen turnover during treatment with 800 micrograms of inhaled budesonide administered once daily in the morning and 400 micrograms administered twice daily. PATIENTS: Twenty-four children with asthma aged 5.6 to 12.5 years. SETTING: An outpatient secondary referral center. METHODS: A randomized, double-blind, crossover trial with 2 treatment periods of 4 weeks was conducted, and growth was assessed with a knemometer. The carboxy terminal propeptide of type I procollagen, the amino terminal propeptide of type I procollagen (PINP), the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen, the amino terminal propeptide of type III procollagen (PIIINP), and urinary pyridinoline and deoxypyridinoline were evaluated. RESULTS: Mean lower leg growth rate (P = .04), PINP (P = .03), and PIIINP (P < .01) were suppressed during twice-daily administration of budesonide, 400 micrograms. Otherwise, no statistically significant differences were detected. CONCLUSIONS: As compared with 400 micrograms of inhaled budesonide administered twice daily, 800 micrograms administered once daily in the morning has a sparing effect on short-term growth and collagen turnover.

Administration, Inhalation↗

Calcium absorption from small soft-boned fish.

The prevalence of osteoporosis in developing countries is low compared to most industrialised countries despite an apparent low Ca intake. It is possible, however, that food surveys have overlooked important Ca sources in developing countries. Small fish eaten with the bones can be a rich source of Ca, even though Ca from bone may be considered unavailable for absorption. In the present study, absorption of Ca from indigenous Bengali small fish was compared with the Ca absorption from milk. Ca absorption from single meals was determined in 19 healthy men and women (21-28 y). Each subject received two meal types on two separate occasions. Both meals consisted of white wheat bread, butter and ultra pure water with the main Ca source being either small Bengali fish (397 mg Ca in total) or skimmed milk (377 mg Ca in total). The meals were extrinsically labelled with 47Ca, and whole-body retention was measured on day 8, 12, 15 and 19 after intake of each meal. The labelling procedure was evaluated by an in vitro method. The calculated absorption of Ca as measured with 47Ca whole-body retention was 23.8 +/- 5.6% from the fish meal and 21.8 +/- 6.1% from the milk meal (mean +/- SD), which was not significantly different (p = 0.52). Even after correction for an incomplete isotope exchange, as indicated by the in vitro study, Ca absorption was similar from the two meal types. It was concluded that Ca absorption from small Bengali fish was comparable that from skimmed milk, and that these fish may represent a good source of Ca.

Absorption↗

Medical thoracoscopy, results and complications in 146 patients: a retrospective study.

In a retrospective study the results of medical thoracoscopy in 147 patients were reviewed; 136 of the patients had pleural effusion and 11 patients had diffuse pulmonary infiltration. All the pleural exudates were initially screened three times successively and found to be sterile and without tumour cells. All thoracoscopies were performed with local anaesthesia, with the 'open technique', and nine different doctors performed the thoracoscopies. The overall diagnostic sensitivity was 90.4%. The results demonstrated 62% with malignancy of the pleura, and 38% revealed benign pleural diseases, among them 2% with tuberculosis. The sensitivity for malignancy was found to be 88% and the specificity 96%. The most common primary lung cancer with involvement of the pleura was the adenocarcinoma (62%), and the most common metastatic tumour originated from the breast (28%). The sensitivity for tuberculosis was 100% and the specificity 100%. No mortality was found, and the morbidity was low at about 0.6% (empyema, pleuro-cutaneous fistula, transcutaneous growth of tumour (mesothelioma)). In 64% of the patients the thoracoscopy resulted in treatment (pleurodesis, antituberculous treatment, chemotherapy and peroral steroid therapy). The medical diagnostic thoracoscopy in local anaesthesia is a simple, low-cost investigation with a relatively high diagnostic accuracy, no mortality and a low morbidity.

Adenoma↗

Treatment of malignant pleural effusion: pleurodesis using a small percutaneous catheter. A prospective randomized study.

The aim of this prospective, randomized study was to investigate the possibility of performing pleurodesis using a small percutaneous catheter (Cystofix catheter, CH10, 65 cm) inserted at bedside in patients with recurrent malignant pleural effusion and to compare this catheter with a conventional large bore chest tube (CH24) placed in connection with diagnostic thoracoscopy. After drainage pleurodesis was performed with tetracycline as sclerosing agent. Of 18 evaluable consecutive patients (mean age 67.8 years) nine were randomized for pleurodesis with the small and nine for the large catheter. In the former group, the majority (seven of nine) did not find insertion of the catheter more unpleasant than thoracentesis. In the latter group only a few (two of nine) found insertion comparable with thoracentesis (P < 0.05). All patients found the presence of the large catheter very or somewhat unpleasant (two and seven patients), whereas this was only the case for a few (no and two patients) treated with the small catheter (P < 0.05). In the former group three patients required new thoracentesis, whereas this was only the case for two patients in the latter group (P > 0.05). No complications were seen. We conclude that pleurodesis in patients with recurrent malignant pleural effusion can be performed with a small percutaneous catheter (Cystofix) with an effect similar to that obtained with a large-bore chest tube and with less discomfort for the patient.

Aged↗

Variable expression of apoptotic phenotype in keratinocytes treated with ultraviolet radiation, ceramide, or suspended in semisolid methylcellulose.

Apoptosis is a form of cellular suicide and is activated in various cells, including keratinocytes, in response to physiological and pathological stimuli. A current hypothesis holds that apoptotic cells in a concerted manner express characteristic phenotypic features comprising cytoplasmic budding, pyknosis, chromatin condensation, karyorhexis and internucleosomal DNA fragmentation. In this study we investigated the effects of different potential inducers of apoptosis on cultured human keratinocytes. Viability was determined with vital dyes (ethidium bromide, trypan blue), cell morphology was investigated with electron microscopy, and nuclear and DNA integrity was assessed with TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) or DNA gel electrophoresis. Irradiation with 50 mJ/cm2 ultraviolet B (UVB), treatment with C8 ceramide, or suspension in a semisolid medium caused apoptosis which was ultrastructurally different from necrotic induced by very high (300 mJ/cm2) doses of UVB. However, the phenotype of dying cells did not exhibit all typical features of apoptosis and cell morphology depended on the method used to induce apoptosis. Cells irradiated with ultraviolet B or treated with C8 ceramide developed large and small budding and DNA nicks but not chromatin condensation or classical karyorhexis. In UVB-irradiated cells a novel form of karyorhexis was observed manifested by formation of a few very small chromatin fragments in nuclear periphery. Cells suspended in methylcellulose developed DNA nicks and pyknosis, but not budding or karyorhexis. In neither case could the typical internucleosomal DNA fragments be detected by gel electrophoresis. These morphological results indicate that in keratinocytes induction of effect or death mechanisms is not concerted but depends on the stimulus inducing apoptosis.

Apoptosis↗

Bone metabolism in patients with systemic lupus erythematosus. Effect of disease activity and glucocorticoid treatment.

The bone metabolism in patients with systemic lupus erythematosus (SLE) has previously been examined, but the results are conflicting. In the present study the bone mineral density (BMD) of the axial and the appendicular skeleton was examined by means of dual energy x-ray absorptiometry. The bone turnover was evaluated by means of biochemical markers in serum and urine in a prospective cohort consisting of 36 female and male SLE patients. Repeated measurements of BMD were performed for up to two years. The BMD was decreased in the hand and in the femoral neck but normal in the spine and in the distal forearm. A weak correlation was found between the BMD of the femoral neck and the total consumption of glucocorticoids. Apart from this finding the BMD was uninfluenced by treatment with glucocorticoids and cyclophosphamide. No significant changes of BMD were found during the follow-up period. The serum concentration of the carboxyterminal cross-linked telopeptide of type I collagen was increased in almost all patients, but no other biochemical markers of bone metabolism were abnormal.

Absorptiometry, Photon↗

Collagen-derived markers of bone metabolism in osteogenesis imperfecta.

Markers of bone formation [C-terminal and N-terminal propeptides of procollagen I (PICP, PINP), osteocalcin and alkaline phosphatase] and bone resorption [C-terminal cross-linked telopeptide of collagen I (ICTP) and hydroxypyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr)] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low, and the serum levels were lower in all children and adults with mild OI and a quantitative collagen defect than in patients with severe OI and a qualitative collagen I defect. ICTP, Pyr and Dpyr were generally normal or reduced, but elevated in severely affected adults with a qualitative collagen I defect. The in vivo findings correlated with in vitro results of collagen I SDS-PAGE. Bone turnover is reduced in OI children and mildly affected OI adults, whereas bone resorption is elevated in severely affected adults. These findings may prove helpful for diagnosis and decision-making regarding therapy in OI.

Adolescent↗

Arteriovenous malformations of the head and neck: natural history and management.

This is a retrospective review of 81 patients with extracranial arteriovenous malformation of the head and neck who presented to the Vascular Anomalies Program in Boston over the last 20 years. This study focused on the natural history and effectiveness of treatment. The male to female ratio was 1:1.5. Arteriovenous malformations occur in anatomic patterns. Sixty-nine percent occurred in the midface, 14 percent in the upper third of the face, and 17 percent in the lower third. The most common sites were cheek (31 percent), ear (16 percent), nose (11 percent), and forehead (10 percent). A vascular anomaly was apparent at birth in 59 percent of patients (82 percent in men, 44 percent in women). Ten percent of patients noted onset in childhood, 10 percent in adolescence, and 21 percent in adulthood. Eight patients first noted the malformation at puberty, and six others experienced exacerbation during puberty. Fifteen women noted appearance or expansion of the malformation during pregnancy. Bony involvement occurred in 22 patients, most commonly in the maxilla and mandible. In seven patients, the bone was the primary site; in 15 other patients, the bone was involved secondarily. Arteriovenous malformations were categorized according to Schobinger clinical staging: 27 percent in stage I (quiescence), 38 percent in stage II (expansion), and 38 percent in stage III (destruction). There was a single patient with stage IV malformation (decompensation). Stage I lesions remained stable for long periods. Expansion (stage II) was usually followed by pain, bleeding, and ulceration (stage III). Once present, these symptoms and signs inevitably progressed until the malformation was resected. Resection margins were best determined intraoperatively by the bleeding pattern of the incised tissue and by Doppler. Subtotal excision or proximal ligation frequently resulted in rapid progression of the arteriovenous malformation. The overall cure rate was 60 percent, defined as radiographic absence of arteriovenous malformation. Cure rate for small malformations was 69 percent with excision only and 62 percent for extensive malformations with combined embolization-resection. The cure rate was 75 percent for stage I, 67 percent for stage II, and 48 percent for stage III malformations. Outcome was not affected significantly by age at treatment, sex, Schobinger stage, or treatment method. Mean follow-up was 4.6 years.

Adolescent↗