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Biomedical subjects

E Andersen

Publications and source records attributed to E Andersen.

At least 19 recordsLinked to original sources
PubMed2001

Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.

The prevention of xenograft rejection is substantially dependent on inhibiting antibodies (Ab) produced by B-cells independently of T-cell signals (TI-1). Due to their ubiquitous biochemical mechanisms of action, the immunosuppressants currently employed not only fail to discriminate between B- and T-cells but also have a narrow therapeutic window and, thus, their prolonged use in complex immunosuppressive regimens is problematic. By capitalizing on the target enzyme-bound (DHODH) structure 1b of one of these compounds, leflunomide, and modulating part of its multiple mechanisms of action to gain selectivity, the quinoline-8-carboxamide 3 was designed as a potentially weak enzyme inhibitor but effective immunosuppressant. Compound 3 fulfilled the mechanistic criteria set and had 10-fold B-cell over T-cell selectivity. Its pyridyl analogue 4 was found to be a highly potent and selective B-cell immunosuppressant with a 75-fold selectivity for B- over T-cells (as judged by the MLR data) and no general cytotoxicity at concentrations up to 160-fold higher than those required to inhibit B-cells. In the mouse, 4 effectively blocked TI-1 Ab production and suppressed Ab-mediated xenograft rejection in a xenotransplantation model under a once-daily dosing regimen, with efficacy down to 0.3 mg/kg/day po. These are the first data demonstrating the feasibility of the development of drugs specific for impeding Ab production.

Animals↗
PubMed2001

Changes in proximal femoral strain after insertion of uncemented standard and customised femoral stems. An experimental study in human femora.

We have compared the changes in the pattern of the principal strains in the proximal femur after insertion of eight uncemented anatomical stems and eight customised stems in human cadaver femora. During testing we aimed to reproduce the physiological loads on the proximal femur and to simulate single-leg stance and stair-climbing. The strains in the intact femora were measured and there were no significant differences in principal tensile and compressive strains in the left and right femora of each pair. The two types of femoral stem were then inserted randomly into the left or right femora and the cortical strains were again measured. Both induced significant stress shielding in the proximal part of the metaphysis, but the deviation from the physiological strains was most pronounced after insertion of the anatomical stems. The principal compressive strain at the calcar was reduced by 90% for the anatomical stems and 67% for the customised stems. Medially, at the level of the lesser trochanter, the corresponding figures were 59% and 21%. The anatomical stems induced more stress concentration on the anterior aspect of the femur than did the customised stems. They also increased the hoop strains in the proximomedial femur. Our study shows a consistently more physiological pattern of strain in the proximal femur after insertion of customised stems compared with standard, anatomical stems.

Aged↗
PubMed2000

[Quality assessment of resuscitation].

The object of the study was to evaluate the availability of paediatricians for resuscitation of newborns and the quality of resuscitation. During the period 1.9.95-15.1.96 a prospective registration was made of the initial treatment of all newborns where a paediatrician was involved. It was noted whether the doctor was present when needed. A comparison with the written guidelines was made. The paediatrician was called to 27% of the 1461 babies born during that period. In 93% of the deliveries with maternal risk factors the pediatrician was called before the delivery and was present at the delivery in 89% of the cases. The resuscitation was optimal in 60%, less satisfactory in 38% and unsatisfactory in 2% of the cases. Intensified training and supervision of doctors dealing with resuscitation of newborns and strengthening of the staff on duty is recommended.

Apgar Score↗
PubMed2000

Cervical lymph node metastases from unknown primary tumours. Results from a national survey by the Danish Society for Head and Neck Oncology.

BACKGROUND AND PURPOSE: The management of patients with cervical lymph node metastases from unknown primary tumours is a major challenge in oncology. This study presents data collected from all five oncology centres in Denmark. MATERIAL AND METHODS: Of the 352 consecutive patients with squamous cell or undifferentiated tumours seen from 1975 to 1995, a total of 277 (79%) were treated with radical intent. The general treatment policy at all centres during the entire study period has been to treat all suitable candidates with radiotherapy to both sides of the neck and include elective irradiation of the mucosal sites in nasopharynx, and larynx, hypopharynx and larynx (81%). Irradiation of the ipsilateral neck only was done in 26 patients (10%). Radical surgery was the only treatment in 23 N1-N2 patients (9%). RESULTS: The 5-year estimates of neck control, disease-specific survival and overall survival for radically treated patients were 51, 48 and 36%, respectively. The emergence of the occult primary was observed in 66 patients (19%). About half of the emerging primaries were within the head and neck region with oropharynx, hypopharynx and oral cavity being the most common sites. Emerging primaries outside the head and neck region were primarily located in the lung (19 patients) and oesophagus (five patients). The frequency of emerging primary in the head and neck was significantly higher in patients treated with surgery alone, the actuarial risks at 5-year being 54+/-1% (no RT) vs. 15+/-3% (with RT), P<0.0001. The most important factor for neck control was nodal stage (5-year estimates 69% (N1), 58% (N2) and 30% (N3)). Other important parameters for neck control and disease-specific survival included haemoglobin, gender and overall treatment time. Patients treated with ipsilateral radiotherapy had a relative risk of recurrence in the head and neck region of 1.9 compared with patients treated to both neck and mucosa. At 5 years, the estimated control rates were 27% (ipsilateral) and 51% (bilateral; P=0.05). The 5-year disease-specific survival estimates were 28 and 45%, respectively (P=0.10). CONCLUSIONS: This study has confirmed that patients with neck node metastases from occult head and neck cancer have clinical features and prognosis similar to other head and neck malignancies. Extensive irradiation to both sides of the neck and the mucosa in the entire pharyngeal axis and larynx resulted in significantly less loco-regional failures compared with patients treated with ipsilateral techniques, but only a trend towards better survival. A prospective randomized trial is required to determine the optimal strategy in terms of locoregional control, survival and morbidity.

Adolescent↗
PubMed2000

The prenatal cranial base complex and hand in Turner syndrome.

From early childhood, Turner syndrome patients have a flattened cranial base, maxillary retrognathism, and short hands. There are, however, no studies that show when these genotype-determined abnormalities occur prenatally. The purpose of the present study was to measure craniofacial profile and hand radiographs of second trimester foetuses with Turner syndrome and compare the results with similar measurements from normal foetuses. The subjects consisted of 12 Turner syndrome foetuses, gestational age (GA) varying between 15 and 24 weeks, and crown-rump length (CRL) between 108 and 220 mm. The mid-sagittal block of each cranium was analysed as part of the requested brain analysis (pituitary gland analysis). This block and the right hand from seven foetuses were radiographed, and the skeletal maturity of the cranial base complex, i.e. the cranial base and the maxilla, was evaluated from the profile radiographs. Shape and size measurements in the cranial base were performed, and compared with normal values according to cranial maturity and to CRL. The cranial base angle in Turner syndrome was greater and the maxillary prognathism was reduced compared with the normal group. The dimensions in the cranial complex and in the hand showed that the bone lengths and distances in relation to CRL were generally smaller compared with normal foetuses. This investigation showed that the abnormal shape of the cranial base complex and the short hands in Turner syndrome are present prenatally.

Analysis of Variance↗
PubMed2000

Human gingival crevicular fluid contains MRP8 (S100A8) and MRP14 (S100A9), two calcium-binding proteins of the S100 family.

Human gingival crevicular fluid contains unidentified proteins which might play a role as markers in periodontal diseases. Therefore, low-molecular-weight proteins found in human gingival crevicular fluid (GCF), but absent from serum, were identified in the present study by means of two-dimensional electrophoresis (2-D PAGE) analysis. GCF, serum, and whole saliva were collected from periodontitis and healthy subjects, as well as from edentulous and newborn subjects. Protein samples were separated by two-dimensional polyacrylamide gel electrophoresis, stained with silver, and compared with reference protein maps in the SWISS-2D PAGE database. In GCF and saliva from periodontitis patients and healthy subjects, four dominant low-molecular-mass (from 8 to 14 kDa) acidic spots were observed. They were not found in serum and were less visible in saliva from edentulous and newborn subjects. From N-terminal amino acid sequencing, the two 2-D protein spots of 8 kDa and isoelectric points between 6.5 and 7.0 were both identified as protein MRP8 (SI00A8), a member of the S100 family of calcium-binding proteins. Using peptide mass fingerprinting and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), we identified the other two protein spots, with mass of 14 kDa and isoelectric points between 5.5 and 6.0, as protein MRP14 (S100A9), also belonging to the S100 family. The presence of MRP8 and MRP14 in GCF was confirmed by Western blot, with monoclonal antibodies. The two polypeptides, MRP8 and MRP14, identified in GCF represent the major difference between the 2-D PAGE patterns of serum and GCF, and we hypothesize that they may play an important role in the gingival sulcus and could represent possible markers for periodontal diseases.

Adult↗
PubMed2000

Fc receptor mediated endocytosis of small soluble immunoglobulin G immune complexes in Kupffer and endothelial cells from rat liver.

Soluble circulating immunoglobulin G immune complexes are mainly eliminated by the liver, predominantly by uptake in the Kupffer cells, but also the liver endothelial cells seem to be of importance. In the present study we have followed the intracellular turnover of immune complexes after Fc(gamma) receptor mediated endocytosis in cultured rat liver endothelial cells and Kupffer cells by means of isopycnic centrifugation, DAB cross-linking and morphological techniques. For the biochemical experiments the antigen, dinitrophenylated bovine serum albumin (BSA), was labeled with radioiodinated tyramine cellobiose that cannot cross biological membranes and therefore traps labeled degradation products at the site of formation. The endocytic pathway followed by immune complexes was compared with that followed by scavenger receptor ligands, such as formaldehyde treated BSA and dinitrophenylated BSA, and the mannose receptor ligand ovalbumin. Both Kupffer cells and liver endothelial cells took up and degraded the immune complexes, but there was a clear delay in the degradation of immune complexes as compared to degradation of ligands taken up via scavenger receptors. The kinetics of the endocytosis of scavenger receptor ligand was unaffected by simultaneous uptake of immune complexes. Experiments using both biochemical and morphological techniques indicated that the delayed degradation was due to a late arrival of the immune complexes at the lysosomes, which partly was explained by retroendocytosis of immune complexes. Electron microscopy studies revealed that the immune complexes were retained in the early endosomes that remained accessible to other endocytic markers such as ovalbumin. In addition, the immune complexes were seen in multivesicular compartments apparently devoid of other endocytic markers. Finally, the immune complexes were degraded in the same lysosomes as the ligands of scavenger receptors. Thus, immune complexes seem to follow an endocytic pathway that is kinetically or maybe morphologically different from that followed by scavenger and mannose receptor ligands.

2,4-Dinitrophenol↗
PubMed2000

Development of ARI case management at primary and secondary level in southern Vietnam.

In southern Vietnam it is not uncommon that children under 5 years of age die from pneumonia. Reduction of severity and mortality has to rely on proper case management by mothers and health workers on both grass root level and referral level. The responsibility of training of clinical skills of ARI case management in the southern provinces of Vietnam has been delegated to Pediatric Hospital N1 (PHN1) Ho Chi Minh City (HCMC) by Ministry of Health. A pilot project was carried out by the Danish-Vietnamese Study Group. The immediate objects were: to provide basic epidemiological information about ARI in southern Vietnam, to develop training modules and case management intervention modules at primary and secondary level in order to enable mothers, village workers, health post staff and district hospital emergency department staff to treat moderate and severe pneumonia and acute bronchitis in accordance with the WHO management guide for ARI and to evaluate the effect of those modules after implementation in a limited number of communes. The modules were developed at PHN1. Ten commune health stations were carefully selected. The purpose of the project and the conditions for taking part had been explained to the health workers. The doctors and other commune health workers from the 10 commune health stations and doctors from the connected district hospitals attended the training courses at PHN1, HCMC and also at the belonging provincial hospitals. Essential equipment was provided and a pharmacy with essential drugs established. The registered health statistics was collected yearly during on site visits. The local doctors and commune health workers gave seminars for mothers in the villages of the 10 project communes. The mothers' knowledge, attitude and practice (KAP) was tested in interviews before and two months after the seminars had taken place. The spread of KAP was measured by random interviews of mothers six month later. In the interviews information on social conditions was obtained. The mothers' KAP had risen by 25% two months after attending the seminars. A further increase of KAP by 5-10% within the untrained group appeared in a survey 4-6 months later. It was not possible to obtain reliable statistics on morbidity or mortality of ARI in the project area.

Case Management↗
PubMed1999

Overexpression of a C-terminal fragment of presenilin 1 delays anti-Fas induced apoptosis in Jurkat cells.

Most cases of early onset familial Alzheimer's disease (FAD) involve mutations in presenilins (PS1 and PS2) genes. The C-terminal portion of PS2 is a homologue with an apoptosis-linked gene (ALG-3). To characterise the role of PS1 in apoptosis, we overexpressed the corresponding C-terminal fragment of PS1 (PS1-f) under the control of the tetracycline-responsive transactivator in Jurkat cells. The tight regulation of the expression of the 11 kDa PS1-f peptide was verified. A 50% inhibition of anti-Fas induced apoptosis was observed upon PS1-f transient overexpression compared to the repressed state. Stable transfectants selectively overexpressing PS1-f revealed a transient protective effect of 30% after apoptosis induction.

Alzheimer Disease↗
PubMed1999

[Long-term results of treatment of overweight in self-help groups].

The long-term results achieved by people trying to lose weight by participating in organised self-help groups have previously been reported as quite satisfactory. Our objective was to explore whether a change of diet and treatment policy produced a change of outcome. We report the results of a survey among 1,340 earlier participants in self-help groups, randomly sampled from the files of group leaders all over Norway. 657 (49%) responded; the mean follow-up time since first group participation was three years. The survey results was supplemented by information from the group leaders' files. The participants had on average kept 62% of their initial weight-loss. 39% of the participants had kept their initial weight-loss or had gone further down in weight. The result is among the best reported in the literature. Even if all participants who did not respond had regained all initial weight-loss, 16% of the total sample would in fact have kept their weight-loss. Exercise and adherence to nutrition advice in the groups were factors pointing to positive long-term results.

Adolescent↗
PubMed1999

Determination of Hounsfield value for CT-based design of custom femoral stems.

Ct and advanced computer-aided design techniques offer the means for designing customised femoral stems. Our aim was to determine the Hounsfield (HU) value of the bone at the corticocancellous interface, as part of the criteria for the design algorithm. We obtained transverse CT images from eight human cadaver femora. The proximal femoral canal was rasped until contact with dense cortical bone was achieved. The femora were cut into several sections corresponding to the slice positions of the CT images. After obtaining a computerised image of the anatomical sections using a scanner, the inner cortical contour was outlined and transferred to the corresponding CT image. The pixels beneath this contour represent the CT density of the bone remaining after surgical rasping. Contours were generated automatically at nine HU levels from 300 to 1100 and the mean distance between the transferred contour and each of the HU-generated contours was computed. The contour generated along the 600-HU pixels was closest to the inner cortical contour of the rasped femur and therefore 600 HU seem to be the CT density of the corticocancellous interface in the proximal part of cadaver femora. Generally, femoral bone with a CT density beyond 600 HU is not removable by conventional reamers. Thus, we recommend the 600 HU threshold as one of several criteria for the design of custom femoral implants from CT data.

Adult↗
PubMed1998

Hand development in trisomy 21.

The purpose of the present study was to evaluate hand size and maturity in fetuses with trisomy 21 (Down syndrome). Twenty-five fetuses, crown-rump length (CRL) 55-222 mm, foot length (FL) 8-42 mm, were included in the study. After whole-body radiography (Hewlett Packard Faxitron), special radiographs of the hand and foot were taken. Hand length was measured as the length of the third finger from the distal tip of the distal phalanx to the proximal tip of the metacarpal bone, the digital-metacarpal length (DML). The lengths of the proximal phalangeal bone (PPL) and the metacarpal bone (MCL) of the third finger were also measured. The DML, PPL, and MCL values of each fetus were related to CRL and FL. The individual hand bones were evaluated with regard to time of appearance on radiographs, sequence in comparison with the normal sequence of appearance, and morphology. The hand length is normal during the first half of the fetal period, whereas the length of individual bones in the third finger is reduced. The normal sequence of ossification, with the middle phalanx of the fifth finger last to ossify, also occurred in Down syndrome; however, this bone appeared later in Down syndrome. In four of the fetuses it did not appear.

Bone Development↗
PubMed1998

Pyrazole bioisosteres of leflunomide as B-cell immunosuppressants for xenotransplantation and chronic rejection: scope and limitations.

T-cell immunosuppressant-based therapies efficiently control early graft rejection in allotransplantation settings. They fail, however, to prevent those rejection events which are mediated by transplant-induced antibody (Ab) responses such as those involved in xenograft and chronic allograft rejection. This is mainly due to their inability to block T-cell-independent Ab production against the transplanted organs. The bioactive metabolite 2(Z) of leflunomide (1) inhibits the formation of such Ab, but the drug has pharmacokinetic properties and a therapeutic window incompatible with transplantation indications. Pyrazole 3, a constrained analogue of 2(Z), was designed and shown to be conformationally and biologically similar to 2(Z). Further investigations with derivatives of 3 demonstrated that the pyrazoles had very tight structure-activity relationships, the only equipotent compound being 3o. However, in contrast to 2(Z), both 3 and 3o were inactive in vivo due to short half-life and drug concentrations lower than the in vitro obtained IC50 values. Compound 3o inhibits T-cell-independent Ab production by a different biochemical mechanism from that of 2(Z) and 3 and may therefore represent a valuable tool for the identification of new targets for B-cell inhibition.

Administration, Oral↗
PubMed1998

Isoxazolylthioamides as potential immunosuppressants a combinatorial chemistry approach.

A library of thioamide derivatives of leflunomide 1a and of its bioactive metabolite 1b has been synthesised on solid phase. Thus, para-substituted phenylacetic acids were coupled to TentaGel and were subsequently reacted with aromatic isothiocyanates. Treatment of the resulting enaminothioamides with hydroxylamine led to their simultaneous cyclisation and cleavage from the resin affording 2-25. Their in vitro profiling demonstrated that the amide-thioamide isologous substitution was detrimental of the biological activity.

Animals↗
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

Comparison of the phagocytosis of two types of cyclosporin (SDZ OXL 400 and SDZ IMM 125) by alveolar macrophages from hamsters.

The aim of this study was to compare two types of cyclosporin (Cs) particles, SDZ OXL 400 and SDZ IMM 125, the latter being more hydrophilic, to understand their uptake by airway macrophages. Alveolar macrophages (AM), harvested by bronchoalveolar lavage (BAL) of hamster lungs, were cultured with two different doses (0.1 mg and 0.5 mg) for 1 h, 6 h, and 24 h. Control incubations without Cs particles or with latex particles were carried out simultaneously. Cell viability, cell activation (i.e., respiratory burst, interleukin-6 (IL-6) synthesis) and mean volume of particles phagocytosed per macrophage were measured. Both types of Cs particles did not modify the AM viability, and failed to induce IL-6 synthesis during phagocytosis but slightly decreased the cell oxidative respiratory burst. The comparison between SDZ OXL 400 and SDZ IMM 125 showed that for the lower dose the mean volume of both Cs types phagocytosed was similar at 1 h and 6 h. At 24 h an increase of the mean volume phagocytosed was seen for SDZ IMM 125 but not for SDZ OXL 400. For the higher dose the mean volume of SDZ IMM 125 phagocytosed was higher than SDZ OXL 400 at 1 h and 6 h and comparable for both types at 24 h. SDZ IMM 125 particles were phagocytosed more rapidly than SDZ OXL 400. The mean volume of phagocytosed latex particles increased with time and dose and was higher than for both Cs particle types. In conclusion, AM were seen to phagocytose particles of different physical properties (i.e., form, size, and shape), chemical properties (i.e., inert or peptidic) and degrees of hydrophilicity in a different manner.

Animals↗