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H Eriksen

Publications and source records attributed to H Eriksen.

14 recordsLinked to original sources

Immunochemical characterization of assay for carboxyterminal telopeptide of human type I collagen: loss of antigenicity by treatment with cathepsin K.

The assay for the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) has been shown to reflect increased type I collagen degradation in such pathological conditions as bone metastases and rheumatoid arthritis, but to be rather insensitive to the changes in physiological bone collagen turnover (e.g., induced by estrogen or bisphosphonate treatment). To determine the reasons for this discrepancy we localized the antigenic determinant recognized by the ICTP assay and studied the effects of two major osteoclastic proteinases, cathepsin K (EC 3.4.22.38) and matrix metalloproteinase-9 (MMP-9; gelatinase B; EC 3.4.24.35), on immunoreactivity. The antigenic determinant was shown to reside within the hydrophobic phenylalanine-rich regions of the carboxyterminal telopeptides of the two alpha1 chains of human type I collagen, situated between the triple helical domain and the lysine-derived trivalent cross-link. This conclusion was based on differences between the amino acid sequences and cross reactivities of the corresponding human and bovine antigens before and after proteolytic treatments with chymotrypsin. A trivalent cross-link is necessary for providing such a structure, because the divalently cross-linked and monomeric natural and synthetic peptides from the same region, but containing only one phenylalanine-rich sequence, showed poor immunoreaction. Recombinant human cathepsin K cleaved the trivalently cross-linked ICTP structure at two sites between the phenylalanine-rich region and the cross-link, destroying the reactivity with ICTP antibodies. On the contrary, the treatment of isolated ICTP by the matrix metalloproteinases MMP-9 (gelatinase B), MMP-1 (collagenase 1), or MMP-13 (collagenase 3) had no effect on the immunoreaction. Our results indicate that the increased circulating concentrations of ICTP found in several clinical situations are most likely produced by matrix metalloproteinases, whereas cathepsin K-mediated, osteoclastic bone resorption destroys ICTP antigenicity.

Amino Acid Sequence↗

A new X linked recessive deafness syndrome with blindness, dystonia, fractures, and mental deficiency is linked to Xq22.

X linked recessive deafness accounts for only 1.7% of all childhood deafness. Only a few of the at least 28 different X linked syndromes associated with hearing impairment have been characterised at the molecular level. In 1960, a large Norwegian family was reported with early onset progressive sensorineural deafness, which was indexed in McKusick as DFN-1, McKusick 304700. No associated symptoms were described at that time. This family has been restudied clinically. Extensive neurological, neurophysiological, neuroradiological, and biochemical, as well as molecular techniques, have been applied to characterise the X linked recessive syndrome. The family history and extensive characterisation of 16 affected males in five generations confirmed the X linked recessive inheritance and the postlingual progressive nature of the sensorineural deafness. Some obligate carrier females showed signs of minor neuropathy and mild hearing impairment. Restudy of the original DFN-1 family showed that the deafness is part of a progressive X linked recessive syndrome, which includes visual disability leading to cortical blindness, dystonia, fractures, and mental deficiency. Linkage analysis indicated that the gene was linked to locus DXS101 in Xq22 with a lod score of 5.37 (zero recombination). Based on lod-1 support interval of the multipoint analysis, the gene is located in a region spanning from 5 cM proximal to 3 cM distal to this locus. As the proteolipid protein gene (PLP) is within this region and mutations have been shown to be associated with non-classical PMD (Pelizaeus-Merzbacher disease), such as complex X linked hereditary spastic paraplegia, PLP may represent a candidate gene for this disorder. This family represents a new syndrome (Mohr-Tranebjaerg syndrome, MTS) and provides significant new information about a new X linked recessive sydromic type of deafness which was previously thought to be isolated deafness.

Adolescent↗

The pharmacokinetics of acitretin and its 13-cis-metabolite in psoriatic patients.

The synthetic retinoic acid derivative acitretin has recently been introduced for the treatment of severe psoriasis. Hitherto, the use of the carboxylic acid ester analogue, etretinate, has been hampered by an extremely long elimination half-life of up to 120 days for this drug. In the presented study, 12 patients with severe psoriasis were treated with 30 mg acitretin daily for a period of 6 months. The maximum plasma concentration of the drug occurred within about 0.9 to 4.6 hours with an apparent absorption half-life ranging from 0.2 to 1.7 hours and with half-lives of the distribution phase within the range of 1.2 to 3.5 hours. After stopping therapy, the terminal elimination half-life of acitretin varied between 16.5 and 111.1 hours (mean: 47.1 hr +/- 29.8 SD), whereas that for the 13-cis-metabolite varied between 36.5 and 249.4 hours (mean: 119.4 hr +/- 73.4 SD). Suction blister fluid concentrations of both the parent drug and metabolite were lower than plasma concentrations. The mean concentration of serum triglycerides was significantly elevated during the course of therapy, but still remained within the normal range. Saliva concentrations of drug and metabolite at steady-state were below 1 ng/mL. It is not possible from the observed half-lives of acitretin and its 13-cis-metabolite to draw any definite conclusion with regard to the anticonceptional period after acitretin therapy in psoriatic patients.

Acitretin↗

Mediastinoscopy in bronchogenic carcinoma.

Mediastinoscopy was performed in 470 patients with bronchogenic carcinoma in the ENT Department, Aalborg. The histological diagnoses were 195 squamous cell carcinomas, 149 adenocarcinomas, and 126 anaplastic carcinomas. Metastases in the mediastinal lymph nodes were found in 177 of the 470 patients (38%). Metastatic lymph nodes were found in approximately one fifth of the squamous cell carcinomas, in almost half of the adenocarcinomas, and in about half of the anaplastic carcinomas. The need is emphasized for lymph node biopsy from both right and left tracheobronchial angles and inferior to the bifurcation irrespective of the site of the carcinoma. Contralateral metastasis was found in approximately one third of the cases, and a positive biopsy from the nodes inferior to the bifurcation was found in about 40% of the patients in whom metastasis in the mediastinum were detected. In 10% of the patients, cytological and histological examinations of specimens obtained by bronchoscopy were negative, and the diagnosis of lung cancer was made by mediastinoscopy exclusively. The value of mediastinoscopy was particularly high in the diagnosis of adenocarcinomas.

Adenocarcinoma↗

[Bronchoscopy in monosymptomatic hemoptysis--hemoptysis in bronchial carcinoma].

Blood in sputum, haemoptysis, is a common symptom in mucous membrane disorders of the respiratory tract--it is often seen in conjunction with inflammation but may also be associated with malignant tumours of the respiratory tract. In a survey of 422 patients with monosymptomatic haemoptysis, 15 patients with bronchogenic carcinoma were identified. A cytological examination of the sputum of these 15 patients was carried out, and in 9 of these cases suspected malignant cells were observed. From these and other observations it is concluded that with patients of over 40 years of age who are smokers with haemoptysis, but who display a normal X-ray examination of the thorax, it would be prudent to carry out a cytological examination of the sputum before bronchoscopy.

Adult↗

Changes in CMRO2, EEG and concentration of etomidate in serum and brain tissue during craniotomy with continuous etomidate supplemented with N2O and fentanyl.

Fourteen patients with supratentorial cerebral tumours were anaesthetized with continuous etomidate infusion (30 or 60 micrograms kg-1 min-1) supplemented with N2O 67% and fentanyl. Peroperatively cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice by the Kety and Schmidt method. Simultaneously with the CBF measurements, blood for serum etomidate was sampled and EEG was recorded in 2-min periods in 12 patients. In 10 patients a brain biopsy for etomidate was taken peroperatively and correlated with the other data. The results indicate a dose-dependant increase in serum etomidate and brain tissue etomidate, a decrease in CMRO2 and suppression of EEG activity. In individual studies an increase in serum etomidate or a decrease in CMRO2 correlated to a suppression of the EEG activity, and vice versa. However, the wide variations in these relationships within and between patients make any conclusion regarding CMRO2 impossible from the EEG recording, infusion rate of etomidate or serum concentration of etomidate.

Adult↗

CBF and CMRO2 during continuous etomidate infusion supplemented with N2O and fentanyl in patients with supratentorial cerebral tumour. A dose-response study.

In 14 patients with supratentorial cerebral tumours with midline shift below 10 mm, CBF and CMRO2 were measured (Kety & Schmidt) during craniotomy. The anaesthesia was continuous etomidate infusion supplemented with nitrous oxide and fentanyl. The patients were divided into two groups. In Group 1 etomidate infusion of 30 micrograms kg-1 min-1 was used throughout the anaesthesia, and CBF and CMRO2 were measured twice. In this group CMRO2 (means +/- s.d.) averaged 2.31 +/- 0.43 ml O2 100 g-1 min-1 70 min after induction and 2.21 +/- 0.38 ml O2 100 g-1 min-1 130 min after induction. In Group 2 the etomidate infusion was increased from 30 to 60 micrograms kg-1 min-1 after the first study and a significant fall in CMRO2 from 2.52 +/- 0.56 to 1.76 +/- 0.40 ml O2 100 g-1 min-1 was found. Simultaneously, a significant fall in CBF was observed. The CO2 reactivity was preserved during anaesthesia.

Adult↗

Methylprednisolone half-life during simultaneous barbiturate treatment and mechanical hyperventilation of neurosurgical patients.

The pharmacokinetics of methylprednisolone sodium succinate (MP) were studied in six neurosurgical patients under intensive treatment with large doses of MP, barbiturates, and mechanical hyperventilation. The study showed a remarkable level of enzyme induction within 24 hours after starting treatment, when the first blood samples were taken. The half-life (t 1/2) for MP during barbiturate and hyperventilation therapy was found to be reduced by a mean 55% (p less than 0.01) in relation to the t 1/2 of MP when administered alone. Studies on the day after termination of barbiturate intake indicated a tendency for an increase in the t 1/2 of MP, but it was not significantly different from the pretermination assessment (p greater than 0.05). On the basis of this study it is not possible to determine if the change in t 1/2 alone is governed by enzyme induction or by a combination of this plus a change in the distribution and clearance of the steroid. The clinical implication of these findings is that patients who are undergoing steroid treatment and at the same time are sedated with barbiturates should have their MP dose increased in order to compensate for the marked reduction of t 1/2 of MP.

Adolescent↗

Native and degraded fibronectin: new immunological methods for distinction.

Two methods for quantitative determination of the high molecular weight glycoprotein, fibronectin, have been developed. Both methods are based on enzyme-linked immunoadsorbent (ELISA) techniques. In the first of the methods an antibody against fibronectin is used to trap the antigen. This double antibody technique can detect a slight decrease in the concentration of fibronectin stored for 5 days compared to the amount of fibronectin in the freshly purified preparation. In the second method, gelatin which is known to bind specifically to fibronectin, is used to catch fibronectin. By this method less than 1% of the fibronectin present in a freshly prepared preparation is measured after storage for 5 days. The results obtained with the two methods applied on a freshly prepared and a stored fibronectin are in agreement with sodium dodecylsulphate polyacrylamide gel electrophoresis followed by immunoblotting before and after gelatin-Sepharose adsorption. These techniques demonstrate that all the freshly prepared fibronectin adsorbs to gelatin-Sepharose, while stored fibronectin, which is broken down to numerous peptides, still reacts with the fibronectin antibody, but does not adsorb to gelatin-Sepharose. The two ELISA techniques were applied on amniotic fluid, cerebrospinal fluid and urine. The results indicated significant degradation of fibronectin in urine, and less degradation of fibronectin in amniotic and spinal fluid.

Amniotic Fluid↗

[Achilles legend].

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Dental Materials↗