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Biomedical subjects

K Andersen

Publications and source records attributed to K Andersen.

At least 91 records · Page 5Linked to original sources

Cancer patients, doctors and nurses vary in their willingness to undertake cancer chemotherapy.

Cancer patients' attitude to chemotherapy were compared with those of doctors, nurses and healthy controls. 98 cancer patients, 42 healthy subjects, 44 oncologists, 35 surgeons, 32 oncology nurses and 70 surgical nurses received a questionnaire presenting a hypothetical situation involving a toxic chemotherapy regimen. Each were asked to indicate the minimal benefit with respect to chance of cure, life prolongation and symptom relief they would demand to accept the treatment. The patients and the surgical nurses were most reluctant with regard to the treatment. The subgroup of patients under 50 years which matched the oncologists, surgeons and controls with respect to age, cohabitant status and children were significantly more willing to accept the regimen than the controls and professional groups. Patients under 40 years would accept the toxic treatment with hardly any benefit as chance of cure (7%, median), life prolongation (3 months) and symptom relief (8%). Among the professionals, oncologists were most willing to accept therapy, whereas surgical nurses and surgeons were least willing.

Adult↗

Classification of fish-pathogenic vibrios based on comparative 16S rRNA analysis.

No systematic classification of fish-pathogenic vibrios has been accomplished previously despite the use of serological, physiological, and genetical classification systems. In this study, a comparative 16S rRNA analysis of 34 strains (representing seven species) of fish-pathogenic vibrios was performed. The 16S rRNA sequences were obtained by using reverse transcriptase. Nearly complete sequences were obtained for nine strains. On the basis of the results of this analysis, the remaining strains were investigated by analyzing selected stretches containing a total of 560 nucleotides. With the exception of a few strains, including ATCC 43313 (serovar O9), our comparative 16S rRNA analysis confirmed that strains preliminarily identified as Vibrio anguillarum were phylogenetically closely related. Strains of V. anguillarum could be divided into groups, with the main group containing serotype O1 and O2 strains isolated from Atlantic salmon, rainbow trout, turbot, cod, and saithe. The other distinctive group was represented by type strain NCMB 6. This strain was nearly indistinguishable from the type strains of Vibrio ordalii and Vibrio damsela on the basis of the 16S rRNA stretches compared. The results of a comparative 16S rRNA analysis justified the status of Vibrio salmonicida as a distinct species. Originally, this species was characterized biochemically as a very homogeneous species. However, two strains, which were isolated from diseased halibut and from the intestines of healthy cod, could not be distinguished from V. salmonicida strains phylogenetically, although they differed from the original species description in several phenotypic traits. Our results indicate that V. salmonicida and Vibrio fischeri form a cluster that is clearly separated from the cluster that includes V. anguillarum.

Animals↗

Bone and collagen turnover during treatment with inhaled dry powder budesonide and beclomethasone dipropionate.

OBJECTIVES: To assess bone and collagen turnover in asthmatic children treated with dry powder budesonide from the Turbuhaler and dry powder beclomethasone dipropionate from the Diskhaler in a dose of 800 micrograms/day. SUBJECTS: Thirteen prepubertal children with asthma. DESIGN: Open crossover study with two treatment periods and treatment free run-in and wash-out periods. All periods were of two weeks' duration. At day 14 in each period blood samples were taken for assessment of serum osteocalcin, the carboxyterminal propeptide of type I collagen (PICP), and the aminoterminal propeptide of type III collagen (PIIINP). At the same time urine was collected for assessment of creatinine corrected pyridinoline (uPYR/cr) and deoxypyridinoline (udPYR/cr) crosslinks. RESULTS: Osteocalcin concentrations were not influenced by any of the treatments. During budesonide treatment mean (SEM) PICP was reduced by 18% (8%) (p = 0.03), PIIINP by 24% (3%) (p = 0.0002), uPYR/cr by 16% (6%) (p = 0.03), and udPYR/cr by 21% (13%) (p = 0.12). During treatment with beclomethasone dipropionate mean (SEM) PICP was reduced by 20% (6%) (p = 0.01), PIIINP by 36% (3%) (p = 0.0002), uPYR/cr by 18% (4%) (p = 0.004), and udPYR by 13% (5%) (p = 0.02). The suppressive effect of beclomethasone dipropionate on PIIINP was more marked than that of budesonide (p = 0.001). CONCLUSION: Treatment with dry powder budesonide and beclomethasone dipropionate 800 micrograms/day is associated with suppression of bone and collagen turnover. The suppression seems to be more marked during treatment with beclomethasone dipropionate. Long term effects and effects of lower doses of budesonide and beclomethasone dipropionate on bone and collagen markers needs further study.

Administration, Inhalation↗

Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease? The Rotterdam Study.

Based on reports that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk for Alzheimer's disease (AD), we studied the cross-sectional relation between NSAID use and the risk for AD in a population-based study of disease and disability in older people. After controlling for age, education, gender, and use of benzodiazepines, we found a relative risk (RR) for AD of 0.38 (0.15 to 0.95) when comparing NSAID users (n = 365) to NSAID non-users (n = 5,893). To address confounding by indication or contraindication, we compared NSAID users with a subset of NSAID non-users who were using topical medication for ear, eye, or dermatologic conditions (n = 365). In this comparison, the adjusted RR for AD was 0.54 (0.16 to 1.78). These findings are compatible with a possible protective effect of NSAIDs on the risk for AD.

Aged↗

Fungal arthritis. A review.

Fungal arthritis (FA) due to a candida infection was reviewed in English literature and described in 45 cases. The increasing use of potent antibiotics, immunosuppressives, and especially the use of artificial joints, predisposed to the infection. Weightbearing joints, particularly the knees, were most frequently affected. Symptoms were described as a warm, tender and swollen joint, and the duration of symptoms prediagnosis was described as being up to 4 years. Amphotericin B was the treatment drug of choice, and in cases of no response, supplemented with either flucytosine or ketoconazole. Local FA healed in all cases. FA in an artificial joint resulted in all cases in removal of the prostheses. Mortality in systemic fungal infections including FA was 50%.

Amphotericin B↗

[Septic arthritis].

Septic arthritis (SA) is reviewed in the English literature with reference to registration of localisation of the infected joints, the bacteriological cause, predisposing factors, clinical information and laboratory data related to SA. Seventy-eight publications were available concerning 975 patients with 1086 infected joints caused by 1032 bacteria. Large joints such as the knee and hip were most frequently, however, infected, in recent years, SA in small axial joints has been reported with increased frequency. Gram-positive cocci and especially Staphylococcus aureus are most frequently the cause of infection. High temperatures, elevated sedimentation rate and leucocytosis are often noticed in SA, as is a warm, tender, swollen joint with effusion and painful movements. Investigation of the aspirated fluid from the joint for bacteria and number of leucocytes as well as CT-scanning or scintigraphy are the most important diagnostic tools. With rapid and correct antibiotic treatment the prognosis for good or excellent function of the joint is reported to be from 27-90%, while the mortality is reported as being 7-23%.

Anti-Bacterial Agents↗

[Septic arthritis in intravenous drug abuse].

Septic arthritis (SA) in intravenous abusers is reviewed in the English literature from 1966-1992 with the purpose of registration of the bacteriological development, localization of the infected joints, clinical information and laboratory data. Eighty-three publications are available for the review. We have registered 270 joint infections caused by 264 bacteria in 257 intravenous drug abusers with SA. Since 1985 there has been a change in joint localization and bacteriology. A possible explanation is considered. Diagnosis and treatment is difficult, because of the unstable life-style and frequent compliance problems in intravenous drug abusers. SA should be considered in patients with known intravenous drug abuse, uncharacteristic pain and symptoms of osteoarticular infection. SA is often accompanied by fever, leucocytosis and elevated sedimentation rate. Bacteriological diagnosis is achieved by joint aspiration and/or blood culture. Tc-99m-MDP-(technetium-99m-methylene diphosphonate)-bone scintigraphy should be performed on joints suspected of infection which are difficult to aspirate. With adequate antibiotic treatment the prognosis is good, and the mortality is insignificant.

Anti-Bacterial Agents↗

Development of a receptor-interaction model for serotonin 5-HT2 receptor antagonists. Predicting selectivity with respect to dopamine D2 receptors.

A receptor-interaction model for serotonin 5-HT2 receptor antagonists has been developed by conformational analysis with molecular mechanics (MM2(91)) and superimposition studies of serotonin 5-HT2 receptor antagonists. Substituted 3-(4-piperidinyl)-,1-(4- piperidinyl)-,3-(1,2,3,6-tetrahydropyridin-4-yl)-, and 1-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles, substituted 3-(4-fluorophenyl)-1-(4-piperazinyl)indans, cyprohepatadine derivatives, ritanserin, and danitracene have been used as bases for the model. Other serotonin 5-HT2 receptor antagonists, such as ketanserin and MDL 11,939, are well accommodated into the model. Comparison of the model with a recently described receptor-interaction model for dopamine D2 receptor antagonists suggests a common pharmacophore for dopamine D2 and serotonin 5-HT2 receptor antagonists. Important steric differences between 5-HT2 receptor antagonists with additional high affinity for dopamine D2 receptors and serotonin 5-HT2 receptor antagonists with high selectivity versus D2 receptors are described. The geometry of the receptor-interaction model described is significantly different from that of a recently reported receptor-interaction model for 5-HT2 receptor agonists and antagonists developed by use of (+)-LSD as a template, suggesting the existence of two binding modes at the 5-HT2 receptor.

Indans↗

The effect of phenobarbital on cerebral blood flow in newborn infants with foetal distress.

The effect of phenobarbital on cerebral blood flow (CBF) was investigated by the intravenous Xenon133 clearance technique in seven term newborn infants with signs of mild to moderate hypoxic ischaemic encephalopathy, all on sustained spontaneous ventilation. Phenobarbital treatment had no significant effect on CBF 60 min after loading dosage (20 mg/kg i.v.). Likewise, no significant change in mean arterial blood pressure, heart rate or transcutaneous gas tensions was observed. Though slight changes in CBF of short duration cannot be excluded, conventional dosage of phenobarbital to term newborn infants with foetal distress apparently imposes no risk of cerebrovascular damage.

Brain Ischemia↗

Evaluation of standardized methods for registration of time-dependent orthodontic tooth movements.

An in vitro study was conducted to compare reproducibility of repeated recordings obtained from devices constructed for standardized registrations. An existing radiographic method and a new photographic technique were employed. On five in vitro models, half of the maxilla from dry skulls, special designed splints with a Troll-biten film holder were constructed. A stiff metal bar attached to the splints and to either an X-ray apparatus or a standard photographic camera made it possible to obtain standardized registrations. For each model 10 radiographs and photographs were taken before and after the canine was moved. Subtracting the values from well defined points for these pictures, 10 pairs of coordinates were available for each of the models with both methods. The findings showed very similar reproducibility for the two methods with 95 per cent of the discrepancies within a magnitude of 0.12 mm for the radiographic method and 0.14 mm for the photographic method. When evaluating the canine movements, similar results were observed. No significant difference could be detected in the five in vitro models. In addition, the results showed that a splint can be used as a stable reference for registration of tooth movements. Because of ethical objections to unnecessary radiation, the photographic registration technique might substitute the radiographs in future investigations where standardized periodic records are necessary for the description of tooth movement.

Analysis of Variance↗

Epileptic seizures, arthrogryposis, and migrational brain disorders: a syndrome?

INTRODUCTION: Arthrogryposis multiplex congenita (AMC) may be associated with multiple developmental defects. In some severely affected newborns with AMC, autopsy studies have suggested a common mechanism of malmigration at the spinal and cerebral levels. To our knowledge, a constellation of arthrogryposis, epileptic seizures, and brain migrational anomalies in adult patients has not previously been described in a clinical material. MATERIAL AND METHODS: Six consecutive adult patients with arthrogryposis multiplex congenita and epileptic seizures form the basis of the present study. Five patients had joint contractures and reduced muscle volume restricted to the lower extremities, whereas one patient had predominantly upper extremity affection. They were studied with magnetic resonance imaging (MRI), EEG, EMG, a neuropsychological test battery, and chromosome analysis. RESULTS: Four of them had clear evidence of migrational brain disorders, demonstrated by MRI, in three of them roughly corresponding to the focal epileptiform EEG activity. Five of the patients had partial seizures, whereas one only had generalized tonic-clonic seizures. The MRI findings included polymicrogyria, pachygyria, and fused schizencephaly. Four had neurogenic EMG changes, one had myopathic EMG features, and one had an unremarkable EMG pattern in affected muscles. All patients with demonstrable migrational disorders showed abnormal neuropsychological features. Three patients were mentally retarded. A chromosome abnormality in the form of a ring chromosome 18 was present in one patient. CONCLUSION: We suggest that AMC, epileptic seizures, and migrational brain disorders may form the integral parts of a hitherto undescribed syndrome in adults. A wide-spread defect in neuronal migration along the entire neural axis may be the underlying mechanism of the cerebral and the peripheral symptoms.

Adolescent↗

[Cor triatriatum with atrial fibrillation as initial symptom in adults].

Cor triatriatum is a rare congenital heart disease. In its classic form its consists of a fibromuscular perforated membrane which divides the left atrium and obstructs blood flow from pulmonary veins to mitral orifice. Clinical symptoms and signs resemble those of mitral stenosis. Traditionally cor triatriatum was encountered most often in infancy and childhood. We describe the case of a young man with cor triatriatum and atrial fibrillation, with syncope. He was operated on with total resection of the obstructing membrane. Modern echocardiography has made diagnosis more easy. Thus, an increasing number of cases of cor triatriatum are diagnosed in adults with few or no symptoms. Symptoms, diagnosis and treatment are discussed, with emphasis on these patients.

Adult↗

Hysterothylacium aduncum (Rudolphi, 1862) infection in cod from the Oslofjord: seasonal occurrence of third- and fourth-stage larvae as well as adult worms.

Hysterothylacium aduncum infections in cod from the Oslofjord were followed for 1 year. The recovered worms were grouped according to developmental stage [third-stage larvae (L3), fourth-stage larvae (L4) and adult worms] and according to location (in the gut or encapsulated on the viscera). The cod were found to be infected with H. aduncum (all stages lumped) throughout the whole year, with the prevalence approaching 100%. The abundance of the parasites (mean number per fish studied), however, was clearly lowest during the summer months. L3 and L4 recovered from the intestine dominated most of the time but showed a very clear peak during late winter and early spring. L3 recovered from the body cavity was the only stage that showed a clear peak during the summer months. Adult worms, although adult worms were present in very small numbers throughout the year, they tended to peak in May and then again in December and January. Since there did not seem to be a correlation between the accumulation of L3 in the body cavity and the length or age of the fish, the possibility of self-infection whereby the larvae reenter the gut and continue to develop into L4 and then into adults, is discussed.

Animals↗

Immunological and hormonal responses to lung surgery during one-lung ventilation.

The effects of lung surgery performed during one-lung ventilation and the associated endocrine stress response on natural killer (NK) cell activity and the distribution of white blood cells in peripheral blood were studied in 10 patients with malignant lung tumours. Patients were anaesthetized with general anaesthesia combined with thoracic epidural anaesthesia. The endocrine response was measured as changes in serum cortisol, plasma adrenaline and noradrenaline. A significant decrease of NK cell activity was found post-operatively accompanied by leucocytosis, neutrophilia and lymphopenia. Significant increases in serum cortisol were demonstrated at the end of operation and throughout the study period. Plasma adrenaline increased significantly during one-lung ventilation with a gradual normalization post-operatively. Plasma noradrenaline increased significantly during the whole post-operative course. In conclusion, lung surgery was accompanied by similar changes in NK cell activity, leucocyte and differential counts, serum cortisol and plasma adrenaline levels as demonstrated after other types of major surgery. The elevated noradrenaline level post-operatively is a new observation that may be specific for lung surgery.

Adult↗

Selective, centrally acting serotonin 5-HT2 antagonists. 1. 2- and 6-substituted 1-phenyl-3-(4-piperidinyl)-1H-indoles.

A series of 1-[2-[4-(1H-indol-3-yl)-1-piperidinyl]ethyl]-2-imidazolidinones has been synthesized. The 1-position of the indole is substituted with phenyl groups and in the 2- or 6-positions are additional substituents. An analogous series with the imidazolidinone ring opened to corresponding urea derivatives was also prepared. High potency and selectivity for 5-HT2 receptors (as compared with D2 and alpha 1 receptor affinities) were obtained with medium-large substituents such as 6-chloro, 6-methyl, and 6-trifluoromethyl or a 2-methyl substituent. Larger 6-substituents such as isopropyl considerably reduced activity, while the smaller 6-fluoro substituent afforded unselective compounds. Selective 5-HT2 antagonists were found by combining 6-substitution with both unsubstituted 1-phenyl and substituted 1-phenyl groups (2-F, 4-F, 4-Cl). However, 3-substitution of the phenyl group markedly reduced 5-HT2 receptor affinity, especially with a 3-trifluoromethyl substituent. Introduction of a 3-(2-propyl) substituent in the imidazolidinone ring reduced binding to alpha 1 adrenoceptors with a factor of 3-8. Practically no influence on 5-HT2 and D2 receptor affinities were found by the presence of this substituent compared to the 3-unsubstituted derivatives. Compounds with potent receptor binding also potently inhibited the quipazine-induced head twitch syndrome in rats. The compounds were equally active after oral and subcutaneous administration and they had a long duration of action (> 24 h). Especially urea derivatives were found to be considerably more potent at 24 h than at 2 h after subcutaneous administration. Some of the compounds potently inhibited isolation-induced aggression in mice, an effect which, however, did not correlate to 5-HT2 receptor-mediated activities. On the basis of these structure-activity studies 1-[2-[4-[6-chloro-1-(4-fluorophenyl)-1H-indol-3-yl]-1- piperidinyl]ethyl]-3-(2-propyl)-2-imidazolidinone (Lu 26-042, compound 4c) was selected for further pharmacological and toxicological investigations.

Animals↗

Selective, centrally acting serotonin 5-HT2 antagonists. 2. Substituted 3-(4-fluorophenyl)-1H-indoles.

A series of 3-(4-fluorophenyl)-1H-indoles substituted in the 1-position with 4-piperidinyl, 1,2,3,6-tetrahydro-4-pyridinyl, and 4-piperazinyl was synthesized. By variation of the substituents in the benzene part of the indole nucleus in 1-[2-[4-[3-4-fluorophenyl)-1H-indol-1-yl]-1-piperidinyl]-ethyl]-2- imidazolidinones, the highest 5-HT2 receptor affinity and selectivity with respect to dopamine D2 receptors and alpha 1 adrenoceptors were obtained by 5-methyl substitution. Different substituents were introduced in the 1-position of the piperidine ring in the 5-methyl-substituted derivative. Thus replacement of the 2-(2-imidazolidinon-1-yl)ethyl side chain with a 2-(1,3-dimethyl-1-ureido)ethyl or methyl substituent resulted in unchanged affinity and selectivity for 5-HT2 receptors. Replacement with a 2-[3-(2-propyl)-2-imidazolidinon-1-yl]ethyl side chain reduced binding to alpha 1 adrenoceptors with a factor of four, while affinities for 5-HT2 and D2 receptors were retained, compared to the 3-unsubstituted imidazolidinone. Indoles substituted in the 1-position with 4-piperazinyl had generally weaker affinity for both 5-HT2 and D2 receptors compared to corresponding 4-piperidinyl- and 1,2,3,6-tetrahydro-4-pyridinyl-substituted indoles. Introduction of a methyl group in the 2-position of the 5-methyl-substituted indole resulted in further increase of selectivity for the 5-HT2 receptor. Compounds with potent receptor binding also potently inhibited the quipazine-induced head twitch syndrome in rats. The compounds were equally active after oral and subcutaneous administration and showed a long duration of action (> 24 h). In general, the derivatives were found to be considerably more potent at 24 h than at 2 h after the administration. The compounds within this series were prepared as analogues of the previously described 1-(4-fluorophenyl)-3-(4-piperidyl)-1H-indoles by interchange of the C-3 carbon atom and the nitrogen atom in the indole nucleus. The pharmacological results indicate that this isosteric replacement results in higher selectivity for 5-HT2 receptors compared to the former series. The 1-[2-[4-[2,5-dimethyl-3-(4-fluorophenyl)-1H-indol-1-yl]-1- piperidinyl]ethyl]-2-imidazolidinone has high affinity for 5-HT2 receptors (IC50 = 3.4 nM) and extremely low affinity for both dopamine D2 receptors (IC50 = 6900 nM) and alpha 1 adrenoceptors (IC50 = 2300 nM).

Animals↗