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Biomedical subjects

K Jørgensen

Publications and source records attributed to K Jørgensen.

At least 19 recordsLinked to original sources

Dynamic lipid-bilayer heterogeneity: a mesoscopic vehicle for membrane function?

The lipid-bilayer component of cell membranes is an aqueous bimolecular aggregate characterized by a heterogeneous lateral organization of its molecular constituents. The heterogeneity may be sustained statically as well as dynamically. On the basis of recent experimental and theoretical progress in the study of the physical properties of lipid-bilayer membranes, it is proposed that the dynamically heterogeneous membrane states are important for membrane functions such as transport of matter across the membrane and enzymatic activity. The heterogeneous membrane states undergo significant structural changes in response to changes in compositional, thermodynamic, and environmental conditions. The diverse effects of a variety of molecular compounds interacting with membranes, such as cholesterol and drugs like anaesthetics, may be understood in terms of the ability of these compounds to affect and modulate the dynamic membrane heterogeneity.

Anesthetics

Blood pressure response to low level static contractions.

The present study re-examines the 15% MVC concept, i.e. the existence of a circulatory steady-state in low intensity static contractions below 15% of maximal voluntary contraction (MVC). Mean arterial blood pressure was studied during static endurance contractions of the elbow flexor and extensor muscles at forces corresponding to 10% and 40% MVC. Mean value for endurance time at 10% MVC was significantly longer for flexion [111.3 (SD 56.1) min] than for extension [18.1 (SD 7.5) min; n = 7]. At 40% MVC the difference in mean endurance time disappeared [2.3 (SD 0.7) min for elbow flexion and 2.3 (SD 0.7) min for elbow extension]. Mean arterial blood pressure exhibited a continuous and progressive increase during the 10% MVC contractions indicating that the 15% MVC concept would not appear to be valid. The terminal blood pressure value recorded at the point of exhaustion in the 10% MVC elbow extension experiment was identical to the peak pressure attained in the 40% MVC contraction. For the elbow flexors the terminal pressor response was slightly but significantly lower at 10% MVC [122.3 (SD 10.1) mmHg, 16.3 (SD 1.4) kPa] in comparison with 40% MVC [130.4 (SD 7.4) mmHg, 17.4 (SD 1.0) kPa]. When the circulation to the muscles was arrested just prior to the cessation of the contraction, blood pressure only partly recovered and remained elevated for as long as the occlusion persisted, indicating the level of pressure-raising muscle chemoreflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Modification of myo-electric power spectrum in fatigue from 15% maximal voluntary contraction of human elbow flexor muscles, to limit of endurance: reflection of conduction velocity variation and/or centrally mediated mechanisms?

Isometric flexion of the right elbow at 15% of the maximal voluntary contraction (MVC) was maintained to the limit of endurance (elbow angle 135 degrees). The surface electromyogram (EMG) of the brachioradialis (BR) and biceps brachii (BB) muscles was recorded for calculation of conduction velocity (CV) by the cross-correlation method, and determination of median frequency (fm) and root mean square (rms) amplitude. Perceived exertion was rated for both muscles, and heart rate and blood pressure were measured. The EMG of ten brief 15% MVC contractions distributed over a 30-min recovery period was also recorded. Eleven males in their twenties volunteered for the investigation. The average endurance time was 906 (SD 419) s. Mean CV for the unfatigued muscles was 4.2 (SD 0.41) m.s-1 (BR), and 4.3 (SD 0.29) m.s-1 (BB). The contraction caused a significant decrease in CV of BR (12%, P less than 0.001) whereas CV variation of BB remained insignificant. Concurrently the mean fm of both muscles dropped to approximately 66% of their initial values and their average rms amplitudes grew by approximately 380% (BR and BB: P less than 0.001, both parameters). The 1st min of recovery lowered the rms amplitudes by approximately 60% (BR and BB: P less than 0.01), while the fm increased to approximately 88% of the initial recording (BR, P less than 0.01; BB, P less than 0.05). The accompanying small increases in CV were beyond the level of significance. Over the next 29 min a significant parallel restitution in fm and CV took place; changes in fm evidenced a simple one to one reflection of relative CV variation. A similar uncomplicated linear causality between relative changes in CV and fm was hypothesized for the endurance contraction. Consequently, the 12% CV decrease of the BR accounted for only one-third of the fatigue induced fm reduction of 33%, while two-thirds were assumed to be attributable to centrally mediated regulatory interventions in motor unit (MU) performance. Independent of contributions from the virtually unchanged CV, the fm of the BB muscle decreased by 35%; from one subject exhibiting a remarkably manifest burst-type pattern of MU activity it is argued that synchronization/grouping of MU firing predominantly determined the power redistribution in the BB spectrum.

Adult

Results of uvulopalatopharyngoplasty in snoring.

Twenty-one patients (4 females and 17 males) with very annoying snoring were subjected to UPPP with CO2-laser technique. All patients were overweight (bodymass index average 30.3 kg/m2). In 71%, narrowing were found at the naso/oropharyngeal border. All had either abnormal uvula or soft palate. In 17 patients, snoring was reduced to a degree no longer socially annoying. Three were annoying to some extent. In only one patient, snoring was completely unchanged. UPPP is not very difficult to perform and we did not notice any troublesome sequelae. We think that UPPP is an effective operation for severe snoring, although it does not eliminate the symptom.

Female

Lymph node metastases in the neck from unknown primary tumour.

During a 12-year period a total of 203 patients were referred to the oncologic center of Odense with lymph node metastases in the neck. Routine examinations on admission failed to detect the primary tumour in 37 patients. During follow-up, the primary was revealed in 18 of these patients, and in a further 8 cases it was found at autopsy. The primary was most often located in the head and neck region with a possibility of curative therapy. Patients with small neck node metastases responded well to treatment with neck dissection and radiotherapy, resulting in a 5-year crude survival rate of 53%.

Adenocarcinoma

The effects of density fluctuations on the partitioning of foreign molecules into lipid bilayers: application to anaesthetics and insecticides.

An extensive computer-simulation study is performed on a simple but general molecular model recently proposed (Jørgensen et al. (1991) Biochem. Biophys. Acta 1062, 277-238) to describe foreign molecules interacting with lipid bilayers. The model is a multi-state lattice model of the main bilayer transition in which the foreign molecules are assumed to intercalate at interstitial lattice positions. Specific as well as non-specific interactions between the foreign molecules and the lipid acyl chains are considered. Particular attention is paid to the fluctuating properties of the membrane and how the presence of the foreign molecules modulates these fluctuations in the transition region. By means of computer-stimulation techniques, a detailed account is given of the macroscopic as well as microscopic consequences of the fluctuations. The macroscopic consequences of the fluctuations are seen in the thermal anomalies of the specific heat and the passive trans-membrane permeability. Microscopically, the fluctuations manifest themselves in lipid-domain formation in the transition region which implies an effective dynamic membrane heterogeneity. Within the model it is found that certain anaesthetics and insecticides which are characterised by specific interactions with the lipids have a strong effect on the heterogeneity of the membrane inducing regions of locally very high concentration of the foreign molecules. This leads to a broadening of the specific heat peak and a maximum in the membrane/water partition coefficient. These results are in accordance with available experimental data for volatile general anaesthetics like halothane, local anaesthetics like cocain derivatives, and insecticides like lindane.

Anesthetics

A general model for the interaction of foreign molecules with lipid membranes: drugs and anaesthetics.

A general microscopic interaction model is proposed to describe the changes in the physical properties of phospholipid bilayer membranes due to foreign molecules which, to different degrees, partition between the membrane phases and the aqueous environment. The model is a multi-state lattice model for the main phase transition of lipid bilayers and the foreign molecules are assumed to intercalate as interstitials in the lattice. By varying the model parameters, the diversity in the thermodynamic properties of the model is explored using computer-simulation techniques which faithfully take account of the thermal fluctuations. The calculations are performed in both the canonical and the grand canonical ensembles corresponding to the cases where the concentration of foreign molecules in the membrane is either fixed or varies as the external conditions are changed. A classification of the diverse thermal behaviour, specifically with regard to the phase diagram, the specific heat, the density fluctuations, and the partition coefficient, is suggested with a view to rationalizing a large body of experimental measurements of the effects of different foreign molecules on membrane properties. The range of foreign molecules considered includes compounds as diverse as volatile general anaesthetics like halothane, cocaine-derived local anaesthetics like procaine, calcium-channel blocking drugs like verapamil, antidepressants like chlorpromazine, and anti-cancer agents like adriamycin.

Anesthetics

Significance of skin temperature changes in surface electromyography.

Differing results have been reported concerning the direction and quantity of the electromyogram (EMG) amplitude response to changes in tissue temperature. The EMG signals from the soleus muscle of six healthy human subjects were therefore recorded during dynamic exercise (concentric contractions) at ambient temperatures of 30 degrees C and 14 degrees C. The mean skin temperature (Tsk) above the muscle investigated was 32.9 degrees C and 21.7 degrees C, respectively. The core temperature, estimated by rectal temperature, was unchanged. The cooling of the superficial tissues caused approximately a doubling of the EMG amplitude. For the probability level 0.9 in the amplitude probability distribution function, the average signal level increased from 73 microV to 135 microV (P = 0.02). The average mean power frequency of the EMG signal was reduced from 142 Hz to 83 Hz (P = 0.004). The amplitude increase was not due to shivering but other possible explanations are presented. As the changes in Tsk investigated were within the range which may occur normally during the working hours, it was concluded that Tsk should be carefully controlled in vocational EMG studies.

Adult

Changes in conduction velocity, median frequency, and root mean square-amplitude of the electromyogram during 25% maximal voluntary contraction of the triceps brachii muscle, to limit of endurance.

The objective of the present study was to investigate whether isometric contraction of the right triceps brachii muscle, of maximal duration and at 25% of the maximal voluntary contraction (MVC), would reduce mean fibre conduction velocity (CV) for the active motor units (MU). In addition to the cross-correlation of surface electromyograms (EMG) for CV determination, median frequency (fm) and root-mean-square amplitude (rms-amplitude) were calculated. The initial 5 min of the recovery of the three parameters was also investigated. The MVC were performed before and after the sustained contraction. Seven males-six in their twenties and one aged 43-participated in the investigation. Mean CV for the unfatigued muscle was 4.5 m.s-1, SD 0.38. On average, CV decreased less than 10% during the sustained contraction (P less than 0.05). The fm decreased almost linearly (46%) during the endurance time, while three quarters of the 250% increase in rms-amplitude took place during the last 50% of the contraction (P less than 0.001, both parameters). The MVC was reduced by 39% immediately after exhaustion (P less than 0.05). During the 1st min of recovery the rms-amplitude decreased by 50%, and the fm increased from 54% to 82% of the initial value (both P less than 0.05). No measurable simultaneous CV restitution occurred. A parallel 15% increase in fm and CV took place during the last 4 min of recovery (both P less than 0.001), while the amplitude remained constant. Since mean CV was essentially unchanged during the last 50% of the endurance time where large changes in fm and rms-amplitude occurred, factors supplementary to CV probably caused the striking changes in fatigue EMG, notably-MU recruitment, synchronization of MU activity, and lowering of MU firing frequencies. Nevertheless, during the last 4 min of recovery the entire increase in fm could be accounted for by the simultaneous increase in CV.

Adult

Photobleaching of astaxanthin and canthaxanthin. Quantum-yields dependence of solvent, temperature, and wavelength of irradiation in relation to packaging and storage of carotenoid pigmented salmonoids.

The quantum yield for the photobleaching of astaxanthin (the carotenoid of wild salmonoids) and of canthaxanthin (the closely related carotenoid used as a feeding additive for farmed salmonoids) has been determined for monochromatic light at different wavelengths and in different solvents. Astaxanthin is less sensitive to light than canthaxanthin. The photobleaching is strongly wavelength dependent, and the quantum yield for astaxanthin dissolved in chloroform at 22 degrees C is 3.2 x 10(-1) mol.Einstein-1 at 254 nm, 3.1 x 10(-2) at 313 nm, and 1.6 x 10(-6) at 436 nm, respectively. The quantum yields are less dependent on the nature of the solvent and show no simple correlation with oxygen solubility, i.e. for 366 nm excitation of astaxanthin the quantum yields are 6.1 x 10(-5) mol.Einstein-1 in acetone, 1.2 x 10(-4) in saturated vegetable oil, 1.9 x 10(-4) in chloroform, and 3.4 x 10(-4) solubilized in water, respectively. The photobleaching quantum yield provides an objective measure of the light sensitivity of the carotenoids in relation to the discolouration of carotenoid-pigmented salmonoids. The quantum yield was also found to be independent of the carotenoid concentration and, in a homogenous solution, of light intensities. For astaxanthin solubilized in water, the quantum yield increases for low light intensities. Excitation of astaxanthin solubilized in water using visible light shows that the photobleaching quantum yield is independent of temperature, while excitation at 313 nm shows an increase in the quantum yield with increasing temperatures, corresponding to an energy of activation of 28 kJ.mol-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Sister-chromatid exchanges in cannabis smokers.

The genotoxicity of cannabis smoking was evaluated by means of the sister-chromatid exchange (SCE) test. The SCE test is considered to be a sensitive tool for the discovery of genotoxic agents in the environment. Twenty-two tobacco smokers and 22 persons smoking both tobacco and cannabis were compared. Our findings showed that smoking in itself enhanced the SCE level significantly (18.5%) compared to a group of non-smokers, but adding smoking of cannabis to tobacco smoking did not affect the SCE level further. Based on our observations cannabis smoking could not be considered genotoxic.

Adolescent

Nimorazole as a hypoxic radiosensitizer in the treatment of supraglottic larynx and pharynx carcinoma. First report from the Danish Head and Neck Cancer Study (DAHANCA) protocol 5-85.

Between January 1986 and September 1990, 442 patients with pharynx and supraglottic larynx carcinoma were randomized to receive the hypoxic cell radiosensitizer nimorazole (NIM) or placebo in association with a course of conventional primary radiotherapy. A preliminary analysis including the first 288 patients showed that the stratification parameters were significant (3-year actuarial local-regional tumor control, p less than 0.05) for sex (females 52% vs males 34%), tumor size (T1-T2 47% vs T3-T4 32%) and pre-irradiation hemoglobin (Hb) concentration (high 41% vs low 34%). Overall, the NIM group showed a significantly better local-regional control rate than the placebo group (46% vs 32%). There was an apparent additive effect of Hb concentration and NIM. Thus, in the male group, placebo patients with low Hb had a 23% control rate compared to 46% in NIM treated patients with Hb above 9 mmol/l (p less than 0.05). The similar effect in females could not be evaluated due to the small number of women with this disease. NIM was well tolerated and drug-related side effects were minor and tolerable, with transient nausea and vomiting as the most frequent complication. A final conclusion of the study must await an evaluation including all patients and a longer observation time.

Carcinoma

Peritonsillar abscess: risk of disease in the remaining tonsil after unilateral tonsillectomy à chaud.

The occurrence of disease in the remaining tonsil after unilateral tonsillectomy à chaud in the treatment of peritonsillar abscess, was studied in 536 patients. No patient had a history of previous severe tonsillitis at the time of the unilateral tonsillectomy, 6.1 per cent of the patients were readmitted for surgery of the remaining tonsil during the follow-up period. Ninety-seven per cent of these patients were younger than 30 years of age. Previous investigations have shown increasing frequency by age of pharyngitis after bilateral tonsillectomy. We suggest bilateral tonsillectomy in all cases of patients younger than 30 years old who suffer from peritonsillar abscess irrespective of previous tonsillar disease. Patients older than 30 should be treated with unilateral ablation, unless there is a clear indication for bilateral tonsillectomy.

Adolescent

Inverted papilloma of the nose and paranasal sinuses: a study of 67 patients.

Retrospectively, 67 patients with inverted nasal papillomas were studied. In 12, the lesions were localized exclusively on the nasal septum. In 55, the lesion involved the lateral wall and/or the paranasal sinuses. There was a male predominance of 3:1. After histological revision the most dominating epithelial type was found to be transitional. Inverted papilloma was in one patient associated with squamous cell carcinoma. Ten per cent suffered recurrences from 6 to 37 months after the primary surgical procedure. We found that limited septal lesions could be managed by an intranasal procedure but lateral rhinotomy is recommended as the procedure of choice in the treatment of inverted papilloma of the lateral wall.

Adolescent

Anesthetics affect membrane heterogeneity.

A computer-simulation study is performed on a simple but general molecular model of the interaction of general and local anesthetics with lipid membranes. In the neighborhood of the gel-to-fluid membrane phase transition it is found that anesthetics have a strong effect on the heterogeneity of the membrane-inducing regions of locally high anesthetics concentration. This leads to a broadening of the specific heat peak and a maximum in the membrane/water partition coefficient. These results are in accordance with available experimental data for volatile general anesthetics like halothane and local anesthetics like cocaine derivatives.

1,2-Dipalmitoylphosphatidylcholine

Epidermoid carcinoma of the pharynx. Therapeutic results in a series of 221 patients.

Two hundred and twenty-one cases of epidermoid carcinoma of the pharynx diagnosed between 1965 and 1984 were analysed. Fifty-seven per cent of the carcinomas were poorly differentiated and 57% of the patients had stage IV disease; 65% had lymph node metastases at the time of diagnosis. Radiotherapy was the primary treatment. Between 1977 and 1979, preirradiation chemotherapy was used and from 1979 the effect of the radiosensitizer misonidazole was investigated in split-course radiotherapy. Loco-regional failure occurred in 60% after primary treatment. No changes in treatment results were observed during four consecutive 5-year periods. The five-year corrected actuarial survival rate in the whole series was 33%. It is concluded that the treatment results are still unsatisfactory, and that chemotherapy, optimized radiotherapy, and radiosensitizers as used in the present series did not seem to improve the results. Alcohol and tobacco restriction is emphasized for prevention.

Adolescent