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Biomedical subjects

K Jørgensen

Publications and source records attributed to K Jørgensen.

At least 19 recordsLinked to original sources

Physiological response to submaximal isometric contractions of the paravertebral muscles.

STUDY DESIGN: Brief (30-second) isometric trunk extensions at 5%, 20%, 40%, 60%, and 80% of maximal voluntary contraction (MVC) and 3 minutes of prolonged trunk extension (20% MVC) in erect position were studied in nine healthy male subjects. OBJECTIVES: To investigate the intercorrelation between intramuscular pressure and tissue oxygenation of the paravertebral muscles during submaximal isometric contractions and further, to evaluate paravertebral electromyogram and intramuscular pressure as indicators of force development. SUMMARY OF BACKGROUND DATA: Local physiologic responses to muscle contraction are incompletely understood. METHODS: Relative oxygenation was monitored with noninvasive near-infrared spectroscopy, intramuscular pressure was measured with a transducer-tipped catheter, and surface electromyogram was monitored at three recording sites. RESULTS: The root mean square amplitudes of the paravertebral electromyogram (L4, left and right; T12, right) and intramuscular pressure measured in the lumbar multifidus muscle at L4 increased with greater force development in a curvilinear manner. A significant decrease in the oxygenation of the lumbar paravertebral muscle in response to muscle contraction was found at an initial contraction level of 20% MVC. This corresponded to a paravertebral intramuscular pressure of 30-40 mm Hg. However, during prolonged trunk extension, no further decrease in tissue oxygenation was found compared with the tissue oxygenation level at the end of the brief contractions, indicating that homeostatic adjustments (mean blood pressure and heart rate) over time were sufficient to maintain paravertebral muscle oxygen levels. CONCLUSION: At a threshold intramuscular pressure of 30-40 mm Hg during muscle contraction, oxygenation in the paravertebral muscles is significantly reduced. The effect of further increase in intramuscular pressure on tissue oxygenation over time may be compensated for by an increase in blood pressure and heart rate. Surface electromyogram amplitudes and intramuscular pressure can be used as indicators of paravertebral muscle force.

Adult

Association of ethanol with lipid membranes containing cholesterol, sphingomyelin and ganglioside: a titration calorimetry study.

The association of ethanol at physiologically relevant concentrations with lipid bilayers of different lipid composition has been investigated by use of isothermal titration calorimetry (ITC). The liposomes examined were composed of combinations of lipids commonly found in neural cell membranes: dimyristoyl phosphatidylcholine (DMPC), ganglioside (GM(1)), sphingomyelin and cholesterol. The calorimetric results show that the interaction of ethanol with fluid lipid bilayers is endothermic and strongly dependent on the lipid composition of the liposomes. The data have been used to estimate partitioning coefficients for ethanol into the fluid lipid bilayer phase and the results are discussed in terms of the thermodynamics of partitioning. The presence of 10 mol% sphingomyelin or ganglioside in DMPC liposomes enhances the partitioning coefficient by a factor of 3. Correspondingly, cholesterol (30 mol%) reduces the partitioning coefficient by a factor of 3. This connection between lipid composition and partitioning coefficient correlates with in vivo observations. Comparison of the data with the molecular structure of the lipid molecules suggests that ethanol partitioning is highly sensitive to changes in the lipid backbone (glycerol or ceramide) while it appears much less sensitive to the nature of the head group.

Anesthetics

Interaction of a lipid-membrane destabilizing enzyme with PEG-liposomes.

Polymer grafted PEG-liposomes have come into use as drug-delivery systems with improved therapeutic profiles. However, very little is known about the morphological instability of PEG-liposomes due to enzymatic degradation. To gain further insight into the effect of PEG lipopolymer-concentration on the catalytic activity of a liposome-degrading enzyme, phospholipase A2 (PLA2)-catalyzed phospholipid hydrolysis of PEG-liposomes has been investigated. The temperature dependence of the PLA2 lag-time, denoting the time required before a sudden increase in enzymatic activity takes place, has been determined for submicellar amounts of dipalmitoylphosphatidylethanolaminyl-poly-(ethylene glycol) (DPPE-PEG2000) incorporated into unilamellar dipalmitoylphosphatidylcholine (DPPC)-liposomes. The measurements demonstrate a significant reduction in the lag-time over broad temperature ranges. The results suggest that a close relationship exists between PLA2 catalyzed lipid hydrolysis and lipid-membrane composition, which moreover is of major importance for the overall morphological stability and the release of encapsulated material from the polymer-grafted PEG-liposomes.

Drug Delivery Systems

Influence of lipopolymer concentration on liposome degradation and blood clearance.

It is well known, that a prolonged liposome circulation time can be achieved by incorporation of lipopolymers into the lipid membrane thereby reducing interactions with destabilizing factors in the blood stream, e.g. phagocytic cells and lipoproteins. However, very little is known about the enzymatic degradation of steric hindered liposomes introduced into body fluids. In this study, the blood clearance and the PLA2 catalyzed degradation of unilamellar dipalmitoylphosphatidylcholine (DPPC) liposomes incorporated with increasing amounts of dipalmitoylphosphatidylethanolamine-polyethyleneglycol (DPPE-PEG), was investigated. The results demonstrated an increase in PLA2 activity for increasing amounts of lipopolymer in the lipid membrane, while the liposome blood clearance was prolonged by incorporation of DPPE-PEG into the liposomes. Hence, these results suggest that it may be possible for long circulating liposomes to obtain a site specific liposome degradation and release of drug substance in tissue with high levels of PLA2.

1,2-Dipalmitoylphosphatidylcholine

Fatigue in patients with Parkinson's disease.

OBJECTIVE: To compare the prevalence of fatigue in patients with Parkinson's disease (PD) with that in healthy elderly people and to explore the suggestion that fatigue is an independent symptom of PD. DESIGN: Questionnaire survey. SETTING: Community-based population. PATIENTS AND CONTROL SUBJECTS: 233 patients derived from a prevalence study in the county of Rogaland, Norway and 100 healthy elderly people with the same age and sex distribution as the patients with PD. MAIN OUTCOME MEASURE: A score for fatigue was obtained by combining the results from the rating scale for low energy in the Nottingham Health Profile (NHP) with the results obtained from a 7-point scale devised to evaluate fatigue. RESULTS: 44.2% of the patients with PD and 18% of the healthy elderly control subjects reported fatigue. Fatigue was associated with depression, dementia, disease severity, disease duration, levodopa dose, and the use of sleeping pills. In a multivariate analysis, only depressive symptoms reached statistical significance. The prevalence of fatigue in patients with PD who were not depressed, demented, or had a sleeping disturbance was similar to that found in the total PD population. CONCLUSION: Fatigue is a common symptom in PD. Although fatigue correlated with depressive symptoms, patients with PD who did not have depression, dementia, or sleep disturbances also reported a high prevalence of this symptom. This supports the hypothesis that fatigue is an independent symptom of PD overlapping with, but not causally related to, the concurrence of depressive symptoms.

Adult

Increase in phospholipase A2 activity towards lipopolymer-containing liposomes.

Phospholipase A2 (PLA2)-catalyzed hydrolysis of dipalmitoylphosphatidylcholine (DPPC) liposomes incorporated with submicellar concentrations of polyethyleneoxide covalently attached to dipalmitoylphosphatidylethanolamine (DPPE-PEG2000) has been studied in the gel-to-fluid transition region of the host DPPC lipid bilayer matrix. By means of fluorescence and light-scattering measurements, the characteristic PLA2 lag time has been determined as a function of lipopolymer concentration and temperature. The degree of lipid hydrolysis was followed using radioactive labeled lipids. Differential scanning calorimetry has been applied to characterize the thermodynamic phase behavior of the lipopolymer-containing liposomes. A remarkable lipopolymer concentration-dependent decrease in the lag time was observed over broad temperature ranges. The radioactive measurements demonstrate an increase in catalytic activity for increasing amounts of lipopolymers in the bilayer. Hence, the lipopolymers act as a promoter of PLA2 lipid hydrolysis resulting in a degradation of the bilayer structure and a concomitant destabilization of the liposomes. This behavior is in contrast to the generally observed protective and stabilization effect in biological fluids exerted by lipopolymers in polymer-grafted liposomes. It is proposed that the enhanced activity of the small water soluble and interfacially active enzyme may involve a non-uniform distribution of the lipopolymers in the lipid matrix due to a coupling between local lipid bilayer curvature and composition of the non-bilayer-preferring lipopolymers.

1,2-Dipalmitoylphosphatidylcholine

Significance of mat and shoe softness during prolonged work in upright position: based on measurements of low back muscle EMG, foot volume changes, discomfort and ground force reactions.

The aim of the investigation was to study the significance of mat and shoe softness during prolonged work in an upright position based on some physiological, biomechanical and comfort measurements related to the lower extremities and the low back. Eight healthy female volunteers performed 2 h of simulated standing and 2 h of standing/walking work tasks in the laboratory using four combinations of soft shoes, clogs, soft mat and concrete. Thus, each subject performed a total of eight 2 h work tests. The following parameters were measured pre-experimentally and one or more times during 2 h: total foot volume, vascular volume and interstitial volume of the left foot, EMG from the lumbar paraspinals, movement of centre of gravity (only during standing), biomechanical heel impact (only during standing/walking), perceived discomfort in lumbar back, legs and feet, whole body oxygen uptake, arterial blood pressure and heart rate. Using soft shoes rather than clogs during standing/walking work implies approximately a halving of the foot oedema formation and the heel impact. The effects due to the introduction of the soft mat are negligible. The local circulatory responses in the feet and the EMG-signs of paravertebral muscle fatigue are larger during standing compared to standing/walking work. The two investigated work types in this study differ regarding exposures as well as responses. Thus, it is recommended to shift between these postures and seated work during the working hours to improve job exposures.

Adult

The muscular load on the lower back and shoulders due to lifting at different lifting heights and frequencies.

The aim of the study was to investigate the muscular load on the lower back and shoulders and the circulatory load on employees at a post center during repetitive lifting of mail transport boxes. A mock-up was designed in the laboratory, a total of nine combinations of lifting height and frequency were studied. Surface EMG was recorded bisymmetrically from m. erector spinae (L3-level) and m. trapezius. The circulatory load was evaluated by measuring the heart rate. The results show a trade off between the low back and shoulders. The maximum load on the low back occurred at the low lifting height (363 and 54.4 cm) whereas the maximum load on the shoulders occurred at the high lifting height (144.9 and 163.0 cm).

Adult

Lack of predictive value of potential doubling time and iododeoxyuridine labelling index in radiotherapy of squamous cell carcinoma of the head and neck.

PURPOSE: To investigate the prognostic value of T(POT), S-phase time (TS), iododeoxyuridine (IdUrd) labelling index (LI) and DNA index with loco-regional tumour control as the end-point. MATERIALS AND METHODS: Iododeoxyuridine was given to 99 patients with squamous cell carcinomas of the head and neck before the start of radiotherapy. The analysis included FCM parameters (LI, TS, T[POT] and DNA index, n = 87) and LI determined by immunohistology (IHC, n = 45). A hybrid T(POT) was determined by combining the FCM TS and the IHC LI (n = 45). In diploid tumours (n = 39), the FCM LI was underestimated and the FCM T(POT) was overestimated because the flow cytometer was unable to distinguish between tumour and normal cells. The 'tumour LI' was defined as the IHC LI or the FCM LI of aneuploid tumours when a biopsy for IHC evaluation was not available and similarly the 'tumour T(POT)' was determined by the hybrid T(POT) or the FCM T(POT) of aneuploid tumours (n = 63). RESULTS: There was good agreement between the IHC LI and the FCM LI for aneuploid tumours, but there was disagreement for diploid tumours. The median tumour T(POT) was 4.1 days (range 0.6-19.5 days) and the median tumour LI was 12.9% (range 3.1-46.0%). In a univariate analysis there was no prediction of loco-regional tumour control by the LI, the TS or the T(POT) determined by either of the methods. T-classification, N-classification, clinical stage and tumour diameter were related with loco-regional tumour control, whereas clinical stage was the only parameter that yielded independent prognostic significance in a multivariate analysis. CONCLUSIONS: This study does not confirm the significant prognostic value of T(POT) as indicated in some previous reports. Larger clinical studies are needed to draw final conclusions.

Analysis of Variance

A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85.

PURPOSE: A multicenter randomized and balanced double-blind trial with the objective of assessing the efficacy and tolerance of nimorazole given as a hypoxic radiosensitizer in conjunction with primary radiotherapy of invasive carcinoma of the supraglottic larynx and pharynx. PATIENTS AND TREATMENT: Between January 1986 and September 1990, 422 patients (414 eligible) with pharynx and supraglottic larynx carcinoma were double-blind randomized to receive the hypoxic cell radiosensitizer nimorazole, or placebo, in association with conventional primary radiotherapy (62-68 Gy, 2 Gy per fraction, five fractions per week). The median observation time was 112 months. RESULTS: Univariate analysis showed that the outcome (5-year actuarial loco-regional tumor control) was significantly related to T-classification (T1-T2 48% versus T3-T4 36%, P = 0.0008), neck-nodes (N- 53% versus N+ 33%), pre-irradiation hemoglobin (Hb) concentration (high 46% versus low 37%, P = 0.02) and sex (females 51% versus males 38%, P = 0.03). Overall the nimorazole group showed a significantly better loco-regional control rate than the placebo group (49 versus 33%, P = 0.002). A similar significant benefit of nimorazole was observed for the end-points of final loco-regional control (including surgical salvage) and cancer-related deaths (52 versus 41%, P = 0.002). This trend was also found in the overall survival but to a lesser, non-significant extent (26 versus 16%, 10-year actuarial values, P = 0.32). Cox multivariate regression analysis showed the most important prognostic parameters for loco-regional control to be positive neck nodes (relative risk 1.84 (1.38-2.45)), T3-T4 tumor (relative risk 1.65 (1.25-2.17)) and nimorazole (relative risk 0.69 (0.52-0.90)). The same parameters were also significantly related to the probability of dying from cancer. The compliance to radiotherapy was good and 98% of the patients received the planned dose. Late radiation-related morbidity was observed in 10% of the patients, irrespective of nimorazole treatment. Drug-related side-effects were minor and tolerable with transient nausea and vomiting being the most frequent complications. CONCLUSION: Nimorazole significantly improves the effect of radiotherapeutic management of supraglottic and pharynx tumors and can be given without major side-effects.

Adult

A new look at lipid-membrane structure in relation to drug research.

Lipid-bilayer membranes are key objects in drug research in relation to (i) interaction of drugs with membrane-bound receptors, (ii) drug targeting, penetration, and permeation of cell membranes, and (iii) use of liposomes in micro-encapsulation technologies for drug delivery. Rational design of new drugs and drug-delivery systems therefore requires insight into the physical properties of lipid-bilayer membranes. This mini-review provides a perspective on the current view of lipid-bilayer structure and dynamics based on information obtained from a variety of recent experimental and theoretical studies. Special attention is paid to trans-bilayer structure, lateral molecular organization of the lipid bilayer, lipid-mediated protein assembly, and lipid-bilayer permeability. It is argued that lipids play a major role in lipid membrane-organization and functionality.

Animals

Survey of pork, poultry, coffee, beer and pulses for ochratoxin A.

Surveys have been carried out to estimate the levels of ochratoxin A in pork, poultry, coffee, beer and pulses. A total of 286 samples were analysed. The results show that compared with cereals and cereal products the contribution from the foods surveyed to the total intake of ochratoxin A by the Danish population must be considered to be of less importance.

Animals

Effect of traditional Chinese acupuncture on severe tinnitus: a double-blind, placebo-controlled, clinical investigation with open therapeutic control.

This study aims to determine the effect of intensive acupuncture on severe tinnitus. The structure of the study was a randomized, double-blind, clinical investigation with open therapeutic surveillance and included 54 patients. All were subjected to 25 treatment sessions over a period of two months, each treatment lasting 30 minutes. Fifty-two patients completed the study. The variables used for self-registration were based on the visual analogue scale (VAS), where annoyance, loudness and awareness of the tinnitus were assessed. These were recorded twice daily over a four-month period starting one month before the first treatment and ending one month after the last treatment. Questionnaires, interviews and audiometry were carried out repeatedly. No statistically significant differences were found between the acupuncture group and the placebo group.

Acupuncture Therapy

Phase behavior and permeability properties of phospholipid bilayers containing a short-chain phospholipid permeability enhancer.

The thermodynamic phase behavior and trans-bilayer permeability properties of multilamellar phospholipid vesicles containing a short-chain DC10PC phospholipid permeability enhancer have been studied by means of differential scanning calorimetry and fluorescence spectroscopy. The calorimetric scans of DC14PC lipid bilayer vesicles incorporated with high concentrations of DC10PC demonstrate a distinct influence on the lipid bilayer thermodynamics manifested as a pronounced freezing-point depression and a narrow phase coexistence region. Increasing amounts of DC10PC lead to a progressive lowering of the melting enthalpy, implying a mixing behavior of the DC10PC in the bilayer matrix similar to that of a substitutional impurity. The phase behavior of the DC10PC-DC14PC mixture is supported by fluorescence polarization measurements which, furthermore, in the low-temperature gel phase reveal a non-monotonic concentration-dependent influence on the structural bilayer properties; small concentrations of DC10PC induce a disordering of the acyl chains, whereas higher concentrations lead to an ordering. Irreversible fluorescence quench measurements demonstrate a substantial increase in the trans-bilayer permeability over broad temperature and composition ranges. At temperatures corresponding to the peak positions of the heat capacity, a maximum in the trans-bilayer permeability is observed. The influence of DC10PC on the lipid bilayer thermodynamics and the associated permeability properties is discussed in terms of microscopic effects on the lateral lipid organization and heterogeneity of the bilayer.

Calorimetry, Differential Scanning

Characterization of the sub-main-transition in distearoylphosphatidylcholine studied by simultaneous small- and wide-angle X-ray diffraction.

Simultaneous small- and wide-angle X-ray diffraction was used to investigate the structural conversions in the so-called sub-main-transition of fully hydrated multilamellar vesicles of distearoyl phosphatidylcholine (DSPC). The small-angle diffraction patterns show a modification in the supramolecular structure of the corrugated lipid bilayer and reveal that the sub-main-transition does not abolish the general features of the ripple phase (P(beta')). Concomitantly in the wide-angle region the diffraction patterns exhibit a rearrangement of the hydrocarbon chain packing and an onset of chain melting. The presence of KCl show an enhancement of the effects of the sub-main-transition. Moreover, in the ripple phase (P(beta')) below the sub-main-transition the hydrocarbon chains are positioned on an orthorhombic lattice in the presence of KCl.

Calorimetry, Differential Scanning

The effects of ethylene oxide containing lipopolymers and tri-block copolymers on lipid bilayers of dipalmitoylphosphatidylcholine.

A comparative study is conducted on the influence of two types of polymeric compounds on the phase behavior of 1,2-dihexadecanoyl-s,n-glycero-3-phosphotidylcholine (DC16PC) lipid bilayers. The first polymeric compound is a lipopolymer, with two different lengths of a hydrophilic polyethylene oxide moity, anchored to the bilayer by a 1,2-dioctadecanoyl-s,n-glycero-3-phosphoethanolamine (DC18PE) lipid. The second type, which is a novel type of membrane-spanning object, is an amphiphilic tri-block copolymer composed of two hydrophilic stretches of polyethylene oxide separated by a hydrophobic stretch of polystyrene. Hence the tri-block copolymer may act as a membrane-spanning macromolecule mimicking an amphiphilic protein or polypeptide. Differential scanning calorimetry is used to determine a partial phase diagram for the lipopolymer systems and to assess the amount of lipopolymer that can be loaded into DC16PC lipid bilayers before micellization takes place. Unilamellar and micellar phase structures are investigated by fluorescence quenching using bilayer permeating dithionite. The chain length-dependent critical lipopolymer concentration, denoting the lamellar-to-micellar phase transition, compares favorably with a theoretical prediction based on free-energy considerations involving bilayer cohesion and lateral pressure exerted by the polymer chains.

1,2-Dipalmitoylphosphatidylcholine