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Biomedical subjects

M Kjaer

Publications and source records attributed to M Kjaer.

At least 163 records · Page 9Linked to original sources
PubMed1993

Bioavailability of a new oral formulation of medroxyprogesterone acetate compared with the standard formulation: a single dose randomized study.

Twenty-six female patients with breast cancer participated in an open, randomized, cross-over study comparing single dose bioavailability of a recently developed oral medroxyprogesterone acetate (MPA) formulation (200 mg sachet where MPA is loaded in a polyvinylpyrrolidone cross-linked polymer, MPA/PVP) with the standard formulation (500 mg tablet). Blood tests were performed under standardized conditions for 120 h in all patients and MPA plasma concentrations determined by means of HPLC. Dose-normalized AUC(0-tz), AUC (0-infinity) and Cmax were all significantly higher for the MPA/PVP formulation than for the standard formulation. The relative bioavailability of the MPA/PVP formulation was on average three times superior to that of the standard formulation. This new MPA formulation might have important clinical implications for the treatment of hormone-sensitive cancer.

Administration, Oral↗
PubMed1993

Regulation of hepatic glucose production during exercise in humans: role of sympathoadrenergic activity.

To investigate the role of sympathoadrenergic activity on glucose production (Ra) during exercise, eight healthy males bicycled 20 min at 41 +/- 2 and 74 +/- 4% maximal O2 uptake (VO2max; mean +/- SE) either without (control; Co) or with blockade of sympathetic nerve activity to liver and adrenal medulla by local anesthesia of the celiac ganglion (Bl). Epinephrine (Epi) was in some experiments infused during blockade to match (normal Epi) or exceed (high Epi) Epi levels during Co. A constant infusion of somatostatin and glucagon was given before and during exercise. At rest, insulin was infused at a rate maintaining euglycemia. During intense exercise, insulin infusion was halved to mimic physiological conditions. During exercise, Ra increased in Co from 14.4 +/- 1.0 to 27.8 +/- 3.0 mumol.min-1.kg-1 (41% VO2max) and to 42.3 +/- 5.2 (74% VO2max; P < 0.05). At 41% VO2max, plasma glucose decreased, whereas it increased during 74% VO2max. Ra was not influenced by Bl. In high Epi, Ra rose more markedly compared with control (P < 0.05), and plasma glucose did not fall during mild exercise and increased more during intense exercise (P < 0.05). Free fatty acid and glycerol concentrations were always lower during exercise with than without celiac blockade. We conclude that high physiological concentrations of Epi can enhance Ra in exercising humans, but normally Epi is not a major stimulus. The study suggests that neither sympathetic liver nerve activity is a major stimulus for Ra during exercise. The Ra response is enhanced by a decrease in insulin and probably by unknown stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Incidence and prevalence of myasthenia gravis in western Denmark: 1975 to 1989.

We studied the epidemiology of myasthenia gravis (MG) in western Denmark from 1975 to 1989, basing case identification on records from all hospitals in the survey area. The population surveyed was 2.80 million in 1985. The average annual incidence rate was 5.0 per million population (women, 5.9; men, 4.2). The point-prevalence rate (January 1, 1990) was 78 per million population (women, 102; men, 53). In men, the incidence increased after 40 years. In women, the incidence rates showed a bimodal pattern with a peak of 7.0 in the age group 20 to 29 years and a second peak of 11.7 in the age group 70 to 79 years. The differences in sex- and age-specific incidence rates suggest that younger women are more susceptible to MG than younger men. Old men and postmenopausal women had similar rates. When last examined, 21% of the 220 prevalent cases were in remission and 18% were moderately or severely disabled.

Adolescent↗
PubMed1993

Estimated treatment responses in metastatic colorectal carcinoma based on longitudinal carcinoembryonic antigen series.

Patients presenting with advanced or metastatic colorectal carcinoma were randomized to treatment with either 5-Fluoro-Uracil + leucovorin or 5-Fluoro-Uracil + interferon alpha-2-a. Longitudinal series of Carcino-embryonic-antigen were obtained and analyzed with a dynamic model in seven of 16 patients had CEA levels above 10 ng ml-1. Clinical evaluation based on X-ray, ultrasound and CT-scans showed a partial response to the given treatment in three of the seven patients. The dynamic model consistently estimated the maximal accumulated cell kill (approximately three logs) in the patients experiencing a clinical response. The remaining four patients with CEA levels above 10 ng ml-1 showed some reduction in CEA as a consequence of the treatment cycles, although no clinical response could be established. No response was seen among the remaining nine patients with CEA levels below 10 ng ml-1.

Adult↗
PubMed1992

Physiological profile and incidence of injuries among elite figure skaters.

The physiological responses to skating and the incidence of injuries were recorded in young, Danish elite figure skaters (n = 8) over a 1-year period. The skaters' maximum oxygen uptake (VO2 max) ranged from 54.7 to 68.8 ml kg-1 min-1, and work intensity during simulated competitive figure skating corresponded to 89% VO2 max. Before the onset of competitive skating, but after a warm-up, blood lactate (BLa) concentration was measured as 2.0 +/- 0.05 mM (means +/- S.E.). After a 4-min run, BLa increased to 8.0 +/- 0.6 mM. The subjects' resting heart rates were measured each morning over a 1-year period and corresponded to 53 +/- 2 and 58 +/- 3 beats min-1 for the males and females respectively, with no systematic season-related variations. The skaters trained for 15-41 h per week, 60-95 min of this time being spent on warm-up activities. The injury incidence rate during competitive skating was recorded as 1.4 injuries per 1000 h of training, 56% of these being acute and 44% chronic injuries. Of those injuries registered, 83% were recalled by the skaters when a retrospective questionnaire was given to them at the end of the observation period. This study indicates that ice figure skating is associated with high aerobic power. Furthermore, Danish skaters spend large amounts of time on training, including warm-up and stretching. Despite the amount of training and the intensity of ice-skating programmes, injury rates are low compared with other sporting events.

Adolescent↗
PubMed1992

Effect of arm-cranking on leg blood flow and noradrenaline spillover during leg exercise in man.

Controversy exists whether recruitment of a large muscle mass in dynamic exercise may outstrip the pumping capacity of the heart and require neurogenic vasoconstriction in exercising muscle to prevent a fall in arterial blood pressure. To elucidate this question, seven healthy young men cycled for 70 minutes at a work load of 55-60% VO2max. At 30 to 50 minutes, arm cranking was added and total work load increased to (mean +/- SE) 82 +/- 4% of VO2max. During leg exercise, leg blood flow average 6.15 +/- .511 minutes-1, mean arterial blood pressure 137 +/- 4 mmHg and leg conductance 42.3 +/- 2.2 ml minutes-1 mmHg-1. When arm cranking was added to leg cycling, leg blood flow did not change significantly, mean arterial blood pressure increased transiently to 147 +/- 5 mmHg and leg vascular conductance decreased transiently to 33.5 +/- 3.1 ml minutes-1 mmHg-1. Furthermore, arm cranking doubled leg noradrenaline spillover. When arm cranking was discontinued and leg cycling continued, leg blood flow was unchanged but mean arterial blood pressure decreased to values significantly below those measured in the first leg exercise period. Furthermore, leg vascular conductance increased transiently, and noradrenaline spillover decreased towards values measured during the first leg exercise period. It is concluded that addition of arm cranking to leg cycling increases leg noradrenaline spillover and decreases leg vascular conductance but leg blood flow remains unchanged because of a simultaneous increase in mean arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of 5 wk of detraining on epinephrine response to insulin-induced hypoglycemia in athletes.

Long-term endurance-trained subjects are known to have an enhanced capacity to secrete epinephrine. It is, however, unknown to what extent this is a reversible phenomenon, i.e., whether the adrenal medullary secretory capacity is diminished during a period of abstinence from training. Hormonal responses to insulin-induced hypoglycemia were studied in seven endurance-trained young male athletes at the onset and the termination of a 31- to 44-day period of detraining necessitated by a sports injury that required leg casting. During insulin infusion, plasma glucose decreased to a mean range of 2.0-2.1 mM for the two conditions. The epinephrine response to hypoglycemia did not decrease significantly during the 4-6 wk of detraining (P greater than 0.05). Responses of other counterregulatory hormones, i.e., norepinephrine, glucagon, growth hormone, and cortisol, were identical in trained and detrained subjects (P greater than 0.05). Heart rate and blood pressure responses to hypoglycemia were similar in the two conditions (P greater than 0.05). In conclusion, in endurance athletes the enhanced capacity to secrete epinephrine is maintained during 5 wk of detraining.

Adolescent↗
PubMed1992

Neural influence on cardiovascular and endocrine responses to static exercise in humans.

At the onset of exercise, signals from the central nervous system result in immediate vagal withdrawal and resulting increases in heart rate and arterial blood pressure. From the second heart beat peripheral nerve (reflex) influence from exercising muscle can be detected. With continued exertion, especially with large muscle groups, this influence becomes increasingly important. Sympathetic nerve signals to resting muscle can be influenced by the central nervous system, but are dominated by influence from 'metaboreceptors' in exercising muscle, while sympathetic nerve signals to skin are more influenced by the central nervous system. Cardiovascular responses to static contractions increase with the percentage of maximum contraction intensity as well as with the muscle mass involved. Plasma catecholamines rise in proportion to increases in cardiovascular variables and are influenced by a central nervous mechanism early in the contraction. Furthermore, during static contractions the increase in plasma adrenaline (epinephrine) is larger relative to that of noradrenaline than during dynamic exercise. Both catecholamine responses and the responses of pituitary hormones depend on the active muscle mass, but are small compared to those established during dynamic exercise. Experiments designed to enhance central command, resulting in increased cardiovascular and endocrine responses compared to control experiments and experiments in which an attenuation of peripheral nerve influence resulted in reduced changes in these variables during exercise, contrast with the notion that the 2 neural control mechanisms are redundant. Rather, the 2 neural influences on the autonomic nervous system work in concert in eliciting the responses manifest during static exercise.

Cardiovascular Physiological Phenomena↗
PubMed1992

Bioavailability and analgesic effect of sustained release cetobemidone capsules in cancer patients with chronic pain of malignant origin.

Ever since its introduction in 1952, Ketogan has consisted of a combination of the opioid cetobemidone and a spasmolytic drug, A29, in the ratio of 1:5. Its main limitations are the relatively short duration of action and an apparent ceiling effect due to A29. We therefore developed a cetobemidone formulation with sustained release properties (cetobem. s.r.). Forty-seven patients with advanced cancer with moderate/severe pain, treated with regular doses of Ketogan tablets took part in an open phase 1 type pharmacologic/toxicologic study comparing Ketogan tablets and cetobem. s.r. The patients spent at least 4 days in the department. After evaluation during 12 h with Ketogan tablets (3-4 dosing intervals), a loading phase lasting for 36 h with cetobem. s.r. given twice/24 h (total dose of Ketogan tablets per 24 h divided by 2), and synchronous reduction of the dose of Ketogan tablets, a similar evaluation period of 12 h was performed when on treatment with cetobem. s.r. alone. Comparison of data from the two observation periods showed the following: Average relative bioavailability 0.77 SD 0.28. Only 2 patients were remedicated before 12 h when on cetobem. s.r. Duration of action mean 11.9 h, SD 0.3 h. There was no significant difference between Ketogan tablets and cetobem. s.r. periods concerning 'time with no pain'. Side-effects were few. The only significant difference was dry mouth being more severe during the tablet period. Vital signs were unaffected by treatment. It is concluded that cetobem. s.r. can be given every 12 h to cancer patients with chronic pain with satisfactory analgesic effect, a very modest change in side-effect profile and no significant effects on vital signs when substituting cetobem. s.r. for Ketogan tablets in equal daily doses.

Adult↗
PubMed1992

The effect of normoxic or hypobaric hypoxic endurance training on the hypoxic ventilatory response.

Cross-sectional studies in endurance athletes have demonstrated a diminished hypoxic ventilatory response (HVR) compared with mountaineers or sedentary controls. Conversely, short-term altitude acclimatization may increase the HVR. The longitudinal effect of training, either at sea level or altitude, on HVR has not been previously reported. We therefore studied 21 untrained men and women before and after 5 wk of cycle ergometer training at either sea level or 2,500 m. HVR was determined using the steady-state method (16). Minute ventilation (VE) was measured with a Tissot spirometer during the last minute of 5 min breathing room air, 8% and 12% O2, administered in random order. CO2 was added at the mouth in an effort to maintain end-tidal CO2 at baseline levels. Oxyhemoglobin saturation was measured directly from arterial blood with a hemoximeter (OSM 3). HVR was defined as the positive slope of the line relating VE to O2 saturation in l.min-1%-1. One group of subjects trained at sea level at 70% maximal oxygen uptake (VO2max; N = 7). A second group trained at 2,500 m in a hypobaric chamber, at the same relative exercise intensity (i.e., 70% altitude VO2max) or same absolute intensity (same power output) as group 1 (N = 14). Both groups trained on a bicycle ergometer for 45 min.d-1, 5 d.wk-1 for 5 wk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Refinement of the three-dimensional solution structure of barley serine proteinase inhibitor 2 and comparison with the structures in crystals.

The three-dimensional structure of barley serine proteinase inhibitor, CI-2, has been determined using nuclear magnetic resonance spectroscopy. The present structure determination is a refinement of the structure previously determined by us, using in the present case stereo-specific assignments, and a virtually complete set of assignments of the two-dimensional nuclear Overhauser spectrum. The structure determination is based on the identification of more than 1300 nuclear Overhauser effects, of which 961 were used in the structure calculation as distance restraints, and on 94 dihedral angle restraints, of which 31 are for chi 1 angles in defined chiral centers. These have been used to calculate a series of 20 three-dimensional structures using a combination of distance geometry, simulated annealing and restrained molecular dynamics. Each of the 20 structures was in agreement within less than 0.5 A of each of the distance restraints and with all dihedral angle restraints. When compared to the geometric average structure of the 20 refined structures the root-mean-square differences for the backbone atoms were 0.8 (+/- 0.2) A and for all atoms were 1.6 (+/- 0.2) A. By comparison, the values obtained for the structures determined previously were 1.4 (+/- 0.2) A and 2.1 (+/- 0.1) A, respectively. The structures were also compared to the structure determined in the crystalline state by X-ray diffraction showing root-mean-square differences of 1.6 (+/- 0.2) A and 2.8 (+/- 0.2) A for the backbone and all atoms, respectively. Common features of the solution structure and the two crystal structures are the four-stranded beta-structure, composed of a pair of parallel strands, and three pairs of antiparallel beta-strands flanked on one side by a 12-residue alpha-helix and on the other side by a loop containing the serine proteinase binding site. The new analysis of the structure has revealed an additional pair of antiparallel beta-strands, consisting of residues 65 to 67 and 81 to 83, that was not seen in either of the crystal structures or the previous solution structure. Identification of this was based on nuclear magnetic resonance evidence for the hydrogen bond (67HN to 81CO) not reported previously. Also the presence of a bifurcated hydrogen bond involving Phe69 CO and HN atoms of Ala77 and Gln78 was observed in solution but not in crystals. Minor differences between the two structures were observed in the phi-angles of residues Met59 and Glu60 in the inhibitory site.

Crystallography↗
PubMed1991

A nuclear magnetic resonance study of the hydrogen-exchange behaviour of lysozyme in crystals and solution.

Amide hydrogen/deuterium exchange behaviour has been studied for all of the peptide amides of hen lysozyme by means of two-dimensional n.m.r. spectroscopy. The amides have been grouped into four categories on the basis of their rates of exchange in solution at pH 4.2 and 7.5. The distribution of the amides into the different categories has been examined in the light of the crystallographic structural information, considering the type of secondary structure, the nature of hydrogen bonding and the distance from the protein surface. None of these features was found to determine uniquely the pattern of hydrogen exchange rates within the protein. The exchange behaviour of the individual amides could, however, in general be rationalized by a combination of these features. Hydrogen exchange was also monitored in both tetragonal and triclinic crystals of lysozyme, by allowing exchange to take place in the crystals prior to dissolution and recording of n.m.r. spectra under conditions where further exchange was minimized. This enabled direct comparison to be made of the exchange behaviour in the crystals and solution. A reduction in exchange rate was observed in the crystalline state relative to solution for a substantial number of amides and distinct differences between exchange in the different crystals could be observed. These differences between the solution and the different crystal states do not, however, correlate in a simple manner with proximity to intermolecular contacts in the crystals. However, the existence of these contacts, which are on the surface of the protein molecule, have a profound effect on the exchange of amides in the interior of the protein. The results indicate that the spectrum of fluctuations giving rise to hydrogen exchange may be significantly altered by the intermolecular interactions present within the crystalline state.

Amides↗
PubMed1991

[Acquired severe aplastic anemia. Therapeutic effect and prognosis after allogeneic bone marrow transplantation].

During 1980-1988 bone marrow transplantation was performed in 14 patients with acquired severe aplastic anemia. Twelve of these patients had HLA identical and two patients incompatible family donors. Two patients died before marrow engraftment. Twelve patients engrafted 12-30 days after marrow transplantation with continued normal marrow function. The actuarial probability for long term survival was found to be 67% after HLA identical allogeneic sibling marrow transplantation. The longest time of observation was 9 years and the patient is still alive. All deaths occurred during the first six months posttransplant. It is concluded that the serious prognosis for patients with SAA has improved if the patients have the possibility for allogeneic HLA identical family donor transplantation.

Adolescent↗
PubMed1991

Double-blind randomized cross-over trial comparing methylprednisolone with placebo in chemotherapy-induced nausea and vomiting: a study with special reference to efficacy parameters.

Sixty-one patients with breast cancer who received chemotherapy participated in a double-blind randomized cross-over study with methylprednisolone (MP) 250 mg as a single i.v. injection before chemotherapy and placebo as antiemetic treatment. The determining efficacy parameter was preference. Other parameters used were a visual analogue scale for nausea, a categorical four-point nausea intensity scale recorded by a nurse observer, emetic amounts, emetic episodes, acceptance of nausea and vomiting, and global assessments for nausea and vomiting. MP showed a significant antiemetic effect compared with placebo which was most pronounced for moderately emetogenic chemotherapy. The visual analogue scale, emetic amounts, acceptance and global assessments were easy to handle and showed coherence with preference, whereas nausea intensity and emetic episodes were resource demanding to record and showed no coherence with preference. It is concluded that for a precise evaluation of nausea and vomiting the visual analogue scale and emetic amounts are most reliable; for ambulatory patients global assessments seem to be sufficient.

Adult↗
PubMed1991

Hormonal, metabolic, and cardiovascular responses to static exercise in humans: influence of epidural anesthesia.

To determine the role of reflex neural mechanisms for hormonal, metabolic, heart rate (HR), and blood pressure (MABP) changes during static exercise, seven health young males performed 10-min periods of two-legged static knee extension both during control and during epidural anesthesia. Comparisons were made at identical absolute (29 Nm) and relative [15% maximal voluntary contraction (MVC)] force. Afferent nerve blockade was verified by hypesthesia below T10-T12 and attenuated postexercise ischemic pressor response. Leg strength was reduced to 67 +/- 5% of control. At same relative force, increases in MABP and HR occurred more rapidly without than with epidural anesthesia (P less than 0.05). This difference was diminished during identical absolute force. Changes in plasma concentrations of catecholamines followed the pattern of HR and MABP responses, with differences between epidural and control experiments being most pronounced early in the work period. Plasma beta-endorphin was elevated only after control exercise. No response at 15% MVC was found for growth hormone, adrenocorticotropic hormone, insulin, glucagon, cortisol, glycerol, free fatty acids, or glucose (P greater than 0.05). In conclusion, during static exercise with large muscle groups and moderate relative force, modest changes in plasma hormones and metabolites take place. Furthermore, afferent nervous feedback from contracting muscles is important in regulation of blood pressure, heart rate, and catecholamine responses during static exercise in humans.

Adult↗
PubMed1991

Evidence that the effect of physical exercise on NK cell activity is mediated by epinephrine.

The present study was designed to test the hypothesis that the changes in natural killer (NK) cell activity in response to physical exercise were mediated by increased epinephrine concentrations. Eight healthy volunteers 1) exercised on a bicycle ergometer (60 min, 75% of maximal O2 uptake) and 2) on a later day were given epinephrine as an intravenous infusion to obtain plasma epinephrine concentrations comparable with those seen during exercise. Blood samples were collected in the basal state, during the last minutes of exercise or epinephrine infusion, and 2 h later. The NK cell activity (lysis/fixed number of mononuclear cells) increased during exercise and epinephrine infusion and dropped below basal levels 2 h afterward. The increased NK cell activity during exercise and the epinephrine infusion resulted from an increased concentration of NK (CD16+) cells in the peripheral blood. On the other hand, the decreased NK cell activity demonstrated 2 h after exercise and epinephrine infusion did not simply reflect preferential removal of NK cells from the blood, because the proportion of CD16+ cells was normalized. On the basis of the finding that indomethacin abolished the suppressed NK cell activity in vitro and the demonstration of a twofold increase in the proportion of monocytes (CD14+ cells) 2 h after exercise and epinephrine infusion, we suggest that, after stress, prostaglandins released by monocytes are responsible for downregulation of NK cell function. Our findings support the hypothesis that increased plasma epinephrine during physical stress causes a redistribution of mononuclear subpopulations that results in altered function of NK cells.

Adult↗
PubMed1991

Influence of active muscle mass on glucose homeostasis during exercise in humans.

To study the effect of increasing amounts of exercising muscle mass on the relationship between glucose mobilization and peripheral glucose uptake, seven young men (23-28 yr) bicycled for 70 min at a work load of 55-60% VO2max. From minute 30 to 50, arm cranking was added and total work load increased to 82 +/- 4% VO2max. During leg exercise, hepatic glucose production (Ra) increased in parallel with peripheral glucose uptake (Rd) and euglycemia was maintained. During arm + leg exercise, Ra increased more than Rd and accordingly plasma glucose increased from 5.11 +/- 0.22 to 8.00 +/- 0.66 mmol/l (P less than 0.05). Plasma catecholamines increased three- to four-fold more during arm + leg exercise than during leg exercise. Leg glucose uptake increased with time regardless of arm cranking. Net leg lactate release during leg exercise was reverted to a net leg lactate uptake during arm + leg exercise. The rate of glycogen breakdown in exercising leg muscle was not altered by addition of arm cranking. In conclusion, when large amounts of muscle mass are active, plasma catecholamines increase sharply and mobilization of glucose exceeds peripheral glucose uptake. This indicates that mechanisms other than feedback regulation to maintain euglycemia are involved in hormonal and substrate mobilization during intense exercise in humans.

Adult↗