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Biomedical subjects

M Kjaer

Publications and source records attributed to M Kjaer.

At least 145 records · Page 8Linked to original sources

Acute effects of caffeine ingestion at rest in humans with impaired epinephrine responses.

Caffeine ingestion has been demonstrated to increase circulating epinephrine (Epi) and norepinephrine (NE), elevate free fatty acids (FFAs), and alter heart rate, blood pressure (BP), and ventilation in humans. Whether these physiological responses are a result of caffeine acting through direct stimulation of specific tissues via adenosine receptors or secondary to Epi increases is not known. In the present experiment, six tetraplegics (level of spinal cord lesions C4-C6) were tested at rest for 3 h to investigate the effects of 6 mg/kg caffeine in capsule form on subjects with impaired Epi responses. Ventilatory, cardiovascular, metabolic, and hormonal data were collected every 15-20 min after caffeine ingestion. There were no significant (P > 0.05) increases in plasma Epi after caffeine ingestion [0.19 +/- 0.04 (SE) nM (preingestion); 0.20 +/- 0.04 nM (80 min postingestion)] or in plasma NE [0.53 +/- 0.16 nM (preingestion); 0.49 +/- 0.09 nM (80 min postingestion; P > 0.05)]. However, significant increases were found in serum FFAs [0.53 +/- 0.08 nM (preingestion); 1.03 +/- 0.20 mM (40 min postingestion; P < 0.05] and in glycerol. These concentrations remained elevated throughout the experiment. BP increased in the first hour postingestion. These data demonstrate that caffeine in physiological doses directly stimulates specific tissues, i.e., adipose and peripheral vascular tissue, and these effects are not secondary to increases in Epi after caffeine ingestion.

Adult↗

Hormonal and metabolic responses to electrically induced cycling during epidural anesthesia in humans.

Hormonal and metabolic responses to electrically induced dynamic exercise were investigated in eight healthy young men with afferent neural influence from the legs blocked by epidural anesthesia (25 ml of 2% lidocaine) at L3-L4. This caused cutaneous sensory anesthesia below T8-T9 and complete paralysis of the legs. Cycling increased oxygen uptake to 1.90 +/- 0.13 (SE) l/min, and fatigue developed after 22.7 +/- 2.7 min. Compared with voluntary exercise at the same oxygen uptake and heart rate, concentrations of blood and muscle lactate (musculus vastus lateralis) as well as plasma potassium increased more while muscle glycogen decreased more during electrically induced exercise. Hepatic glucose production always rose during exercise. However, during involuntary exercise with sensory blockade, it did not match the rise in peripheral glucose uptake and plasma glucose decreased (P < 0.05). Plasma glycerol increased less in electrically induced vs. voluntary exercise, and free fatty acids and beta-hydroxybutyrate decreased only during electrically induced exercise. Epinephrine, growth hormone, adrenocorticotropic hormone, and cortisol levels were higher during involuntary vs. voluntary exercise (P < 0.05). In conclusion, neural and humoral mechanisms exert redundant control with regard to responses of catecholamines and pituitary hormones (growth hormone and adrenocorticotropic hormone). In contrast, neural input from motor centers and feedback from working muscle are important for glucose production and lipolysis during exercise in humans. Humoral feedback is apparently not sufficient to trigger normal mobilization of extramuscular fuel stores.

Adult↗

Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: a randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group.

PURPOSE: To test for possible correlations between dose of single-drug epirubicin and efficacy/toxicity in postmenopausal women with metastatic breast cancer. The study also included analysis of a correlation between pharmacokinetic and pharmacodynamic parameters. PATIENTS AND METHODS: Two hundred eighty-seven women were randomized to receive either 40, 60, 90, or 135 mg/m2 of epirubicin intravenously (IV) every 3 weeks. Treatment consisted of first-line cytotoxic therapy for metastatic disease. In patients with early progressive disease after either 40 or 60 mg/m2, dose escalation to 135 mg/m2 was performed. A full pharmacokinetic analysis was performed in 78 patients. RESULTS: Among 263 eligible patients, an increase in response rate and time to progression was found with an increase in dose from 40 to 90 mg/m2, while no increase in efficacy was found from 90 to 135 mg/m2. Multivariate analysis, using the Cox proportional hazards model with time to progression as the end point, confirmed that epirubicin dose more than 60 mg/m2 was an independent prognostic covariate. Furthermore, a significant association was established between randomized dose and both hematologic and nonhematologic toxicity. No association between pharmacokinetic parameters and efficacy parameters was demonstrated. On the other hand, a significant correlation between pharmacokinetic parameters and both hematologic and nonhematologic toxicity was found. CONCLUSION: An increase in dose of epirubicin from 40 to 90 mg/m2 is accompanied by increased efficacy. Further increases in dose do not yield increased efficacy. A positive correlation between epirubicin dose and toxicity, as well as a correlation between pharmacokinetic parameters and toxicity, was also established.

Adult↗

Associated autoimmune diseases in myasthenia gravis. A population-based study.

During a comprehensive epidemiological study of myasthenia gravis (MG) in Western Denmark 1975-1989, we analyzed the occurrence, clinical characteristics and prognosis of associated autoimmune diseases (AAD) in MG patients. AAD were found in 20 of 212 incident cases (9%) and in 30 of 220 prevalent cases (14%). The most common diseases were: thyroid disorders and rheumatic arthritis. Clinically, it was not possible to identify a subgroup of MG patients with a higher risk of AAD. In most MG patients the AAD occurred before thymectomy. The severity of the AAD was not influenced by thymectomy. The remission rate was lower in MG patients with AAD than in MG patients without AAD suggesting that the autoimmune response in MG patients with AAD is more severe.

Arthritis, Rheumatoid↗

Viscoelastic response to repeated static stretching in the human hamstring muscle.

The purpose of this study was (1) to evaluate the reproducibility of a new method of measuring passive resistance to stretch in the human hamstring muscle group, in vivo, using a test re-test protocol and 2) to examine the effect of repeated stretches. Passive resistance offered by the hamstring muscle group during knee extension was measured in 10 subjects as knee flexion moment (Nm) using a KinCom dynamometer. The knee was passively extended at 5 deg/s to the final position where it remained stationary for 90 s (static phase). EMG of the hamstring muscle was also measured. The test re-test protocol included 2 tests (tests 1 and 2) administered 1 h apart. On a separate occasion 5 consecutive static stretches were administered (stretches 1-5) separted by 30 s. Stretch 6 was administered one hour after stretch 5. In the static phase passive resistance did not differ between test 1 and test 2. Resistance declined in both tests 1 and 2, whereas EMG activity remained unchanged. The decline in resistance was significant up to 45 s. For the repeated stretches there was an effect of time (90 s) and stretch (1-5) with a significant interaction i.e., resistance diminished with stretches, and the 90-s decline was less as more stretches were performed. Passive resistance in stretch 6 was lower than in stretch 1. The present study has demonstrated a reliable method for studying resistance to stretch of the human hamstring muscle group. A viscoelastic response of the human hamstring muscle was shown. With 5 repeated stretches, resistance to stretch diminished and each stretch exibited a viscoelastic response, albeit less with each subsequent stretch. The effect of 5 repeated stretches was significant 1 h later.

Adult↗

Contraction specific changes in passive torque in human skeletal muscle.

The present investigation examined passive torque and electromyographic response in human skeletal muscle during passive static stretch within 60 s after maximal repetitive eccentric and concentric contractions. Passive torque (Nm) offered by the hamstring muscle group was measured during passive knee extension in a modified dynamometer in 10 subjects. The distal thigh was elevated to 0.52 rad from horizontal and the backrest was positioned at 1.57 rad. The lever arm moved the leg passively at 0.09 rad s-1 from a starting position of 1.48 rad below horizontal to the final position where it remained stationary for 90 s. Gross electrical activity of the human hamstring muscle group was recorded simultaneously. The effect of concentric or eccentric contraction was tested on separate days. Two stretch manoeuvres with a 45 min hiatus were administered on a control and experimental side. The experimental side performed 40 maximal effort repetitive concentric or eccentric hamstring muscle contractions at 1.05 rad s-1 prior to the second stretch. Passive torque during the 90 s stretch declined 30-35% on the experimental and control side in all stretches, P < 0.001, without a significant effect of prior contraction mode. Passive peak and final torques were lower on the experimental side, P < 0.01 after concentric contractions. Passive peak and final torques remained unchanged after eccentric contractions on the experimental side. The low level EMG response of the hamstring muscle during the stretch was unchanged after maximal repetitive concentric or eccentric contractions. These data demonstrate acute contraction specific alteration in passive torque in human skeletal muscle, which cannot be accounted for by EMG activity. Furthermore, the lack of difference on the control side implies that one 90 s stretch has no effect on passive torque of the muscle 45 min later.

Adult↗

Glucose homeostasis during exercise in humans with a liver or kidney transplant.

To investigate the role of liver nerve activity on hepatic glucose production during exercise, liver-transplant subjects (LTX, n = 7, 25-62 yr, 4-18 mo postoperative) cycled for 40 min, 20 min at 52 +/- 3% (SE) maximal O2 consumption (VO2max) and 20 min at 83 +/- 1% VO2max, respectively. Kidney-transplant (KTX) and healthy control subjects (C) matched for sex and age exercised at the same %VO2max as LTX. VO2max was lower in both LTX (1.59 +/- 0.12 l/min) and KTX (1.59 +/- 0.07) than in C (2.60 +/- 0.26). At rest plasma renin and insulin were higher and plasma adrenocorticotropic hormone and cortisol lower in transplant corticosteroid-treated subjects compared with C. In LTX, hepatic glucose production (Ra) increased from 11.9 +/- 0.9 (rest) to 17.6 +/- 1.8 and 25.5 +/- 1.8 mumol.min-1.kg-1 at 52 and 82% VO2max, respectively. Peripheral glucose uptake was similar to Ra, and glucose remained at basal postabsorptive levels. During exercise the Ra increase as well as norepinephrine, insulin, and growth hormone responses were similar in LTX compared with both KTX and C. The increase in epinephrine was smaller in LTX than in C, the only group showing an increase in cortisol. The increase in plasma renin activity during exercise was attenuated in KTX compared with LTX and C. During exercise blood lactate rose more and plasma glycerol and free fatty acid levels were lower in LTX and KTX compared with C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Natural killer cell response to exercise in humans: effect of hypoxia and epidural anesthesia.

For the response of immunologically competent blood cells to exercise, the importance of afferent nerve impulses was evaluated. On separate days, seven males cycled in a recumbent position approximately 60% of maximal O2 uptake with and without sensory nerve blockade by lumbar epidural anesthesia. Blood samples were collected after 60 min of rest, 20 min of exercise, and 120 min postexercise. Subsequently, on each day, the subjects were exposed to 11.5% O2-88.5% N2 for 10 min. This was followed by 20 min of hypoxic exercise at the same work rate, and a final blood sample was obtained. The concentrations of lymphocytes expressing the cluster designation (CD) cell-surface antigens CD3, CD4, CD8, and CD14 became elevated during exercise, and these responses were enhanced by hypoxia (P < or = 0.01). The most pronounced changes were within the concentrations of CD16+ and CD56+ natural killer cells, which increased twofold during normoxic and fivefold during hypoxic exercise (P < or = 0.01). Sensory nerve blockade decreased the number of CD3+ and CD4+ cells and increased the percentage of CD16+ cells, independent of exercise and hypoxia (P < or = 0.05). Sensory nerve blockade caused minor enhancement in the increase of unstimulated natural killer cell activity during exercise (P = 0.07) and enhanced the interferon-alpha-stimulated activity at normoxia (P < or = 0.05), whereas no effect was detected at hypoxia. The results demonstrate that the responses of immunological competent cells to normoxic and hypoxic exercise are not abolished by blockade of nerve impulses from active muscle.

Adult↗

Tropisetron (Navoban) in the prevention of chemotherapy-induced nausea and vomiting--the Nordic experience.

An open, noncomparative, Nordic multicenter study was carried out during 1991-1992 to evaluate the 5-HT3 receptor antagonist tropisetron (Navoban) as an antiemetic agent for various types of cancer chemotherapy. A total of 630 patients were recruited from 15 centers in Sweden, Denmark, and Finland. Gynecological cancers (60%), breast cancer (15%), and lung cancer (10%) were the main diagnoses. Prior experience of chemotherapy was documented in 338 patients (54%). In 260 patients (41%), cisplatin was part of the cytostatic regimen. Carboplatin (23%), doxorubicin (27%), and epidoxorubicin (24%) were also frequently included. In all, 23 cytostatic agents were used in various combinations. The mean number of courses studied was 4.6 (range 1-19). Altogether, 394 of 619 evaluable patients (64%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting were completely prevented in 45%-73% (days 2-6) in the complete series. Treatment efficacy remained stable (60%-79%) during ten consecutive courses of chemotherapy. With noncisplatin regimens, complete protection from acute nausea and vomiting was achieved in 72% compared with 52% for cisplatin regimens (P < 0.0001). Patients without prior experience of chemotherapy had higher control rates of acute nausea and vomiting (72%) compared to patients treated before (57%) during the first course, but not later on. There were no differences in delayed nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hypoxia and training-induced adaptation of hormonal responses to exercise in humans.

To establish whether or not hypoxia influences the training-induced adaptation of hormonal responses to exercise, 21 healthy, untrained subjects (2) years, mean (SE)] were studied in three groups before and after 5 weeks' training (cycle ergometer, 45 min.day-1, 5 days.week-1). Group 1 trained at sea level at 70% maximal oxygen uptake (VO2max), group 2 in a hypobaric chamber at a simulated altitude of 2500 m at 70% of altitude VO2max, and group 3 at a simulated altitude of 2500 m at the same absolute work rate as group 1. Arterial blood was sampled before, during and at the end of exhaustive cycling at sea level (85% of pretraining VO2max). VO2max increased by 12 (2)% with no significant difference between groups, whereas endurance improved most in group 1 (P < 0.05). Training-induced changes in response to exercise of noradrenaline, adrenaline, growth hormone, beta-endorphin, glucagon, and insulin were similar in the three groups. Concentrations of erythropoietin and 2,3-diphosphoglycerate at rest did not change over the training period. In conclusion, within 5 weeks of training, no further adaptation of hormonal exercise responses takes place if intensity is increased above 70% VO2max. Furthermore, hypoxia per se does not add to the training-induced hormonal responses to exercise.

Adaptation, Physiological↗

No reinnervation of hepatic sympathetic nerves after liver transplantation in human subjects.

Transplantation of the liver results in surgical denervation of the organ. However, it is not known whether and to what extent sympathetic reinnervation occurs postoperatively in the transplanted human liver. Thirty-two liver biopsies (right lobe) were obtained from 13 liver-transplanted patients 1, 3, 6, 12 or 30 months after transplantation and 11 biopsies were obtained from 11 non-transplanted subjects with normal liver tests. The concentrations of the sympathetic neurotransmitter norepinephrine and of epinephrine were determined in liver tissue homogenates. The concentration of norepinephrine was 0.019 +/- 0.05 nmol. g wet liver tissue-1 (mean and SE, n = 32) in the transplanted patients, which was only 1% of the concentration in biopsies from control subjects (2.180 +/- 0.420 nmol.g wet liver tissue-1). The hepatic norepinephrine concentration did not increase significantly over time in liver-transplanted patients during the observation period (0.015 +/- 0.008 nmol.g wet wt-1 (1 month post) (n = 8) vs. 0.024 +/- 0.018 nmol.g wet wt-1 (12 months post) (n = 6) and 0.012 +/- 0.006 nmol.g wet wt-1 (30 months post) (n = 5)) (p < 0.05). The liver tissue concentration of epinephrine was markedly lower in liver-transplanted subjects (0.01 +/- 0.003 nmol.g wet tissue-1) than in control subjects (0.04 +/- 0.007 nmol.g-1) (p < 0.01). This study indicates that within the first years after transplantation, there is no evidence of sympathetic liver nerve reinnervation in liver-transplanted patients.

Epinephrine↗

Evidence that the effect of bicycle exercise on blood mononuclear cell proliferative responses and subsets is mediated by epinephrine.

The present study was designed to test the hypothesis that the exercise-induced changes in blood mononuclear cell (BMNC) subsets, BMNC proliferative responses and lymphokine activated killer (LAK) cell activity are mediated by increased epinephrine concentrations. Healthy male volunteers 1) exercised on a bicycle ergometer (75% of VO2max, 1 h) and 2) on another 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. During both perturbations the %CD3+ and %CD4+ T cells declined and the %CD16+ NK cells increased. Two h afterwards the CD14+ monocytes increased, while no changes were observed in %CD8+ T cells or %CD20+ B cells. The phytohemagglutinin (PHA) response declined during both epinephrine infusion and exercise experiments. The changes in interleukin-2 (IL-2) effect on proliferation and cytotoxic activity (LAK cell activity) were more pronounced in exercise experiments than during epinephrine. Exercise and epinephrine caused increase in concentrations of lymphocytes and neutrophils, but the changes were more pronounced in exercise experiments. The results indicate that, in response to physical exercise, the rise in plasma epinephrine may contribute to the changes in cellular immunity.

Adult↗

On-demand antiemetic treatment with the serotonine antagonist tropisetron in cisplatin-treated cancer patients.

Fourteen cancer patients treated with cisplatin received repeated infusions of tropisetron on-demand in conjunction with emesis. In subsequent chemotherapy courses, prophylactic tropisetron was given in a dose identical to the cumulated dose in study course 1. Tropisetron in study course 1 abolished emesis after 7.5 min (5 mg). Duration of effect was more than 7 h in 50% of the patients. No relationship between dose and duration of effect was seen. After study course 2, eight of 10 patients preferred prophylactic tropisetron. Two patients with hypertension had a severe increase in blood pressure probably related to tropisetron. It is concluded that tropisetron has an instant and lasting effect on nausea and vomiting when given on-demand. The majority of patients, however, prefer prophylactic treatment. Hypertension may be a side effect from tropisetron and caution should be displayed in hypertensive patients.

Adult↗

Cardiovascular and ventilatory responses to electrically induced cycling with complete epidural anaesthesia in humans.

Cardiovascular and ventilatory responses to electrically induced dynamic exercise were investigated in eight healthy young males with afferent neural influence from the legs blocked by epidural anaesthesia (25 ml 2% lidocaine) at L3-L4. This caused cutaneous sensory anaesthesia below T8-T9 and complete paralysis of the legs. Cycling was performed for 22.7 +/- 2.7 min (mean, SE) (fatigue) and oxygen uptake (VO2) increased to 1.90 +/- 0.13 1 min-1. Compared with voluntary exercise at the same VO2, increases in heart rate (HR) (135 +/- 7 vs. 130 +/- 9 beats min-1) and cardiac output (16.9 +/- 1.1 vs. 17.3 +/- 0.91 min-1) were similar, and ventilation (54 +/- 5 vs. 45 +/- 41 min-1) was higher (P < 0.05). In contrast, the rise in mean arterial blood pressure during voluntary exercise (93 +/- 4 (rest) to 119 +/- 4 mmHg (exercise)) was not manifest during electrically induced exercise with epidural anaesthesia [93 +/- 3 (rest) to 95 +/- 5 mmHg (exercise)]. As there is ample evidence for similar cardiovascular and ventilatory responses to electrically induced and voluntary exercise (Strange et al. 1993), the present results support the fact that the neural input from working muscle is crucial for the normal blood pressure response to exercise. Other haemodynamic and/or humoral mechanisms must operate in a decisive manner in the control of HR, CO and VE during dynamic exercise with large muscle groups.

Adult↗