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Biomedical subjects

M Kjaer

Publications and source records attributed to M Kjaer.

At least 181 records · Page 10Linked to original sources
PubMed1990

Evaluation of radiotherapy in high-risk breast cancer patients: report from the Danish Breast Cancer Cooperative Group (DBCG 82) Trial.

The role of postmastectomy irradiation together with systemic treatment was evaluated in high-risk patients included in the Danish Breast Cancer Cooperative Group (DBCG) protocol 82. As of June 1989, a total of 1473 pre- and menopausal patients were randomized to postmastectomy irradiation + CMF versus CMF alone (protocol 82-b). A total of 1202 postmenopausal patients were randomized to postmastectomy irradiation + Tamoxifen versus Tamoxifen alone (protocol 82-c). At 5 years the actuarial loco-regional recurrence rate was significantly lower in the irradiated patients (82-b: 9% vs 28%, 82-c: 6% vs 36%). Further, disease-free survival was significantly improved in both pre- and postmenopausal irradiated patients compared with those who had only systemic treatment (82-b: 54% vs 47%, 82-c: 52% vs 38%). At present, overall survival is significantly different in 82-b patients (68% vs 63%) but not in post-menopausal 82-c patients (62% vs 61%). Thus, adjuvant systemic treatment alone (chemotherapy or tamoxifen) did not prevent loco-regional recurrences in high-risk patients after mastectomy and axillary lymph node sampling. However, a longer observation time is necessary to evaluate the consequence of primary optimal loco-regional tumor control in high-risk breast cancer patients with respect to overall survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Cardiovascular and ventilatory responses to dynamic exercise during epidural anaesthesia in man.

1. In order to evaluate the importance of afferent neural feedback from the working muscles for cardiovascular and ventilatory responses to dynamic exercise, epidural anaesthesia was induced at L3-L4. Six healthy males cycled for 20 min at 57% of maximum oxygen uptake and for 8-12 min at increasing work intensities until exhaustion at 238 +/- 30 W without as well as with epidural anaesthesia. 2. Presence of afferent neural blockade was verified by cutaneous sensory analgesia below T10-T11 and attenuated post-exercise ischaemic pressor response (45 +/- 8-24 +/- 6 mmHg). Efferent sympathetic nerves appear to be intact since basal heart rate and blood pressure as well as the cardiovascular responses to a Valsalva manoeuvre and to a cold pressor test were unchanged. 3. During dynamic exercise with epidural anaesthesia, blood pressure was lower than in control experiments; however, ventilation and heart rate were not affected. 4. The results indicate that afferent neural activity from the working muscles is important for blood pressure regulation during dynamic exercise in man but may not be necessary for eliciting the ventilatory and heart rate responses.

Adult↗
PubMed1990

Diminished epinephrine response to hypoglycemia despite enlarged adrenal medulla in trained rats.

Studies in humans have indicated that trained athletes compared with sedentary subjects have an increased capacity to secrete epinephrine. To investigate whether this is due to an adaptation induced by physical training or a selection phenomenon, rats were swim trained (T) 10 wk for 6 h/day or served as controls being either sedentary freely eating (C), food restricted (FR), sham swim trained (ST), or cold stressed (CS). Adrenal glands were weighted and cross sectioned for light microscopic determination of size of the adrenal medulla. Endurance-trained compared with control rats had heavier adrenal glands (P less than 0.05), higher catecholamine content in the glands (P less than 0.05), and higher adrenal medulla volumes (P less than 0.05) [males: 2.74 +/- 0.16 (T) vs. 2.05 +/- 0.16 (C), 1.90 +/- 0.10 (ST), and 2.21 +/- 0.08 mm3 (CS)] [females: 2.55 +/- 0.11 (T) vs. 1.92 +/- 0.06 mm3 (C)]. Cold stress or sham swim training did not increase adrenal weight or volume of adrenal medulla (P greater than 0.05). To stimulate adrenal medulla secretion, rats had an insulin-induced hypoglycemia. Insulin dose needed to suppress plasma glucose below 4.0 mM was four times greater in sedentary compared with trained rats. During hypoglycemia the epinephrine response was much smaller in trained than in untrained rats (P less than 0.05). In conclusion, in rats strenuous endurance training causes an enlargement of the adrenal medulla. However, possibly reflecting an adaptation within the central nervous system to reduced blood glucose levels induced by repeated exercise bouts, the epinephrine response to insulin-induced hypoglycemia is markedly diminished after training.

Adrenal Medulla↗
PubMed1990

Glucoregulation and hormonal responses to maximal exercise in non-insulin-dependent diabetes.

Maximal dynamic exercise results in a postexercise hyperglycemia in healthy young subjects. We investigated the influence of maximal exercise on glucoregulation in non-insulin-dependent diabetic subjects (NIDDM). Seven NIDDM and seven healthy control males bicycled 7 min at 60% of their maximal O2 consumption (VO2max), 3 min at 100% VO2max, and 2 min at 110% VO2max. In both groups, glucose production (Ra) increased more with exercise than did glucose uptake (Rd) and, accordingly, plasma glucose increased. However, in NIDDM subjects the increase in Ra was hastened and Rd inhibited compared with controls, so the increase in glucose occurred earlier and was greater [147 +/- 21 to 169 +/- 19 (30 min postexercise) vs. 90 +/- 4 to 100 +/- 5 (SE) mg/dl (10 min postexercise), P less than 0.05]. Glucose levels remained elevated for greater than 60 min postexercise in both groups. Glucose clearance increased during exercise but decreased postexercise to or below (NIDDM, P less than 0.05) basal levels, despite increased insulin levels (P less than 0.05). Plasma epinephrine and glucagon responses to exercise were higher in NIDDM than in control subjects (P less than 0.05). By use of the insulin clamp technique at 40 microU.m-2.min-1 of insulin with plasma glucose maintained at basal levels, glucose disposal in NIDDM subjects, but not in controls, was enhanced 24 h after exercise. It is concluded that, because of exaggerated counter-regulatory hormonal responses, maximal dynamic exercise results in a 60-min period of postexercise hyperglycemia and hyperinsulinemia in NIDDM. However, this event is followed by a period of increased insulin effect on Rd that is present 24 h after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1990

Current status of epirubicin (Farmorubicin) in the treatment of solid tumours.

Epirubicin (Farmorubicin) is a drug of significant interest in the treatment of a variety of solid tumours and a comprehensive review of reported investigations is given. From experimental and clinical studies it appears that in general doxorubicin and epirubicin exhibit no qualitative, but only some quantitative, differences. Thus, the pharmacokinetic and pharmacodynamic characteristics of the two drugs are essentially similar, as are the tumour spectrum and the level of their clinical efficacies. To achieve haematological equitoxicity of the two drugs the dose of epirubicin should be approximately 20% higher than that of doxorubicin, giving rise to a higher cumulative dose of epirubicin. On the other hand, epirubicin is significantly less cardiotoxic than doxorubicin. Thus, the recommended cumulative dose of doxorubicin is 500 mg/m2 and the corresponding figure for epirubicin is 1,000 mg/m2. For either drug a number of questions are still left open, the most important of which include the questions about optimal treatment schedules and the existence of a clinical relevant dose/efficacy relationship.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Drug treatment of nausea and vomiting caused by cancer chemotherapy].

Only two classes of antiemetics have documented effect and acceptable side effects on nausea and vomiting induced by cancer chemotherapy: Phenothiazines in non-cisplatinum containing chemotherapy and the dopamine antagonist metoclopramide in cisplatinum treatment. Steroids have no effect as single drugs with cisplatinum and their effect with other types of chemotherapy has not been clarified in detail. The combination of metoclopramide and steroids has documented superiority compared with single drug treatment in cisplatinum containing chemotherapy. The newly developed and still experimental serotonin antagonists have initially shown very promising results but further studies are required to define their role in the antiemetic treatment with cancer chemotherapy. Treatment of chemotherapy induced nausea and vomiting has improved considerably in the last few years but, generally, the results are still unsatisfactory. There is an urgent need for new drugs and combinations in the amelioration of these troublesome side effects of cancer chemotherapy.

Antiemetics↗
PubMed1989

Hormonal and metabolic responses to exercise in humans: effect of sensory nervous blockade.

Previous studies have indicated that motor center ("feedforward") activity is important for hormonal and metabolic responses to exercise. Now, epidural blockade at vertebrae L3-L4 was used to evaluate the importance of afferent neural feedback from working muscles. Six healthy, young males cycled for 20 min at 55 +/- 4% (mean +/- SE) of maximal oxygen uptake with, as well as without, epidural anesthesia. During anesthesia cutaneous sensory blockade was present below segment T11-12, the postexercise ischemic pressor response was attenuated from 34 +/- 9 to 14 +/- 4 mmHg, muscle strength reduced to 80 +/- 5% of control, and perceived exertion (Borg scale) was increased. At rest hormonal and metabolic parameters did not change in response to epidural anesthesia. During exercise, responses of catecholamines, insulin, glucagon, and growth hormone (GH) in plasma as well as glucose production and utilization, plasma free fatty acids, and plasma glycerol were similar in epidural and control experiments (P greater than 0.05). In contrast during submaximal exercise, plasma concentrations of adrenocorticotropin (ACTH) and beta-endorphin increased only in experiments without epidural anesthesia. The data indicate that impulses in afferent nerves from the working muscles are essential for the ACTH and beta-endorphin responses to submaximal dynamic exercise in humans. Afferent nervous activity is probably less important than efferent activity from motor centers for responses of GH, catecholamines and insulin, and, in turn, extramuscular fuel mobilization in exercise.

Adrenocorticotropic Hormone↗
PubMed1989

Misteltoe (Iscador) therapy in stage IV renal adenocarcinoma. A phase II study in patients with measurable lung metastases.

The public interest in alternative cancer therapy is considerable. Since the 1920s advocators of anthroposophical medicine have postulated a highly significant effect of misteltoe plant extracts on life quality and survival of patients with most solid tumours. Fourteen patients, 8 men and 6 women, median age 65, range 47-74 years, with earlier untreated histologically verified renal adenocarcinoma stage IV and clearly measurable lung metastases were treated with subcutaneous injections of Iscador every second day in escalating doses over 3 weeks followed by maintenance therapy, 20, 30, and 50 mg/ml on respective days. Patients were evaluated monthly and disease status classified according to WHO criteria. No response was demonstrated. 2/14 patients died without change of the disease (NC) after 30 and 60 days respectively. The median time to progressive disease (PD) was 108 days, range 33-348 days. First site of PD was lungs in 10/12, outside lungs in 2/12 patients. All patients have died. The median survival was 330 days, range 44-694, which in a retrospective comparison was quite similar to earlier phase 2 studies in the same type of patients. Apart from local reactions around the injection sites and moderate fever on the day of injection the treatment was well tolerated with no major toxicities. It is concluded that Iscador under the conditions chosen for the study had no objective or life prolonging effects postulated for most solid tumour types by advocators of anthrosophy.

Adenocarcinoma↗
PubMed1988

High-dose ketoconazole to untreated stage D prostate cancer.

Eleven previously untreated patients with stage D prostate cancer were treated with ketoconazole in a dosage of 400 mg p.o. every 8 h. s-Testosterone was used as a measure of antiandrogen effect. Nine patients had a reduction in s-testosterone to castrate levels (less than 2.9 nmol/l) within 3 days. In the remaining two patients, dose escalation of ketoconazole to 400 mg every 6 h did not lead to sufficient reduction in s-testosterone. Two patients had a complete response and four patients had a partial response of 6/11. Additionally, two patients had bone pain relief without normalization of acid phosphatase. Side-effects and adverse reactions were prominent, causing discontinuation of the treatment in nine patients. It is concluded that high-dose ketoconazole is effective in disseminated prostate cancer, but the high frequency of side-effects makes it less attractive than conventional hormone manipulations like castration or estrogens.

Acid Phosphatase↗
PubMed1988

Arterial blood pressure at the onset of dynamic exercise in partially curarized man.

In six young men, heart rate and arterial mean blood pressure responses to the onset of light dynamic exercise 99 W (range 59-138) on a stationary bicycle were followed during partial neuromuscular blockade with tubocurarine. Tubocurarine was used in order to accentuate the central nervous (central command) influence on the cardiovascular variables and reduced hand-grip strength to 42% (36-47) of control. At the onset of exercise heart rate increased immediately and similarly with and without neuromuscular blockade. Mean arterial blood pressure remained constant during the first 6 s of control exercise and then increased. With tubocurarine a decrease of 9 mmHg (3-12) was seen during the first 6 s (P less than 0.01) before blood pressure increased. The similar heart rate responses seen with and without neuromuscular blockade indicate that central command has little influence on this variable at the onset of dynamic exercise. The constant blood pressure at the onset of control exercise suggests that the immediate changes in cardiac output and peripheral vascular resistance, respectively, are accurately matched. The decrease in blood pressure at the onset of exercise with tubocurarine suggests that central command stimulates vasodilatating nerves to arterioles in the working muscles.

Adult↗
PubMed1988

Hormonal response to exercise in humans: influence of hypoxia and physical training.

Hypoxia and physical training alter the responses of glucoregulatory hormones to absolute work loads in opposite directions. These effects have tentatively been ascribed to changes in maximal O2 consumption (VO2 max) and ensuing changes in relative work loads. However, hypoxia as well as training may more specifically influence the hormonal response. We therefore differentiated the influence of hypoxia, training, and VO2 max, respectively, on the hormonal response to bicycle exercise. Responses to hypoxia in a low-pressure chamber (PB = 465 vs. 730 Torr) were studied at given absolute and relative (85% VO2 max) work loads in seven endurance-trained athletes (T) and 7 age and weight-matched sedentary subjects (C). Concentrations in plasma of norepinephrine, growth hormone, adrenocorticotropic hormone, and cortisol were always closely related to the relative work load. However, the epinephrine response in T, but not in C, was at the same relative work load higher during hypoxia (5.84 +/- 0.83 nmol/l) than during normoxia (4.26 +/- 0.44, P less than 0.05). These results indicate that the hormonal response is influenced by hypoxia and physical training, mainly via changes in the relative work load. However, in trained subjects both at rest and during exercise, an enhancing effect of hypoxia per se on the epinephrine response is seen, probably due to an increased adrenal medullary secretory responsiveness in long-term endurance-trained subjects.

Adrenocorticotropic Hormone↗
PubMed1988

Effect of physical training on the capacity to secrete epinephrine.

Epinephrine responses to hypoglycemia and to identical relative work loads have been shown to be higher in endurance-trained athletes than in untrained subjects. To test the hypothesis that training increases the adrenal medullary secretory capacity, we studied the effects of glucagon (1 mg/70 kg iv), acute hypercapnia (inspired O2 fraction = 7%), and acute hypobaric hypoxia (inspired Po2 = 87 Torr), respectively, on the epinephrine concentration in arterialized hand vein blood in eight endurance-trained athletes [T, O2 uptake = 66 (62-70) ml.min-1.kg-1] and seven sedentary males [C, O2 uptake = 46 (41-50)]. In response to identical increments in glucagon concentrations, plasma epinephrine increased more in T than in C subjects [0.87 +/- 0.11 vs. 0.38 +/- 0.14 (SE) nmol/l, P less than 0.05]. In response to hypercapnia [arterial PCO2 = 56 +/- 0.7 Torr (T) and 55 +/- 0.4 (C), P greater than 0.05], the increment in epinephrine was significant in T (0.38 +/- 0.11 nmol/l) but not (P less than 0.1) in C subjects (0.22 +/- 0.11). Hypoxia [arterial PO2 = 42 +/- 2 Torr (T) and 41 +/- 2 (C), P greater than 0.05] increased epinephrine in T (0.22 +/- 0.10 nmol/l, P less than 0.05) but not in C subjects (0.01 +/- 0.07). The plasma norepinephrine concentration never changed, whereas heart rate always increased, the increase being higher (P less than 0.05) in T than in C subjects only during hypercapnia. The results indicate that training increases the capacity to secrete epinephrine.

Adrenal Medulla↗
PubMed1988

Analgesic effect and bioavailability of oral ketogan given as tablets or mixture to patients with chronic pain of malignant origin.

Thirteen cancer patients with moderate to severe chronic pain of malignant origin on treatment with Ketogan tablets were included in an open non-randomized cross-over study comparing the analgesic effect, side effects and serum concentrations of Ketogan tablets and mixture. The patients were six days in hospital and were dosed two days with tablets, two days with mixture and finally another two days with tablets. Recordings of pain and side effects and collection of blood samples prior to dosing and hourly thereafter until remedication were performed on the second day of each dosing period in a morning dose interval. The analgesic effect judged by visual analog score (VAS) and pain intensity differences (PID), the areas under the serum concentration time curves, and the average serum concentrations for the three groups were compared. It was not possible do detect any differences among the three groups concerning the analgesic effect, duration of analgesic effect, the serum concentrations and the side effects. The mean plasma half-life of ketobemidone was 2.74 h +/- 0.90 (SD) and the mean relative bioavailability of the mixture was slightly above 100%. Linear regression analysis revealed a significant correlation between ketobemidone serum concentrations and analgesic effect, VAS, for tablet one and for the mixture but not for tablet two, possibly due to the fixed dosing schedule and to the positive effect of hospitalization on the pain.

Administration, Oral↗
PubMed1987

The treatment and prognosis of patients with renal adenocarcinoma with solitary metastasis. 10 year survival results.

From 1969-1976, 25 patients with renal adenocarcinoma and solitary metastasis were treated and are now eligible for 10-14-year survival analysis. There were 17 men and 8 women, mean age 60 years, range 37-75 years. Twelve patients had focus in bone and 13 patients in other localizations: lungs 6, thyroid 3, flank 3, and epididymis 1. Sixteen out of twenty-five patients were treated with the radiotherapy 45-50 Gy in 23-25 fractions as the only treatment. The median survival was 4.3 years, the 5-year survival 36%, and the 10-year survival 16%. Women had 5- and 10-year survival rates of 76% and 38% respectively. Men had 5-year survival of 18% and 10-year survival of 12% (p = 0.05). There were no significant differences between the survival of patients with bone metastases and patients with soft tissue metastases. Three patients are living NED at 14 years. Seventeen of twenty-two patients died of progressive renal adenocarcinoma whereas 5/22 died from other causes. We conclude: It is possible to obtain long term survival greater than 10 years and maybe even cure in a fraction of these patients by aggressive treatment. Radiotherapy is a highly potential treatment modality giving the same or better results as those reported in the literature after extensive and disabling surgical resections. However, it cannot be excluded that the favorable prognosis for these patients merely reflects the natural clinical course of the disease in this specific subgroup.

Adenocarcinoma↗