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Biomedical subjects

K Overgaard

Publications and source records attributed to K Overgaard.

At least 73 records · Page 4Linked to original sources
PubMed1992

Dose-response of rt-PA and its combination with aspirin in a rat embolic stroke model.

The efficacy and safety of thrombolysis with different dose regimens of recombinant tissue plasminogen activator (rt-PA) and its combination with aspirin was tested in an embolic stroke model. In rats the carotid territory was embolized with a single clot formed in a polyethylene tube and washed with saline. Fifteen minutes after embolization 10 animals were treated with rt-PA 10 mg kg-1; 11 with 15 mg kg-1; 12 with 20 mg kg-1 and 9 with 10 mg kg-1 + 20 mg kg-1 aspirin and 34 animals with saline. Rt-PA 10 mg kg-1 reduced median infarct volume (in percent of the ipsilateral hemisphere volume) from 19.5 to 4.8; rt-PA 15 mg kg-1 to 2.0; rt-PA 20 mg kg-1 to 0.0, while rt-PA 10 mg kg-1 + aspirin resulted in a median infarct volume of 9.5%. Thrombolytic therapy significantly and dose dependently (p = 0.001) reduced the infarct volume, improved the presacrifice clinical score and increased (p = 0.02) angiographically verified reperfusion. There was no additional benefit of coadministration of aspirin.

Animals↗
PubMed1992

Reduction of infarct volume and mortality by thrombolysis in a rat embolic stroke model.

BACKGROUND AND PURPOSE: Thrombolytic therapy with recombinant tissue plasminogen activator was tested in a rat embolic stroke model. METHODS: The rat carotid territory was embolized with arterial-like microthrombi formed under pressure. Hemispheric cerebral blood flow before and after embolization was measured by the intraarterial Xenon-133 injection method. Fifteen minutes after embolization, 24 rats were treated with 3 mg/kg or 10 mg/kg tissue plasminogen activator, and 27 were treated with saline. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed and evaluated neuropathologically and infarct volume was measured. RESULTS: Cerebral blood flow was reduced 70-86% after embolization. The comparison of pretreatment and posttreatment angiography showed significant (p = 0.0005) reperfusion in the treated rats. Thrombolytic therapy significantly reduced the infarct volume from 55.1% to 24.4% of embolized hemisphere volume (p = 0.007) and increased the survival rate from 0.48 to 0.96 (p = 0.0004). Fifty-three percent of the embolized rats recanalized completely after thrombolytic treatment and developed almost no infarction (median volume 2.8%), and all survived. No hemorrhagic complications were observed. CONCLUSIONS: Early thrombolytic therapy induced recanalization and reduced mortality and infarct volume after embolic stroke in this model.

Animals↗
PubMed1992

Two new combinations of estrogen and progestogen for prevention of postmenopausal bone loss: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding.

Bone mass, calcium and lipid metabolism, climacteric symptoms, bleeding, blood pressure, and weight changes were studied in 62 healthy postmenopausal women at 3-month intervals throughout 2 years of treatment with continuous estradiol valerate (2 mg) plus cyproterone acetate (1 mg), sequential estradiol valerate (2 mg) plus levonorgestrel (75 micrograms), or placebo. During the 2 years of the study, bone mineral content of the distal and ultradistal regions of the forearm (measured by single-photon absorptiometry) remained unchanged in the hormone groups, whereas bone mineral content at these sites decreased by 5 and 6%, respectively, in the placebo group. Bone mineral density in the spine (measured by dual-photon absorptiometry and dual-energy x-ray absorptiometry) increased by 3-4% in the hormone groups and decreased by 2% in the placebo group. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium/creatinine) decreased significantly to premenopausal levels in the hormone groups, but remained unchanged in the placebo group. Serum concentrations of total and low-density lipoprotein cholesterol were significantly reduced by 5-10% (P less than .05-.01) in the estradiol + cyproterone acetate group and by 10-15% (P less than .001) in the estradiol valerate + levonorgestrel group. There were no significant changes in high-density lipoprotein cholesterol in the hormone groups. Virtually no changes were observed in the placebo group. Climacteric symptoms and hot flushes were significantly reduced in both hormone groups compared with the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density↗
PubMed1991

Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study.

OBJECTIVE: To examine the role of peak bone mass and subsequent postmenopausal bone loss in the development of osteoporosis and the reliability of identifying women at risk from one bone mass measurement and one biochemical assessment of the future bone loss. DESIGN: Population based study. SETTING: Outpatient clinic for research into osteoporosis. SUBJECTS: 178 healthy early postmenopausal women who had participated in a two year study in 1977. 154 of the women underwent follow up examination in 1989, of whom 33 were excluded because of diseases or taking drugs known to affect calcium metabolism. MAIN OUTCOME MEASURES: Bone mineral content of the forearm and values of biochemical markers of bone turnover. RESULTS: The average reduction in bone mineral content during 1977-89 was 20%, but the fast losers had lost 10.0% more than had the slow loser group (mean loss 26.6% in fast losers and 16.6% in slow losers; p less than 0.001). Prediction of future bone mineral content using baseline bone mineral content and estimated rate of loss gave results almost identical with the actual bone mineral content measured in 1989. Seven women had had a Colles' fracture and 20 a spinal compression fracture. The group with Colles' fracture had low baseline bone mineral content (34.7 (95% confidence interval 31.3 to 38.1) units v 39.4 (38.1 to 40.8) units in women with no fracture) whereas the group with spinal fracture had a normal baseline bone mineral content (38.1 (35.0 to 41.1) units) but an increased rate of loss (-2.4 (-3.5 to -1.3)%/year v -1.8 (-2.1 to -1.5)%/year in women with no fracture). CONCLUSIONS: One baseline measurement of bone mass combined with a single estimation of the rate of bone loss can reliably identify the women at menopause who are at highest risk of developing osteoporosis later in life. The rate of loss may have an independent role in likelihood of vertebral fracture.

Age Factors↗
PubMed1991

Potential risk factors for development of postmenopausal osteoporosis--examined over a 12-year period.

In a longitudinal study, we investigated the influence of risk factors on bone mass at menopause and postmenopausal bone loss in 121 healthy postmenopausal women. These women had completed a 2-year prospective study in 1979 and a follow-up examination in 1989. Measurements of the bone mineral content in the distal forearm (single photon absorptiometry) were performed 9 times during the initial study and once at the follow-up examination. Bone mass at menopause (initial measurement), rate of early postmenopausal bone loss, and the subsequent rate of bone loss over 10 years were thus determined. In addition, the bone mineral density of the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry (DXA) in 1989. Information about risk factors was assessed by standardized questionnaires and included reproductive history and lifestyle factors (intake of calcium and vitamin D supplements, consumption of alcohol and caffeine, smoking habits, and physical activity). Lactation, oral contraceptive use, and dietary calcium intake above 1500 mg per day was associated with significantly increased bone mass at menopause. The number of pregnancies reduced the rate of early postmenopausal bone loss, whereas moderate alcohol consumption reduced the subsequent rate of bone loss. Smoking significantly reduced femoral bone mineral density. In conclusion, the present prospective study showed that some of the examined putative risk factors positively influenced bone mass at menopause, especially calcium intake, whereas the postmenopausal bone loss was virtually unaffected. Assessment of risk factors in postmenopausal women thus seems to have limited value for reducing future risk of osteoporosis.

Aged↗
PubMed1991

Long-term treatment of established osteoporosis with intranasal calcitonin.

We examined the long-term effects of intranasal administration of salmon calcitonin on bone and calcium metabolism in women with established osteoporosis (forearm fracture). Over a period of 5 years, 14 women received discontinuous calcitonin (200 IU) plus calcium (500 mg) daily for 3 years or 4 years. To allow assessment of the optimum duration of therapy, patients in whom treatment had been for shorter intervals were also included. At the end of the first 2 years, a group receiving placebo had lost significantly more bone from their spines and forearms than the group receiving calcitonin in the first year (P less than 0.01). In the 14 women who completed a further 3 years on calcitonin, the bone mineral contents of the spines increased continually. Bone loss in the forearm was arrested for 1 year. Treatment lasting for about 2 years prevented bone loss in both areas. Treatment for 3 years resulted in net gains in spinal bone but no further benefits in relation to forearms. Biochemical parameters of bone turnover (serum alkaline phosphatase levels, plasma bone Gla protein levels, and fasting urinary hydroxyproline/creatinine levels) exhibited similar declines irrespective of the duration of treatment. It is concluded that long-term intranasal treatment with calcitonin produced net gains in spinal bone and that optimum response in forearms was achieved using discontinuous therapy. The ratio between periods with and without treatment was between 1:2 and 2:3.

Administration, Intranasal↗
PubMed1991

Evoked potentials in urology: a method to make an exact diagnosis?

Due to the complex innervation of the lower urinary tract, many neurological diseases will lead to disturbances in the function of the lower urinary tract. The usual urodynamic procedures leave a group of patients where definitive diagnosis is impossible. Fifty-three patients were evaluated with evoked potentials of the bulbocavernosus reflex at the Urological Laboratory, Herlev Hospital. In 5 cases (2 with operative sequelae after prolapsed intervertebral discs, 1 with tethered cord syndrome and 2 with early multiple sclerosis) the examination gave a definitive diagnosis. The cases are reported.

Adult↗
PubMed1991

Dose-response bioactivity and bioavailability of salmon calcitonin in premenopausal and postmenopausal women.

We investigated the acute, dose-response to three intranasal doses of salmon calcitonin (sCT) (50 IU, 100 IU, and 200 IU) and one im dose (50 IU) in eight premenopausal and eight early postmenopausal women. Total serum calcium and serum beta-endorphin revealed significant changes after all four administrations (P less than 0.05). After the two highest intranasal and the im doses cAMP increased 10% and 35%, respectively (P less than 0.05). All administrations except the 50 IU intranasal dose produced significant increases in plasma sCT (P less than 0.05). The areas under the concentration-time curves, calculated for the period with the maximal changes (i.e. 120-240 min), illustrated a significant dose-related response in total serum calcium, beta-endorphin, and sCT (P less than 0.01-0.001). cAMP showed a dose-related tendency, the response to the im injection being significantly higher than that to the two lowest doses of intranasal sCT (P less than 0.05). We conclude that the doses administered produce a dose-related biological response and bioavailability. In women with normal and high bone turnover, sCT 100 IU intranasally seems as optimal as 50 IU im. The response to sCT should, furthermore, be assessed on bioactivity rather than on bioavailability.

Administration, Intranasal↗
PubMed1991

Cytotoxic activity in plasma from patients with amyotrophic lateral sclerosis.

The present study evaluates an assay of cytotoxic effect of plasma from patients with amyotrophic lateral sclerosis. Plasma from 20 recently diagnosed ALS patients induced hemolysis of normal red blood cells with a significantly greater intensity than that of normal controls. After at least 1 month of treatment with prednisone and azathioprine, the hemolytic activity of ALS plasma was reduced but was still higher than that of control plasma.

Aged↗
PubMed1990

Discontinuous calcitonin treatment of established osteoporosis--effects of withdrawal of treatment.

PURPOSE: The purpose of this study was to examine the effects of discontinuous treatments with intranasal salmon calcitonin on bone and calcium metabolism in postmenopausal women and to establish the effects of withdrawing treatment. PATIENTS AND METHODS: This report presents data from 26 postmenopausal women with established osteoporosis (forearm fracture) 12 months after withdrawal of a 1-year double-blind, placebo-controlled therapy with intranasal calcitonin. The women then resumed treatment with calcitonin 200 IU plus calcium 500 mg daily in an open design for an additional 1-year period. A control group of 19 age-matched women (no forearm fracture) did not receive any treatment. RESULTS: At the end of the 3 years, the control group had lost significantly more bone in the forearm (single photon absorptiometry) and spine (dual photon absorptiometry) than had the group treated with intranasal calcitonin for 2 years, whereas the group receiving calcitonin for 1 year had intermediate values. During the year of withdrawal, the rate of bone loss was similar in the women who had received calcitonin and those who had received placebo. Calcitonin was especially effective in women with initially high bone turnover and low bone mass. The bone response in the spine could, furthermore, be estimated by the changes in bone turnover. CONCLUSION: Discontinuous treatment with intranasal calcitonin affects bone and calcium metabolism in established osteoporosis. In women with high-turnover osteoporosis, therapy results in a net gain of bone in both the peripheral and axial skeleton. Response to treatment may be monitored by changes in bone turnover.

Absorptiometry, Photon↗
PubMed1990

Bone mass measured by photon absorptiometry: comparison of forearm, heel, and spine.

We assessed bone mass quantification at different skeletal sites by single and dual photon absorptiometric (SPA and DPA) methods. Improved DPA measurement of spinal bone mineral density in young healthy subjects showed a short- and long-term precision of 1.2% and 1.6%. Compared to the conventional DPA method the imprecision was reduced by more than 50%. The appendicular measurements were more precise (0.5-1.2%). We present the intercorrelations and predictive errors between peripheral measurements and improved spinal and total body bone measurements in early postmenopausal women (n = 144) recruited in 1988. To compare the improved system with the conventional methods, we retrieved data on age-matched early postmenopausal women (n = 151) recruited in 1983. In the 1988 population all peripheral methods had similar predictive errors in estimation of spinal bone mineral density (SEE = 11-13%) and total body bone mineral density (SEE = 4-5%). Measurement of trabecular bone in the heel and distal forearm did not improve the validity of predicting spinal bone mass. In a cadaver study (n = 11) the predictive error in estimation of the spinal ash weight from forearm measurements was of the same magnitude (15%) as that in estimation of the spinal BMC from the forearm (16%). We conclude that the predictive error in estimation of spinal bone mass from peripheral bone measurements is more likely to be caused by intra-skeletal variation in bone mass than by precision errors. However, this does not reflect the inability of peripheral bone mass measurements to predict fracture risk.

Absorptiometry, Photon↗
PubMed1990

Thrombolytic therapy of cerebral arterial occlusion with recombinant tissue plasminogen activator.

This report describes three patients, with acute cerebral arterial occlusion, treated with recombinant tissue plasminogen activator (rt-PA). In one patient with basilar artery occlusion thrombolytic treatment was initiated 12 h after onset of the symptoms. In two patients with angiographically verified occlusion of the middle cerebral artery, the treatment was initiated approximately 4.5 h after onset of the symptoms. Recombinant tissue plasminogen activator 80-120 mg, was infused intra-arterially over 90-100 min via a catheter the tip of which was close to the occlusion. This regimen resulted in recanalization in all the patients; however, in two patients it was verified by repeat CT scan only. In two patients the thrombolytic treatment was successful (the patients improved clinically); the third patient died of massive cerebral infarct-related oedema. In none of the patients did significant bleeding or other obvious side-effects occur. From this preliminary report it is concluded that angiographically proven thrombolytic recanalization in acute cerebrovascular occlusion is possible with rt-PA. In some patients, however, the treatment is initiated too late. Further investigation of the possible indication for thrombolytic therapy in stroke is needed.

Adult↗
PubMed1990

The age-related incidence of meconium ileus equivalent in a cystic fibrosis population: the impact of high-energy intake.

During the decade from 1976 to 1986, the age-related incidence of meconium ileus equivalent (MIE) was calculated on the basis of 240 Danish cystic fibrosis (CF) patients. In the first 5 years, the patients were given enteric-coated granules of pancreatic enzymes (Pancreatin, Rosco, Denmark), and a low fat diet was recommended. In the last 5 years, the Center recommended supplementation with acid-resistant, enteric-coated, encapsulated microspheres (Pancrease, Cilag, Birkerød, Denmark), and high-energy intake with a 40% fat content and no dietary restrictions. There was no difference in the incidence of MIE when these two 5-year periods were compared, and the overall incidence of MIE was low (5.4 MIEs/1,000 patient years). This may, at least in part, be due to the rather high intake of exocrine pancreas enzyme supplementation (EPES) (a mean intake of 0.9 capsules/kg/day). MIE occurred almost exclusively among patients greater than 15 years old and peaked in young adults aged 20-25 years (35.5 MIEs/1,000 patient years). The daily intake of EPES/kg of body weight declined significantly with age, and the patients who developed MIE received even less than average per day. Both of these points strengthen the view that a low enzyme dosage is likely to have an effect on the incidence of MIE.

Acetylcysteine↗
PubMed1990

Vitamin D metabolism in osteoporotic women during treatment with estrogen, an anabolic steroid, or calcitonin.

We assessed the effects of a continuous oral combination of estradiol and norethisterone acetate, nandrolone decanoate, or salmon calcitonin on the vitamin D endocrine system. One hundred and nineteen postmenopausal women, aged 55-75 years, with at least one osteoporotic fracture, were randomly allocated to one year of treatment with estradiol and norethisterone acetate, nandrolone decanoate, or calcitonin, all drugs with a beneficial effect on bone. All three trials were double-blind and placebo-controlled; 104 women (87%) completed the study. We measured the total serum concentration of 1,25-dihydroxyvitamin D (1,25(OH)2D) and vitamin D-binding protein, and estimated the free 1,25(OH)2D index and the "24-hydroxylase activity" initially, and at 6 and 12 months. Furthermore, the 24-h urinary excretions of calcium, phosphate, and adenosine 3'-5'-cyclic monophosphate were assessed initially and at 12 months. The serum concentration of vitamin D-binding protein and 1,25(OH)2D increased transiently during estradiol and norethisterone acetate treatment and vitamin D-binding protein decreased transiently during nandrolone decanoate treatment. None of the other parameters were significantly affected by any of the three treatments. The risk of type II errors was below 10 per cent for all vitamin D measurements. We conclude that the vitamin D metabolites are unlikely to be of major importance for the mechanism by which these drugs exert their positive skeletal effects.

Aged↗
PubMed1990

Effects of methylamine and heparin on a rapid chromogenic assay of C1-esterase inhibitor in plasma.

We describe a rapid assay of C1-esterase inhibitor (C1-inh) activity in plasma. After adding purified C1s serine protease (EC 3.4.21.42) in excess to plasma, we determine the residual C1s activity towards a new chromogenic tripeptide, CH3CO-Lys(CbO)-Gly-Arg-pNA. Optimal conditions include the addition of methylamine (final concentration 0.12 mol/L) to reduce the potential inhibitory capacity of alpha 2-macroglobulin towards C1s and the addition of heparin (final concentration 3000 int. units/L) to enhance the reaction of C1s with C1-inh. The correlation with C1-inh antigen concentrations in plasma was excellent. The estimated interassay CV was 4.3%, whereas the intra-assay CV was 2.0% for activity concentrations within the range of normal individuals (means +/- 2 SD: 70-124%), 1.3% at lower concentrations. The method is more convenient, rapid, and precise than previous methods, and C1-inh activity in plasma can be assessed within 30 min. We found that concentrations of C1-inh in plasma were low during open-heart bypass surgery.

Antigens↗
PubMed1990

Dual-energy x-ray absorptiometry: a precise method of measuring bone mineral density in the lumbar spine.

We compared two methods of measuring spinal bone mineral content and density (BMC/BMD): conventional dual-photon absorptiometry (DPA) and a more recent method, dual-energy x-ray absorptiometry (DEXA). The clinical usefulness of both methods was compared in the measurement of BMC in the forearm. DEXA had a long-term in vivo precision of 1% which was significantly better than that of DPA. Changes in the distribution of fatty tissue influenced the accuracy of the two spinal methods in different ways. Forearm BMC discriminated between the bone mass of early and late postmenopausal women to the same degree as DPA and DEXA. The variability in the response to estrogen treatment and placebo was much lower with DEXA and forearm BMC than with DPA. We conclude that DEXA provides a fast and precise measurement of spinal BMC/BMD. The accuracy remains to be evaluated for in vivo studies.

Absorptiometry, Photon↗
PubMed1989

Effect of salcatonin given intranasally on early postmenopausal bone loss.

OBJECTIVE: To study the effect of salmon calcitonin (salcatonin) given intranasally on calcium and bone metabolism in early postmenopausal women. DESIGN: Double blind, placebo controlled, randomised group comparison. SETTING: Outpatient clinic for research into osteoporosis. SUBJECTS: 52 Healthy women who had had a natural menopause two and a half to five years previously. INTERVENTIONS: The 52 women were allocated randomly to two years of treatment with either salcatonin 100IU given intranasally (n = 26) or placebo (n = 26). Both groups received a calcium supplement of 500 mg daily. Seven of the women receiving salcatonin and six of those receiving placebo left the study before its end. MAIN OUTCOME MEASURES: Bone mineral content in the spine, the total skeleton, and the forearms after two years of treatment. RESULTS: Bone mineral content in the spine was significantly higher in the women who had received salcatonin than in those who had received placebo both after one year and after two years of treatment. After one year the difference was 3.8% (95% confidence interval 0.0 to 7.6%) and after two years it was 8.2% (3.8 to 12.6%). In contrast, the bone mineral content in the distal and proximal forearms and in the total skeleton declined similarly in both groups by about 2% each year, and after two years of treatment the differences between the groups were not significant. Biochemical estimates of bone turnover were not affected by salcatonin. CONCLUSION: The results suggest that salcatonin given intranasally in the dose used prevents bone loss in the spine of early post menopausal women but does not affect the peripheral skeleton.

Administration, Intranasal↗