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Biomedical subjects

C Strömberg

Publications and source records attributed to C Strömberg.

At least 37 records · Page 2Linked to original sources

Angiotensin AT2 receptors regulate cerebral blood flow in rats.

LARGE cerebral arteries have been reported to contain angiotensin receptors that are exclusively of the AT2 subtype. We measured the effect of the AT2 receptor selective ligand PD 123319 on cerebral blood flow (CBF) in rats, using laser-doppler flowmetry. PD 123319 (1-10 mg kg-1) dose-dependently inhibited the increase in CBF, when the blood pressure was increased by a norepinephrine infusion. However, PD 123319 did not alter baseline CBF at normal blood pressures. Therefore PD 123319 appears to interfere with the autoregulatory mechanisms of CBF. The participation of AT2 receptors in the regulation of CBF confirms a physiological role for this receptor subtype, and may give clues for future treatment of various cerebrovascular disorders.

Angiotensin II↗

Balloon angioplasty enhances the expression of angiotensin II AT1 receptors in neointima of rat aorta.

Angiotensin II is a vasoactive peptide and may act as a growth factor in vascular smooth muscle cells. Experimental injury of the rat aorta causes rapid migration of medial smooth muscle cells and their proliferation resulting in the formation of neointima. We have examined, using quantitative autoradiography, the expression of angiotensin II receptor subtypes AT1 and AT2, and angiotensin-converting enzyme, in the neointima formed in the rat thoracic aorta 15 d after balloon-catheter injury. In contrast to the normal aortic wall, which contained both AT1 and AT2 receptors (80% and 20%, respectively), neointimal cells expressed almost exclusively angiotensin II AT1 receptors. The apparent number of these receptors was fourfold higher in the neointima compared to that in the normal aortic wall. The affinities of the neointimal receptors to angiotensin II or to the AT1 receptor antagonist, losartan, were not different from those in the normal aortic wall. Angiotensin-converting enzyme binding in the neointima was not different from that in the media of the uninjured aorta. Our data suggest that angiotensin II AT1 receptors may have a significant role in injury-induced vascular smooth muscle proliferation and migration.

Angioplasty, Balloon↗

Prognostic importance of the DNA ploidy pattern in malignant mesothelioma of the pleura.

Malignant mesotheliomas often raise a difficult diagnostic problem: once the diagnosis is made, the possibilities of predicting the biologic activity and prognosis of the tumor are limited. DNA ploidy patterns have been used as a prognostic instrument for other tumors, and this pattern was therefore studied in 37 cases of verified mesothelioma. The measurements were made on Feulgen-stained smears from pleural effusions using a Leica Miamed computer microscope. When a highly aneuploid tumor was defined as a condition with greater than 5% of the cells within defined intervals outside the ranges of the stem-line and the peaks representing polyploidization thereof, a near-diploid/polyploid pattern was obtained in 41% of the cases, while the remaining 59% were classified as highly aneuploid. The prognosis was significantly better among the near-diploid/polyploid cases. This estimate of the outcome could not be improved by using alternative algorithms for high-grade aneuploidy.

Aneuploidy↗

Angiotensin II AT1 receptors in rat superior cervical ganglia: characterization and stimulation of phosphoinositide hydrolysis.

Angiotensin II receptor number was higher in superior cervical ganglia of 2-week-old when compared to 8-week-old rats. In both young and adult rats, specific binding of [125I][Sar1]angiotensin II was displaced competitively by the AT1-receptor antagonist DuP 753 but not by the AT2-receptor competitor PD 123177. In ganglia from adult rats, DuP 753 competed with an IC50 of 113 nM. The stable guanine nucleotide GTP gamma S inhibited binding of [125I][Sar1]angiotensin II in young and adult rats by approximately 50% with IC50 values of 105 and 120 nM, respectively, suggesting that the angiotensin receptor is G-protein linked. Angiotensin II at a dose of 1 microM stimulated inositol phosphate formation 58% over control values in superior cervical ganglia from 8-week-old rats. This effect was totally blocked by 10 microM DuP 753 but not by 10 microM PD 123177. Our findings demonstrate that rat superior cervical ganglia contain AT1-type angiotensin receptors that are probably G-protein linked, and their stimulation results in increased inositol phospholipid metabolism.

Angiotensin II↗

Type-1 and type-2 angiotensin II receptors in fetal rat brain.

Brain angiotensin II receptors were located in 18-day-old rat embryos by quantitative autoradiography. In the nucleus of the solitary tract and choroid plexus, binding was displaced by the type-1 antagonist DuP 753. In the inferior olive, paratrigeminal and hypoglossal nuclei, binding was displaced by the type-2 antagonist CGP 42112 A. Meninges and cephalic soft tissues contained predominantly type-2 angiotensin II receptors. Our results indicate a role for type-1 and type-2 angiotensin II receptors during brain development.

Angiotensin II↗

Echocardiographic and psychometric effects of amitriptyline or imipramine plus alcohol.

The echocardiographic and psychometric effects of amitriptyline or imipramine combined with alcohol have been studied in a double-blind cross-over trial in 7 healthy volunteers. Amitriptyline or imipramine 25 mg b.d. were given for three days and then the dose was doubled. On Days 1 and 10-13 echocardiographic measurements were done, and on Day 15 psychomotor tests were performed. Ethanol 1 g/kg in each session was administered 1 h after drug intake. Alcohol alone increased heart rate and decreased the systolic blood pressure and ejection fraction. It also impaired most of the psychomotor measures, horizontal nystagmus being the most sensitive test. On Day 1, the first dose of imipramine decreased the heart rate and increased diastolic blood pressure. These effects were partly counteracted by alcohol. Imipramine + alcohol decreased the WSTR. Amitriptyline alone did not affect the echocardiographic findings on Day 1. In combination with alcohol it reduced cardiac output and prolonged PEP, and increased the PEP/LVET ratio. During subacute treatment (Days 10-13) WSTR was increased by both antidepressants, but only amitriptyline increased the heart rate. Unlike imipramine + alcohol, amitriptyline + alcohol decreased WSTR and MCSR. Digit symbol substitution was the only pschometric test in which the alcohol effect was clearly enhanced by both amitriptyline and imipramine.

Administration, Oral↗

Angiotensin-II receptor subtypes in fetal tissue of the rat: autoradiography, guanine nucleotide sensitivity, and association with phosphoinositide hydrolysis.

Quantitative autoradiography revealed large numbers of angiotensin-II (AT) receptors in the 18-day-old rat embryo. The selective AT-1 antagonist DuP 753 readily competed for AT receptors in liver, lung parenchyma, and choroid plexus, and these receptors are classified as AT-1 receptors. The selective AT-2 displacers CGP 42112 A and/or PD 123177 competed with high affinity with AT bound to most receptors located in skeletal muscle, skin, diaphragm, bronchi, and stomach, and these receptors are classified as AT-2 receptors. The amount of AT-2 receptors in fetal tissue was more than 10-fold higher than that of AT-1 receptors. In skeletal muscle and skin, DuP 753 competed with AT in the presence of 10(-7) M CGP 42112 A, indicating the presence of small numbers of AT-1 receptors. In liver and lung parenchyma, binding to AT-1 receptors was sensitive to guanine nucleotides. AT binding to AT-2 receptors in fetal skin and skeletal muscle was insensitive to guanine nucleotides. AT stimulated phosphoinositide hydrolysis in liver (ED50, 64 nM) and in skin and skeletal muscle (ED50, 62 nM); this was inhibited by DuP 753 (liver IC50, 38 nM; skin and skeletal muscle IC50, 26 nM), but not by PD 123177 in concentrations up to the micromolar range. AT-1 receptors are probably coupled to G-proteins, and their stimulation increases phosphoinositide hydrolysis. AT-2 receptors may not be linked to G-proteins, their stimulation is not associated with phosphoinositide hydrolysis, and the nature of their second messenger system(s) is presently unknown.

Angiotensin I↗

Saving money with effective in-line filters.

The Intensive care unit at Umeå Regional Hospital has during the past year, 1988, used PALL ELD 96 inline-filters on all patients with a central venous catheter. Two different time-periods were investigated, one when inline-filters were used and one without in-line filters. By counting the amount of intravenous disposables that were used and with TISS registration (therapeutic intervention scoring system) which is registered daily on all patients, cost and savings were derived 'per occupied bed day'. The study shows that through using in-line filters which are changed every 96 hours we may save approximately 35,000 pounds every year.

Catheterization, Central Venous↗

Multicenter clinical trials and their value in assessing total joint arthroplasty.

Multicenter clinical trials (MCT) have an important role in the assessment of total joint arthroplasty. The primary reason for such MCT is the need to have access to a large number of patients. In Sweden, failure after total hip arthroplasty has been recorded prospectively since 1979. Medical records from every reoperation are documented and computer analyzed. This MCT has shown that patient-related, surgical, and implant-related parameters are of importance to rates of failure. There were an increasing number of revisions after total hip arthroplasty in Sweden between 1979 and 1986. Male gender and young age increase the risk of revision. The primary diagnosis is very important for type of failure. The risk of deep infection is small but increases with the number of previous operations. Aseptic loosening has emerged as the main problem and is the cause for 74% of all revisions. Prosthetic design is of utmost importance for the rate of failure, and significant differences exist among different prosthesis types with respect to long-term survival. Finally, this MCT has shown that revisions for total hip arthroplasty in patients younger than 70 years of age eventually have failed in Sweden whenever the cemented technique has been used.

Aged↗

Interaction of alcohol with maprotiline or nomifensine: echocardiographic and psychometric effects.

Eight healthy volunteers received low doses of maprotiline and nomifensine up to 50 mg b.d. for 15 days in a double-blind, cross-over, placebo controlled study, during which echocardiography and psychomotor testing were carried out before and after the intake of alcohol 1 g/kg. Maprotiline increased heart rate and cardiac output and reduced peripheral resistance compared to placebo and nomifensine. Nomifensine alone was associated with a slight decrease in heart rate. Alcohol alone caused a significant increase in diastolic blood pressure, but did not otherwise modify the cardiovascular measures. The antidepressants did not augment the effects of alcohol. Antidepressants alone had no effect on psychomotor skills, but alcohol always impaired performance. No additional effects of alcohol were produced by the antidepressants. It appears that practically important peripheral or central consequences are unlikely to follow drinking a moderate amount of alcohol during regular therapy with low therapeutic doses of catecholamine reuptake inhibiting antidepressants. Experimental studies of the interaction of antidepressants and alcohol in patients with chronic heart disease seem to be justified.

Adolescent↗

Effects of the novel 5-hydroxytryptamine reuptake inhibitor indalpine and ethanol on psychomotor performance.

Twelve healthy male volunteers were treated double-blind and cross-over with 4-(3-indolyl-2-ethyl)piperidine (indalpine), a selective 5-hydroxytryptamine uptake inhibitor with antidepressant and anxiolytic properties, and placebo for two weeks. Soon after starting the treatment with indalpine (50 mg/d) they felt subjectively mild sedative-like effects which were abolished when retested after two weeks' maintenance (150 mg/d). Objectively measured psychomotor performance (coordinative and reactive skills, standing steadiness, nystagmus, flicker recognition) was not, however, affected by indalpine. The only adverse effect attributable to indalpine was ejaculatory dysfunction which was spontaneously reported by 67% of the subjects. When alcohol (1 g/kg) was administered during the treatment periods most tests showed impairment. However, indalpine neither enhanced nor counteracted the effects of alcohol in this trial.

Adult↗

Acute and subchronic effects of Org 2305 and diazepam on psychomotor performance in man.

Three doses (15, 30 and 60 mg) of Org 2305 (O 15, O 30 and O 60 respectively), a novel anxiolytic drug chemically related to mianserin, were compared with placebo and 15 mg diazepam (DZ) on human psychomotor performance in a double-blind, cross-over study with 15 healthy volunteers. Objective measurements (choice reaction, tracking, flicker fusion, Maddox wing, digit symbol substitution, memory recall) and subjective assessments (visual analogue scales) were done at baseline and 2 and 13 h after the first dose. This testing procedure was repeated on day 7 when administering the seventh consecutive daily night-time dose. After the first dose O 15 did not differ from placebo and O 30 rarely differed from placebo. O 60 impaired various objective functions similarly to, or less than DZ. Subjectively, DZ and O 60 were felt as sedative. During subchronic treatment, DZ caused some impairment of baseline due to accumulation of bioassayable benzodiazepines, but significant responses to the last DZ dose were less than those to the first dose. DZ but not O 60 was reported to have caused lethargy and clumsiness during subchronic treatment. In the doses used Org 2305 impaired psychomotor performance less than diazepam did. A dose of 60 mg Org 2305 may offer some advantage over 15 mg diazepam, provided that their anxiolytic effects are about similar.

Adult↗

Acute comparison of clovoxamine and mianserin, alone and in combination with ethanol, on human psychomotor performance.

Objective and subjective effects on human performance of clovoxamine and mianserin were measured in 12 student volunteers who participated in 12 test sessions and received single doses of clovoxamine 50 mg, 100 mg and 150 mg, mianserin 20 mg, and placebo in a double-blind and cross-over manner. Each test drug was given twice, both in combination with alcohol 0.8 g/kg and with a non-alcoholic drink. The tests included tracking, body balance, flicker fusion, horizontal nystagmus, digit symbol substitution, recall memory, and subjective assessments on visual analogue scales. Mianserin and alcohol impaired objective performance in most tests, and their combination showed at least an additive effect. Alcohol counteracted rather than increased mianserin-induced subjective sedation. Clovoxamine neither differed significantly from placebo nor increased alcohol effects. On the contrary, clovoxamine 150 mg reduced significantly alcohol-induced body sway. No evidence of pharmacokinetic interactions were found between the study drugs and alcohol.

Adult↗

Acute and subacute effects on psychomotor performance of femoxetine alone and with alcohol.

The effects on human psychomotor performance of femoxetine (FEMO), a 5-hydroxytryptamine-selective antidepressant, alone and in combination with alcohol (EtOH) were compared with those of amitriptyline (AMI) and placebo in a controlled double-blind crossover trial in 11 student volunteers. Objective measurements (body sway, choice reaction, flicker fusion, tracking, nystagmus, digit symbol substitution, backwards recall) and subjective self-assessment (visual analogue scales, reporting of side-effects) were done after single doses of FEMO, AMI and placebo, and subacute administration of FEMO and placebo. Single doses of 200 mg FEMO did not impair psychomotor performance, but 50 mg AMI did so in several respects. AMI but not FEMO increased the objective and subjective effects of EtOH. After FEMO 600 mg/d for 10 days almost no objective difference from placebo was noted, although mild sedation at home was reported as a side-effect. FEMO either did not increase or slightly decreased the effect of EtOH on reactive and co-ordination skills. The plasma concentrations of FEMO varied widely from 0 to 156 ng/ml, as in previous clinical trials but reduced a blood 5-hydroxytryptamine concentration in each subject indicating an effect of FEMO on serotoninergic mechanisms.

Adult↗

Effects of zimeldine, mianserin and amitriptyline on psychomotor skills and their interaction with ethanol a placebo controlled cross-over study.

13 healthy volunteers participated in a double-blind, four-period, cross-over study. In each period, the trial drugs (placebo, zimeldine, amitriptyline and mianserin) were given in fixed dosages for 8 days; amitriptyline 10-50 mg twice daily, mianserin 10-30 mg twice daily and zimeldine 200 mg once daily. Ethanol 1 g/kg bodyweight was drunk 2 hours after drug intake on Days 1 and 8 of each period, the latter being separated by a 2 week wash-out period. Ratings of subjective feelings and side effects, and performance tests were done on Days 1 and 8 of each period before, 1.5, 3 and 4.5 h after drug intake, i.e. 2 of the tests were performed under the influence of ethanol. Mianserin decreased critical flicker frequency, slowed reactions under discriminative stimulation and tended to cause nystagmus, but only on Day 1 (after the first 10 mg dose). Amitriptyline impaired coordination on Days 1 (after the initial 10 mg dose) and 8, and lowered the flicker threshold on Day 8 at "steady state" (after the 50 mg morning dose). Both these antidepressants were felt to be sedative, especially in the initial phase of the treatment, and they interacted additively with ethanol. No impairment of psychomotor skills was associated with zimeldine, only a subjective sedative effect of the 200 mg dose was seen on Day 1. Zimeldine did not enhance the effects of ethanol; it even showed some antagonism of ethanol-induced body sway in the standing steadiness test. In contrast to amitriptyline and mianserin, zimeldine was regarded as not harming psychomotor skills, and as not having any observable interaction with ethanol.

Adult↗

Objective and subjective assessment of hangover during subacute administration of temazepam and nitrazepam to healthy subjects.

Fourteen, healthy students volunteered for a double-blind, cross-over trial of temazepam 20 mg (soft gelatine capsule), nitrazepam 10 mg (uncoated tablet) and placebo in matched formulations, single doses of each being given for 10 nights with a three-week wash-out period between each treatment. Residual drug effects were measured objectively (psychomotor skills) and subjectively (visual analogue scales) in the morning and afternoon of Days 0 (before the first tablet), 1 and 10. The subjects also recorded various events during each treatment period. Serum benzodiazepine concentrations were bioassayed in blood samples taken after the last assessment. Both benzodiazepines shortened sleep latency during the first few nights, and nitrazepam prolonged the duration of sleep. The residual effect of drowsiness was noted during the nitrazepam period, whilst temazepam proved less sedating. The 'morning after' effect was a subjective observation and not an objective measurement. The learning effect interfered with the complex objective assessments, and simple measurement of exophoria with the Maddox wing test provided the clearest objective evidence of drug effects. On Day 10 residual concentrations of nitrazepam were detectable in the serum whereas the level of temazepam was found to be low or negligible. It is concluded, that temazepam 20 mg in a soft gelatine capsule is a suitable hypnotic for subjects whose daily work requires constant alertness.

Activity Cycles↗