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Biomedical subjects

M Nielsen

Publications and source records attributed to M Nielsen.

At least 271 records · Page 15Linked to original sources

The effect of labour and epidural analgesia on pain threshold.

Pain thresholds were measured using forehead pressure in 30 women before amniotomy and then during labour up to the point of their requesting analgesia. Measurements continued subsequently only in those having epidural analgesia alone. No significant change in pain threshold was seen in any patient up to the administration of analgesia, nor thereafter in the ten patients having epidurals. This study fails to confirm previous reports in animals of significant rises in pain threshold during parturition. It calls into question the view that previously reported changes in plasma endorphin levels may be associated with altered pain thresholds.

Anesthesia, Epidural↗

Five years experience of breast augmentation using silicone gel prostheses with emphasis on capsule shrinkage.

The results of a five-year retrospective study on breast augmentation using silicone gel-filled prostheses are presented. A total of 115 breasts (45%) out of 254 developed capsules of type II-IV. The incidence in the hypoplasia group was 46%. The capsules were treated with closed and/or open capsulotomy. Biopsies showed fibrous capsules containing alcianophilic droplets, suggesting the presence of silicone in the tissue. The authors find the above incidences to be unacceptably high, and as the treatment is costly, we advocate a more restrictive approach towards operations for mammary hypoplasia.

Adolescent↗

Reduction of 3H-spiroperidol binding in rat striatum and frontal cortex by chronic amphetamine: dose response, time course and role of sustained dopamine release.

After 5 days of continuous treatment with d-amphetamine base in doses greater than 0.5 mg/kg/h maintained by subcutaneously implanted osmotic minipumps, specific binding of 3H-spiroperidol was reduced in rat striatum and frontal cortex as previously reported. These effects were dose-dependent at lower doses of amphetamine, whereas with higher doses an apparent ceiling for the reduction in binding was reached at approximately 70% of control values. Similarly, increasing the exposure time to amphetamine for up to 14 days only slightly augmented the reduction in 3H-spiroperidol binding already present after 5 days of treatment. In rats treated for 5 days with amphetamine, concomitant treatment with the dopamine (DA) synthesis inhibitor alpha-methyl-p-tyrosine prevented the decrease in 3H-binding in corpus striatum, and attenuated the decrease in frontal cortex. Furthermore, in rats with unilateral 6-hydroxydopamine lesions of the nigro-striatal DA tract, 5 days of chronic amphetamine had no significant effect on 3H-spiroperidol binding in the denervated striatal tissue. Since a major effect of amphetamine is to release DA from nerve terminals, these results indicate that the reduction of DA receptors by chronic amphetamine in the striatum is mediated by sustained release of DA.

Amphetamine↗

Binding of 3H-DMCM to benzodiazepine receptors; chloride dependent allosteric regulation mechanisms.

DMCM is a convulsant agent with negative efficacy at benzodiazepine (BZ) receptors. 3H-DMCM binds to benzodiazepine receptors in vitro. The sensitivity of 3H-DMCM binding to agents presumed to act on chloride channels associated with the BZ/GABA-receptor-complex was investigated at 37 degrees C. Chloride ions (200 mM) enhanced the specific binding of 3H-DMCM four-fold. Similarly the specific binding of 3H-DMCM was enhanced by picrotoxinine in the absence but not in the presence of chloride ions. (+)-Etomidate and pentobarbital reduced the specific 3H-DMCM binding in a partially chloride ion dependent and picrotoxinine sensitive manner. The results obtained are consonant with the idea that 3H-DMCM binds to the BZ/GABA-receptor-chloride ionophor complex; furthermore, binding of 3H-DMCM seems to involve a chloride dependent allosteric regulation mechanism.

Animals↗

Effect of chronic renal failure and methylprednisolone treatment on the uptake of labelled plasma cholesterol into the aorta of normocholesterolemic rabbits.

The effects of chronic renal failure (CRF) and corticosteroid treatment on the aortic uptake of labelled free and esterified cholesterol (FC and EC) were investigated in normocholesterolemic rabbits. Methylprednisolone, 0.4 mg/day, or placebo was administered for 14 weeks to rabbits with normal renal function and with CRF. Then [3H]- and [14C]cholesterol were administered intravenously and orally, respectively. The radioactivity levels of FC and EC in plasma were measured at regular intervals. After 48 h the accumulation of 3H and 14C radioactivity of FC and EC in the intima-media of the thoracic aorta was determined. An aortic uptake coefficient was calculated by dividing the tissue radioactivity (dpm/cm2/h) by the mean plasma radioactivity (dpm/ml). The mean uptake coefficient of EC in normal rabbits was 6 nl/cm2/h, the value for FC being 180 nl/cm2/h. In normal rabbits treated with methylprednisolone the uptake coefficients of both FC and EC were significantly decreased to about 50% of the values in normal rabbits receiving placebo. A similar significant decrease in the uptake coefficients was found in the CRF rabbits receiving placebo. No further decrease was observed in the CRF rabbits treated with methylprednisolone. The cholesterol content of the aortic intima-media was significantly decreased only in CRF rabbits on methylprednisolone treatment. The results do not indicate an acceleration of uremic arterial disease by steroid treatment in the rabbit.

Animals↗

Benzodiazepine receptor ligands with positive and negative efficacy.

Recent studies have shown that benzodiazepine receptors can be affected not only by benzodiazepine agonists and antagonists but also by a new class of ligands which produce effects opposite to those of benzodiazepines, that is they produce convulsions and anxiety. These ligands can be described as having a negative efficacy at the receptor; tentatively they are named "inverse agonists". Pharmacological experiments indicate that agonists, antagonists and inverse agonists comprise a whole continuum of agents with a graduated variety of efficacy at the receptor. Biochemical studies, supported by published electrophysiological data, indicate that the benzodiazepine receptor allosterically up- or down-regulates the gain in the GABAergic system depending on the nature of the ligand.

Acoustic Stimulation↗

Binding of [3H]DMCM, a convulsive benzodiazepine ligand, to rat brain membranes: preliminary studies.

DMCM (methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) produces convulsions in mice and rats, probably by interacting with benzodiazepine (BZ) receptors. Investigation of specific binding of [3H]DMCM to rat hippocampus and cortex revealed polyphasic saturation curves, indicating a high-affinity site (KD = 0.5-0.8 nM) and a site with lower affinity (KD = 3-6 nM). BZ receptor ligands of various chemical classes, but not other agents, displace [3H]DMCM from specific binding sites--indicating that [3H]DMCM binds to BZ receptors in rat brain. The regional distribution of [3H]DMCM binding is complementary to that of the BZ1-selective radioligand [3H]PrCC. Specific binding of [3H]DMCM (0.1 nM) was reduced by gamma-aminobutyric acid (GABA) receptor agonist to approximately 20% of the control value at 37 degrees C in chloride-containing buffers; the reduction was bicuculline methiodide- and RU 5135-sensitive. The effective concentrations of 10 GABA analogues in reducing [3H]DMCM binding correlated closely to published values for their GABA receptor affinity. Specific binding of [3H]DMCM is regulated by unknown factors; e.g. enhanced binding was found by Ag+ treatment of membranes, in the presence of picrotoxinin, or by exposure to ultraviolet light in the presence of flunitrazepam. In conclusion, [3H]DMCM appears to bind to high-affinity brain BZ receptors, although the binding properties are different from those of [3H]flunitrazepam and [3H]PrCC. These differences might relate in part to subclass selectivity and in part to differences in efficacy of DMCM at BZ receptors.

Animals↗

Decreased number of benzodiazepine receptors in frontal cortex of rat brain following long-term lithium treatment.

Chronic administration of lithium led to a decreased number of benzodiazepine receptors (ca. 20%) in frontal cortex of rat brain, whereas no change was observed in the binding characteristics in the remaining part of the cortex and in the hippocampus and the cerebellum. Long-term lithium treatment did not change the binding of [3H]lysergic acid diethylamide and [3H]quinuclidinyl benzilate to membranes of various brain regions in the rat. We concluded that the effect of lithium on the benzodiazepine receptor is brain region specific and cannot be explained as a consequence of a reduced gamma-aminobutyric acid-ergic stimulation of benzodiazepine receptor, as the change in receptor binding was due to a change in the number of receptors rather than in the affinity constant.

Animals↗

Inhibition by methylprednisolone treatment of the aortic mineral accumulation in rabbits with chronic renal failure.

The effect of methylprednisolone treatment on the mineral accumulation in the rabbit aorta during chronic renal failure (CRF) was investigated. Groups of rabbits with surgically induced CRF and sham operated controls were treated for 14 weeks with 0.40 mg of methylprednisolone per day and compared to corresponding groups receiving placebo. After sacrifice the thoracic aorta was excised and divided into an inner intima-media and an outer media layer before determination of the content of cholesterol and minerals. The surface area and wet weight of both layers were significantly increased in the CRF groups but methylprednisolone treatment had no effect on these parameters. Neither CRF nor methylprednisolone caused significant changes of the cholesterol content of the intima-media. Methylprednisolone treated CRF rabbits had a significantly decreased mineral content of the intima-media layer compared to CRF rabbits receiving placebo although the treatment caused no significant changes in the serum concentrations of calcium and phosphate. In rabbits with normal renal function a similar effect could not be demonstrated.

Animals↗

Endometriosis of the vermiform appendix.

The pathological findings and clinical aspects of 22 patients with endometriosis of the vermiform appendix are presented. The cases were found among 10,000 appendices examined from 1950 to 1981. During this period of 32 years, 800 cases of pelvic endometriosis were seen. In 10 patients no other locations of pelvic endometriosis were found.

Abdomen, Acute↗

The basement membrane component laminin in breast carcinomas and axillary lymph node metastases.

The occurrence of the basement membrane (BM) glycoprotein laminin was investigated in 91 malignant breast tumors and in 359 axillary lymph nodes of which 70 contained metastases. The indirect double-layer immunoperoxidase technique was applied using rabbit anti-rat laminin. Positive cytoplasmic staining for laminin was found in all breast carcinomas. BM could be demonstrated around in situ carcinomas and in the higher differentiated carcinomas around islands of infiltrating tumor cells. Lymph node metastases resembled the primary tumors in the cytoplasmic staining reaction for laminin, but no BM staining was found. Tissue from 50 benign breast lesions showed cytoplasmic staining for laminin in both the secretory and the myoepithelial cells, but consistently weaker than in the carcinomas. BM was always present.

Adolescent↗

Effect of 1 alpha-hydroxyvitamin D3 and dietary calcium and phosphate on the aortic mineral content in rabbits with mild azotemia.

The effect of treatment with 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3) and different diets on uremic arterial disease was studied. Three groups of rabbits with chronic renal failure (CRF) were kept on three diets with a low, medium or high content of calcium and phosphate. Half the rabbits in each group were treated for 18 weeks with 1 alpha-OH-D3, 0.02 micrograms/kg/day, without any significant changes in the serum concentrations of calcium or phosphate compared to placebo treatment. In the thoracic aorta, the content of calcium and phosphate was significantly increased in placebo-treated CRF rabbits on medium and high calcium and phosphate intakes compared to rabbits with normal renal function (p less than 0.05). The cholesterol content was unchanged. Treatment with 1 alpha-OH-D3 caused a further increase in the aortic content of calcium and phosphate in the CRF rabbits on medium and low calcium and phosphate intakes (p less than 0.05). No increase in the aortic cholesterol content was observed. The histological changes in the abdominal aorta consisted of medial proliferations with calcifications and intimal proliferations. The severity of these changes paralleled the mineral content of the thoracic aorta. Aggravation of uremic arterial disease may be a hitherto unrecognized side-effect of treatment with 1 alpha-OH-D3 in CRF.

Animals↗