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Biomedical subjects

J A Nielsen

Publications and source records attributed to J A Nielsen.

At least 19 recordsLinked to original sources

[Relationship between distal systolic blood pressure and wound healing. A retrospective study of patients with crural ulcers].

To anticipate the need for ensuring quality in treatment of patients with ulceration of the lower leg and complicating arterial occlusive disease, three authors examined the files of 56 patients with systolic digital blood pressure (SDBP) below 60 mmHg, all admitted to the geriatric in-patient department over a 11-year period in a retrospective study. In 40 patients (71%) the ulcer healed. Eight patients (14%) required amputation, six patients (11%) died and two patients (4%) were unsolved. We found a significant correlation between SDBP and ulcer healing (p = 0.006). In patients with SDBP < or = 35 mmHg, healing on conservative pharmacotherapy was demonstrated even with critical ischaemia.

Aged

[The post-thrombotic syndrome. A review].

The post-thrombotic syndrome which is caused by deep venous thrombosis and characterized by pain, oedema, pigmentation, eczema, lipodermatosis, varices and ulceration, is due to deficient function of the venous valves and/or obstruction of the deep veins with venous hypertension. The diagnosis may be established by investigation of the investigation of the muscular-venous pump by pletysmography or dynamic phlebography and invasive measurement of the venous pressure is not employed to any great extent. The results of valvuloplasty have, by and large, been negative. The main form of treatment is, therefore, conservative compressive bandaging which can reduce the symptoms, facilitate healing of venous ulcers and prevent recurrence of ulcers. It is emphasized, however, that this treatment must be continued consequently during the remainder of the patient's life, regardless of other treatment.

Humans

Sertraline, a serotonin-uptake inhibitor, reduces food intake and body weight in lean rats and genetically obese mice.

Sertraline was found to inhibit weight gain and decrease food intake without affecting locomotion in rats and genetically obese (ob/ob) mice. Doses of 10, 17.8, and 32 mg/kg, administered intraperitoneally, (bid) significantly reduced the time rats spent in contact with their feeders and body weight in a dose-related manner. During a 5-d bid treatment regimen, vehicle-treated rats gained 37 +/- 3 g (mean +/- SEM), whereas animals treated with 32 mg sertraline/kg lost 34 +/- 4 g. The effects of sertraline on feeding and body weight in rats appeared to be specific because locomotor activity was not altered. In ob/ob mice, sertraline (44 mg/kg, ip, bid) lowered body weight relative to vehicle-treated controls for the duration of a 12-d study. There was no evidence for tolerance to the hypophagic and weight-loss effects of sertraline during either of the chronic dosing studies. These results suggest a potential role for sertraline in the treatment of human obesity.

1-Naphthylamine

Nicotinamide ethers: novel inhibitors of calcium-independent phosphodiesterase and [3H]rolipram binding.

The synthesis and biological properties of a series of nicotinamide ethers are described. These compounds, structurally novel calcium-independent phosphodiesterase inhibitors, also inhibit the binding of [3H]rolipram to rat brain membranes and reverse reserpine-induced hypothermia in the mouse. Several compounds exhibited potent in vivo activity comparable to the standard agent, rolipram.

Animals

Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl]-2-imidazolidinones.

The synthesis and biological properties of a novel series of selective calcium-independent phosphodiesterase inhibitors are described. These compounds also inhibit the specific binding of [3H]rolipram to rat brain membranes and exhibit efficacy in preclinical models of antidepressant activity in mice, such as reducing immobility in the forced-swim test and reversing reserpine-induced hypothermia. Imidazolidinones 4 and 16 were found to be the most potent compounds studied.

Animals

Structure-activity relationship of quinazolinedione inhibitors of calcium-independent phosphodiesterase.

A series of quinazolinediones and azaquinazolinediones is described which possess potent inhibitory activity toward the calcium-independent phosphodiesterase enzyme (CaIPDE). In vivo testing showed that this in vitro activity translates to animal models predictive of chronic diseases such as depression and inflammation. These results support the hypothesis that inhibition of CaIPDE may lead to useful activity in such chronic diseases.

Animals

[Epicrisis. A report from the county of Copenhagen].

During a random week in 1987, 35% of the general practitioners from all of the municipalities in the County of Copenhagen participated in a questionnaire survey whose objective was to illuminate the quality, expedition time, and possible problems associated with the letter of discharge (LD), an important link between the primary and secondary medical services. It can be concluded that the expedition time for a large number of LD's from the hospitals of Copenhagen County is unacceptably lengthy. A surprisingly large number of patients visited their own general practitioner during the week following discharge with questions about the information which had been given them during their hospital stay, regardless of agreements for ambulatory monitoring at the department from which they had been discharged. A preliminary LD can, to a certain extent, alleviate the problems brought about by the lack af an LD but ought not to replace or delay the issuance of the actual LD, and is a more expensive solution. The quality and content of the LD can be evaluated generally as good, but could be improved if the recommended follow-up treatment and information to the patients and relatives is routinely carried out.

Denmark

3-(1,2,5,6-Tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one: a potent and selective serotonin (5-HT1B) agonist and rotationally restricted phenolic analogue of 5-methoxy-3-(1,2,5,6-tetrahydropyrid-4-yl)indole.

The synthesis and in vitro and in vivo characteristics of 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (1, CP-93,129) are described. This rotationally restricted phenolic analogue of RU-24,969 is a potent (15 nM) and selective (200x vs the 5-HT1A receptor, 150x vs the 5HT1D receptor) functional agonist for the 5-HT1B receptor. Direct infusion of 1 into the paraventricular nucleus of the hypothalamus of rats significantly inhibits food intake, implicating the role of 5-HT1B receptors in regulating feeding behavior in rodents. 3-(1,2,5,6-Tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (1) has also been shown to be biochemically discriminatory in its ability to selectively inhibit forskolin-stimulated adenylate cyclase activity only at the 5-HT1B receptor. The source of the selectivity of 1 appears to lie in the ability of a pyrrolo[3,2-b]pyrid-5-one to act as a rotationally restricted bioisosteric replacement for 5-hydroxyindole.

Adenylyl Cyclase Inhibitors

Correlation of brain levels of 9-amino-1,2,3,4-tetrahydroacridine (THA) with neurochemical and behavioral changes.

9-Amino-1,2,3,4-tetrahydroacridine (THA) has been reported to cause improvement in patients with senile dementia of the Alzheimer's type. We have examined some effects of THA in vitro and in vivo to define its mechanism of action. In vitro, THA inhibits acetylcholinesterase (AChE) (IC50 = 223 nM) and blocks [3H]AFDX-116 (M2) and [3H]telenzepine (M1) binding (IC50 s of 1.5 and 9.1 microM respectively). In vivo levels of THA were 10-fold higher in brain than plasma following 3.2 mg/kg i.p., a dose which was found to be active in reversing amnesia induced by scopolamine assessed in T-maze tests in rats and passive avoidance tests in mice. Additionally, these brain concentrations were above the IC50 of THA for AChE inhibition. THA (5.6-17.8 mg/kg i.p.) also elevated acetylcholine levels in the rat CNS. THA-induced side effects were blocked by the central muscarinic antagonist, scopolamine, but not by the peripheral antagonists methscopolamine and glycopyrrolate, nor by nicotinic antagonists. We conclude that brain AChE inhibition by THA is sufficient to explain its purported therapeutic activity in Alzheimer's disease and that its favorable brain/plasma distribution in vivo may account for its central cholinergic action without inducing the severe peripheral cholinergic effects typically seen with other AChE inhibitors.

Acetylcholinesterase

Stressful life events preceding the acute onset of schizophrenia: a cross-national study from the World Health Organization.

This study reports on the findings from a WHO sponsored cross-national investigation of life events and schizophrenia. Data are presented from a series of 386 acutely ill schizophrenic patients selected from nine field research centers located in developing and developed countries (Aarhus, Denmark; Agra, India; Cali, Colombia; Chandigarh, India; Honolulu, USA; Ibadan, Nigeria; Nagasaki, Japan; Prague, Czechoslovakia; Rochester, USA). On a methodological level, the study demonstrates that life event methodologies originating in the developed countries can be adapted for international studies and may be used to collect reasonably reliable and comparable cross-cultural data on psychosocial factors affecting the course of schizophrenic disorders. Substantive findings replicate the results of prior studies which conclude that socioenvironmental stressors may precipitate schizophrenic attacks and such events tend to cluster in the two to three week period immediately preceding illness onset.

Adolescent

Comfort care: an alternative treatment programme for seriously burned patients.

Modern intensive care is capable of keeping burned patients alive for substantial periods of time, despite burn severity with an 'unprecedented' or a marginal probability of survival. When the patient is initially judged to be that severely injured, or when, later in the course of the illness, a point is reached when further curative treatment is clearly futile (Civetta, 1981), the patient and/or the close relatives should be presented with the option of changing the treatment regimen from curative to comfort care. We (Frank and Wachtel, 1984) have described a process for reaching such decisions and a protocol for administering comfort care. During a 5-year period we offered this option to 24 patients. This paper reports the outcome in these cases.

Adult

Effects of acute and chronic bupropion on locomotor activity and dopaminergic neurons.

Acute administration of bupropion (10 or 30 mg/kg) to rats increased locomotor activity in a dose-related manner. The highest dose increased the dopamine (DA) concentration while both doses reduced the concentration of dihydroxyphenylacetic acid (DOPAC) in the striatum. The enhancement of locomotor activity and the decrease of striatal DOPAC concentrations were increased with chronic administration (up to 40 days) of bupropion. The rate of DA synthesis in the striatum was increased by the acute administration of d-amphetamine but was not altered by acute or chronic administration of bupropion.

3,4-Dihydroxyphenylacetic Acid

Cathinone affects dopamine and 5-hydroxytryptamine neurons in vivo as measured by changes in metabolites and synthesis in four forebrain regions in the rat.

Cathinone is an active ingredient in the leaves of the Khat shrub. Cathinone affects behavior, neurochemistry and electrophysiology in a manner similar to the stimulants amphetamine, cocaine and methylphenidate. The present study extended these studies by evaluating the effects of (+/-)cathinone on dopamine (DA) and 5-hydroxytryptamine (5-HT)-containing neurons in several regions of the rat brain in vivo. An index of the rate of synthesis of DA and 5-HT in vivo was determined in the nuclei caudatus putamen (CP), accumbens (NA), amygdaloideus centralis (AC), septi lateralis (SL), preopticus pars suprachiasmatica (PSCN) and dorsomedialis (hypothalami; DMN) of male rats (175-225 g) by measuring the concentration of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) after the administration of NSD 1015 (100 mg/kg, i.p.) an inhibitor of aromatic L-amino acid decarboxylase. Concentrations of DA, 5-HT and their major metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA), respectively, were analyzed by high pressure liquid chromatography coupled to an electrochemical detector. Cathinone decreased levels of DOPAC in a time- and dose-related manner in the caudatus putamen, accumbens, amygdaloideus centralis and septi lateralis with the peak effect occurring 30-60 min after a dose of 6 mg/kg (i.p.). Cathinone had no effect on DOPAC in the preopticus pars suprachiasmatica or dorsomedialis (hypothalami). The drug also decreased the accumulation of DOPA in the caudatus putamen, accumbens, amygdaloideus centralis and septi lateralis, but in the preopticus pars suprachiasmatica and dorsomedialis (hypothalami), there was no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid

Indomethacin facilitates acute tolerance to and dependence upon morphine as measured by changes in fixed-ratio behavior and rectal temperature in rats.

The effects of indomethacin, a prostaglandin (PG) synthetase inhibitor, on acute tolerance to and dependence on morphine were investigated. Twelve mature, male Long-Evans rats were trained to lever press for food reinforcement on a fixed-ratio 30 schedule (FR 30 behavior) and have their rectal temperature taken. The experimental protocol began with taking the rat's temperature followed by a 30 minute behavioral session. Immediately after this session the animal was injected with indomethacin or its vehicle. Two-and-a-half hours later this procedure was repeated, except that morphine or saline was administered. After an additional 2.5 hours had elapsed, a 60 minute behavioral session occurred. Half-way through the session the rat was injected with morphine (tolerance), naloxone (dependence), or saline. Immediately after the session the rat's temperature was recorded. Indomethacin potentiated the acute tolerance to the behavioral suppressant and hyperthermic effects of morphine. Indomethacin pretreatment also greatly enhanced the capacity of naloxone to decrease temperature and suppress FR 30 behavior in morphine-treated rats. These effects were not due to indomethacin altering the acute effects of morphine or the amount of morphine in the brain. These data suggest that indomethacin is inhibiting synthesis of PGs which are important in morphine tolerance and dependence.

Animals