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Biomedical subjects

K Rasmussen

Publications and source records attributed to K Rasmussen.

At least 37 records · Page 2Linked to original sources

Is There a Causal Relationship between Iron Deficiency or Iron-Deficiency Anemia and Weight at Birth, Length of Gestation and Perinatal Mortality?

An extensive literature review was conducted to identify whether iron deficiency, iron-deficiency anemia and anemia from any cause are causally related to low birth weight, preterm birth or perinatal mortality. Strong evidence exists for an association between maternal hemoglobin concentration and birth weight as well as between maternal hemoglobin concentration and preterm birth. It was not possible to determine how much of this association is attributable to iron-deficiency anemia in particular. Minimal values for both low birth weight and preterm birth occurred at maternal hemoglobin concentrations below the current cut-off value for anemia during pregnancy (110 g/L) in a number of studies, particularly those in which maternal hemoglobin values were not controlled for the duration of gestation. Supplementation of anemic or nonanemic pregnant women with iron, folic acid or both does not appear to increase either birth weight or the duration of gestation. However, these studies must be interpreted cautiously because most are subject to a bias toward false-negative findings. Thus, although there may be other reasons to offer women supplemental iron during pregnancy, the currently available evidence from studies with designs appropriate to establish a causal relationship is insufficient to support or reject this practice for the specific purposes of raising birth weight or lowering the rate of preterm birth.

Anemia↗

Attention deficit hyperactivity disorder, reading disability, and personality disorders in a prison population.

Attention Deficit Hyperactivity Disorder (ADHD) has long been recognized in children, and for many the disorder persists into adulthood. There is a growing concern that the adults with ADHD who have the least favorable outcome, are among those who end up in prison. The aim of this study was to assess childhood ADHD and its persistence into adulthood among a representative sample of Norwegian prison inmates, as well as personality disorders and reading difficulties, which in previous studies have been linked to ADHD. The results indicate that persistent ADHD is very common among prison inmates. Personality disorders and reading difficulties are also common. Psychiatric comorbidity complicates the diagnosis of ADHD in adults. A greater awareness about ADHD in adults certainly is warranted, especially within the prison system because of the risk of misdiagnosing psychiatric disorders and also the risk of missing a condition possibly amenable to treatment.

Adult↗

[DANAMI. A Danish study of invasive versus conservative treatment of patients with post-infarction ischemia who had received thrombolytic therapy].

INTRODUCTION: To compare an invasive strategy employing percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass grafting (CABG) with a medical strategy in patients who had received thrombolytic treatment for first acute myocardial infarction (AMI), and with signs of inducible ischaemia. METHODS: In a prospective study 1008 patients were randomized, 503 to invasive treatment, of whom 266 (52.9%) had PTCA, and 147 (29.2%) CABG, 505 to conservative treatment, of whom eight (1.6%) were revascularized within two months. RESULTS: After a median follow-up of 2.4 years the mortality in the invasive group was 3.6% vs. 4.4% (p = 0.45) in the conservative group, re-infarction incidence was 5.6% vs. 10.5% (p = 0.0038) and percentage of admissions with unstable angina was 17.9% vs. 29.5% (p < 0.00001). DISCUSSION: We conclude that post-infarct patients with inducible ischaemia should be referred to coronary angiography and revascularised accordingly.

Adult↗

[Clinical studies on glycoprotein IIb/IIIa receptor antagonist].

Platelet activation plays a major role in the pathophysiology of acute coronary syndromes (ACS), and inhibition of platelet function is the basic pharmacological treatment of ACS. Platelet membrane glycoprotein IIb/IIIa inhibitors, a new class of potent antiplatelet agents, have been used in the treatment of ACS, as well as in the prevention of complications after percutaneous coronary interventions. The aim of this article is to describe the potential possibilities of platelet inhibition and to review the pharmacology of glycoprotein IIb/IIIa inhibitors, the results of the clinical trials with these agents, and their current use in the pharmacological treatment of ACS and in relation to percutaneous coronary intervention.

Controlled Clinical Trials as Topic↗

Moxonidine, a selective imidazoline-1 receptor agonist, suppresses the effects of ethanol withdrawal on the acoustic startle response in rats.

BACKGROUND: There is a need for improved treatments for ethanol withdrawal in humans. Previously, ethanol withdrawal has been shown to enhance the acoustic startle response in rats. Because many ethanol withdrawal symptoms are caused by autonomic hyperactivity, we examined the effects of two antihypertensives, the imidazoline(I)(1) agonist moxonidine and the alpha(2)-adrenergic partial agonist clonidine, on the ethanol-withdrawal-enhanced acoustic startle response in rats. d-amphetamine-enhanced startle served as a positive control. METHODS: Male, Long-Evans rats were made ethanol-dependent through unlimited access to liquid diet containing 6.7% v/v ethanol for 10 days. The concentration of ethanol was reduced to 3.3% v/v on the 11th day. On the 12th day, the rats received control diet. The acoustic startle response was tested 24 hours following the withdrawal of ethanol. Control rats were maintained on control liquid diet throughout the experiment. RESULTS: As has been shown previously, withdrawal from the chronic ingestion of ethanol significantly enhanced the acoustic startle response. Pretreatment with moxonidine (0.01, 0.1, and 1.0 mg/kg, subcutaneously), but not clonidine (0.3, 1.0, and 3.0 mg/kg, subcutaneously), significantly attenuated the ethanol withdrawal-induced elevation of the acoustic startle response. Moxonidine did not suppress the elevation in the startle response caused by d-amphetamine. CONCLUSIONS: These results indicate that I(1) receptors can play an important role in ethanol withdrawal and that moxonidine may be useful for the treatment of ethanol withdrawal in humans.

Animals↗

Xanomeline, an M(1)/M(4) preferring muscarinic cholinergic receptor agonist, produces antipsychotic-like activity in rats and mice.

Xanomeline is an M(1)/M(4) preferring muscarinic receptor agonist which decreased psychotic behaviors in patients with Alzheimer's disease, suggesting that xanomeline might be useful in the treatment of psychotic symptoms in patients with schizophrenia. The purpose of the present studies was, therefore, to compare the pharmacologic profile of xanomeline with that of known antipsychotic drugs. Electrophysiologically, xanomeline, after both acute and chronic administration in rats, inhibited A10 but not A9 dopamine cells in a manner which was blocked by the muscarinic receptor antagonist scopolamine. Behaviorally, xanomeline, like haloperidol, clozapine and olanzapine, blocked dopamine agonist-induced turning in unilateral 6-hydroxydopamine-lesioned rats, as well as apomorphine-induced climbing in mice. However, unlike the dopamine antagonist antipsychotic haloperidol, xanomeline did not produce catalepsy in rats. Moreover, xanomeline, like haloperidol, clozapine and olanzapine, inhibited conditioned avoidance responding in rats, an effect which also was blocked by scopolamine. The present results thus demonstrate that xanomeline has a pharmacologic profile which is similar to that of the atypical antipsychotics clozapine and olanzapine, thus indicating that xanomeline has the potential to be a novel approach in the treatment of psychotic symptoms in patients with schizophrenia.

Alzheimer Disease↗

[Epoxy in occupational environment--an old acquaintance in a new dress].

This article describes a cluster of epoxy related contact dermatitis in a glassfibre reinforcement plant, using mostly preimpregnated epoxylaminate (Pre-Preg), but also fluid epoxy-products. An occupational medical and dermatological examination revealed nine of 26 cases as allergic contact eczema, 14 as toxic epoxyrelated eczema and three cases of other non-occupationally related skin diseases. The plant uses seven different epoxyresins with 15 epoxyhardeners. Preventive measures were gradually improved, but even then it was difficult to rule the production into safe procedures with this potent allergen used in large scale production of windmill wings.

Denmark↗

Incidence of unintentional injuries in farming based on one year of weekly registration in Danish farms.

BACKGROUND: In Denmark, farming ranks as the industry with the highest incidence rate of fatal injuries. For nonfatal injuries, insufficient registration practices prevent valid comparisons between occupations. This study examines the occurrence of farm accidents and injuries, as well as work-specific factors, via weekly registration in a representative sample of 393 farms in one county during 1 year. METHODS: From a random sample of 794 farms, (10% of farms in the county of Ringkoebing, Denmark) 393 farms with 1,597 residents and employees participated in a 1-year self-registration of work-related unintentional incidents. The procedure included a detailed registration of hours spent on all main working tasks. Weekly recording of incident occurrence or nonoccurrence resulted in the completion of 19,782 registration forms. Three months after incident occurrence, a telephone interview was conducted about the related work situation and resulting injuries. RESULTS: During the 12-month period, 479 occupational accidents were reported, of which 389 resulted in an injury. The absolute number of injuries increased with number of work hours, but there was no relative increase of incidence by work hours. Persons below the age of 50 had slightly less than a doubled risk compared with those over 50 years of age. No other marked, reliable age effect was found. There was, however, a seasonal variation, with summer and autumn having a double relative incidence compared with winter and spring. Among farm owners, 35% experienced at least one injury per year, while this was the case for 17% of farm laborers. When adjusting for work hours, the increased frequency of injuries among farm owners was reduced to a factor of 1.5. Animal-related work was the most common injury mechanism. Repair and maintenance work was found to be the most dangerous task relative to the number of task-specific work hours. Subgroups of tasks with a markedly increased injury rate were moving animals within the farm, veterinary procedures, and repair of field machinery and stable equipment. CONCLUSIONS: Farm injuries occur among 32% of full-time farmers and farm laborers each year. A quarter of these require professional treatment. This area calls for preventive action.

Accidents, Occupational↗

Effects of acute and chronic administration of fluoxetine on the activity of serotonergic neurons in the dorsal raphe nucleus of the rat.

The gradual recovery of activity of serotonergic neurons following an initial inhibition has been hypothesized to play an important role in the delayed onset of efficacy of selective serotonin reuptake inhibitors. This study explored the clinical relevance of this hypothesis by examining the effects of different doses and routes of administration of fluoxetine on the recovery of activity of serotonergic neurons over the course of a 21-day exposure. Single-unit, extracellular recordings of serotonergic neurons were made in the dorsal raphe nucleus of anesthetized male rats. Acute i.v., s.c. and i.p. administration of fluoxetine inhibited the activity of serotonergic neurons. With chronic administration of fluoxetine, at clinically relevant doses, the activity of serotonergic neurons gradually recovered to baseline levels over the course of 14-21 days. The dose of fluoxetine (5, 10 or 20 mg/kg per day) did not make a significant difference in the time course of the recovery of activity of serotonergic neurons. A significant, non-parallel shift in the dose-response curve of serotonergic neurons to the serotonin-1A (5-HT1A) agonist 8-OH-DPAT occurred over the 21 days of treatment with fluoxetine, indicating a desensitization of the 5-HT1A receptor during this period. The recovery of firing did not correlate with either plasma or cerebrospinal fluid levels of fluoxetine or norfluoxetine. These results indicate that, similar to the effects of dose on the speed of onset of the clinical effects of SSRIs, increasing the dose of fluoxetine does not hasten the recovery of firing of serotonergic neurons during chronic administration. These results support the hypothesis that desensitization of the 5-HT1A receptor and consequent recovery of firing of 5-HT cells in the dorsal raphe nucleus plays a role in the delayed therapeutic onset of fluoxetine.

Animals↗

Activation of the mesocorticolimbic dopaminergic system by stimulation of muscarinic cholinergic receptors in the ventral tegmental area.

OBJECTIVE: To investigate the function of muscarinic receptors in the ventral tegmental area in vivo, the release of endogenous monoamines was simultaneously measured in the somatodendritic (ventral tegmental area) and terminal (frontal cortex and nucleus accumbens) regions of the mesocorticolimbic dopaminergic system in rats, using dual probe microdialysis. METHODS: Rats were implanted with dual microdialysis probes ipsilaterally into the ventral tegmental area (VTA) and nucleus accumbens (NAC) or frontal cortex (FC). RESULTS: Intrategmental infusion of the muscarinic agonist oxotremorine M (OXO M, 0.1 and 1 mM) increased extracellular levels of dopamine and serotonin, but not noradrenaline, in the VTA to a maximum of 200% over baseline in both urethane-anaesthetized and unanaesthetized rats. In freely moving animals, this effect was accompanied by strong motor agitation. Both VTA dopamine and serotonin levels dropped to 60% or less of baseline when the perfusion medium was replaced by a calcium-free medium containing OXO M. In the NAC and FC, a similar increase in extracellular dopamine, but not serotonin and noradrenaline, was observed during OXO M infusion in the VTA. The removal of calcium during OXO M infusion in the VTA did not cause a decrease in NAC dopamine levels. Activation of serotonin and dopamine release by OXO M in the VTA and FC was dramatically reduced or prevented by the co-infusion of the muscarinic antagonist N-methylscopolamine (0.1 mM). CONCLUSION: These data demonstrate that VTA dopamine cells possess functional muscarinic receptors whose activation stimulates the release of dopamine in the VTA, NAC and FC. These results also suggest that muscarinic receptors may modulate the synaptic release of serotonin in the VTA.

Animals↗

Relationship between methylmalonic acid and cobalamin in uremia.

UNLABELLED: Relationship between methylmalonic acid and cobalamin in uremia. BACKGROUND: To evaluate the requirement for routine supplementation with vitamin B12 and to study the effect of a change from injection to oral B12 supplementation, we examined the relationship between cobalamin and methylmalonic acid in plasma from 67 patients on chronic hemodialysis, all in regular therapy with intramuscular cobalamin injections (1 mg) every third month. METHODS: Starting just before one cobalamin injection, blood samples were collected once a month during a nine-month withdrawal from regular cobalamin substitution to a final three-month period with cyanocobalamin tablets (1 mg) administered once daily. RESULTS: Plasma cobalamin was above the lower reference limit in all subjects, and from a peak value one month after the regular injection, the cobalamin concentration during the withdrawal period decreased to a level below the point of origin, followed by a significant rise after cyanocobalamin tablets. The methylmalonic acid concentrations were above the reference interval. In the withdrawal period, the concentrations significantly increased further, followed by a significant decrease after oral cyanocobalamin substitution. CONCLUSION: We demonstrated a within-patient inverse relationship between the concentrations of methylmalonic acid and cobalamin in plasma from these uremic patients. Despite the fact that only two of the patients developed subnormal plasma cobalamin values, we demonstrated a B12 depletion during the withdrawal period. Treatment with cyanocobalamin tablets once daily was found efficient, but the oral doses should possibly be increased.

Adult↗

Mitral flow derived Doppler indices of left ventricular diastolic function in a general population; the Tromso study.

AIMS: Left ventricular diastolic dysfunction has been proposed as the basis of heart failure in patients with normal left ventricular systolic function. Doppler indices of mitral inflow have been widely used to diagnose this condition and have been shown to correlate well with increased left atrial pressure in patients with cardiovascular disease. We wanted to establish age-specific criteria for normality of these indices in a large population and to determine the association of abnormal values to age and cardiovascular disease. METHODS AND RESULTS: In our sample of subjects aged 25-85 years, 3022 had pulsed Doppler measurements of mitral inflow velocities and early inflow deceleration time. The association of these indices to age and gender were established in a 'healthy' reference subsample of 949 subjects. Age-specific percentiles showed a significant decline with increasing age for peak early mitral inflow velocity and the ratio of peak early and atrial inflow velocities (E/A ratio), whereas early inflow deceleration time and peak atrial inflow velocity showed a significant increase with increasing age. According to current criteria for diastolic dysfunction, the prevalence of dysfunction decreases with increasing age in the general population, as well as in the subgroup with cardiovascular disease. Only 7% of the variance in deceleration time was explained by cardiovascular disease or risk factors. For the E/A ratio, however, 41 and 48% of the variance were explained for men and women, respectively. CONCLUSION: Age- and gender-specific criteria for normality are provided. Our data confirm the existence of a significant effect of age and gender on mitral Doppler indices of diastolic dysfunction. However, Doppler criteria for diastolic dysfunction based on these measurements need revision.

Adult↗

DGGE analysis of the coproporphyrinogen oxidase gene: two new mutations in DNA from Danish patients with hereditary coproporphyria.

The knowledge of at least 21 different mutations and several polymorphisms in the coproporphyrinogen oxidase (CPO) gene demonstrates that the molecular basis of hereditary coproporphyria is heterogeneous. We developed a DGGE-based assay for the analysis of exons 2 to 7, including 14-96 nucleotides of the flanking intronic sequences of the CPO gene. To render it suitable for the clinical diagnostic laboratory, we designed the assay to allow use of identical PCR conditions and the same DGGE gel for analyses of all the regions. Using this assay, and subsequent sequencing of gene regions containing interallelic variations, two novel mutations in the CPO gene were identified: a missense mutation (607G-->A), leading to the substitution of an alanine with a threonine, and a nonsense mutation (1281G-->A), giving rise to a stop codon 28 codons upstream to the wild-type stop codon.

Amino Acid Sequence↗

Percutaneous transluminal coronary angioplasty versus thrombolysis in acute myocardial infarction.

The aim of this study was to evaluate the outcome of primary percutaneous transluminal coronary angiography (PTCA) in the treatment of acute myocardial infarction (AMI) The study included patients with electrocardiographic signs of transmural AMI, symptom duration of less than 12 h, and with no contraindications to thrombolytic therapy. Patients who had undergone primary PTCA were matched consecutively, for age, gender, infarct localization and duration of symptoms, to patients who had received thrombolytic therapy (82 patients to each group). Patients who were admitted to hospital during daytime had a primary PTCA, whereas those admitted outside daytime were given thrombolytic therapy. In the primary PTCA group, 9 patients had a combined endpoint compared with 22 patients in the thrombolysis group (p < 0.02 ). In-hospital mortality was 3.7% in the PTCA group and 4.9% in the thrombolysis group (ns). At six months, a combined endpoint occurred in 23 patients in the primary PTCA group and in 50 patients in the thrombolysis group (p < 0.00005). Six months' mortality was 4.9% in the PTCA group and 7.3% in the thrombolysis group (ns). Among patients in the PTCA group, left ventricular ejection fraction was significantly higher, stay in hospital was shorter and there were significantly fewer incidences of heart failure and severe arrhythmias than among patients in the thrombolysis group. The results of primary PTCA implemented in our departments are comparable with those reported in randomized trials from experienced centres. Our study indicates that patients treated with primary PTCA have fewer complications, a better left ventricular systolic function and a shorter hospital stay compared with patients treated with thrombolysis.

Adult↗

Disease associated balanced chromosome rearrangements: a resource for large scale genotype-phenotype delineation in man.

Disease associated balanced chromosomal rearrangements (DBCRs), which truncate, delete, or otherwise inactivate specific genes, have been instrumental for positional cloning of many disease genes. A network of cytogenetic laboratories, Mendelian Cytogenetics Network (MCN), has been established to facilitate the identification and mapping of DBCRs. To get an estimate of the potential of this approach, we surveyed all cytogenetic archives in Denmark and southern Sweden, with a population of approximately 6.6 million. The nine laboratories have performed 71 739 postnatal cytogenetic tests. Excluding Robertsonian translocations and chromosome 9 inversions, we identified 216 DBCRs ( approximately 0.3%), including a minimum estimate of 114 de novo reciprocal translocations (0.16%) and eight de novo inversions (0.01%). Altogether, this is six times more frequent than in the general population, suggesting a causal relationship with the traits involved in most of these cases. Of the identified cases, only 25 (12%) have been published, including 12 cases with known syndromes and 13 cases with unspecified mental retardation/congenital malformations. The remaining DBCRs were associated with a plethora of traits including mental retardation, dysmorphic features, major congenital malformations, autism, and male and female infertility. Several of the unpublished DBCRs defined candidate breakpoints for nail-patella, Prader-Willi, and Schmidt syndromes, ataxia, and ulna aplasia. The implication of the survey is apparent when compared with MCN; altogether, the 292 participating laboratories have performed >2.5 million postnatal analyses, with an estimated approximately 7500 DBCRs stored in their archives, of which more than half might be causative mutations. In addition, an estimated 450-500 novel cases should be detected each year. Our data illustrate that DBCRs and MCN are resources for large scale establishment of phenotype-genotype relationships in man.

Chromosome Aberrations↗

Familial thrombophilia associated with homozygosity for the cystathionine beta-synthase 833T-->C mutation.

Severe hyperhomocysteinemia due to cystathionine beta-synthase (CBS) deficiency is a strong risk factor for premature cardiovascular disease. Among untreated patients, approximately 50% have suffered a thromboembolic event by 30 years of age. We report on 3 sisters with severe hyperhomocysteinemia due to homozygosity for the CBS 833T-->C mutation. These patients, who displayed no other known thrombophilic predisposition, had suffered single or multiple venous thrombosis before CBS deficiency was diagnosed relatively late in life. In this family, homozygosity for the 833T-->C mutation was associated with a mild phenotype with respect to other sequelae of CBS deficiency. Consequently, our results indicate that most cases with this genotype may remain undiagnosed. Investigated family members heterozygous for the 833T-->C mutation displayed normal total homocysteine in plasma (tHcy) levels, even when they were homozygous for the methylenetetrahydrofolate reductase 677C-->T polymorphism. The prevalence of homozygosity for the 833T-->C mutation has previously been estimated at no less than 1:20 500 in our population. Because a reduction of the severely elevated levels of tHcy in CBS deficiency reduces cardiovascular risk and because homozygosity for the 833T-->C mutation is more prevalent than previously thought, our results emphasize the importance of measuring tHcy routinely in thrombophilia screening.

Cardiovascular Diseases↗