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K Rasmussen

Publications and source records attributed to K Rasmussen.

At least 19 recordsLinked to original sources

Effects of short-term and chronic olanzapine treatment on immediate early gene protein and tyrosine hydroxylase immunoreactivity in the rat locus coeruleus and medial prefrontal cortex.

Atypical antipsychotic drugs, such as olanzapine, have been reported to activate the locus coeruleus (LC) and lead to acute expression of the Fos-like immediate early gene (IEG) protein in the LC and medial prefrontal cortex (mPFC). Stimuli that activate the LC have been reported to increase expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. However, the effects of chronic treatment with olanzapine on IEG expression and the dose-dependence of the effects of olanzapine on IEG and TH expression are not known. Thus, we examined Fos-like, c-Jun, activating transcription factor 2 (ATF-2), early growth response 1 (Egr-1), early growth response 2 (Egr-2), and TH immunoreactivity expression in the LC and mPFC in rats receiving 2, 4, 8, or 15 mg/kg/day olanzapine by s.c. osmotic minipump for 4 h, 1 week, 2 weeks, or 4 weeks. ATF-2 expression was up-regulated at all treatment durations, while Egr-1 and Egr-2 were down-regulated in both the LC and mPFC. Fos-like expression was up-regulated through 2 weeks, but not 4 weeks, in both the LC and mPFC. C-Jun expression was up-regulated for 4 weeks in the LC and for 2 weeks, but not 4 weeks, in the mPFC. At all doses, there were rapid and sustained increases in TH immunoreactivity in the LC, but only delayed increases in the mPFC. These data indicate that olanzapine has rapid effects on IEG in the LC and mPFC, many of which are sustained through four weeks of treatment. Further, these data indicate that the delayed increase in TH expression in the mPFC parallels, and may play an important role in, the increased efficacy of olanzapine that emerges over time in humans.

Analysis of Variance↗

Predictive value of parathyroid scintigraphy in the preoperative evaluation of patients with primary hyperparathyroidism.

BACKGROUND AND AIMS: The surgical gold standard in primary hyperparathyroidism was until recently exploration of all four parathyroid glands. Today more patients undergo minimal invasive procedures demanding more accurate preoperative localization studies. The aim of the study was to determine the positive predictive value (PPV) of parathyroid scintigraphy (PS) and to some extent ultrasonography (US), defined as the probability of finding one single adenoma on the affected side at surgery when the scans had shown one single focus. MATERIAL AND METHODS: Eighty-eight surgically treated patients (76 women and 12 men, 8 with multiglandular disease) were included. The PS consisted of 99mTc-sestamibi scan with dual-phase technique, both planar and SPECT imaging, followed by 99mTc-pertechnetate scan. A positive scan was defined as a single focus accumulating sestamibi. Focal lesions on US were defined as hypoechoic nodules. RESULTS: PS was positive in 80 patients. Seventy-nine had only one focus, of which 64 were correctly localized adenomas (PPV 81%). Forty-seven of 77 US examinations were positive. In 44 there was only one focus of which 38 were correctly localized (PPV 86%). PPV was 97% when both examinations were positive. CONCLUSIONS: Both PS and US have acceptably high PPVs defined as the ability to predict whether or not one single focus represents a parathyroid adenoma. Concordant positive results were accompanied by a PPV close to 100%.

Adult↗

Risk of contact allergy and dermatitis at a wind turbine plant using epoxy resin-based plastics.

AIMS: To identify workplace and individual risk factors for occupational contact allergy and dermatitis. METHODS: A cross-sectional study was carried out at an international company producing wind turbine systems in Denmark. A cohort of 724 production workers at four facilities was highly exposed to epoxy resin as well as other chemicals. A screening questionnaire (participation rate 84.7%) was followed by an interview by an occupational physician and a dermatological examination, including patch testing, for a comprehensive list of potential workplace sensitizers. RESULTS: Clinically diagnosed dermatitis was found among 214 workers (35.8%) and contact allergy to materials used in the workplace was found in 66 workers (10.9% of the total population and 20.3% of those who underwent patch testing). Of the 66 workers with a work-related allergy, 40 (60.6%) were allergic to epoxy compounds, 25 (37.9%) to hardeners and ten (15.2%) to other workplace materials, where one person showed an allergy only to these materials. Experiencing contact allergy was related to older age and longer employment in the workplace-however, neither of these risk factors was significant. The main risk factor for current dermatitis was contact allergy to materials used in the workplace, determined by patch testing, OR=5.4 (95% CI 3.9-9.9). Fewer days of absence from work was also related to current dermatitis, OR=2.0 (95% CI 1.2-3.5). CONCLUSIONS: In a cohort of workers with extensive exposure to chemicals related to epoxy-resin systems, contact dermatitis and allergy was prevalent. Older age and longer duration of employment at the workplace were individual risk factors for allergy to workplace materials, whilst work-related allergies and longer duration of employment at the workplace were significant risk factors for current dermatitis.

Adolescent↗

An analysis of PAX1 in the development of vertebral malformations.

An analysis of PAX1 in the development of vertebral malformations. Due to the sporadic occurrence of congenital vertebral malformations, traditional linkage approaches to identify genes associated with human vertebral development are not possible. We therefore identified PAX1 as a candidate gene in vertebral malformations and congenital scoliosis due to its mutation in the undulated mouse. We performed DNA sequence analysis of the PAX1 gene in a series of 48 patients with congenital vertebral malformations, collectively spanning the entire vertebral column length. DNA sequence coding variants were identified in the heterozygous state in exon 4 in two male patients with thoracic vertebral malformations. One patient had T9 hypoplasia, T12 hemivertebrae and absent T10 pedicle, incomplete fusion of T7 posterior elements, ventricular septal defect, and polydactyly. This patient had a CCC (Pro)-->CTC (Leu) change at amino acid 410. This variant was not observed in 180 chromosomes tested in the National Institute of Environmental Health Sciences (NIEHS) single nucleotide polymorphism (SNP) database and occurred at a frequency of 0.3% in a diversity panel of 1066 human samples. The second patient had a T11 wedge vertebra and a missense mutation at amino acid 413 corresponding to CCA (Pro)-->CTA (Leu). This particular variant has been reported to occur in one of 164 chromosomes in the NIEHS SNP database and was found to occur with a similar frequency of 0.8% in a diversity panel of 1066 human samples. Although each patient's mother was clinically asymptomatic and heterozygous for the respective variant allele, the possibility that these sequence variants have clinical significance is not excluded.

Base Sequence↗

Epoxy-based production of wind turbine rotor blades: occupational dermatoses.

Occupational dermatoses were investigated in a factory producing rotor blades for wind turbines by an epoxy-based process. In a blinded study design, 603 workers were first interviewed and thereafter clinically examined. Based on a history of work-related skin disease, clinical findings of dermatitis, or both, 325 (53.9%) of the workers were patch tested with a specially profiled occupational patch-test series and the European standard patch-test series. Calculated on all investigated workers, 17.1% of the workers were diagnosed with occupational dermatoses caused by work. Occupational allergic contact dermatitis was found in 10.9% of the workers. The estimated frequency of irritant contact dermatitis caused by work was 6.1%. Dermatitis on the hands was associated with contact allergy to epoxy resin (P = 0.017). The number of days on leave before the clinical examination was negatively associated with the presence of dermatitis (P = 0.001). Among workers employed 7-12 months, the frequency of occupational contact allergy was higher than that among workers employed for </=6 months (P = 0.004). Females both washed their hands more often (P < 0.001) and used more moisturizers/protection creams at work (P < 0.001) than males. No sex differences were found concerning dermatitis on the hands.

Adolescent↗

Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is a rare disorder with one per 6000-10,000 affected individuals in the general Caucasian population. HHT is genetically heterogeneous, involving at least two loci HHT1 mapping to chromosome 9q34.1 and HHT2 mapping to chromosome 12q31. The loci have been identified as endoglin (ENG) and activin receptor-like kinase 1 (ALK1). In order to gain knowledge of the genotype distribution and prevalence in the Danish population and to establish a reproducible and sensitive molecular genetic test method, we developed a denaturating gradient gel electrophoresis protocol for mutation scanning of the two loci. Twenty-five Danish HHT families were tested. A total of eight new as well as seven previously reported mutations were identified. A founder mutation was characterized present in seven families and possibly introduced around 350 years ago. In one individual, a presumed spontaneous mutation was characterized. The method developed proved to be very sensitive for mutation detection in both ENG and ALK1. Genetic screening in HHT families facilitates an early treatment strategy for silent HHT manifestations in first degree relatives.

Activin Receptors, Type I↗

Evidence that central 5-HT2A and 5-HT2B/C receptors regulate 5-HT cell firing in the dorsal raphe nucleus of the anaesthetised rat.

1. Systemic administration of phenethylamine-derived, 5-hydroxytryptamine(2) (5-HT(2)) receptor agonists inhibits the firing of midbrain 5-HT neurones, but the 5-HT receptors involved are poorly defined, and the contribution of peripheral mechanisms is uncertain. This study addresses these issues using extracellular recordings of 5-HT neurones in the dorsal raphe nucleus of anaesthetised rats. 2. The 5-HT(2) receptor agonists DOI ((+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride) and DOB ((+/-)-2,5-dimethoxy-4-bromoamphetamine hydrobromide), caused a dose-related (10-100 micro g kg(-1) i.v.) inhibition of 5-HT neuronal activity, with the highest dose reducing firing rates by >80%. 3. Pretreatment with the 5-HT(2) receptor antagonist ritanserin (1 mg kg(-1) i.v.) completely blocked the action of DOI. The 5-HT(2A) receptor antagonist MDL 100,907 (0.2 mg kg(-1) i.v.) blocked the action of both DOI and DOB. In comparison, the 5-HT(2B/C) receptor antagonist SB 206553 (0.5 mg kg(-1) i.v.) caused a small, but statistically significant, shift to the right in the dose response to DOI and DOB. 4. Pretreatment with the peripherally acting 5-HT(2) receptor antagonist BW 501C67 (0.1 mg kg(-1) i.v.) had no effect on the DOI-induced inhibition of 5-HT cell firing, but completely blocked the DOI-induced rise in mean arterial blood pressure. 5. These data indicate that the inhibition of 5-HT cell firing induced by systemic administration of DOI and DOB is mediated predominantly by the 5-HT(2A) receptor-subtype, but that 5-HT(2B/C) receptors also play a minor role. Moreover, central and not peripheral mechanisms are involved. Given evidence that 5-HT(2) receptors are not located on 5-HT neurones, postsynaptic 5-HT feedback mechanisms are implicated.

Alfaxalone Alfadolone Mixture↗

Pigmentary mosaicism with mosaic chromosome 5p tetrasomy.

Pigmentary mosaicism with mosaic chromosome 5p tetrasomy is described. A 5-year-old girl had phylloid hyperpigmentation segregated in the midline, and neurological deficits. Chromosome analysis performed on blood lymphocytes was normal, whereas skin fibroblasts from affected skin areas revealed chromosomal mosaicism.

Aneuploidy↗

Dimerization of organic free radicals in solution. 1. Temperature dependent measurements.

Dimerization enthalpies and equilibrium constants have been determined for the radical anion of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), the radical cations of N,N,N',N'-tetramethyl-p-phenylenediamine, N,N-dimethyl-p-phenylenediamine, 2,3,5,6-tetramethyl-p-phenylenediamine, N,N,N',N'-tetraethyl-p-phenylenediamine, N,N-diethyl-p-phenylenediamine and N,N,N'-trimethyl-p-phenylenediamine. Neutral radicals investigated are 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and galvinoxyl. Solvent used was acetone, EtOH/Et2O-mixture (2:1 volume), propionitrile/butyronitrile-mixture (1:1 M) and dichloromethane. Measured dimerization enthalpies deltaHdim vary from -72.1 to -16.6 k/mol.

Acetone↗

Renal and cardiac function during alpha1-beta-blockade in congestive heart failure.

UNLABELLED: The kidney and the neurohormonal systems are essential in the pathogenesis of congestive heart failure (CHF) and the physiologic response. Routine treatment of moderate to severe CHF consists of diuretics, angiotensin-converting enzyme (ACE) inhibition and beta-blockade. The need for control of renal function during initiation of ACE-inhibition in patients with CHF is well known. The aim of this study was to investigate whether supplementation by a combined alpha1-beta-blockade to diuretics and ACE-inhibition might improve cardiac function without reducing renal function. METHODS: Fourteen patients treated for moderate to severe CHF with diuretics and ACE inhibitors were investigated at baseline, after 4 months of maximum carvedilol treatment and after withdrawal of carvedilol. RESULTS: Carvedilol lowered blood pressure and heart rate but increased left and right ventricular ejection fractions without changing cardiac output or pulmonary blood volume. At the same time, a minor fall was seen in glomerular filtration rate (GFR). but renal blood flow was unchanged and effective renal plasma flow slightly increased. Carvedilol also lowered the plasma levels of angiotensin II and aldosterone. All changes were reversed after withdrawal of carvedilol. CONCLUSIONS: Carvedilol augments ACE-inhibitor-induced vasodilation by lowering blood pressure, and angiotensin II beside reducing heart rate. The heart adapts to the haemodynamic alterations without changes in cardiac output and pulmonary blood volume. GFR is slightly lowered despite no changes in renal blood flow and a slight increase in effective renal plasma flow. The study emphasizes the need for control of renal function during treatment with carvedilol in patients with CHF.

Adrenergic beta-Antagonists↗

Prepregnancy body mass index in non-diabetic women with and without shoulder dystocia.

OBJECTIVE: To investigate the distribution of prepregnancy body mass index (BMI) in non-diabetic women with and without shoulder dystocia. STUDY DESIGN: Cases were 142 non-diabetic women experiencing shoulder dystocia during the period from 1 January 1993 to 31 December 1999. Shoulder dystocia was defined as the impossibility of delivering the fetal shoulders by standard procedures. Controls were 142 women vaginally delivering during the same period without experiencing shoulder dystocia. Cases and controls were matched for parity (primi-/multipara) and birthweight (+/-250 g). Women with diabetes mellitus, gestational diabetes or a history of shoulder dystocia in a previous birth were excluded. The BMI and selected obstetric data were extracted from an internal database in the department. RESULTS: Delivery was performed using McRoberts maneuvre (42%), Woods screw (50%) or by primary delivery of the posterior arm (8%). Women experiencing shoulder dystocia had significantly more labor augmentation and more instrumental deliveries. No differences were shown in the prevalence of low Apgarscores. The proportion of children with Erbs palsy and clavicular fracture was very close to be significantly different in cases or controls. However, these data does not allow any conclusion. The distribution of BMI was equal in cases and controls. CONCLUSION: Non-diabetic women experiencing shoulder dystocia do not have a higher BMI than non-diabetic women delivering without this experience, given a fixed fetal weight.

Birth Weight↗

Olanzapine activates the rat locus coeruleus: in vivo electrophysiology and c-Fos immunoreactivity.

BACKGROUND: Activation of central noradrenergic pathways by atypical antipsychotics has been hypothesized to play a role in their efficacy in treating the negative symptoms and cognitive impairment of schizophrenia. Because acute administration of the atypical antipsychotic olanzapine has been shown to increase extracellular levels of norepinephrine in the medial prefrontal cortex, we examined the effects of olanzapine on the noradrenergic cells of the locus coeruleus (LC). METHODS: The effects of olanzapine (0.25-16 mg kg(-1), IV) on the firing rates and patterns of LC neurons were determined by extracellular, single-unit recordings in chloral hydrate-anaesthetized rats. The effects of olanzapine and clozapine on c-Fos expression in the LC, nucleus subcoeruleus part alpha (SubCA), and nucleus A5 (A5) were studied by immunohistochemistry. RESULTS: Olanzapine increased LC cell firing rates, de-regularized firing, and induced burst firing. Induction of c-Fos expression in the LC by olanzapine and clozapine was confirmed and was also found in the SubCA, but not in A5. CONCLUSIONS: Acute administration of olanzapine activates the noradrenergic neurons of the rat LC. This increased activity of LC neurons may play an important role in the efficacy of olanzapine and clozapine in treating both the negative symptoms and cognitive impairment observed in schizophrenic patients.

Animals↗

[Homocysteine and cardiovascular disease].

Treatment of highly increased plasma concentrations of homocysteine in patients with rare inborn errors of metabolism reduces their risk of vascular thromboses. Many, but not all, epidemiological studies show a relation between slightly increased plasma homocysteine and ischaemic cardiovascular disease. Folic acid supplements reduce plasma homocysteine. The results of ongoing studies of the effect of folic acid and other vitamins on the incidence of cardiovascular disease are expected within the next five years. The available data support the measurement of plasma homocysteine as a part of screening of patients with early and/or frequent vascular thromboses and a disparity between established risk factors and symptoms. Plasma homocysteine > 30 mumol/l in such patients should prompt a search for an inborn error of metabolism.

Amino Acid Metabolism, Inborn Errors↗

[Audiometric surveillance of occupational environment].

Noise levels in Danish workplaces at which hearing impairment will occur in more than 10% of the workers are still frequent. Annually 300 cases are compensated for noise induced hearing loss at a national level. This may indicate that the current national hearing protection strategy, which relies on noise reduction only, is insufficient. By audiometric screening early hearing loss will be detected and further progression may be halted. This paper reviews the methods of continuous audiometric screening of noise exposed worker populations. Reliability and validity are discussed, and an overview of quality assurance programmes is given. It is concluded that a national hearing conservation program should be implemented in Denmark.

Audiometry↗

Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families.

Mutations in the ENG gene on chromosome 9 (HHT 1) and in the ALK-1 gene on chromosome 12 (HHT 2) have been reported as causes of hereditary hemorrhagic telangiectasia (HHT). HHT 1 has been correlated with a higher prevalence of pulmonary arteriovenous malformations than HHT 2. Other distinct phenotype-genotype correlations have not been described. The prevalence of HHT in the county of Fyn, Denmark, was 15.6 per 100,000 on January 1, 1995. All living patients and their first-degree relatives were invited to attend a detailed clinical examination and blood was drawn for mutation analysis. In two families mutations were identified in exon 8 of the ALK-1 gene. In family 6 we found a T1193A mutation. In this family a high prevalence of PAVM and severe GI bleeding was documented, while in family 8 with a C1120T mutation no individuals with PAVM were identified and only one patient had a history of severe GI bleeding. No mutations in the endoglin locus were found in either family.

Activin Receptors↗

Transesophageal and transthoracic echocardiography and Doppler-examinations in systemic lupus erythematosus.

OBJECTIVE: To search for cardiac abnormalities in systemic lupus erythematosus (SLE). METHODS: 35 patients examined by 2-D transthoracal Doppler and transesophageal echocardiography. RESULTS: Mitral and aortic valve abnormalities were seen in 12 patients (34%) respectively, and occurred altogether in 16 patients (46%). They were in general significantly associated with longer disease duration, but not with anticardiolipin antibodies (aCL), disease activity, or any other variable, except for time on corticosteroids. which was significantly longer in patients with aortic valve calcifications. CONCLUSION: Valve masses and valve thickening--often in combination--are the most frequent structural findings in SLE, occurring more often on the aortic than on the mitral valves. Factors other than antiphospholipid antibodies, medication, hypertension, or coronary heart disease seem to be responsible for this phenomenon. Drugs that modulate inflammation in endo- and pericardial tissue may, at least in part, be responsible for the observed mitral valve calcifications and pericardial fibrosis.

Adrenal Cortex Hormones↗