Total homocysteine measurement in clinical practice.
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Blood Chemical Analysis↗
Biomedical subjects
K Rasmussen
Publications and source records attributed to K Rasmussen.
Association between plasma testosterone and work-related neck and shoulder disorders among female workers.
OBJECTIVES: The aims were to study the association between anabolic hormone testosterone in plasma and the presence of musculoskeletal disorders among female workers and to study the association between changes in testosterone and changes in musculoskeletal complaints. METHODS: In a cross-sectional design 145 women from 2 different industries filled out questionnaires about current musculoskeletal complaints, participated in a clinical examination of the neck and upper extremities, and gave a blood sample for the analysis of free testosterone in plasma. Individual characteristics, psychosocial job factors, and stress reactions were evaluated by questionnaires. In a follow-up study a subgroup of 73 sewing machine operators from the cross-sectional study was reexamined after 1 year. RESULTS: The group of women with clinically verified neck or shoulder disorders had significantly lower plasma testosterone than the women with no disorders. Furthermore, the testosterone level showed a negative association with age and a positive association with smoking and body mass index. Changes in pain status or clinically diagnosed musculoskeletal disorders were not associated with changes in testosterone levels. However, this finding may well be due to a strong plant influence in that marked changes in testosterone levels were observed for 2 of the 3 participating plants. CONCLUSIONS: There is some indication of an association between musculoskeletal disorders in the neck and shoulders and a low level of free plasma testosterone. The study failed to clarify the associations found between changes in testosterone and changes in musculoskeletal complaints over time.
Adult↗
Intermediate and severe hyperhomocysteinemia with thrombosis: a study of genetic determinants.
Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. In search of genetic factors causing elevated levels of total homocysteine in plasma (tHcy), we investigated a cohort of consecutively identified, unrelated thrombosis patients (n = 28) having intermediate or severe hyperhomocysteinemia (30 micromol/l 100 micromol/l, respectively). The methylene-tetrahydrofolate reductase (MTHFR) 677C-->T genotype, and the complete cystathionine beta-synthase (CBS) genotype was determined in all patients. We found that the MTHFR T/T genotype was strongly correlated with intermediate hyperhomocysteinemia, being present in 73.9% of those cases (17 of 23). In three of five patients with severe hyperhomocysteinemia, compound heterozygosity for CBS mutations was detected. Among the mutations, two novel missense mutations: 1265C-->T (S422L) and 1397C-->T (S466L) were detected. The phenotype in those patients was quite mild, thromboembolism apart. This indicates that a search for CBS mutations in patients with severe hyperhomocysteinemia is important to ensure the detection of a possible CBS deficiency, thus enabling treatment. Co-existence of the MTHFR T/T genotype and the common CBS 844ins68 variant was significantly higher among patients (10.7%) as compared to controls (1.2%), indicating that this genotype combination is a thrombotic risk factor (P <0.05). In a few patients, hyperhomocysteinemia could not be explained by this genetic approach, suggesting that other genetic risk factors were implicated.
Adult↗
The novel 5-Hydroxytryptamine(1A) antagonist LY426965: effects on nicotine withdrawal and interactions with fluoxetine.
LY426965 [(2S)-(+)-1-cyclohexyl-4-[4-(2-methoxyphenyl)-1-piperazinyl]2-methyl- 2-phenyl-1-butanone monohydrochloride] is a novel compound with high affinity for the cloned human 5-hydroxytryptamine (HT)(1A) receptor (K(i) = 4.66 nM) and 20-fold or greater selectivity over other serotonin and nonserotonin receptor subtypes. Both in vitro and in vivo studies indicate that LY426965 is a full antagonist and has no partial agonist properties. LY426965 did not stimulate [(35)S]guanosine-5'-O-(3-thio) triphosphate (GTPgammaS) binding to homogenates of cells expressing the cloned human 5-HT(1A) receptor in vitro but did inhibit 300 nM 5-HT-stimulated [(35)S]GTPgammaS binding with a K(i) value of 3.07 nM. After both p.o. and s.c. administration, LY426965 blocked the lower lip retraction, flat body posture, hypothermia, and increase in rat serum corticosterone induced by the 5-HT(1A) agonist 8-OH-DPAT (8-hydroxy-2-dipropylaminotetralin). In pigeons, LY426965 dose-dependently blocked the stimulus cue induced by 8-OH-DPAT but had no 8-OH-DPAT-like discriminative properties. LY426965 completely reversed the effects of nicotine withdrawal on the auditory startle reflex in rats. In microdialysis experiments, LY426965 administered together with fluoxetine significantly increased extracellular levels of serotonin above those achievable with fluoxetine alone. In electrophysiological studies, the administration of LY426965 produced a slight elevation of the firing rate of 5-HT neurons in the dorsal raphe nucleus of anesthetized rats and both blocked and reversed the effects of fluoxetine on 5-HT neuronal activity. These preclinical results indicate that LY426965 is a selective, full 5-HT(1A) antagonist that may have clinical use as pharmacotherapy for smoking cessation and depression and related disorders.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Evaluation of novel assays in clinical chemistry: quantification of plasma total homocysteine.
BACKGROUND: There is a need for systematic evaluation of methods before their release to the market. We addressed this problem in novel homocysteine assays as part of an European Demonstration Project involving six centers in four countries. METHODS: Two immunological methods for measurement of plasma total homocysteine (P-tHcy), the fluorescence polarization immunoassay (FPIA) and the enzyme immunoassay (EIA), were compared with two comparison methods, HPLC and gas chromatography-mass spectrometry (GC-MS). All laboratories performed the following procedures: (a) familiarization; (b) determination of linearity and precision by analyzing five plasma samples with interrelated concentrations for 20 days; (c) correlation using patients' samples; and (d) assessment of long-term performance. RESULTS: Both immunological methods were linear for P-tHcy between 5 and 45 micromol/L. The intralaboratory imprecision (CV) was <5% for FPIA and <9% for EIA used with a sample processor. The bias was -2% to 3% for FPIA and 2-4% for EIA used with a sample processor. CONCLUSIONS: The immunological methods provide results with little bias compared with HPLC and GC-MS. The imprecision of the assays must be considered in the context of their intended use(s).
Fluorescence Polarization Immunoassay↗
[Agricultural occupational accidents in the county of Ringkoebing. Local registration].
The aim of the study was to obtain knowledge of accidents and working conditions related to farm accidents for purposes of a preventive intervention. The survey was a prospective study following a cohort of 393 farms in the county of Ringkoebing in West-Jutland, Denmark. Every farm in the study registered work activity and farmwork related incidents that required a break in work. Every farm reporting an incident was interviewed by phone. The owner himself and the part-time farmer had the highest injury rate per working hour. There was no difference between animal and field related work looking at the incidence rate per workhour, but the incidence rate whilst repairing machinery and buildings was five times higher and highly significant. The results indicate the existence of groups and areas of risk, where a preventive effort is needed. The study is followed by a randomised intervention study among 200 Danish farms.
Accidents↗
Regulatory requirements for biocides on the market in the European Union according to Directive 98/8/EC.
In early 1998, the European Commission and Parliament adopted a new Directive concerning the placing on the market of biocidal products. The Directive is to be implemented in the member states by May 2000. The member states are currently concerned with the national implementation into legislation whereas the Commission is setting up the proposal for a review programme for the existing active substances and the products in which they are used. This paper describes the effort currently undertaken (up to the end of December 1998) to define the procedures to be used and characterise the substances covered.
European Union↗
[Hereditary neuropathy with liability to pressure palsies].
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent transient pressure palsies of peripheral nerves and slowing of nerve conduction velocity of the peripheral nerves at common sites of compression. In most cases the molecular basis of the disease is a 1.5 Mb deletion on chromosome 17p11.2. We report four members of a family with different clinical phenotypes. Electrophysiological and genetic studies were consistent with the diagnosis of HNPP. Nerve biopsy is only necessary in patients with a normal result of the molecular genetic analysis. The variability of the clinical phenotype along with asymptomatic individuals could account for an under-recognition of this inherited neuropathy.
Adult↗
AMPA antagonist LY293558 blocks the development, without blocking the expression, of behavioral sensitization to morphine.
Morphine (3.0 mg/kg, s.c.) stimulates locomotor activity in rats, and this effect sensitizes with repeated intermittent treatment. We examined the ability of the AMPA antagonist LY293558, administered systemically over a range of doses (0.1-3.0 mg/kg), to alter morphine sensitization. Pretreatment with 3.0 mg/kg LY293558 attenuated the acute (session 1) locomotor-stimulating actions of morphine, whereas 1.0, 0.3, and 0.1 mg/kg were without effect. No sensitization was observed after repeated morphine treatment (3.0 mg/kg, s.c., every other day for 9 days) when morphine injections were preceded by 0.3, 1.0, or 3.0 mg/kg LY293558, whereas significant sensitization was observed when morphine injections were preceded by vehicle or 0.1 mg/kg of the antagonist. When all rats were challenged with morphine (3.0 mg/kg, s.c.) alone on day 11, the locomotor activity of rats previously exposed to LY293558 at 3.0, 1.0, or 0.3 mg/kg--but not at 0.1 mg/kg--was significantly lower than that of rats previously given morphine preceded by vehicle. On day 13, pretreatment with 1.0 mg/kg LY293558 failed to alter preestablished morphine sensitization in rats previously pretreated with vehicle. These data indicate that LY293558 blocks the development but not the expression of morphine sensitization, confirming a role for AMPA receptors in the initiation of neurobiological adaptations that occur with chronic morphine treatment.
Animals↗
[Development of post-traumatic stress following severe work-related accidents].
The diagnostic criteria for posttraumatic stress disorder (PTSD) employed by the American DSM-IV from 1994 and ICD-10 from 1993 are reviewed. The literature concerning PTSD, with particular focus on PTSD in relation to occupational accidents, is discussed. A single epidemiological study of the occurrence of PTSD following serious nonfatal occupational accidents reports a one to two years prevalence of PTSD of 4.3%. Physicians and safety and health organisations within companies should be aware of the potential for the occurrence of acute and chronic stress conditions following occupational accidents, primarily with respect to providing supportive psychological treatment and social support aimed at preventing the development of chronic symptoms.
Accidents, Occupational↗
[Post-traumatic stress after occupational accidents].
This study focuses on post-traumatic stress disorder in a follow up one to two years after the occupational accident. The aim was to estimate the prevalence of PTSD, changes in general health status and issues of compensation. The material was all serious accidents registered in the Danish National Register of Work Accidents during 1991. Seriousness was defined by type of injury, including all cases of amputations, bone fractures and extensive body lesions. Of 4745 possible, 3663 persons (77%) participated in a questionnaire study. The prevalence fulfilling the complete set of criteria of posttraumatic stress disorder as a chronic state was 2.8% (102 persons), of whom half had been given compensation. Among the most severe accidents the prevalence was 7.6%. In conclusion, in a large cohort of persons with moderate and severe occupational injuries this study demonstrated that post-traumatic stress disorder and lasting psychological distress should be a matter for concern in addition to the physical injury.
Accidents, Occupational↗
[Post-traumatic stress disorder following an occupational accident].
Two cases of occupational accidents and post-traumatic stress disorder (PTSD) of various types are described. These accidents occurred in different occupations and encompass dramatic, life-threatening situations. The cases were compatible with a diagnosis of chronic PTSD. In both cases compensation for occupational injury was awarded on the basis of a PTSD diagnosis.
Accidental Falls↗
Coenzyme Q10 treatment in serious heart failure.
Several noninvasive studies have shown the effect on heart failure of treatment with coenzyme Q10. In order to confirm this by invasive methods we studied 22 patients with mean left ventricular (LV) ejection fraction 26%, mean LV internal diameter 71 mm and in NYHA class 2-3. The patients received coenzyme Q10 100 mg twice daily or placebo for 12 weeks in a randomized double-blinded placebo controlled investigation. Before and after the treatment period, a right heart catheterisation was done including a 3 minute exercise test. The stroke index at rest and work improved significantly, the pulmonary artery pressure at rest and work decreased (significantly at rest), and the pulmonary capillary wedge pressure at rest and work decreased (significantly at 1 min work). These results suggest improvement in LV performance. Patients with congestive heart failure may thus benefit from adjunctive treatment with coenzyme Q10.
Adult↗
Potential role of muscarinic receptors in schizophrenia.
The role of muscarinic receptors in schizophrenia was investigated using the muscarinic agonist PTAC. PTAC was highly selective for muscarinic receptors, was a partial agonist at muscarinic M2/M4 receptors and an antagonist at M1, M3 and M5 receptors. PTAC was highly active in animal models predictive of antipsychotic behavior including inhibition of conditioned avoidance responding in rats and blockade of apomorphine-induced climbing behavior in mice. d-Amphetamine-induced Fos expression in rat nucleus accumbens was inhibited by PTAC, thus directly demonstrating the ability of PTAC to modulate DA activity. In electrophysiological studies in rats, PTAC acutely inhibited the firing of A10 DA cells and after chronic administration decreased the number of spontaneously firing DA cells in the A10 brain area. However, PTAC did not appreciably alter the firing of A9 DA cells. Thus, PTAC appears to have novel antipsychotic-like activity and these data suggest that muscarinic compounds such as PTAC may represent a new class of antipsychotic agents.
Animals↗
The selective mGlu2/3 receptor agonist LY354740 attenuates morphine-withdrawal-induced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal.
Naltrexone-precipitated morphine withdrawal induces hyperactivity of locus coeruleus (LC) neurons, as well as a plethora of behavioral withdrawal signs. Previous research has demonstrated that an increased release of glutamate and activation of AMPA receptors, particularly in the LC, play an important role in opiate withdrawal. LY354740 is a novel Group II metabotropic glutamate mGlu2/3 receptor agonist that decreases the release of glutamate. Therefore, we investigated the effect of LY354740 on naltrexone-precipitated morphine-withdrawal-induced activation of LC neurons and behavioral signs of morphine withdrawal. In in vivo recordings from anesthetized rats, pretreatment with LY354740 (3-30 mg/kg, s.c.) dose-dependently attenuated the morphine-withdrawal-induced activation of LC neurons. In unanesthetized, morphine-dependent animals, pretreatment with LY354740 (3-30 mg/kg, s.c.) dose-dependently suppressed the severity and occurrence of many naltrexone-precipitated morphine-withdrawal signs. These results indicate mGlu2/3 receptor agonists: (1) can attenuate the morphine-withdrawal-induced activation of LC neurons and many behavioral signs of morphine withdrawal; and (2) may have therapeutic effects in man for the treatment of opiate withdrawal.
Analysis of Variance↗
Pertussis toxin treatment differentially affects cholinergic and dopaminergic receptor stimulation of midbrain dopaminergic neurons.
Extracellular single-unit recordings and iontophoresis were used to compare the effect of a single administration of pertussis toxin (PTX, 1 microg), into midbrain dopamine (DA) nuclei (A9 and A10 regions), on the muscarinic, NMDA and DA receptor responses of midbrain DA cells in the anesthetized rat. Iontophoretic applications of DA, or apomorphine (50 microg/kg, i.v.), markedly reduced the firing of DA cells in control rats. In PTX-treated animals, these inhibitory responses were totally abolished, indicating that, in both DA nuclei, the inhibitory DA receptors are coupled to Gi/o proteins. In parallel, there was a significant decrease in the number of active DA cells per track which returned to baseline 5 weeks after the treatment. Applications of the muscarinic agonist oxotremorine M (OXO M) or of NMDA produced a potent increase in the firing of DA cells in control rats. DA neurons treated with PTX were still responsive to OXO M, although their sensitivity to the agonist was significantly reduced by 40%. In contrast, NMDA-induced activation remained unchanged, indicating that PTX did not non-selectively dampen all excitatory responses. Applications of cell-permeable cAMP derivatives did not change the basal firing of DA neurons. On the other hand, the phospholipase C inhibitors neomycin and ET-18-OCH3 (200 microg, i.c.v.), reduced significantly the activation of DA cells induced by OXO M. These data suggest that muscarinic activation of DA cells involves an M1-like receptor, possibly coupled to Gq/11 proteins, but also the participation of a PTX substrate.
Action Potentials↗
What determines echogenicity in a general population? The Tromsø Study.
BACKGROUND: It is widely recognized that in some people it is difficult or impossible to acquire adequate measurements of cardiac performance and anatomy by any echocardiographic technique. We used our population-based screening to determine the characteristics of such unmeasurable subjects. METHOD: In a sample of 3287 subjects aged 25 to 85 years, we used standard 2-dimensional guided M-mode echocardiography and pulsed and color Doppler to assess left ventricular (LV) structure and function. RESULTS: Of 3287 subjects only 0.4% could not be measured by any technique. In 2794 subjects M-mode registrations of good quality were obtained, which allowed calculation of LV mass and LV ejection fraction. Those in whom measurements could not be obtained had a significantly higher age, body mass index, blood pressure, waist/hip ratio, and were more likely to smoke, be a man, be taking antihypertensive medication, have a history of ischemic heart disease, and have a low level of physical activity. CONCLUSION: Because subjects with high cardiovascular risk factor levels are less likely to be measurable with echocardiography, a need exists for other noninvasive diagnostic methods in these persons.
Adult↗
A comparison of the angiotensin II antagonists valsartan and losartan in the treatment of essential hypertension.
We compared the angiotensin II receptor antagonist valsartan to losartan as an antihypertensive agent in an 8-week trial. Adults with uncomplicated essential hypertension (baseline seated diastolic blood pressure < 115 mm Hg and > or = 95 mm Hg) were randomized to receive 80 mg valsartan, 50 mg losartan, or placebo once daily. After 4 weeks doses of active medication and placebo were doubled. Seated systolic and diastolic blood pressures were measured and the response rate evaluated. Tolerability was assessed by the incidence of adverse events. Both angiotensin II receptor antagonists produced similar significant reductions in mean blood pressures at 4 and 8 weeks compared to placebo. Valsartan produced a significantly higher number of responders (62%) than losartan (55%, P = .02) at the 8 week treatment endpoint. The incidence of adverse experiences (AE) was similar in all three groups, with headache and dizziness reported most often. Valsartan (80/160 mg) monotherapy in this trial was as effective and well tolerated as 50/100 mg losartan in treating mild to moderate essential hypertension, and at 160 mg has a significantly higher responder rate than 100 mg losartan.
Adolescent↗