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Biomedical subjects

M Møller

Publications and source records attributed to M Møller.

At least 55 records · Page 3Linked to original sources

Comparison of magnesium and methyldopa for the control of blood pressure in pregnancies complicated with hypertension.

OBJECTIVES: Although magnesium is now the drug of choice for the prevention of eclamptic seizures only few studies have evaluated whether magnesium may reduce blood pressure in pregnancies complicated with hypertension. METHODS: A total of 33 patients with pregnancy-induced hypertension were randomized to either magnesium or methyldopa treatment. Of these 16 received magnesium and 17 methyldopa. The treatment comprised a 48-hour magnesium infusion followed by oral magnesium tablets until 3 days after delivery or 250 mg methyldopa 4 times a day in a similar period. RESULTS: Patients treated with magnesium had 1 day after inclusion a statistically significantly lower systolic blood pressure compared to the level in the methyldopa group (138.1 +/- 11 vs. 147.6 +/- 11 mm Hg; p < 0.05), but no difference was observed in diastolic blood pressure (92.0 +/- 6.6 vs. 96.0 +/- 10.1 mm Hg; NS). From the 5th day of inclusion and until delivery both systolic and diastolic blood pressure were significantly lower in the magnesium group (p < 0.05). Including all blood pressure measurements in a single analysis showed that both systolic (138 +/- 13 vs. 148 +/- 15 mm Hg; p < 0.0001) and diastolic (92 +/- 10 vs. 94 +/- 10 mm Hg; p < 0.05) blood pressure were lower in the magnesium group compared to the methyldopa group. There was no difference between the two groups regarding gestational age at delivery, birth weight, Apgar scores and pH in umbilical cord blood. CONCLUSION: This preliminary study demonstrates that magnesium treatment lowers blood pressure in pregnancies complicated with hypertension. The effect is without any adverse effect on maternal and neonatal well-being.

Adult↗

A follow-up study of birth outcome in users of pivampicillin during pregnancy.

BACKGROUND: Pivampicillin is a prodrug which is widely used in Scandinavian countries for oral antibiotic therapy. The pivaloyl moiety has a carnitine depleting effect, which has caused doubts about the safety of administering pivampicillin during pregnancy. The aim of the study was to evaluate the risk of congenital malformations in general, preterm delivery and low birth weight in users of pivampicillin. METHODS: Seven hundred and ninety-one women who had redeemed a prescription of pivampicillin during their first pregnancy from 1 January 1991 to 31 December 1996 were identified in the North Jutland Pharmaco-Epidemiological Prescription Database. By linkage to the Danish Medical Birth Registry and Regional Hospital Discharge Registry we compared their birth outcomes (malformations, preterm delivery and low birth weight) with the outcomes in 7472 reference pregnancies on which the mother had not redeemed any prescription at all during pregnancy. RESULTS: The prevalence of malformations was 5.5% (11 cases) in offspring of 199 women who had used pivampicillin during the first trimester, and 5.6% (420 cases) in offspring of controls (OR: 0.95, 95% CI: 0.51-1.76). Furthermore, we did not find any significant risk of preterm delivery (OR: 0.75, 95% CI: 0.54-1.05) or low birth weight (OR: 0.93, 95% CI: 0.55-1.57). CONCLUSION: This study showed no increased risk of congenital malformations, preterm delivery or low birth weight in offspring of women who had redeemed a prescription for pivampicillin during pregnancy.

Abnormalities, Drug-Induced↗

Immunohistochemical localization of substance P in the pineal gland of the domestic pig.

An immunohistochemical study of the pig pineal gland was carried out using polyclonal rabbit antiserum raised against substance P (SP). The pineal glands were taken from the newborn, 21-day- and 7-month-old female pigs. Immunoreactive nerve fibers were observed in the pineal gland as well as in the posterior commissure and habenular areas. The bundles of SP-immunoreactive fibers were also seen in the subependymal layer of the pineal tissue. The single SP-immunoreactive nerve fibers and few small bundles of nerve fibers were located with equal density throughout the pineal gland, in the connective tissue septa and in the parenchyma. SP-immunoreactive cell bodies were observed in the medial habenular nucleus. The obtained results point to this nucleus as one of the central sources of SP innervation in the pig pineal gland. The study did not show any differences in the distribution and the density of SP-immunoreactive nerve fibers between newborn, 21-day- and 7 month-old pigs.

Age Factors↗

Birth outcomes in pregnant women treated with low-molecular-weight heparin.

BACKGROUND: Pregnancy and puerperium are associated with an increased risk of venous thromboembolism. Low-molecular-weight heparin is the anticoagulant of choice in pregnant women because, unlike warfarin, it does not cross the placenta. However, there are limited data on the risk of adverse birth outcomes following use of low-molecular-weight heparin in pregnancy. PATIENTS AND METHODS: We performed a population-based cohort study to examine the safety of low-molecular-weight heparin use in pregnancy using data from the Pharmacoepidemiological Prescription Database, The Danish Medical Birth Registry and the Regional Hospital Discharge Registry in North Jutland County, Denmark. The birth outcomes in a cohort of 66 pregnant women treated with low-molecular-weight heparin between 1991-98 were compared with the birth outcomes of 17,259 pregnant women who did not receive any prescriptive drugs during pregnancy. RESULTS: No increased risk of malformations, low birth weight or stillbirth was found. However, an increased risk of pre-term delivery was found (odds ratio: 2.11, 95%, confidence interval: 0.96-4.65), which could reflect inherited thrombophilia as an indication of low-molecular-weight heparin. CONCLUSION: We have provided additional evidence of the safety of low-molecular-weight heparin use in pregnancy.

Abnormalities, Drug-Induced↗

Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.

BACKGROUND: Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization. Sinus rhythm may be maintained with antiarrhythmic drugs, but some of these drugs increase the risk of death. METHODS: We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals. We randomly assigned 762 patients to receive dofetilide, a novel class III antiarrhythmic agent, and 756 to receive placebo in a double-blind study. Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment. The primary end point was death from any cause. RESULTS: During a median follow-up of 18 months, 311 patients in the dofetilide group (41 percent) and 317 patients in the placebo group (42 percent) died (hazard ratio, 0.95; 95 percent confidence interval, 0.81 to 1.11). Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure (risk ratio, 0.75; 95 percent confidence interval, 0.63 to 0.89). Dofetilide was effective in converting atrial fibrillation to sinus rhythm. After one month, 22 of 190 patients with atrial fibrillation at base line (12 percent) had sinus rhythm restored with dofetilide, as compared with only 3 of 201 patients (1 percent) given placebo. Once sinus rhythm was restored, dofetilide was significantly more effective than placebo in maintaining sinus rhythm (hazard ratio for the recurrence of atrial fibrillation, 0.35; 95 percent confidence interval, 0.22 to 0.57; P<0.001). There were 25 cases of torsade de pointes in the dofetilide group (3.3 percent) as compared with none in the placebo group. CONCLUSIONS: In patients with congestive heart failure and reduced left ventricular function, dofetilide was effective in converting atrial fibrillation, preventing its recurrence, and reducing the risk of hospitalization for worsening heart failure. Dofetilide had no effect on mortality.

Adult↗

[Botulism caused by a commercially produced product].

Insufficient conserved home-made products are the main cause of botulism in Denmark. We present a case of botulism caused by a commercially produced vegetable pie conserved by traditional bottling without addition of preservatives. Clostridium botulinum was grown from faeces of the index case indicating an intestinal infection. An action plan set up by the medical and veterinarian authorities functioned well and further spread of the disease was avoided. More cases of botulism may be seen in the future, if procedures ensuring proper conservation in food production are not adhered to.

Botulism↗

Immunohistochemical localization of the somatostatin receptor subtype 2 (sst2) in the central nervous system of the golden hamster (Mesocricetus auratus).

The many actions of somatostatin in the central nervous system are mediated through specific membrane receptors of which five have been cloned. In this study, we have investigated the distribution of one of these receptors, the sst2 subtype, in the brain and spinal cord of the golden hamster (Mesocricetus auratus). Immunohistochemistry was carried out by using polyclonal antibodies raised against the C-terminal part of the human sst2 receptor. sst2 immunoreactivity was found in the forebrain, brainstem, cerebellum, and spinal cord. In the forebrain, strong immunoreactivity was observed in the deep layers of the neocortex as well as in the endopiriform cortex, claustrum, and basolateral amygdaloid nucleus. Immunoreactivity was also found in the CA1 area of the hippocampus and in the subiculum. In the diencephalon, staining was observed in the periventricular area, the dorsomedial and arcuate nuclei of the hypothalamus, and the medial habenular nucleus. Other areas such as the thalamus, striatum, and globus pallidus were almost devoid of staining. In the brainstem, strong immunoreactivity was observed in the locus coeruleus and the parabrachial nucleus. In addition, immunostaining was observed in the cortex of the cerebellum. In the spinal cord, intense immunoreactivity was seen in lamina I and II of the dorsal horn. Finally, immunoreactive cells were widely distributed in the anterior pituitary. The localization of the sst2 receptor in many brain regions suggests that this receptor subtype is involved in different neuromodulatory actions of somatostatin such as somatosensory, motor, memory, and neuroendocrine functions.

Animals↗

Innervation of the rat pineal gland by pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive nerve fibres.

Pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive nerve fibres were demonstrated in the rat pineal gland. These fibres entered the pineal gland through the conarian nerve at the distal tip of the gland. A high density of the fibres was observed in the capsule of the gland, from where the immunoreactive elements penetrated into the pineal perivascular spaces and parenchyma. The majority of PACAP-immunoreactive nerve fibres also contained calcitonin gene-related peptide (CGRP). Some PACAP-immunoreactive nerve fibres contained neuropeptide Y (NPY), but only occasionally was PACAP colocalized with vasoactive intestinal peptide (VIP). After removal of both superior cervical ganglia, a high number of PACAP-containing nerve fibres were still present in the gland. In the nervous system PACAP is present in two isoforms, PACAP-38 and PACAP-27. The concentration of PACAP-38 in the superficial pineal gland was determined by radioimmunoassay to be 20.4 pmol/g tissue at midday and 18.9 pmol/g tissue at midnight. The concentration of PACAP-27 was only about 3% of the concentration of PACAP-38. In summary, this study is the first demonstration of a PACAP-containing innervation of the rat pineal gland. The PACAP concentration in the pineal gland does not exhibit a day-night difference. The colocalization of PACAP with calcitonin gene-related peptide in the pincalopetal nerve fibres indicates that the majority of PACAP-immunoreactive nerve fibres might originate from the trigeminal ganglion.

Animals↗

Parasympathetic function during deep breathing in the general population: relation to coronary risk factors and normal range.

OBJECTIVES: To examine the association between the parasympathetic function assessed by deep breathing-induced heart rate variability (HRV) and coronary risk factors and to establish a reference range for deep breathing-induced HRV. DESIGN: Cross-sectional population-based study. SETTING: The municipality of Horsens, Denmark. SUBJECTS: One hundred and ninety-four individuals aged 40-67 years without diabetes, atrial fibrillation or a pacemaker randomly selected from the population. MAIN OUTCOME MEASURES: During deep breathing at 6 respiratory cycles min-1, an ECG was taken and in three consecutive cycles the longest R-R interval during expiration (E) and the shortest during inspiration (I) were selected. The mean ratio (E/Iratio) and the mean difference in instantaneous heart rate (E/Idiff) were taken as expressions of the parasympathetic function. RESULTS: In multivariate analysis, E/Idiff was reduced with increasing age (P < 0.0005) and left ventricular mass (P = 0.008), with ECG sign of probable previous myocardial infarction (P = 0.020) and the use of cardiac medication (P = 0.018) and positively correlated to heart rate (P = 0.030). The E/Iratio was diminished with increasing age (P = 0.001), left ventricular mass (P = 0.003), waist-hip ratio (P = 0.044), with ECG sign of probable previous myocardial infarction (P = 0.012) and use of cardiac medication (P = 0.020), but no association was found with heart rate (P = 0.92). In both E/Idiff and E/Iratio, no correlation was found to lipids, blood pressure or alcohol consumption. In the group not on cardiac medication, without left ventricular hypertrophy or ECG sign of probable myocardial infarction, E/Idiff and E/Iratio were still independently correlated to age and left ventricular mass. In this group, equations defining the age-corrected 5th percentile were calculated. CONCLUSIONS: The parasympathetic function as assessed by deep breathing-induced HRV in the general population is reduced in older people, and in individuals on cardiac medication, with left ventricular hypertrophy or ECG signs of myocardial infarction. Even in healthy persons the parasympathetic function is inversely associated with age and left ventricular mass. Values of E/Idiff above (4.39-0.033 x age)2 and readings of E/Iratio above 1 + exp (-1.12-0.0198 x age) can be regarded as normal.

Adult↗

Stress-induced release of anterior pituitary hormones: effect of H3 receptor-mediated inhibition of histaminergic activity or posterior hypothalamic lesion.

The effect of stress- or lipopolysaccharide (LPS) endotoxin-induced release of ACTH, beta-endorphin (beta-END) and prolactin (PRL) was investigated in two groups of conscious male rats: (1) Rats pretreated with different H3 receptor agonists, which inhibit neuronal histamine (HA) synthesis and release, and (2) rats with bilateral posterior hypothalamic lesion, which destroys the histaminergic perikarya exclusively localized in the mammillary nuclei. The H3 receptor agonists R(alpha)methyl-HA, BP 2-94 or imetit injected intraperitoneally (ip) had no effect on basal secretion of ACTH or PRL but inhibited the ACTH and PRL responses to restraint stress and the ACTH response to LPS endotoxin. LPS had no effect on PRL secretion. The inhibitory effect of the agonists was prevented by prior ip administration of the H3 receptor antagonist thioperamide. Bilateral lesion of the posterior hypothalamus inhibited the ACTH, beta-END and PRL responses to restraint stress, ether stress and LPS endotoxin, whereas sham operation had no effect compared to nonoperated control rats. In addition, posterior hypothalamic lesion inhibited the PRL response but not the ACTH and beta-END responses to activation of serotonergic neurons induced by ip administration of the 5-HT precusor 5-hydroxytryptophan in combination with the 5-HT re-uptake inhibitor fluoxetine. Thus, serotonergic pathways were not damaged by the lesions. The present results support our previous findings that inhibition of neuronal HA synthesis by alpha-fluoromethylhistidine as well as blockade of H1 or H2 receptors inhibit the ACTH, beta-END and PRL responses to stress and LPS endotoxin and further substantiate an important role of histaminergic neurons in the mediation of the stress-induced release of pituitary stress hormones. Furthermore, in accordance with our previous findings, the lesion experiments indicated the existence of an interaction between the histaminergic and serotonergic system in regulation of the stress- and LPS-induced PRL release.

5-Hydroxytryptophan↗

Immunohistochemical localization of somatostatin receptor subtypes sst1 and sst2 in the rat retina.

PURPOSE: To investigate the distribution of somatostatin receptor subtypes sst1 and sst2 in the rat retina by immunohistochemistry and to characterize further the neurotransmitters of the sst1- and sst2-immunoreactive cells. METHODS: Polyclonal antibodies raised against sst1 and sst2 receptors were applied to 12-microm cryostat sections of rat retinas fixed in paraformaldehyde. Further, immunofluorescence double labeling was performed for the sst1 and sst2 receptors with somatostatin, tyrosine hydroxylase (TH) and glutamate decarboxylase (GAD). RESULTS: Immunoreactivity for sst1 was present in somatostatinergic amacrine cells located in the inner nuclear layer (INL) and in displaced amacrine cells in the ganglion cell layer of the retina. Also, a small number of ganglion cells were sst1 immunoreactive. Immunoreactivity for sst2 was observed in many medium-sized amacrine cells in the middle part of the INL, with a central process projecting to the sublaminae of the inner plexiform layer. Furthermore, sst2 immunoreactivity was found in large amacrine cells of the INL. These cells also contained TH. Inner segments of cone receptors were stained with the sst2 antiserum. Immunostaining for sst2, and to a minor extent for sst1, was found in Müller cell fibers. None of the somatostatin receptors colocalized with GAD. CONCLUSIONS: These findings suggest that the sst1 receptor may function as an autoreceptor on retinal somatostatinergic cells. The presence of sst2 receptors on the TH-immunoreactive amacrine cells indicates an influence of somatostatin on the secretion of dopamine in rat retina.

Animals↗

Neuronal projections from the mesencephalic raphe nuclear complex to the suprachiasmatic nucleus and the deep pineal gland of the golden hamster (Mesocricetus auratus).

Neuronal projections from the mesencephalic raphe system to the suprachiasmatic nucleus and the pineal complex were mapped in this study of the golden hamster, by use of the anterograde tracer Phaseolus vulgaris-leucoagglutinin and the retrograde tracer cholera toxin subunit B. From the median raphe nucleus, a rostral projection ascended in the ventral part of the mesencephalon to continue in the medial forebrain bundle of the forebrain. Nerve fibres from this bundle innervated the ventral and medial parts of the suprachiasmatic nucleus. At the level of the interpeduncular nucleus of the mesencephalon, fibres of the ventral bundle bent dorsally to reach the epithalamic area and to continue in the forebrain in a periventricular position. Some of these fibres innervated the dorsal tip of the suprachiasmatic nucleus. The dorsal raphe nucleus was the origin of a nerve fibre bundle, located in the periaqueductal gray of the mesencephalon, innervating the deep pineal gland and pineal stalk. Injection of cholera toxin B into the suprachiasmatic nucleus labelled cells in the median raphe. Combination of the retrograde tracing from the suprachiasmatic nucleus and serotonin transmitter immunohistochemistry showed that some of the cholera toxin B-immunoreactive nerve cells also contained serotonin. Thus, this study of the golden hamster shows a serotonergic projection from the median raphe nucleus to the suprachiasmatic nucleus and a projection from the dorsal raphe nucleus to the deep pineal gland supporting physiological indications of an influence of serotonin on the photoreceptive circadian system of the brain.

Animals↗

Neuropeptide Y2 receptors on nerve endings from the rat neurohypophysis regulate vasopressin and oxytocin release.

Neuropeptide Y and peptide YY are important central and peripheral modulators of cardiovascular and neuroendocrine functions, that act through multiple receptor subtypes, Y1 through Y5. A neuropeptide Y-binding site of the Y2 type was characterized by ligand-binding studies in isolated nerve terminals from the rat neurohypophysis. Functionally, neuropeptide Y and peptide YY dose-dependently triggered arginine 8-vasopressin and oxytocin release from perfused isolated terminals, and potentiated the arginine-8-vasopressin release induced by depolarization. Osmotic stimulation by salt loading of rats for two and seven days caused a more than three-fold increase in the neuropeptide Y content of the nerve endings. However, the Y2 receptor expression and arginine-8-vasopressin content declined, showing that the neuropeptide Y system is dynamic and suggesting that it plays a physiological role in salt and water homeostasis. Two sets of observations suggest the arginine-8-vasopressin release by neuropeptide Y may not be explained by neuropeptide Y effects on intracellular Ca2+. First, absence of Ca2+ from the perfusion medium did not affect the arginine-8-vasopressin release, and secondly neuropeptide Y did not change intraterminal Ca2+ concentrations. Pretreatment with pertussis toxin blocked arginine-8-vasopressin secretion by neuropeptide Y, suggesting activation of Gi or Go heterotrimeric G-proteins are required for secretion. It is concluded, that the nerve endings of the neurohypophysis contain a complete neuropeptide Y system with ligand and receptors. Neuropeptide Y may act in an autocrine fashion via activation of Y2 neuropeptide Y receptors to stimulate the release of vasopressin and oxytocin via a Gi/Go dependent secretory mechanism.

Animals↗

African trypanosomiasis in the rat alters melatonin secretion and melatonin receptor binding in the suprachiasmatic nucleus.

Rats infected with Trypanosoma brucei brucei, a subspecies of the extracellular parasites that cause African sleeping sickness, were examined for disturbances in the circadian rhythms of melatonin secretion (evaluated by determination of the excretion of melatonin in the urine) and the binding of melatonin to its receptor in the suprachiasmatic nuclei of the anterior hypothalamus. In normal and infected rats, Cosinor analysis showed a significant nocturnal peak. The amplitude of this peak was, however, significantly decreased in the infected rats. The peak of melatonin receptor binding in the suprachiasmatic nuclei showed a 4-h phase advance in the infected rats, compared with the controls (0400 and 0800, respectively). These data point to a disturbance in the circadian rhythm of the melatonin-generating systems in the pathogenesis of African sleeping sickness.

Animals↗

Direct neuronal projection from the dorsal raphe nucleus to the pineal complex of the rat: a Phaseolus vulgaris-leucoagglutinin in vivo neuronal tracing study.

By use of Phaseolus vulgaris-leucoagglutinin as an anterograde in vivo tracer, a direct projection from the dorsal raphe nucleus to the pineal complex of the rat was demonstrated. The nerve fibers extended from the dorsal raphe nucleus rostrally through the mesencephalic periaqueductal grey and entered the deep pineal from both the posterior commissure and the habenular area. A dense innervation of the deep pineal and the pineal stalk was observed, but the nerve fibers were not observed to enter the superficial pineal gland. This new neural pathway might connect the visual system with the pineal complex of the rat.

Animals↗

Opioidergic innervation of the tree shrew pineal gland: an immunohistochemical study.

The tree shrew (Tupaia glis) has been described as a missing link relating primate to insectivore stock. The pineal gland of the tree shrew consists of a superficial pineal and a deep pineal, which are connected by a long and slender pineal stalk. A monoclonal antibody against leu-enkephalin was used in an immunohistochemical investigation of the tree shrew pineal gland. A moderate innervation of leu-enkephalin immunoreactive nerve fibers has been demonstrated in both superficial and deep pineal gland of the tree shrew. The density of the nerve fibers was slightly higher in the superficial pineal than that of the deep one. The number of immunoreactive nerve fibers were observed in the capsule of the pineal gland from where they entered the pineal parenchyma. Only a few immunoreactive fibers were found in the habenular area and the area rostral to the pineal recess, connecting the habenula and the deep pineal. Furthermore, some positive fibers were located in the pineal stalk. There was no evidence of leu-enkephalin immunoreactive intrapineal cells as seen in the other species of mammal. Therefore, the interspecies variation of opioidergic innervation among the mammals may exist. The lack of intrapineal perikarya is interpreted to indicate that the sources of leu-enkephalin nerve fibers were outside the gland. The anatomical location of the leu-enkephalin immunoreactive nerve fibers in the tree shrew pineal gland supports to both central and peripheral pinealopetal pathways in this species.

Animals↗