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M Møller

Publications and source records attributed to M Møller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Presence of oxytocinergic neuronal-like cells in the bovine pineal gland: an immunocytochemical and in situ hybridization study.

In the last decade, there is more and more evidence showing the role of the central innervation of the pineal gland, but there are controversies around the intra or extrapineal origin of oxytocin found within the pineal tissue. In order to check the amount and the site of synthesis of oxytocin in the bovine pineal gland, we performed a morphological and chromatographic study. The anatomical distribution of the pineal oxytocin was explored by immunohistochemistry and in situ hybridization for the corresponding mRNA. The results confirm the presence of oxytocinergic fibres in the bovine pineal, some of them endowed with big varicosities. Immunohistochemistry also displayed neuronal-like cells in the pineal body. The in situ hybridization for the mRNA encoding pre-pro/oxytocin-NFZ I used a mixture of three oligonucleotide probes labelled with (35)S. This allowed identification of positive cells in the bovine pineal. The content in oxytocin was evaluated by radioimmunoassay during 5 months, from July to November, and the peptidic extract revealed an increase of pineal oxytocin immunoreactivity in September as compared with July or November. The significance of intrinsic oxytocin innervation of the bovine pineal gland, as well as the threefold increase of the oxytocin content in the pineal in September, remains to be elucidated.

Animals↗
PubMed2001

Plastination of dissected brain specimens and Mulligan-stained sections of the human brain.

The difficulties in obtaining human brain material for teaching neuroanatomy have increased the demand for more durable brain specimens. In this paper, we describe results obtained by preparing large, plastinated, dissected human brain specimens and Mulligan-stained sections of the human brain. The brains were fixed in formalin, washed and dissected in order to visualize the fibre tracts and larger nuclei in the central nervous system. This was followed by dehydration at -20 degrees C in acetone. The specimens were then impregnated with silicone, Biodur S10, in vacuo and hardened in Biodur S6 vapour. The grey and white substance in the central nervous system as well as the larger fibre tracts and nuclei were clearly visible in the dissected, plastinated specimens. Coronal and sagittal sections of the human brain were stained according to Tompsett's modification of the Mulligan method. The sections were then dehydrated in cold acetone followed by forced impregnation with Biodur S10 and hardening. The plastinated sections stained distinctly and strongly and the nuclei in the forebrain, cerebellum and brain stem could be identified easily. The sections did not fade when exposed to light and could be easily handled in the classroom without damage. Therefore, the distinct visualization of neuroanatomical structures, the improved durability of the specimens, as well as the lack of odour make plastinated specimens and stained sections of the central nervous system a valuable tool for teaching neuroanatomy that compliments the use of wet preparations.

Brain↗
PubMed2001

Birth outcome and risk of neonatal hypoglycaemia following in utero exposure to pivmecillinam: a population-based cohort study with 414 exposed pregnancies.

Concerns have been raised as to the safety of using pivaloyl-conjugated beta-lactam antibiotics during pregnancy as they cause carnitine depletion. Restrictions have been recommended in some Scandinavian countries as drug-induced carnitine depletion could constitute a risk to the developing foetus. One of these drugs, pivmecillinam, is widely used against urinary tract infections but few data exist concerning its safety in pregnancy. In a cohort study, we compared the prevalences of congenital abnormalities, pre-term delivery, low birth weight, low Apgar score and neonatal hypoglycaemia in the offspring of 414 women who had at least 1 prescription for pivmecillinam redeemed during pregnancy with those of the offspring of 7472 pregnant women for whom no drugs were prescribed during pregnancy. The prevalence of congenital abnormalities was 1.7% among 119 infants exposed in the first trimester and 3.7% among the reference group [odds ratio (OR) 0.46; 95% confidence interval (CI) 0.11-1.86]. We found no significantly increased risks in either pre-term delivery (OR 0.91, 95% CI 0.11-1.86), low birth weight (OR 0.57, 95%, CI 0.23-1.41), low Apgar score (OR 2.32, 95% CI 0.30-18.16) or hypoglycaemia (OR 0.73, 95% CI 0.18-3.00) that were induced by carnitine depletion. No significantly increased risk in adverse birth outcome was therefore found in women treated with pivmecillinam.

Abnormalities, Drug-Induced↗
PubMed2001

Thrombolytic therapy preserves vagal activity early after acute myocardial infarction.

OBJECTIVE: The purpose of this study was to evaluate the effects of thrombolytic therapy on vagal tone after acute myocardial infarction (AMI). DESIGN: Holter monitoring for 24 h was performed at hospital discharge and 6 weeks after AMI in 74 consecutive male survivors of a first AMI, who fulfilled established criteria for thrombolytic therapy. Thirty-five patients received thrombolyses, while the remaining 39 patients did not (controls). In each Holter recording 24-h heart rate variability was calculated as pNN50, which represents the percentage of successive RR interval differences >50 ms. Alterations in pNN50 are known to reflect changes in vagal tone. RESULTS: The analysis showed that controls early after AMI had low pNN50 values without any diurnal changes. Six weeks after AMI pNN50 values in controls exhibited a circadian rhythm with higher values during night-time. This pattern was similar to the pattern observed in thrombolysed patients early after AMI. In thrombolysed patients pNN50 values, particularly at night, were further improved 6 weeks after AMI (p = 0.037). CONCLUSION: These observations indicate that thrombolytic therapy, given for a first AMI, preserves vagal activity when compared with patients who are not thrombolysed. The enhanced parasympathetic tone may be a part of the beneficial mechanisms responsible for the reduction in mortality after thrombolysis in AMI.

Electrocardiography, Ambulatory↗
PubMed2001

Effects of intravenous dofetilide on induction of atrioventricular re-entrant tachycardia.

OBJECTIVE: To assess the efficacy and safety of intravenous dofetilide in preventing induction of atrioventricular re-entrant tachycardia. DESIGN: A multicentre, open, dose ranging trial. Fifty one patients with electrically inducible atrioventricular re-entrant tachycardia were allocated to one of five doses of dofetilide (1.5, 3, 6, 9, and 15 microgram/kg), two thirds of the dofetilide dose being given over a 15 minute loading period and the remainder over a 45 minute maintenance period. MAIN OUTCOME MEASURE: Responders were defined as patients in whom dofetilide prevented reinduction of atrioventricular re-entrant tachycardia at the end of the infusion. RESULTS: Intravenous dofetilide had no effect on tachycardia inducibility at the two lower doses (1.5 and 3 microgram/kg) but prevented the reinduction of tachycardia at the three higher doses (6, 9, and 15 microgram/kg) at a rate of 36% (11/31). There was a clear relation between plasma dofetilide concentrations and efficacy (p = 0.009). In non-responders, dofetilide increased the cycle length of induced atrioventricular re-entrant tachycardia. Dofetilide increased the atrial and ventricular effective refractory periods, as well as the antegrade and retrograde effective refractory period of the accessory pathway. Treatment related side effects were reported in four patients, one with a new sustained incessant supraventricular tachycardia. CONCLUSIONS: Dofetilide shows promise as an agent for the prevention of atrioventricular re-entrant tachycardia in patients without structural heart disease.

Adolescent↗
PubMed2000

Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial.

BACKGROUND: Arrhythmias cause much morbidity and mortality after myocardial infarction, but in previous trials, antiarrhythmic drug therapy has not been convincingly effective. Dofetilide, a new class III agent, was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infarction. METHODS: In 37 Danish coronary-care units, 1510 patients with severe left-ventricular dysfunction (wall motion index < or = 1.2, corresponding to ejection fraction < or = 0.35) were enrolled in a randomised, double-blind study comparing dofetilide (n=749) with placebo (n=761). The primary endpoint was all-cause mortality. Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths. Analyses were by intention to treat. FINDINGS: No significant differences were found between the dofetilide and placebo groups in all-cause mortality (230 [31%] vs 243 [32%]), cardiac mortality (191 [26%] vs 212 [28%]), or total arrhythmic deaths (129 [17%] vs 140 [18%]). Atrial fibrillation or flutter was present in 8% of the patients at study entry. In these patients, dofetilide was significantly better than placebo at restoring sinus rhythm (25 of 59 vs seven of 56; p=0.002). There were seven cases of torsade de pointes ventricular tachycardia, all in the dofetilide group. INTERPRETATION: In patients with severe left-ventricular dysfunction and recent myocardial infarction, treatment with dofetilide did not affect all-cause mortality, cardiac mortality, or total arrhythmic deaths. Dofetilide was effective in treating atrial fibrillation or flutter in this population.

Adult↗
PubMed2000

Experimental microneurosurgery of the trigeminal ganglion and ophthalmic-maxillary nerve in the rat: subtemporal fossa approach.

In the researches of the innervation relationship between trigeminal ganglion and a particular structure in the head, it is usually necessary to apply neural tracers into the ganglion for anterograde nerve tracing study or perform bilateral trigeminal nerve transecting for degeneration study. A common surgical approach for exposing these structures in the rat was to remove a piece of skull and a portion of brain. While investigating the innervation of rat's pineal gland from its trigeminal ganglion, we used a subtemporal fossa approach, whereby the mortality of the animal was remarkably reduced and the contamination of the intracranial structures by the tracer was proved to be least. This is the first description of bilateral surgeries of the trigeminal ganglion and trigeminal nerve in rat using extracranial approach. Detailed surgical procedures were presented and their advantages discussed.

Animals↗
PubMed2000

[Dofetilide to patients with heart failure and left ventricular dysfunction].

INTRODUCTION: Dofetilide, a new class III antiarrhythmic drug, was tested for its ability to reduce mortality and morbidity in patients with congestive heart failure and left ventricular dysfunction. METHODS: In 34 Danish centers, 1518 patients with NYHA class III or IV heart failure and wall motion index of the left ventricle < or = 1.2 (ejection fraction < or = 35%) were randomized to receive dofetilide or placebo in a double blind study. The dose of dofetilide was adjusted to renal function and the QT interval. Patients were monitored continuously with ekg during the first three days in the study. Minimum follow up was one year. RESULTS: Dofetilide did not affect mortality. Hospitalizations for worsening of heart failure were reduced significantly, hazard ratio 0.75 (0.63-0.89) Dofetilide effectively converted atrial fibrillation to sinus rhythm. After one year, 61% of patients with atrial fibrillation had converted on dofetilide and 33% on placebo (p < 0.001). DISCUSSION: Dofetilide can be used to convert atrial fibrillation to sinus rhythm and to maintain sinus rhythm in patients with congestive heart failure and left ventricular dysfunction. Dofetilide does not affect mortality.

Adult↗
PubMed2000

N-terminal and core-domain random mutations in human topoisomerase II alpha conferring bisdioxopiperazine resistance.

Random mutagenesis of human topoisomerase II alpha cDNA followed by functional expression in yeast cells lacking endogenous topoisomerase II activity in the presence of ICRF-187, identified five functional mutations conferring cellular bisdioxopiperazine resistance. The mutations L169F, G551S, P592L, D645N, and T996L confer > 37, 37, 18, 14, and 19 fold resistance towards ICRF-187 in a 24 h clonogenic assay, respectively. Purified recombinant L169F protein is highly resistant towards catalytic inhibition by ICRF-187 in vitro while G551S, D645N, and T996L proteins are not. This demonstrates that cellular bisdioxopiperazine resistance can result from at least two classes of mutations in topoisomerase II; one class renders the protein non-responsive to bisdioxopiperazine compounds, while an other class does not appear to affect the catalytic sensitivity towards these drugs. In addition, our results indicate that different protein domains are involved in mediating the effect of bisdioxopiperazine compounds.

Adenosine Triphosphate↗
PubMed2000

Somatostatin and somatostatin receptors in the pig pineal gland during postnatal development: an immunocytochemical study.

An immunohistochemical study of the pineal gland of the domestic pig was carried out using rabbit antisera raised against synthetic peptide fragments corresponding to different amino acid sequences of the prosomatostatin, the somatostatin-14, and the somatostatin-28 molecule. The study was supplemented by immunohistochemical staining with rabbit antisera raised against five subtypes of somatostatin receptors. The pineal glands were taken from the newborn, 21-day-old and 7-month-old pigs. Immunoreactive nerve fibers and cells were observed in the pineal gland with all the antisera against somatostatin and prosomatostatin. The nerve fibers were located throughout the pineal gland-in the capsule, connective septa, and parenchyma-with the highest density in proximo-ventral part of the gland. The somatostatin positive fibers were also found in the habenular and posterior commissurae areas. Somatostatin-immunoreactive cell bodies were observed mostly in the central part of the gland. These results point to the existence of two somatostatin sources in the pig pineal gland: 1) nerve fibers, probably of central origin; and 2) cells that may represent intrapineal neurons or specialised pinealocytes. A clear difference in the immunoreactivity between newborn, 21-day-old, and 7-month-old pigs was found. Generally, the density of nerve fibers was lower in adult than young animals. The number of the cells also decreased with age. By using the antisera against the five somatostatin receptors, only sst3 - receptor immunoreactivity could be detected. The receptor-immunoreactivity was confined to varicose and smooth fibers and some cells. The sst(3)-receptor positive structures were localised in all parts of the gland and their number was higher in younger pigs.

Animals↗
PubMed2000

PACAP and glutamate are co-stored in the retinohypothalamic tract.

The retinohypothalamic tract (RHT) relays photic information from the eyes to the suprachiasmatic nucleus (SCN). Activation of this pathway plays a role in adjusting circadian timing to the light/dark environment. Two transmitters, glutamate and pituitary adenylate cyclase activating polypeptide (PACAP) having phase shifting capacity during the night and day, respectively, are located in the RHT. Using double staining immunohistochemistry at the light and electron microscopic level, we showed that PACAP was co-stored with glutamate in a subset of retinal ganglion cells and in nerve terminals in the retino-recipient area of the SCN. These findings provide an anatomical basis for the recent demonstration of the interaction between these two transmitters on the SCN phase response at night.

Animals↗
PubMed2000

Innervation of the rat pineal gland by PACAP-immunoreactive nerve fibers originating in the trigeminal ganglion: a degeneration study.

In order to establish that the pineal gland is innervated by pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive nerve fibers originating in the trigeminal ganglion, ophthalmic and maxillary nerves were transected by using a subtemporal fossa approach. The number of PACAP-immunoreactive nerve fibers in the pineal gland of rats with a total transection of the nerve was compared with that of rats without surgery. In the operated rat, PACAP-immunoreactive nerve fibers in the superficial pineal decreased remarkably, indicating that the trigeminal ganglion was the origin of these nerve fibers. This research provides evidence supporting the hypothesis that PACAP-immunoreactive nerves regulate the synthesis and/or secretion of melatonin in the pineal gland.

Animals↗
PubMed2000

A population-based cohort study of birth and neonatal outcome in older primipara.

OBJECTIVES: To examine the risk of adverse birth outcome in older primiparous women. METHODS: We identified 14,676 primiparae of 20 years of age or more from 1991 to 1996 using the Birth Registry in the North Jutland County, Denmark. We evaluated the risk of adverse birth outcome in the primiparous women aged 30-34 years and above 35 years using the primiparae aged 20-29 years at time of birth as reference. RESULTS: The risks of induced labor, perineotomy, stimulating contraction and vacuum extraction were significantly higher (adjusted odds ratio: 1.3 to 1.7) in the primiparae of 35 years or more. The odds ratio for cesarean section delivery was 2.1 (95% confidence interval: 1.7-2.6) and the odds ratio for delivering a low birth weight child among the primiparae of 35 years or more was 2.2 (95% confidence interval: 1.4-3.3) compared with the primiparae of 20-29 years of age. These risk estimates were independent of women's infertility treatment history. CONCLUSIONS: A negative effect of maternal age on birth and neonatal outcome may be seen even after 30 years of age and is partly related to chronic diseases. However, it is impossible to rule out selection bias, but the actual risk must be taken into consideration in antenatal care.

Adult↗
PubMed2000

Localization of somatostatin receptors at the light and electron microscopial level by using antibodies raised against fusion proteins.

Somatostatin mediates its multiple biological effects via specific plasma membrane receptors belonging to the family of G-protein coupled receptors with seven putative membrane-spanning domains. Five somatostatin receptor subtypes (sst1-sst5) have been cloned in human, mouse, and rat. We have raised specific antibodies against the five human somatostatin receptors by using the fusion protein technique. DNA sequences encoding C-terminal parts of the somatostatin receptors were inserted into a pGEX-2T plasmid vector. E. coli bacteria were transformed with the recombinant plasmid and fusion proteins were expressed and purified using the glutathione S-transferase Gene Fusion System. The fusion proteins were emulsified with Freund's complete adjuvant and polyclonal antibodies were raised in rabbits. The antisera were tested for specificity in Western blot analysis of membrane preparations from cell lines expressing the receptors and in membrane preparations of brain tissues. The receptors were visualized at the light microscopical level in paraformaldehyde fixed tissue sections by use of biotin labelled secondary antibodies as well as by amplification with biotinylated tyramide. The final step in the immunohistochemical visualization of the receptors was done by both peroxidase labelled streptavidin/biotin and different fluorophores. At the electron microscopical level, some of the receptors could be visualized in tissues fixed with a combination of paraformaldehyde and low concentrations of glutaraldehyde. In the hamster brain, sst2 receptors labelling was observed in both neuronal processes and perikarya. The staining was present in neo-, and allocortical areas of the forebrain, the hypothalamus, brain stem, and spinal cord. In the rat and human, sst1 receptor was shown to be an auto receptor on somatostatinergic neurons located in the hypothalamus. In the retina both sst1 and sst2 receptors were present. sst1 receptors were confined to amacrine cells, few ganglionic cells, and Müller cell-end feet. sst2 receptors were more widespread than the sst1 receptors. sst2-immunoreactivity was present in dopaminergic amacrine cells, the Müller cell-end feet, and in the inner segments of the cone photoreceptors. Thus, the availability of subtype specific antibodies against the five somatostatin receptors makes it possible to identify the receptors involved in the multiple somatostatinergic system in the body.

Animals↗
PubMed2000

Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2.

In a four-generation family with long QT syndrome, syncopes and torsades de pointes ventricular tachycardia (TdP) were elicited by abrupt awakening in the early morning hours. The syndrome was associated with a novel KCNH2 missense mutation, G572R, causing the substitution of a glycine residue at position 572, at the end of the S5 transmembrane segment of the HERG K(+)-channel, with an arginine residue. This segment is involved in the channel pore and the mutation may cause a reduction in the rapidly activating delayed rectifier K+ current (Ikr), or changed gating properties of the ion channel, leading to prolonged cardiac repolarization. The electrocardiograms of affected persons showed prolonged QT interval and notched T waves. Despite treatment with atenolol, 200 mg twice daily, the proband still experienced TdP episodes. Three untreated relatives of the proband died suddenly, and unexpectedly, at 18, 32, and 57 years of age. The G572R mutation is thus associated with a high mortality rate, and the clinical presentation illustrates that some mutations may not be controllable by just beta-blockade.

Adolescent↗
PubMed2000

Updated appraisal of pacing lead performance from the Danish Pacemaker Register: the reliability of bipolar pacing leads has improved.

The Danish Pacemaker Register was established in January 1982, and the 12 implanting centers in Denmark report to the Register on a continuous basis by use of the European Pacemaker Patient Identification Card. As of August 1999, the Register contained data on 33,164 bradycardia, endocardial, and epicardial (n = 159) lead implants performed in Denmark on 27,738 generators in 24,180 patients for a total of 17,988 (54.2%) ventricular unipolar, 5,610 (16.9%) ventricular bipolar, 2,056 (6.2%) atrial unipolar, and 7,242 (21.8%) atrial bipolar leads. Lead failure was defined as need for replacement or surgical abandonment of the lead due to pacing or sensing problems with the exception of lead displacement. The 10-year survival rate for unipolar leads was 97.2 +/- 0.4% (+/- 2 SE) as compared to 79.6 +/- 3.2% for bipolar leads (P < 0.001). The Medtronic 4012, the Telectronics 284, and the Siemens (Pacesetter) 1010T, 105T, and 1050T bipolar lead models were poor performing leads that needed careful monitoring and appropriate replacement. Excluding those five poor performing bipolar leads, the models yielded a 10-year survival rate of 94.3 +/- 2.4% for bipolar leads. The 5-year survival for all bipolar leads implanted after January 18, 1993 (this was the date that the last of the five poor performing bipolar lead models were implanted in Denmark) was 98.7 +/- 0.4% compared with 98.9 +/- 0.3% for all unipolar leads implanted after January 18, 1993 and 86.8 +/- 1.6% for all bipolar leads implanted on or before January 18, 1993. These results indicate a significant improvement in bipolar lead reliability.

Actuarial Analysis↗