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Biomedical subjects

V Pedersen

Publications and source records attributed to V Pedersen.

At least 19 recordsLinked to original sources
PubMed2004

Randomized clinical trial of the effect of pneumoperitoneum on cardiac function and haemodynamics during laparoscopic cholecystectomy.

BACKGROUND: Conventional laparoscopic cholecystectomy (CLC) with carbon dioxide pneumoperitoneum may cause major cardiovascular changes. The aim of this study was to evaluate the effect of carbon dioxide pneumoperitoneum and positional changes on haemodynamics and cardiac function in patients assigned randomly to CLC or gasless laparoscopic cholecystectomy (GLC). METHODS: Fifty patients with American Society of Anesthesiologists physical status I and II were randomly allocated to CLC (28 patients) or GLC (22). Left ventricular end-diastolic and end-systolic diameters, fractional shortening and cardiac output were determined by transoesophageal echocardiography. Measurements were performed before (phase 1) and 10 and 30 min (phases 2 and 3 respectively) after pneumoperitoneum or abdominal wall traction, and after desufflation or release of abdominal wall traction (phase 4) in supine, Trendelenburg and reverse Trendelenburg positions. RESULTS: Mean diastolic diameter, systolic diameter, mean arterial pressure and heart rate were significantly higher, and fractional shortening was significantly lower, with carbon dioxide pneumoperitoneum than with the gasless procedure during phases 2 and 3. There were no significant differences in cardiac output between the two groups. CONCLUSION: Carbon dioxide pneumoperitoneum was associated with increased preload and afterload in patients undergoing laparoscopic cholecystecomy. It also decreased heart performance (fractional shortening), but did not affect cardiac output.

Adult↗
PubMed2001

Cervical sprouting of corticospinal fibers after thoracic spinal cord injury accompanies shifts in evoked motor responses.

The adult central nervous system (CNS) of higher vertebrates displays a limited ability for self repair after traumatic injuries, leading to lasting functional deficits [1]. Small injuries can result in transient impairments, but the mechanisms of recovery are poorly understood [2]. At the cortical level, rearrangements of the sensory and motor representation maps often parallel recovery [3,4]. In the sensory system, studies have shown that cortical and subcortical mechanisms contribute to map rearrangements [5,6], but for the motor system the situation is less clear. Here we show that large-scale structural changes in the spared rostral part of the spinal cord occur simultaneously with shifts of a hind-limb motor cortex representation after traumatic spinal-cord injury. By intracortical microstimulation, we defined a cortical area that consistently and exclusively yielded hind-limb muscle responses in normal adult rats. Four weeks after a bilateral transsection of the corticospinal tract (CST) in the lower thoracic spinal cord, we again stimulated this cortical field and found forelimb, whisker, and trunk responses, thus demonstrating reorganization of the cortical motor representation. Anterograde tracing of corticospinal fibers originating from this former hind-limb area revealed that sprouting greatly increased the normally small number of collaterals that lead into the cervical spinal cord rostral to the lesion. We conclude that the corticospinal motor system has greater potential to adapt structurally to lesions than was previously believed and hypothesize that this spontaneous growth response is the basis for the observed motor representation rearrangements and contributes to functional recovery after incomplete lesions.

Animals↗
PubMed2001

Sensitization of prepulse inhibition deficits by repeated administration of dizocilpine.

RATIONALE: Repeated administration of psychoactive drugs results in a progressive enhancement of the behavioral effects of these compounds, a phenomenon termed sensitization. OBJECTIVE: We tested whether repeated administration of the non-competitive NMDA receptor antagonist dizocilpine (MK-801) induces sensitization of the disruptive effects of this compound on prepulse inhibition (PPI) of startle. METHODS: Rats received nine daily i.p. injections of 0.1 mg/kg MK-801 in the startle cage and were tested for PPI, startle in the absence of prepulses and motor activity in the startle cage. Another group of rats received MK-801 in the home cage on 9 days without daily testing. Controls were injected with saline and tested daily, while a separate group of rats received saline in the home cage without daily testing. On day 10, all rats received saline injections and were tested. On day 11, all rats were injected with 0.1 mg/kg MK-801 and tested again. On day 12, all rats received 1 mg/kg dl-amphetamine i.p. and were tested for PPI, to assess a possible cross-sensitization. RESULTS: MK-801 had no effect on day 1 of testing but induced a PPI deficit after 6-9 days of daily treatment and testing in those rats that received the drug in the startle cage, but not in the home cage. Motor activity was increased after repeated treatment and testing. There was also a trend towards sensitization of enhancement of the startle magnitude by MK-801 in these rats. dl-Amphetamine reduced PPI in those rats that received daily MK-801 injections in the startle cage to a similar extent as saline injections. CONCLUSIONS: Since PPI is considered as a measure of sensorimotor gating, our data indicate that sensorimotor gating deficits induced by MK-801 are subject to a sensitization process. These findings may be relevant for current hypotheses relating schizophrenic symptoms to sensitization.

Acoustic Stimulation↗
PubMed2001

Enhancement of central nervous system pathology in early simian immunodeficiency virus infection by dopaminergic drugs.

Human immunodeficiency virus infection (HIV) at late stages of the disease is accompanied by neurological complications, including motor, behavioral and cognitive impairment. Using simian immunodeficiency virus (SIV)-infected rhesus monkeys, an animal model of HIV infection, we found that during the asymptomatic SIV infection dopamine (DA) deficits are early components of central nervous system (CNS) dysfunction. To investigate the role of the DA system in SIV infection and to restore the DA deficiency, we administered selegiline, an agent with DAergic and neuroprotective properties, to SIV-infected monkeys. Selegiline increased DA availability but induced CNS vacuolization, SIV encephalitic lesions, and enhanced CNS viral replication during early SIV infection. The pathological changes seem to be mediated by DA, as treatment with L-DOPA, the precursor of DA, had similar effects. We propose that any natural or induced DAergic dysregulation which results in increased DA availability may potentiate HIV-associated neurological disease (ND). Our findings raise new questions regarding the pathogenesis of HIV-ND and generate concerns about the safety of dopaminergic drugs in the clinical management of HIV-infected patients.

AIDS Dementia Complex↗
PubMed2001

Randomized study of coagulation and fibrinolysis during and after gasless and conventional laparoscopic cholecystectomy.

BACKGROUND: Carbon dioxide pneumoperitoneum may be an important pathophysiological factor stimulating the coagulation system during conventional laparoscopic cholecystectomy. The aim of this study was to test the hypothesis that gasless laparoscopy produces smaller changes in the coagulation and fibrinolytic system than carbon dioxide pneumoperitoneum in patients undergoing laparoscopic cholecystectomy. METHODS: Fifty patients were allocated randomly to conventional (n = 26) or gasless (n = 24) laparoscopic cholecystectomy. Blood samples were obtained on admission, after induction of anaesthesia, after insufflation or traction, 30 min after introduction of the laparoscope, 10 min after exsufflation of carbon dioxide or traction, 4 h after extubation and 24 h after operation. RESULTS: The two groups were comparable with respect to age, sex, body mass index and duration of operation. Plasma levels of prothrombin fragment 1 and 2 (F1 + 2), soluble fibrin and D-dimer did not differ between the two groups. F1 + 2 levels varied significantly in both groups during and after operation (P < 0.001). Soluble fibrin and D-dimer levels did not change during operation in either group, but after operation the levels increased significantly in both groups (P < 0.001). CONCLUSION: Carbon dioxide pneumoperitoneum does not enhance the activation of coagulation and fibrinolysis associated with laparoscopic cholecystectomy. The coagulation and fibrinolytic systems are activated during and after gasless as well as conventional laparoscopic cholecystectomy.

Adult↗
PubMed2000

Preference for various nest box designs in farmed silver foxes (Vulpes vulpes) and blue foxes (Alopex lagopus).

Nest box choice experiments were carried out outside the breeding season on adult silver and blue fox vixens with no previous permanent nest box experience. Nest boxes were varied in height of placement, number of rooms, presence of entrance room or platform and light conditions. Only one parameter was varied in any one experiment. Both fox species clearly preferred an elevated multi-room nest box; while silver foxes showed preference for boxes supplied with a platform, blue foxes preferred boxes with an entrance room. There was no significant box preference with respect to light conditions. The possible welfare implications of the preferences are discussed.

Journal Article↗
PubMed2000

Immediate early gene expression in rat basal ganglia after destruction of the dopaminergic system.

In the present study, we performed immunocytochemical mapping of cFos and c-Jun as markers for changes in neural activity in the brains of dopamine denervated rats. We observed a prolonged c-Fos and c-Jun expression in basal ganglia motor and limbic circuits over 96 h. This might be due to alterations in transmitter balances. We conclude, that changes in neural activities are involved in the development of 'extranigral' pathology of Parkinson's disease.

Journal Article↗
PubMed2000

The neuroprotectant properties of glutamate antagonists and antiglutamatergic drugs.

In the slowly progressive neurodegenerative disorders like Parkinson's disease and Alzheimer's disease very different neuronal populations undergo degenerative processes, although the cascades of cellular events leading to death are supposed to be similar. We suggest that the complex pattern of degeneration in Parkinson's disease depends on two processes, a 'primary neurodegeneration' that takes place in the striato-nigral dopamine neurons and a 'secondary degeneration', occurring in distant structures of the basal ganglia network. For the purpose of explaining the regionally different expression of 'primary neurodegeneration' in different diseases, we postulate that the origin of neurodegeneration is associated with the local release of a neurotransmitter. For Parkinson's disease this would mean that the metabolism of dopamine in the striatum, nucleus accumbens and presumably the pedunculopontine tegmental nucleus, together with one or more pathological factors contribute to the initial neurodegeneration. There are recent studies indicating that a transneuronal retrograde degeneration of the substantia nigra pars compacta neurons might be induced by a loss of function of dopaminergic synapses in the striatum. We have recently established an animal model of retrograde striato-nigral degeneration, where the assessment of markers for cellular stress is possible. In Parkinson's disease, several structures distal from the substantia nigra pars compacta undergo neuropathological changes, characterizing the 'secondary neurodegeneration. Our recent studies provide experimental evidence for a chronic cellular stress in these structures because of a relative or absolute glutamatergic overactivity due to the initial loss of dopaminergic innervation. Thus, a loss of dopamine transforms the basal ganglia to a 'destructive network'. Both processes, the 'primary' and 'secondary neurodegeneration', affecting each other, characterize the progress of chronic neurodegeneration. From this point of view, we would further like to develop strategies for symptomatic amendment. Excitatory amino acids seem to be involved not only in the secondary processes of neurodegeneration, but also in initiation of the 'primary degeneration' of the substantia nigra pars compacta. Therefore, a reduction of glutamatergic overactivity constitutes a promising neuroprotective strategy. Especially the new antagonists of the NMDA-receptors with high affinity to the NR2B subunit of the receptor are in focus of our interest, since they reveal a favourable profile of side effects, therefore providing a promising tool for neuroprotection.

Journal Article↗
PubMed1999

Characterization and regional distribution of nitric oxide synthase in the human brain during normal ageing.

Nitric oxide (NO) is a highly diffusible cellular mediator generated from L-arginine by the enzyme nitric oxide synthase (NOS). As little is known about the regional distribution of NOS in the human brain, we examined the distribution pattern of nitric oxide synthase activity in 28 regions of the human brain using the [(3)H]L-citrulline formation assay. To elucidate which isoforms contribute to the total NOS activity we performed Western blot analysis of neuronal, inducible and endothelial NOS. We further determined brain levels of arginine and citrulline as a potential index of NOS activity pre mortem. NOS activity appears to remain unaltered during ageing and is independent of post mortem delay, gender or sample storage time. We identified a regional pattern of NOS distribution with highest levels of NOS activity in the substantia innominata, cerebellar cortex, nucleus accumbens and subthalamicus, whereas lowest levels were measured in the corpus callosum, thalamus, occipital cortex, and dentate nucleus. nNOS was measured throughout the brain, in contrast iNOS and eNOS were not detectable. We therefore conclude that primarily nNOS is responsible for NOS activity in the human brain. Levels of citrulline were higher than those of arginine, but did not correlate with the enzyme activity, suggesting that these parameters are unsuitable for testing NOS activity premortem. The characterization and topographical pattern of NOS in the human brain during normal ageing may assist our understanding of the physiological role of NO and its relevance in Parkinson's and Alzheimer's disease, alcoholism, schizophrenia and AIDS.

Adolescent↗
PubMed1998

Single-dose pharmacokinetics of citalopram in patients with moderate renal insufficiency or hepatic cirrhosis compared with healthy subjects.

OBJECTIVE: To compare the pharmacokinetics of the antidepressant citalopram and its metabolites demethylcitalopram and didemethylcitalopram in subjects with moderate renal insufficiency and subjects with hepatic cirrhosis with that in healthy subjects. METHODS: Pharmacokinetic parameters from three individual, open-label, phase I trials were derived following single oral or intravenous citalopram dose (40 mg) to healthy subjects and a single oral dose (20 mg) to patients. Serum and urine concentrations of citalopram and metabolites were determined using a validated HPLC method. RESULTS: The absolute bioavailability of citalopram tablets in healthy subjects was 80%. The renal clearance was a minor component (<20%) of the total elimination of citalopram. Serum Cmax and t(max) for citalopram were essentially unaffected by the occurrence of renal or hepatic disease. In comparison with healthy subjects, renal impairment was associated with a significant reduction in the renal elimination of citalopram and its two metabolites and a slight prolongation of serum citalopram t1/2 (49.5 h vs 36.8 h in healthy subjects). Cirrhosis resulted in significant decrease in citalopram CLoral (0.21 vs 0.331 x h(-1) x kg(-1) in healthy subjects) and increase in Vz x f(-1) with an approximately twofold increase in t1/2 (83.4 h vs 36.8 h in healthy subjects). Indices of renal (creatinine or 51Cr-EDTA clearances) and hepatic (galactose elimination capacity or Child-Pugh score) function were poor predictors of the changes in the pharmacokinetics of citalopram and its metabolites in these populations. CONCLUSION: No reduction of citalopram dosage is warranted in patients with moderately impaired renal function. However, that may not apply for patients with severe renal failure. In patients with impaired hepatic function, prescription of a lower dosage of citalopram may be appropriate.

Administration, Oral↗
PubMed1997

The effect of citalopram in panic disorder.

BACKGROUND: Citalopram is a serotonin reuptake inhibitor which has been demonstrated to be highly selective and with a superior tolerability profile to the classical tricyclic antidepressants. This study was designed to test whether there was any difference in efficacy in the management of panic disorder (PD) between citalopram and placebo. METHOD: This was a double-blind, placebo and clomipramine controlled, parallel group eight-week study. A total of 475 patients with PD, with or without agoraphobia, were randomised to treatment with either placebo, clomipramine 60 or 90 mg/day, or citalopram 10 or 15 mg/day, or 20 or 30 mg/day, or 40 or 60 mg/day. Doses were increased over the first three weeks, stabilised during the fourth week and fixed between weeks five and eight. RESULTS: Treatment with citalopram at 20 or 30 mg, 40 or 60 mg and clomipramine were significantly superior to placebo, judged by the number of patients free of panic attacks in the week prior to the final assessment. All rating scales examined suggested that citalopram 20 or 30 mg was more effective than citalopram 40 or 60 mg. CONCLUSION: The most advantageous benefit/risk ratio for the treatment of PD was associated with citalopram 20 or 30 mg/day.

Adolescent↗
PubMed1994

The optimal dosing regimen for citalopram--a meta-analysis of nine placebo-controlled studies.

Optimal dosing schedules for an antidepressant drug can only be established during clinical studies in depressed patients. The benefits of antidepressant therapy are usually progressive, and thus patients must be maintained on a particular treatment for at least 3-4 weeks to assess the efficacy of different doses. Meta-analysis, a widely accepted statistical technique which allows the combination of the results of multiple studies, was used to assess the efficacy of several doses of citalopram over nine placebo-controlled clinical trials. Statistically significant differences between citalopram and placebo were found at both the 20 and 40 mg dose levels. The minimal effective dose of citalopram was shown to be 20 mg. However, analysis of patient subgroups revealed a tendency for those patients suffering from severe or recurrent depression to achieve better results with a higher dosage (40 mg), while patients experiencing their first period of depression or with less severe depression responded well to the minimally effective dose of 20 mg.

Adolescent↗
PubMed1993

A controlled Nordic multicentre study of zuclopenthixol acetate in oil solution, haloperidol and zuclopenthixol in the treatment of acute psychosis.

Zuclopenthixol acetate--a new injectable formulation with a duration of action of 2-3 days--was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed, psychotic patients. The patients were stratified into 3 diagnostic categories: acute psychoses (48 patients), mania (22 patients), and exacerbation of chronic psychoses (73 patients). The patients were rated on the Brief Psychiatric Rating Scale (BPRS), the Bech-Rafaelsen Mania Rating Scale (BRMAS) (only manic patients) and globally on the Clinical Global Impression (CGI). The study was an open, randomized multicentre trial with a 6-day treatment period. The zuclopenthixol acetate patients received 1-4 doses, the haloperidol patients 1-26 and the zuclopenthixol patients 1-22 doses. The assessments on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories, with no differences between treatments. The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments. All 3 treatments caused a rapid remission of symptoms on the BRMAS. Haloperidol induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments. Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients.

Acute Disease↗
PubMed1992

Zuclopenthixol and haloperidol in patients with acute psychotic states. A double-blind, multi-centre study.

A double-blind, multi-centre study was carried out in 49 hospitalized patients with an acute psychosis or an exacerbation of a chronic psychosis to compare the wanted and unwanted effects of the neuroleptics, zuclopenthixol and haloperidol. Patients were allocated at random to receive treatment with one or other of the trial drugs for 8 weeks or until discharge. Five patients on zuclopenthixol and 6 on haloperidol were excluded from the efficacy analyses because they did not complete a minimum of 4-weeks' treatment. Dosage was chosen and adjusted to the individual patient's condition and response. The average daily doses in Week 4 were 33.5 mg and 10.3 mg, respectively. Clinical assessments, including CGI, BPRS and the UKU side-effect scale, were done at baseline, and after 1, 2, 4, 6 and 8 weeks of treatment or at discharge if the patient was discharged earlier than Week 8. Both treatments caused a significant reduction in scores with no between-group differences. More patients in the zuclopenthixol group were discharged early indicating slightly more rapid onset of action. Zuclopenthixol caused a significantly greater improvement in 'anxious-depression' factor score than haloperidol. The most frequent unwanted effects were extrapyramidal symptoms and there were no significant differences between the groups. The extrapyramidal symptoms tended to be transient in the zuclopenthixol group, but not in the haloperidol group. The study confirmed that both zuclopenthixol and haloperidol were effective drugs in the treatment of acute, psychotic patients. There was a trend towards a slightly more rapid onset of effect and a somewhat stronger anxiolytic-antidepressant effect by zuclopenthixol compared to haloperidol.

Adult↗
PubMed1991

Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia.

Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect. This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia (TD) and less rebound aggravation after withdrawal than pure D2 antagonists. In this study the effect of zuclopenthixol (mixed D1/D2 antagonist) and haloperidol (D2 antagonist) was evaluated in chronic psychotic patients with TD. Fifteen patients completed a randomized crossover study with blind evaluation of TD and parkinsonism. The test medications, haloperidol and zuclopenthixol, caused a significant suppression of TD and a significant increase of parkinsonism. No significant differences between haloperidol and zuclopenthixol were observed. No TD aggravation was seen. The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD.

Adult↗