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Biomedical subjects

L Goossens

Publications and source records attributed to L Goossens.

At least 19 recordsLinked to original sources

Conformation of the tripeptide Cbz-Pro-Leu-Trp-OBzl(CF3)2 deduced from two-dimensional 1H-NMR and conformational energy calculations is related to its affinity for NK1-receptor.

Chemical modifications of dual NK1/NK2 ligand Cbz-Gly-Leu-Trp-OBzl(CF3)2 (1) enabled us to create a high NK1 selective ligand Cbz-Pro-Leu-Trp-OBzl(CF3)2 (2). A determination of the conformational behavior of tripeptide 2 in solution is described. The 1D and 2D 1H-NMR techniques (COSY and ROESY) were used to assign resonances. Observed interproton distance restraints were considered to characterize conformational behavior. Spectral data indicate that tripeptide 2 presents a rigidified structure in DMSO stabilized by H-bond in two gamma-turns. Agreement with experimental data was obtained by averaging the 1H-NMR parameters over several combinations of low-energy conformations.

Animals↗

A flexible approach to the design of new potent substance P receptor ligands.

The development of small-molecule antagonists of the substance-P-preferring tachykinin NK1 receptor offers an excellent opportunity to exploit these molecules as novel therapeutic agents in diverse pathologies such as depression, emesis or asthma. GR71251 has previously been identified as a potent and selective substance-P-receptor antagonist. We have therefore undertaken the synthesis of new pseudopeptidic analogues based on the C-terminal sequence of GR71251. The evaluation of binding affinities toward NK1 and NK2 receptors has enabled us to propose new selective NK1 ligands with high affinity. Structure-activity relationships showed that the Trp-OBzl(CF3)2 moiety is essential for NK1 affinity and that the introduction of building units such as spirolactam, lactam or proline, leading to a constrained peptide, increased selectivity for NK1 receptors. These compounds constitute a useful starting point for new substance P antagonists and represent an attractive lead series for further studies on the design of specific NK1 antagonists.

Animals↗

Indigenous malaria in a suburb of Ghent, Belgium.

We report here details of a patient with Plasmodium falciparum malaria which was acquired in the vicinity of Ghent (Evergem) in July 1997. Indigenous malaria disappeared from Belgium in 1938. Due to an increase in international travel, the influx of migrant labor and the changing environmental conditions, there has been an upsurge of imported malaria. Airport- and port-malaria is acquired through the bite of a tropical anophelline mosquito by people whose geographical history excludes exposure to this vector in its natural habitat. As far as we know, only two cases of port-malaria have been reported: in Marseille. We describe here another possible case of port-malaria due to infection with P. falciparum in a 42-year-old woman with an underlying non-Hodgkin lymphoma.

Adult↗

Relationships during adolescence: constructive vs. negative themes and relational dissatisfaction.

The present study set out to test Coleman's focal theory of adolescence in a cross-national context. The London Sentence Completion Test (LSCT) and the Louvain Loneliness Scale for Children and Adolescents (LLCA) were administered to 370 adolescents (11 to 17 years of age) in the Dutch-speaking part of Belgium. The findings confirm those of earlier work using the London Sentence Completion Test (LSCT) and other questionnaire-type measures in various English-speaking countries (England, Scotland, New Zealand and United States). The general pattern of peak ages for adolescents' interpersonal concerns provided support for the focal model. Negative feelings about being alone, relationships with parents, heterosexual relationships, small groups and rejection from larger groups do not emerge all at once, but seem to be dealt with issue by issue. The results for the Louvain Loneliness Scale for Children and Adolescents (LLCA), which measures loneliness in relationships with both parents and peers, and adolescents' attitudes towards being alone, confirmed the age trends observed with the sentence completion measure. Taken together, these findings strongly suggest that the changes in adolescent relationships are intimately linked to the general process of individuation, as implied by the focal model. It should be pointed out, however, that important parts of the focal theory remain at present untested. Suggestions for future empirical and conceptual work related to these aspects of Coleman's model are outlined.

Adolescent↗

Emotional autonomy, psychosocial adjustment and parenting: interactions, moderating and mediating effects.

Following inconsistent results on the developmental outcomes of emotional autonomy, this study examined the consequences of emotional and behavioural autonomy for different aspects of psychosocial adjustment in the context of the parenting process as perceived by the adolescent. Measures of emotional autonomy, behavioural autonomy, perceived parenting and various aspects of psychosocial adjustment were completed by a sample of 558 adolescent boys and girls (aged 12-17 years) from the Dutch-speaking part of Belgium. A continuous measure of authoritativeness was constructed for this study. Correlations revealed that authoritativeness was associated with a positive pattern of adjustment, while autonomy was associated with a negative pattern of adjustment, except for self-reliance. Analyses indicated that authoritativeness and autonomy did not interact to produce mean differences in adjustment. Further, hierarchical multiple regression analyses showed that it was only for self-reliance that the interaction between emotional autonomy and authoritativeness explained significantly more variance than a model that comprised only the main effects. Finally, path analysis clarified the difference between emotional and behavioural autonomy, in that emotional autonomy predicted only higher levels of internal distress, while behavioural autonomy predicted only lower school grades and higher levels of deviant behaviour, at least when authoritativeness was partialled out. These results reveal that it is useful to study autonomy and its developmental outcomes in the broader family context, but they also reveal the limitations of such an approach.

Adolescent↗

Interictal and ictal video-EEG monitoring.

PURPOSE: The purpose of this paper is to demonstrate the diagnostic efficacy and therapeutic relevance of video-EEG monitoring in an large patient population with long-term follow-up. PATIENTS AND METHODS: Between October 1990 and May 1997, 400 patients were monitored at the Epilepsy Monitoring Unit (EMU) of the University Hospital in Gent. In all patients, the following parameters were retrospectively examined: reason for referral, tentative diagnosis, prescribed antiepileptic drugs (AEDs), seizure frequency, number of admission days, number of recorded seizures, ictal and interictal EEG, clinical and electroencephalographic diagnosis following the monitoring session. During follow-up visits at the Epilepsy Clinic, we prospectively collected data on different types of treatment and post-monitoring seizure control. RESULTS: 255/400 (64%) patients were referred for refractory epilepsy. 145/400 (36%) patients were evaluated for attacks of uncertain origin. Mean follow-up, available in 225 patients, was 28 months (range: 6-80 months). Mean duration of a single monitoring session was 4 days (range: 2-7 days). Prolonged interictal EEG was recorded in all patients and ictal EEG in 258 (65%) patients. Following the monitoring session, the diagnosis of epilepsy was confirmed in 217 patients. Pseudoseizures were diagnosed in 31 patients (8%). AEDs were started in 19 patients, stopped in 6 and left unchanged in 110. The type and/or number of AEDs was changed in 111 patients. Sixty patients underwent epilepsy surgery. In 48 surgery patients, follow-up data were available, 29 of whom became seizure-free, and 16 of whom experienced a greater than 90% seizure reduction. Vagus nerve stimulation was performed in 11 patients, 2 became seizure-free, and 7 improved markedly. Of the non-invasively treated patients in whom follow-up was available (n = 135), 70 became seizure-free or experienced a greater than 50% reduction in seizure frequency; 51 patients experienced no change in seizure frequency. Outcome was unrelated to the availability of ictal video-EEG recording. In patients with complex partial seizures, seizure control was significantly improved when a well-defined ictal onset zone could be defined during video-EEG monitoring. CONCLUSION: Prolonged interictal EEG monitoring is mandatory in the successful management of patients with refractory epilepsy. Ictal video-EEG monitoring is very helpful but not indispensable, except in patients enrolled for presurgical evaluation or suspected of having pseudoseizures.

Adolescent↗

Epilepsy surgery in Belgium, the experience in Gent.

Between January 1992 and July 1998, 320 patients were presurgically evaluated for medically refractory epilepsy at the University Hospital of Gent. All patients underwent a comprehensive presurgical evaluation, including extensive neurological history and examination, video-EEG monitoring of interictal EEG and habitual seizures, and optimum magnetic resonance (MR). In a large subgroup of these patients, a comprehensive neuropsychological examination and interictal 18FDG-PET were performed. Subsequently, a bilateral carotid angiography and intracarotid amytal procedure (Wada-test) were planned in 49 patients to establish hemispheric language dominance and bilateral memory function. After proper selection, 23 patients underwent invasive video-EEG monitoring with intracranial implantation of parenchymal and/or subdural electrodes to further document the area of seizure onset. From the initial group of 320 potential surgical candidates, 75 patients (42 males, 33 females) with mean age of 29 years (range: 2 months-55 years) and mean duration of uncontrolled seizures of 15 years (range: 2 weeks-38 years) eventually underwent a surgical procedure. Sixty of 75 patients were on high dose antiepileptic polytherapy. Optimum MR detected structural abnormalities, confined to a limited brain area, in 71 patients. These abnormalities were of space-occupying nature in 31 cases; an atrophic lesion was suspected in 39 patients; a combination of space-occupying and atrophic lesion was seen in 1 case. Structural abnormalities were most frequently located in the temporal lobe (n = 53) and the frontal lobe (n = 10). Video-EEG monitoring documented complex partial seizures in 67 patients with occasional secondary generalisation in 32. Most patients had complex partial seizures of temporal lobe as defined by clinical and EEG criteria. Two patients had only simple partial seizures. Ultimately, an area of seizure onset could be determined in all patients. Temporal lobectomy with hippocampectomy was the most commonly performed procedure (n = 42). In 13 patients, complete lesionectomies were performed for epileptogenic structural lesions in and outside the temporal lobe. In 2 patients, only partial lesionectomies were possible; in 5 patients, only biopsies in combination with partial lesionectomies could be performed. Anterior 2/3 callosotomy was performed in 4 patients and hemispherectomy was performed in 2 patients. Postsurgical seizure control, after average follow-up of 50 months (range: 12-98 months), was excellent in 49 patients who became seizure-free. In these patients, antiepileptic therapy was tapered 2 years after surgery. Patients in whom only biopsies or partial lesionectomies were performed have poor seizure control. Epilepsy surgery is a rewarding therapeutic alternative for patients with medically refractory epilepsy. Comprehensive presurgical evaluation and epilepsy surgery provide excellent neurological, neurophysiological, neuropsychological and imaging research opportunities.

Adolescent↗

Dipole modelling and intracranial EEG recording: correlation between dipole and ictal onset zone.

This study includes 11 patients (3 males, 8 females) with mean age of 29 years (range: 15-42 years) who underwent a presurgical evaluation for refractory complex partial seizures (CPS). In all patients, neuroimaging (1.5 T optimum-MR) demonstrated intracranial structural abnormalities (space-occupying: n = 2; atrophic: n = 8; dysplastic: n = 1) and video-EEG monitoring showed CPS, because of discrepancies in the non-invasive examinations, all underwent additional intracranial EEG monitoring. After tailored resective procedures, all but one patient became seizure free. Mean follow-up was 30 months (range: 12-52 months). Results of intracranial EEG recording were compared with spatiotemporal dipole mapping of interictal and ictal epileptic discharges. Interictal dipole modelling revealed two distinct dipole patterns. Patients with lesions located in the medial temporal lobe uniformly presented a combined dipole that consisted of a radial and a tangential component with a high degree of elevation relative to the axial plane. Patients with extrahippocampal lesions had a less stable dipole with a predominant radial component. Dipole modelling of early ictal discharges revealed a striking correspondence with the interictal findings in individual patients. Elevation of ictal dipoles was always congruent with localisation based on intracranial EEG recordings. Interictal and ictal dipole mapping of medial temporal lobe sources may limit the number of surgical candidates for refractory CPS that need intracranial EEG recording. Whether ictal dipole modelling can be equally useful in extratemporal epilepsy remains to be proven.

Adolescent↗

A comparison of N-butylscopolammonium bromide and butorphanol tartrate for analgesia using a balloon model of abdominal pain in ponies.

The analgesic effect of N-butylscopolammonium bromide (0.3 mg/kg) using a balloon-induced model of colic in ponies was evaluated and compared with butorphanol tartrate (0.1 mg/kg). Eight adult ponies were used and each received both treatments during the two different trials. The order in which the treatment was received was randomly assigned. At the start of each trial, moderate abdominal pain was induced by inflation of a balloon placed in the lumen of the caecum. The ponies were evaluated every 5 minutes, and a cumulative pain score (CPS) was assigned. Two baseline measurements were recorded, followed by the administration of one of the two treatments. Assessments were continued for 60 minutes, or until moderate abdominal pain returned. Three ponies out of 8 responded to treatment with butorphanol tartrate, while 6 out of 8 ponies responded to N-butylscopolammonium bromide. There were no statistical differences in the CPS or duration of drug action between treatments.

Abdominal Pain↗

Effects of alpha 2-agonists on intrauterine pressure and sedation in horses: comparison between detomidine, romifidine and xylazine.

The effect of three alpha 2-agonistic sedatives, Detomidine (0.04 mg/kg), Romifidine (0.08 mg/kg) Xylazine (1.1 mg/kg) and placebo (NaCl), on intrauterine pressure was investigated with an intrauterine balloon model in four non-pregnant warmblood mares. Within 6.0 (+/- 2.2) min mean pressure increases of 9.80 (+/- 3.74), 6.88 (+/- 3.95) and 13.95 (+/- 5.19) mmHg were recorded for Detomidine, Romifidine and Xylazine, respectively. Placebo had no significant effect. The mean duration of pressure increase was 30.0 (+/- 5.10), 17.67 (+/- 9.87) and 19.50 (+/- 13.78) min for Detomidine, Romifidine and Xylazine, respectively. There was no significant difference in the degree and duration of sedation between the three treatment groups. It is concluded that alpha 2-agonists exert a marked pressure increase in the uterus with no statistically significant differences in degree and duration between the three substances. With equipotent doses no difference in duration and degree of sedation could be calculated.

Adrenergic alpha-Agonists↗

Facts and fiction about memory aging: a quantitative integration of research findings.

A meta-analytic literature review on adult age differences in speed of search in short-term memory (12 studies), memory span (40 studies), list recall (68 studies), paired-associate recall (21 studies), and prose recall (39 studies) is presented. Results show that age differences are quite large (depending on the task, elderly people can be situated between the 3rd and the 38th percentile of the adult age memory performance distribution) and quasi-omnipresent, even under conditions of cued recall or semantic task orientation. Evidence for age sensitivity is found for the process of categorization of lists, but not for semantic processing, association strategies, imagery, nor for extracting main points from prose material. The elderly population benefits more than the young from the possibility of reviewing lists or texts. Differences between young adults and old-old adults are larger than between young adults and the young-old for speed of search in short-term memory and prose recall only. In two out of the five tasks, lower education is reliably associated with larger age differences.

Adolescent↗

The airway response of horses with recurrent airway obstruction (heaves) to aerosol administration of ipratropium bromide.

The airway response to aerosol administration of the anticholinergic agent ipratropium bromide was determined in 8 horses with recurrent airway obstruction (heaves). The reversibility of airway obstruction was confirmed by measuring lung function before and during stabling; and by determining the response to atropine administration (0.02 mg/kg bwt intravenously). The dose-response to ipratropium bromide was determined using a Williams square design experiment in which 25, 50 or 75 micrograms ipratropium bromide/ml (4 ml/100 kg bwt) or the same volume of vehicle was administered to each horse by nebulisation. Lung function was measured before and 1 and 4 h after nebulisation. Vehicle had no effect on lung function. Ipratropium decreased the maximal change in pleural pressure during tidal breathing (delta Pplmax) and pulmonary resistance (RL) and increased dynamic compliance (Cdyn). At the 1 h measurement period, the effect on RL and Cdyn was dose-dependent. A separate experiment demonstrated that the duration of action of ipratropium was between 4 and 6 h.

Administration, Inhalation↗

Improving memory performance in the aged through mnemonic training: a meta-analytic study.

The effectiveness of memory training for the elderly was examined through a meta-analysis of pre-to-posttest gains on episodic memory tasks in healthy subjects aged 60 or above. Pre-to-posttest gains were found to be significantly larger in training groups (0.73 SD, k = 49) than in both control (0.38 SD, k = 10) and placebo (0.37 SD, k = 8) groups. Treatment gains in training groups were negatively affected by age of participants and duration of training sessions and positively affected by group treatment, pretraining, and memory-related interventions. No differences in treatment gain were obtained as a function of type of mnemonic taught nor the kind of pretraining used.

Aged↗

A comparison of the sedative effects of three alpha 2-adrenoceptor agonists (romifidine, detomidine and xylazine) in the horse.

The sedative effects of a new alpha 2-adrenoceptor agonist, romifidine, were compared with those of xylazine and detomidine. Five horses were treated with two doses of romifidine (40 micrograms/kg body weight and 80 micrograms/kg body weight), two doses of detomidine (10 micrograms/kg body weight and 20 micrograms/kg body weight) and one dose of xylazine (1 mg/kg body weight) given by intravenous injection using a Latin-square design. The dose of 80 micrograms/kg romifidine appeared equipotent to 1 mg/kg xylazine and 20 micrograms/kg detomidine, although at these doses both xylazine and detomidine had a shorter action. Detomidine 20 micrograms/kg and xylazine both produced greater lowering of the head and a greater degree of ataxia than romifidine at either dose. Romifidine produced sedation similar to that of the other drug regimes. The effect upon imposed stimuli was similar.

Acoustic Stimulation↗

Detection of subtle reciprocal translocations by fluorescence in situ hybridization.

Three different subtle reciprocal translocations were detected on long, well-banded chromosomes. The same translocations were examined using fluorescence in situ hybridization (FISH) with chromosome-specific libraries and unique DNA sequences. Our findings show that FISH allows rapid and unequivocal detection and characterization of this type of chromosome rearrangement. This approach is especially useful for prenatal diagnosis when one of the parents is a balanced carrier of such small fragment translocations.

Adult↗