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Biomedical subjects

A Verstraete

Publications and source records attributed to A Verstraete.

At least 19 recordsLinked to original sources

[Use of gamma-hydroxybutyric acid (GHB) at rave parties and in date rape in France: myth of reality?].

Since many years gamma-hydroxybutyric acid (GHB) is presented as very popular in rave-parties and for bodybuilders. It seems to be a controversy between media coverage and the results of toxicological analysis done in high-level laboratories. In order to clarify this problem, we compiled the data of 6 laboratories. They used the same analytical method by GC/MS. Depending the laboratory, the limit of detection was 1-2 micrograms/mL and the limit of quantification was 2.5-5 micrograms/mL. Two labs where looking for GHB in each forensic case (100 and 150 cases a year). Others labs performed GHB analysis only on specific request (each 10 cases a year). Mean time between ingestion of GHB and blood/urine sampling was 12-48 h. Mean time between sampling and analysis was much higher (a few hours to a few month. All samples were stored at +4 degrees C. Only 3 cases were considered as positive (blood GHB: 165, 132 and 114 micrograms/mL, urine GHB: 7450 and 436 micrograms/mL) They were admitted in an hospital EU. Interpreting results remains very difficult because GHB is endogenous, present in blood and urine, and its half-life is very short. One has to report only "positive" GHB results when amounts are higher than 5 micrograms/mL in blood and 10 micrograms/mL in urine. Obviously, forensic toxicologists have to play a very important part in diagnosis of GHB intoxications and estimating its frequency. Actually, because the lack of data in France, it is not possible to answer the question asked in the title of this paper.

Forensic Medicine↗

Influence of preoperative combined radiochemotherapy on surgical outcome and colonic anastomotic healing: experimental study in the rat.

PURPOSE: To study the influence of combined preoperative hyperfractionated irradiation with intraperitoneal 5-fluorouracil (5-FU) on surgical outcome and colonic anastomotic healing in a rat model. METHODS: Male Wistar rats were given 41.6 Gy of preoperative radiotherapy (RT) or sham irradiation, with intraperitoneal 5-FU at low dose (10 mg/kg) or high dose (20 mg/kg). Animals were arranged in 6 groups: RT + low-dose 5-FU (RCT-L), RT + high-dose 5-FU (RCT-H), sham RT + low-dose 5-FU (CT-L), sham RT + high-dose 5-FU (CT-H), RT alone (R), and a control group (sham RT + intraperitoneal saline). Side-to-side colonic anastomoses were constructed from one irradiated and one nonirradiated limb 4 days after radiochemotherapy. Animals were sacrificed 10 days after surgery. RESULTS: Compared to controls, more complications occurred in group RCT-H (50% versus 0%, p = 0.01). Adhesion formation was more intense in groups RCT-H and CT-H (p < 0.001 and p = 0.001, respectively). After therapy, white blood cell counts dropped significantly in all irradiated animals (p < 0.01), and platelet counts decreased significantly in group RCT-H (p = 0.01). No significant differences were noticed in anastomotic bursting pressure when the treated groups were compared to each other or to the control group. CONCLUSIONS: Neoadjuvant radiochemotherapy has no adverse effect on the strength of colonic anastomosis in this rat model. However, the combined RT with high-dose 5-FU does increase operative morbidity and adhesion formation.

Anastomosis, Surgical↗

The effect of duration and timing of systemic cyclosporine therapy on corneal allograft survival in a rat model.

BACKGROUND: Systemic cyclosporine A (CsA) remains a valuable treatment option in the prevention of corneal graft rejection, but the question of timing and duration of this systemic therapy remains unresolved. The effect of a pre- and postoperative dosing schedule, related to the expected moment of rejection, was examined in a rat model. METHODS: All AO (strain) recipients of PVG grafts were assigned to the following treatment groups: Group 1 (controls), groups 2-5 (a postoperative treatment regimen of CsA for 5, 10, 15 and 30 days respectively) and groups 6 and 7 (CsA preoperatively for 5 days and postoperatively for another 5 or 10 days respectively). Corneal allografts were clinically evaluated and blood CsA levels were measured at various time points. RESULTS: Untreated controls rejected their allografts after 13 days. Regression analysis showed a strongly significant positive correlation between graft survival time and duration of cyclosporine therapy. There was no difference in graft survival between groups 3 (CsA 10 days) and 4 (CsA 15 days). A pre-operative dosing schedule of CsA followed by postoperative treatment had no advantage over a solely postoperative treatment regimen. The moment of rejection was characterized by a low to undetectable CsA concentration. CONCLUSION: The present study demonstrates a significant influence of the duration of systemic CsA administration on allograft survival time. However, preoperative administration of CsA does not seem to have an additional influence on graft survival, which is in line with the biological evidence of the mechanism of action of CsA on the efferent arm of graft rejection.

Animals↗

Quantification of the size of primary spontaneous pneumothorax: accuracy of the Light index.

BACKGROUND: The size of a pneumothorax (PTX) is usually estimated by the Light index. Treatment strategies of (primary, spontaneous) PTX partially depend upon the size of the PTX. To our knowledge, the Light index has not yet been correlated with the actual volume of the PTX. OBJECTIVES: To correlate the estimated size of a primary spontaneous PTX by means of the Light index, with the actual amount of air present in the pleural space. METHODS: Actual PTX volumes were measured by means of manual aspiration of air present in the pleural space in 18 patients with primary spontaneous PTX and correlated with the size estimation obtained by the Light index. RESULTS: Light index and volume measurements were strongly correlated (r = 0.84, p < 0.0001). CONCLUSIONS: The Light index is a good estimate of the actual size of a (primary spontaneous) PTX.

Adolescent↗

Heparin-induced release of protein-bound solutes during hemodialysis is an in vitro artifact.

BACKGROUND: Several studies have pointed to a release of drugs or protein-bound solutes from their binding sites during heparinization. The effect is attributed to the metabolism of triglycerides to free fatty acids (FFAs), which compete with drugs for protein binding sites. This study evaluated the impact of intradialytic heparin on the free concentration of the uremic toxin p-cresol and on FFAS: METHODS: Blood samples from hemodialysis (HD) patients, before and during HD, were collected with selected anticoagulation strategies. We assessed the effects of standing time, temperature, pH, and the addition of a lipase inhibitor, tetrahydrolipstatin (THL) to blood samples on the free p-cresol concentration. p-Cresol was analyzed by HPLC with fluorescence detection. We measured FFAs by gas chromatography, and the free fractions of added valproic acid and phenytoin were evaluated by fluorescence polarization immunoassay. RESULTS: In blood samples (n = 22) not submitted to a specific treatment, free p-cresol increased from 9.9 +/- 5.1 to 31.9 +/- 22.3 micromol/L after 30 min of heparin HD (P < 0.001) and correlated significantly with FFAs (r = 0.80; P = 0.002; n = 12). There was no increase in free p-cresol during heparin-free HD (n = 6) and trisodium citrate HD (n = 9). In addition, p-cresol in ultrafiltrates (n = 3) did not correspond to the free p-cresol in heparinized blood, suggesting that the increase in free p-cresol was artifactual. The release of p-cresol in the test tube was enhanced by standing time (n = 6), sample temperature (n = 6), and alkaline pH (n = 6). Inhibition of lipase activity with THL prevented the increase of FFAs (n = 6) and the release of free p-cresol during HD (n = 22). These results were corroborated by the study of the free fraction of valproic acid (n = 6) and phenytoin (n = 6). CONCLUSIONS: The free concentrations of protein-bound solutes in plasma of heparinized patients are influenced by external factors that alter the lipase activity in the test tube. The free fraction does not increase during HD when lipase activity is neutralized at the time of blood sampling, so that previously reported increases are probably artifacts.

Aged↗

Cortisol in violent suicidal behaviour: association with personality and monoaminergic activity.

BACKGROUND: According to recent theories, suicidal behaviour is associated with depressive disorders that are commonly induced by social stressors in persons with a trait-dependent vulnerability. Stressor-induced increased cortisol secretion may interfere with this vulnerability that can be defined in terms of (possibly inter-related) biological and psychological or personality-related characteristics. Delineation of such trait-like characteristics may increase the specificity in the prediction of suicidal behaviour and thus lead to new approaches to the treatment and prevention of suicidal behaviour. METHODS: Psychiatric symptomatology, personality dimensions (Cloninger's Temperament and Character), peripheral markers of serotonergic (whole blood serotonin, platelet MAO activity) and noradrenergic (plasma MHPG) activity, and urinary cortisol were measured in a random sample of patients with a history of violent suicidal behaviour and compared to those of patients without such a history. RESULTS: When compared to patients without a history of violent suicidal behaviour (n=23), patients with such a history (n=17) were characterised by higher urinary cortisol levels, a significantly lower mean score on Reward Dependence, a borderline significantly increased score on Novelty Seeking and a significantly lower mean plasma MHPG level. Urinary cortisol level correlated significantly with Reward Dependence and Novelty Seeking scores. There were no differences between patient groups regarding severity of anxiety or depressive symptomatology. No differences with regard to the biological parameters were found between patients who recently attempted suicide and those with a history of suicidal behaviour. LIMITATIONS: Limitations of this study included a relatively small number of study subjects and the use of peripheral markers to assess central neurotransmission functions. CONCLUSIONS: Violent suicidal behaviour is associated with increased cortisol secretion, a personality profile defined by low Reward Dependence (reflecting the degree of sensitivity to social stressors) and a tendency of increased Novelty Seeking (related to impulsivity and the regulation of anger), and reduced noradrenergic functioning (possibly reflecting an inability to adapt to stressors).

Adult↗

Physical performance of patients with numerous psychosomatic complaints suggestive of hyperventilation.

In some patients exercise induces numerous complaints which cannot be attributed to an organic disorder, and which are suggestive of hyperventilation. The study was designed to investigate in this type of patient: 1) exercise capacity and muscle force; 2) breathing pattern and symptoms during maximal exercise and recovery; 3) relationships between symptoms and breathing pattern. Twenty-four patients were compared with 20 healthy subjects. They performed a maximal incremental cycle ergometer test and peripheral and respiratory muscle strength were measured. Patients tended to have a decreased exercise capacity and presented with moderately reduced muscle strength. At comparable minute ventilation, breathing frequency was higher (mean: 24 versus 21 per minute) and tidal volume smaller (mean: 1.42 versus 1.67 L). End-tidal partial pressure of carbon dioxide (PET,CO2) was not significantly different. A significant relation was observed between PET,CO2 and respiratory frequency during recovery in patients, suggesting a reduced flexibility of the ventilatory response to exercise. In patients respiratory complaints and paresthesias were weakly correlated to PET,CO2 at moderate exercise. It is suggested that the physical deconditioning observed in those patients is rather a consequence than a cause of the response to exercise. The link between symptoms and breathing pattern might be explained by a psychological conditioning process.

Adult↗

Classification of medicines according to their influence on driving ability.

Within the scope of an information campaign of the Belgian Institute for Road Safety an attempt was made to classify 179 medicinal drugs from 9 therapeutic groups, listed in the Belgian "Commented Repertory of Drugs--1997", according to their effect on driving performance. The categorisation was based on literature data from about 500 references and used the system proposed by Wolschrijn et al [1]: 7 classes ranging from no effect (I) over minor and moderate (II.1,II.2) to severe effects (III), completed with the respective* categories (I*,II*,III*) for presumed classes with insufficient scientific data. Forty-two drugs (24%) were considered having severe effects (III/III*). Only 28/179 molecules (16%) were classed in I/I*: no hypnotics-sedatives (33), anticonvulsants (10), antidepressants (25), neuroleptics (29), nor narcotic analgesics and antitussives (18) were listed in this no-effect category, while for 7/24 antihistamines (5/20 H1 and 2/4 H2), 12/20 beta blockers and 9/10 central stimulants the effect was considered negligible. Antidiabetics were not classified, as the danger lies in the risk of hypoglycemia due to inadequate use. The classification of the molecules proved to be problematic due to the lack of study data (42% of molecules in presumed categories) and the diversity in the study protocols. The effect on driving ability is dose-dependent and time-related, which makes the use of a single category inadequate; the effect further depends on co-ingestion of other medicines or alcohol, the development of tolerance and the condition of the subject. Physicians and pharmacists can use the proposed categorisation as a scientific base for guiding their patients, but should take into account the factors involved for each patient when estimating the driving ability.

Automobile Driving↗

Bone turnover during short-term therapy with methylprednisolone or budesonide in Crohn's disease.

BACKGROUND: Glucocorticosteroids are used frequently for the treatment of relapses of Crohn's disease. AIM: To investigate the influence of the new topically active glucocorticosteroid budesonide in comparison with methylprednisolone on bone turnover in a randomized open trial. METHODS: Twenty-nine patients received either budesonide (controlled ileal release formulation) 9 mg for 10 weeks, or methylprednisolone 32 mg (equivalent to 40 mg prednisone) orally for 3 weeks with subsequent tapering. RESULTS: Patients who completed the trial with methylprednisolone (n = 8) had suppression of serum osteocalcin (30.2 +/- 2.6 to 20.4 +/- 2.0 ng/mL. P < 0.01), whereas no changes in this parameter of bone synthesis were observed during budesonide treatment (n = 11) (34.8 +/- 3.1 to 33.0 +/- 3.5 ng/mL). Urinary pyridinolines and deoxypyridinolines, highly sensitive markers of bone degradation, did not change in either group. CONCLUSION: Short-term methylprednisolone therapy impairs osteoblast activity in patients with Crohn's disease whereas budesonide does not.

Administration, Oral↗

Attitude of laboratory personnel towards accreditation.

A multiple choice questionnaire was submitted to medical technologists in three medical laboratories, at varying times after obtaining an EN 45001 accreditation. A large majority (85-90 per cent) considered that their workload was increased by the accreditation process. In two laboratories, the technologists did not think that the accreditation process had improved the quality of the results. The major advantages were the fact that everything was traceable, that the technologists felt more sure about the procedures to follow, received more responsibilities and had a better knowledge of the tests they performed. The major disadvantages were the increased paperwork, discrepancies between the procedures and the reality, the fact that more attention is paid to the formalities than to the quality of the results and that the accreditation process decreased the adaptability. The number of advantages mentioned seemed to increase with the interval since the accreditation. A small majority of the technologists preferred working in an accredited laboratory than in a non accredited one.

Accreditation↗

Penetration of gentamicin and ofloxacin in human vitreous after systemic administration.

BACKGROUND: Data on the penetration of antibiotics into the aqueous humor in man and animals, as well as on the intravitreal penetration in animals, are numerous. Data on their intravitreal penetration in humans, however, are sparce. The intravitreal penetration of gentamicin was studied in different ocular pathologies to see whether these alter the vitreal pharmacodynamics. The intravitreal penetration of ofloxacin, a fluoroquinolone, was determined to see whether levels sufficient to treat infectious endophthalmitis could be reached. METHODS: The intravitreal penetration of gentamicin and ofloxacin was studied in patients undergoing pars plana vitrectomy for various ocular pathologies. Those with recent hemorrhages and those already receiving general antibiotic treatment were excluded. RESULTS: Gentamicin was found to penetrate the vitreous very poorly. No difference could be found between the various pathologies: trauma, diabetes, proliferative vitreoretinopathy, longstanding vitreous hemorrhage and macular pucker gave the same poor penetration. The ofloxacin levels were higher but did not reach the MIC90 levels of most organisms involved in bacterial endophthalmitis. CONCLUSION: The hemato-ocular barrier is more difficult to cross than originally thought. Different ocular pathologies do not alter the ocular barrier substantially. Ofloxacin alone does not seem to be sufficient for the treatment of established bacterial endophthalmitis.

Adolescent↗

Hepatotoxicity of N, N-dimethylformamide (DMF) in acute poisoning with the veterinary euthanasia drug T-61.

1. We report on a patient who was resuscitated after a suicide attempt with the veterinary euthanasia product T-61 and treated with N-acetylcysteine (NAC) to prevent hepatotoxicity from N,N-dimethylformamide (DMF), the solvent of T-61. 2. Serum concentrations of DMF were high as compared with values published on occupational exposure. 3. The patient showed only a transient increase in liver enzymes with eventually a full recovery. 4. The hepatoprotective effect of NAC was studied in a rat model using the rise in serum sorbitol dehydrogenase (SDH) as a marker for DMF-induced hepatotoxicity. 5. Four series of randomized, controlled and double-blind experiments were carried out and consistently showed a lower increase in SDH in NAC-treated animals in each series. The difference was statistically significant only when the data of the 4 series were pooled. This is probably due to the large interindividual variations in the effect of DMF. 6. We hypothesize that in the rat NAC may have a protective effect. Whether NAC is also protective in patients, in which it is administered after exposure to DMF, cannot be concluded from the present experiments.

Acetylcysteine↗

Protein binding of propranolol and verapamil enantiomers in maternal and foetal serum.

The protein binding of the enantiomers of propranolol and verapamil was measured in 19 pairs of maternal and foetal serum obtained at delivery. The binding of the enantiomers of both drugs was lower in foetal than in maternal serum. In maternal serum the mean (+/- s.d.) unbound percentages were 22.4 +/- 6.2 and 20.7 +/- 6.6 for R- and S-propranolol, and 16.8 +/- 5.5 and 22.5 +/- 6.2 for R- and S-verapamil; in foetal serum the values were 38.8 +/- 8.6 and 40.4 +/- 10.6 for R- and S-propranolol, and 34.7 +/- 10.5 and 44.8 +/- 10.7 for R- and S-verapamil. For propranolol, in maternal, but not in foetal serum, the difference between the binding of the R- and S-enantiomers was significant; the R/S ratio was significantly (P < 0.01) larger in the mother (1.099 +/- 0.072) than in the foetus (0.973 +/- 0.068). For verapamil, the difference in binding between the R- and S-enantiomers was significant in both maternal and foetal serum, but the R/S ratio was similar in mother (0.735 +/- 0.098) and foetus (0.763 +/- 0.070). Serum alpha 1-acid glycoprotein (AAG) concentrations were markedly higher and albumin concentrations slightly lower in maternal than in foetal samples. The binding of the four enantiomers in maternal and foetal serum was correlated (P < 0.001) with the AAG concentration (r propranolol: R 0.749, S 0.746; r verapamil: R 0.753, S 0.782). Our findings show that measurement of concentrations of total, unresolved drug allow a reasonably accurate assessment of transplacental gradients of individual isomers.

Adult↗

Fatal intoxication with amlodipine.

Although poisoning with calcium channel blocking agents is frequent, to our knowledge no cases involving amlodipine have been published. We describe here a case of amlodipine intoxication, in which protracted hypotension did not respond to vasopressor therapy alone. After the addition of continuous calcium chloride and glucagon infusion, blood pressure was restored and vasopressor therapy could be tapered off substantially. When calcium and glucagon were interrupted because of severe hypercalcemia and hyperglycemia, the patient developed irreversible hypotension and died. Either glucagon or calcium or both, and to some extent vasopressors, seem to have constituted effective treatment of hypotension in this case.

Amlodipine↗