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Biomedical subjects

A Meulemans

Publications and source records attributed to A Meulemans.

At least 37 records · Page 2Linked to original sources

Measurement of nitrite and nitrate levels in biological samples by capillary electrophoresis.

Nitrite is one of the products of NO-synthase in biological media. It is slowly oxidized in animals to nitrate. We developed a simple and rapid method to determine simultaneously nitrite and nitrate in biological samples. Capillary ion electrophoresis with direct UV detection at 214 nm was used employing a carrier electrolyte consisting of 10 mM sodium sulfate and an electroosmotic flow modifier. The detection limit in ultrafiltrates of plasma, urine and brain tissue extracts was 25 ng/ml for both compounds. Nitrate levels in human plasma and urine were in the microgram/ml range. Nitrite could not be detected. Rat brain tissue extracts contained detectable amounts of nitrite and nitrate.

Animals↗

Diffusion coefficients and half-lives of nitric oxide and N-nitroso-L-arginine in rat cortex.

In vivo voltammetry was performed in rat brain cortex and in rat brain endothelial constitutive NO-synthase preparations. The use of a recent microcaptor detecting N-hydroxy- and N-nitroso-L-arginine permitted to find only the latest in biological preparations. The construction of a new membrane selective electrode for nitric oxide (NO) allowed to assert its absence in these preparations at micromolar level. Half-live of N-nitroso-L-arginine was 4 s in rat brain cortex and the washout curve of NO after over brain insufflation gave an half-life of 10.5 min; their diffusion coefficients in brain were 3.810(-5) for NO and 3.910(-6) cm2.s-1 for N-nitroso-L-arginine. These facts indicate that N-nitroso-L-arginine is degraded directly into nitrites and citrulline after its synthesis by endothelial NO-synthase.

Amino Acid Oxidoreductases↗

Systematic biopsies accurately predict extracapsular extension of prostate cancer and persistent/recurrent detectable PSA after radical prostatectomy.

OBJECTIVES: To determine if methodic analysis of systematic echo-guided biopsies associated with prostatic-specific antigen (PSA) and PSA density can accurately predict the actual pathologic stage of prostate cancer (Ca P). METHODS: One hundred patients with clinically localized (T1, T2) Ca P who underwent radical prostatectomy (RP) were preoperatively staged by digital rectal examination (DRE), measurement of serum PSA (Yang Pros-check) and PSA density (PSAD), and transrectal echo-guided systematic biopsies (three in each lobe aiming to sample prostatic capsule) to evaluate T stage, Gleason grade, number of positive biopsies, and presence of cancer in the periprostatic tissues. Radical prostatectomy specimens were processed following the McNeal method. The PSA levels were measured every month for 2 years. RESULTS: Extracapsular disease was detected on the specimen in 45% of the patients, persistent/recurrent detectable PSA in 47% (mean follow-up 18 months). Clinical stage T2 B, presence of Gleason grade 4, PSA > 25 ng/mL, PSAD > 0.6, number of positive biopsies > 66% of the total number of cores taken had a positive predictive value (PPV), respectively, of 72%, 66%, 80%, and 87%. Periprostatic tissue was evaluable on the core biopsies in 77% of the cases. Presence of cancer in the periprostatic fat on the core biopsies had a PPV of 94% for extracapsular disease/biological recurrence. CONCLUSIONS: The presence of extracapsular cancerous tissue on prostatic core biopsies accurately predicts extracapsular extension of Ca P. Therefore, care should be taken when performing prostate biopsies to sample the prostate capsule and surrounding tissues to obtain a more accurate staging of the disease. The second best predictor of extracapsular disease is the percentage of positive biopsies.

Adult↗

Prostate-specific antigen density: a means to enhance detection of prostate cancer.

The ability of serum prostate-specific antigen (PSA) and PSA density (PSAD) to distinguish patients with prostate cancer from those with benign diseases of the prostate was assessed in 495 men. All men were evaluated with PSA determination, digital rectal examination (DRE), transrectal ultrasonography (TRUS) and ultrasound-guided prostatic biopsies. PSA was analysed by the polyclonal (Yang) assay. Prostate volume was estimated from TRUS. PSAD was determined by dividing the serum PSA by the volume of the prostate. Prostatic biopsies identified cancer in 246 of the 495 patients (49.7%). The entire group was divided into 6 subgroups according to PSA level at presentation. Cancer and noncancer patients were compared in each subgroup with respect to the values of PSA, prostate volume and PSAD. For the entire group of patients, there was no statistically significant advantage, for PSAD over serum PSA alone, in distinguishing between benign and malignant prostatic conditions. However, when patients were stratified according to PSA level, PSAD was statistically significantly superior to serum PSA alone in the detection of prostate cancer for PSA values in the intermediate range (2.6-30 ng/ml). This analysis with respect to the DRE and TRUS results showed PSAD to be superior to PSA when both examinations are normal. Our results demonstrate that the influence of PSAD level on cancer detection proportionally increases as the PSAD value increases. Curves constructed from the incidence of prostate cancer according to PSAD values may be useful to select patients with intermediate levels of serum PSA, and normal DRE and TRUS for prostatic biopsies.

Adult↗

Predictive value of pathological features for progression after radical prostatectomy.

OBJECTIVE: 10-30% of patients with T1/T2 prostate cancer submitted to radical prostatectomy ultimately fail. It may be important to detect failure as early as possible in order to evaluate the extent of recurrent/residual disease and initiate adjuvant therapy. SUBJECTS AND METHODS: 100 consecutive patients with localized prostate cancer treated by radical prostatectomy have been monitored using the hypersensitive Pros-check prostate-specific antigen (PSA) assay (detection level 0.1 ng/ml). The predictive value of positive surgical margins, involvement of seminal vesicles and perineural spaces as well as Gleason's score for biological failure (persistent or recurrent detectable PSA) has been retrospectively evaluated. RESULTS: Overall 40% of the patients had biological failure (defined as persistence of a detectable or rising PSA after undetectability) and 38% had positive surgical margins. The three main predictive criteria of biological failure were capsular perforation, involvement of seminal vesicles and/or positive margins. All patients in whom these criteria were positive progressed. Seminal vesicle invasion was associated with biological failure in 95% of the cases. 66.7% of the patients with extracapsular disease but no seminal vesicle invasion progressed. 15% of pT2 patients experienced a persistent/recurrent postoperative PSA and were upstaged to pT3 after reevaluation of the specimen. CONCLUSION: Efforts should be made to increase the preoperative evaluation of seminal vesicle and pericapsular status by a more sophisticated technique of prostate biopsy in order to avoid noncurative surgery.

Adult↗

[Role of biological and anatomo-pathologic criteria in the prognosis evaluation of patients before and after radical prostatectomy].

Radical prostatectomy is the treatment of choice for organ-confined prostatic cancers (T1-T2). However, it has been reported to improve the long-term survival of patients and achieve its oncological objectives in only one half of patients despite a serious morbidity. Based on a consecutive series of one hundred patients, the authors performed univariate statistical analysis to determine the predictive value of eight preoperative criteria for biological progression and capsular effraction: clinical stage, PSA (using a highly sensitive test derived from the Yang Proscheck and lowering the limit of detection to 0.1 ng/ml), PSA density (PSAD), percentage and topography of positive biopsies, capsular effraction, perineural spaces and Gleason's score. The predictive value for progression of five postoperative histological criteria (Gleason's score, capsule, perineural spaces, seminal vesicles and resection margins) was also studied in the same group of patients. The presence of capsular effraction on the biopsy was shown to have a positive predictive value of 90%. The three preoperative criteria most closely correlated with tumour progression were PSA, PSAD and percentage of positive biopsies (p < 0.001). Analysis of the combined predictive value of PSAD, percentage of positive biopsies and capsular effraction revealed that progression was always present when two of these criteria were positive. Seminal vesicle invasion on the operative specimen is the most pejorative element for progression. In conclusion, analysis of the histological features of biopsies associated with PSA and PSAD allows a more accurate selection of patients with a high risk of progression and seminal vesicle invasion is so pejorative that it could be detected in subjects with a preoperative PSA greater than 25 ng/ml.

Adult↗

Continuous monitoring of N-nitroso-L-arginine using micro carbon electrode in rat brain.

Constitutive brain nitric oxide (NO) synthase is described as converting L-arginine into NO. NO is thought to be the cellular messenger released by endothelial cells, and was originally termed endothelial-derived relaxing factor (EDRF). The mechanisms of its synthesis remain unclear. Using microelectrode differential pulse voltammetry in the presence of cortical constitutive rat brain NO synthase, a peak was recorded at -1.66 V with respect to a Ag/AgCl reference electrode. This voltage peak, due to the reduction of N-nitroso-L-arginine, was increased in rat brain cortex after pharmacological stimulation with L-arginine or A-23187; whereas it was abolished following application of D-arginine, N-nitro-L-arginine or pure NO. Using laser doppler measurements, the secretion of N-nitroso-L-arginine was correlated to brain blood flow. These preliminary results suggest that N-nitroso-L-arginine is synthetized by constitutive brain NO synthase of vascular endothelial cells in rat brain cortex.

Amino Acid Oxidoreductases↗

Influence of rhein anthrone on peristaltic reflex of guinea-pig isolated ileum: involvement of prostaglandins.

1 The influence of rhein anthrone on the peristaltic reflex was studied with a modified Trendelenburg technique in a range from 10(-8) M to 4 x 10(-5) M, on a normal and reversed guinea-pig ileum segment. Rhein anthrone had no significant effects on longitudinal muscle tension, intraluminal pressure or volume displacement when tested on the normal segment in doses up to 10(-5) M. When applied to the mucosal side (reversed segment), rhein anthrone produced a dose-dependent increase of longitudinal muscle tension (significant from 10(-7) M), of intraluminal pressure (significant from 3 x 10(-6) M) and of volume displacement (significant from 10(-7) M). The data show that rhein anthrone possesses in vitro activity which is dependent on contact with the mucosa. 2 The action of rhein anthrone on the reversed segment was inhibited by BW755C (a dual inhibitor of cyclo-oxygenase and lipoxygenase), by indomethacin and by SC19220 (an antagonist of prostaglandin E2 (PGE2) and PGF2 alpha). The effects remaining on longitudinal muscle tension, intraluminal pressure and volume displacement, calculated as percentage (mean +/- s.e.mean) of the initial value, were respectively: 13 +/- 8; 23 +/- 13; 112 +/- 5 for BW755C; 66 +/- 19; 51 +/- 8; 53 +/- 8 for indomethacin and 27 +/- 12; 13 +/- 7; 50 +/- 5 for SC19220. It is concluded that arachidonic acid metabolites, especially PGE2 and PGF2 alpha are involved in the effects of rhein anthrone on the reversed segment.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

In vitro demonstration of a positive effect of rhein anthrone on peristaltic reflex of guinea pig ileum.

The influence of rhein anthrone on the peristaltic reflex was studied with a modified Trendelenburg technique in the range from 10(-8) to 4 x 10(-5) mol/l, using a normal and reversed guinea pig ileum segment. Rhein anthrone had no significant effects on longitudinal muscle tension, intraluminal pressure or volume displacement when tested on the normal segment in doses up to 10(-5) mol/l. When applied to the mucosal side (reversed segment), rhein anthrone produced a dose-dependent increase of longitudinal muscle tension, of intraluminal pressure and of volume displacement. The data show that rhein anthrone possesses in vitro activity which is dependent on contact with the mucosa. The action of rhein anthrone on the reversed segment was inhibited by BW755C (a dual inhibitor of cyclo-oxygenase and lipoxygenase), by indomethacin and by SC19220 (an antagonist of PGE2 and PGF2 alpha). It is concluded that arachidonic acid metabolites, especially PGE2 and PGF2 alpha are involved in the effects of rhein anthrone on the reversed segment.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Diffusion from gel in brain: modelisation and identification.

A mathematical model is proposed for describing the mechanism of diffusion from gel (Tissucol) into the extracellular space. After diffusion of the antibiotic in one dimension, the gradient concentration was determined with microvoltametric electrodes. These microelectrodes measure the free diffusible form of electroactive antibiotics in the extracellular brain space. The aim of this study was to find simultaneously the coefficient of diffusion and extraction of some antibiotics (in our case the Fotemustin) using the Alienor Algorithm. These coefficients are useful for predicting the concentration gradient into abscesses, fibrin, etc.

Algorithms↗

A model of cefoperazone tissue penetration: diffusion coefficient and protein binding.

The apparent diffusion coefficient of a bound drug, cefoperazone, was studied. The protein binding of cefoperazone was studied by voltammetry, a technique which permitted instant measurements. The apparent diffusion coefficients were similar in agar and fibrin and lower in rat brain tissue. The influence of protein on the value of the apparent diffusion coefficient was negligible. The hypothesis that only the free drug diffuses was supported. The percentage of binding determined by voltammetry corresponded to the true concentration of drug which diffuses and is much lower than the percentage of binding determined by the ultrafiltration centrifugation method. This discrepancy could be explained by the rate of dissociation of the protein-drug complex.

Animals↗

Magnesium deficiency as a cause of acute intractable seizures.

Clinical and experimental investigations have shown that magnesium depletion causes a marked irritability of the nervous system, eventually resulting in epileptic seizures. Although magnesium deficiency as a cause of epilepsy is uncommon, its recognition and correction may prove life-saving. Two case reports are presented which emphasize the importance of recognizing hypomagnesaemia in patients with acute intractable seizures.

Adult↗

Comparative diffusion study of two nitrosoureas: carmustine and fotemustine in normal rat brain, human and rat brain biopsies.

In order to assess the apparent diffusion coefficient of two nitrosoureas (carmustine and fotemustine) in the brain, a model of planar diffusion was used in the rat brain and in rat and human brain biopsies. Drugs were deposed on the brain surface at a constant concentration for 30 min. At the end of the diffusion time, the concentration gradient was determined with microelectrodes using voltammetry at 5 different depths in the extracellular space of the gray matter (0-304 microns). Voltammetry with microelectrodes measured quantitatively intact drug in the brain extracellular space (CV 4% for the 2 drugs) in the range studied. The same procedure was used for human and rat brain biopsies which were held in a small cup. The apparent diffusion coefficients in living animals were 0.49 x 10(-6) cm2.s-1 for carmustine and 0.23 x 10(-6) cm2.s-1 for fotemustine; in human biopsies, they were 0.84 x 10(-6) cm2.s-1 for carmustine and 0.37 x 10(-6) cm2.s-1 for fotemustine. Significant differences in the apparent diffusion coefficients of the drugs were accounted for by the fact that the intracellular penetration of fotemustine was better than that of carmustine.

Adult↗

High-performance liquid chromatographic determination of the binding of ceftriaxone to human serum albumin solution and albumin from diluted human serum.

The binding of ceftriaxone to human serum albumin has been studied by high-performance liquid chromatography. The gel permeation method of Hummel and Dreyer was used. Ceftriaxone was tested with two sources of albumin (aqueous solution and diluted serum). After internal calibration the binding parameters were determined for each albumin, and results compared. These data are in agreement with those from classical methods for the determination of protein binding of ceftriaxone.

Buffers↗

Gastrointestinal decontamination for acute poisoning.

Acute poisoning remains a common cause of morbidity and even mortality in children and adults. The goal of gastrointestinal decontamination is to eliminate or to reduce the potentially life-threatening effects of the ingested poison. Methods of gastrointestinal detoxication in case of acute poisoning, such as induced emesis, gastric lavage, administration of activated charcoal and intestinal cleansing are discussed. As far as induced emesis is still concerned, only the administration of Ipecac-syrup can be retained. The controversy between emesis and gastric lavage still remains. For those toxins well adsorbed by activated charcoal, the administration of activated charcoal, followed or not by gastric lavage, is the treatment of choice. Single doses of activated charcoal can be insufficient. In certain kinds of poisoning, repeated doses of activated charcoal are advisable because of the interruption of the entero-hepatic and entero-enteric circulation. The benefit and the indications for intestinal cleansing in case of acute poisoning seem to be very limited.

Cathartics↗

Measurement and clinical and pharmacokinetic implications of diffusion coefficients of antibiotics in tissues.

A method for determining diffusion coefficients of four antibiotics in extracellular tissue space according to Fick's law is described. This new method was applied to rat brain tissue and to agar. After diffusion of the antibiotic in one axis, the gradient concentration was determined with microvoltammetric electrodes. These microelectrodes (1 micron at the extreme tip) measured the free diffusible form of electroactive antibiotics in the extracellular brain space. Metronidazole, chloramphenicol succinate, cefsulodin, and piperacillin gave diffusion coefficients ranging from 0.1 x 10(-6) to 0.2 x 10(-6) cm2 . s-1 in tissue; chloramphenicol base, which is positively charged, gave a coefficient of 0.04 x 10(-6) cm2 . s-1. The coefficient ranged from 0.6 x 10(-6) to 1.2 x 10(-6) cm2 . s-1 in agar. These coefficients were used to simulate antibiotic concentrations in infectious sites and between capillaries by using a simple model of plane diffusion.

Animals↗

Pharmacokinetics of cefsulodin in rat cerebrospinal fluid during experimental Pseudomonas aeruginosa meningitis.

Experimental meningitis was induced in rats with Pseudomonas aeruginosa. Bacteria were inoculated in the second ventricle. Twenty hours later cefsulodin penetration was studied in CSF by on-line cannula system which permitted sampling of CSF in the third ventricle. Comparison with healthy animals indicated breakdown of the blood-CSF barrier and high concentrations of cefsulodin were found in CSF.

Animals↗