Search PubMedSearch

Biomedical subjects

D Vogelaers

Publications and source records attributed to D Vogelaers.

13 recordsLinked to original sources

Plasma concentrations of pralidoxime methylsulphate in organophosphorus poisoned patients.

Using pharmacokinetic data from healthy human volunteers in a bicompartmental pharmacokinetic model, a repeated dose scheme for pralidoxime methylsulphate (Contrathion) was developed producing plasma levels remaining above the assumed "therapeutic concentration" of 4 mg.l-1. Using the same data, it was found that a concentration of 4 mg.l-1 could also be obtained by a loading dose of 4.42 mg.kg-1 followed by a maintenance dose of 2.14 mg.kg-1.h-1. In order to study the pharmacokinetic behaviour of pralidoxime in poisoned patients, this continuous infusion scheme was then applied in nine cases of organophosphorus poisoning (agents: ethyl parathion, ethyl and methyl parathion, dimethoate and bromophos), and the pralidoxime plasma levels were determined. The mean plasma levels obtained in the various patients varied between 2.12 and 9 mg.l-1. Pharmacokinetic data were calculated, giving a total body clearance of 0.57 +/- 0.27 l.kg-1.h-1 (mean +/- SD), an elimination half-life of 3.44 +/- 0.90 h, and a volume of distribution of 2.77 +/- 1.45 l.kg-1.

Dose-Response Relationship, Drug

Intermediate syndrome due to prolonged parathion poisoning.

A parathion-poisoned patient with prolonged cholinesterase inhibition due to impaired hepatic metabolism and urinary excretion is reported. An intermediate syndrome characterized by respiratory paresis, weakness in the territory of several motor cranial nerves and of proximal limb and neck flexor muscles, persisted for 3 weeks. During this whole period, cholinesterase remained markedly reduced. Serial EMGs with repetitive nerve stimulation pointed to a combined pre- and postsynaptic disorder of neuromuscular transmission. Electron microscopy of an intercostal muscle biopsy showed focal degeneration at the poorly branched postsynaptic folds, and was considered to be nonspecific.

Acetylcholinesterase

Prolonged toxicity with intermediate syndrome after combined parathion and methyl parathion poisoning.

A prolonged type of organophosphate toxicity, previously characterized as the Intermediate Syndrome, has been recognized in 6 out of 7 prospectively studied patients poisoned by insecticide containing parathion and methyl parathion in equal proportions. The clinical characteristics included respiratory paresis, weakness in the territories of several motor cranial nerves, neck flexors and proximal limb muscles, and depressed tendon reflexes, all lasting for several days or weeks. Electromyography in the early stages disclosed diverse types of impaired neuromuscular transmission. EMG normalization preceded clinical recovery. Severe plasma butyrylcholinesterase and erythrocyte acetylcholinesterase inhibition persisted along with the occurrence of Intermediate Syndrome-related symptoms. We conclude that combined parathion and methyl parathion poisoning is more likely to induce Intermediate Syndrome than parathion poisoning alone. The mechanisms underlying this difference remain obscure. The Intermediate Syndrome shows clinical and electromyographic hallmarks of combined postsynaptic impairment of neuromuscular transmission.

Adult

Fibrinolysis and coagulation in patients with infectious disease and sepsis.

Sepsis is often associated with hemostatic dysfunction. This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome. Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease. The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 +/- 9.4 versus 1.6 +/- 1.5 ng/ml, p less than 0.0001). PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 +/- 390 ng/ml versus 120 +/- 200 ng/ml, and 3.0 +/- 3.6 IU/ml versus 1.0 +/- 0.7 IU/ml, respectively, p less than 0.01). AT III was decreased in sepsis patients (58 +/- 28% in sepsis versus 79 +/- 26% in severe infectious disease, p less than 0.01) as was protein C (30 +/- 18% versus 58 +/- 27%, p less than 0.001). No significant difference was found for t-PA antigen nor for PAI activity. Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity. It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection. u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease.

Adult

Postsynaptic neuromuscular dysfunction in organophosphate induced intermediate syndrome.

A 65-year-old Caucasian female developed an intermediate syndrome seven days after an acute cholinergic crisis, caused by the ingestion of fenthion. Cholinesterase activity in the blood, plasma and red cells was monitored daily by the method according to Nenner and serial serum fenthion levels were measured by capillary gas chromatography. Electromyographic studies showed fade on tetanic stimulation by means of surface electrodes at 20 Hz of the left M. abductor digiti quinti at day 7, which could no longer be observed at day 19. Fade on low-frequency stimulation and post-tetanic facilitation were both absent. A biopsy of the N. suralis was normal. A biopsy of the M. tibialis anterior revealed a limited rhabdomyolysis with a very weak staining for cholinesterase. It is hypothesized that the pathophysiologic process underlying the syndrome is the result of a time-confined phenomenon, which includes both changes in the postsynaptic structures by a desensitization process and a gradually restoring ratio of acetylcholine to acetylcholinesterase. This hypothesis is suggested by the similarity in the EMG-findings of this patient and those in myasthenia gravis, which is known to be characterized by a postsynaptic transmission defect.

Acetylcholinesterase

Influence of chest physiotherapy on arterial oxygen saturation.

Two groups of ventilated patients were compared for chest physical therapy on an ICU: respiratory insufficient patients on one side and a control population on the other were submitted either to percussion or vibration therapy, and to postural drainage. Our data show a decrease in arterial oxygen saturation after CPT and after 2h monitoring; the lateral position results in a better SaO2 in the pneumonia group while SaO2 tend to decrease in the control population. However, no significant therapeutic influence of vibration nor percussion was found. Our data suggest CPT does not result in a short term respiratory benefit. Further investigations with prolonged sessions of postural drainage are required.

Adult

Measured attenuation correction using the Maximum Likelihood algorithm.

Quantitative determination of local radioactivity concentration in positron emission tomography (PET) requires a good attenuation correction procedure to reconstruct the emission image. Using a similar Maximum Likelihood (ML) algorithm as for the reconstruction of the emission image, a method is proposed to reconstruct a transmission image, i.e. a map of absorption coefficients. This reconstructed transmission image is then used to calculate the attenuation correction factors needed for the ML reconstruction of the emission image. This approach takes automatically into account the convolution step in the acquisition process (caused by various smoothing factors, e.g. the detector width). This results in appreciable noise suppression without loss of resolution due to filtering, thus making the reconstructed images easier to interpret. A comparison is made with other estimates for the measured attenuation correction using phantom studies.

Algorithms

Prompt recovery from severe cholinesterase-inhibitor poisoning--remarks on classification and therapy of organophosphate poisoning.

In organophosphate intoxication the assessment of both the degree of severity of poisoning and the initial dose of pralidoxime and atropine are as yet based only on clinical symptoms. We present three patients with clinically severe organophosphate poisoning in whom a prompt recovery from central nervous symptoms occurred after the administration of low doses of atropine and pralidoxime. It is suggested that the true severity of organophosphate intoxication as well as the initial therapy should be determined by the amount ingested, the propensity for aging, and the pharmacodynamic properties of the organophosphorus compound, as well as by the time interval between exposure and initiation of appropriate treatment, as far as these data can be verified in the individual patient.

Acetylcholinesterase

Production of carrier-free 66Ga and labeling of antimyosin antibody for positron imaging of acute myocardial infarction.

A method for labeling monoclonal antimyosin antibodies with 66Ga is described. The radionuclide is a positron emitter (t1/2: 9.4h) produced by means of the 63Cu (4He, n) 66Ga reaction. Purification of the 66Ga from the copper target is described in detail. Monoclonal antimyosin antibodies are labeled with 66Ga at a high yield (99%) by transcomplexation from an acetate buffer with the diethylenetriamine pentaacetic acid (DTPA)-labeled antibody and preliminary evaluated in two dogs for imaging of myocardial necrosis by positron emission tomography.

Animals

Serum tumor necrosis factor levels in patients with infectious disease and septic shock.

The role of tumor necrosis factor (TNF-alpha) in the pathogenesis of septic shock has been assessed by daily measurements of serum TNF-alpha levels in 60 patients admitted to the medical intensive care unit. All patients in the study had infectious disease and were at risk for the development of sepsis and septic shock. Sepsis was diagnosed in 34 patients, 24 of whom died (six within the first 24 hours). The 26 patients who did not evolve toward sepsis served as a control group. The clinical condition of all patients was monitored by daily APACHE II scoring. Blood was drawn once a day and additional samples were taken in patients whose clinical condition underwent sudden deterioration. TNF-alpha levels were measured with a commercially available immunoradiometric assay. At time of patient admission, TNF-alpha levels were higher in the group with sepsis than in the control group (median 79 iqr 329 vs median 0.5 iqr 5; p less than 0.001). In the group with sepsis, extremely high TNF-alpha levels were found in patients who died within 24 hours. These patients had TNF-alpha levels of 917 iqr 755 pg/ml, whereas the patients who died more than 24 hours after admission had TNF-alpha levels of 58 iqr 59 pg/ml. Survivors had lower TNF-alpha levels (26 iqr 347 pg/ml). APACHE II scores correlated with TNF-alpha levels in the total sepsis group (Spearman rank correlation coefficient 0.477; p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections

Infections in patients in intensive care units: can the combination of a monobactam and a penicillin replace the classic combination of a beta-lactam agent and an aminoglycoside?

An open, comparative, randomized study was performed in two medical intensive care units to compare the efficacy of the combination of aztreonam and either cloxacillin or oxacillin [(cl)oxacillin] with that of the combination of tobramycin and a cephalosporin. Of the 92 patients who were included in the study, 76 were evaluable. All patients suffered from severe, mostly pulmonary, infections and received ventilatory support. The aztreonam combination yielded an 80% rate of clinical cure; mortality was 15%. Use of the aminoglycoside combination resulted in a 51% rate of clinical cure; mortality was 23%. The difference in cure rate between the two combinations was statistically significant. Adverse effects were negligible in patients who received the aztreonam combination, and superinfection was seen in only 2%. Of the patients who received the aminoglycoside combination, 20% developed a superinfection and 11% developed a new renal insufficiency. Therefore, the combination of aztreonam and (cl)oxacillin is a valuable alternative to the combination of an aminoglycoside and a cephalosporin.

Adult