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Biomedical subjects

J W Meijer

Publications and source records attributed to J W Meijer.

At least 37 records · Page 2Linked to original sources
PubMed1997

Discussion of the AED workshop.

An overview is given of the different issues that have been discussed, with subsequent recommendation. Standardisation of measurement and reporting of efficacy parameter and side-effects is essential; not only the number of patients achieving complete seizure controlled or have a decrease in seizure frequency and severity should be mentioned but also the number who dropped out and the reasons therefore. More information is needed on the teratogeneticy of a drug, either by performing control trials or by registration of all pregnancies with new anti-epileptic drugs. Appropriate bio-marker for efficacy and toxicity should be developed. Health-related quality of life scales, collecting both subjective and objective information should be developed and used as complimentary tools in understanding more about the disease. A drug that improves the quality of life but is less effective in suppressing seizures should be marketed. Finally, pharmaco-economic studies should be encouraged in the field of epilepsy.

Anticonvulsants↗
PubMed1997

No additional value of bismuth subcitrate to combination omeprazole/amoxicillin therapy in the eradication of Helicobacter pylori.

BACKGROUND: We investigated whether addition of bismuth subcitrate (BSC, 4 x 120 mg) to a two week therapy scheme of omeprazole (OME, 2 x 40 mg)/amoxicillin (AMO, 4 x 500 mg) increases Helicobacter pylori eradication. MATERIALS AND METHODS: Patients with dyspepsia underwent upper endoscopy. H. pylori positive patients were randomized to treatment A (OME/AMO, 83 patients) or treatment B (OME/AMO/BSC, 84 patients). RESULTS: In 65 patients of group A (78%) H. pylori was eradicated as determined from the histological assessment (Sydney classification) of antrum and corpus biopsies. In comparison, in 68 patients of group B (81%) H. pylori was eradicated (p = NS between groups). H. pylori eradication in both groups was associated similarly with a decrease of inflammation and activity whereas atrophy and intestinal metaplasia were not affected. A positive association was revealed between the decrease of H. pylori score and the decrease of both inflammation and activity scores for antrum as well as corpus biopsies. CONCLUSIONS: Addition of BSC to OME/AMO does not increase H. pylori eradication in patients with dyspepsia. Eradication of H. pylori is associated with disappearance of epithelial damage (inflammation and activity) in antral and corpus mucosa.

Adult↗
PubMed1996

Beclomethasone dipropionate (3 mg) versus 5-aminosalicylic acid (2 g) versus the combination of both (3 mg/2 g) as retention enemas in active ulcerative proctitis.

Sixty patients with active distal ulcerative colitis participated in a multicentre randomized double-blind trial to compare the effect of a beclomethasone dipropionate (BDP) enema (3 mg/100 ml) with 5-aminosalicylic acid (5-ASA) enemas (2 g/ 100 ml) and enemas with a combination of BDP/5-ASA (3 mg/2 g/100 ml). The patients were treated for 4 weeks and the efficacy of the drugs was evaluated by sigmoidoscopy, histology and subjective symptoms after that time. The overall results after 28 days of treatment were: clinical improvement 100% (BDP/5-ASA) vs. 70% (BDP) and 76% (5-ASA); endoscopic improvement 100% (BDP/5-ASA) vs. 75% (BDP) and 71% (5-ASA); histological improvement 95% (BDP/5-ASA) vs. 50% (BDP) and 48% (5-ASA). After 4 weeks of treatment seven of 19 patients (37%) receiving BDP/5-ASA had healed endoscopically, compared with six of 20 receiving BDP (30%) and two of 21 receiving 5-ASA (10%). Two patients on 5-ASA and three on BDP had a marked deterioration during treatment. The combination of BDP and 5-ASA was significantly superior to single-agent therapy in terms of both improved sigmoidoscopic and improved histological score. No differences in improvement between the 5-ASA vs. BDP-treated patients were noticed. No side effects were seen. The results of the study show that topical treatment of active distal ulcerative colitis with either 5-ASA or BDP is equally efficacious. So far, no data on topical combination therapy have been described. However, combination therapy with BDP/5-ASA seems superior to single-agent therapy and causes no adverse reactions.

Adult↗
PubMed1994

Comparison of clinical examination, current and vibratory perception threshold in diabetic polyneuropathy.

The study of diabetic polyneuropathy is complicated by a lack of clear definitions and the absence of a simple reliable test procedure. Recently, a new sensory perception testing device has been introduced for detection of thresholds for electrical stimuli (current perception: CPT) at different frequencies (Neurometer). We compared standardized clinical examination scores with measurements of vibratory perception threshold (VPT) and CPT (foot) and obtained reproducibility figures. Participants in the study were healthy controls (H, n = 33), diabetic patients without clinical signs of neuropathy (DN-, n = 23), diabetics with overt diabetic neuropathy (DN+, n = 22), and patients with a diabetes duration of over 20 years (D20, n = 38). As expected, there were highly significant differences (Wilcoxon) in CPT, VPT and neurological scores between H/DN- and DN+ (p < 0.001), but not between H and DN-. Correlation between CPT and total as well as partial (reflecting small and large fibre functions) neurological examination score were highest at 2000 Hz (r = 0.88); no advantage of lower frequency CPT could be identified. CPT seemed rather insensitive in detecting neuropathy. Correlations between CPT and VPT were only moderate and maximal at 2000 Hz (r = 0.61). Reproducibility of CPT was good at 2000 Hz (coefficient of variation 13.3-20.2%), but moderate to poor at lower frequencies (ranging to 62%). We conclude that CPT and VPT quantitative sensory testing is only of limited value, mainly because of high variability and poor reproducibility.

Adult↗
PubMed1993

[A female patient with Werner's syndrome].

We describe a 42-year old female with Werner's syndrome, an autosomal recessive connective tissue disorder, characterised, in her case, by juvenile cataract, chronic ulcers on the feet, characteristic skin changes, a typical appearance of the face ('bird-like face'), severe deformities of the feet, generalised osteoporosis, soft tissue calcifications and a high pitched hoarse voice. Werner's syndrome has to be distinguished from systemic sclerosis in particular. No causal therapy is available.

Adult↗
PubMed1993

The 10,11-epoxide-10,11-diol pathway of carbamazepine in early pregnancy in maternal serum, urine, and amniotic fluid: effect of dose, comedication, and relation to outcome of pregnancy.

Epoxide metabolites of carbamazepine (CBZ) have been suggested to play a role in the occurrence of congenital malformations observed in infants exposed to CBZ. We have investigated the 10,11-epoxide-10,11-diol pathway of CBZ in pregnant epileptic patients receiving CBZ alone or in combination with other antiepileptic drugs in relation to the outcome of pregnancy in a prospective manner. The women were referred to our clinic before 16 weeks of gestation for prenatal diagnosis of fetal malformations, including neural tube defects, by ultrasound and amniocentesis. The availability of amniotic fluid samples enabled us to determine to what extent CBZ and its main metabolites reached the amniotic fluid. In 100 pregnancies with first trimester CBZ exposure (including 7 with malformed outcome), parent drug and metabolite concentrations in maternal serum were evaluated. CBZ-10,11-epoxide concentrations increased with increasing dose. Comedication with phenobarbital led to lower 10,11-epoxide concentrations in maternal serum and a higher percentage of the dose recovered in urine as 10,11-diol. Valproate comedication led to slightly higher 10,11-epoxide concentrations in maternal serum, in combination with lower CBZ concentrations and a lower percentage of the dose recovered in the urine as 10,11-diol. In amniotic fluid, concentrations of CBZ and its main metabolites in most patients were 2 to 2.5 times higher than the free concentrations in maternal serum. Metabolites and parent drug concentrations in amniotic fluid correlated with their free concentration in maternal serum, but stronger with each other in amniotic fluid. No significant differences in levels of CBZ and its metabolites were observed between pregnancies with normal and malformed outcome.

Abnormalities, Drug-Induced↗
PubMed1992

[A surprising double tumor of the liver 60 years following thoratrast diagnosis].

A 66-year-old man with thorotrastosis of the reticuloendothelial system is described. Post mortem two tumours were found in an enlarged liver: a cholangiocarcinoma and an angiosarcoma. Coincidentally, a hilar neurofibroma was found. The former two tumours most probably developed because of a lifelong endogenous alpha-irradiation by thorium disintegration. The exceptional latency period of 60 years' duration is emphasized.

Adenoma, Bile Duct↗
PubMed1992

Antiepileptic drugs and teratogenesis in two consecutive cohorts: changes in prescription policy paralleled by changes in pattern of malformations.

We analyzed the influence of changes in the prescribing of antiepileptic drugs to pregnant women on frequency and pattern of malformations in their offspring by comparing two consecutive cohorts (1972 to 1979, cohort A; 1980 to 1985, cohort B). In cohort A, 15 (10%) of 151 exposed, live-born infants had one or more congenital anomalies, which consisted primarily of congenital heart defects, facial clefts, and syndromes of dysmorphia with developmental retardation, in association with polytherapy (carbamazepine plus phenobarbitone plus valproate, with or without phenytoin, or phenobarbitone plus phenytoin plus primidone). In cohort B, the prescribing of phenobarbitone, phenytoin, or primidone had dropped markedly, whereas monotherapy with valproate and carbamazepine had increased. Thirteen (7.6%) of 172 exposed, live-born infants had congenital anomalies. The most frequent anomalies were spinal defects (four) and glandular hypospadias (three), all in association with maternal therapy with valproate, carbamazepine, or both. The results underline the need for continuation of prospective studies to monitor the effect of change in prescribing policies and to evaluate the role of metabolic interactions between drugs prescribed in combination.

Abnormalities, Drug-Induced↗
PubMed1991

Prognostic value of morphometry and DNA flow-cytometry features of invasive breast cancers detected by population screening: comparison with control group of hospital patients.

Using the prognostic value of morphometric and flow-cytometric features, a group of patients with invasive breast cancers detected with population screening (PS, n = 70) has been evaluated and compared with a random control group in 2 hospitals (H group, n = 225) diagnosed in the same period. The results show that the PS patients had smaller tumors, less positive lymph nodes, better differentiated tumors with a lower mitotic activity index (MAI) and lower values of the morphometric prognostic index (MPI). Furthermore, the women more frequently had diploid tumors and tumors with small nuclei. The second purpose was to evaluate whether quantitative microscopical features, in comparison with other prognostic features such as size of primary tumor, nodal status and histologic grade, are as strong prognosticators in PS tumors as in H-detected breast cancers. In comparison with H tumors, morphometric and flow-cytometric features, as well as tumor size, had the same prognostic value for the PS tumors. In contrast, nodal status was not significant within the PS group, and the same phenomenon was found in a subgroup of H patients with similar sized tumors. Of all quantitative microscopical features (MPI, MAI, mean nuclear area (MNA) and DNA Index (DI], the MAI had the strongest prognostic value. DI showed additional prognostic value to the MAI for patients with small tumors and with small tumor-cell nuclei, because a diploid pattern in these cases (this combination occurred in 21 patients of the total group = 30%) was correlated with a 95% 10-year survival rate. Histologic grade, although significant within the large H group, was of no prognostic value within the PS group, and also not as in the H sub-group with small tumors. It is concluded from morphometric and DNA flow-cytometric criteria that these prognostic features in invasive breast cancers detected by PS were all more favorable than in randomly detected hospital breast cancers. This may account for the reported better survival rate of PS patients. Furthermore, the prognosis of patients with small invasive breast cancers detected by population screening can be more accurately deduced by quantitative microscopical features than by axillary-lymph-node status.

Aged↗
PubMed1990

Pilot study to determine the interaction of oxiracetam with antiepileptic drugs.

Oxiracetam, a nootropic drug, could be of potential use in the treatment of memory disturbances in patients with epilepsy who are using antiepileptic drugs. The half-life of oxiracetam appears to be influenced by the concomitant use of carbamazepine or valproic acid, necessitating more frequent administration of oxiracetam than is recommended for other conditions. No effect was observed on the serum concentrations of these antiepileptic drugs by oxiracetam. Long term concurrent use of oxiracetam and antiepileptic agents does not appear to be contraindicated.

Adult↗
PubMed1990

In vivo distribution of hydrocortisone over whole blood: a novel method for the extraction of erythrocytes.

Ten mg hydrocortisone (HC) was administered intravenously to a healthy volunteer after a dexamethasone suppression test and HC concentrations were determined from 1-270 min in plasma, plasma water and on erythrocytes. HC was extracted from erythrocyte concentrates with high efficiency by HC-poor plasma or by human or bovine albumin solutions. Determination of HC in the plasma of the volunteer mainly gave insight about the concentration time course of HC bound to plasma proteins. One minute after HC injection the amount associated with erythrocytes was about half the amount bound to plasma proteins. Decrease of HC in plasma, and hence on plasma proteins, was monophasic from 30-270 min with a half-life of 116 min. Decrease of HC associated with erythrocytes and HC free in plasma water was biphasic from 30-270 min and initially HC diminished about five times faster from these compartments than from plasma proteins. At the end of the observation period half-lives on plasma proteins, erythrocytes and in plasma water were similar, i.e., at 120 min. It is concluded from these as well as from previous in vitro experiments that erythrocytes gain importance as HC carriers at increasing HC blood concentrations. Once charged, erythrocytes yield HC much more readily than do plasma proteins. This "last come first go" phenomenon of association of HC with erythrocytes is known also to exist for certain drugs. It indicates erythrocytes as important transporters of non-freely in water soluble compounds.

Blood Proteins↗
PubMed1990

Serum protein binding of antiepileptic drugs in Sri Lankans.

The percentage protein binding of antiepileptic drugs was investigated in epileptic patients (n = 90) undergoing treatment with phenobarbitone, phenytoin and carbamazepine either as a single drug therapy or in different combinations. When administered individually, the percentage (mean +/- SEM) protein binding of phenobarbitone, phenytoin and carbamazepine were 50.84 +/- 7.03, 87.23 +/- 2.98 and 76.80 +/- 6.30 respectively. Combination of phenobarbitone and phenytoin resulted in percentage (mean +/- SEM) protein binding of 51.94 +/- 6.09 for phenobarbitone and 83.54 +/- 7.01 for phenytoin, while the combination of phenobarbitone and carbamazepine resulted in percentage (mean +/- SEM) protein binding of 49.60 +/- 2.59 for phenobarbitone and 79.10 +/- 3.31 for carbamazepine. When phenytoin was given with carbamazepine percentage (mean +/- SEM) protein binding was 87.22 +/- 4.48 for phenytoin and 72.50 +/- 5.92 for carbamazepine.

Adolescent↗
PubMed1989

Comparison of the effects of lamotrigine and phenytoin on the EEG power spectrum and cortical and brainstem-evoked responses of normal human volunteers.

Phenytoin and lamotrigine (a new antiepileptic drug with an animal experimental profile resembling phenytoin) have closely similar effects on the quantitative pharmaco-electroencephalogram. These characteristics do not provide a basis for the functional classification of antiepileptic drugs nor for prediction of clinical efficacy, but they do give some insight into the probable secondary psychotropic effects which may arise with use of these drugs. Central conduction in cortical (visual) and brainstem (auditory) event-related potentials are not influenced by either drug, but peripheral nerve conduction is delayed with the use of phenytoin as reflected in increased latency wave I in the brainstem auditory-evoked response. The evidence suggests that in equivalent therapeutic dosage, lamotrigine may be less neurotoxic than phenytoin.

Adult↗
PubMed1989

Distribution of drugs over whole blood: I. The transport function of whole blood for valproate.

A method is presented for the determination of valproate (VPA) in approximately 40 microliters erythrocyte concentrations. Valproate partition between plasma proteins, ultrafiltrate, and erythrocytes at various concentrations was studied in vitro and in vivo. Partition ratios depended on VPA concentration in whole blood and the ratio of erythrocytes/ultrafiltrate, which increased with rising concentrations in the ultrafiltrate fraction. Shifts in ratios were studied by expanding the ultrafiltrate fraction of VPA-spiked blood. It appeared that VPA delivery to the expanded ultrafiltrate compartment originated in a disproportionately large part from erythrocytes. In vivo the half-life of VPA in the erythrocyte fraction was 0.7 h, whereas in the ultrafiltrate fraction and protein-bound fraction half-lives of 2 and 5 h were observed. It is concluded that for VPA in relation to erythrocytes a "last-come-first-go" system is plausible.

Blood Proteins↗
PubMed1989

Distribution of drugs over whole blood: II. The transport function of whole blood for phenytoin.

Phenytoin (DPH) partition between the three main blood compartments, i.e., plasma proteins, erythrocytes, and plasma water, was studied at various concentrations in vitro and in vivo. In vitro, the partition ratio of DPH in a system of erythrocytes in plasma water was 4.5 at concentrations between 0.8 and 100.8 micrograms DPH/ml. In vitro in whole blood (hence, in the presence of plasma proteins), this ratio was approximately 3.9. At 38 degrees C, blank erythrocytes were already in equilibrium with DPH-spiked plasma 3 min after contact, whereas at 20 degrees C, equilibration took 10 minutes or more. By adding blank ultrafiltrate to blood containing DPH, DPH concentrations of blood compartments shifted. It appeared that with the added blank ultrafiltrate, DPH was delivered overproportionally from erythrocytes and less from the protein fraction. In vivo, the elimination half-life of DPH in erythrocytes was 21.4 h and in plasma proteins 67.9 h. These results are similar to those obtained with valproate. It is concluded that erythrocytes have a low affinity for DPH. Their high-capacity transport system, having a "last-come-first-go" mechanism, plays a quantitatively important role in the transport of DPH.

Blood Proteins↗