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Biomedical subjects

W K Amery

Publications and source records attributed to W K Amery.

At least 19 recordsLinked to original sources
PubMed1992

Levamisole, the story and the lessons.

The history of the use of levamisole in man is summarized, from its start as an anthelmintic in the early sixties, through its world-wide recognition as an immunotropic agent especially in the seventies and early eighties, and its return to clinical prominence in 1989-90 as an effective adjuvant treatment for operable colon cancer. The knowledge accumulated from experimental tumour models and from clinical use in various types of cancer, supplemented with the recent evidence obtained from large-scale controlled trials in resectable colon cancer is reviewed. It is speculated that we may not have seen the end of levamisole story yet; also, the role of serendipidity in drug research is emphasized.

Chemotherapy, Adjuvant↗
PubMed1989

Aromatase inhibition by R 76713: experimental and clinical pharmacology.

R 76713 is a new non-steroidal compound which inhibits aromatase in vitro and in vivo with a potency of at least 1000-fold that of aminoglutethimide. In male cynomolgus monkeys peripheral conversion of labeled androstenedione to estrone is decreased by 85%, 4-5 h after a single intravenous dose of 0.003 mg/kg of R 76713, without altering steroid metabolic clearance rates. In rats fed a sodium-depleted diet for 3 weeks, plasma levels of aldosterone and plasma renin activity remain unchanged 2 h after a single oral dose of up to 20 mg/kg of R 76713. This confirms previous data on the selectivity of R 76713 for aromatase inhibition as compared to inhibition of other enzymes involved in steroid biosynthesis. In male volunteers, a single oral dose of 5 or 10 mg of R 76713 lowers median plasma estradiol levels from 70 pM to the detection limit of the assay (30 pM) 4 and 8 h after intake, whereas no important changes are detected after placebo administration. In 15 premenopausal female volunteers receiving a single oral dose of 20 mg of R 76713, mean plasma estradiol levels decrease from 415 pM (before) to 179, 149 and 185 pM respectively 4, 8 and 24 h after intake whereas they remain above 380 pM after placebo (n = 7).

Adult↗
PubMed1989

The role of the gut in migraine: the oral 51-Cr EDTA test in recurrent abdominal pain.

Sixteen children with recurrent abdominal pain (or: "recurrent syndrome"), regarded as migraine equivalent in childhood, were submitted to the 51-Cr EDTA gut permeability test. The results were compared with those obtained in 10 healthy young adults and in 11 control children. The gut permeability in the recurrent syndrome was significantly higher than in healthy adults and control children (p less than 0.0006): The following results were obtained: 4.83 +/- 0.40 (mean +/- SEM) in the children with recurrent abdominal pain, and 2.35 +/- 0.24 2.51 +/- 0.21 in the healthy young adults and control children, respectively. The implications of these findings as far as migraine is concerned, are discussed.

Abdominal Pain↗
PubMed1989

Prophylactic and curative treatment of migraine with calcium antagonists.

The present review discusses the available clinical information dealing with the treatment of migraine with calcium entry blocking agents. The data on prophylactic therapy are limited to 3 compounds, of which flunarizine is the most extensively studied and the only substance whose activity is well established. Clinical experience with these agents in the acute treatment of migraine attacks is still very limited.

Adult↗
PubMed1988

The effect of sabeluzole (R 58735) on memory retrieval functions.

In a first double-blind, placebo-controlled parallel experiment, 20 volunteers with a median age of 45 years were treated for 1 week with either sabeluzole (R 58735) or placebo. Before and after the treatment period, they were subjected to a Selective Reminding Procedure in which a 20-word list had to be learned. No differences between the two groups were seen for total recall, short-term retrieval, total long-term retrieval, random long-term retrieval and long-term storage. However, a significant improvement in consistent long-term retrieval (cLTR) was seen for the subjects treated with sabeluzole. This effect was restricted to the group of the poor performers, i.e. those with a baseline cLTR of 50% or less. In a second experiment, 12 healthy elderly volunteers with a median age of 59 years were subjected to the same test procedure. They were treated with sabeluzole in a single-blind fashion. Again the cLTR improved significantly in the group of poor performers. It was thus confirmed that sabeluzole ameliorates retrieval functions and primarily so in poor performers.

Adult↗
PubMed1988

The effect of R 58 735 (Sabeluzole) on memory functions in healthy elderly volunteers.

The effects of chronic treatment (5 mg b.i.d. for 2 days followed by 10 mg b.i.d. for 5 days) with R 58 735 on human memory functions were studied in healthy elderly (age greater than or equal to 50 years) volunteers in a double-blind placebo-controlled study. Serial learning of nonsense syllables was better under R 58 735, and relearning 1 week after termination of the treatment was superior to relearning of similar material initially learned under placebo. Free recall of nonsense syllables was significantly better when these were learned under active compound. Proactive inhibition induced by consecutive presentation of word lists was attenuated by R 58 735. Short-term memory functions, retrieval accuracy from semantic memory and unprepared reaction times were unchanged. R 58 735 ameliorated both learning and recall in conditions of age-related mild hypofunction in healthy volunteers. The compound seems to have had positive effects on encoding and consolidation of new material.

Cognition↗
PubMed1988

The sensorium of the migraineur.

The occurrence of perceptual disturbances in migraineurs, particularly during the headache-free interval, has been scrutinized rather rarely. This subject was studied via a mail survey in 134 patients presenting perceptual changes before or during their migraine attacks. The patients had to complete a 5-part questionnaire covering history, events before, during as well as after the attack, and the attack-free interval. Sensory alterations during the headache-free interval were not reported by 36.6% of the patients. Alterations of equilibrium and/or spatial orientation, mainly susceptibility to motion sickness, were present in 47.8%, increased sensitivity to cold or heat in 40.3%, intolerance of tight clothes or being touched in 34.3%, altered visual function in 32.8%, changes in olfactory acuity in 31.1%. These percentages show that these 5 types of interictal sensory disturbances may not be rare in migraineurs. The exact frequency of these symptoms and how they correlate with perictal phenomena, sex, age and disease characteristics has to be further studied.

Adult↗
PubMed1988

Hepatic cytochrome P450-mediated oxidation function in migraine.

Hepatic cytochrome P450-dependent oxidation is deficient in 5% to 10% of the Caucasian population. A similar percentage seems to suffer from migraine. The hypothesis was tested that an oxidation deficiency possibly relevant to potential dietary triggers plays a role in the pathogenesis of migraine. In 37 migraine sufferers and 26 controls age- and sex-matched to 26 of these patients, debrisoquine hydroxylation following an oral dose of 10 mg was employed as a marker of oxidation status, determined by calculating the metabolic ratio (MR): urinary debrisoquine/urinary 4-hydroxydebrisoquine. MR was similarly distributed in migraineurs and controls. Three subjects in each group were poor metabolizers (MR greater than 30, versus normal range, 0.1-12). MR in patients did not depend on type of migraine (common versus classic), attack frequency, the presence of trigger factors, smoking or a history of adverse reactions or sensitivity to medicines.

Adult↗
PubMed1988

Onset of action of various migraine prophylactics.

Four studies were pooled to study the onset of action of three pharmacologically different migraine prophylactics: flunarizine, pizotifen and propranolol. Inter-drug differences in reduction of baseline attack frequency were subjected to analysis of variance. At months 1, 2, and 3 the inter-drug differences in number of patients showing a first 50% decrease in attack rate were subjected to the Chi-square test. Both tests showed that there were no significant differences in onset of action between the three drugs. It is concluded that migraine responds to flunarizine and to other commonly used prophylactics in a similar way and with similar kinetics.

Adolescent↗
PubMed1987

Some comments on the use of statistics in the evaluation of drug trials in migraine.

Statistical aspects need particular attention in reporting on drug studies in migraine. It is important to report on all patient and disease characteristics which have contributed to the diagnosis and on all variables used for the evaluation of the result; the use of median values, accompanied by the extremes, is recommended in this context. Comparability of the study groups should be examined and possibly repeated after exclusion of the defaulters, if their number is substantial. As regards the presentation of the results, it does not suffice to give p values only: the magnitude of the response should be given and the use of techniques estimating the reliability of this magnitude (e.g. confidence intervals) and/or its reproducibility (e.g. power calculations) is recommended. An analysis of three unrelated groups of migraineurs demonstrates that most pertinent variables show a non-Gaussian distribution, and this includes the distribution of treatment results. For this reason, the use of nonparametric tests is advocated.

Adolescent↗