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Biomedical subjects

P J Lewi

Publications and source records attributed to P J Lewi.

At least 19 recordsLinked to original sources
PubMed1991

A comparative test of fifteen compounds against all known human rhinovirus serotypes as a basis for a more rational screening program.

A systematic evaluation of 15 rhinovirus capsid-binding agents against all 100 serotyped human rhinoviruses revealed the existence of two virus groups, based upon differential susceptibility to antiviral compounds. Elongated and short-chained compounds preferentially inhibited groups A and B. The positions of the rhinoviruses within a map derived from a multivariate analysis allow for the selection of a panel of 17 rhinoviruses, for which the median antiviral inhibitory value against them will accurately predict the median value against 100 serotypes. This rationalizes the search for broad-spectrum capsid-binding antirhinovirus drugs, or combinations of drugs with complementary spectra that may be necessary to effectively inhibit both type A and type B viruses.

Antiviral Agents↗
PubMed1990

Two groups of rhinoviruses revealed by a panel of antiviral compounds present sequence divergence and differential pathogenicity.

A variety of chemically different compounds inhibit the replication of several serotypes of rhinoviruses (common-cold viruses). We noticed that one of these antiviral compounds, WIN 51711, had an antiviral spectrum clearly distinctive from a consensus spectrum or other capsid-binding compounds, although all of them were shown to share the same binding site. A systematic evaluation of all known rhinovirus capsid-binding compounds against all serotyped rhinoviruses was therefore initiated. Multivariate analysis of the results revealed the existence of two groups of rhinoviruses, which we will call antiviral groups A and B. The differential sensitivity of members of these groups to antiviral compounds suggests the existence of a dimorphic binding site. The antiviral groups turned out to be a reflection of a divergence of rhinovirus serotypes on a much broader level. Similarities in antiviral spectra were highly correlated with sequence similarities, not only of amino acids lining the antiviral compound-binding-site, but also of amino acids of the whole VP1 protein. Furthermore, analysis of epidemiological data indicated that group B rhinoviruses produced more than twice as many clinical infections per serotype than group A rhinoviruses did. Rhinoviruses belonging to the minor receptor group were without exception all computed to lie in the same region of antiviral group B.

Amino Acid Sequence↗
PubMed1989

Relevance and significance of pre-CPR conditions in cardio-pulmonary-cerebral resuscitation. A graphic analysis by means of Spectramap. The Cerebral Resuscitation Study Group.

The effects of pre-arrest conditions on success rates of CPCR have been studied in 4501 circulatory arrests that have been recorded by the Belgian CPCR-Registry from 1983 to 1987. A graphical technique called Spectramap has been used for the simultaneous perception of clinical relevance and statistical significance. The success of CPCR is determined to a large extent by pre-arrest conditions. Arrests occurring inside hospitals possess a far better prognosis than those observed outside. (Overall success rate inside hospitals is 18% vs. 7% outside). Site of arrest, time to call, time to CPR, and bystander intervention appear to be relevant and significant conditions outside the hospital. Age, underlying disease and degree of disability are shown to be relevant and significant inside hospitals. The Belgian CPCR-Registry, combined with Spectramap, also allows assessment of the efficiency of emergency services and the efficacy of life supporting treatments. This article describes the graphical method of Spectramap and its application to the Belgian CPCR-Registry.

Belgium↗
PubMed1989

Early prognostic indices after cardiopulmonary resuscitation (CPR). The Cerebral Resuscitation Study Group.

An early prediction score (EPS) is constructed as the sum of five events: the type of cardiac arrest is ventricular fibrillation; the type of respiratory arrest is gasping; pupil reaction is unequal, slow or normal, but present; swallowing activity is present and the cardiac arrest has been witnessed. Presence of any of these events contributes one point to the score, while absence contributes nothing to it. EPS during resuscitation results in a comparable amount of information, whether used to predict success, alive and conscious 14 days post-CPR or no-success. EPS early (10 min) after initially successful resuscitation is more effective in predicting no-success than success. EPS during CPR does not allow decision making as far as stopping or continuing CPR efforts. EPS early after CPR does neither allow decision making as far as stopping or continuing critical care efforts after initially successful CPR. EPS does, however, weigh the likelihood of success against that of no-success, which can be used when discussing the chances of the patient with his relatives.

Deglutition↗
PubMed1989

Are inter-center differences in EMS-management and sodium-bicarbonate administration important for the outcome of CPR? The Cerebral Resuscitation Study Group.

The hospital of Brugge relies on selection of the emergency calls and sends a Mobile Intensive Care Unit (MICU) whenever cardiac arrest (CA) is suspected. The University Hospital of Leuven does no selection of calls and responds to every emergency call by sending an ambulance with an advanced life support (ALS) trained nurse. The MICU is called when the ambulance crew recognizes the emergency to be a CA. The Leuven system is a so-called tiered system. Although MICU-response times are significantly longer in Leuven than in Brugge, no difference is found as to the success of CPCR. The immediate response to all emergency calls by specialized E.D. nurses (paramedic) capable of ALS, seems to make up for the difference in MICU-response times. The University Hospital of Jette has a higher success-rate for CPCR for in-hospital CA, than the University Hospitals of Leuven. Due to size and lay-out differences, the MICU-response times are shorter in Jette than in Leuven. Basic life support (BLS) provided by doctors and nurses present at the scene, does not seem to be able to compensate for longer MICU-arrival times. The introduction of semi-automatic or automatic defibrillators, to be used by the BLS trained medical and nursing personnel, might be able to make up for the longer MICU-intervention times. Inter-center differences were witnessed as far as the amount of sodium-bicarbonate infused during CPR. Within each group of total duration of CPR an inverse correlation exists between the amount of bicarbonate infused and the success rate of CPCR. Partial correlation between the bicarbonate infused and the survival with regaining of consciousness at 14 days post-CPR, with constant CPR-time, is statistically significant. This indicates that long-term CPCR success is inversely correlated with increasing amounts of sodium-bicarbonate infused. Short duration of CPR and low adrenaline dosage correlate with immediate and long-term success of CPR. On the contrary, low versus high bicarbonate dosage has hardly any influence on immediate success (restoration of spontaneous circulatory activity) but low bicarbonate dosage favours long-term success (survival accompanied by recuperation of brain function). Our data support a negative effect on long-term survival with recuperation of consciousness from infusion of more than 1 mEq/kg body weight of sodium-bicarbonate during CPR. No final conclusions can be drawn so far as to the mechanisms of this negative effect at the level of the brain.

Ambulances↗
PubMed1982

Toxicology reference data for the Wistar rat.

Sixty-six observations on Wistar rats, including body and organ weights, biochemistry, hematology, and urinalysis have been compiled over a period of 16 years. A statistical analysis of these observations involved 3,400 Wistar rats that served as controls in toxicity studies. The results have been recorded on synoptic charts, which provide frequency distributions, cumulative distributions and variations according to the time of observation, the sex and the age of the rats. The construction of the statistical charts, the prominent features of the distributions and the use of reference data in toxicology are discussed.

Animals↗
PubMed1980

A comparison between manual and semiautomatic white cell differentiation.

Manual and semiautomatic white cell differentiations have been found to produce comparable results. Semiautomatic counting can be accomplished with a smaller number of cells than required in manual counting without significant loss of accuracy. Cell types have been compared one by one to detect systematic deviations between the counting procedures. Complete differentials have been compared by means of a multivariate method called canonical correlation. The result of the canonical correlation is displayed graphically. Highly significant correlations have been found between 100-cell manual and 100-, 50-cell semiautomatic differentials.

Animals↗
PubMed1978

Levamisole in rheumatoid arthritis--a multivariate analysis of a multicentric study.

Statistical analysis of the data from a multicentric study of six months of treatment with levamisole in rheumatoid arthritis involved two steps. In a first step, the differences between observations before and after treatment have been made independent of their initial values. Differences after treatment have been transformed into responses to treatment using a proportionality factor that is related to the initial values before treatment. The second step involved a reduction of the various responses into a single global response by means of a discriminant analysis between two classes. Class membership has been defined by the type of treatment (either placebo or drug) predicted by the investigators at the end of treatment and before breaking of the code of the double-blind study. This method of analysis allows for the combination of multiple clinical observations with a subjective evaluation. Its results can be easily represented graphically and tested for statistical significance. The use of global responses to treatment is illustrated with a comparison of placebo and drug treatments and can be extended to comparisons between investigators or between different dose and time regimens.

Arthritis, Rheumatoid↗
PubMed1978

Degree of responsiveness to levamisole and factors influencing responsiveness and adverse reactions.

The individual response to treatment, and factors influencing this response, were evaluated by means of Lewi's mathematical model in patients with rheumatoid arthritis. Patients showed a graded response to anti-inflammatory agents ranging from deterioration through moderate to marked improvement. Levamisole was superior to anti-inflammatory agents in preventing deterioration or inducing marked improvement. Patients in an early stage of disease were the best responders and had fewest idiosyncratic reactions. The responses were independent of the treatment schedule used. A threshold dose of levamisole exists, but it is not critically dependent on body weight.

Anti-Inflammatory Agents↗
PubMed1976

On the classification of antidepressant drugs.

Clinical, pharmacologic, and biochemical profiles of antidepressant drugs have been analyzed statistically. A method derived from multivariate statistics separates mere drug potency from the spectral information contained in the profiles. The dimensionality of the spectra is also reduced and this results in a diagram of associations and dissociations between the antidepressants and their scales of observation. The spectra of antidepressants show three poles which have been labeled as D (desipraminelike), A (amitriptylinelike), and M (MAOI). Clinical spectra agree better between one another than various pharmacologic spectra do. Monoamine oxidase inhibitors are readily differentiated from the tricyclic compounds. The latter appear in the sequence: desipramine, nortriptyline, imipramine, and amitriptyline. This sequence can also be reproduced from biochemical spectra of central and peripheral blockade of norepinephrine and serotonin reuptake.

Affect↗
PubMed1976

Classification and discrimination for data analysis in pharmacology.

Classification and discrimination are described as methods of inference and decision-making in pharmacological data analysis. Principal components and multiple discriminant analysis are applied to animal and human spectra of the neuroleptics. A preliminary step is required to separate differences in potency from the spectral information.

Animals↗
PubMed1976

Clinical and pharmacological spectral maps of the neuroleptics.

The clinical and pharmacological activity spectra of the neuroleptics can be projected into a map where compounds with similar spectra, but with possibly different potencies, are grouped together. The spectral maps were devised for classification and for the prediction of therapeutic effects from pharmacological observations. Significant correlations are observed within and between pharmacological and clinical classifications (Spearman test, p less than 0.01). Pharmacological maps appear to be one-dimensional and resemble the Lambert incisive/sedative bipolar scale. The Liége clinical physiognomy of neuroleptics shows an additional component which may be related to antimanic/antiaustistic effects.

Animals↗
PubMed1976

Spectral mapping, a technique for classifying biological activity profiles of chemical compounds.

A mathematical technique is described that separates potency from spectral information in biological activity spectra. The technique is a preliminary step in the classification of chemical compounds and in the structuring of pharmacological assays. The method is illustrated using previously reported results on 40 neuroleptics in 12 assays on rats. Principal component analysis and cluster analysis are shown to provide complementing information.

Animals↗
PubMed1976

Antagonism of maximal metrazol seizures in rats and its relevance to an experimental classification of antiepileptic drugs.

The antagonism of various components of maximal Metrazol-seizures (MMS) (i.e. tonic hindpaw extension, tonic backward extension of the forepaws, generalized clonic seizures and tremors), ataxia and loss of righting reflex-activity have been studied in a standardized procedure comparing 41 antiepileptics and related compounds. Appropriate analyses (Cluster Analysis and Principal Component Analysis) resulted in the distinction of seven clusters which could be considered along two continua. A first continuum is characterized by a progressive strengthening of loss of righting reflex-inducing properties, a decreasing dissociation of ataxia and loss of righting reflex and the disappearance of a selective anticonvulsant effect. The second continuum is characterized by an increasing relative potency of ataxia-inducing properties, an increasing dissociation of ataxia and loss of righting reflex and a decreasing antagonism of tremors. Three main types of anticonvulsants could be defined: drugs with a complete anti-MMS effect antagonizing both clonic and tonic seizures; drugs selectively abolishing tonic seizures, i.e., tonic extension of hind- and forepaws; and drugs exclusively blocking tonic hind-paw extension. The neurological and clinical significance of these different types of anticonvulsant activity has been discussed. Finally, the described modification of the maximal Metrazol-seizures test is proposed for routine screening purposes.

Animals↗
PubMed1976

Intravenous pharmacokinetic profile in rats of etomidate, a short-acting hypnotic drug.

Etomidate is a novel short-acting drug, whose pharmacokinetic profile was studied in 14 organs and tissues after i.v. administration to rats. Four dose levels, ranging from 224 to 1800 mug, were assayed between 1.75 and 112 min after administration. A three-compartment open linear model has been fitted to the plasma concentrations, assuming a central, peripheral and deep compartment. The fast component of the plasma curve, has a half-life of 1.19 min. Brain tissue rapidly enters in equilibrium with plasma and shows the highest concentration. Muscle, subcutaneous fat and possibly skin and connective tissues contribute most to the total amount of drug in the body. Many tissues are heterogeneous and exhibit combinations of central, peripheral and deep compartments. Elimination of etomidate occurs by ester-hydrolysis in plasma and in the liver with approximately equal rate constants. Metabolization of etomidate in the liver is a capacity-limited Michaelis-Menten process.

Animals↗
PubMed1975

Spectral maps of the Liege-physiognomies of the neuroleptics.

Spectral mapping is a classification technique that has been applied to the Liege physiognomies of the neuroleptics. The method makes use of a special projection that separate potency from spectral information. Principal component analysis revealed a dominant component resembling a bipolar incisive/sedative scale. A second antimanic/antiautistic scale is apparent in the revised. Liege physiognomie. Spectral mapping allows to compare observations on neuroleptics in different frames of reference and from different methodologies (e.g. clinical and pharmacological).

Basal Ganglia Diseases↗