RESUMO
Provision of a comprehensive interpretative service is an important challenge facing chemical pathologists. Attempts to automate report interpretation using expert systems have been limited in the past by the difficulties of rule base maintenance. We have applied a novel knowledge acquisition technique, ripple down rules, in the development of PEIRS (Pathology Expert Interpretative Reporting System), a user-maintained expert system for automating chemical pathology report interpretation. We created over 950 rules for thyroid function tests, arterial blood gases and other test sub-groups in 9 mths of operation. A staff pathologist performed all maintenance tasks as part of his routine duties without any need for computer programming skills. No clerical staff involvement was required. Duplication of rule addition for reports requiring multiple comments was the only limitation to coverage of other high volume test groups. PEIRS is the first expert system for the automated interpretation of a range of chemical pathology reports which operates in routine use without extra staffing requirements. PEIRS does not require "knowledge engineering" expertise. Thus, the knowledge base is flexible and can be easily maintained and updated by the pathologist. Expert systems based on ripple down rules should enable pathologists to provide a comprehensive automated interpretative service within the context of the total testing process.
Assuntos
Química Clínica/métodos , Tomada de Decisões Assistida por Computador , Sistemas Inteligentes , Prontuários Médicos , Patologia Clínica/métodos , HumanosRESUMO
Adenosine triphosphatase (ATPase) activity which could be stimulated maximally by either Ca2+ or Mg2+ was identified in a synaptosomal fraction from rat brain caudate nucleus. The thermodynamic properties of the Ca2+ and Mg2+ stimulated enzymes were similar to each other. Oligomycin, sodium azide and dinitrophenol had no significant inhibitory effects on stimulation by either cation. In vitro incubation of the ATPase with cis- or trans-flupenthixol, chlorpromazine or trifluoperazine, but not with haloperidol, significantly inhibited stimulation by either cation. The DA receptor agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) inhibited stimulation of the enzyme by either cation, while d-amphetamine, SKF 38393, pergolide and LY-171555 had no significant effects. Nomifensine at 10(-3) M inhibited the cation stimulation by about 33%. In vivo administration of dopamine (DA) receptor antagonists (haloperidol, cis- and trans-flupenthixol, spiperone, chlorpromazine and trifluoperazine) and the agonist apomorphine neither inhibited nor stimulated ATPase activity. It appears from these data that the ATPase activity is not under DA receptor modulation. In addition, our tentative conclusion is that one enzyme is involved, because both Ca2+ and Mg2+ produced similar maximal stimulations, the activities as a function of temperature were similar, the enzyme could not be further stimulated with Ca2+ after maximal stimulation by Mg2+ (and vice versa), and the behaviour of the ATPase activity to all drugs tested was similar.
Assuntos
ATPase de Ca(2+) e Mg(2+)/metabolismo , ATPases Transportadoras de Cálcio/metabolismo , Núcleo Caudado/enzimologia , Animais , ATPase de Ca(2+) e Mg(2+)/antagonistas & inibidores , ATPases Transportadoras de Cálcio/antagonistas & inibidores , Antagonistas de Dopamina , Cinética , Masculino , Ratos , Ratos Endogâmicos , Receptores Dopaminérgicos/fisiologia , Sinaptossomos/enzimologia , Tetra-Hidronaftalenos/farmacologia , TermodinâmicaRESUMO
The effects of L-Dopa + benserazide (L-Dopa + B) treatment on pre- and postsynaptic dopamine (DA) receptors were studied. Mice treated once daily P.O. with L-Dopa (200 mg/kg) + B (50 mg/kg) or vehicle for 10 days were used on the 11th day. After premedication with reserpine and alpha-methyltyrosine (alpha-MT), apomorphine (0.5-2.0 mg/kg) produced locomotor stimulation which was of equal intensity in the 3 treatment groups, even when the treatment dose of L-Dopa was increased to 400 mg/kg per day. In contrast, low doses of apomorphine (0.1-0.5 mg/kg) produced locomotor depression in B- and vehicle-treated mice but not in L-Dopa + B-treated mice. In rats treated I.P. twice daily with L-Dopa (200 mg/kg) + B (50 mg/kg), B (50 mg/kg) or vehicle for 12 days, apomorphine produced an equivalent degree of stereotypy on the 13th day in each of the 3 treatment groups. There were no treatment group differences in the binding of [3H]-spiperone or [3H]-leu-enkephalin to rat striatal membranes. The data suggest that long-term L-Dopa + B treatment of mice and rats does not change the sensitivity of postsynaptic DA receptors but may affect the sensitivity of DA autoreceptors.
Assuntos
Levodopa/farmacologia , Receptores Dopaminérgicos/efeitos dos fármacos , Animais , Apomorfina/farmacologia , Benserazida/farmacologia , Humanos , Masculino , Metiltirosinas/farmacologia , Camundongos , Atividade Motora/efeitos dos fármacos , Ratos , Receptores Dopaminérgicos/fisiologia , Reserpina/farmacologia , Comportamento Estereotipado/efeitos dos fármacosRESUMO
The effect of delta 9-tetrahydrocannabinol (THC), morphine, haloperidol and chlordiazepoxide on the exhibition of the signs of the quasi-morphine withdrawal syndrome was studied in rats. In preliminary studies approximately equi-sedative doses of these drugs were chosen. Morphine and THC produced a very similar degree of suppression of the signs of the quasi-morphine withdrawal, but unlike morphine, the effects of THC were not reversed by the narcotic antagonist, naloxone. The dopamine receptor antagonist, haloperidol, produced a moderate suppression of the withdrawal syndrome and chlordiazepoxide was without significant effect. It is concluded that THC is of very similar potency to morphine in suppressing the quasi-morphine withdrawal syndrome, but its activity in this regard does not appear to be dependent upon the availability of opiate or dopamine receptors, nor is it due to sedation alone.
Assuntos
Dronabinol/farmacologia , Dependência de Morfina/psicologia , Morfina/farmacologia , Síndrome de Abstinência a Substâncias/psicologia , 1-Metil-3-Isobutilxantina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Clordiazepóxido/farmacologia , Haloperidol/farmacologia , Humanos , Masculino , Naloxona/farmacologia , RatosAssuntos
Dronabinol/farmacologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Membranas Sinápticas/enzimologia , Tiopental/farmacologia , Animais , Sinergismo Farmacológico , Fluidez de Membrana/efeitos dos fármacos , Lipídeos de Membrana/metabolismo , Camundongos , Fosfolipídeos/metabolismo , Membranas Sinápticas/efeitos dos fármacosAssuntos
Dopamina/fisiologia , Dronabinol/farmacologia , Ácidos Graxos não Esterificados/sangue , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Canabinoides/farmacologia , Interações Medicamentosas , Feminino , Técnicas In Vitro , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos , Estimulação QuímicaRESUMO
delta 9-Tetrahydrocannabinol (2.5-80.0 mg/kg) significantly prolonged the anaesthesia induced by ketamine, pentobarbitone, thiopentone, propanidid, and Alfathesin in a dose-dependent manner. Cannabinol and cannabidiol (both 5.0-80.0 mg/kg) were essentially inactive, except that cannabidiol prolonged pentobarbitone-induced anaesthesia. The interaction of delta 9-tetrahydrocannabinol with the anaesthetic agents was postulated to be due to a centrally mediated action, whereas the effect of cannabidiol on pentobarbitone-induced anaesthesia probably depended on a metabolic interaction. The interaction between the cannabinoids in influencing anaesthesia induced by the above agents was examined, and the interactions were found to be complex.
Assuntos
Anestésicos/antagonistas & inibidores , Canabinoides/farmacologia , Mistura de Alfaxalona Alfadolona/antagonistas & inibidores , Animais , Relação Dose-Resposta a Droga , Dronabinol/farmacologia , Interações Medicamentosas , Feminino , Ketamina/antagonistas & inibidores , Camundongos , Pentobarbital/antagonistas & inibidores , Propanidida/antagonistas & inibidores , Tiopental/antagonistas & inibidoresAssuntos
Dronabinol/farmacologia , Ácidos Graxos não Esterificados/sangue , Administração Oral , Animais , Relação Dose-Resposta a Droga , Dronabinol/administração & dosagem , Epinefrina/antagonistas & inibidores , Epinefrina/farmacologia , Feminino , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos , Veículos Farmacêuticos , Propranolol/farmacologia , Fatores de TempoRESUMO
The interaction between delta9-tetrahydrocannabinol (THC) and PGE1 was studied using two pharmacological parameters-the rate of passage of a charcoal meal through mouse small intestine and the abdominal constriction response in the mouse. PGE1 administered intraperitoneally produced a dose-dependent decrease in intestinal motility, and this effect was antagonized by low (0.25 mg/kg) doses of THC and potentiated by higher doses of THC (1 mg/kg). Kinetic analysis suggested that the interaction was of a mixed but predominantly competitive type. PGF2alpha produced an increase in intestinal motility but this was not dose-dependent. THC antagonized the effect of PGF2alpha in a dose-dependent manner suggestive of a physiological antagonism. THC (0.25-2 mg/kg) antagonized the dose-dependent PGE1 abdominal constriction response in a fashion which suggested a mixed (though mainly competitive) antagonism. It would ssem, therefore, that on the two pharmacological parameters studied THC appears to be interacting with PGE1 at the same receptor site. Although the doses of THC used are within the range of those used in man, it is not implied that these results are necessarily implicated in the psychoactivity of the drug.
Assuntos
Analgesia , Cannabis/farmacologia , Dronabinol/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Prostaglandinas E/antagonistas & inibidores , Animais , Ligação Competitiva , Feminino , Cinética , Camundongos , Prostaglandinas E/farmacologia , Prostaglandinas F/antagonistas & inibidoresAssuntos
Anestesia por Inalação , Cannabis/farmacologia , Éter/antagonistas & inibidores , Etil-Éteres/antagonistas & inibidores , Animais , Canabidiol/farmacologia , Cannabis/administração & dosagem , Relação Dose-Resposta a Droga , Dronabinol/farmacologia , Interações Medicamentosas , Feminino , Camundongos , FitoterapiaRESUMO
The onset and duration of tolerance to three effects of delta9-tetrahydrocannabinol (delta9-THC) given orally to mice were compared. The effects of delta9-THC studied were: hypothermia, the depression of intestinal motility and the effect on spontaneous locomotor activity. When mice were dosed and tested at 24 hrs intervals it was apparent that tolerance was complete to its hypothermic and locomotor depressant effects after the first doses and to depression of intestinal motility after the fourth dose. Duration of tolerance also differed so that the normal hypothermic response had returned after 12 dose-free days, but not after 5 drug-free days; the effect on locomotor activity had returned within 4 days; and apparent partial tolerance to the depressant effect of an acute challenging dose of delta9-THC on intestinal motility still existed after 19 dose-free days. It is apparent that the time of onset and the duration of tolerance to delta9-THC in mice showed a different pattern in the three parameters studied. It seems unlikely therefore that any one mechanism, such as metabolic tolerance, explains all the results observed and that several mechanisms should be explored to explain the phenomenon of tolerance to delta9-THC.
Assuntos
Temperatura Corporal/efeitos dos fármacos , Cannabis/farmacologia , Dronabinol/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Animais , Depressão Química , Tolerância a Medicamentos , Feminino , Camundongos , Fatores de TempoRESUMO
Kinematographic traces enable an assessment of jaw movements in the sagittal and coronal planes and the relationship of centric relation to centric occlusion can be determined. Centric relation in this context does not necessarily imply the ligamentous position but rather to an actively obtained physiological border position possibly corresponding to the retruded direct contact position. This position in normal subjects is either postero-inferior to or coincident with centric occlusion. Normal subjects were able to make lateral movements of the jaws to and from centric occlusion on either side and certain subjects were able to describe a plateau in or about the horizontal position of centric occlusion. Rhythmic traces showed that opening and closing movements of the jaws could be made in about 550 msec and reflex jaw opening was usually elicited after centric occlusion had been achieved. The significant correlation coefficients found by measuring the angles of opening, terminal opening and closing indicated that jaw movement was integrated. The TMJ series differed from the normal series in nearly all phases of jaw movement recorded. Centric relation was found to be lateral and antero-inferior to centric occlusion. On the side of the first interceptive tooth contact the patient was not able to return the jaws to centric occlusion. Intermittent traces indicated that there was no significant correlation between the angles of opening, terminal opening and closing suggesting that jaw movement were incoordinated. This was reflected in rhythmic traces which were considerably longer than those of the normal series. This increase in duration was found to be due partially to centric slides and partially to asynergistic movements of the mandible. The jaw-opening reflex was not usually elicitable. It is considered that in the TMJ series centric occlusion is a strained position and is usually lateral to and postero-superior to centric relation. This relationship of centric occlusion to centric relation is the reverse of normal relations and indicates that the mandible is displaced in centric occlusion. In general, patients with the TMJ syndrome have a postero-lateral displacement of the mandible.