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PubMed2001

Inhibition of the cyclin D1/E2F pathway by PCA-4230, a potent repressor of cellular proliferation.

1. Tight control of cellular growth is essential to ensure normal tissue patterning and prevent pathological responses. Excessive vascular smooth muscle cell (VSMC) proliferation is associated with the pathophysiology of atherosclerosis and restenosis post-angioplasty. Thus, drug targeting of pathological VSMC growth may be a suitable therapeutic intervention in vascular proliferative diseases. 2. In the present study, we investigated the mechanisms underlying VSMC growth arrest induced by the pharmacological agent PCA-4230. Addition of PCA-4230 to cultured VSMCs blocked the induction of cyclin D1 and cyclin A expression normally seen in serum-restimulated cells. Moreover, PCA-4230 inhibited cyclin-dependent kinase 2 (CDK2) activity and abrogated hyperphosphorylation of the retinoblastoma (Rb) gene product. Similarly, PCA-4230-dependent growth arrest of transformed cell lines correlated with reduced level of cyclin D1 protein and inhibition of CDK2 activity. Consistent with these findings, PCA-4230 repressed serum-inducible cyclin A promoter activity, and overexpression of either cyclin D1 or E2F1 efficiently circumvented this inhibitory effect. Importantly, adenovirus-mediated overexpression of E2F1 restored S-phase entry in PCA-4230-treated VSMCs, demonstrating that PCA-4230 represses cyclin A gene expression and VSMC growth via inhibition of the cyclin D1/E2F pathway. 3. Because of its ability to inhibit the growth of human VSMCs and transformed cell lines, future studies are warranted to assess whether PCA-4230 may be a suitable therapeutic intervention for the treatment of hyperproliferative disorders, including cardiovascular disease and cancer.

Animals↗

PubMedDate not supplied

Nutritive sucking and neurobehavioral development in preterm infants from 34 weeks PCA to term.

PURPOSE: To investigate changes in nutritive sucking patterns, behavioral state, and neurobehavioral development of preterm infants from the 34 weeks postconceptional age (PCA) to term. DESIGN: Nonexperimental descriptive correlational design was used. METHODS: A convenience sample included 66 preterm infants with a gestational age between 24 and 34 weeks at birth. Mean gestational age was 29.7 weeks, with a mean birthweight of 1379 grams. Instruments included the Kron Nutritive Sucking Apparatus, the Anderson Behavioral State Scale (ABSS), and the Brazelton Neonatal Behavioral Assessment Scale (BNBAS). A feeding procedure was administered at 34 and 40 weeks PCA with BNBAS administered at 40 weeks PCA. Data analysis strategies included t-tests, Spearman rho correlations, Wilcoxon matched-pairs signed-ranks test, and a Random Coefficients Model. RESULTS: There were significant differences in number of sucks (p < 0.001), intensity of sucking pressures (p < 0.001), average time between sucks (p < 0.001), and average time between bursts (p < 0.001) from 34 weeks PCA to term. With maturation, it was noted that the preterm infants were significantly more alert during the sucking protocol from 34 weeks to term (p < 0.001). Yet, infant sucking parameters at 34 weeks PCA and term were not significantly related to the BNBAS or to the infant's state. CLINICAL IMPLICATIONS: These results demonstrate that high risk preterm infants mature significantly in their sucking behaviors and in their ability to maintain a more alert behavioral state from 34 weeks PCA to term. However, unlike full term infants--where state is positively correlated to feeding (sucking) success--the preterm infant state of alertness may not enhance sucking skills at 34 weeks PCA. These infants may be too stressed to manage both feeding and stimulation from the environment that is unavoidable when alert. However, this relationship does appear to change by 40 weeks PCA.

Female↗

PubMed2006

Gabor-based kernel PCA with doubly nonlinear mapping for face recognition with a single face image.

In this paper, a novel Gabor-based kernel principal component analysis (PCA) with doubly nonlinear mapping is proposed for human face recognition. In our approach, the Gabor wavelets are used to extract facial features, then a doubly nonlinear mapping kernel PCA (DKPCA) is proposed to perform feature transformation and face recognition. The conventional kernel PCA nonlinearly maps an input image into a high-dimensional feature space in order to make the mapped features linearly separable. However, this method does not consider the structural characteristics of the face images, and it is difficult to determine which nonlinear mapping is more effective for face recognition. In this paper, a new method of nonlinear mapping, which is performed in the original feature space, is defined. The proposed nonlinear mapping not only considers the statistical property of the input features, but also adopts an eigenmask to emphasize those important facial feature points. Therefore, after this mapping, the transformed features have a higher discriminating power, and the relative importance of the features adapts to the spatial importance of the face images. This new nonlinear mapping is combined with the conventional kernel PCA to be called "doubly" nonlinear mapping kernel PCA. The proposed algorithm is evaluated based on the Yale database, the AR database, the ORL database and the YaleB database by using different face recognition methods such as PCA, Gabor wavelets plus PCA, and Gabor wavelets plus kernel PCA with fractional power polynomial models. Experiments show that consistent and promising results are obtained.

Algorithms↗

PubMed1977

Effect of changing the composition of the bathing solutions upon the isometric tension-pCa relationship in bundles of crustacean myofibrils.

1. The relative isometric tension-pCa relationship has been determined for isolated bundles of barnacle myofibrils under a variety of ionic conditions using [Ca(2+)]-buffered solutions which also contained an ATP regenerating system (creatine phosphate and creatine kinase).2. The results are in better agreement with the ;consecutive' scheme of reaction rather than with the ;independent' alternative (Ashley & Moisescu, 1972) for the co-operative action of two Ca(2+) ions in the process of tension activation in crustacean skeletal muscle.3. Variations in the pH of the activating solutions did have a marked effect on the relative tension-Ca curve, although no effect was observed on the absolute maximum value for isometric tension. A shift in pH by 0.5 u. in the range 6.6-7.6 shifted the Ca(2+)-activation curve by 0.5 log u. towards lower free Ca(2+) concentrations.4. Changes in the free Mg(2+) concentration of the activating solutions in the millimolar range produced a pronounced shift of the relative tension-pCa curve along the pCa axis. Increasing [Mg(2+)] from 1 to 5 mM shifted the curve by about 0.7 log u. to higher free Ca(2+) concentrations, without significantly modifying its steepness.5. Changes in the MgATP concentration of the activating solutions in the range of 1-13 mM had no significant effect on the relative tension-pCa relationship.6. Varying the K(+) concentration in the activating solutions was also observed to have a marked effect upon the tension-pCa relationship in barnacle. An increase in the K(+) concentration from 90 to 170 mM shifted the curve by some 0.6 log u. towards higher free Ca(2+) concentrations.7. Cooling the standard activating solutions from room temperature to +4 degrees C made no apparent difference to the relative tension-pCa relationship, but decreased significantly the absolute tension responses.8. The results presented show that tonicity by itself has a marked effect upon the absolute steady-state tension levels in isolated bundles of myofibrils.9. Maximum isometric tension in this preparation was not simply related to ionic strength, or to the monovalent cation concentration, but it depended, as well, upon the anionic composition of the activating solution. In addition, a change in ionic strength of 25 mM over the range of 245-270 mM did not appear to modify the relative tension-pCa relationship.10. The effect of the physiologically occurring cations H(+), K(+), Mg(2+) upon the relative isometric tension-pCa relationship can be accounted for on the basis of a model of competitive inhibition between these cations and Ca(2+) for the functional unit for tension. This inhibitory effect appears to involve at least one H(+), one Mg(2+) and two K(+) per each Ca(2+) ion participating in the activation process of the functional unit for tension.

Adenosine Triphosphate↗

PubMed1989

[Individual differences in PCA response in the guinea pig].

Experiments were carried out to determine the cause of individual differences in the passive cutaneous anaphylaxis (PCA) response in guinea pigs. The intensity of 4-h homologous PCA produced by anti-penicillin G serum was not markedly different among eight reactive sites on the back of a specified animal, whereas considerable individual differences were observed in the PCA response, even at a specified reactive site. PCA was significantly inhibited by an antihistaminic agent, promethazine, and the tissue histamine content was significantly reduced after PCA, suggesting histamine release as a mediator. The intensity of PCA in individual animals was highly correlated with that of the histamine-induced cutaneous reaction elicited at a site adjoining the PCA but was unrelated to skin histamine content. These results suggest that the difference in susceptibility to histamine has a considerable effect on individual differences in the PCA response in guinea pigs.

Animals↗

PubMed2005

[Differential effect of temperature on Plt and PCA synthesis in a rsmA inactivated mutant strain of Pseudomonas sp. M-18].

Rsm (repressor of secondary metabolite) A is an mRNA binding protein which functions as a global repressor to control multiple genes at the posttranscriptional level. Using homologous recombination technique a chromosomal rsmA inactivated mutant strain M-18R was constructed in Pseudomonas sp. M-18, a strain of plant-growth-promoting rhizobacteria, which could inhibit several soilborn phytopathogens by producing secondary metabolites including phenazine-1-carboxylic acid (PCA) and pyoluteorin (Plt) in one single strain. To further study the effect of RsmA on the synthesis of Plt and PCA in the wild type strain M-18, the dynamic curves of Plt and PCA produced respectively by M-18 and M-18R were measured in KMB medium under different temperature conditions such as 37 degrees C constant, 28 degrees C constant and nonconstant (37 degrees C 4 hours at first and then 28 degrees C constant) cultivation. The synthesis of both Plt and PCA were almost inhibited in the cultures under the condition of 37 degrees C. At 28 degrees C, however, compared with the wild type strain M-18, the mutant strain produced tenfold amount of Plt, while the production of PCA decreased only about 50%. When cultivated under the nonconstant condition, the amount of Plt produced by M-18R could reach 400 microg/mL while the PCA production was not significantly affected, but in the wild type strain M-18, the amount of Plt production decreased obviously while the PCA production was not affected in comparison with the results at 28 degrees C constant. These results suggest that a temperature sensitive factor exists to function as an activator independent of RsmA to promote the synthesis of Plt in the rsmA mutant strain M-18R while it may bind with RsmA to repress the synthesis of Plt in the wild type strain M-18. But this factor did not exert any affect on the synthesis of PCA.

Bacterial Proteins↗

PubMed1990

Pharmacological actions of PCA 4248, a new platelet-activating factor receptor antagonist: in vivo studies.

The ability of PCA 4248 [2-(phenylthio)ethyl-5-methoxycarbonyl- 2,4,6-trimethyl-1,4-dihydropyridine-3-carboxylate] to block PAF-induced systemic hypotension and protein-rich plasma extravasation in rats, and PAF-induced death in mice, was tested. These studies were complemented with experiments using soluble aggregates of immunoglobulin G (A-IgG), bacterial endotoxin and the cytokine tumor necrosis factor as putative inducers of the generation of endogenous PAF. Significant inhibition of PAF-induced systemic hypotension was observed with i.v. PCA 4248 at doses of 0.3 to 1 mg/kg (IC50 value, 0.45 mg/kg, with PAF 0.33 micrograms/kg). Reversal of the hypotension was rapidly observed when PCA 4248 was administered after PAF. The extravasation induced by 1 microgram/kg PAF was also blocked by PCA 4248 (IC50 value, 0.36 mg/kg). Inhibition of the extravasation induced by A-IgG and endotoxin was also provided by PCA 4248 at the dose of 1 mg/kg, and lasted for at least 1 hr in the experiments carried out with endotoxin, which caused extravasation with a temporal pattern more protracted than that of PAF and A-IgG. Intradermal extravasation induced by PAF reached a maximum at 30 min after injection, and was also inhibited by PCA 4248. In contrast, PCA 4248 caused a less remarkable, but statistically significant reduction of the intradermal extravasation caused by tumor necrosis factor. Pretreatment of mice with an oral dose of 30 mg/kg PCA 4248, 5 min before challenge with PAF (LD84 = 80 micrograms/kg PAF, i.v.) increased the survival rate from 16% to 68%. These data indicate that compounds containing a 1,4-dihydropyridine structure can antagonize PAF effects on experimental animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Clinical and roentgenographic evaluation of noncemented porous-coated anatomic medullary locking (AML) and porous-coated anatomic (PCA) total hip arthroplasties.

Eighty-four primary noncemented porous-coated total hip arthroplasties (THAs) in 78 patients were reviewed clinically and roentgenographically at an average follow-up period of 37 months. The average patient age was 51.9 years. Sixty-four Anatomic Medullary Locking (AML) devices were placed in 58 patients, and 20 Porous-Coated Anatomic (PCA) devices were placed in 20 patients. The AML devices had been in situ an average of 36 months (range, 24-49 months), and the PCA devices had been in situ an average of 40 months (range, 29-51 months). The average patient ages were 52.7 and 49.2 years for AML and PCA patients, respectively. The AML devices included three that were fully coated, 59 that were five-eighths coated, and two that were one-third coated. The average preoperative Harris hip score was 38.2 for the AML devices and 33.2 for the PCA devices. The average postoperative Harris hip score was 80.7 for the AML devices and 83.8 for the PCA devices. Pain related to the implant was present in 30% of the AML devices and 30% of the PCA devices. Roentgenographically, no component demonstrated complete radiolucency, and all components demonstrated roentgenographic evidence of bone ingrowth. Roentgenographic changes with time noted for both the AML and PCA devices included: neck roundoff, neck osteolysis, neck corticocancellization, endosteal bone bridging, and distal hypertrophy. On roentgenographic zonal analysis, radiolucency greater than 1 mm was observed most frequently in the most proximal lateral zone and distal tip of the femoral component. The current series of cases, although clinically acceptable, does not support the current widespread enthusiasm for primary noncemented AML and PCA total hip systems. Cemented THA appears to produce superior clinical results, particularly when contemporary cementing techniques are employed.

Adult↗

PubMed1978

Influence of the new 5-HT-uptake inhibitor paroxetine on hypermotility in rats produced by p-chloroamphetamine (PCA) and 4,alpha-dimethyl-7-tyramine (H 77/77).

Two different forms of hypermotility produced by the amphetamine derivatives PCA and H 77/77, 5 mg/kg of each, was studied in rats treated s.c. with the new 5-HT uptake inhibitor paroxetine. The substance inhibited the effect of PCA but did not influence that of H 77/77. The 5-HT-uptake inhibitors paroxetine, imipramine, and chlorimipramine were also administered p.o. at various times before PCA. The three substances inhibited PCA-induced hypermotility. Paroxetine 0.5-2 mg/kg, was active at intervals of 1-4 h and 4 mg/kg was active at 18-h interval. Imipramine and chlorimipramine 25-30 mg/kg showed PCA inhibition at treatment intervals of 1-2h, but 80-100 mg/kg or more was required to inhibit PCA at intervals of 4 and 18 h. Previous results have shown that PCA-induced hypermotility is antagonized by substances inhibiting 5-HT synthesis and uptake, whereas H 77/77-induced hypermotility is inhibited by substances blocking NA synthesis, uptake, and receptors. The previous and present results indicate that paroxetine is a selective 5-HT-uptake inhibitor. After oral administration paroxetine presumably produces a more potent and long-lasting 5-HT-uptake inhibition than imipramine and chlorimipramine.

Amphetamines↗

PubMed1994

p-Chloroamphetamine (PCA), 3,4-methylenedioxy-methamphetamine (MDMA) and d-fenfluramine pretreatment attenuates d-fenfluramine-evoked release of 5-HT in vivo.

Previous work has suggested that repeated treatment with substituted amphetamines including PCA, MDMA and d-fenfluramine produces a persistent neurodegeneration which is relatively selective for the fine serotoninergic terminals arising from the dorsal raphe nucleus. The aim of the present study was to investigate whether the acute releasing effect of d-fenfluramine might also be sensitive to lesions produced by PCA, MDMA and d-fenfluramine itself. Basal and 5-HT release evoked by d-fenfluramine or 100 mM KCl was measured by microdialysis in frontal or parietal cortex of rats 2 weeks after they had been treated with a neurodegenerative regime of PCA, MDMA, d-fenfluramine, or vehicle. In frontal cortex of vehicle controls, d-fenfluramine (10 mg/kg IP) and KCl (100 mM via microdialysis probe) evoked an increase in 5-HT of 1740% and 779% of basal, respectively. PCA pretreatment reduced d-fenfluramine-evoked 5-HT release by 90.9% while potassium-evoked release was reduced by only 66.8%. Similar results were obtained in parietal cortex. MDMA (20 mg/kg x 8) and d-fenfluramine (1.25 mg/kg x 8) pretreatment reduced d-fenfluramine-evoked release of 5-HT in frontal cortex by 45.2% and 72.0%, respectively. Overall, the present data are consistent with the hypothesis that the acute release of 5-HT evoked by d-fenfluramine occurs via those terminals destroyed by pretreatment with PCA, MDMA and d-fenfluramine, while KCl evokes release from both PCA-sensitive and PCA-insensitive terminals. The significance of these results for the interpretation of neuroendocrine data from d-fenfluramine challenge tests is discussed.

Amphetamines↗

PubMed2000

Patient-controlled intranasal analgesia: effective alternative to intravenous PCA for postoperative pain relief.

PURPOSE: To investigate whether the nasal route for fentanyl administration in patient-controlled analgesia (PCA) provides as effective postoperative analgesia as intravenous PCA. METHODS: Patient-controlled intranasal or intravenous analgesia with fentanyl was investigated in 48 patients (ASA I-III) on the day of surgery (orthopedic, abdominal or thyroid) in a prospective, randomized, double-blind, double-dummy study. Fentanyl was given in a bolus of 25 microg for intranasal and 17.5 microg for i.v. PCA, lockout interval six minutes. The first requested dose was doubled in both groups. Pain intensity (101-point numerical rating scale) and vital parameters were observed at 11 measurement points during the 240 min study. Patients were asked for side effects at every measurement point and for their satisfaction at the end of the study by the same investigator (J.M.). RESULTS: Onset of analgesia, the first reduction in pain intensity on the numerical rating scale, was 21 +/- 11 min (range 15-45 min) in intranasal and 22 +/- 16 min (range 15-90 min) in i.v. PCA. Pain intensity was reduced from 55 +/- 11 to 11 +/- 10 in the intranasal group and from 53 +/- 8 to 11 +/- 6 in the i.v. PCA group. Vital parameters remained stable and side effects were comparable in both groups. The judgement "excellent" or "good" was given by 21 of 23 patients treated intranasally and 24 of 25 patients treated intravenously. CONCLUSION: Intranasal PCA with fentanyl was an effective alternative to i.v. PCA in postoperative patients.

Administration, Intranasal↗

PubMed2001

[Postoperative pain therapy with hydromorphone and metamizole. A prospective randomized study in intravenous patient-controlled analgesia (PCA)].

Most potent opioid analgesics available in Germany have been investigated for use in postoperative patient-controlled analgesia (PCA). To conclude an older comparative series, it was the aim of the present study to define analgesic potency, side effects and patient acceptance of hydromorphone and its interaction with the non-opioid analgesic metamizole. A total of 120 patients recovering from elective abdominal or orthopaedic surgery, performed under standardised general anaesthesia, were randomised into 3 double-blind treatment groups to receive intravenous PCA demand doses of hydromorphone 283 micrograms (low dose, LD), 566 micrograms (high dose, HD) or a combination of hydromorphone 283 micrograms and metamizole 50 mg (low dose hydromorphone + metamizole, LM). Demand-independent low-dose background infusions were added to deliver hydromorphone at 67.9 micrograms/h in all groups, with additional metamizole at 12 mg/h in group LM. Lockout times were set to 2 min. After an average observation time of 24.5 +/- 2.6 h (mean, SD) since start of PCA, cumulative PCA hydromorphone doses in groups LD, HD and LM were 7.8 +/- 3.3, 12.1 +/- 4.8 and 7.5 +/- 2.0 mg, respectively, with the well known large inter-individual variability in all groups. Although hydromorphone consumption was significantly higher in group HD, self-reported pain intensities (VAS, retrospective pain scores) were quite comparable between the groups. Low dose, PCA bolus-linked metamizole did not significantly reduce hydromorphone consumption nor improve patient acceptance. Side-effects were typical for potent postoperative opioids, but never required special treatment; haemodynamic or respiratory complications were not observed in any patient. It can be concluded by comparison with other PCA opioid investigations performed under the same study protocol that hydromorphone is about 3-4 times as potent an analgesic as morphine under the conditions of intravenous postoperative PCA. Due to a favourable patient acceptance, hydromorphone can be recommended as a suitable alternative to other opioids for the treatment of postoperative pain.

Adolescent↗

PubMed1976

p-Chloroamphetamine (PCA): acute and chronic effects on habituation and sensitization of the acoustic startle response in rats.

In a series of 6 experiments the effects of p-chloroamphetamine (PCA) on the acoustic startle response in rats were investigated. 15 min after 5 mg/kg PCA startle amplitude was inhibited, 2-15 hr after PCA startle was facilitated. Rate of habituation however was not altered. Both the inhibitory and excitatory effects of PCA were blocked by pretreatment with p-chlorophenylalanine but not by alpha-methyl-p-tyrosine. 24 hr, 1 week and 4 weeks after PCA, initial startle amplitude was unchanged but PCA increased rate of sensitization over successive tone blocks. Increased sensitization was most pronounced at 10 mg/kg and absent at 2.5 mg/kg. The early inhibitory effect of PCA but not the later facilitatory effect was eliminated by reducing the level of background noise. The results suggest that inhibition of startle sensitization is associated with enhanced release of serotonin (5-HT) whereas enhancement of startle sensitization is associated with 5-HT depletion.

Acoustic Stimulation↗

PubMed1993

PCA 50941, a novel Ca2+ channel agonist.

PCA 50941 is a novel 1,4-dihydropyridine derivative. Its vasoconstricting effects prompted a systematic comparison with the prototypic Ca2+ channel activator, Bay K 8644. The two compounds exhibit marked analogies and differences in their cardiovascular profiles. PCA 50941 exhibits a pronounced vascular over cardiac selectivity while Bay K 8644 has both potent vasoconstrictor effects and strong cardiac positive inotropic actions. PCA 50941 exhibits either poor positive inotropic effects (isolated guinea-pig atria) or clear negative inotropic effects (isolated perfused rat heart). Both compounds reduced by 10-40% the coronary flow in the perfused rat heart. However, PCA 50941 had slight vasoconstrictor effects in pig coronary arteries, causing their relaxation at nanomolar/micromolar concentrations; this contrasts with the almost pure, marked vasoconstrictor effects of Bay K 8644 in coronary arteries. In the rat aorta PCA 50941 exhibited a biphasic pattern of vasoconstriction and vasorelaxation, and in portal vein it markedly reduced the Ca(2+)-evoked contractions; Bay K 8644 behaved as a pure vasoconstrictor in these two preparations. It is concluded that the racemic compound, PCA 50941, exhibits different degrees of Ca2+ agonism and Ca2+ antagonism by acting upon 1,4-dihydropyridine receptors of different cardiovascular tissues. Its tissue selectivity and its prolonged duration of action give PCA 50941 a cardiovascular profile more favourable than that of other 1,4-dihydropyridine Ca2+ agonist existing to date.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1994

Opposite effects of PCA and chlorimipramine on ICSS and on its facilitation by amphetamine.

The long-term effects of chloramphetamine (PCA) and chlorimipramine (CHLOR) on intracranial self-stimulation (ICSS) were investigated in sessions lasting 13 h. PCA, 5 mg/kg given IP, led first to an attenuation of ICSS lasting 3 h, then to a slow recovery to baseline rates, and then to a facilitation of ICSS lasting 6 h. Repeating the treatment 7 days later resulted in less attenuation of ICSS, more rapid recovery, and longer-lasting facilitation. Again, repeating the treatment with PCA 7 days later but injecting simultaneously amphetamine (AMPH) 2 mg/kg IP, altered the response seen with PCA alone. The attenuation phase was missing but the facilitatory phase remained except that it occurred early and was of shorter duration than after PCA given alone. Pretreatment with haloperidol (HALO) 0.5 or 1.0 mg/kg IP before PCA blocked the facilitatory phase of the response. CHLOR injected at a dose of 15 mg/kg IP attenuated ICSS. The combined administration of CHLOR and AMPH led to the CHLOR-attenuation of ICSS being replaced by a modest facilitation. These results are discussed in terms of the biochemical actions of PCA and CHLOR on the serotonin and dopamine systems.

Animals↗

PubMed1985

Inhibition of passive cutaneous anaphylaxis (PCA) by azelastine: dissociation of its antiallergic activities from antihistaminic and antiserotonin properties.

Azelastine and methysergide injected i.v. 5 min prior to antigen challenge and disodium cromoglycate (DSCG) injected i.v. immediately before antigen challenge produced dose-dependent inhibition of IgE-mediated 72 h passive cutaneous anaphylaxis (PCA) responses with ID50S of 0.3, 0.2 and 1.0 mg/kg, respectively. Thus, azelastine is about three times as effective as DSCG (a mast cell stabilizing agent) and somewhat less active than methysergide (a specific serotonin "D" receptor antagonist). Oral administration of azelastine and other drugs 2 h prior to antigen challenge produced strong inhibitory effects on PCA. The ID50S (mg/kg) were as follows: azelastine = 1.4; astemizole = 1.6; ketotifen = 2.0; aminophylline = 4.6; and diphenhydramine = 10.9. After 4 h of oral administration, azelastine and other drugs inhibited PCA responses with the following ID50S (mg/kg): azelastine = 1.8; astemizole = 2.3; ketotifen = 2.3; and aminophylline = 12.5. Azelastine administered orally 24 h before antigen challenge was still capable of exerting significant anti-PCA activity with an ID50 of 2.6 mg/kg, whereas none of the other drugs tested produced any significant inhibitory effects on PCA. In subsequent experiments, it was established that the antiallergic and antihistaminic activities of azelastine are inseparable 2 h after oral administration (ID50 of azelastine mg/kg, p.o., 2 h: PCA = 2.6 and histamine = 3.1). However, the persistence of the oral antiallergic (anti-PCA) effects of azelastine for 24 h (ID50 = 3.7 mg/kg) does not seem to be associated with its antihistaminic or antiserotonin activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2005

Description and critical appraisal of principal components analysis (PCA) methodology applied to pulsed-field gel electrophoresis profiles of methicillin-resistant Staphylococcus aureus isolates.

Principal components analysis (PCA) has been described for over 50 years; however, it is rarely applied to the analysis of epidemiological data. In this study PCA was critically appraised in its ability to reveal relationships between pulsed-field gel electrophoresis (PFGE) profiles of methicillin-resistant Staphylococcus aureus (MRSA) in comparison to the more commonly employed cluster analysis and representation by dendrograms. The PFGE type following SmaI chromosomal digest was determined for 44 multidrug-resistant hospital-acquired methicillin-resistant S. aureus (MR-HA-MRSA) isolates, two multidrug-resistant community-acquired MRSA (MR-CA-MRSA), 50 hospital-acquired MRSA (HA-MRSA) isolates (from the University Hospital Birmingham, NHS Trust, UK) and 34 community-acquired MRSA (CA-MRSA) isolates (from general practitioners in Birmingham, UK). Strain relatedness was determined using Dice band-matching with UPGMA clustering and PCA. The results indicated that PCA revealed relationships between MRSA strains, which were more strongly correlated with known epidemiology, most likely because, unlike cluster analysis, PCA does not have the constraint of generating a hierarchic classification. In addition, PCA provides the opportunity for further analysis to identify key polymorphic bands within complex genotypic profiles, which is not always possible with dendrograms. Here we provide a detailed description of a PCA method for the analysis of PFGE profiles to complement further the epidemiological study of infectious disease.

Cluster Analysis↗

PubMed1996

Patient-controlled analgesia (PCA) in the domiciliary care of tumour patients.

Patient-controlled analgesia (PCA) was administered in the domiciliary environment in 143 pre-terminally and terminally ill tumour patients suffering either from excruciating chronic pain or severe chronic/acute complex pain that could not be relieved adequately by oral analgesia. Morphine solutions were infused subcutaneously in concentrations between 1% and 3%. The intravenous route was preferred in patients with indwelling catheters or those susceptible to inflammatory skin reactions at the infusion site. After initial dose adjustment, lasting 2-3 days, the morphine amounts infused by PCA reached a median of 93 mg day(-1) (range 12-464 mg day(-1)). The median was 28% lower than the median dose administered orally. A total of 84% of patients utilized the option of bolus self-administration. The median percentage administered via the bolus mode amounted to 5.3% of the total requirements. During the course of treatment, morphine requirements increased by a median of 2.3 mg day(-1) (range -29 +52 mg day(-1)). Most patients were treated continuously in the home care setting until death, the median duration being 27 days (range 1-437 days). The terminal morphine demands reached a median of 188 mg day(-1) (range 15-1008 mg day(-1)). PCA turned out to be safe and effective, attaining excellent results in 95 (66%) patients and satisfactory pain relief in 43 (30%). PCA proved to be insufficient in five (4%) cases. Side-effects were mild: constipation, fatigue, nausea and local inflammatory skin reactions occurred in 9%. Thus, with support from an experienced mobile nursing team, PCA can be safely administered in the terminal domiciliary care of tumour patients. PCA is superior to oral analgesia, especially in the treatment of severe oscillating pain. PCA provides adequate pain control in about 96% of patients who are poorly responsive to oral opioids.

Analgesia, Patient-Controlled↗