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Biomedical subjects

M L Taylor

Publications and source records attributed to M L Taylor.

At least 55 records · Page 3Linked to original sources

Magnetic resonance imaging of cerebrospinal fluid volume and the influence of body habitus and abdominal pressure.

BACKGROUND: Although the cerebrospinal fluid (CSF) is the pathway of anesthetic delivery and the diluent for neuraxially administered drugs, little is known about its volume, including variability among individuals, longitudinal distribution, or influence of body habitus. Models made to investigate subarachnoid anesthetic distribution lack valid dimensions. CSF volume was measured in volunteers, and the effect of obesity and abdominal compression on CSF volume was evaluated using magnetic resonance imaging. METHODS: Low thoracic and lumbosacral axial magnetic resonance images of 25 healthy volunteers were obtained at 8-mm intervals by fast spin-echo sequence, which highlights CSF. A repeat image series was performed in 15 subjects during external abdominal compression. In two subjects, images were obtained without compression for the entire vertebral column. Dural sac and spinal cord areas were determined in a blinded fashion for each image using video/digital analysis. Area of the sac minus area of the cord constituted area of CSF and roots ("CSF/root"); this area multiplied by 8 mm resulted in CSF/root volume per section. RESULTS: There is great interindividual variability in CSF/root volume. From the T11-T12 disc to the sacral terminus of the dural sac, the mean volume for all subjects is 49.9 +/- 12.1 ml (mean +/- SD; range 28.0-81.1 ml). This volume was significantly less in relatively obese subjects (42.9 +/- 9.5 ml) than in nonobese subjects (53.5 +/- 12.9 ml). Abdominal compression decreased CSF/root volume by 3.6 +/- 3.2 ml. Sections through intervertebral foramina showed the biggest decrease with abdominal compression, with a lesser change in sections with veins and no change in the absence of these anatomic features. Total vertebral CSF/root volume in two subjects was 94.84 and 120.01 ml, respectively. CONCLUSIONS: CSF volume is widely variable between individuals. The decreased CSF volume that results from increased abdominal pressure, such as with obesity or pregnancy, may produce more extensive neuraxial blockade through diminished dilution of anesthetic. The mechanism by which increased abdominal pressure decreases CSF volume is probably inward movement of soft tissue in the intervertebral foramen, which displaces CSF.

Abdomen↗

Differential expression of platelet activation markers in aspirin-sensitive asthmatics and normal subjects.

BACKGROUND: Activation of platelets and expression of adhesion molecules (e.g. CD62P and CD63) which mediate interactions between platelets and other cells may be important in the pathogenesis of aspirin-sensitive asthma. OBJECTIVE: To determine the expression of CD62P and CD63 on platelets from aspirin-sensitive asthmatic (ASA+), aspirin-tolerant asthmatic (ASA-) and normal subjects and to assess the modulatory effect of aspirin on platelet CD62P and CD63 expression following stimulation with either platelet-activating factor (PAF), arachidonic acid (AA) or collagen (COL). METHODS: Platelet-rich plasma was obtained from 10 ASA+, 10 ASA- and 10 normal control subjects, and expression of CD62P and CD63 was measured by flow cytometry. Platelets were stimulated with PAF (10, 80 nM), AA (0.1, 1 mM) or COL (80, 800 micrograms/mL) with or without aspirin (concentration range 0.4-4 mg/mL). RESULTS: In the absence of aspirin, CD62P expression induced by AA and COL was greater in ASA+ patients compared with control subjects (P < 0.001) while CD62P expression with PAF, AA and COL was reduced in ASA- when compared with ASA+ and control subjects (P < 0.001). CD63 expression with PAF and AA was reduced in both ASA+ and ASA- patients compared with control subjects (P < 0.001). Aspirin inhibited the expression of both CD62P and CD63 after agonist stimulation. Greater inhibition of CD62P expression was observed in ASA+ compared with ASA- patients (P < 0.001) and normal subjects (P < 0.05) while greater inhibition of CD63 expression was observed in normal subjects compared with both ASA+ and ASA- patients (P < 0.05). In ASA+ patients and normal subjects, stimulation with PAF and COL resulted in only one platelet population while in contrast with 1 mM AA two populations were observed. CONCLUSIONS: Enhanced AA- and collagen-induced platelet CD62P expression in ASA+ patients compared with normal subjects and greater inhibition by aspirin of CD62P expression in ASA+ may be relevant to the pathogenesis of this syndrome. Reduced expression of CD62P and CD63 in platelets of ASA- patients following stimulation with PAF and AA may also have implications for the role of platelets and these mediators in the pathogenesis of other forms of asthma.

Adult↗

Cerebral CT venography.

PURPOSE: To produce cerebral venograms with thin-section helical computed tomography (CT) and to assess their diagnostic utility. MATERIALS AND METHODS: Thirty-six CT venograms were obtained in 33 patients after intravenous administration of iodinated contrast material. Eighteen patients had suspected dural sinus thrombosis. Twelve patients had tumor adjacent to a major venous structure. Three patients underwent CT venography during CT angiography. RESULTS: Superior sagittal, transverse, and straight sinuses were identified on every CT venogram. Other veins were seen with high frequency. Dural sinus thrombosis was diagnosed in seven patients, with magnetic resonance (MR) venographic correlation in five patients. CT venograms were easier to interpret and had fewer artifacts than MR venograms. Relationships of tumor to adjacent cerebral venous structures were well shown on CT venograms. CONCLUSION: CT venography yields detailed images of the intracranial venous circulation with consistently high quality. It is a rapid, useful method for diagnosis of dural sinus thrombosis and for preoperative mapping of venous structures in patients with neoplasm.

Adult↗

The role of a community coalition in the development of health services for the poor and uninsured.

Access to primary health care for indigent citizens presents a dilemma for many communities in the United States. In response, communities have developed a variety of strategies to effectively deal with the problem. This article describes the evolution of a small free clinic into a comprehensive primary care clinic developed through the actions of a community-based coalition. The clinic originated within an umbrella organization for indigent residents as free medical service provided at a night shelter by a local physician once a week. Through a coalition of business, religious, medical, hospital, foundation, lay volunteer, county health department, and chamber of commerce representatives, the service was enlarged into a formal clinic operation with a small staff and volunteers providing services for about 3,500 patient visits each year. As the demand for services increased beyond resources, an expanded coalition created HealthServe Medical Center, a comprehensive primary care clinic operating 40 hours per week. The HealthServe Board is currently active in supporting service delivery at the clinic, with plans to serve 24,000 medical and dental visits annually by mid-1995. The evolution process was based upon the characteristics of effective community coalitions and the commitment of individuals from diverse community sectors.

Community Health Services↗

The prevalence of sexual abuse in women with fibromyalgia.

OBJECTIVE: To determine the prevalence of sexual abuse in women diagnosed as having fibromyalgia (FM) compared with controls. METHODS: A self-administered questionnaire designed to obtain information regarding demographics, health care utilization, and history of sexual and physical abuse was completed by 40 women with FM and by 42 women who had no evidence of connective tissue disease or other major medical condition. RESULTS: Women with FM reported more physical symptoms and were significantly different on multiple indices of health compared with controls. Twenty-six FM subjects (65%) reported sexual abuse, in comparison with 22 controls (52%). The prevalence and type of abuse were not significantly different between groups. Sexually abused FM subjects reported significantly more symptoms than did non-sexually abused FM women, but did not differ in the number of symptoms for which they sought medical treatment. CONCLUSION: Sexual abuse does not appear to be a specific factor in the etiology of FM, but is correlated with the number and severity of associated symptoms.

Adolescent↗

Dimethyl sulfate uptake and methylation of DNA in rat respiratory tissues following acute inhalation.

Adult male CrlCD:BR rats were exposed nose-only to several concentrations of dimethyl sulfate (DMS) vapors to determine the relationships between vapor uptake and DNA methylation. Following DMS exposure, nasal respiratory and olfactory mucosa and lung tissue were removed and DNA was isolated for the analysis of methylated purines. DMS vapor uptake was complex and related to exposure concentration; clearance appeared to increase with increasing DMS concentrations between 0.5 and 8 ppm. Plethysmorgraphic measurements correlated with the time-dependent disappearance of dimethyl sulfate from a closed exposure apparatus. Above an initial DMS concentration of 8 ppm, sensory irritancy apparently altered normal respiratory parameters, clearance, and regional DNA methylation. DMS-dependent N7-methylguanine formation in DNA isolated from nasal respiratory mucosa was detectable 30 min following a 20-min exposure to an initial DMS concentration of 1 ppm. DMS-dependent methylation of DNA, as evidenced by N7-methylguanine and N3-methyladenine formation, showed concentration-response relationships in all tissues examined and was correlated with vapor uptake. DNA adduct formation showed regional differences characteristic of the absorption of a water-soluble vapor; methylation was greatest in DNA isolated from respiratory mucosa, less in olfactory, and little in lung. Repair of N7-methylguanine did not appear to be significantly different between nasal respiratory and olfactory tissues. These experiments demonstrate that DMS is a potent methylating agent of nasal mucosa in vivo.

Administration, Inhalation↗

Characterization of an inhibitory seric factor from tuberculosis anergic patients that acts on non-adherent PPD reactive cells.

Non-adherent cells from PPD+ tuberculosis patients (TBP PPD+) and from healthy individuals treated with whole tuberculosis anergic immune sera or with its protein A-Sepharose IgG fraction, or with sera fraction separated by PPD-Sepharose chromatography, were submitted to immunofluorescence assays. Anti-human IgG or IgM FITC-conjugate were used to reveal the assays, and results were expressed by a fluorescence percentage or fluorescence index. The presence of IgG over the surface of PPD+ non-adherent cells was detected. High fluorescence percentages were observed only in those PPD+ cells treated with whole anergic serum or with its IgG fraction. Positive fluorescence index values were obtained only in those PPD+ cells treated with anergic serum, meanwhile fluorescence index was always negative when non-bound fractions from PPD-Sepharose were used. Results suggest that non-adherent population are the cell targets for the serum inhibitory factor, which previously has been detected to inhibit antigen response in PPD reactive cells and, point out the specific behavior of this factor, since it was eliminate by PPD-Sepharose chromatography. The IgG nature of the factor was demonstrated by SDS-PAGE and immunoelectrophoresis.

Adolescent↗

Study of Fc gamma murine macrophage receptors (Fc gamma R) in the internalization of Histoplasma capsulatum yeasts.

Reports about Fc gamma R involvement in the phagocytosis of Histoplasma capsulatum yeast are contradictory. Fungal cells were incubated with anti-Histoplasma murine IgG or normal IgG as control. The opsonized yeasts were adjusted and spread on a J774.2 macrophage cell line monolayer. Yeast cells were allowed to attach to the monolayers at 4 degrees C for 1 h prior to initiating the internalization step of the phagocytic process, by shifting the cells to 37 degrees C. The participation of Fc gamma R in the internalization of yeast was monitored by radioiodination labelling of the macrophage surface proteins, and rosette-forming cells for erythrocytes coated with antibodies (RFC-EA). Results showed decreased [125I]-incorporation on the macrophage surface proteins at 15 min post-anti-Histoplasma IgG opsonized yeast infection. The same was observed when high and low virulent H. capsulatum strains were used. A decrease of RFC percentage was also observed at 15 min after IgG opsonized yeast phagocytosis. Results support the disappearance of Fc gamma R at 15 min from the surface of the macrophage that had ingested anti-Histoplasma IgG opsonized yeasts. The recovery of [125I]-counts and the RFC response at a longer time of phagocytosis suggest a possible Fc gamma R recycling mechanism.

Animals↗

Combining bioreductive drugs (SR 4233 or SN 23862) with the vasoactive agents flavone acetic acid or 5,6-dimethylxanthenone acetic acid.

PURPOSE: To determine whether 5,6-dimethylxanthenone acetic acid (DMXAA), a potent analogue of flavone acetic acid (FAA) inhibits blood flow in mouse mammary tumors, and to assess whether DMXAA enhances the antitumor effects of Tirapazamine (SR 4233) and the novel bioreductive drug SN 23862 (a dinitrobenbenzene mustard). METHODS AND MATERIALS: MDAH-MCa-4 mouse mammary tumors were grown i.m. in the leg of C3H/HeN mice. Tumor blood flow was assessed by the pertechnetate clearance method and subsequent growth delay was determined in the same tumors. RESULTS: Administration of DMXAA (65-70 mumol/kg) resulted in inhibition of tumor blood flow to approximately 25% of control values, with no recovery observed up to 36 h post-treatment. Combination of DMXAA with SR 4233 provided a significant increase in tumor growth inhibition relative to either drug alone. In this effect, DMXAA was qualitatively similar to FAA, but was approximately 10 x more potent. The interaction between DMXAA (65 mumol/kg) and SR 4233 (200 mumol/kg) was maximal with SR 4233 given between 15 min before and 60 min after DMXAA. For SN 23862, a similar enhanced growth delay was observed in combination with DMXAA, with no obvious time dependence between 15 min before and 4 h after DMXAA. When mean values for groups treated with SR 4233 (200 mumole/kg) alone and in combination with DMXAA (65-90 mumole/kg) were compared, a correlation was observed between tumor blood flow inhibition and subsequent growth delay. CONCLUSION: DMXAA is a potent inhibitor of blood flow in MDAH-MCa-4 tumors. Combination of this vasoactive drug with bioreductive agents leads to an enhanced antitumor effect. For SR 4233 and DMXAA, this enhanced effect may be predictable by measurement of tumor blood flow inhibition shortly after drug administration.

Aniline Mustard↗

Effects of medium acidification by alteration of carbon dioxide or bicarbonate concentrations on the resorptive activity of rat osteoclasts.

Little is known about the extracellular conditions or factors that stimulate mature osteoclasts to resorb mineralized tissues. Isolated mammalian osteoclasts are strongly stimulated by protons in HEPES-buffered culture media in the absence of CO2 and HCO3-, but it has been reported that cell-mediated Ca2+ release from bone organ cultures is increased only when media are acidified by reduction of HCO3- concentrations, and not by increasing PCO2 (considered models of metabolic and respiratory acidosis, respectively). We investigated this question using disaggregated rat osteoclasts cultured on dentin slices for 24 h. The number of pits resorbed per osteoclast was stimulated in media acidified by manipulation of either HCO3- or CO2 concentrations. In experiments in which incubator CO2 was varied, resorption was almost abolished in the presence of 2.5% CO2 at pH 7.61 but increased in a stepwise manner up to 1.3 pits per osteoclast when dentin slices were cultured with 10% CO2 at pH 6.97. The depths and widths of pits, measured using a confocal laser reflection microscope, also tended to increase with increasing CO2 and decreasing pH. However, in experiments where pH was lowered by reducing medium HCO3-, pit size decreased, partially offsetting the increased number of pits resorbed per osteoclast. These findings suggest that rat osteoclasts may be more sensitive to stimulation by CO2 acidosis than by HCO3- acidosis, at least in the short term, and may possibly reflect local regulatory processes in bone.

Acid Phosphatase↗

The syndrome of presumed ocular histoplasmosis in Mexico: a preliminary study.

A study to screen for the syndrome of presumed ocular histoplasmosis (SPOH) among native populations from three Mexican states was performed. Two of these states, Guerrero and Querétaro, were selected as histoplasmosis is endemic there, whereas Tlaxcala was considered a control, due to the absence of reported cases. A total of 253 individuals were submitted to ocular fundus examination to obtain evidence of SPOH. A high percentage of positive reactors to histoplasmin skin test (ST) was observed in Guerrero (83%) and Querétaro (53%), whereas in Tlaxcala positive ST were almost absent (2.04%). Only five individuals had retinal lesions, although these lesions were not characteristic of the syndrome. Stimulation of these individual's cells showed different patterns in the histoplasmin-induced lymphocyte transformation response, and two out of five individuals with retinal lesions presented a stimulated response, as well as three controls without lesions. Histocompatibility antigens (HLA) were determined in a sample of each population and no particular allele, including HLA-B7, was found to be related to SPOH as reported in the USA; however, HLA-B22 was found in three individuals who developed pulmonary histoplasmosis. Results do not provide clinical evidence or data on specific HLA risk factors, for the presence of SPOH in the population studied.

Alleles↗

Success rates in producing sympathetic blockade by paratracheal injection.

OBJECTIVE: Cervical paratracheal local anesthetic injections (stellate ganglion blocks) are performed to determine the sympathetic contribution to painful and other conditions of the head, neck, and arm. A block is useful for diagnosis only if the desired physiological effect is confirmed, but the frequency with which sympathetic function is successfully blocked is unclear. The goal of this study is to examine the rates of achieving various endpoints of sympathetic interruption by these injections, using commonly available measures of sympathetic change. DESIGN: Retrospective review. SETTING: Training center. PATIENTS: One hundred unselected consecutive blocks in 40 patients. INTERVENTION: Paratracheal sympathetic block at sixth cervical level. OUTCOME MEASURES: Bilateral hand temperature, ophthalmic changes. RESULTS: Horner's syndrome was successfully produced in 84 blocks and the ipsilateral hand warmed by > or = 1.5 degrees C in 60 blocks. However, the contralateral hand also warmed in 31 blocks so that ipsilateral warming exceeded contralateral warming in only 27 blocks, with diminished success by this criterion when the hand was warm before the block. CONCLUSIONS: We conclude that (a) identifying a Horner's syndrome and ipsilateral warming are not by themselves adequate to confirm selective sympathetic blockade; (b) selective sympathetic blockade of the arm is confirmed only if the temperature increase of the blocked side exceeds that of the contralateral side; and (c) cervical paratracheal blocks frequently fail to produce evidence of sympathetic interruption to the arm. Pathophysiological inferences based on these blocks should be made with caution and only with adequate documentation of physiological evidence of sympathetic blockade.

Anesthesia, Local↗

Cytotoxicity and DNA-protein crosslink formation in rat nasal tissues exposed to vinyl acetate are carboxylesterase-mediated.

Vinyl acetate is used in the paint, adhesive, and paper board industries. Vinyl acetate is a nasal carcinogen in rats exposed by inhalation for 2 years to 200 and 600 ppm, but not 50 ppm. Previous studies from our laboratory suggest that rat liver microsome-activated vinyl acetate induces plasmid DNA-histone crosslinks, in vitro, through esterase-mediated metabolism. Since nasal tissues contain high levels of carboxylesterase, tumorigenesis may be related to in situ production of the hydrolysis products acetaldehyde and acetic acid. Vinyl acetate was cytotoxic to both respiratory and olfactory tissues in vitro at 50-200 mM, but not 25 mM, after 2 hr exposure. Pretreatment of rats with the carboxylesterase inhibitor, bis-(p-nitrophenyl) phosphate (BNPP), attenuated the cytotoxic effects and metabolism of vinyl acetate in both tissue types. Semicarbazide, an aldehyde scavenger, was unable to protect the tissues from vinyl acetate-induced cytotoxicity. When the metabolites were tested, acetic acid, but not acetaldehyde, was cytotoxic to both tissues. The induction of DNA-protein crosslink (DPXL) formation by acetaldehyde and vinyl acetate in rat nasal epithelial tissues was detected using a sodium dodecyl sulfate/KCl precipitation technique. Endogenous crosslink levels ranged from 0.5 to 2.0% of total DNA and were considered background. Epithelial cells isolated from both olfactory and respiratory turbinates exhibited dose- and time-dependent increases in DPXL formation when exposed to 10-150 mM acetaldehyde for 1-2 hr at 37 degrees C. Similarly, respiratory and olfactory epithelial cells exposed to 5-75 mM vinyl acetate for 1-2 hr accumulated up to 12- and 15-fold higher crosslink levels than untreated cells, respectively. However, vinyl acetate appears to induce much higher levels of DPXLs at equimolar doses than acetaldehyde. This is thought to be related to stimulation of acetaldehyde-induced DPXL formation by the pH lowering effect of acetic acid production (via vinyl acetate hydrolysis). Pretreatment of the nasal turbinates with 1 mM BNPP reduced 25 mM vinyl acetate-induced DPXL formation by over 75% in both tissues. These data support a hypothesis that carboxylesterase-mediated hydrolysis of vinyl acetate is necessary to generate the active intracellular cross-linking agent, acetaldehyde, and the cytotoxic metabolite, acetic acid.

Acetaldehyde↗

Two-dimensional immunoelectrophoresis of histoplasmin and a purified polysaccharide-protein antigen of Histoplasma capsulatum.

Crude histoplasmin and a polysaccharide-protein complex (PPC-histo) antigens obtained from culture filtrates of Histoplasma capsulatum were analyzed by single and tandem two-dimensional immunoelectrophoresis (TD-IEP) using a rabbit hyperimmune anti-histoplasmin polyvalent serum. Single TD-IEP showed 14 arc precipitates for histoplasmin. Continuity of arcs 2, 6, and 7, and 9 and 10 was observed, suggesting a different polymeric configuration of the same antigen. This was also confirmed in tandem TD-IEP of histoplasmin with homologous (PPC-histo) and heterologous PPC's from Blastomyces dermatitidis, Paracoccidioides brasiliensis and Coccidioides immitis. Tandem TD-IEP of histoplasmin and PPC-histo displayed a similar antigenic pattern to histoplasmin alone, being arcs 1 and 3 more evident and apparently present only in histoplasmin and PPC-histo. Tandem TD-IEP showed common antigens among the other heterologous fungal purified antigens, and seems useful to observe the multiplicity of antigens present in fungal preparations and to identify those precipitates (arcs 1 and 3) that are predominant in the purified preparation.

Animals↗

Acetyl-CoA:lyso-platelet-activating factor acetyltransferase activity in neutrophils from asthmatic patients and normal subjects.

1. Platelet-activating factor is a putative mediator of inflammation in asthma and the enzyme acetyl-CoA:lyso-platelet-activating factor acetyltransferase appears to be important in regulating platelet-activating factor production by leucocytes. To determine whether there are differences in acetyltransferase activity between asthmatic patients and normal subjects, enzyme activity was assayed in neutrophil lysates from atopic asthmatic patients (n = 20), aspirin-sensitive asthmatic patients (n = 12) and healthy, non-atopic, non-asthmatic control subjects (n = 20), both basally and after stimulation with the calcium ionophore A23187. 2. For a range of acetyl-CoA concentrations, acetyltransferase activity (nmol of [acetyl-3H]PAF min-1 mg-1 of protein) in unstimulated neutrophils from atopic asthmatic patients was significantly higher than that for normal subjects (P = 0.038) and the mean Vmax. for atopic asthmatic patients [18.4 (SD 6.9) nmol min-1 mg-1 of protein] was significantly greater than that for the control subjects [14.9 (SD 4.6) nmol min-1 mg-1 of protein P < 0.05]. The mean Vmax. for aspirin-sensitive asthmatic patients [15.9 (SD 6.9) nmol min-1 mg-1 of protein] was not significantly different from that for the normal subjects. 3. The mean ratio Vmax. stimulated/Vmax. unstimulated for acetyltransferase from atopic asthmatic patients (1.71, SD 0.45) was significantly less than that for the normal subjects (2.13, SD 0.63, P < 0.05), suggesting that acetyltransferase from atopic asthmatic patients was less sensitive to stimulation with A23187 in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases↗

The effect of aspirin on mononuclear cells in aspirin-sensitive asthmatics and control subjects.

Three groups, comprising normal subjects (n = 10), aspirin-sensitive asthmatics (ASA+; n = 10) and aspirin-insensitive asthmatics (ASA-; n = 10) were entered into a blinded, parallel group study to asses the modulating effect of aspirin (ASA; 0.0275, 0.275, 1.385, 2.75, 6.9, 13.8 and 27.5 microM) on lymphocyte proliferation in vitro, either alone or in combination with the mitogen, phytohemagglutinin (PHA; 10, 25, 50, 100, 200 and 500 micrograms/ml). The percentage and absolute numbers of CD4-positive T cells (normals: 51.3%; ASA+: 51.1%; ASA-: 46.1%; p = 0.4038) and CD8-positive T cells (normal: 27.5%; ASA+: 26.4%; ASA-: 28.4%; p = 0.8408) did not differ significantly between the groups. Significant differences in mean PHA responses between ASA+, ASA- and normal subjects were observed when peripheral blood lymphocytes (PBL) were exposed to PHA concentrations over the range 10-50 micrograms/ml; PHA 10 micrograms/ml (p < 0.005), PHA 25 micrograms/ml (p < 0.005) and PHA 50 micrograms/ml (p < 0.01), the lowest and highest proliferative responses being obtained with PBL from ASA+ and ASA-, respectively. However, at higher PHA concentrations (100-500 micrograms/ml), differences between the three groups were not observed. When ASA was added in combination with PHA, augmentation of the PHA response was observed with cells from all three groups but was most marked in the ASA+ group, especially at lower PHA concentrations (10-50 micrograms/ml) in combination with 0.275-13.8 microM ASA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗

The differential effect of aspirin on human platelet activation in aspirin-sensitive asthmatics and normal subjects.

1. The in vitro effect of aspirin on platelet aggregation and ATP release induced by platelet activating factor (PAF), arachidonic acid (AA) and collagen (COL) was assessed in 10 aspirin-sensitive (ASP+) asthmatic patients and 10 normal subjects. 2. For PAF, but not AA or COL, both the baseline EC50 and minimum concentration required to produce a maximum response for aggregation were significantly increased in ASP+ asthmatics compared with normal subjects (P < 0.05). Maximum ATP released was greater in ASP+ patients for all agonists but the difference was most significant for PAF (P < 0.025). 3. In ASP+ asthmatics COL induced, but not AA induced, aggregation was less sensitive to inhibition by aspirin compared with normals (P < 0.01). Similarly, analysis of the area under the percent inhibition concentration-response curve showed aspirin to be less effective in inhibiting platelet aggregation induced by PAF in ASP+ asthmatics than in normal subjects (normal subjects: 155 +/- 11 mg% ml-1, ASP+ asthmatics: 115 +/- 19 mg% ml-1; P < 0.05). 4. Regression analysis showed a poor correlation (r = 0.25, P < 0.4933) between the degree of aspirin induced inhibition of ATP release and platelet aggregation induced by PAF in ASP+ asthmatics. 5. The significant differences observed in platelet responses to PAF, COL and to aspirin in ASP+ asthma patients further suggests an abnormality in platelet function exists in this syndrome.

Adenosine Triphosphate↗