The potential use of chilling to control the growth of Enterobacteriaceae on porcine carcasses and the incidence of E. coli O157:H7 in pigs.

AIMS: To (i) monitor the presence of Enterobacteriaceae as indicators of faecal contamination on pig carcasses, (ii) examine the potential use of chilling as a critical control point (CCP) and establish its influence on pig carcass categorization by Decision 471/EC and (iii) determine the incidence of E. coli O157:H7 in pigs. METHODS AND RESULTS: Porcine faecal samples and carcass swabs were collected before and after chilling at four Irish pig abattoirs and examined for Enterobacteriaceae and E. coli O157:H7. Chilling generally reduced Enterobacteriaceae counts on carcasses, but increases were also observed, particularly in one abattoir. E. coli O157:H7 was absent from carcasses before chilling, present on 0.21% after chilling and was recovered from 0.63% of faecal samples. All of the isolates were found to contain virulence genes associated with clinical illness in humans. CONCLUSIONS: The data show that overall chilling had the capacity to reduce the numbers of carcasses positive for the presence of Enterobacteriaceae. SIGNIFICANCE AND IMPACT OF STUDY: The influence of chilling on the categorization of pig carcasses suggests that it has the potential to improve the numbers of acceptable carcasses and the process could be used as a CCP within a HACCP plan.

A prospective comparison of pedal ergometry with conventional treadmill testing in the investigation of lower extremity pain.

BACKGROUND: Investigation of lower extremity pain is compromised by comorbid disorders that may interfere with conventional testing. AIMS: To compare pedal ergometry with conventional treadmill testing. METHODS: A prospective study was performed where patients presenting with a diagnosis of intermittent claudication were assessed by both methods of testing. RESULTS: Of 78 patients studied with both tests, no exercise-induced ankle pressure changes occurred in 26, two were unable to complete either test despite normal pressure measurements, while 24 had exercise-induced pressure drop detected by both tests. Of patients who completed pedal ergometry, 21 were unable to complete the treadmill test, 14 of whom had negative ergometry, while seven had a pressure drop detected by pedal ergometry. Three had pressure changes with pedal ergometry, but not with treadmill testing and two had pressure changes on the treadmill not reproduced by pedal ergometry. CONCLUSIONS: Pedal ergometer is more sensitive than treadmill testing in detecting arterial insufficiency, as indicated by a 20% or greater fall in ankle pressure, and more suitable in a subgroup of patients unable to tolerate conventional treadmill testing.

Steatosis in donor and transplant liver biopsies.

The purpose of this study was to identify the significance and clinical correlation of steatosis in donor and posttransplantation liver biopsies. One hundred twenty-six liver biopsies with fatty change from 86 liver transplant patients were reviewed. Micro- and macro-steatosis were graded semiquantitatively and correlated with clinical and other pathologic parameters. Fifty-one donor biopsy specimens, from 50 patients, had combinations of micro- (predominantly) and macro-steatosis. One of 2 patients with high-grade micro- and macro-steatosis required a retransplantation on the third day. Three early deaths were not related to graft dysfunction. In 36 patients, steatosis developed after transplantation. In 13 of 36, steatosis was seen in the early postoperative period with a background of severe ischemic injury, 6 of whom died within 45 days posttransplantation. Other causes of steatosis developing after liver transplantation included hepatitis C (n = 12), alcoholic steatohepatitis (n = 3), diabetes mellitus or obesity (n = 7) and poor nutrition (n = 2). The presence of steatosis in 1 patient's donor and all posttransplantation biopsy specimens remained unexplained. In conclusion, (1) microsteatosis in donor liver biopsy specimens has no effect on graft function; (2) ischemic injury with development of steatosis in the early posttransplantation period may be associated with poor clinical outcome; and (3) steatosis in the posttransplantation period is uncommon and usually related to recurrent or acquired hepatitis C.

Ultrastructural localization of gustducin immunoreactivity in microvilli of type II taste cells in the rat.

Gustducin is a transducin-like G protein (guanine nucleotide-binding protein) that is expressed in taste bud cells. Gustducin is believed to be involved in bitter and possibly sweet taste transduction. In the present study, we demonstrate that a subset of type II cells displays immunoreactivity to antisera directed against gustducin in taste buds of rat circumvallate papilla. Immunogold particles are present both in the microvilli and cytoplasm of the immunoreactive cells. Quantitative analysis of the data suggests that the number of colloidal gold particles (P<0.001) and nanogold particles (P<0.01) in the immunoreactive type II cells are much greater than in type I cells. There are also approximately 2.5 times (P<0.05) as many colloidal gold particles associated with the microvilli versus the cytoplasm in the immunoreactive type II cells. The ultrastructural distribution of gustducin immunoreactivity is consistent with its proposed role in the initial events of sensory transduction by gustatory receptor cells.

Taste cells with synapses in rat circumvallate papillae display SNAP-25-like immunoreactivity.

SNAP-25 is a 25 kDa protein believed to be involved in the processes of membrane fusion and exocytosis associated with neurotransmitter release. In the present study we present evidence that SNAP-25-like immunoreactivity can be used as a marker for taste cells with synapses in rat circumvallate papillae. SNAP-25 immunoreactivity is present in most intragemmal nerve processes and a small subset of taste cells. Intense immunoreactivity is associated with the nerve plexus located below the base of the taste bud. Of a total of 87 taste cells with synapses onto nerve processes, 80 of the presynaptic taste cells had SNAP-25 immunoreactivity. The association of SNAP-25 immunoreactivity with taste cells possessing synapses suggests that these cells may be gustatory receptor cells. Because this SNAP-25 antibody can label taste cells with synapses, it may also serve as a useful tool for future studies correlating structure with function in the taste bud.

Cues for perception of synthetic and natural diphthongs in either noise or reverberation.

The relationship between relative intensity of transition segments and identification of diphthongs has been investigated. In the first experiment, synthesized stimuli were used. The stimuli differed in the amount of attenuation of the transition segment which ranged from 0 to 15 dB. It was expected that [diphthong in text] responses would be obtained for stimuli with attenuated transitions. The stimuli were tested in quiet, noise, and reverberation with ten normal-hearing and seven hearing-impaired subjects. For the stimulus with the most attenuated transition, the normal-hearing subjects gave no [diphthong in text] responses and the hearing-impaired subjects gave only 20% [diphthong in text] responses in quiet. However, in noise, both groups of subjects gave 70% [diphthong in text] responses and in reverberation, the normal-hearing subjects gave 95% and the hearing-impaired subjects gave 90% [diphthong in text] responses. Generally, less transition attenuation was needed for the hearing-impaired than for the normal-hearing subjects to give [diphthong in text] responses. These findings indicated that identification errors in noise and reverberation for naturally produced diphthongs might be related to the intensity of their transition segments. In the second experiment, naturally produced diphthongs [diphthongs in text] from the Nábelek et al. [J. Acoust. Soc. Am. 92, 1228-1246 (1992)] study were spectrally analyzed. There were 30 different tokens for each diphthong. The results of the analyses indicated significant correlations between the number of identification errors for these diphthongs made by either normal-hearing or hearing-impaired subjects and the relative intensities of the F2 transition segment. In both noise and reverberation there were fewer errors for the diphthong tokens characterized by high intensity F2 transitions.

Estimation of client-assessed hearing aid performance based upon unaided variables.

The purpose of this study was to investigate the possibility of estimating client-assessed hearing aid performance before hearing aids are purchased. Aided performance was represented by the Profile of Hearing Aid Performance (PHAP, Cox & Gilmore, 1990). Multiple regression was applied to 16 unaided predictor variables and to 8 response variables. The response variables were the scores from the seven PHAP subscales plus the overall PHAP score, which were obtained from 46 participants. Audiologic, demographic, and psychological information was included among the 16 predictor variables. The average widths of 95% prediction intervals showed that, with the exception of the Aversiveness of Sounds and Ease of Communication subscales, PHAP subscale scores were predicted within 15% on average. Eighty percent or more of the individual participants' PHAP scores were predicted within 15% for all but the Aversiveness of Sounds subscale. The predictor variables appearing in regression equations for the greatest number of PHAP subscales include age, Communication Strategies and Personal Adjustment scores from the Communication Profile for the Hearing Impaired (Demorest & Erdman, 1986), Revised Speech Perception in Noise (Bilger, Neutzel, Rabinowitz, & Rzeczkowski, 1984; Kalikow, Stevens, & Elliott, 1977) test scores, comfortable loudness levels, and the difference between National Acoustic Laboratories' target gain (Byrne & Dillon, 1986) and actual insertion gain. Further testing of the models on additional participants would be needed to determine their clinical applicability. In addition to being potentially useful for predicting client-assessed aided performance, the equations obtained in this study identify relationships between the aided and unaided variables that can be applied in the counseling of new hearing aid users.

Problems in the recognition of aortoembolic stroke.

Recent reports suggest aortoembolism is an important cause of stroke. Although transesophageal echocardiography visualizes the aortic arch, diagnosis of aortoembolism stroke is not common. We investigated reasons for this discrepancy at our institution. We reviewed charts and transesophageal echocardiography videotapes of 16 patients with recent ischemic stroke or transient ischemic attack who had undergone transesophageal echocardiography. For each patient, we determined the most likely cause of cerebral ischemia, and we compared the official transesophageal echocardiography report to our interpretation of the videotape. In our videotape review, 13 patients had good visualization of the aortic arch. Of 6 patients with atherosclerosis in the arch, 1 had high-grade carotid stenosis, 1 had atrial fibrillation, 1 had "small-vessel disease," and 3 had cerebral ischemia of unknown cause. The official reports did not mention aortic arch disease in 4 of 6 patients. A possible cause of cerebral ischemia was identified in 6 of 7 patients with normal aortic arches. Of 3 patients who had poor visualization of the aortic arch, one had "small-vessel disease," and 2 had ischemic stroke of unknown cause despite extensive workups. We conclude that aortic arch disease is common in patients with ischemic stroke and transient ischemic attack and may be a cause of cerebral ischemia, especially in patients with stroke or transient ischemic attack due to small-vessel occlusion or of unknown cause. Aortic arch disease may not be identified as the cause of stroke or transient ischemic attack because (a) transesophageal echocardiography is not done, (b) transesophageal echocardiography is done but the aortic arch is not visualized, (c) transesophageal echocardiography is done, the aortic arch is visualized, but the examiner does not comment on aortic arch disease, or (d) despite transesophageal echocardiography identification of arotic arch disease, the treating physician does not consider the aorta to be a potential source of embolization.

Cues for perception of the diphthong /aI/ in either noise or reverberation. Part I. Duration of the transition.

Location of boundaries (the 50% response point) and slopes of identification functions were determined for synthesized /a-aI/ vowel continua. Within each continuum, the stimuli contained a steady-state segment followed by a transition in which the frequencies of formants changed in time. Here, F1 changed in a downward direction and F2 changed in an upward direction. Total duration of each stimulus was 200 ms. The duration of the transition was increased in steps from 0 to 140 ms. Two patterns of formant transition were used: (1) formants changing in the direction of, but not reaching, target frequencies (except in the end-point stimulus), and (2) formants reaching F1 and F2 targets. The data were collected with ten normal-hearing and ten hearing-impaired subjects. The boundaries and slopes were determined for four listening conditions: quiet, noise, short reverberation (0.8 s), and long reverberation (1.1 s). The location of boundaries depended upon: (1) pattern of formant transitions, (2) listening condition, and (3) status of subjects' hearing. Generally, longer transitions were needed for formants changing in the direction of, but not reaching, target frequencies, than for those reaching F1 and F2 targets. The required transition durations were similar in quiet and noise, but were longer in reverberation. The hearing-impaired subjects generally required longer transitions to reach the boundaries than normal-hearing subjects. The slopes of the identification functions were shallower in either noise or reverberation than in quiet and were shallower for hearing-impaired than for normal-hearing subjects. In reverberation, the slopes for formants reaching targets were shallower than the slopes for stimuli with formants changing in the direction of target frequencies. The relationships between these findings and identification errors for naturally produced tokens of the diphthong /aI/ are discussed.

Vowel boundaries for steady-state and linear formant trajectories.

Locations of boundaries and slopes of identification functions were tested for /I-epsilon/ vowel continua with steady-state and linearly changing formant trajectories. In experiment 1, the boundaries and slopes for arbitrarily selected trajectory directions were determined for ten normal-hearing and ten hearing-impaired subjects in three listening conditions: Quiet, noise, and reverberation. The boundaries did not depend upon the group of subjects or the listening condition. A boundary shift was found for stimuli with F1 changing in a downward direction relative to boundaries for stimuli with either only F1 or with both F1 and F2 changing in an upward direction. The slope of the identification function for stimuli with F1 changing in a downward direction was shallower than the slopes for stimuli with steady-state formants or stimuli with F1 changing in an upward direction. The slopes obtained from the hearing-impaired subjects were shallower than those of the normal-hearing subjects and were shallower in noise than in either quiet or reverberation. In experiment 2, boundaries and slopes for the trajectory directions found in the natural vowels /I/ and /epsilon/, F1 changing in an upward direction and F2 in a downward direction, were determined for nine normal-hearing subjects in two listening conditions, quiet and reverberation. The boundary for stimuli with both F1 and F2 changing in directions characteristic for natural vowels was shifted relative to the boundary for stimuli with steady-state formants. The directions of the boundary shifts in experiments 1 and 2 indicated a perceptual emphasis on the initial sections of changing F1 and F2. Sound quality of the end-point /I/ and /epsilon/ stimuli depended upon F1 and F2 trajectories. For both vowels, the best quality judgments were found for the stimuli with natural F1 and F2 trajectory directions. The quality judgments were weakly correlated with the slopes of identification functions, with better quality judgments being associated with steeper slopes.

Internalization of surfactant protein A (SP-A) into lamellar bodies of rat alveolar type II cells in vitro.

Pulmonary surfactant is thought to be internalized and processed for reuse by alveolar Type II cells. In the present study we followed the internalization and intracellular trafficking of purified surfactant protein A (SP-A) by primary cultures of alveolar Type II cells. Internalization of native rat SP-A was compared with that of recombinant rat and human SP-A isolated from a patient with alveolar proteinosis. All SP-A species were conjugated with colloidal gold for visualization by electron microscopy. The gold conjugates were biologically active, as demonstrated by inhibition of phospholipid secretion from alveolar Type II cells. The SP-A-gold conjugates were internalized to lamellar bodies (LB) via the endosomal system, which included both electron-lucent and -dense multivesicular bodies. Labeling of LB was time dependent, and after 7 hr 30-40% of these organelles were labeled. Alkylation of SP-A greatly reduced internalization, as did an excess of non-conjugated SP-A. No qualitative differences in uptake were observed with the three forms of SP-A. The percent of labeled LB was similar (30-40%) after 7 hr of internalization with the three species of SP-A. The recombinant SP-A produced using a baculovirus vector lacked hydroxyproline and had an altered oligosaccharide, but these features did not affect its internalization or the rate of LB labeling. Internalization of the gold-conjugated SP-A and endocytosis of the fluid-phase marker Lucifer Yellow were related to the shape of Type II cells. Both uptake of SP-A, which is receptor mediated, and fluid-phase endocytosis were found to be less active in the flattened than in the rounded cells. Therefore, cell shape and hence cytoskeletal organization may play an important role in SP-A recycling. However, it is possible that both morphology and decreased endocytosis are independent manifestations related to the loss of differentiated function of cultured Type II cells.

Pharmacologic actions of Ro 24-5913, a novel antagonist of leukotriene D4.

Ro 24-5913, (E)-4-[3-[2-(4-cyclobutyl-2- thiazolyl)ethenyl]phenylamino]-2,2-diethyl-4-oxobutanoic acid, has been identified as a chemically unique, potent and selective LTD4 antagonist. In vitro, Ro 24-5913 competes with [3H]LTD4 for its binding site on guinea pig lung membranes with an IC50 of 6.4 +/- 2.2 nM. In isolated guinea pig tracheal smooth muscle, Ro 24-5913 produces concentration-dependent rightward shifts of LTD4-induced contraction curves (pA2 value of 9.6 +/- 0.2). The slope of the Schild plot is not significantly different from 1, indicating that the antagonism is of a competitive nature. In the human bronchus, Ro 24-5913 is an effective antagonist of LTD4-induced contractions (pKB of 9.3 +/- 0.1). In vivo, Ro 24-5913 dose-dependently inhibits LTD4-induced bronchoconstriction in guinea pigs by the i.v. (ID50 0.13 mg/kg), oral (ID50 0.12 mg/kg) and aerosol (IC50 0.008%) routes of administration. This in vivo activity is specific as evidenced by the inability of Ro 24-5913 to inhibit bronchoconstriction induced by LTB4, PAF or histamine. In comparison with other LTD4 antagonists evaluated in this guinea pig model, Ro 24-5913 is markedly superior in terms of oral potency, bioavailability and oral duration of action. Ro 24-5913 also blocks allergic bronchospasm mediated by endogenously generated leukotrienes in guinea pigs; the potency and duration of action is nearly equivalent to that seen as an antagonist of bronchoconstrictions produced by exogenous LTD4. In summary, Ro 24-5913 is representative of a novel chemical class of LTD4 receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacology of a potent platelet-activating factor antagonist: Ro 24-4736.

Ro 24-4736, (5-(3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepin-2-yl]-2-propynyl)phenanthri din- 6(5H)-one), has been identified as a potent, selective, p.o.-active platelet-activating factor (PAF) antagonist with a long duration of action. In vitro, Ro 24-4736 competes with [3H]PAF for its receptor site on dog platelets with an IC50 of 9.8 +/- 1.0 nM and selectively inhibits PAF-induced aggregation of guinea pig, dog and human platelets with concentration dependence. Ro 24-4736 dose-dependently inhibits in vivo bronchoconstriction (ID50 of 0.006-mg/kg p.o.) and ex vivo platelet aggregation (ID50 of 0.004 mg/kg p.o.) induced by PAF in guinea pigs. Time course studies show complete blockade of PAF-induced platelet aggregation (ex vivo) up to 8 hr after a single p.o. dose of 0.03 mg/kg as well as a long duration of action in vivo (30 hr). The in vivo PAF antagonistic activity is specific because, even at high p.o. doses (up to 10 mg/kg), Ro 24-4736 shows no inhibitory activity toward the bronchoconstrictor effects of leukotriene D4 or histamine. In comparison with other PAF antagonists evaluated in this guinea pig model, Ro 24-4736 is markedly superior in terms of p.o. potency, bioavailability and p.o. duration of action. Studies were also performed with Ro 24-4736 in additional in vivo models. When administered p.o. to sensitized guinea pigs, the drug attenuates inhaled antigen-induced airway hyper-reactivity without effect on bronchoalveolar lavage leukocyte accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Thienotriazolodiazepines as platelet-activating factor antagonists. Steric limitations for the substituent in position 2.

The preparations of thienotriazolodiazepines bearing a substituted ethynyl group at the 2-position, and the corresponding cis-olefins and fully saturated analogues are described. The compounds were evaluated as potential antagonists of platelet-activating factor (PAF) in in vitro and in vitro test models. The new thienotriazolodiazepines are compared with known related compounds such as WEB 2086 (compound 6) and the phenylethyl derivatives 27 and 28.

Triazolobenzo- and triazolothienodiazepines as potent antagonists of platelet activating factor.

A series of [1,2,4]triazolo[4,3-alpha][1,4]benzodiazepines bearing an ethynyl functionality at the 8-position and the isosteric thieno[3,2-f][1,2,4]triazolo[4,3-alpha][1,4]diazepines were prepared and evaluated as antagonists of platelet activating factor. The effects of substitution were explored in in vitro and in vivo test systems designed to measured PAF-antagonistic activity. Results are discussed and compared with previously published data. Many of the compounds had activity superior to WEB 2086, compound 1. In general, the thieno analogues exhibited better oral activity than the corresponding benzodiazepines. The duration of activity upon oral administration was modulated by the substitution on the acetylenic side chain. Compounds 71 and 81 were selected for further pharmacological evaluation as a result of their good oral potency and exceptionally long duration of action.

Propenyl carboxamide derivatives as antagonists of platelet activating factor.

A series of N-[4-(3-pyridinyl)butyl] 3-substituted propenyl carboxamide derivatives bearing an unsaturated bicyclic moiety in the 3-position was prepared and evaluated for PAF (platelet activating factor) antagonist activity. These compounds represent conformationally constrained direct analogues of the corresponding potent 5-aryl-pentadienecarboxamides (5). Most of the new compounds were active in a PAF-binding assay employing whole, washed dog platelets as the receptor source and inhibited PAF-induced bronchoconstriction in guinea pigs after intravenous administration. However, oral activity in the PAF-induced bronchoconstriction model was highly sensitive to the nature and substitution of the bicyclic ring system. The most interesting compounds included [R-(E)]-(1-butyl-6-methoxy-2-naphthyl)-N-[1-methyl-4-(3- pyridinyl)butyl]-2-propenamide (4b), [R-(E)]-(3-butyl-6-methoxy-2- benzo[b]thiophene-yl)-N-[1-methyl-4-(3-pyridinyl)butyl]-2-propenamide (4k), and [R-(E)]-(3-butyl-6-methoxy-1-methyl-2-indoly)-N-[1-ethyl-4- (3-pyridinyl)butyl]-2-propenamide (4l) which inhibited PAF-induced broncho-constriction in guinea pigs with IC50s of 3.0-5.4 mg/kg, when the animals were challenged 2 h after drug treatment. They were also highly effective 6 h after a 50 mg/kg oral dose. This study supports the notion that the key remote aromatic ring present in the 5-arylpentadienecarboxamides (5) is preferentially coplanar with the diene system for good PAF antagonist activity.

Elimination or reduction of wrinkles in semithin epoxy sections by vacuum drying.

Vacuum drying, under appropriate conditions, diminishes the warping and buckling of epoxy semithin sections and enhances visualization with light microscopy. Treatment of sections with chloroform or variations in the drying times or temperatures did not reduce wrinkling.

Biphenylcarboxamide derivatives as antagonists of platelet-activating factor.

A series of N-[4-(3-pyridinyl)butyl]-1,1'-biphenyl-4-carboxamides was prepared, and the compounds were evaluated for platelet-activating factor (PAF) antagonist activity in a binding assay employing washed, whole dog platelets and in vivo for their ability to inhibit PAF-induced bronchoconstriction in the guinea pig. The inclusion of a methyl group in the R configuration on the side-chain carbon adjacent to the carboxamide nitrogen atom of these derivatives resulted in a marked enhancement of potency in the binding assay for compounds unsubstituted in the biphenyl 2-position and, more importantly, in improved oral bioavailability. Previous work with related pyrido[2,1-b]-quinazoline-8-carboxamides suggests that the presence of such an alkyl group improves bioavailability by rendering the resulting compounds resistant to degradation by liver amidases. The most interesting compounds to emerge from this work are (R)-2-bromo-3',4'-dimethoxy-N-[1-methyl-4-(3-pyridinyl)butyl]-1,1'-bi phe nyl- 4-carboxamide (33) and (R)-2-butyl-3',4'-dimethoxy-N-[1-methyl-4-(3-pyridinyl)butyl]- 1,1'-biphenyl-4-carboxamide (40) each of which inhibits PAF-induced bronchoconstriction in the guinea pig by greater than 55%. 6 h after an oral dose of 50 mg/kg.

Pentadienyl carboxamide derivatives as antagonists of platelet-activating factor.

A series of N-[4-(3-pyridinyl)butyl]-5,5-disubstituted-pentadienamides was prepared and evaluated for PAF-antagonist activity. Compounds were assayed in vitro in a PAF-binding assay employing washed, whole dog platelets as the receptor source and in vivo after intravenous or oral administration for their ability to prevent PAF-induced bronchoconstriction in guinea pigs. Criteria required for good oral activity in the latter model include an (E,-E)-5-phenyl-2,4-pentadienamide, a second phenyl or a four- or five-carbon alkyl moiety in the 5-position of the diene, and an (R)-[1-alkyl-4-(3-pyridinyl)butyl] substituent on the carboxamide nitrogen atom. The alkyl substituent on this side chain can be methyl, ethyl, or cyclopropyl. Two members of this series, [R-(E)]-5,5-bis(4-methoxy-phenyl)-N- [1-methyl-4-(3-pyridinyl)butyl]- 2,4-pentadienamide (31) and [R-(E,E)]-5-(4-methoxyphenyl)-N-[1-methyl-4- (3-pyridinyl)butyl]-2,4-decadienamide (58), were selected for further pharmacological evaluation. Both were found to be substantially longer acting after oral administration than the corresponding S enantiomers in the guinea pig bronchoconstriction assay. A second in vivo model used to evaluate PAF antagonists determines the ability of test compounds to decrease the area of skin wheals induced by an intradermal injection of PAF. In this model, using both rats and guinea pigs, compounds 31 and 58 were found to be as active as the reference PAF antagonist 3-[4-(2-chlorophenyl)-9-methyl-6H- 1-(4-morpholinyl)-1-propanone (45).