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The siliciclastic sediments of the Klipheuwel Group mark the transition from Pan-African tectonism and amalgamation of Southwest Gondwana to the shallow marine deposits of the Cape Supergroup in the Western Cape. The rocks are preserved in a number of seemingly isolated depositories and previous studies have mainly focused on selected occurrences. The lack of any integration of regional sedimentological or structural characteristics has, to date, resulted in only tentative stratigraphic correlations and subdivisions of the Klipheuwel Group. Lithological and structural data from the Klipheuwel Group indicate at least two separate depocentres that accommodated the post Pan-African peneplanation of the Saldania Belt and clastic detritus in distinctly different palaeoenvironments. A northern depocentre can be distinguished from a southern depocentre, each characterised by distinct architectural elements and facies associations that reflect topographic and structural controls. The northern depocentre, including Klipheuwel Group occurrences at Eendekuil, Redelinghuys and Elands Bay, show laterally persistent braided fluvial facies associations that developed multi-storey superimposed 'braided sheet' deposits. Here, the rocks show gentle dips and thicknesses range from 300 to 450 m. The southern depocentre, including the Klipheuwel and Klapmutskop localities, are characterised by much larger thicknesses (up to >2 000 m), steep dips of the rocks and laterally discontinuous braided fluvial facies associations that developed staggered channelised braided deposits. The lateral continuity of fluvial facies in the northern depocentre reflect sedimentation on a peneplained basement. The larger thickness, steep dips and strongly channelised deposits in the southern facies, in contrast, indicate deposition in actively subsiding half-graben structures that reactivated basement faults. The spatially closely associated Franschhoek Formation shares numerous characteristics with the Klipheuwel Group but preserves Pan-African strains similar to that of the underlying Malmesbury Group, that may indicate its formation as compressional piggyback basins with synorogenic sedimentation. [ABSTRACT FROM AUTHOR]

The Tra-Tra Formation is a predominantly argillaceous, shallow marine to paralic sedimentary succession of Eifelian (Middle Devonian) age within the Bokkeveld Group (Cape Supergroup) that crops out extensively within the Cape Fold Belt of South Africa. It comprises three discrete lithofacies associations (termed E-G) which are interpreted as deposits of channelised tidal flat-lagoons, transgressive beach-barriers and wave-influenced prodeltas to distal deltafronts. They accumulated within a series of incised coastal-plain valley-fill system along the palaeoshoreline of the Cape Basin following a protracted forced regressive phase during sedimentation of the underlying Hex River Formation. A discrete, geographically-extensive, 25 to 30 m thick, single or double, positive-weathering tabular sandstone within the Tra-Tra Formation is recognised herein as the Grootrivier Member. Palaeontologically, the Tra-Tra Formation comprises a restricted fauna of Malvinokaffric Realm invertebrates, fish and plant fossils that are of biostratigraphic importance in inferring its Eifelian age. [ABSTRACT FROM AUTHOR]

A drone was used to study the richness and behaviour of scavengers attracted to the carcass of a sperm whale (Physeter microcephalus) in Seychelles, Western Indian Ocean. Over 30 sharks of 3 species (tiger shark Galeocerdo cuvier , bull shark Carcharhinus leucas and tawny nurse shark Nebrius ferrugineus) were recorded scavenging on the carcass. Tiger sharks dominated the scavenging, but with no evidence of agonistic behaviours or hierarchy, and may have facilitated scavenging by other species. Drone use allowed the analysis of such behaviours without observer influence, providing new insights into communal scavenging events. For the first time, multiple tiger, bull and nurse sharks were all recorded feeding on the same sperm whale carcass. Moreover, the event was observed using a drone, meaning that the sharks were undisturbed by humans and exhibited natural behaviour. Contrary to expectation, there was no aggression between any of the sharks. Instead, they all fed calmly alongside each other during this communal scavenging event. [ABSTRACT FROM AUTHOR]

The Lower Carboniferous, probably Tournaisian, Floriskraal Formation is part of the Witteberg Group (Cape Supergroup) of South Africa. Together with the underlying Kweekvlei and overlying Waaipoort Formations, it forms part of the Lake Mentz Subgroup. The Floriskraal Formation essentially comprises mud-, silt- and sandstones arranged as two-to-four laterally continuous upward coarsening successions suggested to have been deposited in a storm-wave dominated shallow-marine setting. It contains a low diversity trace fossil assemblage, reworked vascular plant debris, and possibly acanthodian fish fossils. There are no know stratigraphic equivalents in South Africa. [ABSTRACT FROM AUTHOR]

A large, pregnant, female bull shark Carcharhinus leucas was tracked migrating from Seychelles across open ocean to south-east Madagascar, c. 2000 km away, and back again. In Madagascar, the shark spent a prolonged period shallower than 5 m, consistent with entering estuarine habitat to pup, and upon return to Seychelles the shark was slender and no longer gravid. This represents an unprecedented return migration across the open ocean for a C. leucas and highlights the need for international collaboration to manage the regional C. leucas population sustainably. [ABSTRACT FROM AUTHOR]

There is a lack of studies on how provisioning may influence shark numbers and behaviour. The effects of long-term provisioning were investigated at a Red Sea reef, where both grey reef shark (Carcharhinus amblyrhynchos) and silky shark (Carcharhinus falciformis) occurred. Initially, grey reef sharks outnumbered silky sharks, but over 6 years, silky shark numbers increased almost 20-fold, whereas grey-reef sightings decreased >90%. Following this, silky-shark sightings also declined considerably (>80%). It is suggested that these declines could relate to local overfishing. Many silky sharks were identified individually through distinctive markings or conventional tagging. Some individual silky sharks were recorded regularly over 2 years or more, but most appeared to be transient visitors. Sighting records indicated that provisioning extended the residency of transient individuals. If visiting silky sharks were drawn from a larger regional population, this would explain both their initial accumulation and why, to begin with, sightings were sustained despite local fishing pressure. Conversely, the site fidelity typical of grey reef sharks would have made them more susceptible to local depletion. Silky sharks were recorded as behaving more boldly when present in greater numbers, but the decline in grey reef sharks appears to be unrelated to the initial increase in the numbers of silky shark. It remains unclear exactly how tourism affects the behaviour and ecology of feeding predators like sharks. Here, long-term records from a shark-feeding site in the Red Sea reveal increasing sightings and bold behaviour, followed by severe declines that may relate to overfishing. This highlights how the regular provision of food may serve to aggregate predators over time, potentially making them more susceptible to targeted fishing efforts. [ABSTRACT FROM AUTHOR]

Eucalyptus wood has become one of the most important hardwood resources for pulp mills worldwide. Furthermore, bleached Eucalyptus pulp is used extensively both in paper-making globally where it is included in such diverse products as tissue, packaging, as well as printing papers and in chemical cellulose products such as viscose, acetate and microcrystalline cellulose. This paper investigates and highlights the physical and chemical attributes of the wood and pulp fibre from Eucalyptus that contribute to its popularity in the pulp and paper-making industries and to suggest how these can be enhanced or conserved in the manufacturing process to add maximum value. The fibre properties of macerated wood samples from a range of Eucalyptus species used commercially in South Africa are compared with those of North American hardwoods such as birch, maple and aspen. In comparison to the American hardwoods, the Eucalyptus species were found to have short and thin fibres (on average, fibre length from 0.6 to 0.8 mm and fibre width between 15 and 17 μm, compared with 0.6-1.4 mm and 17-30 μm, respectively, for the American hardwoods. This particular combination of dimensions for the Eucalyptus fibre produces a low fibre coarseness, which is a highly desirable attribute for products such as coated and uncoated papers. The Eucalyptus fibre is therefore reasonably fragile and this makes it particularly vulnerable to damage during the pulp and bleaching processes. Fibre damage occurs throughout the pulp process but is most severe in the mechanical sections such as digester blowing, high shear mixers, medium- and high-consistency pumps as well as low-consistency refining. These areas are highlighted in this paper and possibilities for fibre conservation are discussed. [ABSTRACT FROM AUTHOR]

Homer, L. M., Clarke, C. R., Weingarten, A. J. Effect of dietary fat on oral bioavailability of tepoxalin in dogs. J. vet. Pharmacol. Therap. 28, 287–291. A pharmacokinetic study was conducted to compare the oral bioavailability of tepoxalin and its pharmacologically active acid metabolite in fasted dogs and dogs fed either a low-fat or high-fat commercial diet. Using a cross-over design, six beagles were administered tepoxalin (10 mg/kg) intravenously (i.v.) and orally (p.o.) after being fed one of three diets (fasted, low-fat, or high-fat). Thereafter, blood samples were collected at frequent intervals, concentrations of tepoxalin and acid metabolite in plasma were determined by high performance liquid chromatography, and pharmacokinetic parameters were estimated. After i.v. dosing, the mean (±SD) half-life of elimination ( t1/2( β)) was 2.45 ± 1.47 h. After p.o. administration, plasma concentrations of acid metabolite were consistently higher than corresponding concentrations of the parent tepoxalin, indicating that tepoxalin is subject to a substantial first-pass effect. Mean (±SD) peak concentrations of tepoxalin were significantly higher after feeding of low-fat (1.08 ± 0.37 μg/mL) and high-fat (1.19 ± 0.29 μg/mL) diets than in fasted dogs (0.53 ± 0.20 μg/mL), suggesting that feeding improves oral bioavailability. [ABSTRACT FROM AUTHOR]

Washburn, K., Johnson, R., Clarke, C. R., Anderson, K., Lucas, M., Bryson, W., Robinson, J., Dame, K., Hubbard, V., Callahan, K., Robb, E. Penetration of ceftiofur into sterile vs. Mannheimia haemolytica-infected tissue chambers in beef calves after subcutaneous administration of ceftiofur crystalline free acid sterile suspension in the ear pinna. J. vet. Pharmacol. Therap. 28, 247–251. The effect of Mannheimia haemolytica infection on the penetration of ceftiofur and desfuroylceftiofur metabolites into tissue chambers was studied in cattle after subcutaneous administration of ceftiofur crystalline free acid sterile suspension (CCFA-SS). Four tissue chambers were implanted subcutaneously in each of 12 calves. Approximately 45 days after implantation, two chambers were inoculated with M. haemolytica (106 colony-forming units per chamber) while the remaining two chambers were inoculated with sterile phosphate-buffered saline. Twenty-four hours after inoculation, CCFA-SS was administered subcutaneously in the middle third of the caudal ear pinna of each calf. Chamber fluid and blood samples were collected at predetermined times for 10 days following dosing and analyzed for ceftiofur and desfuroylceftiofur metabolites by high-performance liquid chromatography. Concentrations of ceftiofur and desfuroylceftiofur metabolites in plasma and tissue chamber fluid remained above a threshold of 0.2 μg/mL for at least 8 days. Infected tissue chamber fluid concentrations of ceftiofur and desfuroylceftiofur metabolites were significantly higher than those in non-infected tissue chamber fluid, which correlated with significantly higher total protein concentration in infected tissue chambers. These results indicate that single subcutaneous administration of CCFA-SS at 6.6 mg/kg can be expected to provide effective therapy of susceptible bacterial infections for a period of at least 1 week. [ABSTRACT FROM AUTHOR]

Erkert, R. S., MacAllister, C. G., Campbell, G., Payton, M. E., Shawley, R., Clarke, C. R. Comparison of topical lidocaine/prilocaine anesthetic cream and local infiltration of 2% lidocaine for episioplasty in mares. J. vet. Pharmacol. Therap. 28, 299–304. Local anesthesia and tissue inflammation associated with lidocaine infiltration and lidocaine/prilocaine topical anesthetic cream for episioplasty in mares were compared. Twenty-two mares were randomly assigned to lidocaine or lidocaine/prilocaine topical anesthetic cream treatment groups. Perineum and vulva were cleaned, 8–12 g (approximately 1 g/cm per side of vulva) of topical anesthetic cream was applied, and the area was covered by plastic wrap 30 min prior to beginning procedure. Alternately, lidocaine was injected (1 mL) every centimeter just prior to the procedure. Episioplasty was conducted using standard methods, but employing simple interrupted sutures. Horses were not sedated and use of a twitch was recorded. Four millimeter punch biopsies were harvested 1, 3, and 10 days following episioplasty and scored for degree of inflammation by a blinded pathologist. Clinical inflammation scores were assigned when biopsies were obtained. Seven of 11 horses receiving lidocaine infiltration required twitching, but none of the horses that received the anesthetic cream required twitching. Six of 11 and seven of 11 of the lidocaine and anesthetic cream groups, respectively, required twitching for episioplasty. Except for the clinical scores on day 3, no statistical differences for clinical and histopathologic scores between samples from the two treatment groups for a given day were identified. Use of lidocaine/prilocaine topical anesthetic cream was as effective as lidocaine infiltration in providing local anesthesia when performing episioplasty in mares. Its use decreased the need for twitching horses as well as the risk of deformation of the labia caused by lidocaine infiltration. [ABSTRACT FROM AUTHOR]

Patients with subarachnoid haemorrhage often have warning symptoms which are unrecognized. Specific neurological signs such as cranial nerve palsies due to aneurysm expansion may occur. Sudden and severe 'out-of-the-blue' headache following minor haemorrhage may be misinterpreted as migraine. Focal neurological signs from secondary ischaemia may be misinterpreted as thromboembolic events. Computed tomography (CT) head scans can be misleading especially if performed too late. [ABSTRACT FROM AUTHOR]

The chemotactic role of eicosanoids in the pathogenesis of Pasteurella haemolytica infection was studied, using a tissue chamber infection model and pharmacological inhibitors of eicosanoid synthesis. Tissue chambers were implanted subcutaneously in 12 calves allotted to three treatment groups of equal size. At 45 days after implantation, calves received saline, dexamethasone, or phenylbutazone treatments, and tissue chambers in all animals were then inoculated with P. haemolytica. Chamber fluid samples were collected before inoculation and at 2, 6, 18, 40, and 90 h after inoculation. Bacterial counts, total leukocyte counts, pH and albumin concentrations in chamber fluids were determined using standard bacteriological and clinical pathological methods. Concentrations of eicosanoids and activity of interleukin-1 (IL-1) were measured by radioimmunoassay and a helper T cell bioassay, respectively. Concentrations of leukotriene B4 (LTB4), thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (PGF1α) and prostaglandin E2 (PGE2) increased markedly after inoculation. An inhibitory effect of dexamethasone on both LTB4 production and neutrophil influx, together with the temporal relationship between these two events, suggested that LTB4 served as a chemo-attractant. Activity-time profiles for IL-1 in chamber fluids were similar to those of the eicosanoids. Phenylbutazone and dexamethasone reduced the severity of the inflammatory responses as measured by lower concentrations of albumin and higher pH in treated versus control chamber fluids. The results of this study suggest that eicosanoid inflammatory mediators play an important chemotactic role in the pathogenesis of P. haemolytica infection. [ABSTRACT FROM AUTHOR]

Phonocardiographic evidence of extreme variability of the time interval between the aortic sound (A) and the opening click (OC) with intermittent absence of the OC of a partially detached mitral prosthesis of the Starr-Edwards type has not hitherto been reported. This case illustrates the diagnostic use of phonocardiography in a malfunctioning mitral Starr-Edwards prosthesis. [ABSTRACT FROM PUBLISHER]

Objective: To develop and validate an ex vivo model for study of adherence of Mannheimia haemolytica (formerly Pasteurella haemolytica) to respiratory tract mucosa of cattle and to use this model to confirm adherence of M haemolytica serovar 1 (Mh1) to several relevant respiratory mucosal surfaces., Sample Population: Excised nasal, nasopharyngeal, turbinate, and tonsillar mucosal tissue from the bovine upper respiratory tract., Procedure: Mh1 was radiolabeled by use of tritiated leucine. Various concentrations of labeled bacteria were incubated with bovine upper respiratory tract tissues for various times. Tissue was washed to remove nonadherent bacteria, and percentage of bacteria adhered (percentage of adherence) was estimated using radioactivity. Using an optimal inoculum concentration and incubation time, percentage of Mh1 adherence was compared on nasal, nasopharyngeal, turbinate, and tonsillar mucosal tissue, and adherence to nasopharyngeal tissue was confirmed by scanning and transmission electron microscopy., Results: The optimal Mh1 inoculum concentration was 1 X 10(7) colony forming units/ml and incubation time was 3 hours. Percentage of adherence of Mh1 to nasopharyngeal tissue was greater than adherence to other tissue types., Conclusions and Clinical Relevance: The ex vivo model maintained the functional and structural integrity of bovine upper respiratory tract mucosa, as confirmed by light and electron microscopy. Electron microscopy revealed participation of epithelial cell cilia and surface mucus in adherence of Mh1 to nasopharyngeal tissue. Adherence of Mh1 was confirmed in repeated assays, indicating that this organism adheres to upper respiratory tract mucosa of cattle.

Penicillin G and antipyrine, which served as model drugs to assess the relative capacities of renal and hepatic elimination pathways, respectively, were each administered intravenously to six ostriches (Struthio camelus) and to six emus (Dromaius novaehollandiae). Drug concentrations in blood samples collected over a period of 12 hr after administration were assayed, and elimination half-life, mean residence time, clearance, and steady-state volume of distribution were calculated. Mean values for elimination half-life and mean residence time of penicillin G were significantly higher in emus than in ostriches; no significant differences in antipyrine pharmacokinetics between species were demonstrated.

Objective: To investigate the concentration-dependent effects of Mannheimia haemolytica (formerly Pasteurella haemolytica) leukotoxin (LKT) on apoptosis and oncosis in bovine neutrophils and to examine the role of calcium ions (Ca2+) in LKT-induced apoptosis., Sample Population: Neutrophils isolated from blood samples obtained from healthy calves., Procedure: Neutrophil suspensions were exposed to lytic or sublytic dilutions of LKT and then examined by use of transmission electron microscopy (TEM) or gel electrophoresis. Contribution of extracellular Ca2+ to LKT-induced apoptosis was investigated by incubating neutrophils with LKT or control solutions in buffer containing 1 mM CaCl2 or in Ca2+-free buffer containing 1 mM ethylene glycol-bis (b-aminoethyl ether)-N,N-tetraacetic acid (EGTA) prior to diphenyl amine analysis., Results: Examination by TEM revealed that bovine neutrophils exposed to lytic dilutions of LKT had changes consistent with oncosis, whereas neutrophils exposed to sublytic dilutions of LKT and staurosporin, an inducer of apoptosis, had changes consistent with apoptosis. Effects of sublytic dilutions of LKT on apoptosis were confirmed by gel electrophoresis. Replacement of extracellular Ca2+ with EGTA, a Ca2+ chelator, reduced apoptosis attributable to the calcium ionophore A23187, but it did not have significant effects on apoptosis induced by LKT or staurosporin., Conclusions and Clinical Relevance: The ability of LKT to cause apoptosis instead of oncosis is concentration-dependent, suggesting that both processes of cell death contribute to an ineffective host-defense response, depending on the LKT concentration in pneumonic lesions. Furthermore, although Ca2+ promotes A23187-induced apoptosis, it is apparently not an essential second messenger for LKT-induced apoptosis.

Objective: To determine the pharmacokinetics of acetazolamide administered IV and orally to horses., Animals: 6 clinically normal adult horses., Procedure: Horses received 2 doses of acetazolamide (4 mg/kg of body weight, IV; 8 mg/kg, PO), and blood samples were collected at regular intervals before and after administration. Samples were assayed for acetazolamide concentration by high-performance liquid chromatography, and concentration-time data were analyzed., Results: After IV administration of acetazolamide, data analysis revealed a median mean residence time of 1.71 +/- 0.90 hours and median total body clearance of 263 +/- 38 ml/kg/h. Median steady-state volume of distribution was 433 +/- 218 ml/kg. After oral administration, mean peak plasma concentration was 1.90 +/- 1.09 microg/ml. Mean time to peak plasma concentration was 1.61 +/- 1.24 hours. Median oral bioavailability was 25 +/- 6%., Conclusions and Clinical Relevance: Oral pharmacokinetic disposition of acetazolamide in horses was characterized by rapid absorption, low bioavailability, and slower elimination than observed initially after IV administration. Pharmacokinetic data generated by this study should facilitate estimation of appropriate dosages for acetazolamide use in horses with hyperkalemic periodic paralysis.

Objective: To characterize ultrastructural changes of bovine lymphocytes exposed to Pasteurella haemolytica leukotoxin (LKT)., Sample Population: Partially purified LKT from a wild type P. haemolytica A1 strain and inactive pro-LKT from an isogeneic mutant Phaemolytica strain. Isolated bovine lymphocytes were obtained from 2 healthy calves., Procedure: Isolated bovine lymphocytes were incubated with various concentrations of LKT and pro-LKT for 3 hours at 37 C and examined by use of transmission electron microscopy. A cytochemical Klenow DNA fragmentation assay was used to examine lymphocytes for DNA fragmentation., Results: Lymphocytes incubated with LKT at a high concentration (1.0 toxic U/ml) had ultrastructural evidence of cytoplasmic and nuclear membrane rupture and swelling or lysis of mitochondria. Low concentrations of leukotoxin (0.1 toxic U/ml) induced DNA fragmentation in 80% of lymphocytes. Ultrastructurally, these cells had nuclear membrane blebbing, cytoplasmic vaculation, chromatin condensation, nuclear fragmentation, and membrane-bound apoptotic bodies. Incubation of lymphocytes with LKT at extremely low concentrations (0.001 toxic U/ml) or with pro-LKT did not alter their ultrastructure. Inclusion of 0.5 mM ZnCl2 in the medium blocked leukotoxin-induced ultrastructural changes in bovine lymphocytes., Conclusions and Clinical Relevance: Low concentrations of LKT induce apoptosis and high concentrations induce oncotic cell lysis in bovine lymphocytes. The ability of low LKT concentrations to induce apoptosis in host leukocytes may allow bacteria to escape host immune surveillance and colonize the host.

Ten healthy horses were injected intravenously with 99mTc-MAG3 and the disappearance of radioactivity from the blood was measured. The total body clearance (Cl(B)) and elimination half-life (t1/2(beta)) were 7.9 +/- 1.5 ml/kg/minute and 32.8 +/- 4.1 minutes, respectively. The disappearance of 99mTc-MAG3 from the blood of 2 horses with compromised renal function was also measured. The data suggest that 99mTc-MAG3 is a useful and clinically applicable radiopharmaceutical for measurement of effective renal blood flow in the horse.

Pasteurella haemolytica, the causative agent of shipping fever pneumonia in cattle, produces a leukotoxin (LKT) which lyses ruminant leukocytes with high efficiency but is reputed to not affect leukocytes from nonruminant species. In this study, we tested the supposition that LKT binding correlates positively with susceptibility to intoxication of susceptible isolated bovine lymphocytes and lymphoma tissue culture cells (BL3 cells) and negatively with reputed nonsusceptible equine, porcine, and canine lymphocytes and human lymphoid tissue culture cells (Raji cells). Bovine lymphocytes and BL3 cells were highly susceptible to LKT intoxication, exhibiting both substantial increase in intracellular Ca(2+) concentration and marked leukolysis. Exposure of reputed LKT-nonsusceptible porcine lymphocytes and Raji cells to LKT caused a slightly increased intracellular Ca(2+) concentration but no leukolysis. No LKT effect was detected for equine and canine lymphocytes. LKT bound to lymphoid cells from all species tested. Intact 102-kDa LKT was recovered from exposed isolated lymphoid cell membranes. Pro-LKT acylation was not required for LKT binding to BL3 cells. LKT binding was rapid, with maximal binding occurring by 3 min, and was proportional to the LKT concentration in the range 0.04 to 4.0 microg/ml. For this LKT concentration range, BL3 cells bound more LKT than did porcine lymphocytes or Raji cells, suggesting that LKT binds to BL3 cells with higher affinity than to porcine lymphocytes or Raji cells. Above 4.0 microg/ml, LKT demonstrated saturable binding to BL3 cells. Neutralizing anti-LKT monoclonal antibody (MAb) MM601 diminished LKT binding to BL3 by 36% while decreasing leukolysis by 81%. In contrast, MM601 did not diminish LKT binding to Raji cells. Pretreatment of target cells with 120 microg of protease K per ml diminished LKT binding to BL3 cells by 75%, with only a 25% decrease in leukolysis. However, pretreatment with 150 microg of protease K per ml abolished the remaining 25% of LKT binding and 75% leukolysis. Therefore, P. haemolytica LKT binds rapidly to susceptible and to reputed nonsusceptible lymphoid cells. LKT binding resulting in species-specific leukolysis was characterized by high affinity, inhibition by MAb MM601, and relative resistance to protease K pretreatment of lymphoid cells. Two types of LKT binding to lymphoid cells are proposed. High-affinity binding leads to efficient leukolysis. In some lymphoid cells from reputed LKT-nonsusceptible species, low-affinity LKT binding may cause a low-efficiency increase in the intracellular Ca(2+) concentration without leading to leukolysis.

The effects of Pasteurella haemolytica leukotoxin (LKT) on the activity of phospholipase D (PLD) and the regulatory interaction between PLD and phospholipase A(2) (PLA(2)) were investigated in assays using isolated bovine neutrophils labeled with tritiated phospholipid substrates of the two enzymes. Exposure of [(3)H]lysophosphatidylcholine-labeled neutrophils to LKT caused concentration- and time-dependent production of phosphatidic acid (PA), the product of PLD. LKT-induced generation of PA was dependent on extracellular calcium. Both production of PA and metabolism of [(3)H]-arachidonate ([(3)H]AA)-labeled phospholipids by PLA(2) were inhibited when ethanol was used to promote the alternative PLD-mediated transphosphatidylation reaction, resulting in the production of phosphatidylethanol rather than PA. The role of PA in regulation of PLA(2) activity was then confirmed by means of an add-back experiment, whereby addition of PA in the presence of ethanol restored PLA(2)-mediated release of radioactivity from neutrophil membranes. Considering the involvement of chemotactic phospholipase products in the pathogenesis of pneumonic pasteurellosis, development and use of anti-inflammatory agents that inhibit LKT-induced activation of PLD and PLA(2) may improve therapeutic management of the disease.

Research interviews with seriously ill patients are now often undertaken in quality of life research. Clinicians may be approached by researchers wishing to study their patients, and may be worried at some ethical aspects of interviewing. Concerns may include potential distress which interviews may cause, that they may interfere with the doctor-patient relationship, and perhaps, a scepticism that techniques addressing psychosocial concerns produce only 'soft' data. However, interview methods are a valuable tool for medical sociologists, nurse researchers and others. We discuss here some reflections following a study that involved interviewing severely ill patients with incurable malignant cerebral glioma. We use our observations to answer concerns and to discuss problems that arose. We suggest areas researchers and clinicians might consider before embarking on such collaboration.