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Potato virus S (PVS) is prevalent within potato (Solanum tuberosum) production worldwide. Traditionally, PVS has been split into two strains, Ordinary (PVS O ) and Andean (PVS A ), based on reaction in herbaceous indicator species such as Chenopodium quinoa. However, recent research has identified further strain designations, such as PVS O-CS (Ordinary and Chenopodium systemic). Forty-four isolates of PVS were collected from potato seed lines in different geographical regions within Tasmania, Australia. Isolates were initially characterized by reactions in C. quinoa. Nineteen isolates were characterized as PVS O , based on the development of local lesions and serological detection in inoculated leaves only. Three isolates were identified as PVS A -like, based on local lesion development in inoculated leaves, mild mottling or chlorotic spots on noninoculated leaves, and serological detection in both inoculated and noninoculated leaves. Thirteen isolates produced no symptoms, and were detected serologically in inoculated leaves only (PVS O -like). Four isolates produced no symptoms but were detected serologically in both inoculated and noninoculated leaves (PVS A -like). Five isolates produced symptoms in inoculated leaves only but were detected serologically in both inoculated and noninoculated leaves (also PVS A -like). The ability of isolates to infect tomato has also been used as a criterion to assist in PVS strain differentiation. A subsample of isolates (n = 16) was unable to infect tomato 'Grosse Lisse'. Seventeen isolates representative of these groupings based on reactions in C. quinoa were also characterized by coat-protein sequencing. Phylogenetic comparisons suggested that all isolates were PVS O rather than PVS A . Therefore, whereas some of these PVS isolates were systemic in C. quinoa, findings from this study suggest that they were not PVS A , and that only PVS O and PVS O-CS isolates are present in Tasmania. The implications of this finding for disease management are discussed.

Ray blight, caused by Phoma ligulicola var. inoxydabilis, causes substantial annual losses in Australian pyrethrum fields. Fifty-nine P. ligulicola var. inoxydabilis isolates were randomly selected from fields in three distinct geographical regions in Tasmania, Australia. Genetic diversity was characterized using random amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP). Based on genetic similarities of less than 99%, 56 distinct genotypes (putative clones) were observed. Mean haploid gene diversity of clone-corrected populations ranged between 0.05 and 0.31, and 0.11 and 0.32, for the RAPD and AFLP data sets, respectively. Cluster analysis indicated two distinct groups of isolates supported by all bootstrap replicates. The first cluster contained all but four isolates with representatives from all three populations. The second cluster contained two isolates from the Western and Central populations, respectively, while the remaining isolates were not able to be grouped with any distinct cluster. Analysis of the population structure suggested no evidence for spatial autocorrelation at the smallest distance classes. The presence of linkage disequilibrium was indicated regardless of population scale. Collectively, these findings provided further evidence for the absence or minor role of the teleomorph in the epidemiology of ray blight in Australian pyrethrum fields.

Biomaterial nerve cuffs are a clinical alternative to autografts and allografts as a means to repair segmental peripheral nerve defects. However, existing clinical biomaterial constructs lack true incorporation of physical guidance cues into their design. In both two- and three-dimensional systems, it is known that substrate geometry directly affects rates of axon migration. However, the ability to incorporate these cues into biomaterial scaffolds of sufficient porosity to promote robust nerve regeneration in three-dimensional systems is a challenge. We have developed fibrin constructs fabricated by a sacrificial templating approach, yielding scaffolds with multiple 10-250 μm diameter conduits depending on the diameter of the template fibers. The resulting scaffolds contained numerous, highly aligned conduits, had porosity of ∼ 80%, and showed mechanical properties comparable to native nerve (150-300 kPa Young's modulus). We studied the effects of the conduit diameters on the rate of axon migration through the scaffold to investigate if manipulation of this geometry could be used to ultimately promote more rapid bridging of the scaffold. All diameters studied led to axon migration, but in contrast to effects of fiber diameters in other systems, the rate of axon migration was independent of conduit diameter in these templated scaffolds. However, aligned conduits did support more rapid axon migration than non-aligned, tortuous controls., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Pale purple coneflower, Echinacea pallida (Nutt.) Nutt., is an herbaceous perennial cultivated for its ornamental and medicinal properties. In 2005, phytoplasma-like symptoms, including virescence, phyllody, and chlorotic leaves, were first observed in coneflower fields in northern Tasmania, Australia. During the 2010-2011 growing season, the incidence of affected plants was estimated to be 12% within a single field. Total DNA was extracted from symptomatic plants with a DNeasy Plant Mini Kit (QIAGEN Inc., Valencia, CA) according to the manufacturer's instructions. DNA was also extracted, as described above, from asymptomatic coneflower seedlings obtained by germinating surface-sterilized seed on water agar. DNA was amplified via a nested PCR using universal primer pairs P1/P7 followed by R16F2n/R16R2 to detect putative phytoplasmas (2). Amplifications yielded expected products of 1.8 and 1.2 kb, respectively, only from symptomatic samples. Subsequently, PCR products from six arbitrarily selected samples were used for sequencing (Genome Lab Dye Terminator Cycling Sequence with Quick Start Chemistry) and read in a CEQ8000 sequencer (Beckman Coulter Inc., Brea, CA). Sequence homology indicated 100% similarity between isolates designated EWB1 to EWB4 (GenBank Accession Nos. JF340075 and JF340077 to JF340079) and between EWB5 and EWB6 (JF340076 and JF40080). Sequence homology between the two observed groups was 99.7%, resulting from a 4-bp difference in the R16F2n primer region. Blast search revealed isolates EWB1 to EWB4 were 100% homologous with Catharanthus roseus phytoplasma (EU096500.1), Tomato big bud phytoplasma (EF193359.1), Scaevola witches'-broom phytoplasma (AB257291.1), and Mollicutes sp. (Y10097.1 and Y10096.1). Moreover, isolates EWB5 and EWB6 shared 99% sequence identity with the above isolates. iPhyClassifier (4) was used to perform sequence similarity and generate virtual restriction fragment length polymorphism (RFLP) profiles. The 16S rDNA sequence of isolates EWB1 to EWB4 and EWB5 to EWB6 shared 100 and 99.7% similarity, respectively, to the 'Candidatus Phytoplasma australasiae' reference strain (Y10097). RFLP profiles from all isolates suggested that they belonged to the 16SrII-D subgroup. To our knowledge, this is the first report of a 16SrII-D subgroup phytoplasma infecting E. pallida in Australia. Aster yellow phytoplasmas (16SrI-C subgroup) infections of E. purpurea have been recorded in Slovenia (3) and southern Bohemia (1). References: (1) J. Franova et al. Eur. J. Plant Pathol. 123:85, 2009. (2) I. M. Lee et al. Int. J. Syst. Bacteriol. 48:1153, 1998. (3) S. Radišek et al. Plant Pathol. 58:392, 2009. (4) Y. Zhao et al. Int. J. Syst. Evol. Microbiol. 59:2582, 2009.

Oxylipins, a class of oxygenase-derived unsaturated fatty acids, are important signal molecules in many biological systems. Recent characterization of an Aspergillus flavus lipoxygenase gene, lox, revealed its importance in maintaining a density-dependent morphology switch from sclerotia to conidia as population density increased. Here, we present evidence for the involvement of four more oxylipin-generating dioxygenases (PpoA, PpoB, PpoC, and PpoD) in A. flavus density-dependent phenomena and the effects of loss of these genes on aflatoxin production and seed colonization. Although several single mutants showed alterations in the sclerotia-to-conidia switch, the major effect was observed in a strain downregulated for all five oxygenases (invert repeat transgene [IRT] strain IRT4 = ppoA, ppoB, ppoC, ppoD, and lox). In strain IRT4, sclerotia production was increased up to 500-fold whereas conidiation was decreased down to 100-fold and the strain was unable to switch into conidial production. Aflatoxin (AF) production for all mutant strains and the wild type was greatest at low population densities and absent in high populations except for strain IRT4, which consistently produced high levels of the mycotoxin. Growth on host seed by both IRT4 and IRT2 (downregulated in ppoA, ppoB, and ppoD) was marked by decreased conidial but increased AF production. We propose that A. flavus oxygenases and the oxylipins they produce act in a highly interdependent network with some redundancy of biological function. These studies provide substantial evidence for oxylipin-based mechanisms in governing fungus-seed interactions and in regulating a coordinated quorum-sensing mechanism in A. flavus.

Simple sequence repeat (SSR) markers for Fusarium pseudograminearum with 2 to 3 bp repeat motifs were identified by screening the genome database of the related species Fusarium graminearum. Twelve SSRs amplified single loci in both F. graminearum and F. pseudograminearum. Forty F. pseudograminearum and six F. graminearum individual isolates were screened to determine levels of polymorphism, with all SSRs displaying three to 14 alleles across all isolates. Eleven SSRs were polymorphic across F. pseudograminearum isolates tested proving the usefulness of genome databases of closely related species in identifying genetic markers., (© 2007 The Authors.)

Fusarium pseudograminearum causes crown rot of wheat in Australia and most other wheat growing regions, but its evolutionary history is largely unknown. We demonstrate for the first time that F. pseudograminearum is a single phylogenetic species without consistent lineage development across genes. Isolates of F. pseudograminearum, F. graminearum sensu lato, and F. cerealis, were collected from four countries and four single copy, nuclear genes were partially sequenced, aligned with previously published sequences of these and related species, and analysed by maximum parsimony and Bayesian inference. Evolutionary divergence varied between genes, with high phylogenetic incongruence occurring between the gene genealogies. The absence of geographic differentiation between isolates indicates that the introduction of new fungal strains to a region has the potential to introduce new pathogenic and toxigenic genes into the native population through sexual recombination.

Objectives: To compare the quality and consistency of single-use adenotonsillectomy instruments available in the UK with reusable instruments and examine their performance in a clinical setting., Design: A laboratory assessment of each reusable instrument created a detailed specification for the respective single-use equivalent. A surveillance system monitored the performance of a selected set of specified single-use instruments., Setting: Single-use instruments were withdrawn shortly after their introduction in 2001. Persisting concerns from the Spongiform Encephalopathy Advisory Committee led to an investigation into the feasibility of continuing to use such instruments., Main Outcome Measures: The numbers of instruments from each set judged as unacceptable or as good as the original. The number and cause of instrument failure during clinical surveillance., Results: Between 40% and 93% of the instruments on each set were as good as the original and between 0% and 40% of the instruments were unacceptable from six sets of steel and one set of polymer instruments. 4151 procedures were monitored between 1 February 2003 and 31 March 2004 using a total of 41 376 instruments. Problems were reported with 335 (0.8%) instruments, 46% attributable to instrument design, 14% to poor design control and 13% to instruments escaping quality control systems. Following correction of the faults, between 1 January 2004 and 31 March 2004 the problem rate fell to 0.4%., Conclusions: High quality single-use instruments for tonsil and adenoid surgery are available in the UK. Some companies offered inferior instruments not fit for their purpose. The procurement, introduction and subsequent clinical approval of single-use instruments requires a radically different approach to that currently applied to the purchase of reusable surgical equipment. Careful monitoring of their introduction is essential.

Downy mildew of oilseed poppy (Papaver somniferum) has become a serious disease issue for the Tasmanian poppy industry since its first record in 1996. Previous reports have reported the pathogen as Peronospora arborescens, which is differentiated from the related species P. cristata, also known to infect Papaver spp., by conidium dimensions alone. This study investigated the taxonomic status of the downy mildew pathogen, using both morphological characters and molecular analysis of the internal transcribed spacer (ITS) region of the ribosomal DNA (rDNA). The inherent variability of conidium dimensions made differentiation of species difficult. Sequence homology and phylogenetic analyses of the ITS region showed the pathogen to be more closely related to P. cristata than P. arborescens. It is therefore proposed that downy mildew of oilseed poppy in Tasmania be reattributed to the pathogen P. cristata. In addition to this work, PCR primers have been developed for the specific detection of the downy mildew pathogen in Tasmania.

Downy mildew, caused by Peronospora arborescens, has become the major disease affecting oilseed poppy (Papaver somniferum) since its first record in Tasmania in 1996. Two field trials conducted in 2000 and 2001 studied the progression and spatial distribution of downy mildew epiphytotics. The logistic and exponential models best described the progression of disease incidence and severity, respectively. Incidence and severity increased rapidly following canopy closure. In 2001, incidence increased from 0.16%, prior to canopy closure, to 100% at late flowering (40 days). Spatial analyses of epiphytotics were conducted by fitting the beta-binomial and binomial distributions, median runs analysis, and the spatial analysis by distance indices. All analyses demonstrated that the distribution of incidence and severity was strongly spatially aggregated from canopy closure until at least late flowering. These results suggest that secondary spread from a few primary infections is the major factor in epiphytotics.

Seizures are a common neurologic consequence of various etiologies in the end-stage cancer patient. Because dying cancer patients and their families are often coping with new challenges daily, any intervention that can prevent further patient or family discomfort should be implemented. The purpose of this study was to evaluate four pharmacy interventions aimed at improving nursing care to cancer patients at a facility for the terminally ill. The four interventions were development of a seizure risk factor assessment toll, assembly or availability of a diazepam seizure kit, nursing education via in-service training, and development of a manual for nursing stations. Successful implementation of this project indicated that nurses perceived an empowerment in improving quality of life of their patients.

Objective: To determine signalment, clinical signs, concurrent diseases, response to surgical treatment, and long-term outcome of ferrets with bilateral adrenal tumors or adrenal hyperplasia., Design: Retrospective study., Animals: 56 ferrets with bilateral adrenal tumors or adrenal hyperplasia confirmed histologically following subtotal bilateral adrenalectomy., Procedure: Medical records of all ferrets with bilateral adrenal tumors or hyperplasia examined between 1994 and 1997 were reviewed. Ferrets underwent a subtotal bilateral adrenalectomy or a unilateral adrenalectomy initially, followed by a unilateral subtotal adrenalectomy when tumors or hyperplasia later developed on the contralateral adrenal gland. A long-term follow-up of a minimum of 18 months after final adrenal gland surgery was obtained by examination of medical records and follow-up telephone conversations., Results: Clinical signs of hyperadrenocorticism included bilaterally symmetric alopecia, return to male sexual behavior in castrated male ferrets, or swollen vulva in spayed female ferrets. Surgical treatment of bilateral adrenal disease by subtotal bilateral adrenalectomy (or unilateral adrenalectomy followed by contralateral unilateral subtotal adrenalectomy) was effective with a mortality rate of < 2%. Only 3 (5%) ferrets required glucocorticoid or mineralocorticoid replacement following subtotal bilateral adrenalectomy. Recurrence after bilateral adrenalectomy was 15% with a mean long-term follow-up period of 30 months., Conclusions and Clinical Relevance: Bilaterally symmetric alopecia, return to male sexual behavior in castrated male ferrets, or swollen vulva in spayed female ferrets are indicative of adrenal tumors or adrenal hyperplasia in ferrets. Surgical treatment of bilateral adrenal disease by subtotal bilateral adrenalectomy is effective, with a low rate of complications and postoperative recurrence rate.

A synthetic cell-binding peptide (P-15) combined with anorganic bovine-derived hydroxyapatite bone matrix (ABM) was compared to demineralized freeze-dried bone allograft (DFDBA) and open flap debridement (DEBR) in human periodontal osseous defects in a controlled, monitored, multi-center trial. Following appropriate initial preparation procedures, flap surgery with defect and root debridement was performed. Three osseous defects per patient were treated randomly with one of three procedures after surgical preparation. Appropriate periodontal maintenance schedules were followed, and at 6 to 7 months re-entry flap surgery was performed for documentation and finalization of treatment. Analysis of variation (ANOVA) and t test analyses of patient mean values from 31 patients revealed that the combination ABM/P-15 grafts demonstrated significantly better mean defect fill of 2.8 +/- 1.2 mm (72.3%) versus a mean defect fill of 2.0 +/- 1.4 mm (51.4%) for defects treated with DFDBA (P <0.05) and a mean defect fill of 1.5 +/- 1.3 mm (40.3%) (P <0.05) for defects treated with DEBR. Other hard tissue findings showed similar clinically superior results with the use of ABM/P-15. Relative defect fill results showed 87% positive (50% to 100% defect fill) responses with ABM/P-15, 58% positive responses with DFDBA, and 41% positive responses with DEBR. There were 8 to 9 times more failures (minimal response) with DFDBA and DEBR (26% to 29% frequency) than with ABM/P-15. Soft tissue findings showed no significant differences among treatments except for greater clinical attachment level gain with ABM/P-15 compared to DEBR. These results suggest that the use of the P-15 synthetic cell-binding peptide combined with ABM yields better clinical results than either DFDBA or DEBR. Further studies are needed to determine the relative roles of the ABM and/or the P-15 in these improved results.

Several studies have found incomplete calculus removal during periodontal treatment with traditional hand curets, sonic, and ultrasonic instruments. This study evaluated the speed and effectiveness of subgingival calculus removal with new diamond-coated ultrasonic tips on single-rooted teeth. Single session subgingival scaling and root planing was performed on 80 teeth with 5 to 12 mm probing depths in 15 patients. Each patient provided groups of 4 teeth that were randomly treated with either hand curets (HAND); standard smooth ultrasonic tip (US); or fine grit (FINDIAM) or medium grit (MEDDIAM) diamond-coated ultrasonic tips. The time taken to reach the therapeutic endpoint of a clean, smooth root surface in a defined region on each tooth with each instrument by the 3 therapists with differing experience levels was recorded. The teeth were then atraumatically extracted, stored in a surfactant, photographed at 10X, and the percent of calculus present in the area of the pocket or on a comparable control surface calculated by histometric point counting. ANOVA and paired t tests showed that mean percent remaining calculus on treated versus control surfaces was HAND 4.6 +/- 5.3 versus 57.5 +/- 28.2, US 4.7 +/- 6.4 versus 54.4 +/- 25.9, FINDIAM 4.3 +/- 5.2 versus 37.5 +/- 22.1, and MEDDIAM 3.4 +/- 4.2 versus 50.7 +/- 20.1, respectively (all P < 0.01). The mean time in seconds to reach the clinical endpoint ranged from HAND 289 +/- 193, US 194 +/- 67, FINDIAM 167 +/- 71, to MEDDIAM 147 +/- 92. All powered instruments were significantly faster than HAND (P < 0.05), but did not differ from each other. On a 0 = "smooth" to 3 = "rough" scale, most often HAND resulted in "smooth" surfaces (10/20), the powered tips of all types "slight" surface roughness (10/20 each), and US the most "moderate" roughness (7/20). There were no differences in percent calculus remaining, surface roughness, or time spent among the 3 treating clinicians despite their varying experience levels. The results of this study showed that percent calculus remaining was <5% with all the instruments given time ad libitum on a given root surface. Root roughness was generally slightly greater with all 3 powered tips. All of the powered instruments took significantly less time than the HAND. Both DIAM tips took less time than US. Diamond-coated ultrasonic tips appeared to be much more efficient than HAND or US in removing calculus in moderate-deep probing depths on single-rooted teeth in vivo.

The actual length of clinically exposed tooth structure between planned restoration margin and alveolar crest ("biologic width") obtained during surgical crown elongation procedures was compared to the textbook goal of 3.0 mm. Sixteen (16) patients with 21 teeth requiring surgical crown lengthening for restoration placement participated. Oral hygiene instructions were given and optimal plaque control was mandatory. At each clinician's discretion, surgical techniques consisted of either gingivectomy or an apically positioned flap with and without osseous resection. Utilizing a reference stent, measurements were obtained at the facial, mesial-facial, lingual, and distal-lingual of the treated teeth both before and after osseous reduction. Parameters evaluated were gingival margin position, probing depth, mucogingival junction position, alveolar crest location, mobility, plaque index, and gingival index. These measurements were again recorded 8 weeks after surgery with the exception of alveolar crest. Statistical analysis with the paired t-test and linear correlation showed no significant change from baseline or among operators with varying experience in any of these parameters. Overall the results showed that the default objective of 3 mm between planned restoration margin and alveolar crest was not routinely achieved (mean 2.4 +/- 1.4 mm). The post-treatment distance from the planned restoration margin to the alveolar crest was greatest at the facial aspect of the teeth (mean 2.6 +/- 1.2 mm) and least at the distal-lingual (mean 2.2 +/- 1.7 mm). In addition, although more experienced periodontists removed a larger amount of bone, the amount of root surface exposed was still short of the initially desired biologic width.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Excimer laser photoablation effectively and precisely removes corneal tissue but may not smooth irregularities on the anterior corneal surface. An even surface might be obtained by applying a smoothing substance that fills in irregularities and ablates at the same rate as corneal tissue. Evaluation of collagen gel as a smoothing agent is reported., Methods: Pure, type I collagen solutions were prepared to remain soluble at physiological pH and to spontaneously gel when exposed to cationic buffers. Collagen gels were formed on the surface of enucleated porcine corneas and on human donor corneas and exposed to varying pulses of 193-nanometer excimer laser energy. Effects of collagen gel on ablation depth, corneal surface smoothness, and smoothing of roughened cornea were evaluated by examining scanning electron micrographs of control and treated specimens., Results: Collagen gels formed from 5 mg/ml collagen solutions dramatically altered the depth of photoablation. Photoablation of roughened cornea with collagen gels produced smooth corneal surfaces, whereas control eyes remained roughened and irregular. The smoothness of photoablated cornea surfaces improved when collagen gels were applied prior to photoablation., Conclusions: The rapidly gelling collagen solution appears to exhibit the functional properties required for an effective smoothing agent for excimer laser photoablation. The substance has low viscosity when applied to the corneal surface and forms a rigid gel when exposed to cationic buffer solution. In addition, the concentration of the collagen gel can be adjusted to provide different ablation rates.

Both synthetic and biological materials have been used for smoothing wrinkle lines and depressed scars. Injectable fillers provide a convenient and easy alternative to surgical methods to treat dermal defects. Optimally, injectable fillers augmenting dermal tissue should exhibit properties similar to the dermal collagen network, providing a stable matrix for long-term correction but also being subject to the dynamic changes that occur to dermal tissue during the aging processes. At present, only biological materials are available on a commercial basis, although a number of synthetic injectables are being evaluated in clinical trials. The long-term effectiveness of most commercial materials has been limited prompting questions about the cost-benefits of such treatment. In this regard, the effectiveness of the injectable fillers, particularly of biological materials, will be discussed as will the difficulties involved in determining the expected result (effectiveness) for specific materials and in providing methods of measuring effectiveness.

The effects of a 60-minute IV infusion of histamine (0.5 mg of histamine base/minute) on the systemic, pulmonary, and digital vasculature were investigated in mature ponies. Immediately after the start of histamine infusion, there were a transient decrease in systemic pressure lasting less than 1 minute and then a brief period of systemic hypertension. Systemic pressure then returned to preinfusion levels for the remainder of the infusion period. Pulmonary arterial pressure increased transiently coincident with systemic hypotension. Histamine increased cardiac output and decreased both total peripheral and pulmonary vascular resistances. In the digit, blood flow increased for the duration of the systemic hypertension, but was otherwise unchanged. Digital lymph flow and protein concentration were unchanged by histamine. Hematocrit increased significantly after 60 minutes of histamine infusion, but plasma and blood volumes were unchanged. Histamine caused cyanosis, hyperpnea, and sweating in all ponies. The effects of histamine given IV do not mimic the systemic and digital vascular effects of acute alimentary laminitis.

The applicability of the waterfall model was tested using the Starling resistor and different viscosities of fluids to vary the Reynolds number. The waterfall model proved adequate to describe flow in the Starling resistor model only at very low Reynolds numbers (Reynolds number less than 1). Blood flow characterized by such low Reynolds numbers occurs only in the microvasculature. Thus, it is inappropriate to apply the waterfall model indiscriminately to flow through large collapsible veins.

Twelve Shetland ponies were fed a high-starch ration. Seven ponies which had a transitory metabolic acidosis developed laminitis 56 hours (+/- 3.5, SEM) after overfeeding. These ponies also developed persistent hypokalemia, hyperthermia, and increased heart rate 24 hours before the onset of lameness. Serum sodium, serum chloride, hematocrit, plasma volume, and blood volume were unchanged. At the onset of clinical signs of laminitis, cardiac output and blood pressure increased, but total peripheral resistance was unchanged. None of the measured or calculated values predicted the onset of laminitis. Hypertension appeared to be a response to, rather than a cause of, lameness. Three of the remaining ponies apparently died of shock 29.3 +/- 2.7 hours after overfeeding. All 3 had severe metabolic acidosis; decreased cardiac output, systemic arterial pressure, and plasma volume; and increased hematocrit, total peripheral resistance, and pulmonary vascular resistance. The 11th pony was unaffected and the 12th pony was euthanatized.

The effects of acute brain hypoxia on pulmonary hemodynamics were investigated in anesthetized dogs with the vagus and carotid sinus nerves intact and cut. Following ligation of collateral vessels, brain hypoxia was induced by pumping arterial blood through a ventilated extracorporeal lung to the external carotid arteries for 5 min. In the intact-nerve group brain hypoxia caused no change in pulmonary and systemic vascular pressures and resistances. In the cut-nerve group brain hypoxia caused an increase in mean pulmonary artery, left atrial, pulmonary artery pulse, and mean aortic pressures. Cardiac output, dP/dt, central blood volume, and total peripheral resistance increased but pulmonary vascular resistance and lung extravascular thermal volume were unchanged. It is concluded that acute brain hypoxia does not increase pulmonary vascular resistance but may increase pulmonary blood volume resulting from increased left ventricular afterload.

In two series of experiments we studied the effects of indomethacin on (a) coronary reactive hyperemia and, (b) renal blood flow, autoregulation, and reactive dilation. Coronary blood flow was measured in closed-chest dogs. Reactive hyperemia was induced by coronary occlusion for 5 and 15 sec. Indomethacin, an inhibitor of prostaglandin synthesis, was infused intra-arterially in doses of 90-200 mg over periods ranging from 30-120 min. Coronary reactive hyperemia was not affected by indomethacin. The canine renal vascular bed was studied under conditions of natural flow, controlled flow, and controlled pressure. Intra-arterial infusion of 90 mg of indomethacin over a 30- to 60- min period caused increased renal vascular resistance and an attenuation of reactive dilation (induced by stopping renal blood flow for 90 sec). Indomethacin slightly attenuated the autoregulatory response to decreasing perfusion pressures, but did not affect the respone to increasing pressures. Thus the study fails to provide evidence for participation of the prostaglandins in regulation of coronary blood flow and suggests only minimal participation of prostaglandings in renal blood flow regulation.

The digital circulation was isolated in 12 ponies under pentobarbital anesthesia. Blood flow was either controlled by a pump or measured under natural perfusion. The responses to rapid changes and stoppages of blood flow indicated no evidence of autoregulation or reactive hyperemia. Local administration of acetylcholine, histamine, and prostaglandins E1 and E2 decreased prevenous resistance, whereas epinephrine and serotonin caused prevenous constriction. Large doses of epinephrine and serotonin decreased venous caliber. The effects of prostaglandins A1 and F2alpha were variable. The equine digital vasculature responds to changes in flow and to vasoactive agents like the canine forelimb skin vasculature.

Histamine (4 microgram base/min) infused into the brachial artery for 60 min greatly increases skin lymph flow and lymph protein concentration in forelimbs perfused either naturally or at constant inflow. In contrast, the simultaneous intrabrachial infusion of histamine and norepinephrine (4 microgram base/min of each) or histamine and isoproterenol (4 microgram base/min and 3 microgram/min, respectively) for 60 min failed to alter lymph protein concentration in forelimbs perfused either naturally or at constant inflow. The edema in forelimbs naturally perfused by histamine (4 microgram base/min) infused into the brachial artery for 60 min was also greatly reduced by the simultaneous histamine-catecholamine infusions. Phentolamine (in concentrations that antagonize the vascular actions of norepinephrine) failed to prevent the antagonism of histamine protein efflux by norepinephrine. Hence, it must be concluded that catecholamines antagonize the protein efflux by locally infused histamine, independent of alpha-adrenergic receptor activity.

Previous studies in live chickens have measured heart rate, blood pressure, and cardiac output during drug administration or asphyxia and made assumptions concerning the peripheral vasculature. The present study employs a constant-flow, isolated hindlimb perfusion technique to measure directly changes in skeletal muscle vascular resistance induced either by local intra-arterial (i.a.) bolus, or continuous i.a. infusion, of various vasoactive substances. Prostaglandin E1 (0.5 microgram, bolus) produced arteriolar vasodilation lasting 10 min, as indicated by a fall ian perfusion pressure. Bolus injection of histamine (10 microgram diphosphate) or adenosine (5 and 10 microgram) produced vasodilation of less than 2-min duration. Theophylline infusion (5 microM infused at 1 mL/min, i.a.) blocked the effect of adenosine. Norepinephrine (1 microgram) produced vasoconstriction which was reduced 60% by systemic alpha-adrenergic blockade with phenoxybenzamine (7.5-10 mg/kg). Tracheal occlusion produced intense vasoconstriction which was reduced 70% by alpha-adrenergic blockade. Electrical stimulation of the peripheral end of the cut sciatic nerve (6 Hz) produced an immediate vasodilation lasting several minutes.

The old and recent literature bearing on the role of metabolic factors in exercise hyperemia has been reviewed. Two general conclusions have gradually emerged over the years. First, no one factor is by itself a sufficient explanation for the hyperemia. Second, the contributions of the various factors appear to change with time of exercise. While additional temporal studies are needed to firmly establish more specific conclusions, those now available suggest that factors related to skeletal muscle cell depolarization initiate the hyperemia while factors related to oxygen consumption in excess of oxygen delivery contribute more to the maintenance of the hyperemia. For example, the potassium that leaves the skeletal muscle cell on depolarization appears to contribute more to the initiation of the hyperemia than to its maintenance. Hydrogen, on the other hand, appears to have little to do with initiation but may contribute to maintenance, at least with grades of exercise that reduce cellular oxygen tension. The picture that emerges from the review seems to be one of multiple factors acting in concert with a changing temporal pattern.

Recovery times from exercise and ischemic dilation in gracilis muscle were compared during constant pressure (natural flow) and constant flow perfusion. Recovery times were longer at constant flow. This finding provides additional support for the metabolic hypothesis for the regulation of blood flow in skeletal muscle.

The effects of 90 min intravenous histamine (10 micrograms base . kg-1 . min-1) with and without beta (propranolol)-receptor blockade on lung water and hemodynamics were studied. In anesthetized dogs cold 3% saline was used as the indicator to determine cardiac index, central blood volume, and lung extravascular thermal volume. Propranolol alone decreased stroke volume and cardiac index but increased central blood volume, total peripheral resistance, and mean pulmonary arterial and pulmonary arterial wedge pressures. Pulmonary vascular resistance, mean arterial pressure, and lung extravascular thermal volume were not changed. Histamine with propranolol further reduced stroke volume and cardiac index, whereas mean pulmonary arterial and pulmonary arterial wedge pressures returned to control values. Mean arterial pressure, central blood volume, and total peripheral resistance decreased, pulmonary vascular resistance increased, and lung extravascular thermal volume remained unchanged. In all experiments postmortem extravascular lung water-to-dry weight ratio was unchanged. We conclude that histamine does not increase lung water content and that beta-receptor blockade does not modify this response.

Hemodialysis was used to study the direct effects of acute hypoosmolality upon the resistance to blood flow through the gracilis and coronary vascular beds and upon left ventricular contractile force in the dog. When sodium chloride was removed from the blood perfusing the gracilis vascular bed, resistance increased linearly over the range 300-225 mOsm/kg. A 10% decrease in osmolality produces a 20% increase in resistance. When the removed sodium dhloride was replaced with mannitol such that plasma osmolality did not change, resistance rose slightly but failed to regularly return to the control value. Hypoosmolality also raised coronary vascular resistance and this was associated with an increase in left ventricular force. Thus direct effects of hypoosmolality on peripheral vascular beds and perhaps myocardium may participate in the compensatory mechanisms that tend to stabilize blood pressure during hypoosmotic states such as acute salt depletion.

Histamine (4-64 microgram base/min) infused into the brachial artery clearly promotes edema formation in forelimbs perfused at natural flow. In contrast, intravenously administered histamine, even in blood concentrations exceeding those achieved by local infusion, not only fails to promote edema formation, but rather causes net extravascular fluid reabsorption. In this study, high concentrations of histamine were infused into the left ventricular chamber to bypass the pulmonary circuit. Histamine (400-800 microgram base/min) infused into the left ventricle of the heart for 90 min produced marked hypotension and only very slight increases in forelimb skin lymph flow and lymph protein concentration and failed to produce visible signs of edema. Thus the differential actions of local and intravenous histamine on lymph flow, protein efflux, and fluid fluxes cannot be explained by uptake or destruction of histamine in the lung during intravenous infusions of this agent. It seems more likely that they result from different actions on microvascular pressure, surface area, and/or permeability to plasma proteins. Prior hypotension produced either by acetylcholine, systemically infused histamine, or arterial hemorrhage almost completely prevents the increase in skin lymph flow and lymph protein concentration by histamine infused locally into the brachial artery, even in forelimbs perfused at constant flow.

Digital vascular pressures, blood flow, and vascular resistances were measured in 11 control ponies and in 8 animals (7 ponies and 1 horse) affected with laminitis created by feeding a high starch ration. Animals with laminitis had increased digital blood flow, increased arterial, small vein, and large vein pressures, and decreased vascular resistances. Comparison of digital lymph flow rates and protein concentrations in animals with laminitis and control animals revealed no differences. Digital vascular responses of the 2 groups to acetylcholine, epinephrine, histamine, or serotonin also did not differ. Thus, the increased digital blood flow observed in animals with laminitis could not be attributed to altered responsivenss to the previously mentioned vasoactive agents. The studies also provided no evidence for increased capillary permeability in digits of animals affected with laminitis.

The aim of this study was to determine if edema develops in the canine forelimb after relief of prolonged ischemia. Two hours of ischemia was induced either by interrupting brachial artery inflow in collateral-free innervated, naturally and constantly perfused preparations or by applying a pressure cuff in intact preparations. Changes in extravascular fluid volume were inferred from changes in limb weight. Relief of ischemia produced a transient 1.7% increase in weight in the collateral-free, naturally perfused preparation but had no effect on weight in the collateral-free, constantly perfused or intact preparations. Skin lymph flow failed to change significantly and total lymph protein concentration increased only slightly. Thus, relief of 2 hr of ischemia does not produce marked edema or a large increase in microvascular permeability to plasma proteins in the dog forelimb.

1. Eight mongrel dogs were anaesthetized with sodium thiamylal and chloralose-urethane, ventilated, vagotomized and heparinized. Five Poland-China pigs were anaesthetized with sodium thiamylal and nitrous oxide, ventilated, vagotomized and heparinized. 2. Extracorporeal perfusion of the right coronary artery at constant pressure (100 mmHg) was instituted. A lung from a donor animal was interposed in the coronary perfusion circuit to effect changes in CO2 and O2 tensions in the coronary arterial blood while systemic blood gases were maintained at normal levels. 3. Local hypoxia (PO2 range 17-22 mmHg) produced a 25-75% decrease in coronary vascular resistance (P less than 0.05) and a 0-24% (not significant) decrease in right ventricular dP/dt. 4. Local changes in PCO2 over the range 8-105 mmHg were associated with a 17-58% decrease in coronary vascular resistance (P less than 0.05), a 19-24% decrease in right ventricular dP/dt (P less than 0.05) with no change in right ventricular end-diastolic pressure, and a 1-18% (not significant) decrease in heart rate. 5. These studies suggest that local decreases in O2 or increases in CO2 tensions produce decreases in right coronary vascular resistance that are in the opposite direction to those that would be expected from the observed changes in heart rate and contractility (two primary determinants of myocardial oxygen consumption). 6. These data support the hypothesis that CO2 and O2 are locally vasoactive in the coronary circulation.

Previous studies using bioassay demonstrated the presence of a vasoactive substance or substances in coronary sinus blood during myocardial reactive hyperemia which had, on bioassay, characteristics of adenosine and/or AMP. In the present studies, specific blockers were applied to an improved bioassay system to define more precisely the nature of the substance or substances and to determine whether it also appears during local cardiac hypoxia. In the anesthetized dog, coronary sinus blood was bioassayed in an isolated autologous kidney during reactive and hypoxic dilation. During reactive dilation, the bioassay kidney responded with a large resistance increase which was blocked by theophylline and adenosine deaminase and converted to a decrease by adenosine autoblockade. The same was true for hypoxic dilation, except in this instance, only adenosine deaminase reduced the response (40%). Theophylline and adenosine autoblockade eliminated responses of the bioassay organ to both exogenous adenosine and exogenous AMP, but adenosine deaminase was specific for adenosine. These results confirm that one or more vasoactive substances appear in sinus blood in vasoactive quantities during cardiac reactive dilation, and that the peak concentration correlates roughly with the peak flow. In addition, they show that this also is the case for hypoxic dilation. More importantly, they demonstrate that the substance almost certainly is adenosine in the case of reactive dilation, and that increased adenosine levels also are present during hypoxic dilation, but in addition, suggest that AMP sometimes appears in coronary sinus blood during severe cardiac hypoxia in the dog heart.

Chickens have been reported to have a rate of posthemorrhagic fluid mobilization twice that of mammals and lack a phase of shock irreversible to transfusion. In the present study we measured several hemodynamic and hematologic parameters in chickens subjected to sustained hemorrhagic hypotension. Total peripheral resistance was unaffected or fell slightly and skeletal muscle vascular resistance judged from changes in gastrocnemius resistance was not affected by hemorrhage. Blood compositional changes included a progressive hyperkalemia, hyperglycemia, and hemodilution as evidenced by linear falls in hematocrit, hemoglobin, and plasma total protein concentration. Plasma sodium and osmolality were unchanged, as were arterial pH and oxygen tension; however, there was a fall in carbon dioxide tension. These studies demonstrate that fluid mobilization in the chicken after hemorrhage does not require an increase in precapillary resistance and suggest that, because the chicken does not exhibit intense precapillary constriction, it is spared some of the deleterious effects of inadequate tissue perfusion. Thus, the findings tend to incriminate the peripheral action of the sympathetic nervous system as a major contributor to the development of irreversibility in other species.

This study was designed to evaluate the effects of the sympathetic nervous system on right ventricular and right coronary hemodynamics in the anesthetized vagotomized dog and pig during constant-pressure coronary perfusion. Carotid occlusion in the dog resulted in an increase in heart rate, aortic pressure, right ventricular dP/dt, and a sustained 13% decrease in right coronary artery blood flow and a 14% increase in coronary vascular resistance. This coronary vasoconstriction was not modified during beta-blockade with propranolol but was prevented by alpha- blockade with phentolamine. Similar hemodynamic data was obtained in the pig and, in addition, it was found that the O2 consumption of the right ventricle is low (4.8 +/- 0.4 ml O2.min-1.100 g-1) and is only slightly increased (5.l5 +/- 0.8 ml.min-1.100 g-1) during carotid occlusion. These data suggest that baroreflex-mediated sympathetic stimulation to the heart evokes only a minor increase in metabolic activity in the right ventricular myocardium so that the direct neural (alpha-vasoconstrictor) effect predominates over the metabolic vasodilator mechanism.

An extracorporeal shunt circuit interposed between the left carotid artery and the left coronary ostium employs an electromagnetic flowmeter to measure coronary blood flow in the closed-chest anesthetized dog. Flow may be measured with the animal's arterial pressure as the driving force; introduction of a roller pump, or a roller pump and a negative feedback pressure controller allows for constant flow or constant pressure modes. During occlusion of the circuit or cessation of pump flow, retrograde coronary blood flow can be collected for measurement. The construction of the circuit is relatively simple and inexpensive, using common laboratory materials and a commercially available electromagnetic flowmeter and probe.

We measured the flow rate and protein concentration of lymph collected from a digital lymphatic in eight anesthetized ponies. Additionally, we recorded systemic arterial pressure (Part), and small vein pressure (Psv). Control lymph flow averaged 0.068 ml/min, and contained 3.11 g/100 ml of protein with albumin/globulin ratio of 0.75. Twenty-minute local intra-arterial infusion of acetylcholine (10 mug/min.) elevated Psv but did not increase lymph flow rate or protein concentration. A 60-min local intra-arterial infusion of histamine (10 mug/min) produced a marked sustained increase in Psv and both lymph flow and protein concentration. Edema developed in the digit receiving histamine. These data support the conclusion that in the horse, as in other species, histamine edema is due primarily to a decreased transcapillary colloid osmotic pressure gradient rather than an increased transcapillary hydrostatic pressure gradient.

A commercially available, inexpensive, nose-only exposure chamber was modified to include removable equilibration zones, and the effect of these zones on chamber performance was determined. Since limited performance data were available concerning this unit, a more extensive characterization was performed. EPA limit concentrations (greater than or equal to 5 mg/liter) of toluene vapor or corn oil aerosol, and relatively low concentrations of uranine aerosol (less than or equal to 50 micrograms/liter) were produced by standard techniques. The presence or absence of equilibration zones did not affect the stability or uniformity of toluene vapor atmospheres, with the coefficient of variation (CV) not exceeding 3.33% in all experiments. In contrast, the presence of two equilibration zones was found to progressively enhance the uniformity of the inhalable test aerosols in the animal exposure zone (CV less than or equal to 3.16%). Matrix sampling revealed that in both uranine and corn oil experiments, the center matrix point concentration was consistently lower than samples taken in the actual animal breathing zone. Equilibration zones markedly reduced the difference between breathing zone and center point concentrations. These performance data indicated that the modified ADG nose-only exposure system performed exceptionally well with the materials that were studied. Results were comparable to those describing whole-body chamber performance. The ready availability of this inexpensive prototype lends itself to standardization of techniques between laboratories.

The pressure-flow relationships of collapsible tubes were studied utilizing the Starling resistor model. Reynolds numbers much higher than previously reported were used to simulate high cardiac output states. Alterations which occur in vivo, including longitudinal tension, stretch, tubing diameter, length, and outflow resistance were also simulated and systematically investigated. The pressure-flow curves showed an initial rising phase, a plateau phase, as well as a late-rising phase which has not been reported previously. Self-induced oscillations occurred during the plateau phase and persisted throughout the late-rising phase. These perturbations were markedly increased by longitudinal tension and stretch, but were attenuated by increased diameter, length, and outflow pressure. These instabilities may prove to be an explanation for the "venous hum."

Steady-state collateral resistance (Rcoll), residual volume (RV), and lung pressure-volume (PV) relations were determined in an isolated perfused dog lung as pulmonary venous pressure (Ppv) was increased. Increased Ppv had no effect on the lung PV curve except for a significant increase in RV when Ppv equaled or exceeded 20 Torr. When compared to the value at Ppv = 5 Torr, significant decreases in Rcoll occurred when Ppv was raised to 15 Torr or above at transpulmonary pressure, PL = 0 cmH2O, to 20 Torr or above when PL = 2 cmH2O, and to 25 Torr or above when PL = 4 cmH2O. In most dogs the decrease in Rcoll with increased Ppv could be explained by increased lung volume.