9-Benzyladenines: potent and selective cAMP phosphodiesterase inhibitors

A 6-year-old Quarter Horse gelding with acute onset of a grade-4/5 lameness of the left forelimb 21 days after an encounter with a porcupine was examined. Quills had been removed by the referring veterinarian, and the horse had been treated with antibiotics and hydrotherapy for 14 days. The horse was pyretic and had effusion in the digital synovial sheath. Signs of pain were elicited on palpation of the area. A tentative diagnosis of septic tenosynovitis caused by a porcupine quill was made. Exploratory tenoscopy revealed large amounts of fibrin in the sheath and a 1.2-cm quill. Bacteriologic culture of synovial fluid yielded a pure growth of Staphylococcus aureus. The horse improved dramatically after tenoscopic removal of the quill, debridement of fibrin, and lavage to dilute inflammatory mediators and bacteria, debridement of fibrin, discovery and removal of a quill, and complete evaluation of the sheath for prognostic purposes. Tenoscopy can provide a means for direct observation and enhance the ability of clinicians to debride a septic synovial sheath in a minimally invasive manner.     

Peripheral noxious stimulation induces CREM expression in dorsal horn: involvement of glutamate

Thermal washout curves have been proposed as noninvasive tools for analysing lower airway dimensions and pulmonary blood flow, but how upper airway heat transfer affects these washout curves is unclear. The present study was designed to compare extrathoracic and tracheobronchial contributions to thermal washout curves. Respiratory frequency, air ambient temperature, and body core temperature (tc) were varied in six male subjects before and after immersion in cold (1.1 degrees C) water for up to 2 h under three conditions: 1) control: ambient temperature (tamb) = 25 degrees C, rectal temperature change (delta tre) = 0 degrees C; 2) pre-immersion: tamb = 4 degrees C, delta tre = 0 degrees C; and 3) post-immersion: tamb = 25 degrees C, delta tre = -0.7 degrees C. Both peak expiratory nasal (tpn) and oral (tpo) airstream temperatures were measured. Each subject was tested twice. Expiratory tpo was generally higher than tpn in all conditions. Increasing breathing rates lowered tpn and tpo in the control and cold air environments. Orifice temperatures, which are presumed to reflect upper airway blood temperatures, correlated with both tpn and tpo. Lowering tc had no effect on washout curves during quiet breathing and affected only tpn during rapid breathing. The results suggest that while tracheobronchial conditions may contribute to thermal washout curves, extrathoracic conditions predominate. Strong correlations between orifice temperatures, peak expiratory nasal temperatures and peak expiratory oral temperature demonstrate the dominant role of upper airway heat exchange in determining thermal washout curves.     

Tissue factor pathway inhibitor in endothelial cells colocalizes with glycolipid microdomains/caveolae. Regulatory mechanism(s) of the anticoagulant properties of the endothelium

Tissue factor pathway inhibitor (TFPI), the main downregulator of the procoagulant activity of tissue factor.factor VIIa complex, locates in human endothelial cells (EC) in culture as well-defined clusters uniformly distributed both on the cell surface and intracellularly. We here demonstrate by immunofluorescence that TFPI colocalizes in EC with caveolin, urokinase-type plasminogen activator receptor, and glycosphingolipids. The localization of TFPI in caveolae in resting endothelium is proved by double immunogold electron microscopy for TFPI and caveolin. After ultracentrifugation of rat lung or EC homogenates through density gradients of Nycodenz, TFPI was highly enriched at densities of 1.05 to 1.08 g/mL, together with caveolin and alkaline phosphatase. By ELISA, more than half of the cellular TFPI was detected in Triton X-100-insoluble extracts of EC. TFPI incorporates [1-3H]ethanolamine and is cleaved from the cell surface by phosphatidylinositol-phospholipase C, indicating a specific glycosylphosphatidylinositol-anchorage mechanism for TFPI in the plasma membrane. Clustering of TFPI and its localization in caveolae are dependent on the presence of cholesterol in the membrane. Agonist-induced stimulation of EC caused marked changes of distribution for both TFPI and caveolin at subcellular level, with subsequent increase of the cell surface-associated inhibitory activity toward tissue factor.factor VIIa. Our findings suggest that, beside their function in transcytosis, potocytosis, cell surface proteolysis, and regulation of signal transduction, caveolae also play a direct role in the regulation of EC anticoagulant properties.     

Detection of West Nile virus by the polymerase chain reaction and analysis of nucleotide sequence variation

A polymerase chain reaction (PCR) assay was developed to rapidly detect and identify West Nile (WN) virus. The RNA from seven isolates of WN virus from six countries and four other flaviviruses (Kunjin, Japanese encephalitis, St. Louis encephalitis, and yellow fever viruses) was reverse-transcribed (RT) and amplified by PCR. The nucleotide sequences of the amplified products were determined by a rapid, automated DNA sequencing method. The WN virus RT/PCR assay detected the target gene segment of sequencing method. The WN virus RT/PCR assay detected the target gene segment of isolates from both the African-Middle Eastern group and the Indian group with a sensitivity of approximately 0.05 pg of viral RNA. Kunjin virus was the only other flavivirus tested that produced a band of the appropriate size. Five of seven WN virus isolates showed 92-98% homology in the nucleotide sequence of their PCR products. The sequence of one isolate was virtually identical to the published sequence of the Nigerian isolate (99.5% homology). No correlation was established between the degree of nucleotide homology, geographic location, time of isolation, or source of the isolates.     

The geographic variation of cancer incidence in Ontario

OBJECTIVES: Our objectives were (1) to describe an analysis of the spatial pattern of cancer incidence in Ontario and (2) to discuss the quality of data in the Ontario Cancer Registry with respect to the accuracy of local cancer rates. METHODS: Cancer incidence rates were calculated for 22 cancer sites in 49 counties of Ontario during 1976 to 1986. Capture-recapture methods were used to estimate completeness of case registration, and completeness of residence information was also assessed. Spatial autocorrelation was used in measuring the geographic pattern of incidence rates. Comparisons were also made between sexes and with earlier data from 1966 to 1975. RESULTS: The quality of the geographic data in the registry appeared good, and corrections for incomplete or inaccurate registration had little impact. About one third of the sex-site combinations showed some evidence of spatial patterning in the cancer rate. Particularly strong regional variation was noted for cancers of the stomach, lung, uterus, and prostate. CONCLUSIONS: The analysis revealed a number of cancers with significant spatial patterning of risk. Further work is needed to relate the cancer data to other information on potential life-style and environmental factors.     

Perfluorocarbons are effective oxygen carriers in cardiopulmonary bypass

Intravascular perfluorochemical (PFC) emulsions together with a high oxygen (O2) tension may increase the delivery of dissolved O2 to useful levels. A severely anemic model of cardiopulmonary bypass (CPB) was used to test the hypothesis that a novel PFC emulsion (PFCE; Oxygent [Alliance Pharmaceutical Corp., San Diego, CA] 90% w/v perflubron) used at a high PO2 during bypass delivers sufficient O2 to ameliorate hypoxic myocardial contractile dysfunction. Acutely anemic dogs (N = 42; hematocrit = 15.8 +/- 0.6% [mean +/- SEM] before CPB and 10.9 +/- 0.1% during CPB) were divided into four groups. Group 1 was a control (n = 12). As CPB was initiated, groups 2 (n = 10), 3 (n = 10), and 4 (n = 10) had 1.35 g PFC.kg-1, 2.7 g PFC.kg-1, or 5.4 g PFC.kg-1 added via the venous return cannula. Pre-CPB and post-CPB cardiac function was measured by the first derivative of left ventricular pressure (dP/dtmax). The dP/dtmax on separation from CPB was: group 1, 619 +/- 96; group 2, 738 +/- 56; group 3, 782 +/- 101; and group 4, 828 +/- 100 (p < 0.05 groups 3 and 4 versus group 1). Mortality during the first hour after separation from CPB was higher in group 1 than in PFCE treated dogs; however, this trend did not attain statistical significance (p < 0.065). The PFC dose was higher in survivors than in nonsurvivors (2.6 +/- 0.4 g PFC.kg-1 versus 1.2 +/- 0.5 g PFC.kg-1; p < 0.05). A PFCE used at a high PO2 provides sufficient physically dissolved O2 to relieve myocardial hypoxic injury in a severely anemic model of CPB. Current PFCEs are effective O2 carriers. This finding suggests that they can be used as a temporary erythrocyte substitute to diminish the need for allogeneic transfusions during cardiac operations.