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Biomedical subjects

Ronald W Wood

Publications and source records attributed to Ronald W Wood.

7 recordsLinked to original sources
PubMed2006

Early detection and measurement of urothelial tumors in mice.

OBJECTIVES: To establish reliable noninvasive in vivo methods to detect, measure, and monitor experimentally induced urothelial tumors in mice. METHODS: UPII-SV40T transgenic mice reliably develop bladder tumors by expression of simian virus 40 large T antigen specifically in bladder urothelium through the use of the uroplakin II promoter. Two wild-type and 10 UPII-SV40T transgenic mice were monitored for microhematuria two to three times weekly using dipstick analysis. A unique flat panel detector-based cone beam computed tomography (FPD-CBCT) system imaged the urinary tracts of anesthetized mice after tail vein injection of an iodinated contrast agent (Omnipaque) that is excreted in urine. Within 10 seconds, the FPD-CBCT system acquired 290 two-dimensional images, which produced three-dimensional volumes with true isotropic resolution (180 microm)3 using a filtered back projection-based modified Feldkamp reconstruction algorithm. Amira, version 3.1.1-1, for MacOSX was used for data analysis and advanced visualization of the three-dimensional reconstructed FPD-CBCT images. RESULTS: Hematuria was present in UPII-SV40T transgenic mice at 32 days of age; the wild-type animals exhibited no hematuria. Filling defects, associated with histologically confirmed tumors, in the bladders of the UPII-SV40T transgenic mice were visualized in the reconstructed FPD-CBCT images 1 to 45 minutes after contrast agent injection. Longitudinal FPD-CBCT imaging sessions showed the tumor position, volume, and growth. CONCLUSIONS: The combination of early detection of hematuria and high-resolution in vivo FPD-CBCT imaging of murine bladder tumors enabled accurate longitudinal assessment of tumor growth and progression in individual animals. This approach could provide an important alternative to serial sacrifice experimental designs, while refining statistical power and reducing animal use.

Animals↗
PubMed2006

Initial observations of reduced uroflow in transgenic adenocarcinoma of murine prostate.

OBJECTIVES: To characterize the voiding function in a transgenic adenocarcinoma of murine prostate (TRAMP) mouse of advanced age, because it might provide a useful model of slow-onset bladder outlet obstruction. Spontaneous death from urinary outlet obstruction occurs in the TRAMP mouse. METHODS: A metabolic cage without a fecal separation screen was placed above a precision balance that reported the mass of the excreta pan every 100 ms. A computational algorithm identified voids suitable for uroflow assessment from other excretory events. A series of images were obtained automatically before and during the excretory events. RESULTS: The TRAMP mouse displayed a pulsatile voiding pattern characterized by a reduction in uroflow, prolongation of voiding, and droplet formation at the tip of the prepuce. Postmortem histologic examination revealed gross enlargement of the prostate, a suburethral tumor, dilation of the lumen of the urethra, and proteinaceous debris in the urethra and bladder. CONCLUSIONS: The observed changes were consistent with urethral obstruction induced by prostate enlargement and/or suburethral tumor. Additional studies are required to ascertain whether prostate enlargement per se is sufficient to produce urethral obstruction in the TRAMP mouse. This transgenic mouse strain may provide a model of slow-onset outlet obstruction that is more representative of bladder outlet obstruction caused by benign prostatic hyperplasia than is the obstruction produced by urethral ligation.

Adenocarcinoma↗
PubMed2005

Effects of intradermal foot and forearm capsaicin injections in normal and vulvodynia-afflicted women.

Cutaneous response to capsaicin has been used to assess central sensitization in pain research. This study compared the response to intradermal capsaicin in the forearm and foot of vulvar vestibulitis (vestibulodynia)-afflicted cases and controls. We hypothesized that cases will experience greater spontaneous pain, larger cutaneous areas of punctate hyperalgesia and dynamic allodynia, and greater vascular flow than controls. We also hypothesized enhanced post-injection pain in the foot compared to the forearm based on dermatome proximity of the foot and vulva. Methods. Ten vulvar vestibulitis syndrome (VVS) cases and 10 age and ethnically matched controls underwent two randomized, cross-over trials with intra-dermal injections of capsaicin or a saline placebo in the forearm and foot. Outcome measures included spontaneous pain level, surface area of punctate hyperalgesia, surface area of dynamic allodynia, cutaneous blood flow, regional skin temperature and vital signs. Results. VVS cases experienced greater spontaneous pain, punctate hyperalgesia and dynamic allodynia than pain-free controls. Within the VVS group, post-capsaicin spontaneous pain, punctate hyperalgesia and dynamic allodynia were similar in the forearm and foot. Post-capsaicin blood flow did not differ between cases and controls by anatomic site. Measures of depression and anxiety correlated with spontaneous pain intensity but did not correlate with measures of hyperalgesia, allodynia, or blood flow. VVS cases had higher resting pulse rates and lower resting systolic blood pressures than in controls. Conclusion. VVS patients show enhancement of post-capsaicin pain response extending far beyond the anatomic location of the primary complaint.

Adult↗
PubMed2004

Uroflow in murine urethritis.

OBJECTIVES: To develop a noninvasive method to measure urinary flow rate in the mouse. This could be useful for the study of bladder outlet obstruction, as well as processes affecting detrusor function in the awake animal. Genetically engineered mice can improve our understanding of a variety of human bladder diseases. METHODS: A metabolic cage without a fecal separation screen was placed above a precision balance that reported the mass of the excreta pan every 100 ms. A computational algorithm identified voids suitable for assessment of uroflow from other excretory events. These algorithms were verified by comparison with a series of images obtained automatically before and during the excretory events. Intraurethral acetic acid was used to induce urethritis and to verify the sensitivity of the measurement technique. RESULTS: Automatic categorization and characterization of uroflow was successful. Brief exposures of the urethra of the female C57BL6/J mouse to 2% acetic acid decreased uroflow and increased the void duration without a change in the voided volume. CONCLUSIONS: This method will enable studies of urologic function in mice of differing age, sex, strain, and genetic constitution. Murine urethritis can be differentiated from cystitis, known to be associated with a decrease in voided volume. The observed changes were consistent with urethral obstruction induced by local swelling and inflammation.

Acetic Acid↗
PubMed2003

Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate.

Methylecgonidine is formed from cocaine base when smoked and has been identified in biological fluids of crack smokers. Ecgonidine, a metabolite of methylecgonidine formed via esterase activity, also has been identified in similar samples collected from crack smokers. Methylecgonidine and ecgonidine can be used as biomarkers to differentiate smoking from cocaine use via other routes of administration. We determined the pharmacokinetic properties of methylecgonidine and ecgonidine in sheep after intravenous administration of methylecgonidine at doses of 3.0, 5.6, and 10.0 mg/kg using gas chromatography-mass spectrometric assays. Methylecgonidine clears quickly from blood with a half-life of 18 to 21 min, whereas ecgonidine has a longer half-life of 94 to 137 min. Because ecgonidine clears more slowly, it may be a more effective biomarker of cocaine smoking. The cardiovascular stimulant effects of cocaine contrast with reported in vitro muscarinic agonist effects of methylecgonidine, decreasing contractility and stimulating nitric oxide production in cardiac cells and tissues. To test the hypothesis that methylecgonidine produces cardiovascular effects in vivo consistent with muscarinic agonism, methylecgonidine was administered to sheep intravenously (0.1-3.0 mg/kg) while monitoring heart rate and blood pressure. Significant hypotension and tachycardia occurred in all three sheep. Two of the three sheep demonstrated mild bradycardia 3 to 5 min after methylecgonidine injection. Intravenous pretreatment with atropine methyl bromide (15 microg/kg) antagonized methylecgonidine-induced hypotension in all three sheep, supporting the hypothesis that methylecgonidine acts as a muscarinic agonist in vivo.

Animals↗
PubMed2002

Continuous bladder infusion methods for studying voiding function in the ambulatory mouse.

OBJECTIVES: To develop a method for chronic cannulation of the mouse bladder that would enable repeated intravesical drug delivery and measurement of voiding patterns in unrestrained mice under controlled infusion conditions. METHODS: Fifteen female mice were anesthetized with halothane and implanted with a 3F polyurethane bladder catheter. The catheter exited from the back through mesh and a polysulfone button into a spring coil that protected the catheter and tethered the mouse. A counterbalanced swivel and infusion pump permitted unencumbered mobility during continuous intravesical perfusion. RESULTS: Patent catheterization was consistently achieved for at least 5 weeks. The voiding patterns produced with an infusion pump were stable not only within a study session but also during the course of several weeks. The catheters remained patent but eventually withdrew from the bladder in 9 mice, at which point the mice were killed. The mesh eventually emerged from the skin in 4 animals without evidence of infection and was associated with catheter leakage at the level of mesh exposure. The subcutaneous placement of the mesh and tether assembly adequately transferred torque to the swivel without catheter obstruction. One mouse died unexpectedly during anesthesia; another was killed 1 week after catheter implantation because of an intraperitoneal leak. No bladder stones were identified. The results of the urine cultures were inconclusive. CONCLUSIONS: Continuous, patent catheterization of the murine bladder can be achieved consistently for a period of 5 weeks. When used in combination with counterbalanced swivel assemblies and electronic balance technology, these methods permit prolonged evaluation of micturition patterns in the awake, ambulatory mouse.

Administration, Intravesical↗