A diminazene-resistant strain of Trypanosoma brucei brucei isolated from a dog is cross-resistant to pentamidine in experimentally infected albino rats.

Trypanosomosis is a major cause of mortality for dogs in Nigeria and treatment with diminazene aceturate has steadily become less effective, either as a result of low quality of the locally available diminazene preparations or of drug resistance. To investigate these alternatives, samples of locally obtained drugs were analysed for diminazene aceturate content and a strain of Trypanosoma brucei brucei was isolated from a diminazene-refractory dog in Nsukka, south-eastern Nigeria, and used to infect albino rats. The quality of diminazene aceturate-based preparations was variable, with two preparations containing less than 95% of the stated active compound. Rats infected with T. brucei isolated from the dog were treated 7 and 10 days after infection either with 7 mg/kg diminazene aceturate (intraperitoneally, once) or with 4 mg/kg pentamidine isethionate (intramuscularly, 7 consecutive days). Relapse rates were 100% for both trypanocides in the groups of rat treated 10 days post-infection, and 83% and 50% of rats treated 7 days after infection relapsed to diminazene aceturate and pentamidine isethionate, respectively. Careful consideration of physiological parameters showed that pentamidine was only marginally superior to diminazene aceturate as applied in this study. It was concluded that dogs in Nigeria are infected with genuinely diminazene aceturate-resistant trypanosomes that appear to be cross-resistant to pentamidine isethionate.

Functional, dynamic, and anatomic MR urography: feasibility and preliminary findings.

RATIONALE AND OBJECTIVES: The authors assessed the feasibility of using magnetic resonance (MR) urography to acquire functional, dynamic, and anatomic information in human subjects with normal and hydronephrotic kidneys. MATERIALS AND METHODS: In subjects known to have or suspected of having hydronephrosis, split renal filtration fractions were measured with a customized magnetization-prepared, inversion-prepared gradient-recalled echo sequence to determine the T1 of flowing blood in the inferior vena cava and aorta before and after contrast medium administration and in the renal veins and arteries after contrast medium administration. Multiple timed sets of coronal fast spoiled gradient-echo 70 degrees flip-angle images were acquired before and after contrast medium administration to derive MR renograms from changes in the signal intensity of the cortex and medulla. Precontrast T2-weighted images were obtained with a three-dimensional fast spoiled gradient-echo maximum intensity projection pulse sequence, and postcontrast T1 maximum intensity projection images were also obtained to depict the renal anatomy. RESULTS: Split filtration fraction differentiated normal from hydronephrotic kidneys. MR renograms depicted vascular, tubular, and ductal phases and differentiated between normal and hydronephrotic kidneys (P < .05, n = 20). Contrast medium dose correlated with the peak of the cortical signal intensity curves on the renogram (r = 0.7, P < .0005; n = 20). The sensitivities for the visual determination of hydronephrosis and unilateral delayed excretion of contrast material were both 100%, and the specificities were 64% and 85%, respectively. CONCLUSION: The preliminary findings show promise for the use of MR urography in the comprehensive assessment of renal function, dynamics, and anatomy.

Radio-frequency electrocautery ablation of mammary tissue in swine.

PURPOSE: To establish the size, configuration, and histopathologic features of acute, subacute, and chronic radio-frequency (RF) electrocautery of mammary tissue in swine. MATERIALS AND METHODS: Eighteen RF treatments were performed in the mammary tissue of three domestic swine under ultrasonographic (US) guidance. Histopathologic examination was performed immediately after (acute animal); 2 weeks after (subacute animal); and 4 weeks after (chronic animal) treatment. RESULTS: In the acute animal, lesions were firm nodules on palpation and had a distinct line of demarcation between necrotic and viable mammary tissue (mean lesion volume, 14.24 cm(3); largest volume, 29.06 cm(3)). In the subacute animal, there was diffuse coagulation necrosis with neutrophilic infiltrates at the periphery (mean lesion volume, 6.46 cm(3); largest volume, 9.47 cm(3)), and two treatment areas had a secondary bacterial infection. In the chronic animal, lesions were still palpable and firm (mean lesion volume, 11.67 cm(3); largest volume, 25.5 cm(3)), and five of six treatment sites had an area of gray to white fibrotic tissue that blended with the surrounding tissue. However, one site had a pale yellow area of central necrosis surrounded by a fibrotic area. In both the subacute and chronic animals, two and one treatment site, respectively, had minimal areas of skin necrosis. CONCLUSION: RF ablation of breast tissue is feasible in this animal model. Problems included minimal skin erythema, residual firm treatment regions at 4 weeks, slightly variable margins of coagulation necrosis, and occasional bacterial infection.

Novel vascular sealing device for closure of percutaneous vascular access sites.

To investigate the hemostatic capabilities of a novel vascular sealing device consisting of a balloon catheter and procoagulant, vascular sheaths were placed percutaneously in the femoral arteries of dogs. The sealing device was evaluated using the balloon catheter alone in six femoral arteries and with the addition of a procoagulant, in 21 femoral arteries. The balloon catheter alone was successfully deployed in six of six femoral arteries achieving immediate hemostasis. In a second study in which the procoagulant was delivered following balloon placement, the sealing device was successfully deployed and hemostasis was achieved in 20 of 21 attempts (95%) despite removal of the balloon catheter. In a subset of fully anticoagulated animals, hemostasis was achieved in the sealing device-treated arteries at 6.5+/-3.4 minutes, but in none of the controls (P < 0.001). This novel vascular sealing device successfully achieves rapid hemostasis in normal and anticoagulated dogs following percutaneous vascular procedures.

Hepatic ablation using bipolar radiofrequency electrocautery.

RATIONALE AND OBJECTIVES: Percutaneous methods have been used to treat primary and secondary hepatic neoplasms. In the current study, we evaluated the potential of bipolar radiofrequency (RF) electrocautery to increase in vitro liver tissue destruction when compared with monopolar RF electrocautery. METHODS: Two needles (electrodes) were placed into fresh bovine liver tissue for use with bipolar electrocautery. Needle tip exposure was kept constant at 3 cm while other parameters, including treatment time, power (wattage), interneedle distance, and needle tip temperature, were changed. Pathologic and histologic correlation was performed, and tissue necrosis was weighed in grams for individual parameters. RESULTS: There was a minimal threshold of approximately 45 degrees C where tissue coagulation occurred. Tissue coagulation increased the longer treatment went on. Increasing temperature, wattage, or both increased tissue coagulation such that necrosis was too rapid and char formation occurred, which prevented further coagulation. For all wattages and temperatures, there was increasing tissue necrosis with increasing needle separation, until a point at which further needle separation produced less tissue necrosis. Optimizing parameters allowed tissue coagulation of greater than 30 g. CONCLUSION: Bipolar RF electrocautery shows promise for increasing the tissue coagulation in fresh bovine liver compared with the previously described monopolar technique.

Needle aspiration lung biopsy: reevaluation of the blood patch technique in an equine model.

PURPOSE: To reexamine the blood patch technique in a laboratory model of lung biopsy free of confounding clinical variables. MATERIALS AND METHODS: An equine model of lung biopsy was developed with an excised lobe connected to an insufflation bulb and pressure monitor. Patched and control unpatched punctures were made in the lung surface, and the pressure within the lung was raised to the maximum achievable. Whether air leakage from the puncture sites could be induced was determined and, if so, at what pressure it occurred. RESULTS: At statistical analysis with the Kaplan-Meier test and the Cox proportional hazards regression model, the difference between failure of the patched and unpatched punctures was statistically significant (P < .0001). CONCLUSION: The blood patch technique is effective in the laboratory setting and deserves reevaluation in a clinical series with updated biopsy techniques.

Arabinogalactan-coated superparamagnetic iron oxide: effect of particle size in liver MRI.

OBJECTIVE: We evaluated the effect of particle size on MR contrast-enhancing properties of arabinogalactan-coated superparamagnetic iron oxide (AG-SPIO) in tumor-bearing rats. MATERIALS AND METHODS: T2*-weighted gradient-recalled echo MR studies were performed on rats with surgically implanted liver tumors before and after AG-SPIO administration. Contrast-to-noise ratio (CNR) and percent contrast enhancement (PCE) were calculated for animals given small (15.7 +/- 9.5 nm: n = 6), medium (49.1 +/- 19.7 nm; n = 4), and large (86.9 +/- 27.5 nm; n = 4) particles intravenously (10 mumol Fe/kg). RESULTS: Postcontrast CNRs were 15.8 +/- 6.9, 8.9 +/- 4.1, and 10.0 +/- 1.8 for small, medium, and large particle groups, respectively. The PCE was -60.0 +/- 3.3, -75.5 +/- 7.9, and -80.5 +/- 1.2%. There was a significant difference in preversus postcontrast CNR for all particle sizes (p < 0.001) and in PCE for small particles as compared with the two larger sizes (p < 0.001). There was no between-group statistical difference in postcontrast CNR for any particle size. CONCLUSION: Larger AG-SPIO particles slightly improve liver contrast enhancement, but have no significant effect on hepatic lesion detection as assessed by CNR.

Electromagnetic flow measurement using a magnetic resonance imaging static field.

RATIONALE AND OBJECTIVES: Electromagnetic flowmeters have been used for many years as a standard method to determine blood flow in animal models. The use of a modified probe to measure electromagnetic induction in response to an external, large direct current (DC) field magnetic resonance (MR) imaging system was investigated. METHODS: Extracted sheep iliac vessels were inserted into a pumped saline circuit with a modified probe and placed into a 2.0-T MR research imaging system. Voltage readings were collected at various flow rates ranging from 100 to 400 ml/min. Actual flows were measured with a graduated cylinder. RESULTS: A correlation of .937 (p < .001) was observed between the measured voltage changes and the actual flows. Baseline drift was also linear and within specified limits. CONCLUSION: The results indicate that electromagnetic induction in a conductive fluid can be accurately measured using electrodes and an MR imaging system and that this technique provides possible opportunities for in situ flow measurements in humans.

Preclinical evaluation of manganese carbonate particles for magnetic resonance imaging of the liver.

RATIONALE AND OBJECTIVES: We characterized the physical, biological, and imaging properties of a manganese (Mn) carbonate particle suspension, a contrast agent for hepatic magnetic resonance (MR) imaging. METHODS: Mn carbonate suspensions were produced by controlled precipitation and characterized using light microscopy, transmission electron microscopy, and in vitro relaxivity studies. Efficacy of the agent was studied in normal and tumor-bearing rats using T1-weighted MR imaging. RESULTS: Following intravenous injection of Mn carbonate particles at doses ranging from 10 to 100 mumol Mn/kg, peak hepatic contrast enhancement of approximately 35% occurred from about 125 min until the termination of the MR imaging studies that varied from 125 to 305 min. Lesion conspicuity was increased because of relative intensity differences between normal liver and tumor. Data also showed that Mn carbonate particles dissolved on delivery to the liver, allowing Mn to interact with intrahepatic macromolecular complexes to provide positive contrast enhancement. CONCLUSION: Mn carbonate particles produce significant and sustained hepatic enhancement and should improve detection of small or isointense liver lesions.

Percutaneous ultrasound-guided radiofrequency electrocautery ablation of prostate tissue in dogs.

RATIONALE AND OBJECTIVES: We investigated the feasibility of percutaneous radiofrequency (RF) electrocautery in ablation of prostate tissue in dogs. METHODS: We used six dogs in whom a specially designed needle was placed percutaneously into the prostate. RF electrocautery was applied to the needle and treatment was monitored with ultrasound. Animals were sacrificed and gross examination of the prostate and surrounding tissues was performed. Histopathologic examinations of the prostate were also performed. RESULTS: The treatment zone appeared as an elliptical echogenic focus on ultrasound that increased in size with the application of current. Gross and histopathologic correlation demonstrated that the treatment area included a central area of char with a surrounding area of coagulation. There were no deleterious effects to surrounding tissues. CONCLUSION: Our results demonstrate the feasibility of percutaneous ultrasound-guided RF electrocautery ablation of canine prostate tissue.

Refinement of a technique for thermocholecystectomy in an animal model.

RATIONALE AND OBJECTIVES: A modification of a thermal ablation system was tested for improved cystic duct occlusion and gallbladder mucosa ablation in an animal model. METHODS: Fourteen domestic swine were included in group 1 with thermal treatment of the cystic duct to 75 degrees C for 15 minutes, followed by heating of the gallbladder lumen with a catheter/heating device to 54 degrees C for 30 minutes. One swine served as a control (group 2). A ligature was placed around the cystic duct without thermal treatment of the cystic duct and with the catheter/heating device placed into the gallbladder for 30 minutes without thermal treatment. All animals were killed after 3 weeks with histologic examination of the gallbladder, cystic duct, and surrounding organs. RESULTS: In group 1, technical failure due to catheter clogging occurred in the first three animals, which were killed immediately. Eleven animals were treated with a redesigned catheter system. Three weeks after treatment, 10 of the 11 animals had complete cystic duct occlusion and complete obliteration of the cystic duct mucosa. One of the 11 animals experienced partial cystic duct ablation. Nine of the 11 treated animals experienced complete mucosal ablation of the gallbladder. Five of the 11 animals had no residual lumen, whereas 6 of the 11 had a luminal volume that averaged 4 mL compared to 35 mL before treatment. In group 2, the control subject had a gallbladder volume of 50 mL and normal gallbladder and cystic duct mucosa. CONCLUSIONS: This study demonstrates improvement in both cystic duct occlusion and gallbladder mucosa ablation with standardization of the technique for thermocholecystectomy in an animal model. However, a better system is required to promote complete obliteration of the gallbladder lumen.

A new method for thermocholecystectomy. Initial experience and comparison with other techniques.

RATIONALE AND OBJECTIVES: The authors tested the feasibility of thermocholecystectomy for gallbladder ablation in an animal model. METHODS: Thermal treatment of the cystic duct followed by heating of the saline-filled gallbladder using a separately designed heater/expander was performed in 13 pigs (group I). In four animals, heating of the gallbladder alone was performed (group II). Two animals served as controls (group III). All animals were killed 12 weeks after treatment. RESULTS: There was cystic duct occlusion in 10 (77%) of 13 of group I animals. In 6 (60%) of 10 of these animals with cystic duct occlusion, there was complete ablation of the gallbladder mucosa and complete obliteration of the gallbladder lumen. In group II animals, all cystic ducts were intact with an unchanged gallbladder volume in all four animals (100%), and normal gallbladder mucosa were intact in three (75%) of four animals. The gallbladders and cystic ducts in group III animals were normal. CONCLUSIONS: This study demonstrates many technical difficulties with thermal cholecystectomy. However, under ideal conditions, permanent gallbladder ablation is feasible in our animal model using a specially designed heating system.

Bronchial vasodilation by histamine in sheep: characterization of receptor subtype.

Histamine has been shown to mediate features of pulmonary allergic reactions including increased tracheobronchial blood flow. To determine whether the increase in blood flow was due to stimulation of H1- or H2-histamine receptors, we gave histamine base (0.1 micrograms/kg iv) or histamine dihydrochloride as an aerosol (10 breaths of 0.5% "low dose" or 5% "high dose") before and after H1- or H2-receptor antagonists. Blood velocity in the common bronchial branch of the bronchoesophageal artery (Vbr) was continuously measured using a chronically implanted Doppler flow probe. Pretreatment with H2-receptor antagonists cimetidine, ranitidine, or metiamide did not affect the increase in Vbr induced by intravenous histamine [106 +/- 45% (SD)]. Addition of the H1-receptor antagonists diphenhydramine or chlorpheniramine, however, reduced the Vbr response to 16 +/- 22, 21 +/- 28, 23 +/- 23, and 37 +/- 32% of the unblocked responses (P less than 0.05) when intravenous histamine was given at 3, 10, 20, and 30 min, respectively, after the H1 antagonist. At 40, 50, and 60 min the H1-receptor blockade appeared to attenuate, but subsequent continuous infusion of chlorpheniramine (2 mg.kg-1.min-1) then blocked the histamine response for 60 min. Low-dose histamine aerosol did not change mean arterial or pulmonary arterial pressures, cardiac output, or arterial blood gases but increased Vbr transiently from 15.2 +/- 3.4 to 37.6 +/- 8.4 (SE) cm/s. After chlorpheniramine, the Vbr response to histamine, 16.3 +/- 2.2 to 22.6 +/- 3.6 cm/s, was significantly reduced (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic ablation with use of radio-frequency electrocautery in the animal model.

The potential of percutaneous radio-frequency (RF) electrocautery hepatic ablation was evaluated in the animal model. RF hepatic ablation was performed under ultrasound (US) guidance in the liver of 10 swine with use of a specifically designed needle. The needle was placed through the liver capsule, and ablation was performed after isolating the liver at laparotomy. Animals were killed immediately (n = 4), at 1 week (n = 1), 2 weeks (n = 3), or at 5 weeks (n = 2). The US findings were correlated with the pathologic results in the animal livers. RF hepatic ablation was successfully performed in the animal model without complications. Lesions in the animal livers were typically 1 x 2 cm, which initially appeared highly echogenic on US scans. These images corresponded to an area of hepatic necrosis. The lesions became less echogenic shortly after initial treatment but could still be visualized with US at 5 weeks. At histologic study at 5 weeks, the treated livers showed central debris, a larger area of necrotic liver, and a zone of granulation tissue surrounded by a fibrotic capsule. No complications were encountered. RF hepatic ablation shows future promise in treatment of hepatic neoplasms.

The effect of intravenous gadolinium on the magnetic resonance appearance of cerebrospinal fluid.

The authors determined whether a sufficient amount of intravenously administered gadolinium enters the cerebrospinal fluid (CSF) to visibly shorten the T1 relaxation time. Transfer of intravenously administered contrast media into the CSF has been previously documented for iodinated contrast materials; however, the change in computed tomography density is not sufficient to have a clinically useful myelographic effect. Visible shortening of the T1 of CSF on gadolinium-enhanced magnetic resonance imaging of the spine may have clinical use. Twelve dogs were given gadolinium, and CSF was sampled at intervals over a 6-hour period. The T1 values of the CSF samples were quantitated and plotted against time. The average decrease in T1 was 23% at 60 minutes, which is nearly the peak effect. The increased signal intensity was visible at clinical window settings at 60 minutes. It is possible that this may be clinically useful for certain types of examinations. Importantly, this should be recognized as a normal appearance, and not necessarily a sign of pathology.

31P spectroscopy in thrombolytic treatment of experimental cerebral infarct.

Ischemic changes produced by autogenous clot embolization of intracranial arteries were monitored by continuous surface-coil 31P spectroscopy in 12 rabbits: six were used as controls and six were treated intravenously with tissue-type plasminogen activator. The animals were sacrificed and the brains were fixed with intravital stains. The results indicate that spectral changes are reversible only when thrombolysis therapy is started within 30 min after ischemic changes are detected. The improvement of the 31P spectrum correlated with postmortem changes.

Evaluation of recombinant tissue plasminogen activator in embolic stroke.

In an effort to determine the value of tissue-type plasminogen activator (TPA) in the treatment of embolic stroke, 17 rabbits were subjected to a model of embolic stroke in which 2-hour-old, tin-impregnated, autologous clots were embolized to the bifurcation of the internal carotid artery at the circle of Willis via retrograde injection into the cannulated external carotid artery. High-resolution digital subtraction radiography was used to localize clots intracranially at the carotid bifurcation. Circulation through the internal carotid artery and intracranial vessels was monitored with serial digital subtraction angiography before and after embolization and during treatment. Disappearance of the tin marker on the digital subtraction radiograph indicated dissolution of clot and was associated with reestablishment of circulation on the digital subtraction angiogram. Experimental animals were treated with human-specific recombinant TPA 30 minutes, 2 hours, or 4 hours after clot embolization. TPA was administered as an intravenous bolus of 0.5 mg/kg followed by an infusion of 1 mg/kg/h for 2 hours. Digital subtraction angiograms were performed every 30 minutes. All clots dissolved, and cerebral circulation was reestablished within 120 minutes of treatment. In control animals treated with saline, embolized clots were stable, and the internal carotid artery remained occluded. At the completion of each study, the animal was perfused with freshly prepared, buffered 2,3,5-triphenyltetrazolium chloride (TTC) for demarcation of cerebral infarction. Control animals demonstrated infarction of 50 +/- 3.6% of the ipsilateral cerebral hemisphere, with an infarct weight of 2.1 +/- 0.2 g.(ABSTRACT TRUNCATED AT 250 WORDS)

Dissolution of gallstones using methyl tertiary-butyl ether in an animal model.

Human gallstones were surgically implanted in the gallbladders of six pigs. Through cholecystostomy catheters, methyl tertiary-butyl ether (MTBE) was infused from 3 to 5 days. MTBE successfully dissolved 19 of the 20 cholesterol stones and partially dissolved one mixed cholesterol-bilirubin stone. Gross and microscopic examination of abdominal organs revealed mild superficial ulcerations of the gallbladder and mild to moderate chronic inflammatory changes in the gallbladder of animals treated with MTBE infusion. There were no other significant changes within other abdominal organs except for mild inflammation of the duodenum in one animal and of the common bile duct in another. Because of its efficacy and limited deleterious effects, MTBE may be a good solvent when dissolving pure cholesterol gallstones in the gallbladder.