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Biomedical subjects

M Girton

Publications and source records attributed to M Girton.

At least 19 recordsLinked to original sources
PubMed1996

Hyperosmolar blood-brain barrier disruption in baboons: an in vivo study using positron emission tomography and rubidium-82.

Hyperosmolar blood-brain barrier (BBB) disruption remains controversial as an adjuvant therapy to increase delivery of water-soluble compounds to extracellular space in the brain in patients with malignant brain tumors. To understand the physiological effects of BBB disruption more clearly, the authors used positron emission tomography (PET) to study the time course of BBB permeability in response to the potassium analog rubidium-82 (82Rb, halflife 75 seconds) following BBB disruption in anesthetized adult baboons. Mannitol (25%) was injected into the carotid artery and PET scans were performed before and serially at 8-to 15-minute intervals after BBB disruption. The mean influx constant (K1), a measure of permeability-surface area product, in ipsilateral, mannitol-perfused mixed gray- and white-matter brain regions was 4.9 +/-2.4 microliter/min/ml (+/- standard deviation) at baseline and increased more than 100% (delta K1=9.4 +/-5.1 microliter/min/ml, 18 baboons) in brain perfused by mannitol. The effect of BBB disruption on K1 correlated directly with the total amount of mannitol administered (p< 0.005). Vascular permeability returned to baseline with a halftime of 24.0 +/- 14.3 minutes. The mean brain plasma volume rose by 0.57 +/- 0.34 ml/100 ml in ipsilateral perfused brain following BBB disruption. This work provides a basis for the in vivo study of permeability changes induced by BBB disruption in human brain and brain tumors.

Animals↗
PubMed1995

Therapeutic monitoring of experimental invasive pulmonary aspergillosis by ultrafast computerized tomography, a novel, noninvasive method for measuring responses to antifungal therapy.

Pulmonary infiltrates in neutropenic hosts with invasive aspergillosis are due to vascular invasion and hemorrhagic infarction. In order to measure the effect of antifungal compounds on this organism-mediated tissue injury, we monitored the course of pulmonary infiltrates by serial ultrafast computerized tomography (UFCT) in persistently granulocytopenic rabbits with experimental invasive pulmonary aspergillosis. The course of pulmonary lesions measured by serial UFCT scans was compared with those measured by conventional chest radiography, histopathological resolution of lesions, and microbiological clearance of Aspergillus fumigatus. Treatment groups included either amphotericin B colloidal dispersion in dosages of 1, 5, and 10 mg/kg of body weight per day intravenously or conventional desoxycholate amphotericin B at 1 mg/kg/day intravenously. Therapeutic monitoring of pulmonary lesions by UFCT demonstrated a significant dose-response relationship. Lesions continued to progress in untreated controls, whereas lesions in treated rabbits initially increased and then decreased in response to antifungal therapy in a dosage-dependent manner (P < or = 0.05 to P < or = 0.005, depending upon the groups compared). This same trend of resolution of lesions in response to antifungal therapy was also demonstrated by postmortem examination and by microbiological clearance of the organism. These data indicated that amphotericin B colloidal dispersion at 5 and 10 mg/kg/day exerted a more rapid rate of clearance of lesions than conventional amphotericin B. UFCT was more sensitive than conventional chest radiography in detecting lesions due to invasive pulmonary aspergillosis (P < 0.05 to P < 0.005, depending upon the groups compared). These findings establish a correlation among UFCT-defined lesions, microbiological response, and resolution of pathologically defined lesions in experimental invasive pulmonary aspergillosis. Serial monitoring of UFCT-defined lesions of aspergillosis provides a novel system for determining the antifungal response of organism-mediated tissue injury.

Amphotericin B↗
PubMed1988

Meningeal carcinomatosis in the VX2 rabbit tumor model: detection with Gd-DTPA-enhanced MR imaging.

Meningeal carcinomatosis developed in 14 of 14 New Zealand White rabbits after infusion of a VX2 tumor cell suspension into the cisterna magna. All died or were killed 7-15 days after inoculation. Within days of the tumor infusion, magnetic resonance (MR) imaging with gadolinium-diethylenetriaminepentaacetic acid (DTPA) at 0.5 or 1.5 T demonstrated enhancement of the cerebrospinal fluid (CSF) secondary to disruption of the blood-CSF barrier by plaquelike lesions along the meninges. Eventually, meningeal enhancement was observed along the base of the brain and cervical spine. Quantitative assessment of the contrast enhancement on T1-weighted images revealed an increase in mean signal intensity of 213% +/- 130%. Contrast enhancement was not observed in four control animals who received an infusion of cell culture medium. These results demonstrate in an animal model that contrast material-enhanced MR imaging can be used to detect meningeal carcinomatosis by revealing breakdown of the blood-CSF barrier.

Animals↗
PubMed1987

Distribution of iodized oil within the liver after hepatic arterial injection.

Radiography and microscopy were used to investigate the hepatic distribution of iodized oil injected into the hepatic artery in a rabbit VX2 tumor model. Iodized oil accumulates within hepatic metastases and in a ringlike fashion around them. Radiographic and histologic appearances were correlated, and it was concluded that ringlike deposition occurs in peritumoral sinusoids. There was no evidence that iodized oil is cleared by hepatic lymphatics. Early clearance of iodized oil into bile may possibly be caused by localized hepatic ischemia from oil microemboli or by direct phagocytosis by Kupffer cells. The remaining oil is washed through hepatic vasculature, circulates systemically, and is cleared by reticuloendothelial cells in lung, spleen, liver, and bone marrow. This mode of clearance, which has not been considered previously, may be important in the prediction of toxic effects caused by lipid and lipophilic antitumor agents administered via the hepatic artery.

Animals↗
PubMed1987

Ocular and cerebral metastases in the VX2 rabbit tumor model: contrast-enhanced MR imaging.

Ocular and cerebral metastases developed after the inoculation of a VX2 tumor cell suspension into the internal carotid artery of 15 rabbits. The hematogenous spread of tumor cells resulted in ocular metastases in 13 of 15 animals (86.7%) and cerebral system metastases in 14 of 15 animals (93%). Magnetic resonance (MR) imaging with Gd-DTPA demonstrated early disruption of the blood-ocular barrier and blood-brain barrier 5-7 days after infusion of tumor cells. Quantitative assessment of contrast enhancement revealed a mean increase in signal intensity of 145% +/- 51% in the anterior chambers, 102% +/- 70% for choroidal metastases, and 51% +/- 29% for central nervous system (CNS) metastases. These results indicate that contrast-enhanced MR imaging can be used to demonstrate a loss of blood-ocular barrier integrity that is similar to the breakdown of the blood-brain barrier associated with metastatic tumors to the CNS and eye.

Animals↗
PubMed1987

A reproducible model of metastatic brain and ocular tumor by hematogenous inoculation of the VX2 tumor in rabbits.

A metastatic brain-tumor model has been developed in rabbits by infusing the VX2 carcinoma into the internal carotid artery to simulate hematogenous dissemination of tumor. In a series of 25 New Zealand White rabbits, multiple metastases arose in the hemisphere of 24 (96%) and in the eye of 22 (92%); in all instances ocular metastases were ipsilateral to the site of infusion. Ocular metastases were visible in the anterior chamber in 80% of animals 3 to 12 days after the infusion of VX2 tumor cell suspension. All rabbits deteriorated neurologically or died by Day 15 after the inoculation. Multiple metastases were demonstrated by magnetic resonance imaging as early as 5 to 7 days after infusion of the tumor cells and were confirmed at autopsy. This technique models hematogenous metastases to the brain and eye and is useful in evaluating the response of metastases to chemotherapy and radiation therapy directed to the brain and eye.

Animals↗
PubMed1986

Spinal Wada test.

Various doses of pentobarbital (1.25-20 mg) and lidocaine (2.5-20 mg) were injected selectively into the artery of Adamkiewicz and anterior spinal artery of 11 monkeys. Pentobarbital produced an acute paraplegia; lidocaine caused a transient paraplegia followed by hyper-reflexia and muscular fasciculation. Duration of effect varied from 5 to 60 minutes with both drugs and was dose related. Effects were totally reversible. The use of intraarterially administered barbiturates and lidocaine may be more sensitive than angiography for predicting cord blood supply during arteriography for spinal arteriovenous malformations or embolization of critical vessels, such as the right bronchial artery.

Animals↗
PubMed1985

Absolute ethanol injection of the adrenal artery: hypertensive reaction.

Transcatheter injection of 0.4 ml of absolute ethanol into the adrenal artery was performed in three Rhesus monkeys. The injection produced a mean increase of 60 mmHg in systolic blood pressure and 50 mmHg in diastolic blood pressure within two minutes. Hypertension was accompanied by cardiac arrhythmias (two monkeys) and sinus tachycardia (one monkey). These changes were probably related to an acute catecholamine release. Embolization of the inferior phrenic artery with Gelfoam powder produced only a mild blood pressure elevation in three monkeys (6 mmHg systolic pressure and 10 mmHg diastolic pressure).

Adrenal Glands↗
PubMed1985

Lipid emulsions as contrast agents for hepatic sonography: an experimental study in rabbits.

An ultrasound contrast agent capable of increasing hepatic echogenicity would be useful for the detection of hepatic tumors and metastases. Fatty liver is known to produce increased liver echogenicity. Intravenously administered lipid emulsions are phagocytosed by cells of the reticuloendothelial system the liver with transient hepatic lipid accumulation. We examined the effectiveness of three lipid emulsions of differing particle size as potential ultrasound contrast agents using a rabbit liver model. None of the tested emulsions showed any consistent ability to alter liver echogenicity at maximum tolerable doses. Lipid emulsions do not appear to have potential as contrast agents for ultrasound examination of the liver.

Animals↗
PubMed1984

Segmental hyperlucent defects in the liver.

When lucent defects in the liver have a segmental configuration, they may be on an ischemic basis and related to decreased vascular perfusion. Portal venous inflow, by virtue of its low pressure, is particularly susceptible to diversion by focal intrahepatic masses, intravenous thrombi, or external compression. Innovative operative techniques for tumor enucleation may also result in lucent defects that can be confused with, or conceal, pathology. A hypothesis relating such defects to diminished portal inflow and reduced glycogen content is proposed.

Female↗
PubMed1984

Adrenal ablation by retrograde venous ethanol injection: an ineffective and dangerous procedure.

Venous injection of ethanol was used to ablate the left adrenal gland in nine monkeys. Severe hypertension and tachycardia occurred in all animals not pretreated with alpha- or beta-adrenergic blockers. On postmortem examination the left adrenal glands were reduced in size but still retained some normal tissue. This procedure, while technically simple, is neither effective nor safe.

Adrenal Glands↗
PubMed1983

Experimental evaluation of five liver-spleen specific CT contrast agents.

We tested five experimental liver-spleen specific computed tomography (CT) contrast agents, all of which are aqueous emulsions of iodinated vegetable oils. These compounds were compared with ethiodized oil emulsion 13 (EOE-13) and with a 5% dextrose in water control. We evaluated three animal/dose level models with both histology and CT to determine the best screening method for compounds of this type. We compared a rat/high dose model, a rat/medium dose model, and a rabbit/low dose model; the best discrimination was seen with the rabbit/low dose model. Histology of liver, spleen, and lung did not correlate with the attenuation values obtained from CT. We conclude that use of CT and a rabbit/low dose model is superior for screening compounds of this type. Of the compounds tested, only one, an emulsion of ethyl monoiodostearate (compound 208E), approached the effectiveness of EOE-13.

Animals↗
PubMed1983

Hemobilia: computed tomographic diagnosis.

A case of postbiopsy hemobilia is presented in which computed tomographic (CT) scanning showed blood within the gallbladder appearing as high-density material measuring 67-91 HU. Residual clots were seen by CT and ultrasound 8 days after the acute episode. These findings were confirmed by serial CT scans in two monkeys in whom blood was experimentally injected into the gallbladder. When the cystic duct is patent, the diagnosis of hemobilia may be excluded if bile of normal density (0-20 HU) is demonstrated by CT scanning. However, when homogeneous or inhomogeneous material of high attenuation (50+ HU) is present in the gallbladder on CT scanning, the diagnosis of hemobilia is strongly suggested if other causes such as stone or contrast material have been eliminated. CT may show residual blood for days after the acute episode.

Adult↗
PubMed1982

Biodistribution study of Ethiodized Oil Emulsion 13 for computed tomography of the liver and spleen.

Biodistribution studies were conducted with a new intravenous lipoid contrast material currently undergoing clinical trials in four hospitals. The contrast material selectively opacifies the liver and spleen for computed tomographic examination. The experiments were performed on rats with 125I-labeled ethiodized oil emulsion. The study showed that the liver accumulates nearly 80% of the injected iodine within 15 min of the injection and retains a high concentration over 3 h. The second highest concentration was found in the spleen. More than 99% of the iodine is eliminated from the liver and spleen within 48 h, primarily through the kidneys.

Animals↗
PubMed1982

The risk of hepatic artery embolization in the presence of obstructive jaundice.

Rhesus and cynomolgus monkeys were used as experimental subjects to determine the extend to which the presence of biliary obstruction increases the risk of hepatic necrosis following hepatic artery embolization. It was found that peripheral hepatic artery embolization without biliary obstruction resulted in acute hepatic swelling and dysfunction and chronic focal infarction with bile cyst formation. However, massive hepatic necrosis and bile lakes were not seen. Distal common bile duct obstruction unaccompanied by arterial occlusion did not seriously damage the liver, although it was found that distal common duct obstruction in monkeys is not strictly comparable to distal common duct obstruction in humans. When peripheral hepatic artery embolization was performed following ligation of the right or left hepatic ducts at the point of their emergence from the porta hepatis, total infarction of the obstructed segment occurred and a massive bile lake formed. The pathophysiologic explanation is probably the decreased portal venous inflow that accompanies biliary obstruction; hepatic artery inflow reciprocally increases and the liver become critically dependent upon an intact arterial system. Clinical evidence suggests that a liver with a recently decompressed biliary tree may also be more susceptible to infarction and abscess formation following hepatic artery ligation or embolization.

Animals↗
PubMed1980

Clinical trials with a new intravenous liposoluble contrast material for computed tomography of the liver and spleen.

Ten patients with disseminated cancer were given intravenous injections of 0.2 ml/kg (40 mg l/kg) of the experimental contrast material EOE 13. Ct scans of the liver and spleen were taken prior to and 30 minutes after contrast infusion. Visualization of the liver was significantly improved in 5, moderately improved in 3, and not appreciably improved in 2. The spleen showed an obvious increase in density in all cases. No significant toxicity was encountered: untoward side effects consisted of fever, headaches, foul metallic taste, and weakness for a short period. Four patients had no side effects, and 2 experienced only abnormal taste sensation. Further experimental and clinical work is needed before the advantages and safety of this contrast material can be documented.

Autopsy↗
PubMed1979

Formulation and evaluation of ethiodized oil emulsion for intravenous hepatography.

A study was conducted to prepare and evaluate an ethiodized oil emulsion for intravenous administration that would selectively opacify the liver. Several formulations with differing globule size were prepared and compared for their in vivo activity (degree of liver opacification obtained) and stability. Results of studies conducted in rabbits and monkeys revealed that the oil globules that concentrate most in liver were 2.0--3.0 micrometer in diameter. The formulation of choice was stable for 6 months at refrigeration temperature (2--6 degree). In monkeys, this formulation produced an improved diagnostic image of the liver using computerized tomography at a dose of 0.2 ml/kg. The potential use of such emulsions in diagnostic radiology is briefly discussed.

Animals↗