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Biomedical subjects

N M Williams

Publications and source records attributed to N M Williams.

At least 55 records · Page 3Linked to original sources
PubMed1997

Experimental induction of equine protozoal myeloencephalitis in horses using Sarcocystis sp. sporocysts from the opossum (Didelphis virginiana).

Sarcocystis sp. sporocysts isolated from eight feral opossums (Didelphis virginiana) were pooled and fed to 18 commercially reared budgerigars (Melopsittacus undulatus), 14 wild-caught sparrows (Passer domesticus), one wild-caught slate-colored Junco (Junco hyemalis) and five weanling horses (Equus caballus). All budgerigars died within 5 weeks post inoculation (wpi). Histologic examination revealed meronts within the pulmonary epithelia and typical Sarcocystis falcatula sarcocysts developing in the leg muscles. Sparrows were euthanized 13 and 17 wpi and their carcasses were fed to four laboratory raised opossums. Sporocysts were detected in the feces of two opossums on 15 days post inoculation (dpi) and in a third opossum on 40 dpi. Fecal samples from the fourth opossum remained negative; however, sporocysts were found in intestinal digests from all four opossums. Sporocysts were not found in feces or intestinal digest of an additional opossum that was fed three uninoculated sparrows. Five foals were fed sporocysts (Foals 2, 3, 4, 5, and 7) and two foals were maintained as uninoculated controls (Foals 1 and 6). Sporocysts from two additional feral opossums also were fed to foals. Foal 5 was given 0.05 mg kg-1 dexamethasone sodium phosphate daily beginning 2 days before inoculation for a total of 2 weeks. Horse sera were tested three times per week, and cerebrospinal fluid (CSF) samples were tested biweekly for anti-Sarcocystis neurona antibodies by Western blot analysis. No foals had any S. neurona-specific antibodies by Western blot analysis prior to sporocysts ingestion. Seroconversion occurred in Foals 3, 5, and 7 by 24 dpi, followed by positive CSF tests on 28 dpi. Foals 2 and 4 seroconverted by 40 dpi. Cerebrospinal fluid from Foal 2 tested positive by 42 dpi, but Foal 4 remained seronegative throughout the study. Sera and CSF from control Foals 1 and 6 remained seronegative. All foals with positive CSF developed neurologic clinical signs. Neurologic disease was evident in Foals 2 and 3 by 42 dpi and in Foal 7 by 28 dpi. The severity of clinical signs progressed to marked spasticity, hypermetria and ataxia in Foal 7 by the end of the trial. Necropsy examination of inoculated foals did not reveal gross lesions; however, microscopic lesions consistent with equine protozoal myeloencephalitis (EPM) were found in Foals 2, 3, and 7. Protozoa were not observed in the tissue sections. Microscopic lesions consistent with EPM were not found in Foals 4 and 5 or in uninoculated control Foals 1 and 6. Foal 5 had unilateral non-inflammatory lesions in the cervical and thoracic spinal cord consistent with cord compression. These data indicate that the opossum is a definitive host of S. neurona.

Animals↗
PubMed1997

Renal metastasis. Detection and characterization on enhanced magnetic resonance imaging using an animal model.

RATIONALE AND OBJECTIVES: A new animal model was developed in rabbits (renal metastasis using the VX-2 tumor line), and magnetic resonance (MR) imaging performed before and after intravenous gadoteridol injection to assess lesion conspicuity and characterization. METHODS: Six New Zealand White rabbits with renal metastases were studied on a 1.5-tesla Siemens Vision MR unit. Iodinated contrast was given intravenously to the rabbits, before implantation, to visualize the kidneys under fluoroscopy. Using a 5/8-inch 25-gauge needle, 0.1 mL of minced, screened VX-2 tumor was injected percutaneously into each kidney at the corticomedullary junction. Animals were studied on day 7 after implantation. Baseline fast low-angle shot (FLASH) T1-weighted and fast spin echo T2-weighted breathhold scans were first obtained. Then, an additional precontrast turbo-FLASH T1-weighted scan was acquired. After these scans, 0.1 mmol/kg gadoteridol (gadolinium HP-D03A; ProHance) was injected intravenously at a rate of 1.5 mL/second. Dynamic breathhold turbo-FLASH T1 images were then obtained at 0, 6, 12, 19, 25, and 31 seconds after injection and at 1, 2, and 10 minutes after injection. The T1 multislice FLASH two-dimensional scan was repeated at 10 minutes after contrast. Imaging results were analyzed by region of interest measurement and correlated with tissue pathology. RESULTS: On dynamic T1-weighted turbo-FLASH scans, lesion conspicuity, specifically (SI(kidney)-SI(tumor)/noise), increased from 7 +/- 7 signal intensity precontrast to a maximum of 14 +/- 8 at 1 minute after contrast. This increase was statistically significant (P = 0.002). An initial rapid increase in tumor conspicuity occurred within the first 30 seconds after contrast, with the curve flattening thereafter. Lesion conspicuity on the precontrast T2-weighted scans was 9 +/- 10, not statistically different from results with either of the precontrast T1-weighted scan techniques. Using T1-weighted FLASH technique, lesion conspicuity increased from 10 +/- 5 precontrast to 31 +/- 12 postcontrast. As with turbo-FLASH, the improvement in tumor conspicuity after contrast on FLASH scans was statistically significant (P = 0.02). The difference between postcontrast FLASH scans and precontrast T2-weighted scans also was statistically significant, with postcontrast scans superior for lesion conspicuity (P = 0.01). Each tumor was confirmed on pathologic exam. CONCLUSIONS: This research establishes a model of metastasis to the kidney for use in imaging studies. The conspicuity of a small renal metastasis is shown to be improved on early dynamic imaging, as well as at 10 minutes after intravenous injection of 0.1 mmol/kg gadoteridol. Observation of dynamic signal intensity changes provides additional information regarding lesion characterization, supplementing that from precontrast scans.

Animals↗
PubMed1997

Detectability of small liver metastases with gadolinium BOPTA.

RATIONALE AND OBJECTIVES: The ability to detect small liver metastases was evaluated with both gadolinium Gd BOPTA and Gd HP-DO3A on high-field (1.5 tesla [T]) magnetic resonance (MR) imaging using a rabbit tumor model. METHODS: Five New Zealand White rabbits with metastatic liver disease (VX-2 adenocarcinoma) were imaged on a 1.5 T Siemens Vision MR system. Magnetic resonance studies were obtained in each animal on days 8 and 9 after tumor implantation. Each animal was studied twice, once after injection of 0.3 mmol/kg Gd HP-DO3A (gadoteridol or ProHance) and once after injection of 0.1 mmol/kg Gd BOPTA (gadobenate dimeglumine or MultiHance). The order of injection for the two agents was randomized with the two studies in any one animal separated by 24 hours to allow for clearance. Magnetic resonance image acquisition was performed in all cases with suspended respiration. Baseline two-dimensional FLASH T1-weighted and turbo-spin echo T2-weighted scans were acquired first. The contrast was then administered as an intravenous bolus. T1-weighted scans were acquired at 1, 5, 15, 30, 45, and 60 minutes after administration of Gd BOPTA and 1, 5, and 15 minutes after administration of Gd HP-DO3A. Each rabbit was killed after completion of imaging, their liver removed and taken to the veterinarian at the University's animal disease diagnostic laboratory for lesion confirmation. RESULTS: Despite acquisition of precontrast T2-weighted scans, lesions could not be identified with certainty in four of five animals in the Gd HP-DO3A study. Normal liver signal intensity increased from 895 +/- 17 to a peak of 1384 +/- 50 at 1 minute after Gd HP-DO3A administration. After Gd BOPTA administration, normal liver signal intensity increased from 899 +/- 105 to a peak of 1433 +/- 76 at 15 minutes. Liver enhancement thereafter decreased gradually to 1297 +/- 84 at 60 minutes. The injection of 0.3 mmol/kg Gd HP-DO3A resulted in parenchymal enhancement, which was statistically superior (P < 0.01) to an injection of 0.1 mmol/kg Gd BOPTA at 1 minute, not statistically different at 5 minutes, and inferior (P < 0.02) at 15 minutes. From region of interest measurements, lesion detectability was statistically superior on scans at 15 to 60 minutes after Gd BOPTA administration compared with precontrast T1- and T2-weighted scans (P values: < 0.03- < 0.005). Lesion detectability was maximum at 30 minutes postcontrast (15.2 +/- 4.5), markedly superior to that precontrast on both T1- (5.7 +/- 5.0) and T2-weighted scans (7.2 +/- 1.5). On masked film review of the Gd BOPTA case set, no lesions were noted prospectively on T2-weighted scans. Lesions in all five animals were well visualized on scans 45 to 60 minutes after Gd BOPTA administration. The Gd HP-DO3A case set was not read masked, as lesions could be identified only in one of the five animals with all films available for inspection. An additional feature of scans with Gd BOPTA (used at a dose of 0.1 mmol/kg), in distinction to those with Gd HP-DO3A (used at a dose of 0.3 mmol/kg), was the diminished enhancement of hepatic vessels. CONCLUSIONS: Using a rabbit model, small metastatic lesions (diameter, 2-4 mm) were well visualized on delayed postcontrast Gd BOPTA scans. These lesions could not be diagnosed prospectively on T2-weighted images. In only one of five animals were lesions detected on early dynamic post-contrast high-dose Gd HP-DO3A scans.

Adenocarcinoma↗
PubMed1997

Contrast-enhanced magnetic resonance imaging in a spinal epidural tumor model.

RATIONALE AND OBJECTIVES: A spinal epidural tumor model was developed, using the VX-2 adenocarcinoma in rabbits, to assess the strengths and weaknesses of magnetic resonance (MR) as a cross-sectional imaging modality for the evaluation of epidural neoplastic disease. High-resolution MR images were acquired both before and after intravenous gadolinium chelate injection, assessing lesion detectability and efficacy of imaging technique. METHODS: An adenocarcinoma tumor (VX-2) was produced in the epidural space of six New Zealand White rabbits and subsequently studied on a 1.5 tesla whole body MR scanner. VX-2 tumor tissue was removed from the thigh of a carrier rabbit, minced, and screened. Under fluoroscopic guidance, 0.2 mL of the tumor preparation was then injected into the epidural space of the experimental rabbits. The injection was performed at the L5-6 level using an epidural needle and polyethylene tubing sleeved within the needle. The rabbits were imaged using a circular small parts surface coil 5 to 15 days after the epidural injection. In all six animals, one complete MR exam was obtained within the time frame of days 9 to 11. T1- and T2-weighted axial scans were obtained before contrast injection, with the T1 scans acquired both with and without fat saturation. Postcontrast T1 scans also were obtained, using fat saturation, after the injection of 0.1 and 0.3 (cumulative dose) mmol/kg gadoteridol (Gd HP-DO3A; ProHance) in all animals. The film images were interpreted in a prospective fashion by a single neuroradiologist who was masked to imaging technique and contrast dosing. The digital data was analyzed by region of interest measurement. At the end of the imaging studies, the animals were sacrificed and the epidural lesion confirmed by gross and microscopic exam. RESULTS: On a prospective masked read of the MR films, epidural tumor was depicted best on postcontrast fat saturation T1-weighted scans using a cumulative contrast dose of 0.3 mmol/kg. Substantial contrast enhancement of the tumor was observed in all instances on postcontrast scans. The precontrast T1-weighted scan was least efficacious for lesion identification and differentiation from the compressed spinal cord. Depending on the pulse sequence used, one (T2-weighted) to three (T1-weighted without fat saturation) of the lesions could not be identified prospectively on precontrast scans. Lesion growth with time after implantation was chronicled by MR imaging, accompanied by progression of symptoms. On region of interest analysis, differentiation of epidural tumor from normal cord was greatest (11.6 +/- 6.1) on postcontrast scans using a cumulative contrast dose of 0.3 mmol/kg. The level of differentiation achieved was twice that of postcontrast scans using a contrast dose of 0.1 mmol/kg (5.9 +/- 3.6). These results were superior on statistical analysis to that with all other scan techniques (P = 0.002-0.0005). Cord and tumor could not be differentiated on the basis of signal intensity, with any statistical significance, using precontrast T1 and T2 scans. The lesions were confirmed in each animal by gross and microscopic exam. On inspection of the gross specimen, the tumors were noted to be located in the epidural space and to cause cord compression. On microscopic exam, the tumor was composed of epithelial cells that were moderately pleomorphic. CONCLUSIONS: In the New Zealand White rabbit, an epidural tumor could be created consistently using the described percutaneous approach. These lesions are suitable for MR imaging studies, examining lesion detectability and efficacy of imaging technique. The lesions created in the current study could not be diagnosed prospectively in all cases on precontrast T1 and T2 scans images. Postcontrast scans were most efficacious for diagnosis and lesion delineation, with high-dose (0.3 mmol/kg) scans superior to standard dose (0.1 mmol/kg).

Adenocarcinoma↗
PubMed1997

Magnetic resonance imaging of experimental pyelonephritis in rabbits.

RATIONALE AND OBJECTIVES: An experimental model of acute focal pyelonephritis was developed in the New Zealand White rabbit, with initial imaging evaluation performed using high-field contrast-enhanced magnetic resonance (MR) in six animals. METHODS: The left kidney was visualized fluoroscopically after intravenous injection of iodinated contrast. A 0.1 mL mixture of agarose/Streptococcus faecalis was then injected percutaneously into the kidney at the corticomedullary junction with a 25-gauge needle. The animals were imaged at 1.5 tesla on day 5 after injection of bacteria. Breathhold T2-weighted and T1-weighted scans were acquired prior to contrast injection. Using an MR-compatible power injector, 0.3 mmol/kg gadoteridol was then administered, with both dynamic and delayed postcontrast scans obtained. The lesion was confirmed in each animal by gross and microscopic exam. RESULTS: The area of acute focal pyelonephritis was somewhat difficult to identify on precontrast scans. The lesion was mildly hyperintense on T2-weighted scans and slightly hypointense to isointense on T1-weighted scans relative to normal surrounding renal parenchyma. On early dynamic turbo-fast low-angle shot scans, the lesion could be identified due to differential tissue enhancement. Direct visualization of the lesion, with increased conspicuity relative to precontrast scans, was possible because of delayed positive enhancement at 60 seconds postcontrast. Lesion conspicuity, assessed by signal difference/noise ratio, increased from 0 +/- 5 precontrast to a peak of 12 +/- 6 at 60 seconds postcontrast (P = 0.003; n = 6). CONCLUSIONS: On dynamic contrast-enhanced MR, acute focal pyelonephritis can demonstrate transient positive contrast enhancement (using a contrast dose of 0.3 mmol/kg) relative to surrounding normal renal parenchyma. This appearance is due to hyperconcentration of the contrast agent in normal parenchyma and T2 effects. The pattern is opposite that seen in spiral computed tomography.

Acute Disease↗
PubMed1997

Association between schizophrenia and a microsatellite polymorphism at the dopamine D5 receptor gene.

An association study of 97 patients with DSM-III-R schizophrenia and 97 matched controls was performed using a polymorphic microsatellite repeat at the dopamine D5 receptor gene. We observed a significant difference between the allele frequencies of patients and controls (chi 2 = 23.4, df = 12, p = 0.019). This reflects an excess of allele 4 (140 bp) in the patients when compared with the control sample (chi 2 = 7.087, p < 0.01; odds ratio = 2.98, 95% CI 1.29-6.86). However, this association remains tentative until confirmation in other samples.

Alleles↗
PubMed1997

Spontaneous pneumoperitoneum and other nonsurgical causes of intraperitoneal free gas.

Intraperitoneal free gas seen radiologically as air under the diaphragm nearly always indicates a perforated abdominal viscus that requires surgical intervention. Rarely, however, the presence of a pneumoperitoneum may not indicate an intra-abdominal perforation and thus may not require laparotomy. Such a situation is termed spontaneous or nonsurgical pneumoperitoneum. In this review, we explore the aetiological mechanisms and the pathophysiology of the appearance of intra-abdominal free gas. An appreciation of the condition and its likely aetiological factors should improve awareness and possibly reduce the imperative to perform an emergency laparotomy on an otherwise well patient with an unexplained pneumoperitoneum.

Child↗
PubMed1997

Immunohistochemical analysis of the proapoptotic protein Par-4 in normal rat tissues.

Prostate apoptosis response 4 (par-4) is a recently identified gene that encodes a transcription factor, Par-4, with a leucine zipper domain. Par-4 protein is constitutively expressed in various cell lines and is functionally required but not sufficient for apoptosis. Induction of Par-4 in cultured cells is found exclusively during apoptosis, and ectopic overexpression of Par-4 enhances the potency of apoptotic stimuli. Western or Northern blot analysis on mRNA or protein extracts, respectively, from rat organs revealed that the expression of Par-4 was ubiquitous and was not restricted to any specific organ(s). To further identify specific cell types that expressed Par-4, we performed an immunohistochemical analysis of the protein in paraffin-embedded sections of various organs from rats. Our findings indicated that consistent with its proapoptotic role, Par-4 is expressed in apoptotic granulosa cells of atretic ovarian follicles and in terminally differentiated cells, such as the cardiomyocytes, cerebellar Purkinje cells, and pyramidal cells of the hypothalamus. Moreover, testosterone ablation by castration of rats caused an early and transient induction of Par-4 in the ductal cells of the prostate that undergo apoptosis. By contrast, in tissues in which the cells could be visually differentiated from their mature counterparts, Par-4 expression was lowest in the mature cells. This was the case for epithelia of the mammary and the prostate gland in which the basal cells maintained higher protein levels of Par-4 than did the terminally differentiated ductal cells. Similarly, cells of the stratum corneum of the skin and cells on top of the duodenal villi stained less intensely for Par-4 as compared to the stem cells in the stratum basale and at the bottom of the crypts of Lieberkühn, respectively. It is possible that Par-4 has to be down-regulated for successful differentiation in these tissues. Taken together, the widespread expression of Par-4 in various adult cell types underscores the physiological importance of the protein. The observation of constitutive Par-4 expression in the stem cell compartments is inconsistent with the probability of apoptosis per se and can be extended to determine whether Par-4 plays a role in other cellular processes.

Animals↗
PubMed1996

Evaluation of gadolinium 2,5-BPA-DO3A, a new macrocyclic hepatobiliary chelate, in normal liver and metastatic disease on high field magnetic resonance imaging.

RATIONALE AND OBJECTIVES: A new hepatobiliary gadolinium chelate, gadolinium (Gd) 2,5-BPA-DO3A, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved extracellular contrast agent, and Gd Cy2-DOTA, a second hepatobiliary chelate in preclinical development. The ligand in Gd 2,5-BPA-DO3A is macrocyclic in nature, as opposed to the linear structure of Gd DTPA. Gadolinium 2,5-BPA-DO3A was evaluated on magnetic resonance imaging at 1.5 T, examining specifically liver parenchymal enhancement and lesion delineation, the latter in metastatic disease. METHODS: Gadolinium 2,5-BPA-DO3A was evaluated in five normal rhesus monkeys and four New Zealand White rabbits with implanted VX-2 liver tumors. These studies were compared with magnetic resonance exams in the same animals using Gd HP-DO3A and Gd Cy2-DOTA. A contrast dose of 0.1 mmol/kg intravenous was employed in each instance, with the sequence of administration (for the three agents) randomized and at least 72 hours between injections. Spin echo breathhold T1-weighted scans were obtained before and at multiple times after contrast administration. Postcontrast scans were acquired from 1 to 60 minutes after injection in the monkeys and from 1 to 240 minutes in the rabbits. RESULTS: Enhancement of normal liver parenchyma was markedly superior with Gd 2,5-BPA-DO3A compared with Gd HP-DO3A and Gd Cy2-DOTA in both monkeys and rabbits. At 2 and 60 minutes after contrast administration, the liver signal intensity in the monkey was 452 +/- 56 and 440 +/- 69 with Gd 2,5-BPA-DO3A compared with 295 +/- 34 and 256 +/- 38 with Gd HP-DO3A. The difference between agents was statistically significant at all postcontrast time points in the rhesus monkey. Excretion of contrast into the gall bladder was consistently observed after Gd 2,5-BPA-DO3A injection in both animal species. Maximum lesion conspicuity occurred in the rabbit at 45 minutes after Gd 2,5-BPA-DO3A administration. At 45 minutes postinjection, liver-lesion contrast was 0.60 +/- 0.15 with Gd 2,5-BPA-DO3A, 0.35 +/- 0.11 with Gd Cy2-DOTA, and 0.12 +/- 0.04 with Gd HP-DO3A, with the differences between agents being statistically significant. CONCLUSIONS: Gadolinium 2,5-BPA-DO3A is superior to both Gd Cy2-DOTA and Gd HP-DO3A in the degree of enhancement of normal liver parenchyma achieved after intravenous injection. This leads to improved liver lesion delineation with Gd 2,5-BPA-DO3A on delayed postcontrast magnetic resonance scans.

Animals↗
PubMed1996

The use of gadolinium-BOPTA on magnetic resonance imaging in brain infection.

RATIONALE AND OBJECTIVES: The use of gadolinium (Gd)-BOPTA as a magnetic resonance contrast agent for central nervous system disease was studied in a canine brain abscess model. METHODS: A Streptococcus faecalis brain abscess was evaluated in five dogs at 1.5T. Imaging was performed during the late cerebritis stage, at 5 to 7 days after surgery. Magnetic resonance scans were acquired before and at 1, 5, 15, 30, 45, and 60 minutes after contrast administration, using a dose of 0.1 mmol/kg. Scans also were acquired both before and after contrast injection with the implementation of magnetization transfer. RESULTS: Lesion enhancement, quantified by region-of-interest measurement, peaked at 5 minutes after contrast injection. Both the increase in lesion enhancement from 1 to 5 minutes after injection and the decrease from 5 to 15 minutes after injection, although small, were statistically significant (P < 0.004 and P < 0.03, respectively). The application of magnetization transfer improved lesion enhancement, as measured by signal difference/noise, by 39%. This result also was statistically significant (P < 0.001). CONCLUSIONS: In intraparenchymal brain infection, Gd-BOPTA provides effective lesion enhancement when used at a dose of 0.1 mmol/kg. Further research is needed to compare the magnitude of enhancement achieved with Gd-BOPTA, which has weak protein binding and both hepatobiliary and renal excretion, with that with Gd chelates, which have pure renal excretion.

Animals↗
PubMed1996

Early dynamic magnetic resonance imaging of liver metastases with 0.3 and 0.6 mmol/kg gadoteridol injection.

RATIONALE AND OBJECTIVES: The potential for improvement in liver-lesion conspicuity on early dynamic scans after bolus intravenous gadolinium (Gd) chelate administration was evaluated using gadoteridol (Gd-HP-DO3A; Prohance) at doses of 0.3 and 0.6 mmol/kg. METHODS: Five New Zealand white rabbits with focal VX-2 adenocarcinoma liver metastases were studied on a 1.5-tesla Siemens Vision scanner. Each rabbit was imaged twice (on two separate days), after injections of 0.3 mmol/kg and 0.6 mmol/ kg Gd-HP-DO3A. The contrast dose (0.3 or 0.6 mmol/kg) was given as a single intravenous injection. The order of injection for the two doses was randomized, with the two studies (in any one rabbit) separated by 24 hours to allow for clearance. Contrast was administered using an autoinjector at a rate of 1.5 mL/second. Turbo-fast low-angle shot scans were obtained before and at 6, 12, 19, 25, 31, 60, 120, 180, 240, 300, and 600 seconds after contrast injection. The lesions were confirmed, after killing the rabbit, by gross and microscopic examination. RESULTS: The enhancement of normal liver parenchyma, assessed by (SIt-SIo)/SIo.100, (SI = signal intensity) peaked at 32% +/- 4% 19 seconds after injection of 0.3 mmol/kg and at 38% +/- 5% 31 seconds after injection of 0.6 mmol/kg. The difference in maximum parenchymal enhancement achieved, comparing the 0.3 and 0.6 mmol/kg doses, was statistically significant (P < 0.03). Lesion conspicuity, specifically (SIliver-SIlesion/noise), increased from 4.5 +/- 2.3 precontrast to a maximum of 6.8 +/- 1.2 at 19 seconds postcontrast using a dose of 0.3 mmol/kg, with the difference statistically significant (P < 0.03). The increase with a dose of 0.6 mmol/kg was from 4.2 +/- 0.7 to 6.5 +/- 1.9 with this difference also statistically significant (P < 0.02). There was no statistically significant difference in lesion conspicuity between the doses of 0.3 and 0.6 mmol/kg. CONCLUSIONS: Conspicuity of liver metastases can be improved substantially with dynamic magnetic resonance imaging and rapid intravenous bolus contrast injection with a dose of 0.3 mmol/kg. No further improvement is noted at a dose of 0.6 mmol/kg, despite greater positive contrast enhancement of normal liver parenchyma.

Adenocarcinoma↗
PubMed1996

Hepatic abscesses. Magnetic resonance imaging findings using gadolinium-BOPTA.

RATIONALE AND OBJECTIVES: Gadolinium (Gd)-BOPTA was evaluated in a rabbit liver abscess model and compared with Gd-HP-DO3A, examining lesion conspicuity and characterization. METHODS: Five New Zealand White rabbits with a liver abscess were studied on a 1.5-tesla Siemens Vision magnetic resonance unit. The disease model was created by surgically implanting a gel capsule filled with fusobacterium into the central or left lobe of the liver. For imaging, the animals were ventilated using a Harvard pump. Pancuronium bromide (0.12 mg/kg) was administered to allow acquisition of breath-hold scans. Magnetic resonance scans were obtained in each animal on days 2 and 3 after surgery. Every animal was studied twice, once after intravenous injection of 0.3 mmol/kg Gd-HP-DO3A (gadoteridol; ProHance) and once after intravenous injection of 0.1 mmol/kg Gd-BOPTA (gadobenate dimeglumine; MultiHance). The order of injection for the two agents was randomized with the two studies in each animal, separated by 24 hours to permit clearance. Image acquisition was performed in each instance with respiration suspended. Baseline two-dimensional spin-echo T1-weighted and fast spin-echo T2-weighted breath-hold scans were obtained first. The voxel dimensions were 5 x 0.8 x 0.8 mm3. Imaging times were 23 seconds for the T1-weighted scan and 26 seconds for the T2-weighted scan. Postcontrast scans, using spin-echo T1-weighted technique, were obtained at 1, 3, 5, and 15 minutes after contrast injection, whether Gd-HP-DO3A or Gd-BOPTA was used. Additional scans were obtained at 30, 45, and 60 minutes after Gd-BOPTA administration. At the completion of imaging on day 3, each animal was killed and the liver was removed and taken to a veterinary pathologist at the University's animal disease diagnostic lab for gross and histologic examination. RESULTS: The enhancement of normal liver parenchyma, assessed by region of interest measurement and specifically as (SI(t) - SI0)/SI0 x 100, peaked at 119 +/- 37% 1 minute after injection of 0.3 mmol/kg Gd-HP-DO3A and at 126 +/- 30% 30 minutes after injection of 0.1 mmol/kg Gd-BOPTA. The difference in enhancement achieved, comparing results at each time point, was statistically significant only at 1 and 3 minutes postcontrast (P = 0.003 and 0.03). Lesion conspicuity, specifically (SIliver - SIlesion/noise), increased from 272 +/- 29 precontrast to a maximum of 639 +/- 73 at 30 minutes postcontrast using a dose of 0.1 mmol/kg Gd-BOPTA, with the improvement statistically significant (P = 0.0003). Lesion conspicuity on the T2-weighted scan was 137 +/- , with the Gd-BOPTA scan markedly superior (P = 0.00004). On scans at 45 and 60 minutes after Gd-BOPTA administration, a progressive increase in signal intensity in the central necrotic portion of the lesion was observed. This was most consistent with gradual diffusion of the agent from the adjacent liver into the lesion. Using Gd-HP-DO3A at 0.3 mmol/kg (three times the dose for Gd-BOPTA), lesion conspicuity increase from 305 +/- 37 precontrast to a maximum of 701 +/- 92 at 1 minute postcontrast, with this difference also statistically significant (P = 0.0004). The abscess rim exhibited moderate contrast enhancement, greater than that of normal liver parenchyma, on early postcontrast images with Gd-HP-DO3A. CONCLUSIONS: The conspicuity of an early liver abscess is improved markedly on delayed imaging after administration of 0.1 mmol/kg Gd-BOPTA. Although a similar magnitude of parenchymal enhancement can be obtained after the administration of an extracellular agent, such as Gd-HP-DO3A, high-contrast dose (0.3 mmol/kg) and early dynamic imaging are required. The appearance of a liver abscess on late scans (45 to 60 minutes) after Gd-BOPTA injection is distinct from that of nonnecrotic metastases, with diffusion of the agent into the lesion noted.

Animals↗
PubMed1996

No evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol O-methyltransferase activity.

OBJECTIVE: Catechol O-methyltransferase (COMT) inactivates catecholamines by methylating their m-hydroxy group. Some previous studies using biochemical methods have found higher levels of COMT activity in schizophrenic patients. Recently, the genetic polymorphism that underlies variation in COMT activity, which results in the creation of a NlaIII restriction site in the low-activity allele, has been elucidated. METHOD: This study investigated this polymorphism in 78 unrelated schizophrenic patients and 78 comparison subjects matched for age and ethnicity. High-molecular-weight DNA was isolated from lymphocytes with routine procedures, and each individual was typed for high and low COMT activity. RESULTS: The frequency of the NlaIII polymorphism was 0.51 in the schizophrenic patients and 0.53 in the comparison subjects, and no significant allelic or genotypic associations were observed. CONCLUSIONS: There was no evidence for variation in COMT activity between a group of schizophrenic patients and matched comparison subjects.

Alleles↗
PubMed1995

Comparison of gadolinium Cy2DOTA, a new hepatobiliary agent, and gadolinium HP-DO3A, an extracellular agent, in healthy liver and metastatic disease.

RATIONALE AND OBJECTIVES: A new gadolinium (Gd) chelate with preferential hepatobiliary uptake, Gd Cy2DOTA, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved contrast agent with extracellular distribution. Liver enhancement was evaluated for these two contrast agents using magnetic resonance imaging, whereas an experimental model of metastatic disease was used to evaluate the agents' efficacy for liver-lesion delineation. METHODS: The two agents were compared in four healthy Rhesus monkeys (eight studies) and five New Zealand White rabbits with implanted VX-2 liver tumors (ten studies). The contrast dose was 0.1 mmol/kg, with the agents given in random order and at least 72 hours between contrast injections. Breathhold T1-weighted spin echo scans were obtained at 1.5 tesla (T) before and after contrast was administered. Postcontrast scans were obtained 1 to 90 minutes after injection in the monkeys and 1 to 240 minutes after injection in the rabbits. RESULTS: Prolonged hepatic enhancement, superior in degree to that with Gd HP-DO3A, was noted in both monkeys and rabbits after injection of Gd Cy2DOTA. Two minutes after contrast, liver SI was 1.94 +/- 0.05 with Gd Cy2DOTA compared with 1.51 +/- 0.05 with Gd HP-DO3A in monkeys. Sixty minutes after contrast, liver SI was 1.60 +/- 0.09 compared with 1.20 +/- 0.02. The difference between agents was significant at all times from 2 to 60 minutes after contrast injection (P < 0.01). Excretion of contrast into the gall bladder was observed in both animal species with Gd Cy2DOTA but not with Gd HP-DO3A. The maximum improvement in lesion conspicuity (rabbit) occurred 45 minutes after injection of Gd Cy2DOTA and 5 minutes after injection of Gd HP-DO3A. Sixty minutes after injection, liver-lesion contrast was 246 +/- 61 with Gd Cy2DOTA and 106 +/- 28 with Gd HP-DO3A, with a significant difference (P < 0.02). CONCLUSIONS: Gd Cy2DOTA provides greater enhancement of the liver parenchyma on immediate and delayed magnetic resonance scans than does Gd HP-DO3A. On delayed scans, Gd Cy2DOTA provides superior delineation of metastatic liver lesions.

Adenocarcinoma↗
PubMed1995

Detectability of early brain meningitis with magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The ability of high-field (1.5 T) magnetic resonance imaging (MRI) to detect early brain meningitis was evaluated in a canine model. Contrast dose, timing postinjection, and imaging technique (specifically the use of magnetization transfer) were assessed. METHODS: Imaging of five canines was performed at 1.5 T 24 hours after injection of Cowans staphylococcus into the cisterna magna. Two control animals also were imaged using the same protocol, with one animal receiving a cisternal injection of nutrient broth only and the other no injection. Contrast doses of 0.1, 0.3, and 0.8 mmol/kg gadoteridol (Gd HP-DO3A or Pro-Hance) were compared. Scans were performed at 2, 12, and 22 minutes after an initial injection of 0.1 mmol/kg. At each time point, paired T1-weighted scans with and without magnetization transfer (MT) were acquired. Thirty minutes after the initial injection of contrast, a supplemental dose of 0.2 mmol/kg was given (for a cumulative dose of 0.3 mmol/kg). Scans were then repeated at 2, 12, and 22 minutes after this dose was administered. A second supplemental contrast injection of 0.5 mmol/kg (for a cumulative dose of 0.8 mmol/kg) was given at 70 minutes, and immediate postinjection scans with and without MT were acquired. RESULTS: In the animals receiving a cisternal injection of bacteria, the degree of meningeal enhancement was greatest at 0.8 mmol/kg, intermediate at 0.3 mmol/kg, and least at 0.1 mmol/kg. These conclusions were constant whether imaging was performed with or without MT. Scans in control studies did not demonstrate abnormal meningeal enhancement. High-contrast dose, MT, and acquisition of immediate postcontrast scans all resulted in statistically significant improvement. On masked film review, abnormal meningeal enhancement was noted in only 2 of 5 experimental dogs at a dose of 0.1 mmol/kg (regardless of the use of MT) compared with all animals at a dose of 0.3 mmol/kg. In 18 of 37 dogs (paired scans with and without MT), when abnormal enhancement was noted, the use of MT improved the visualization of abnormal meningeal enhancement. CONCLUSIONS: In early brain meningitis, high-contrast dose (0.3 mmol/kg), MT, and scanning immediately after injection improve detection of abnormal meningeal enhancement, thus facilitating the diagnosis of meningitis. Of these factors, contrast dose is the most important.

Animals↗
PubMed1994

Respiratory burst activity associated with phagocytosis of Ehrlichia risticii by mouse peritoneal macrophages.

Peritoneal macrophages from two strains of mice, BALB/c and C3H/HeN, were analysed by flow cytometry for a respiratory burst associated with the phagocytosis of Ehrlichia risticii. Resident murine peritoneal macrophages failed to respond with a respiratory burst after phagocytosing E risticii. In contrast, mice previously infected with E risticii yielded peritoneal macrophages that did generate a respiratory burst on phagocytosing ehrlichiae.

Animals↗
PubMed1994

Humoral antibody and lymphocyte blastogenesis responses in BALB/c, C3H/HeJ and AKR/N mice following Ehrlichia risticii infection.

Three strains of mice, two susceptible to Ehrlichia risticii induced disease (BALB/c and C3H/HeJ) and one resistant (AKR/N), were evaluated for the development of humoral and cell mediated immune responses following infection with E risticii. The production of serum antibody was determined by indirect fluorescent antibody testing of sera from mice of each strain challenged with one of three different dose levels of E risticii. Antibody was assayed on days 7, 9, 12, 15 and 20 after inoculation. Cell mediated immune responses were evaluated by measuring the blastogenesis response of spleen cells from E risticii infected mice 28 days after inoculation. All three strains of mice at the high challenge level responded with the production of antibody by day 9 after inoculation. Overall, the antibody response occurred earlier and was of greater magnitude in the susceptible BALB/c and C3H/HeJ strains. A marked blastogenesis response occurred in splenocytes from E risticii infected mice of all three strains upon re-exposure to ehrlichial antigen. The findings of this study indicate that susceptibility to E risticii induced disease was not the result of deficient or delayed humoral immune responses and that E risticii infection induced the development of strong cell mediated immunity.

Animals↗