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R J Boudreau

Publications and source records attributed to R J Boudreau.

At least 37 records · Page 2Linked to original sources
PubMed1991

Molecular determinants in the bioactivation of the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Nineteen analogs of the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have been used as probes to study the structural parameters that influence MAO-catalyzed oxidation. In this study, the efficiency of enzyme-catalyzed substrate oxidation was found to be unrelated to parameters such as the ionization potential, dipole moment, net atomic charge at C5 and the dihedral angle between the phenyl ring and the tetrahydropyridine moiety. Conformational analysis revealed that substitution at the C2' position of MPTP yields atropisomers. It is suggested that one of these atropisomers would be either inactive or substantially less active than the other. Therefore, the relative oxidative efficiency and toxicity of these compounds reported earlier may have been significantly underestimated. Based on the conformational analysis and other data, a rudimentary model of the MAO substrate site has been developed which partially explains the substrate specificities of MAO A and MAO B. Each substrate binding site can be divided into two regions, (a) an amine-binding pocket (for the tetrahydropyridine moiety), and (b) a 'bulky substituent' region (for the phenyl group and its substituents). The length of the substrate binding site (measured along the long axis of MPTP) is approximately 8.5 A, and the width of the 'amine-binding' pocket is approximately 2.5 A (from C3 to C5). The 'bulky substituent' region contains a central area for binding the phenyl group of MPTP. This central area is flanked by two hydrophobic pockets, P2' and P3'. In MAO A, the pocket P2'-A is oriented 45-135 degrees relative to the plane of the tetrahydropyridine moiety, with a radius of 3.1 A from C2' of the phenyl ring. The radius of a similar but smaller pocket, P2'-B, in MAO B, is approximately 2.7 A. In MAO B, the pocket P3'-B (radius 2.36 A from C3') is larger than a similar pocket P3'-A (radius 1.70 A from C3') in MAO A. The foregoing characterization suggests that differences in the size and topography of both of the substituent pockets play an important role in determining the substrate specificities of these two isozymes.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Ectopic splenomegaly in Felty's syndrome.

A 50-year-old woman with Felty's syndrome, who presented with "menopausal" symptoms, was found to have a large pelvic mass on physical exam. Computed tomography of the pelvis led to an incorrect diagnosis of malignancy, while radionuclide imaging using Tc-99m sulfur colloid confirmed the diagnosis of ectopic splenomegaly.

Choristoma↗
PubMed1991

Quantitative I-123-IMP brain SPECT and neuropsychological testing in AIDS dementia.

We performed I-123-IMP SPECT brain imaging on seven mildly demented AIDS patients and seven normal subjects. In an attempt to detect and quantitate regions of decreased I-123-IMP uptake, pixel intensity histograms of normalized SPECT images at the basal ganglia level were analyzed for the fraction of pixels in the lowest quartile of the intensity range. This fraction (F) averaged 17.5% (S.D. = 4.6) in the AIDS group and 12.6% (S.D. = 5.1) in the normal group (p less than .05). Six of the AIDS patients underwent neuropsychological testing (NPT). NPT showed the patients to have a variety of mild abnormalities. Regression analysis of NPT scores versus F yielded a correlation coefficient of .80 (p less than .05). We conclude that analysis of I-123-IMP SPECT image pixel intensity distribution is potentially sensitive in detecting abnormalities associated with AIDS dementia and may correlate with the severity of dementia as measured by NPT.

AIDS Dementia Complex↗
PubMed1991

Correlation of technetium-99m-DISIDA hepatobiliary studies with biopsies in liver transplant patients.

We compared 76 99mTc-DISIDA hepatobiliary studies with corresponding liver biopsies in 36 liver transplant patients to determine the histopathologic abnormalities that corresponded to scintigraphic abnormalities in uptake and excretion. Uptake was judged normal if the cardiac blood pool was barely visible or invisible on the ten minute image. Excretion was judged normal if images subsequent to the 15-min image showed a subjectively normal rate of decreasing parenchymal intensity. Biopsies were graded subjectively for hepatocyte damage and for findings of cholestasis. Uptake criteria were successful in differentiating high from low hepatocyte damage scores (p less than 0.0001), and excretion criteria were successful in differentiating high from low cholestasis scores (p = 0.002), while uptake criteria were not capable of differentiating high from low cholestasis scores, nor were excretion criteria capable of differentiating high from low hepatocyte damage scores (p's greater than 0.05). These results suggest that scintigraphy can distinguish intrahepatic cholestasis from pure hepatocyte damage.

Biopsy, Needle↗
PubMed1990

Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogues: synthesis and monoamine oxidase catalyzed bioactivation.

Eighteen analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and evaluated as substrates of monoamine oxidase. In general, the flexible analogues, characterized by the presence of a methylene (or ethylene) bridge between the aryl/heteroaryl and tetrahydropyridyl moieties, were better substrates of the enzyme than the conformationally restricted MPTP. It is suggested that the increased oxidative activity of these flexible analogues reflects enhanced binding due to the ability of the C-4-aryl/heteroaryl substituent to gain access to a hydrophobic pocket within the substrate binding site.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Perfusion thallium imaging of type I diabetes patients with end stage renal disease: comparison of oral and intravenous dipyridamole administration.

Eighty patients with type I diabetes and end stage renal disease were prospectively evaluated for coronary artery disease with dipyridamole-thallium-201 scintigraphy and quantitative coronary angiography. Forty patients received dipyridamole orally, and 40 received it intravenously. The prevalence of coronary artery disease was 53%. There were no significant differences in the accuracy of the two dipyridamole tests (sensitivity = 85%, specificity = 85%, accuracy = 85% for the oral group; sensitivity = 86%, specificity = 72%, accuracy = 79% for the intravenous group). Combining the 80 patients into a single group gave a sensitivity of 86%, a specificity of 79%, and an accuracy of 83% for the detection of coronary disease. Although the accuracy of this test in this patient population was similar to that previously reported for other groups, the prevalence of disease was high and resulted in a low predictive value of a negative test (83%).

Administration, Oral↗
PubMed1990

Therapeutic embolization: enhanced radiolabeled monitoring.

Radiolabeling of Ivalon (polyvinyl alcohol sponge) particles permits localization of injected particles during embolization through the use of a portable gamma camera and provides a means to prevent potentially fatal complications such as pulmonary embolization. A more efficient technique of labeling Ivalon particles with technetium-99m sulfur colloid was developed. An increase in labeling efficiency allowed more accurate determination of the distribution of injected Ivalon particles. Scanning electron microscopy demonstrated the stability of the Ivalon particles during this new labeling process. Two patients with arteriovenous malformations underwent therapeutic embolization with radiolabeled Ivalon particles; gamma camera imaging of the lesion and chest was performed throughout the procedure.

Adult↗
PubMed1990

Long-term effects of cyclosporine on renal function in organ transplant recipients.

To evaluate whether cyclosporine nephrotoxicity is progressive, glomerular filtration rate and renal plasma flow were determined by isotopic techniques in 24 cyclosporine-treated organ transplant recipients (12 heart, 1 pancreas, and 11 kidney recipients). The cyclosporine group demonstrated reductions in glomerular filtration rate and renal plasma flow, with higher renal vascular resistance and mean arterial pressure as compared with an azathioprine-treated control group. However, longitudinal studies over a mean time period of 23 months in eight cyclosporine-treated renal transplant recipients showed renal function to remain stable. In the entire group of 24 cyclosporine-treated patients, longer duration of cyclosporine treatment was associated with decreased but stable glomerular filtration rate, increased renal plasma flow, decreased renal vascular resistance, and lower daily doses of cyclosporine. Evaluation of intrarenal resistances demonstrated a greater decrease in efferent than afferent arteriolar resistance, consistent with the fall in plasma renin activity that occurred with time. Short-term treatment of 12 patients with prazosin produced no beneficial effect on renal function, whereas treatment of nine patients with captopril produced a 20% increase in renal plasma flow, with a significant reduction in renal vascular resistance. We conclude that although cyclosporine treatment produces decreased renal function, the loss in renal function is not necessarily progressive. Treatment with captopril may improve the abnormal renal hemodynamics of cyclosporine-treated patients.

Blood Flow Velocity↗
PubMed1989

Clinical efficacy of 99mtechnetium mercaptoacetylglycine kit formulation in routine renal scintigraphy.

99mTechnetium mercaptoacetylglycine is a promising new renal radiopharmaceutical undergoing phase III trials in the United States. In a preliminary investigation of the efficacy and safety of mercaptoacetylglycine in 30 adult patients with suspected renal disease we used simultaneous imaging with orthoiodohippurate as the physiological "gold standard". Of these patients 11 had undergone renal transplantation. Factors, such as time to peak renal activity, clearance half-life and regional functional comparison, were similar by orthoiodohippurate and mercaptoacetylglycine imaging. Visual and quantitative analysis of angiograms and renograms was markedly facilitated with the use of mercaptoacetylglycine. Several morphological abnormalities were apparent only during mercaptoacetylglycine evaluation. No adverse effects, changes in vital signs or significant changes in clinical laboratory status were encountered. Since mercaptoacetylglycine combined an excellent technetium image with the pharmacokinetics of orthoiodohippurate, mercaptoacetylglycine may supplant all other agents for routine clinical use.

Adult↗
PubMed1989

Detection of impending pericardial tamponade during skeletal imaging.

Bone imaging using Tc-99m MDP was performed on a 68-year-old man with a newly diagnosed adenocarcinoma of the lung. The image unexpectedly showed increased activity in the heart area. Emergent echocardiography demonstrated impending pericardial tamponade. A malignant pericardial effusion was verified by pericardiocentesis.

Adenocarcinoma↗
PubMed1989

Pancreas transplants: evaluation using perfusion scintigraphy.

To determine the value of scintigraphic perfusion studies in evaluating pancreas transplant patients, we reviewed 56 of these studies in 22 patients who had 27 transplants. Seventeen patients underwent two or more studies. The perfusion studies were performed with 20 mCi (740 MBq) of 99mTc-DTPA injected as a bolus followed by eight to 16 serial 2-sec images and a 500,000-count immediate static image. Images were evaluated for (1) the time and intensity of pancreatic peak radioactivity relative to the time and intensity of the iliac arterial peak; (2) relative pancreatic to iliac arterial intensity on the static image; and (3) size, homogeneity, and definition of the pancreas. Clinical diagnoses at the time of scintigraphy of normal function (n = 36), rejection (n = 13), pancreatitis (n = 6), or arterial thrombosis (n = 1) were based on insulin requirement, urine amylase, serum glucose, serum amylase, response to therapy, cultures, CT, MR, sonography, scintigraphy with 67Ga or 111In-WBCs, percutaneous drainage results, angiography, surgery, and pathologic examination of resected transplants. Three 99mTc-DTPA perfusion studies showed no pancreatic perfusion, four showed decreasing perfusion on serial studies, and five showed progressive loss of definition of the pancreas on serial studies. Of the three patients with no detectable perfusion, one had a normally functioning transplant, one had arterial thrombosis with transplant infarction, and one had severe rejection with minimal function. Decreasing perfusion was associated with rejection in three patients and pancreatitis in one. Decreasing definition was seen in four patients with rejection and one with pancreatitis. We conclude that perfusion scintigraphy is useful, primarily when performed serially, although nonspecific for evaluating pancreas transplants.

Adult↗
PubMed1989

An improved radiolabeling technique of ivalon and its use for dynamic monitoring of complications during therapeutic transcatheter embolization.

Transcatheter embolization by Ivalon particles for treatment of arteriovenous malformations has been an accepted therapeutic technique for many years. We describe a new and efficient radiolabeling technique of Ivalon particles using [99mTc]sulfur colloid. Continuous and dynamic monitoring of injected radiolabeled Ivalon particles is made possible by viewing the persistence scope of a portable gamma camera whose head is positioned over the patient undergoing therapeutic embolization. Therefore, if inadvertent pulmonary embolism or reflux migration of radiolabeled Ivalon particles has occurred, the angiographer is immediately aware of this potentially serious or fatal complication and can take corrective action. We describe two patients, each with an arteriovenous malformation, who had therapeutic embolization with radiolabeled Ivalon particles, one resulting in reflux migration and the other resulting in inadvertent pulmonary embolism.

Adult↗
PubMed1989

Technetium-99m sulfur colloid spleen imaging following partial pancreatectomy and splenic artery and vein resection.

We retrospectively studied the records and [99mTc]sulfur colloid (TSC) spleen studies of 38 patients who underwent distal pancreatectomy with splenic artery and vein resection for donation to HLA-compatible relatives. The spleens in immediate postoperative TSC studies were normal in 11% of cases, showed no uptake in 16%, showed diffusely decreased uptake in 50%, and showed focal defects in 26%. Twenty of the patients, all with abnormal initial TSC studies, had repeat studies 2 wk to 3 yr later; 15% showed no change, 35% showed some improvement, and 45% became normal. One of six patients with no TSC uptake required splenectomy 2 days after pancreatectomy for splenic infarction. These data suggest that the spleen usually survives splenic artery and vein resection. Absent splenic TSC uptake raises the possibility of splenic infarction.

Adult↗