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Biomedical subjects

R J Boudreau

Publications and source records attributed to R J Boudreau.

At least 19 recordsLinked to original sources
PubMed1998

Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone.

Hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) was formulated in a metered-dose inhaler (MDI) to deliver a particle size of 1.1 microm compared with 35 microns for currently marketed chlorofluorocarbon (CFC)-BDP products. Two phase I single-dose human deposition studies were conducted using technetium 99m-radiolabelled BDP in a press-and-breathe actuator without an add-on spacer. A healthy volunteer study (n=6) showed that 55-60% of the HFA-BDP ex-actuator dose was deposited in the lungs, with 29-30% deposited in the oropharynx. CFC-BDP deposition was 4-7% in the lungs and 90-94% in the oropharynx. The pattern of deposition within the lung showed that HFA-BDP was spread diffusely throughout the lung airways, whereas CFC-BDP was confined to the central airways with little, if any, peripheral airway deposition. A second study with asthmatics (n=16) confirmed that 56% of the HFA-BDP dose was deposited in the airways, with 33% in the oropharynx. In conclusion, hydrofluoroalkane-134a-beclomethasone dipropionate deposition was much greater in the airways than chlorofluorocarbon-beclomethasone dipropionate, with a concomitant reduction in oropharyngeal deposition. The increased lung deposition efficiency of the hydrofluoroalkane propellant has led to a reduction in the amount of beclomethasone dipropionate needed to achieve a similar efficacy. The penetration of the hydrofluoroalkane to the small airways may provide asthma treatment not afforded by conventional chlorofluorocarbons.

Adolescent↗
PubMed1997

The prediction of the structure of technician (V) complexes using density-functional techniques.

Electronic structure calculations using the local-density functional method were shown to accurately reproduce the geometry of five oxo-Tc (V)-based radiopharmaceuticals containing a variety of donor ligands. Calculations were performed using the DGauss program on a Cray C90 supercomputer, requiring approximately 40 CPU h for each molecule. The predicted bond lengths were within +/- 0.04 A of the crystallographic coordinates, and bond angles within +/- 4 degrees. Root mean square (RMS) deviations between the predicted and crystallographic coordinates were less than 0.06, and visual inspection demonstrated nearly perfectly superimpossible structures.

Organotechnetium Compounds↗
PubMed1996

Strontium-89 chloride (Metastron) for palliative treatment of bony metastases. The University of Minnesota experience.

Strontium-89 chloride (Metastron) is an FDA-approved treatment for palliation of cancer pain. We evaluated blood count changes and pain relief in 28 patients with widespread painful bony metastasis treated with strontium-89 at the University of Minnesota Hospital and Clinics. Eighteen patients had prostate cancer (all hormone-refractory cancer), seven patients had breast cancer, and three patients had lung cancer, all previously treated with either radiation, chemotherapy, or a combination of the two. Serial blood counts were performed weekly up to 8 weeks and at 12 weeks after administering Metastron. Pain scale and blood values were monitored simultaneously. The mean baselines of hemoglobin (Hgb), white blood count (WBC), and platelets (Plts) were 11.4, 5900, and 258,000, respectively. The mean dose of Metastron was 3 mCi (range 2.2-4.4). The median time (range) to nadir was about 6 weeks. The percentage reductions relative to baseline were 32% (range 0-72%) for WBC; 14% (range 0-50%) for Hgb; 15% (range 0-47%) for the red blood cell (RBC) count; and 40% (range 0-85%)for Plts. We did not find a close relationship among the baseline blood count, reduction of subsequent blood counts, or previously irradiated active bone marrow volume. The median time of survival was 23 weeks (range 2-66 weeks). At 12 weeks, 29% of patients had moderate to dramatic improvement of pain, 32% had some relief of pain, and 50% had no improvement in pain. Thirty-two percent of the treated patients required additional palliative external beam radiation to their bony lesions within the study period. Our results show that Metastron for palliation for bony metastases should be used with caution because of moderate to severe bone marrow toxicity, especially in platelets, associated with its use. Careful evaluation of patients given Metastron is needed to assess accurately its full benefit.

Adult↗
PubMed1994

A comparison of single blood sample and multiple blood sample methods to measure GFR in a pediatric population.

Several single-sample, Cr-51 EDTA based methods of estimating glomerular filtration rate in children have been proposed. The authors retrospectively reviewed our experience in 467 pediatric patients using Tc-99m DTPA and 4 ultrafiltered serum samples drawn 2-4 hours postinjection. The authors used the 2-hour specimens for the single-sample method. Regression analysis of the 2 techniques revealed significant scatter. Mathematically, it was shown that the error of the single-sample method was minimized when the clearance t 1/2 equalled the sampling time x 0.693. This model predicted a 300% error when the t 1/2 was varied to its observed extremes. The observed error of the single-sample method fit this theoretical prediction very well. Analysis of a two-sample method versus the four-sample method showed no improvement in results. In a subset of 18 unfiltered plasma samples, the glomerular filtration rate was falsely low in 12 patients. The authors conclude that multiple blood samples and serum ultrafiltration are required to accurately measure glomerular filtration rate when using Tc-99m DTPA.

Adolescent↗
PubMed1994

Resting Tl-201 scintigraphy in the evaluation of coronary artery disease in children with Hurler syndrome.

Severe coronary artery disease may occur early in the course of mucopolysaccharidosis. The authors present radiologic, scintigraphic, and pathologic findings in five patients with Hurler syndrome. Thallium-201 myocardial scintigraphy and selective coronary angiography obtained within 2 days to 6 months were correlated in five patients. Postmortem examination of the coronary arteries was obtained in one patient within hours of angiography. Interobserver agreement on grading of scintigraphic abnormalities was poor. Nonspecific findings on Tl-201 studies included septal abnormalities in all five patients. Scintigraphic findings were corroborated by angiography and postmortem results in only 3 of 5 patients. Our findings suggest that resting Tl-201 scintigraphy has limited value in the detection of coronary artery disease in patients with Hurler syndrome.

Child, Preschool↗
PubMed1993

Synthesis and biological evaluation of radioiodinated N-2-(4-piperidyl)ethyl benzamides.

Three iodinated benzamides, 5-7, analogues of the potent acetylcholinesterase inhibitor 1-benzyl-4-[N-[4'-(benzylsulfonyl) benzoyl-N-methylamino]ethyl]piperidine (2), were synthesized and evaluated as potential anticholinesterase agents. All three compounds were found to be three orders of magnitude less potent than the parent compound. However, receptor screening revealed that compounds 5-7 exhibit nanomolar affinity for the sigma binding site. Both [125I]5 and [125I]7 were synthesized and evaluated in rats. Following the intravenous administration of [125I]5 into rats, 1.59% of the injected dose was found in the rat brain within 5 min. The level of radioactivity in the brain remained steady for 2 h, the duration of the study. In contrast, 0.42% of the injected dose was detected in the rat brain following the i.v. injection of [125I]7. Coadministration of either [125I]5 or [125I]7 with 0.5 mumol/kg of haloperidol resulted in a 56-73% reduction in the level of radioactivity in the rat brain, suggesting that these compounds bind to the sigma binding site in vivo. Planar imaging studies with [123I]5 revealed significant accumulation of radioactivity within the monkey brain, with a half-life of 6 h. Compound [123I]5 may be potentially useful for studying sigma receptor distribution in the human brain.

Animals↗
PubMed1993

Comparison of Tc-99m DTPA aerosol ventilation studies with pulmonary function testing in cystic fibrosis.

In 43 patients with cystic fibrosis, the results of 122 Tc-99m DTPA aerosol ventilation (DAV) studies were compared with pulmonary function tests (PFTs) that were performed within 24 hours of the DAV studies. The DAV studies were evaluated blindly for (A) number of pulmonary segments showing little or no ventilation, (B) number of foci of bronchial deposition of aerosol, and (C) subjective overall improvement, lack of change, or worsening from the previous study. (A) and (B) correlated significantly with all PFTs (p's < .001, r's = -.51 to -.73). Changes in (A) and (B) also correlated with changes in PFTs (p's < or = .001, r's = -.37 to -.58). The three populations in (C) were significantly different from each other with respect to changes in all PFTs (p < or = .002). Intervals between studies showing subjective improvement, no change, and worsening averaged 60, 133, and 306 days, respectively. These results suggest that DAV is an indicator of both regional and global pulmonary function and may be useful in evaluating patients with cystic fibrosis.

Adolescent↗
PubMed1993

Reverse mismatch between perfusion and aerosol ventilation in transplanted lungs.

Thirty ventilation-perfusion pulmonary scintigraphic studies were performed in 13 patients who had undergone unilateral lung transplantation. Ventilation-perfusion mismatch (ventilation better than perfusion) was judged absent, mild, moderate, or severe in the transplanted and native lungs. Ventilation-perfusion mismatch was significantly worse in the transplanted lungs (p < .0001). Findings of lung biopsies and chest roentgenograms failed to correlate with the severity of ventilation-perfusion mismatch. Hypoxic pulmonary vasoconstriction appears to be significantly impaired in most unilateral lung transplants; the mechanism for this impairment is unclear.

Adult↗
PubMed1993

Postoperative diuresis renography and ultrasound in patients undergoing pyeloplasty. Predictors of surgical outcome.

The authors reviewed 50 pediatric patients (56 renal units) who underwent pyeloplasty and had serial preoperative and postoperative diuresis renogram and ultrasound studies. Of those patients that clinically improved with surgery, 73% and 91% showed improved renographic patterns in postoperative studies at 3 and 12 months, respectively. Ultrasound demonstrated more gradual improvement in grade and pelvic diameters over longer study intervals. Diuresis renography is an excellent predictor of surgical outcome within 3 months of pyeloplasty and showed change well in advance of that seen on ultrasound. Sonography is better suited to longer term evaluation of grade, pelvic diameter, and renal size.

Adolescent↗
PubMed1993

Resolution of severe intrapulmonary shunting after liver transplantation.

A major complication of hepatic cirrhosis is arterial hypoxemia, often the result of intrapulmonary arteriovenous shunting. While previously such hypoxemia was thought to preclude successful hepatic transplantation, more recent studies have suggested that hepatic transplantation should be considered if the hypoxemia is corrected by supplemental oxygen. We report the findings in a cirrhotic patient with severe hypoxemia associated with intrapulmonary arteriovenous shunting. The patient did not respond to supplemental oxygen (PaO2 < 40 mm Hg on O2 at 4 L/min). The patient underwent successful hepatic transplantation, with complete resolution of intrapulmonary shunting. We believe that patients with cirrhosis-associated intrapulmonary shunting, even with hypoxemia resistant to supplemental oxygen, are acceptable candidates for hepatic transplantation.

Adolescent↗
PubMed1992

Liver transplant rejection and cholestasis: comparison of technetium 99m-diisopropyl iminodiacetic acid hepatobiliary imaging with liver biopsy.

To determine whether the scintigraphic evaluation of technetium-99m diisopropyl iminodiacetic acid (DISIDA) uptake and excretion can distinguish among liver transplant patients with biopsy evidence for rejection, cholestasis or neither condition, we reviewed scintigrams and biopsies in 36 patients. There were 76 scintigrams with corresponding biopsies. Uptake and excretion were graded from image data on scales reflecting normal through severely abnormal values. Biopsies were evaluated for findings of cholestasis and rejection. The majority of scintigrams demonstrated normal uptake (60/75, 80%) and delayed excretion (65/76, 85%), which was most marked immediately after transplantation. One-way analysis of variance showed that the mean excretion values significantly differed between patients with normal biopsies and those with cholestasis and/or rejection (P = 0.0003). However, mean uptake scores demonstrated no statistically significant difference between these two groups of patients (P = 0.1). These findings suggest that 99mTc-DISIDA scintigraphy can differentiate between transplants with and without rejection/cholestasis but not between rejection and cholestasis. If 99mTc-DISIDA excretion is normal, rejection and cholestasis are unlikely.

Cholestasis↗
PubMed1992

Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane: potential radiotracer for mapping central cholinergic innervation in vitro.

Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane, 5 (4-HIPP), was synthesized and evaluated as a simple vesamicol-like radiotracer for mapping cholinergic pathways in the brain. Both enantiomers of 5 exhibit significant accumulation (approx. 2% of injected dose) and prolonged retention (t1/2 greater than 3 h) within the rat brain. The accumulation of radioiodinated 5 in the rat brain was reduced by up to 70% in the presence of vesamicol and its analogs. The levorotary isomer (-)-4-[123I]HIPP exhibits significant accumulation in the monkey brain, with a half-life of about 9 h. Radioiodinated 5 may therefore be a useful tool for studying cholinergic pathways in the brain.

Animals↗
PubMed1992

Aerosol scintigraphy in the assessment of therapy for cystic fibrosis.

Thirteen patients with cystic fibrosis (aged 11 to 32 years) who were hospitalized for exacerbation and who had sputum cultures positive for Pseudomonas organisms were treated initially for 4 days with bronchodilators and physiotherapy followed by the addition of antibiotic (14 days, n = 8) or placebo (14 days, n = 4; 7 days, n = 1). Tc-99m DTPA aerosol scintigraphy was performed on the day before bronchodilators and physiotherapy, on the day before antibiotic or placebo, and on the day after completion of antibiotic or placebo therapy. Scintigrams were evaluated for change in the number of nonventilated segments and change in the number of bronchial deposits of aerosol. Sixty-nine percent of patients showed improvement after bronchodilators and physiotherapy alone. Sixty-two percent showed further improvement after antibiotic or placebo was added; this improvement was independent of whether antibiotic or placebo was administered (P greater than 0.1). These aerosol scintigraphy results failed to demonstrate that the effectiveness of bronchodilators and physiotherapy is enhanced by antibiotics in the treatment of cystic fibrosis exacerbations.

Adult↗
PubMed1992

Computer-aided radiopharmaceutical design.

The ultimate goal of a QSAR analysis is prediction, which depends on the elaboration of the most appropriate set of molecular descriptors. As such, molecular description is the nucleus of QSAR and in the absence of exhaustive molecular description, rational drug design may be greatly impeded. As previously discussed, computational methods such as quantum mechanics and molecular mechanics provide molecular description at a fundamental level which then enhances the descriptive capability and predictive power of a QSAR analysis. In recognition of these capabilities, semi-empirical molecular orbital methods and molecular mechanics now have been incorporated into or interphased with QSAR programs. Such integrated packages are being successfully used in computer-aided molecular modeling. Computer-aided molecular modeling can provide the three-dimensional structure of a molecule, its chemical and physical characteristics, comparisons of structures of different molecules, and visualization of complexes formed between them. From the foregoing, predictions may be made about how related new molecules may function. Thus, the combination of quantum and/or molecular mechanics and QSAR provides a formidable weapon in the chemist's armamentarium. The molecular modeling approaches are certainly more practical to use than physicochemical methods. They also provide electronic and thermodynamic data that are not available from x-ray crystallographic data. Of course, these techniques are not confined to radiopharmaceutical development and they also could aid in the development of contrast agents for radiography or magnetic resonance imaging. We believe that as computational resources and capabilities increase over the next decade, computer-aided drug design will become a standard procedure in all drug development laboratories.

Binding Sites↗