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Biomedical subjects

N D LaFrance

Publications and source records attributed to N D LaFrance.

At least 19 recordsLinked to original sources
PubMed2001

Use of a decision-analytic model to support the use of a new oral US contrast agent in patients with abdominal pain.

RATIONALE AND OBJECTIVES: The authors performed this study to compare the cost and diagnostic abilities of ultrasound (US) performed with and without the use of an oral contrast material recently approved by the U.S. Food and Drug Administration. MATERIALS AND METHODS: An interactive decision-analytic model was constructed to compare US performed with and without contrast material (SonoRx; Bracco Diagnostics) for the evaluation of patients with abdominal pain who were suspected of having pancreatic disease. The model considered all resources that might be used to evaluate a patient suspected of having pancreatic disease (eg, US, computed tomography [CT], endoscopic retrograde cholangiopancreatography, fine-needle aspiration biopsy, and open biopsy). The literature and an expert panel were the clinical data sources. Cost estimates were based on Medicare and non-Medicare reimbursements. The primary cost-effectiveness measure was the cost to achieve a diagnosis. RESULTS: SonoRx-enhanced US was less expensive than unenhanced US ($714 vs $808, respectively, with Medicare costs; $1,612 vs $1,878, respectively, with non-Medicare costs) and as effective (0.785 vs 0.782, respectively). SonoRx-enhanced US was more cost-effective than unenhanced US ($909 vs $1,034, respectively, with Medicare costs; $2,052 vs $2,401, respectively, with non-Medicare costs). This relationship was maintained throughout extensive sensitivity analyses. CONCLUSION: SonoRx-enhanced US is more cost-effective than unenhanced US, primarily because it avoids the need for CT. CT may be avoided owing to the higher probability of obtaining optimal US scans with oral contrast material.

Abdominal Pain↗
PubMed1999

Safety and pharmacokinetic profile of gadobenate dimeglumine in subjects with renal impairment.

RATIONALE AND OBJECTIVES: To determine the safety and pharmacokinetics of gadobenate dimeglumine in a group of subjects with moderate or severe renal impairment. METHODS: The safety and pharmacokinetic profile of gadobenate dimeglumine, a gadolinium (Gd3+) chelate complex in development as a contrast agent for MRI, were evaluated in a placebo-controlled, double-blind, multicenter trial. Subjects with moderate or severe renal impairment (creatinine clearances of 31 to 60 or 10 to 30 mL/min, respectively) received a 0.2-mmol/kg intravenous bolus of Gd3+ or saline placebo. Blood samples (up to 72 hours) and urine and fecal samples (up to 216 hours) were assayed for total Gd3+ content by inductively coupled plasma atomic emission spectroscopy. Gd3+ blood concentration/time data were analyzed nonparametrically and parametrically using the software program WinNonlin VI.1. RESULTS: Mean (SD) values for Gd3+ area under the curve, blood clearance, steady-state volume of distribution, renal clearance, and creatinine clearance for the moderate group were 862 (392) micrograms.h/mL, 56 (25) mL/min, 21 (5) L, 47 (23) mL/min, and 46 (16) mL/min. Values for the severe group were 1347 (366) micrograms.h/mL, 31 (7) mL/min, 19 (6) L, 22 (7) mL/min, and 21 (8) mL/min. No Gd(3+)-related adverse events occurred. Mean values for Gd3+ recovery in urine and feces for moderate and severe groups were 74% and 6%, and 69% and 8% of the dose, respectively. Linear regression analysis demonstrated a significant relation between the level of renal function and blood clearance of Gd3+. CONCLUSIONS: Although mean blood clearance and renal clearance values progressively declined with increasing degree of renal impairment, based on the safety profile and the fact that the administered dose was double the standard dose used for MRI purposes, there appears to be no need for dose reduction in this population.

Adult↗
PubMed1994

Altered cortical blood flow in HIV-seropositive individuals with and without dementia: a single photon emission computed tomography study.

OBJECTIVE: To quantitatively demonstrate the pattern of cerebral perfusion abnormalities in HIV-1-infected individuals described as 'patchiness' or inhomogeneity in previous qualitative emission tomographic imaging studies. DESIGN: We aimed to create a quantitative measure of inhomogeneity in HIV-infected individuals. High-frequency variance in cortical profiles is an indication of inhomogeneity in the distribution of radiotracer in the cerebral cortex. Therefore, the study analysis was designed to enable the estimation of variance frequencies in cortical profiles. METHODS: Regional cerebral blood flow was examined in nine mildly demented and 10 cognitively normal HIV-1-seropositive individuals and eight seronegative normal controls using single photon emission computed tomography with the radiotracer [I-123]-N-isopropyl-p-iodoamphetamine. Quantitative analysis was performed using circumferential profiles of cerebral cortical perfusion. Fourier transform power spectra of the profiles were examined as an index of patchiness in tracer distribution. RESULTS: Normal controls were characterized by strong middle frequency and weak high-frequency power. Both HIV-1-infected groups showed a significant power shift from middle to high frequencies. CONCLUSIONS: Increased high-frequency variations in both HIV-1-infected groups indicates diffuse cortical perfusion changes compared with normal controls. This study suggests that there are cerebral bloodflow abnormalities in HIV-1-infected individuals both with and without clinically severe dementia.

AIDS Dementia Complex↗
PubMed1994

Effect of magnetic susceptibility contrast medium on myocardial signal intensity with fast gradient-recalled echo and spin-echo MR imaging: initial experience in humans.

PURPOSE: To show the effect of dysprosium diethylenetriaminepentaacetic acid bis-methylamine injection on the images of normal human myocardium. MATERIALS AND METHODS: T2-sensitive fast gradient-recalled echo (GRE) (repetition time [TR], 10.8 msec; echo time [TE], 4.2 msec) and spin-echo (SE) (TR, three RR intervals; TE, 60 msec) magnetic resonance (MR) imaging with driven equilibrium-preparation pulse was used to produce T2 contrast material enhancement. The contrast agent was injected into 12 healthy subjects at doses of 0.05, 0.1, 0.2, 0.4, and 0.6 mmol/kg. RESULTS: Driven equilibrium-prepared GRE images showed a transient decrease of myocardial signal intensity at doses of 0.2-0.6 mmol/kg. Postcontrast T2-weighted SE images showed a myocardial signal attenuation (30%-45% decrease) at a dose of 0.4 mmol/kg or higher. CONCLUSION: Dynamic MR imaging with a magnetic susceptibility contrast medium can be used to monitor the first pass of contrast media through human myocardium with a conventional MR imager and a fast GRE sequence.

Adult↗
PubMed1991

Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts: studies in a heterotopic rat heart model.

111In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium-99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and signs of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium-99m pyrophosphate accumulation (r = 0.88) but was poorly correlated with labelled antibody uptake (r = 0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labelled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium-99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin.

Animals↗
PubMed1991

Comparison of indium-111 antimyosin antibody and technetium-99m pyrophosphate localization in reperfused and nonreperfused myocardial infarction.

Recent imaging studies suggest that technetium-99m (Tc-99m) pyrophosphate yields a considerably larger estimate of myocardial infarct size than does indium-111 (In-111) monoclonal antimyosin antibody. To determine whether Tc-99m pyrophosphate may be taken up by reversibly injured myocytes, particularly in the setting of coronary reperfusion, the tissue localization of Tc-99m pyrophosphate and antimyosin antibody was compared in 11 dogs 24 to 68 h after anterior descending coronary artery occlusion (4 dogs with permanent occlusion, 7 with reperfusion). Technetium-99m pyrophosphate and In-111 antimyosin antibody content was determined in serial 2 to 3 mm wide endocardial and epicardial samples taken through the infarct zone in multiple short-axis left ventricular slices. The number of samples with increased In-111 antimyosin antibody (defined as greater than or equal to mean + 2 SD of normal) was not significantly different from that with increased Tc-99m pyrophosphate. This was true in both reperfused and nonreperfused infarcts. However, the intensity of uptake of Tc-99m pyrophosphate exceeded that of In-111 antimyosin antibody, particularly in the border zones of reperfused infarcts, and the area with moderate to marked increase in tracer uptake (greater than or equal to 2 times normal) was significantly larger with Tc-99m pyrophosphate than In-111 antimyosin antibody (p less than 0.001). A specific zone of abnormal Tc-99m pyrophosphate with normal In-111 antimyosin antibody content could not be identified. Histologic evidence of myocardial necrosis was found in virtually every sample with increased In-111 antimyosin antibody, Tc-99m pyrophosphate, or both.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Antimyosin imaging in acute transmural myocardial infarctions: results of a multicenter clinical trial.

Murine monoclonal antimyosin antibody has been shown experimentally to bind selectively to irreversibly damaged myocytes. To evaluate the safety and efficacy of monoclonal antimyosin for identifying acute transmural infarction, 50 patients with acute Q wave myocardial infarction were entered into a phase I/II multicenter trial involving three clinical sites. Indium-111 antimyosin was prepared from an instant kit formulation containing 0.5 mg of diethylene triamine pentaacetic acid (DTPA)-coupled Fab fragment (R11D10) and 1.2 to 2.4 mCi of indium-111. Average labeling efficiency was 92%. Antimyosin was injected 27 +/- 16 h after the onset of chest pain. Planar or tomographic imaging was performed 27 +/- 9 h after injection in all patients, and repeat imaging was done 24 h later in 39 patients. Of the 50 patients entered, 46 showed myocardial uptake of antimyosin (sensitivity 92%). Thirty-one of 39 planar scans performed at 24 h were diagnostic; 8 showed persistent blood pool activity that cleared by 48 h. Focal myocardial uptake of antimyosin corresponded to electrocardiographic infarct localization. No patient had an adverse reaction to antimyosin. In addition, 125 serum samples, including 21 collected greater than 42 days after injection, were tested for human antimouse antibodies, and all samples were assessed as having undetectable titers. Intensity of antimyosin uptake was correlated with infarct location and the presence or absence of collateral vessels. There was a significant correlation between faint uptake and inferoposterior infarct location. In 21 patients who had coronary angiography close to the time of antimyosin injection, there was a significant correlation between faint tracer uptake and closed infarct-related vessel with absent collateral flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Homogeneity of bronchopulmonary distribution of 99mTc aerosol in normal subjects and in cystic fibrosis patients.

We characterized the bronchopulmonary distribution of a 0.9 percent saline aerosol (1.12 microM) labelled with 99mTc sulfur colloid in nine normal subjects and five patients with CF. Homogeneity of distribution was quantified using indices derived from computerized analysis of Anger camera pulmonary images including skew (a measure of distribution asymmetry) and kurtosis (a measure of distribution range). Aerosol clearance in 97 minutes (a measure of large, central airway deposition) was also assessed. Values of skew and kurtosis were reproducible for the patients with CF and were significantly elevated compared to the normal subjects. Reproducibility of skew and kurtosis were not studied in the normal subjects. Clearance was not significantly different in the two groups. We conclude that the bronchopulmonary distribution of this radioaerosol is nonuniform in patients with CF, compared to normal subjects, and clearance may be impaired in patients with CF who are severely ill.

Adult↗
PubMed1989

Reciprocal creatinine slopes often give erroneous estimates of progression of chronic renal failure.

In 10 of 22 observation periods (lasting an average of 15 months) in 17 patients with moderate to severe chronic renal failure (GFR 4 to 23 ml/min), rates of progression as estimated from the linear regression on time of reciprocal plasma creatinine concentration (multiplied by average 24 hr creatinine excretion) (b2) differed significantly from rates of progression as estimated from the regression on time of urinary clearance of 99mTc-DTPA (b1), during all or part of the period of observation, b2 exceeded b1 in six cases and was less than b1 in the other four. Owing to these changes, measurements of reciprocal creatinine concentration gave erroneous impressions of the rate or existence of progression, during all or a portion of the period of observation, in nearly half of these patients. However, in the 22 studies as a group, using the entire periods of observation, b2 indicated nearly the same mean rate of progression as b1, and had the same variance. We conclude that sequential plasma or serum creatinine measurements in individual patients are often misleading as measures of progression and should, when feasible, be replaced by urinary clearances of isotopes in following patients with chronic renal failure.

Creatinine↗
PubMed1988

Assessment of [11C]-L-methionine transport into the human brain.

Neutral amino acid transport into human brain was measured using a dual-probe positron detection system or positron emission tomography (PET). Rate constants (ml/min/cc) for brain accumulation of [11C]L-methionine measured with the dual detector ranged from 0.012 to 0.078 (average 0.031) under baseline conditions and from 0.010 to 0.017 (average 0.014) after administration of nonradioactive L-phenylalanine (100 mg/kg). The net rate of brain accumulation of L-methionine ranged from 0.42 to 2.89 (average 1.28) nmol/min/cc, and decreased by 27.5-91.2% (average 53.9%) after L-phenylalanine. PET-estimated accumulation rates (ml/min/cc) of [11C]L-methionine ranged from 0.004 to 0.028 (average 0.016) baseline and from 0.010 to 0.021 (average 0.017) after L-phenylalanine. Initial volumes of distribution (ml/cc) of [11C]L-methionine (dual detector) were 0.044-0.070 (average 0.058) baseline and 0.032-0.074 (average 0.051) after phenylalanine and (PET) 0.026-0.098 (average 0.051) baseline and 0.021-0.061 (average 0.042) after phenylalanine. PET permits more accurate measurement of tracer accumulation by brain, excluding noncerebral regions included in dual-detector measurements. The dual-detector system permits better temporal resolution, facilitating kinetic analysis, and requires only one-fortieth the dose of tracer needed for PET. Multiple studies in the same patient are thus possible at low cost.

Biological Transport↗
PubMed1988

Creatinine measurements often yielded false estimates of progression in chronic renal failure.

In 9 of 22 observation periods (lasting an average of 15 months) in 17 patients with moderate to severe chronic renal failure (GFR 4 to 23 ml/min), rates of progression as estimated from the linear regression on time of 24-hour creatinine clearance (b1) differed significantly from rates of progression as estimated from the regression on time of urinary clearance of 99mTc-DTPA (b2), during all or part of the period of observation. b1 exceeded b2 in four cases and was less than b2 in the other five. Thus there were gradual changes in the fractional tubular secretion of creatinine in individual patients, in both directions. Owing to these changes, measurements of creatinine clearance gave erroneous impressions of the rate or existence of progression during all or a portion of the period of observation in nearly half of these patients. In the 22 studies as a group, using the entire periods of observation, b1 indicated significantly more rapid progression (by 0.18 +/- 0.06 ml/min/month, P less than 0.01) than did b2, and had a significantly greater variance. Measurements of progression based on the rate of change of reciprocal plasma creatinine (multiplied by an average rate of urinary creatinine excretion in each study) were equally misleading, even though less variable. We conclude that sequential creatinine measurements are often misleading as measures of progression and should, when feasible, be replaced by urinary clearance of isotopes in following patients with chronic renal failure.

Creatinine↗
PubMed1988

Effect of exercise hemoconcentration and hyperosmolality on exercise responses.

We investigated the effects of a decrease in plasma volume (PV) and an increase in plasma osmolality during exercise on circulatory and thermoregulatory responses. Six subjects cycled at approximately 65% of their maximum O2 uptake in a warm environment (30 degrees C, 40% relative humidity). After 30 min of control (C) exercise (no infusion), PV decreased 13.0%, or 419 +/- 106 (SD) ml, heart rate (HR) increased to 167 +/- 3 beats/min, and esophageal temperature (Tes) rose to 38.19 +/- 0.09 degrees C (SE). During infusion studies (INF), infusates were started after 10 min of exercise. The infusates contained 5% albumin suspended in 0.45, 0.9, or 3.0% saline. The volume of each infusate was adjusted so that during the last 10 min of exercise PV was maintained at the preexercise level and osmolality was allowed to differ. HR was significantly lower (10-16 beats/min) during INF than during C. Tes was reduced significantly during INF, with trends for increased skin blood flow and decreased sweating rates. No significant differences in HR, Tes, or sweating rate occurred between the three infusion conditions. We conclude that the decrease in PV, which normally accompanies moderate cycle exercise, compromises circulatory and thermal regulations. Increases in osmolality appear to have small if any effects during such short-term exercise.

Body Temperature Regulation↗
PubMed1988

Changes in plasma volume during bed rest: effects of menstrual cycle and estrogen administration.

Bed rest (BR) is associated with a decrease in plasma volume (PV), which may contribute to the impaired orthostatic and exercise tolerances seen immediately after BR. The purpose of this study was to determine whether increases in blood estrogen concentration, either during normal menstrual cycles or during exogenous estrogen administration, would attenuate this loss of PV. Nineteen healthy women (21-39 yr of age) completed the study. Twelve women underwent duplicate 11-day BR without estrogen supplementation. PV decreased significantly (P less than or equal to 0.01) during both BR's, from 2,531 +/- 113 to 2,027 +/- 102 ml during BR1 and from 2,445 +/- 115 to 2,244 +/- 96 ml during BR2. The women who began BR in the periovulatory stage of the menstrual cycle (n = 3), a time of elevated endogenous estrogens, had a transient delay in loss of PV during the first 5 days of BR. Women who began BR during other stages of the menstrual cycle (n = 17) showed the established trend to decrease PV primarily during the first few days of BR. Seven additional women underwent a single 12-day BR while taking estrogen supplementation (1.25 mg/day premarin). PV decreased during the first 4-5 days of BR, then returned toward the pre-BR level during the remainder of the BR (pre-BR PV, 2,525 +/- 149 ml; post-BR PV, 2,519 +/- 162 ml). Thus menstrual fluctuations in endogenous estrogens appear to have only small transient effects on the loss of PV during BR, whereas exogenous estrogen supplementation significantly attenuates PV loss.

Adult↗
PubMed1988

Single photon emission computed tomography of the thyroid.

Single photon emission computed tomography (SPECT) entails imaging at multiple positions along an arc and computed-assisted reconstruction of transaxial, coronal, and sagittal images. To determine if SPECT imaging of the thyroid augments information provided by planar imaging, both SPECT and pinhole planar scans were performed in 52 patients with thyroid disease. After 123I (n = 45), Tc99m (n = 5), or thallium-201 (n = 2) administration, images were acquired at 30 intervals along a 180 degree arc. Nodules that were hypofunctioning on planar scans (n = 4) were equally well shown on SPECT images. SPECT analysis of 123I uptake by 5 palpable nodules with completely normal 123I planar scans demonstrated the nodular tracer uptake was increased (n = 1), equivalent (n = 3), or decreased (n = 1) in comparison with that of extranodular tissue. In 6 of 12 multinodular goiters, transaxial SPECT images showed tracheal compression, which was confirmed by neck x-ray, flow volume loops, or surgery. A neck phantom study was performed to assess the accuracy of SPECT-determined functional thyroid volume. SPECT-estimated volumes (30-173 mL; n = 11) correlated well with true volumes (r = 0.996; P less than 0.001). Our observations suggest that SPECT is a useful adjunct to planar imaging in 1) estimating functional volume for 131I dosimetry; 2) evaluating the size, extension, and tracheal compression of multinodular goiter; and 3) determining the functional properties of palpable nodules with normal 123I planar pinhole images.

Goiter↗