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Biomedical subjects

D A Weber

Publications and source records attributed to D A Weber.

At least 55 records · Page 3Linked to original sources
PubMed1993

Biodistribution of Sn-117m(4+)DTPA for palliative therapy of painful osseous metastases.

Tin-117 has certain physical characteristics (half-life of 13.6 days, low-energy-conversion electrons, gamma photon of 158.6 keV) that suggest that it may be a favorable agent for radionuclide therapy. It has been shown in animal models that Sn-117m in the chemical form Sn(4+)diethylenetriaminepentaacetic acid localizes selectively in bone. The authors therefore studied its whole-body distribution in 10 patients to obtain absorbed dose estimates for therapy. The results showed that more than 50% of the administered activity was absorbed in the bones of patients with metastatic carcinoma. Retention was determined primarily by radioactive decay. For adult men, the radiation absorbed dose estimate averaged 54.8 mGy/MBq (203 rad/mCi) to bone surfaces and 6.1 mGy/MBq (22.6 rad/mCi) to the red marrow. All other tissues received less than 1/10 of the dose received by red marrow. These results suggest that a clinical therapeutic trial should be attempted.

Adult↗
PubMed1993

High resolution pinhole SPECT for tumor imaging.

High-resolution, non-invasive, 3D-imaging techniques would greatly benefit the investigation of the localization properties of tumor-specific radiopharmaceuticals in laboratory animals. The present study reports how pinhole SPECT can be applied to tumor localization studies in small laboratory animals to provide high resolution SPECT images in vivo. Pinhole SPECT was performed using a rotating scintillation camera, equipped with a pinhole collimator. The sensitivity of a 2 mm diameter collimator at 45 mm from the source is 90 cps/MBq for 99mTc. The planar spatial resolution at a 45 mm distance is 2.2 mm. The transaxial spatial resolution, with a distance of 45 mm between the collimator aperture and the axis of rotation, is 3.1 mm. For SPECT imaging, spatial linearity is preserved across the usable field-of-view. The major advantage of the high resolution properties of pinhole tomography is demonstrated by the enhanced lesion-to-normal-brain uptake ratio achieved on tomographic slices as compared to planar images. For example, 201Tl tumor-to-normal-brain uptake ratios of 1.1 to 1.3 observed on planar images, corresponded to ratios ranging from 3.2 to 3.7 on the SPECT slices. Examples of the activity distributions of two radiopharmaceuticals in tumor and in normal brain for sagittal and coronal images are given. In all cases, tumors are clearly delineated on the pinhole SPECT slices. The present study shows that pinhole SPECT performed with standard SPECT instrumentation can give high spatial resolution images, with a FWHM approximately 3 mm and a sensitivity approximately 100 cps/MBq for 99mTc.

Animals↗
PubMed1993

SPECT and planar brain imaging in crack abuse: iodine-123-iodoamphetamine uptake and localization.

The uptake, distribution, and clearance properties of 123I-IMP in the brain were evaluated in controls and asymptomatic crack users to investigate cerebral blood flow alterations in crack abuse. Serial dynamic planar images of the brain (0-25 min), SPECT of the brain (0.5 hr and 4 hr) and whole-body scans (75 min) were obtained in 21 crack abusers and 21 control subjects. Major observations include: (a) foci of abnormally reduced 123I-IMP activity mainly in the frontal and parieto-occipital cortex or marked irregularities in the uptake of 123I-IMP throughout the cerebral cortex consistent with moderate to severe disruption in regional cerebral blood flow were observed on the 0.5 hr SPECT images of 16/21 asymptomatic crack users; (b) no correlation could be demonstrated between the incidence or severity of SPECT perfusion abnormality with the frequency, amount or length of time of crack use; (c) focal perfusion defects observed in 6/21 crack users on the 0.5-hr SPECT images partially or completely filled-in on delayed SPECT at 4 hr in four of six subjects; (d) the rate of cerebral uptake of 123I-IMP in crack users averaged 23% less than observed in control subjects over the first 25 min after tracer administration; and (e) 123I-IMP activity reaching the brain of cigarette smoking control subjects (n = 14) at 25 min after injection averaged 42.5% less than in nonsmoking controls (n = 7). Quantitative measurements of the uptake and distribution properties of 123I-IMP in the brain proved to be an objective, sensitive and useful measure of regional cerebral blood flow in crack abuse.

Adult↗
PubMed1992

Sequences in both class II major histocompatibility complex alpha and beta chains contribute to the binding of the superantigen toxic shock syndrome toxin 1.

Class II major histocompatibility complex (MHC) molecules present peptides derived from processed antigen to antigen-specific CD4-positive T cells. In addition, class II molecules bind with high affinity another class of antigens, termed superantigens. T cell stimulation by superantigens depends almost exclusively on the V beta segment expressed by the T cell receptor (TCR). Mapping of the superantigen binding site on class II molecules should provide valuable information on how MHC and TCR molecules interact. Recombinant mouse I-A class II molecules expressed on transfected L cells were analyzed for their ability to bind the toxic shock syndrome toxin 1. Polymorphic residues in the alpha helices of both the alpha and beta chains of I-A contributed to quantitative toxin binding, suggesting that the toxin binds to either a combinatorial or a conformational site on class II MHC molecules.

Animals↗
PubMed1992

Effect of pattern of aerosol inhalation on clearance of technetium-99m-labeled diethylenetriamine pentaacetic acid from the lungs of normal humans.

The clearance rate of inhaled aerosols of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) from the lungs provides a rapid, clinically useful, noninvasive index of pulmonary epithelial permeability. In order to identify a method that minimizes intrasubject and intersubject variability and thereby provides a reliable means to identify patients with abnormal values, we administered a submicronic aerosol of 99mTc-DTPA to 10 healthy, nonsmoking male subjects with either tidal breathing (Vtidal) or multiple vital capacity maneuvers (VVC). Subjects then spontaneously breathed room air while counting continued for 30 min. Monoexponential clearance rates over 7, 15, and 30 min were compared with a two-compartment, biexponential analysis over 30 min. Intrasubject reproducibility was evaluated by repeating clearance 2 to 156 days later. Monoexponential clearance following VVC at 30 min equaled 1.36 +/- 0.55%/min compared with 0.83 +/- 0.25%/min for Vtidal (p less than 0.025). VVC inhalations resulted in a larger fast compartment of 16 +/- 12% compared with 3 +/- 2% with tidal breathing (p less than 0.01). The least intrasubject variability with coefficient of variation (CV) of +/- 18% was obtained with monoexponential analyses after Vtidal during 15 min of scanning and with either breathing maneuver over 30 min. Monoexponential clearance for 30 min with Vtidal gave the least scatter between subjects, with CV of +/- 30%. These data show that simple tidal inhalations of 99mTc-DTPA followed by a monoexponential analysis of the 30-min time-activity curve from both lungs minimize the degree of variability between and among subjects and provide a predicted normal value of clearance of 0.83 +/- 0.25%/min. The development of a more rapid curvilinear clearance followed by delivery VVC suggests that several deep breaths transiently increase epithelial permeability or reduce the volume of liquid in the alveolar subphase in some regions. Resting for 20 min prior to inhaling the aerosol of 99mTc-DTPA is recommended to avoid alterations in clearance rates from deep breathing.

Administration, Inhalation↗
PubMed1992

Enhanced healing of cutaneous wounds in rats using beads with positively charged surfaces.

The efficacy of electrical fields in soft-tissue repair is unclear. Materials with a charged surface provide a localized charged environment. We examined the effects of surface-charged particles in wound healing in rats with paired dorsal incisions with one side serving as a control. Tensiometry demonstrated that after 10 days, wounds with positively charged particles were 53 percent stronger (p less than 0.001) than controls (10 rats, 30 wound strips), whereas differences with negatively charged (6 rats, 15 strips) or uncharged beads (11 rats, 33 strips) were insignificant. Histologically, wounds with positively charged particles were characterized by large quantities of collagen-rich connective tissue and by prominent bead-associated giant cells. At 94 days, no differences in wound strength were noted. This method of creating charged local environments has potential clinical implications and may add insights into the behavior of cells in response to charged stimuli.

Analysis of Variance↗
PubMed1991

Measuring body fat: calibrating the rulers. Intermethod comparisons in 389 normal Caucasian subjects.

A systematic study of 389 normal Caucasians stratified for sex and age compared all of the traditional methods for measuring fat: body water, underwater weighing, body potassium, and anthropometrics and the newer methods of dual-photon absorptiometry, bioimpedance analysis, and total body electrical conductivity. Measurements by all methods are highly intercorrelated, but methods differences show the population means for fat percent to range from 26 to 35% of body weight across eight methods. All methods show increasing fat (as % body weight) with age in both sexes but vary in secular slope. The goal of this report is to provide direct translations between each of the eight methods. Intermethod comparison equations are given as simple linear regressions by using each method both as dependent and independent variable for each sex, permitting translation for results by any method to any other.

Adipose Tissue↗
PubMed1991

Increased lung permeability following long-term use of free-base cocaine (crack).

The clearance of inhaled 99mTc DTPA aerosol from the lungs is used as an index of lung epithelial permeability. Using the radioaerosol method, we investigated the effects of long-term "crack" (free-base cocaine) inhalation on lung permeability in 23 subjects. Eighteen control subjects (12 nonsmokers and 6 cigarette smokers) with no history of drug use were also studied. Subjects inhaled approximately 150 muCi (approximately 5.6 MBq) of 99mTc DTPA aerosol and quantitative gamma camera images of the lungs were acquired at 1-min increments for 25 minutes. Regions of interest (ROIs) were selected to include the following: (1) both lungs; (2) each individual lung; and (3) the upper, middle, and lower thirds of each lung. 99mTc DTPA lung clearance was determined from the slopes of the respective time-activity plots for the different RIOs. Radioaerosol clearance half-times (T1/2) for the seven nonsmoking crack users (61.5 +/- 18.3 minutes) were longer than for the seven cigarette-smoking crack users (27.9 +/- 16.9 minutes) and nine cigarette-smoking crack plus marijuana users (33.5 +/- 21.6 minutes). T1/2 for the nonsmoking crack users was significantly shorter (p less than 0.001) than for the nonsmoking control group (123.8 +/- 28.7 minutes). T1/2 for the cigarette-smoking drug users was similar to that of the cigarette-smoking control group (33.1 +/- 17.8 minutes), suggesting a similar mechanism of damage from the smoke of crack and tobacco. From these groups, one nonsmoker and 11 cigarette smokers displayed biexponential 99mTc DTPA clearances, indicative of greater lung injury than found in the usual cases of monoexponential clearance. The upper lungs of all crack users groups cleared faster than the lower lungs. The faster and biexponential clearance properties of inhaled 99mTc DTPA aerosol were the principal functional abnormalities found in all the drug users. In contrast, 19 of 23 crack users had normal spirometry and gas exchange. These results indicate that 99mTc DTPA may provide a sensitive and useful assay to evaluate the physiologic effects of cocaine inhalation in the lung.

Adult↗
PubMed1991

Imaging of cocaine-induced global and regional myocardial ischemia.

Severe and often fatal cardiac complications have been reported in cocaine users with narrowed coronary arteries caused by atherosclerosis as well as in young adults with normal coronaries. We have found that in normal dogs cocaine induces severe temporary hypoperfusion of the left ventricle as indicated by a significantly lower 201Tl concentration compared to the baseline state. The most significant decrease in uptake occurred 5 min after injection and was more pronounced in the septal and apical segments. Following intravenous administration of cocaine, instead of gradual disappearance of 201Tl from the left ventricle, there was continuous increase in 201Tl concentration in the left ventricle. These imaging experiments indicate that the deleterious effects of cocaine on the heart are probably due to spasm of the coronaries and decreased myocardial perfusion. Since spasm of the large subpericardial vessels does not seem to explain the magnitude of the increased coronary resistance and decreased coronary flow after cocaine as described in the literature, it is suggested that microvascular spasm of smaller vessels plays a major role in the temporary decrease in perfusion. The data may also suggest that severe temporary myocardial ischemia is probably the initiating factor for the cardiac complications induced by cocaine.

Animals↗
PubMed1991

Effects of visual stimulation on the redistribution of iodine-123-IMP in the brain using SPECT imaging.

A study was performed to validate the assumption that redistribution and clearance of [123I]IMP localization in the brain are unaffected by changes in ambient light levels and visual stimulation occurring after radiopharmaceutical is administered and deposited in the brain. Serial SPECT and planar imaging studies were performed on six healthy, volunteer, adult male subjects under resting, nonactivation conditions. Studies were repeated 7 days later with each subject exposed to strobe light stimulation prior to delayed SPECT procedures at 3 hr. Redistribution and clearance of 123I-IMP in the brain were examined in cortical, subcortical, and cerebellar regions on transaxial slices for the two sets of serial procedures in each subject. Visual stimulation following the initial uptake of [123I]IMP did not affect the distribution or clearance of [123I]IMP in the brain, including the visual cortex, and therefore should not influence the interpretation of delayed SPECT images.

Adult↗
PubMed1990

High precision in-vivo neutron activation analysis: a new era for compartmental analysis in body composition.

We have focused on two topics in body composition research. The first is basic: we must quantitatively define the interrelationships of the body compartments to one another in health before studying these relationships in disease. The precisions now available can enable us to get to do this work, over the full range of age, race, and occupational diversity. The second direction is more modest and more technical, but nonetheless important. It is the calibration and validation of surrogate measurement methods suitable for field research conditions, doctors' offices, intensive care units, etcetera. Our methods have advanced in fundamental ways. We have an obligation to see them applied effectively.

Adipose Tissue↗
PubMed1990

Cross-modal functions in alcoholism and aging.

Two experiments were performed to measure separate aspects of cross-modal functions in normal and alcoholic research participants: matching, and utilization of concepts. In Experiment 1, cross-modal equivalence-matching was measured, i.e. the ability to select in a second modality (e.g. vision), the same stimulus that was first presented in a different modality (e.g. touch). Experiment 2 measured cross-modal transfer of information about stimulus dimensions, i.e. the ability to recognize and use the concepts of texture and form, based upon prior experience solving tactual problems, to solve visual problems. Fifty-five normal and alcoholic research participants comprised the following five groups: 13 young normals (YN) and 10 young alcoholics (YA), 28-48 years of age; 13 older normals (ON) and 14 older alcoholics (OA), 50-71 years of age; and 5 alcoholic Korsakoff patients (K), 55-68 years of age. Separate subgroups of 9 age-matched ONs and 9 OAs were devised for purposes of statistical analyses of data involving the 5 Ks. Results of the experiments indicated that aging is associated with decline in tactual discrimination ability. Further, cross-modal functions appear to be compromised by alcoholic Korsakoff's disease, and--to a lesser extent--by the combined effects of alcoholism and normal chronological aging. Brain mechanisms important for normal cross-modal functions are discussed.

Adult↗
PubMed1990

A novel chromosomal TEM derivative and alterations in outer membrane proteins together mediate selective ceftazidime resistance in Escherichia coli.

A clinical Escherichia coli isolate (MG32) resistant to ceftazidime but susceptible to other third-generation cephalosporins was previously examined and found to harbor TEM-1 and exhibit alterations in outer membrane proteins. Reexamination of this isolate revealed the additional presence of a novel TEM-1 derivative, now designated TEM-12. Evaluation of ceftazidime and cefotaxime minimum inhibitory concentrations for isogenic derivatives demonstrated a major role for TEM-12 in the decreased susceptibility observed. This was selectively enhanced for ceftazidime resistance by the altered porins of E. coli MG32. TEM-12 appeared identical to TEM-101, an in vitro TEM derivative, in both isoelectric point (pI 5.25) and substrate profile. Hybridization and cloning of the TEM-12 determinant revealed that, unlike other TEM derivatives, TEM-12 is chromosomally encoded, not plasmid-encoded.

Bacterial Outer Membrane Proteins↗
PubMed1990

Emotional perception and memory in alcoholism and aging.

The ability to identify and recognize emotional materials was studied in 10 male alcoholic Korsakoff patients, 27 male non-Korsakoff alcoholics, and 31 male nonalcoholic controls, across a wide age range (23 to 77 years). Stimulus materials were presented in two sensory modalities; the materials were photographs of faces expressing one of four emotions (happy, sad, angry, or neutral), and recordings of sentences with emotional intonations or semantic meanings expressing the same four emotions. Results of the experiments showed consistently severe deficits in emotional functions in the Korsakoff patients, but only minor alterations in the non-Korsakoff alcoholics. Older subjects, whether or not they had a history of alcoholism, also exhibited significant deficits on most of the tasks. Results of the study did not provide strong support for the premature aging hypothesis of alcoholism, which suggests that alcoholism accelerates aging, beginning either at the onset of heavy drinking early in adult life, or later in life after the normal manifestations of aging have begun to appear. Results are related to brain mechanisms in emotional perception and memory functions.

Adult↗
PubMed1990

Diverse potential of beta-lactamase inhibitors to induce class I enzymes.

The ability of various beta-lactamase inhibitors to induce class I beta-lactamases was assessed. Clavulanate was the most active compound, inducing Morganella morganii, Aeromonas caviae, and Enterobacter aerogenes over a broad concentration range and Citrobacter freundii, Pseudomonas aeruginosa, and Serratia marcescens at high concentrations. Disk approximation tests paralleled these results, with clavulanate, but not sulbactam or tazobactam, antagonizing the activity of several beta-lactams against these organisms.

Anti-Bacterial Agents↗
PubMed1990

Beta-lactamase production in members of the family Enterobacteriaceae and resistance to beta-lactam-enzyme inhibitor combinations.

Recent reports that members of the family Enterobacteriaceae that produce high levels of certain beta-lactamases are often resistant to ticarcillin-clavulanate prompted this study to assess the relationship between type and amount of enzyme produced and susceptibility to ticarcillin-clavulanate, piperacillin-tazobactam, and cefoperazone-sulbactam. Agar dilution MICs were determined by using 73 strains of Enterobacteriaceae that produced a single beta-lactamase that had been characterized and quantified and a beta-lactamase-negative control strain of Escherichia coli. For E. coli and Klebsiella pneumoniae, MICs of each combination increased as levels of TEM, SHV-1, or class IV enzymes increased. However, the percentage of strains that were resistant was highest for ticarcillin-clavulanate (32%), with only 18 and 6% resistant to piperacillin-tazobactam and cefoperazone-sulbactam, respectively. Strains producing PSE-1, regardless of level, were resistant or moderately susceptible to ticarcillin-clavulanate but were susceptible to piperacillin-tazobactam and cefoperazone-sulbactam. HMS-1 and OHIO-1 beta-lactamases were associated with resistance to ticarcillin-clavulanate and piperacillin-tazobactam, respectively. High levels of class IV enzymes in Klebsiella oxytoca were associated with resistance to all three combinations. These results indicate that the level and type of beta-lactamase produced by members of the family Enterobacteriaceae are important determinants of susceptibility to beta-lactam-inhibitor combinations, especially ticarcillin-clavulanate.

Anti-Bacterial Agents↗