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Biomedical subjects

D A Weber

Publications and source records attributed to D A Weber.

At least 91 records · Page 5Linked to original sources

Lung clearance of inhaled 99mTc-DTPA in the dog.

We studied the reproducibility of measuring an index of permeability of respiratory epithelium in dogs using aerosolized 99mTc-DTPA (diethylenetriaminepentaacetate). The method uses a gamma camera to measure the rate of clearance of soluble radioactive aerosol deposited in the lung. A solution of 99mTc-DTPA in normal saline was aerosolized by an ultrasonic nebulizer. Eleven anesthetized dogs breathing spontaneously inhaled the resulting droplets for 2 min. Mass median aerodynamic diameter of the droplets was 4.4 micron with a geometric standard deviation of 2.1. Clearance from the lung was monitored by quantitative gamma camera imaging for up to 2 h. For a 60-min observation period, the biological half-life for clearance of 99mTc-DTPA from both lungs was 66 +/- 11 (SD) min. Apical regions cleared significantly slower than basal regions, probably because of a larger portion of bronchial tissue in the apical region of the dog's lung. The best reproducibility of absorption of 99mTc-DTPA in the dog was obtained from basal regions and peripheral zones of the lung within 30 min after inhalation of the radioaerosol.

Aerosols↗

Increased susceptibility to pentylenetetrazol-induced seizures in adult rats following electrical kindling during brain development.

The persistence of seizure susceptibility into adulthood following kindling in the immature rat was assessed. Rats kindled electrically at age 30 days were significantly more susceptible to pentylenetetrazol (PTZ)-induced seizures as adults than a control group. These findings demonstrate that kindling in the immature brain results in a permanent alteration in seizure susceptibility.

Animals↗

Immunochemical studies of antisera to human fibrinopeptide-B.

The immunochemical specificity of rabbit antisera to human fibrinopeptide-B (FPB) has been studied by comparing the relative abilities of FPB and of various proteins and peptides containing the NH2-terminal segment of the B beta-chain of human fibrinogen to inhibit the binding of a radioiodinated FPB derivative by each of seven anti-FPB sera. Anti-FBP sera varied in the extent to which they cross-reacted with fibrinogen, the NH2-terminal disulfide knot of fibrinogen (N-DSK), B beta 1(Pyr)-118(Met), B beta 1(Pyr)-42(Arg), and desarginyl-FPB. Anti-FPB sera have been identified that discriminate effectively between FPB and larger FBP-containing peptides; such antisera can be used to measure FPB in the absence of the larger peptides or to demonstrate the presence of larger peptides such as B beta 1(Pyr)-42(Arg) in extracts of clinical plasma samples by means of an increase in FPB immunoreactivity following thrombin treatment. One anti-FPB serum has been identified that is capable of detecting desarginyl-FPB, and this antiserum has been used in the development of a radioimmunoassay for desarginyl-FPB. Thus, by precisely defining the specificity of anti-FPB sera, it has been possible to identify antisera that are useful, not only in the measurement of FPB, but also in the detection of other important related molecules, such as B beta 1(Pyr)-42(Arg) and desarginyl-FPB. The immunochemical detection of these FPB-related peptides should provide useful information concerning the action of proteolytic enzymes, such as plasmin on the NH2-terminal segment of the B beta-chain of fibrinogen, and of carboxypeptidase-B on free FPB, in human plasma.

Cross Reactions↗

A study of irradiated bone. Part II. changes in Tc-99m pyrophosphate bone imaging.

Quantitative Tc-99m pyrophosphate bone imaging was carried out in locally irradiated and control areas of New Zealand albino rabbits to determine the potential role of bone imaging in assessing the time course of radiation effects in bone and surrounding tissues. In vitro Tc-99m tissue assays, and serial radiographs. from the irradiated and contralateral limbs were obtained at regular intervals over the first 12 mo following irradiation for comparison with quantitative results from the camera studies. The autoradiographic localization of TcPPi was also studied in the x-irradiated and contralateral bones of the rabbits. The results show that TcPPi bone imaging is a sensitive in vivo indicator of early radiation effects upon vasculature and bone remodeling. The findings suggest that the quantitative bone-imaging technique may be useful in the evaluation of the effects of treatment modalities on the skeleton.

Animals↗

A study of irradiated bone. III. Scintigraphic and radiographic detection of radiation-induced osteosarcomas.

Within 1 yr after localized irradiation of a hind limb with single (1756 rads) or fractionated (4650 rads in 3 wk) x-ray doses, radiation-induced osteosarcomas were observed in four of nine single-dose rabbits and two of 11 fractionated-dose rabbits. Tumors were observed in the proximal tibia in five cases and the distal femur in one case. In terms of production of osteoid or osseous tissue, three tumors were well differentiated, one slightly differentiated, and two (spindle-cell tumors) undifferentiated. This report summarizes the Tc-99m pyrophosphate (TcPPi) imaging and autoradiographic, radiographic, and histologic studies of these osteosarcomas. The four differentiated osteosarcomas were detected 1--2.5 mo earlier by TcPPi imaging than by radiography, whereas the two undifferentiated tumors were suspected 2 wk or 3.5 mo earlier radiographically. Autoradiograms showed TcPPi localization in bone produced by differentiated osteosarcomas, and in regions of reactive bone resorption and formation peripheral to tumors. The results support a recommendation for combined radiographic and scintigraphic techniques for the early detection of osteosarcomas.

Animals↗

Dynamics of Technetium-99m methylenediphosphonate imaging of the femoral head after hip fracture.

A prospective study of the development of necrosis of the femoral head was performed in 34 patients with fractures of the femoral neck. Technetium-99m MDP images of the hip regions were obtained immediately after nailing of the hip and at four, eight and 12 months. There was a good correlation between qualitative and numeric evaluation of isotope uptake in the femoral heads. Comparison of the activity level in the femoral head on the fracture side with that in the contralateral control site showed activity ratios to vary between < 1.0 for those heads showing a general reduction in activity on conventional images to > 1.4 with a mean of 2.0 for those showing increased activity. The initial postoperative images in 2/7 undislocated fractures showed a marked depression in femoral head activity on the fracture side; 13/21 dislocated fractures showed a similar defect suggesting a significant loss of bone remodeling. Normal Tc-99m activity in the femoral head (category 2) was observed in two fracture cases imaged within 24 hours of fracture, just prior to nailing. Repeat studies within one week of fracture and nailing demonstrated a marked depression in activity (category 0). Radiographic evidence of collapse later developed in both patients. The perfusion and blood pool images were useful for identifying femoral heads with deficient circulation. This investigation has demonstrated that the nailing procedure may threaten the vascular condition of the femoral head in hip fracture, that a dead head may be radiographically normal and clinically asymptomatic, and that the metabolic condition of the femoral head may be expressed in numeric terms suitable for statistical analysis.

Adult↗

[Correlation between radiological, scintigraphic and histological changes in bone in rabbits following irradiation with single and fractionated doses (author's transl)].

The left hind legs of eight rabbits were irradiated with 1.750 rad in a single dose or with 4,650 rad divided over a period of three weeks. These animals, as well as four who had not been irradiated, were examined periodically radiologically and with 99m Technetium pyrophosphate scintigrams during one year. No difference could be detected between the results of the single and fractionated doses. Scintigraphically there was a biphasic increase in uptake, the first peak co-inciding with the irradiation and of vascular origin, whereas the second peak occurred at four months and was due to a change in bone metabolism. At the end of a year uptake in the irradiated limb was slightly reduced. The earliest radiological changes were found after six months, at the end of the second scintigraphic peak; they consisted of coarsening and blurring of the trabeculae, nonhomogeneous spotty mineralisation and endosteal scalloping. Six animals developed a radiation-induced bone sarcoma, first demonstrated either by scintigraphy or radiology depending on its histology. The value of combining radiological and scintigraphic examinations for the early detection of post-radiation abnormalities is stressed.

Animals↗

Electron microscopic observations of polysaccharide components in polymyxin B treated outer membranes from Serratia marcescens.

Treatment of outer membranes of Serratia marcescens with polymyxin B results in the formation of blebs. This effect is thought to be due to the action of the antibiotic on the lipopolysaccharides, proteins, phospholipids or a combination thereof. It is unclear whether this effect is dissociative, degradative or due to an inhibition of the assembly of outer membrane components. Prior studies showed that lipopolysaccharides and polymyxin B form complexes, but direct visualization of the in situ action of polymyxin B had not been accomplished. Isolated outer membranes normally exhibit a periodicity of the polysaccharide molecules when stained by the thiosemicarbazide-silver technique. Polymyxin B treated outer membranes display a change in their basic morphology. This effect is very drastic in the sensitive strain as demonstrated by the large gaps in the deposition of the granules in the modified outer membrane structure. Thus it appears that the polysaccharide molecules (probably the lipopolysaccharide) either alone or in association with protein or phospholipids are the primary targets of the antibiotic.

Cell Membrane↗

A study of irradiated bone: I. histopathologic and physiologic changes.

Histologic and tracer techniques were used to investigate and document alterations in bone pathophysiology subsequent to irradiation of the left hind limb of rabbits. Numerous time-dependent changes were observed. Among these were an inflammatory response shortly after irradiation, and an increase in the remodeling of cortical bone, which peaked between 3 and 6 mo after irradiation. The changes in bone remodeling correlated with changes in vascular patency in a manner consistent with the hypothesis that radiation damage in mature bone is mediated primarily through alterations in the fine vasculature. The findings of this study provide important information on the time course of changes in bone pathophysiology following regional irradiation. They are used in the second of this series of papers to help establish which mechanisms are responsible for postirradiation alterations in the localization of Tc-99m pyrophosphate in these rabbits.

Animals↗

Computers in nuclear medicine: introductory concepts.

Computers play an important role in image and data processing in nuclear medicine. Applications extend from relatively simple mathematical processing of in vitro specimen assays to more sophisticated image reconstruction procedures for emission tomography. The basic concepts and terminology associated with computer applications in image and data processing in nuclear medicine are presented here.

Computers↗

Factors influencing paper chromatographic analysis of technetium-99m phosphorus compounds: concise communication.

A single-paper chromatographic system has been developed, capable of resolving Tc-99m dioxide, [99mTc] pertechnetate and Tc-99m phosphorus compounds. The best separations are obtained with CM82 paper developed in 0.5 m naCl, and 3MM or ashless No. 40 paper developed in 1 M sodium acetate buffer. In these systems, 99TcO2 remains at the origin, while 99mTcO4--and Tc-99m phosphorus compounds move with Rf values of 0.56--0.75 and 0.80--1.0, respectively.

Chromatography, Paper↗

A model for local accumulation of bone imaging radiopharmaceuticals.

A simple models, having phenomenological parameters as variables, is developed for predicting local radioactive tracer accumulation in bone. Blood delivering tracer to one gram of bone is treated as a compartment separate from the remainder of the circulation in order to observe the effects produced by variations in both bone flow and barrier permeability. Kinetic curves derived by analog computer were obtained for normal and perturbed values of the parameters for F-18 and Ca-47 in a segment of rabbit bone. Apparent confirmation of the predicted influence of decreased blood flow on F-18 deposition was obtained by measuring bone uptake following constriction of the right femoral artery in five rabbits. Such models may prove useful in explaining variations in uptake for different agents, in selecting imaging times, and in correlating uptake patterns with disease.

Animals↗

Kinetics and imaging characteristics of 99mTC-labled complexes used for bone imaging.

Activity levels of 99TC-labeled compounds, 18F, and 85Sr were obtained at 1, 3, and 5 hr. postinjection in normal and healing fractured bone and in soft-tissue rat specimens. Serial diagnostic bone images and blood and urine kinetics were obtained in patients with each of the TC-labeled compounds. Computer-processed images were used to evaluate in vivo kinetics. 99mTC pyrophosphate provides the best overall characteristics for bone imaging. Improved quality and bioassay procedures are required, however, before any one agent can be designated the radiopharmaceutical of choice for diagnostic bone imaging.

Animals↗

Evidences for complex formation between polymyxin B and lipopolysaccharides from Serratia marcescens.

In vitro and in vivo complex formations of polymyxin B and lipopolysaccharides (LPS) from resistant and sensitive cells of Serratia marcescens were studied by polyacrylamide gel electrophoresis in sodium dodecyl sulfate and electron microscopy. In vitro treatment of LPS from resistant cells with polymyxin B gave two populations of spherical complexes of differnt molecular weights as determined electrophoretically. Similar treatment of LPS from sensitive cells resulted in dissociation of the LPS-protein and subsequent complexing with the LPS moiety into stable spheres. In vivo treatment of resistant cells with polymyxin B resulted in LPS-polymyxin B complexes which were comparatively smaller and existed in two morphological forms; spheres and linear ribbons. LPS from the sensitive cells were degraded extensively into small rods and an amorphous mass by the in vivo polymyxin B treatment. In both systems, the electrophoretic results consistently matched the electron microscopic evidences for complex formation of LPS with polymyxin B. It is suggested that the disruptive effects of polymyxin B on LPS in the outer membrane of S. marcescens may be the explanation for the change in permeability barrier in the resistant cells and disorganization of the outer membrane and subsequent death in the sensitive cells. Furthermore, the ability of the LPS to complex with the polymyxin B molecules in resistant cells may be the basis of their resistance to the antibiotic.

Bacterial Proteins↗

Effect of polymyxin B on outer membranes of Serratia marcescens: morphological alterations of the outer membranes and their lipopolysaccharide components.

The in vitro or the in vivo treatment of outer membranes and their lipopolysaccharide (LPS) components from Serratia marcescens with the antibiotic polymyxin B appeared to alter their normal morphology in a sequential manner. The normal spherodial morphology was destablized into a flattened structure after the in vitro treatment of either the resistant strain 08 or the sensitive strain Bizio. The more severe in vivo treatment of the outer membranes from the resistant strain converted the flattened forms further into spheres with undefined periphery and diminished sizes. On the other hand, the same treatment of the outer membranes from the sensitive strain resulted in numerous incomplete spheres and short rods, which were similar to the various morphological forms of the LPS components after polymyxin B treatment. The difference in the morphological changes of the outer membranes and their LPS components of the resistant and sensitive strains after polymyxin B treatment may be explained by the variation of the susceptiblity of the membrane components to the degradative effects of the antibiotic.

Cell Membrane↗