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Biomedical subjects

D Ellison

Publications and source records attributed to D Ellison.

At least 55 records · Page 3Linked to original sources

Intramural platelet deposition in cerebral vasculopathy of systemic lupus erythematosus.

AIMS: To test the hypothesis that fragments of platelet thrombi and vascular endothelium are incorporated into the walls of small cerebral vessels in systemic lupus erythematosus (SLE). METHODS: Six varied necropsy cases of central nervous system (CNS) SLE and 15 controls were studied. The controls were selected to represent a wide range of diseases in which the cerebral circulation is compromised. Tissue sections were stained by standard histochemical and immunocytochemical methods, the latter using antibodies to platelet membrane glycoprotein IIIa (CD61), and vascular endothelium (CD31). RESULTS: In four of six cases of CNS SLE characterised by small vessel hyalinization and thickening, fragments of platelet membrane were found in the walls of small cortical and meningeal vessels. Similar findings were not evident in two other SLE cases that were characterised by relatively short clinical histories and an acute vasculitis. One control case of severe polyarteritis nodosa showed platelet fragment deposition in arteries larger than the vessels so affected in SLE. CONCLUSIONS: Previous studies have suggested that neuropsychiatric symptoms in SLE may be related to repeated episodes of vasculitis in small cerebral vessels that are triggered by antiphospholipid antibodies. Concurrent thrombus formation might facilitate the incorporation of platelet fragments into small vessel walls. This process contributes to the thickening and irregularity of small vessels, a major feature of longstanding cases of CNS SLE.

Adult↗

Focal retrograde amnesia following bilateral temporal lobe pathology. A neuropsychological and magnetic resonance study.

A patient who suffered a severe closed head injury was left with a dense retrograde amnesia for events which she had experienced prior to her injury, but she showed only mild, patchy anterograde memory impairment. Her retrograde amnesia included both public events and autobiographical material, and it extended back to her childhood. Previously learned skills such as playing a piano and driving a car were spared, even though she had no recollection at all of the original learning experience. A series of focused magnetic resonance scan images revealed major pathology in the anterior portion of both temporal lobes. No significant abnormality was found in the hippocampus, thalamus or other medial structures in the limbic-diencephalic system. Our findings indicate the independence of anterograde and retrograde memory mechanisms, and point to structures and pathways in the anterior temporal lobes as playing a critical role in memory for past events.

Adult↗

Pituitary imaging using a labelled somatostatin analogue in acromegaly.

OBJECTIVE: A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We have looked at the use of an 123I-labelled Tyr3-octreotide analogue of somatostatin in the visualization and functional characterization of growth hormone-secreting pituitary adenomas. PATIENTS: Fifteen patients with biochemically-proven acromegaly were scanned using this agent. In eight of these we also assessed acute GH responses to octreotide in order to correlate these responses with tumour uptake characteristics. MEASURES: Planar and single-photon-emission computerized tomographic (SPECT) images of the head were obtained using a gamma-camera at 10 minutes, and 4 and 24 hours, after injection of the radiopharmaceutical. Blood for serum GH was sampled for 12 hours after administration of a single dose of 100 micrograms octreotide. RESULTS: Twelve of the acromegalic subjects showed significant uptake of the radiopharmaceutical in the pituitary fossa. Of the eight patients in whom we assessed acute GH responses, five demonstrated a significant fall in GH in response to octreotide. These subjects also showed positive uptake in the pituitary on scanning. The three patients who had no fall in GH had no uptake on scanning. CONCLUSIONS: Uptake of 123I-labelled Tyr3-octreotide in the pituitary fossa appears to correlate closely with the presence of a therapeutic response to octreotide.

Acromegaly↗

A scintigraphic comparison of iodine-123-metaiodobenzylguanidine and an iodine-labeled somatostatin analog (Tyr-3-octreotide) in metastatic carcinoid tumors.

A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We compared an 123I-labeled somatostatin analog Tyr-3-octreotide (TOCT) and 123I-labeled metaiodobenzylguanidine (MIBG) scintigraphy in seven patients with histologically proven metastatic carcinoid tumors. The optimum time for identifying tumor uptake on scanning after [123I]MIBG was 24-48 hr, and after 123I-TOCT 10-30 min postinjection. Both radiopharmaceuticals showed a varying spectrum of tracer uptake ([123I]MIBG showed no uptake in one patient; minimal in two; moderate in two; and intense in two; 123I-TOCT showed no uptake in two patients; minimal uptake in one; moderate uptake in two; and intense uptake in two). In two patients, 123I-TOCT identified metastatic lesions not seen by [123I]MIBG scintigraphy. These preliminary results suggest that [123I]MIBG and 123I-TOCT are useful and complementary imaging techniques for detecting metastatic carcinoid tumors.

3-Iodobenzylguanidine↗

The design of a two-phase radiolabelled meal for gastric emptying studies.

A meal intended for use in gastric emptying studies must be highly reproducible, must provide a normal physiological stimulus in terms of bulk, calorie content and composition and must employ stable radiotracers which accurately reflect in their biodistribution, the fate of the two phases. This is particularly important in a field, such as gastric emptying, where so many variables may influence the results. A conventional pancake and orange juice were chosen as suitable vehicles for the solid and liquid phases. 111In-labelled resin beads were used as the solid-phase marker and a variety of 99Tcm-labelled radiopharmaceuticals including pertechnetate, DTPA and colloid forms were investigated as liquid-phase markers. Prior to administration to patients, the stability of the phases and their interactions in vitro were investigated. The use of 99Tcm-DTPA resulted in a loss of 111In from solid to liquid phase. All non-colloidal markers exhibited a tendency for adsorption onto solid phase. Colloidal markers including rhenium and antimony sulphide colloids showed the truest delineation of the liquid phase.

Drinking↗

Clearance of charged and uncharged dextrans from normal and injured lungs.

To examine how molecular charge affects the transfer of molecules across the alveolar-capillary barrier, we prepared the following dextrans of equivalent molecular size (mol wt 10,000) but varying molecular charge: neutral dextran, cationic DEAE dextran, and anionic dextran sulfate. These were labeled with 99mTc. The lungs of three groups of anesthetized rabbits were insufflated with dextran aerosols, with six rabbits receiving each type, and the half-time pulmonary clearance (t1/2) was measured. Control t1/2's (95% confidence limits) were 95 (74-120), 227 (192-268), and 291 (246-345) min for neutral, cationic, and anionic dextrans, respectively. One week later, when the same animals were restudied 4 h after 3 micrograms/kg iv endotoxin, t1/2's were 102 (75-139), 167 (149-187), and 126 (102-154) min, respectively. After 30 min during this repeat study, animals were ventilated with 20 breaths of cigarette smoke, which acutely increased the clearance rate to 34 (26-46), 25 (20-31), and 13 (7-24) min, respectively. Mean carboxyhemoglobin levels were not significantly different in the three groups: 13.6, 12.7, and 11.1%, respectively. These results demonstrated that neutral dextrans showed the same clearance rate before and after endotoxin, whereas the charged dextrans had a significantly faster clearance after endotoxin. After smoke exposure the anionic dextran left the lung more rapidly than the neutral dextran. Thus molecular charge affects solute transfer across the alveolar-capillary barrier in both normal and injured lungs, and an effect of endotoxin on the lung can be detected with charged dextrans but not with neutral dextran.

Aerosols↗

Molecular analysis of Hodgkin's disease with abundant Reed-Sternberg cells.

The pathogenesis of Hodgkin's disease (HD) has been elusive largely because of the paucity of the Reed-Sternberg cells in comparison to large numbers of normal inflammatory cells in biopsy specimens. This report attempts to characterize Hodgkin's disease by studying subtypes with a high proportion of Reed-Sternberg cells and their variants. We found in 4 out of 6 cases, clonal heavy and light chain immunoglobulin (Ig) gene rearrangements. The Ig rearrangement results are compared with the proportion of RS cells seen in the biopsy specimens and the data are correlated with the current literature.

Cell Count↗

Reduction-mediated technetium-99m labeling of monoclonal antibodies.

A simple and generally applicable method for labeling antibodies with technetium-99m (99mTc) is described. Following reduction of intrinsic disulphide bonds, the antibody is labeled with 99mTc in the presence of a weak competing ligand methylene diphosphonate. High labeling efficiencies (greater than 97%), in a final labeling step taking only a few minutes, can be routinely obtained with high in-vitro stability over 24 hr. No effect upon antibody reactivity is seen.

Animals↗

Atlanto-occipital instability in Down's syndrome.

A patient with Down's syndrome and asymptomatic atlanto-occipital instability is described. The relationship between atlanto-occipital instability, atlanto-axial instability and generalized ligamentous laxity, is discussed.

Adult↗

Isolated pulmonary nodules in head and neck cancer patients.

Not infrequently, a patient with newly diagnosed head and neck cancer is noted on preoperative chest radiography to have a solitary pulmonary nodule. It is initially unclear whether the pulmonary nodule is a benign lesion or a metastatic or primary lung malignancy. Considerable controversy exists regarding the evaluation of such patients as well as the treatment, assuming that the pulmonary lesion is malignant. We have reviewed the UCLA experience with patients who had head and neck cancers and pulmonary cancers no more than 5 years apart, and reviewed the literature on early stage lung cancer. We present a rational approach to the workup and treatment of patients with head and neck cancer and a pulmonary nodule on chest radiography.

Adenocarcinoma↗

Protein binding studies of technetium-99m-labeled phosphine and isocyanide cationic complexes.

Most 99mTc/phosphine/isocyanide complexes synthesized to date show preferential uptake by the myocardium of many animal species but not in man. A new complex has been synthesized, [99mTc(DEPE)2(CNR)2], +(DEPIC), where R = t - butyl isocyanide, which in three animal species images the myocardium very well, but in humans it remains primarily in the blood pool. One reason for the difference in the behavior of these complexes in different species could be the characteristics of their binding to plasma proteins. The protein binding characteristics of DEPIC and two other well-known complexes have therefore been studied. Whereas the other complexes bind nonspecifically to many proteins both in animal and human plasma, DEPIC binds almost exclusively to prealbumin in humans but nonspecifically to other proteins in the rabbit. The binding sites in human plasma appear to be those normally occupied by thyroxine on the prealbumin tetramer and these can be blocked by sodium salicylate.

Animals↗

Relationship between Tl-201, Tc-99m (Sn) pyrophosphate and F-18 2-deoxyglucose uptake in ischemically injured dog myocardium.

We have previously demonstrated that enhanced glucose utilization in reperfused myocardium as assessed by F-18 2-deoxyglucose (FDG) and positron tomography predicts functional recovery. In this study, we compared segmental uptake of F-18 FDG with that of Tl-201 and Tc-99m (Sn) pyrophosphate (Tc-99m PPi) as conventional markers of tissue viability in seven dogs after a 3-hour intracoronary balloon occlusion and 20 hours of reperfusion. Myocardial blood flow was determined with microspheres. Regional retention fractions were calculated from tracer tissue concentrations, the arterial input function, and blood flow. Ischemic injury was assessed by triphenyltetrazolium chloride (TTC) staining and histologic analysis. At 24 hours, blood flow was 22% lower in reperfused than in control myocardium (p less than 0.05). Uptake of Tl-201 was related linearly to blood flow (r = 0.92), while glucose utilization and Tc-99m PPi were 2.9 (p less than 0.01) and 4.7 (p less than 0.05) times higher in reperfused than in control myocardium. Retention fractions of Tc-99m PPi increased with the degree of ischemic injury, while F-18 FDG uptake was highest in segments with mild cell injury. Thus, in ischemically injured myocardium, Tl-201 primarily reflects blood flow. F-18 FDG as a marker of glucose utilization identifies ischemically injured but viable tissue. The admixture of necrotic cells can be determined with Tc-99m PPi. Our results indicate that a dual tracer approach might best characterize the presence and extent of reversibly and of irreversibly injured tissue in a given myocardial region.

Animals↗

The preparation of kits for labelling macromolecules of biological interest with technetium-99m.

A method has been developed for producing 'kits' for labelling porphyrins, dextrans, myoglobin and cytochromes with technetium-99m. The kits have a shelf life of at least 3 months and can be reconstituted by the simple addition of 99TcmO4 from a commercial generator diluted in a buffer. The most suitable buffer was found to be isotonic citrate/saline at pH 9.0 to 9.5. When the kits are prepared as described and reconstituted with the above buffer, labelling yields of more than 95% are routinely achieved and polymerization or stacking of the labelled compounds is prevented.

Cytochrome c Group↗

Sustained regional abnormalities in cardiac metabolism after transient ischemia in the chronic dog model.

Positron emission tomography allows noninvasive assessment of myocardial blood flow and metabolism, and may aid in defining the extent and severity of an ischemic injury. This hypothesis was tested by studying, in chronically instrumented dogs, regional blood flow and metabolism during and after a 3 hour balloon occlusion of the left anterior descending coronary artery. The metabolic findings after ischemia were compared with the recovery of regional function over a 4 week period. N-13 ammonia was used as a blood flow tracer, and C-11 palmitic acid and F-18 deoxyglucose as tracers of fatty acid and glucose metabolism, respectively. Regional myocardial function was monitored with ultrasonic crystals implanted subendocardially. Regional function improved most between 24 hours and 1 week after reperfusion, but was still attenuated at 4 weeks. The slow functional recovery was paralleled by sustained metabolic abnormalities, reflected by segmentally delayed clearance of C-11 activity from myocardium and increased uptake of F-18 deoxyglucose. Absence of blood flow and C-11 palmitic acid uptake at 24 hours of reperfusion correlated with extensive necrosis as evidenced by histologic examination. Conversely, uptake of C-11 palmitic acid with delayed C-11 clearance and increased F-18 deoxyglucose accumulation identified reversibly injured tissue that subsequently recovered functionally and revealed little necrosis. Thus, recovery of metabolism after 3 hours of ischemia is slow in canine myocardium and paralleled by slow recovery of function. Metabolic indexes by positron tomography early after reperfusion can identify necrotic and reversibly injured tissue. Positron tomography may therefore aid in defining the extent and prognosis of an ischemic injury in patients undergoing reperfusion during evolving myocardial infarction.

Animals↗

Postnatal maturation of gonadotropes in the male rat pituitary.

The postnatal maturation of gonadotropes was studied with the use of electron microscopic-immunocytochemical strains for the beta-chains of LH and FSH on serially sectioned fields. A third serially sectioned field was stained with antiserum to ACTH-(17-39). Morphometric studies on semithin and ultrathin plastic sections stained for LH and FSH showed a 200-300% increase in the percentages of LH and FSH cells during the first week of postnatal life. In the 1- to 2-week-old rats, the percentage of gonadotropes in the population was greater than that in the adult. Analysis of the hormone content of serially sectioned gonadotropes showed that storage patterns similar to those in the adult were reached by the seventh day of life. In the neonatal group, 66% of the serially sectioned cells contained both FSH and LH, 20% contained only LH, and 14% contained only FSH. In the 7- to 15-day-old rats, the percentages of gonadotropes containing both hormones increased to 79% while 10-11% of the cells contained only LH or FSH. This is similar to the findings in the adult rat population (75% LH and FSH cells, 14.2% LH cells, and 11% FSH cells). The fields stained for ACTH showed that 35-80% of the gonadotropes contained ACTH-like immunoreactivity during neonatal development, with the highest values seen in the 7- to 15-day-old rats. In the normal adult rats, 2-10% of the gonadotropes contain ACTH activity. Cells containing only ACTH were also seen in all age groups examined. The morphological analysis showed that immature gonadotropic cells contained scattered storage granules, arranged either at the cell periphery or concentrated near the nucleus. They were small, irregularly shaped, and often exhibited a high nucleo-cytoplasmic ratio. They were difficult to distinguish from corticotropes. More mature cell types were found after 1 week of age. These were ovoid and contained numerous large and small granules, features similar to the adult type I cell. The granules, however, were more irregularly shaped (pleomorphic). Immature forms were observed in the gonadotrope population as late as 15 days of age. Most gonadotropes from the 20- to 25-day-old rats resembled those in the adult population. Our findings support the physiological studies which show that the first week of life is an important time for functional and morphological maturation of the gonadotrope population. They also support the finding that immature gonadotropes are larger, more numerous, and more heterogeneous than those in the adult male rat population. Finally, we propose that a subpopulation of gonadotropes may serve as a stem cell or may be involved in the development of adrenal-gonadal interactions.

Adrenocorticotropic Hormone↗

Pathogenic leptospiras isolated from Malaysian surface waters.

Pathogenic leptospiras (1,424) isolated from natural waters and wet soils in Malaysia comprised 29 different serovars (synonym serotypes). All except two of the serovars had been found previously in Malaysia. The exceptional serovars were werrasingha, an Autumnalis serogroup member originally isolated in Ceylon, and a new serovar designated evansi. Serovar evansi had serological affinities with serovar ranarum which was isolated from the kidney of a frog in Iowa. The large variety of serovars found in jungle areas was consistent with similar previous findings of diverse serovar infections in troops who had operated in Malaysian jungles.

Agglutination Tests↗