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Biomedical subjects

D M Lyster

Publications and source records attributed to D M Lyster.

At least 19 recordsLinked to original sources

Potential 67Ga radiopharmaceuticals for myocardial imaging: tris(1-aryl-3-hydroxy-2-methyl-4-pyridinonato)gallium(III) complexes.

A series of highly lipophilic complexes of 1-aryl-3-hydroxy-2-methyl-4-pyridinones with gallium(III)-67 has been evaluated in vitro and in vivo as potential radiopharmaceuticals. The pyridinones have different substituents at the para-position of the phenyl ring: R = H, CH3, OCH3 and NO2. Biodistribution studies of 67Ga complexes have been carried out in rabbits, mice, rats and a dog. High heart uptake of the radionuclide has been shown in rabbits and the dog. The different biodistribution patterns in mice and rats indicate that there is a species difference in the biodistribution of these complexes. Rabbits and the dog show rapid heart uptake and blood clearance. The speciation of the Ga3+ ion in vivo is simulated in vitro with a simple blood plasma model based on the available thermodynamic data.

Animals

Pharmacologic interventions for prevention of spinal cord injury caused by aortic crossclamping.

The efficacy of pharmacologic agents for prevention and control of oxygen-derived free radical damage in ischemia-reperfusion injury of the spinal cord was assessed in a swine model of thoracic and thoracoabdominal aortic crossclamping. Animals were exposed to 30 minutes of ischemia that induced lethal, irreversible injury and paraplegia. The experimental groups were as follows: group A (n = 7), control group, receiving no pharmacologic intervention; group B (n = 7), deferoxamine 50 mg/kg/day administered intravenously over 3 to 4 hours before ischemia; group C (n = 7), allopurinol pretreatment 50 mg/kg/day for 3 days; and group D (n = 7), superoxide dismutase 60,000 units administered with 50,000 units before removal of the aortic crossclamp and 10,000 units over 10 minutes of reperfusion. Proximal hypertension was controlled with sodium nitroprusside and volume depletion. The methods of assessment were neurologic by a modified Tarlov criteria and blood flow by radiolabeled microspheres. Results of blood flow assessment confirmed a true ischemic episode of 30 minutes for all animals in all groups. The blood flow fell significantly during ischemia (p less than 0.01) and a hyperemic response was evident in the early reperfusion period. All animals in control group A were paraplegic. The group B (deferoxamine) results were superior; 85% had grade III function on a modified Tarlov scale, with animals in the group standing and even walking with difficulty. Only one animal in this group had good movements of hind limbs but was unable to stand or walk. Neurologic recovery was limited in the allopurinol group (group C), with 85% showing slight neurologic recovery with limited movement of the hind limbs. The animals in the superoxide dismutase group (group D) all had good recovery, with strong motor response of hind limbs, but were not able to stand. In summary, the results of this experimental protocol confirmed the possible role of oxygen-derived free radicals in the pathophysiology of spinal cord injury, induced by aortic crossclamping. Moreover, it proved that ischemia-reperfusion injury could be altered by pharmacologic interventions.

Allopurinol

Comparison of functional and metabolic assessments in preservation techniques for heart transplantation.

The present study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation using metabolic and functional assessments. In both groups the hearts were initially protected with iso-osmolar potassium Tyers' cardioplegia. The donor hearts of group A were placed in simple hypothermic storage for 5 h. The donor hearts of group B were placed onto a perfusion apparatus for 5 h with perfusion pressure maintained at 28 cm of H2O and a myocardial temperature of 8-10 degrees C. The perfustate consisted of Tyers' solution with the addition of 2 mg/L of mannitol, 12.5 mg/L of glucose, 5 units/L of insulin, and 95% oxygen. The ischemic interval within both groups was 6 h, including orthotoipic transplantation. Investigation was conducted at three time periods: prepreservation (T1) in the donor, and postpreservation (T2) and immediately after loading (T3) in the recipient. Following volume loading for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than .05; stroke index, p less than .05) with no significant change in systemic vascular resistance, systemic blood pressure, and heart rate. There was also significant improvement in myocardial performance (p less than .05) for the hypothermic perfusion group following volume loading. Results of fatty acid turnover using 15-p-iodo (123I)-phenylpentodecanoic acid indicate significantly greater increase in metabolic rate for the perfusion group than for the hypothermic storage group. (p less than .05). This indicates improved metabolic status of the heart treated with the hypothermic perfusion technique. We conclude that a combination of functional and metabolic assessments is a good method for deduction of ischemic-reperfusion injury. We also conclude that hypothermic perfusion is superior to hypothermic storage for in vitro preservation of hearts for heart transplantation.

Animals

The metabolism of 15-p-[123I]-iodophenylpentadecanoic acid in a surgically induced canine model of regional ischemia.

The purpose of this study was to examine the longitudinal effect of gradual coronary occlusion on regional myocardial metabolism of 15-p-123I-iodophenylpentadecanoic acid [( 123I]IPPA). Adult dogs were imaged using [123I]IPPA and planar gamma imaging. A thoracotomy was performed and an ameroid constrictor of appropriate size permanently positioned on the left anterior descending coronary artery. The dogs were imaged after injection of 3-5 mCi [123I]IPPA at various times over a 2-week period. With imaging on days 7 and 14, the dogs were paced at a rate of 185. Time-activity curves were generated and t1/2 values calculated using monoexponential curve fitting. Results indicate a significant increase in t1/2 between control and 14 days after surgery in the apical wall (29 +/- 7 to 53 +/- 18 min; P less than 0.05). Although there was also an increased t1/2 in the lateral wall, this was not significant (27 +/- 8 to 78 +/- 99 min; P greater than 0.05). There was no significant change in t1/2 in the septal wall (27 +/- 9 to 33 +/- 8 min; P greater than 0.05). We conclude that [123I]IPPA is a useful indicator of developing myocardial ischemia.

Animals

Beta-methyl-15-P-[123I] iodophenyl-pentadecanoic acid and thallium-201 in the assessment of myocardial perfusion defects.

The purpose of this investigation was to examine the ability of beta-methyl-15-P-[123I]-iodophenyl-pentadecanoic acid (beta 123IPPA) and thallium-201 to assess the ischemic risk zone associated with myocardial infarction. The hearts of mongrel dogs were infarcted by ligating the left anterior descending coronary artery and at 6 h post infarction injected with thallium-201 (2 mCi; scanning time 30 mins) followed by beta 123IPPA (3 to 5 mCi; scanning time 30 mins). Scintigraphic assessment of the perfusion defect yielded perfusion defect size (percentage of whole slice), which was then compared to the defect when assessed by tetrazolium staining. Myocardial ratios were calculated to assess differences in localization between tracers. Any differences noted may affect identification of the area at risk following acute myocardial infarction. A slice-by-slice comparison of perfusion defect size for scintigraphic methods and histochemical method showed no significant difference between beta 123IPPA and thallium-201. The mean ratio for myocardial defect size expressed as beta 123IPPA/thallium-201 was 1.03 +/- 1.29. Enzymatic analysis demonstrated significant increases in creatine kinase (160.33 +/- 46.44 to 5030.6 +/- 2238 U) and creatine kinase-MB% (31.85 +/- 15.11 to 82.99 +/- 8.14%) post infarction (P less than 0.05 in both cases). Elevated ST segments were also seen in all dogs post infarction. It can be concluded that the combined use of beta 123IPPA and thallium-201 does not allow the identification of the ischemic risk zone (percentage area at risk) often associated with myocardial perfusion defects. Problems continue to exist with image resolution and border demarcation.

Animals

Efficacy of 15-(123I)-p-iodophenyl pentadecanoic acid (IPPA) in assessing myocardial metabolism in a model of reversible global ischemia.

In a canine model of reversible global ischemia, the residual quantity of 123I was assessed following a bolus injection of 15-p-(123I)-iodophenyl pentadecanoic acid (123I-IPPA). This technique was used to assess changes in free fatty acid metabolism following the utilization of three cardioplegic formulations. Cardioplegic arrest was initiated with Tyers' iso-osmolar (IO) solution (Group A); IO + superoxide dismutase (SOD) (Group B) and IO + allopurinol (Group C). Pre and post operative scanning were completed with 2-5 mCi 123I-IPPA. Clearance was assessed by IPPA time activity curve analysis generating t1/2 (half lives in min) for the early and late phases of the curve. The assessment between groups demonstrated that the elimination of 123I-IPPA products (early phase) was faster from the lateral wall in groups B and C versus group A (14 +/- 12 min, 13 +/- 9 min and 24 +/- 10 min, respectively). The elimination of IPPA (late phase) was also faster from the lateral wall in groups B and C when compared to group A (240 +/- 270 min, 132 +/- 85 min and 416 +/- 238 min). Examining the changes between control and postoperative values for each area of the left ventricle within each group demonstrated no significant changes for groups B and C. Group A, however, demonstrated significantly increased t1/2 values for the lateral wall (early and late phases) and the apical wall (late phase).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Comparison of technetium-99m pyrophosphate and technetium-99m methylene diphosphonate with variable amounts of stannous chloride in the detection of acute myocardial infarction.

The authors prospectively compared the ability of Tc-99m pyrophosphate (PYP) and Tc-99m methylene diphosphonate (MDP) to detect acute myocardial infarctions. The agents used were PYP (12 mg) with 3.4 mg of stannous chloride, MDP (10 mg) with 1.0 mg of stannous chloride, and MDP (10 mg) with 3.4 mg of stannous chloride. Imaging was performed on three consecutive days on 34 patients with proven myocardial infarctions, using the same agent on the first and third days of the study and an alternate agent on the second day. Agents were assigned randomly to each of six groups of patients. First images were obtained an average of 3.7 days (range, one to six days) following myocardial infarction. Seventeen of 23 patients (75%) had images positive for acute myocardial infarction with Tc-99m PYP, whereas only two of 21 patients (9.5%) had positive studies with Tc-99m MDP with 3.4 mg of stannous chloride and one of 24 patients (4.2%) had positive studies with Tc-99m MDP and 1.0 mg of stannous chloride. All three myocardial infarctions detected by Tc-99m MDP were extensive and transmural. When MDP and PYP were both positive in the same patient, the apparent size of the myocardial infarction was much smaller with the MDP. It is concluded that MDP can detect only large myocardial infarctions, has poor localization in the infarcted tissue, and varying the stannous chloride content of the preparation does not improve the ability of MDP to detect acute myocardial infarctions.

Adult

Technetium-99m-labelled red blood cell scanning to diagnose occult gastrointestinal bleeding.

The authors, from their experience in 60 patients, demonstrate that technetium-99m-labelled red blood cell scintigraphy is a sensitive (91%) and specific (76%) diagnostic procedure with a high predictive value, when both positive (81%) and negative (92%). It is preferable to and more cost-effective than selective angiography as a first-line diagnostic test for occult gastrointestinal bleeding.

Cecal Diseases

Gamma scintigraphy using Tc-99m labeled antibody to human chorionic gonadotropin.

A case report is presented describing a 27-year-old woman with invasive trophoblastic hydatidiform mole metastatic to the lung. Gamma scintiscanning, using a polyclonal and monoclonal antibody specific to human chorionic gonadotropin, hCG, and labeled with Tc-99m, is described. The area of the primary lesion in the uterus was demonstrated with both antibodies tested without computer subtraction techniques; metastatic deposits in the lung were detected only with the aid of blood pool subtraction techniques.

Adult

Potential use of radiolabelled porphyrins for tumor scanning.

Fe-TMPI, Fe-TCP and protohemins showed high initial uptake using tissue culture techniques with mouse tumor cells (P815). However, the tumor uptake in the in vivo model was poor. Of the radionuclides investigated, iron labelled to TMPI demonstrated the best uptake by tumor in vitro. As has been previously demonstrated, the unnatural meso-arylporphyrin derivatives showed better uptake than did naturally occurring porphyrins and their derivatives.

Animals

Evaluation of formamidine sulfinic acid and other reducing agents for use in the preparation of Tc-99m labeled radiopharmaceuticals.

Various reducing agents have been evaluated for their potential usefulness in the preparation of 99mTc labeled radiopharmaceuticals for use in nuclear medicine. Adequate labeling of various radiopharmaceuticals was accomplished using formamidine sulfinic acid. Nitrogen-purging of solutions is not required, which is an advantage for in-house preparation. Tagging requires heating, however, so heat-labile material cannot be used. Various compounds that could not be labeled when stannous chloride was used, could be tagged with 99mTc when formanidine sulfinic acid was used as the reducing agent.

Amidines

An evaluation of radiocolloid sizing techniques.

Techniques for sizing radiocolloids are reviewed. The small size range (1-100 nm) of many radiocolloids and their polydispersity limit the choice of the technique used. To compare several techniques directly, the particle size of Technetium-99m sulfide colloid was studied using Nuclepore filtration, ultracentrifugation and electron microscopy. The last of these was adopted as the method of choice. Using this technique, the particle size and shape of colloids below 100 nm can be accurately determined. Technetium-99m antimony sulfide colloid and indium-113m hydroxide were then examined by electron microscopy, and the chemical nature of the particles was determined by x-ray fluorescence analysis. Results resolved the size discrepancies reported in the literature and demonstrated the importance of identifying the chemical nature of the particles under examination.

Colloids

99mTc-bioquin-7CA, a potential new hepatobiliary scanning agent.

The complex 99mTc-Sn-8-hydroxyquinoline-7-carboxylate (99mTc-bioquin-7CA) was investigated in animals as a potential hepatobiliary scanning agent. Following intravenous injection, the complex was found to localize in the liver rapidly and in the gallbladder in 5--15 min; after 15 min it was excreted into the biliary tract with a high degree of specificity. Urinary excretion was negligible, reducing scan interference from the kidneys. Distribution studies in mice compared well withe localization of activity observed in rabbit scans. Preparation of the complex was rapid and simple; stannous ion was used as the reducing agent.

Biliary Tract Diseases

Analbuminemia in a neonate.

A small-for-gestational-age infant, found to have analbuminemia in the neonatal period, is reported and the twelve cases recorded in the world literature are reviewed. Patients lacking this serum protein are essentially asymptomatic, apart from minimal ankle edema and ease of fatigue. Apparent compensatory mechanisms which come into play when serum albumin is low include prolonged half-life of albumin and transferrin, an increase in serum globulins, beta lipoprotein, and glycoproteins, arterial hypotension with reduced capillary hydrostatic pressure, and the ability to respond with rapid sodium and chloride diuresis in response to small volume changes. Examination of plasma amino acids, an investigation not previously reported, revealed an extremely low plasma tryptophan level, a finding which may be important in view of the role of tryptophan in albumin synthesis.

Blood Chemical Analysis