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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

Different effects of strenuous eccentric exercise on the accumulation of neutrophils in muscle in women and men.

The purpose of this study was to evaluate the sex differences in delayed onset muscle soreness (DOMS), torque, and accumulation of technetium-99m (Tc-99m) neutrophils in eccentric-exercised muscle. A group of 10 female and 12 male subjects took part in this study. The subjects completed a pre-test using the descriptor differential scale (DDS) to describe DOMS, and tests of concentric and eccentric torque of the right quadriceps. A volume of 100 ml of blood was taken by venipuncture for neutrophil labelling in the early morning of the exercise day. The Tc-99m neutrophils were re-infused intravenously before the eccentric exercise. The exercise stimulus consisted of 300 eccentric repetitions of the right quadriceps muscles. Radionuclide images of both quadriceps muscles (lateral views) were taken at 2 and 4 h. The DDS, and concentric and eccentric torques of the quadriceps were subsequently evaluated at 0 h, 2, 4, 20 and 24 h post-exercise. The presence of Tc-99m neutrophils was greater in the exercised leg than the non-exercised leg at 2 and 4 h post-exercise (P </= 0.013) and greater in the exercised leg of the women compared to the men at 2 h (P = 0.03). The DOMS had increased post-exercise (P < 0.001) and torque had decreased post-exercise (P </= 0.002) but the patterns were different between the sexes. We concluded that the sex influences the presence of Tc-99m neutrophils in the exercised muscle following eccentric exercise. In addition, different patterns of DOMS and torque were observed between the sexes after eccentric exercise, and require further investigation.

Adult↗

Extending the lifetime of anticoagulant oligodeoxynucleotide aptamers in blood.

We have investigated (123)I and (125)I DNA aptamer analogs of anticoagulant DNA aptamers to thrombin exosite 1 and exosite 2 for thrombus imaging potential. Two severe problems are rapid clearance from circulating blood and blood nuclease. With aptamers (unlike antisense) the nucleotide analogs used in polymerase chain reaction-selection cycles also must be used in the radiotracer. We investigated 3'-biotin-streptavidin (SA) bioconjugates of the aptamers to alleviate these problems. Blood nuclease assays and biodistribution analysis were used in the mouse and rabbit. We found that 3'-biotin protected the aptamers significantly from blood nuclease in vitro, but it did not slow in vivo clearance. In contrast, the 3'-biotin-SA bioconjugates were resistant to blood nuclease in vitro and were also longer-lived (10-20 times) in vivo. Bioconjugate aptamers retained affinity for thrombin. Two solutions emerge: 1) In noncirculating blood (within a thrombus) 3'-biotin extends aptamer lifetime, whereas 2) in circulating blood (the transport medium), where more aggressive clearance is encountered, 3'-SA extends aptamer lifetime.

Animals↗

Kinetic analysis and comparison of uptake, distribution, and excretion of 48V-labeled compounds in rats.

Vanadium has been found to be orally active in lowering plasma glucose levels; thus it provides a potential treatment for diabetes mellitus. Bis(maltolato)oxovanadium(IV) (BMOV) is a well-characterized organovanadium compound that has been shown in preliminary studies to have a potentially useful absorption profile. Tissue distributions of BMOV compared with those of vanadyl sulfate (VS) were studied in Wistar rats by using 48V as a tracer. In this study, the compounds were administered in carrier-added forms by either oral gavage or intraperitoneal injection. Data analyzed by a compartmental model, by using simulation, analysis, and modeling (i.e., SAAM II) software, showed a pattern of increased tissue uptake with use of 48V-BMOV compared with 48VS. The highest 48V concentrations at 24 h after gavage were in bone, followed by kidney and liver. Most ingested 48V was eliminated unabsorbed by fecal excretion. On average, 48V concentrations in bone, kidney, and liver 24 h after oral administration of 48V-BMOV were two to three times higher than those of 48VS, which is consistent with the increased glucose-lowering potency of BMOV in acute glucose lowering compared with VS.

Animals↗

Synthesis and radioiodination of a stannyl oligodeoxyribonucleotide.

Synthesis and radioiodination of a stannyl oligodeoxyribonucleotide were undertaken to evaluate a gamma ray emitting ODN ligand for thrombus imaging in vivo . Synthesis of the ODN was based on modified automatedbeta-cyanoethyl phosphoramidite chemistry with an organotin nucleoside (dU*) coupled to a thrombin binding aptamer sequence to give d(U*GGTTGGTGTGGTTGG). The synthesis accommodated dU*, which is destannylated by iodine or acids. Fourteen standard synthesis cycles were followed by one 'stannyl synthesis cycle', distinguished by Fmoc protection, omission of capping, oxidation by an organic peroxide and cleavage by ammonium hydroxide. The organotin nucleoside phosphoramidite {5'-[fluorenylmethoxycarbonyl]-5-(E)-[2-tri-n -butylstannylvinyl]-2'-deoxyuridine-3'-(2-cyanoethyl N,N-diisopropyl phosphoramidite)} was prepared from 5-iodo-2'-deoxyuridine. A customized mild rapid workup included deprotection with methylamine, and reverse phase HPLC with CH3CN/triethylammonium bicarbonate. Pure stannyl ODN was highly retained by reverse phase HPLC. Radioiodination of stannyl ODN (100 microg) provided 123I-labeling yields up to 97%. Five alternative oxidants were effective. High specific activity [123I]- ODN (15 000 Ci/mmol) was recovered, separated from unlabeled isomers. Excellent reverse phase HPLC resolution of ODN isomers (alternatively I, Cl, H or Br in vinyl deoxyuridine) was essential. The affinity of the iodovinyl aptamer analog (Kd = 36 nM) for human alpha-thrombin was similar to the native aptamer (Kd = 45 nM).

Gamma Rays↗

Pulmonary nodules: differential diagnosis using 18F-fluorodeoxyglucose single-photon emission computed tomography.

OBJECTIVE: The objective of this study was to prospectively evaluate the feasibility and efficacy of single-photon emission computed tomography (SPECT) with 18F-fluorodeoxyglucose (FDG) for differentiating malignant from benign pulmonary nodules. SUBJECTS AND METHODS: Twenty-six patients with 28 radiologically indeterminate focal pulmonary lesions were examined. Fasting patients were injected with 5 MBq/kg of FDG (maximum dose, 370 MBq). Imaging was performed with dual-head SPECT cameras equipped with 511-keV collimators. RESULTS: Seventeen of 21 pathologically malignant nodules showed FDG uptake on SPECT imaging (sensitivity, 81%). None of the seven benign modules showed uptake (specificity, 100%). SPECT imaging with FDG was positive in all 16 malignant nodules that were larger than or equal to 2 cm in diameter. However, only one (20%) of five nodules smaller than 2 cm in diameter showed positive on SPECT imaging. CONCLUSION: Using current technology, we found FDG SPECT imaging useful for distinguishing benign from malignant pulmonary nodules that were larger than or equal to 2 cm in diameter. However, because of the relatively low sensitivity of SPECT, smaller malignant nodules were not adequately revealed.

Deoxyglucose↗

Presence of WBC, decreased strength, and delayed soreness in muscle after eccentric exercise.

The purposes of this study were to assess the presence of 99mTc-labeled white blood cells (WBC) in exercised muscle compared with nonexercised muscle over time and to determine the time course of delayed onset muscle soreness (DOMS) and eccentric torque in 10 female subjects. A pretest was followed by 300 eccentric repetitions of the right quadriceps. DOMS and eccentric torque were measured at 2, 4, 20, 24, 48, and 72 h postexercise. Eccentric torque was also tested at 0 h. Radionuclide images of both quadriceps were taken at 2, 4, 20, and 24 h postexercise. The presence of 99mTc-WBC in the exercised muscle was significantly greater (P < 0.001) than in the nonexercised muscle. Eccentric torque declined at 0 and 24 h postexercise. DOMS peaked at 24 h postexercise. The presence of 99mTc-WBC in the exercised muscle in the first 24 h suggests that acute inflammation occurs as a result of exercise-induced muscle injury. The bimodal pattern of eccentric torque supports the hypothesis that more than one mechanism is involved.

Adult↗

No-carrier-added [123I]1-(beta-D-arabinofuranosyl)-5(E)-(2- iodovinyl)uracil (IVaraU): high yield radiolabeling via organotin and exchange reactions.

Organotin intermediates for IVaraU synthesis were obtained following the reaction of 1-(2',3',5'-tri-O-toluyl-beta-D-arabinofuranosyl-5-iodouracil with (E)-1,2-bis(tri-(n-butyl) stannyl)ethene in the presence of catalytic (Ph3P)2PdCl2. A direct precursor for IVaraU, (E)-5-[2-tri-n-butylstannylvinyl]-arabinosyluridine, reacted with [123I]NaI (10 mCi) or alternatively [125I]NaI in the presence of methanol and chloramine T providing no-carrier-added (NCA) [123I]IVaraU in a radiolabeling yield up to 97%; the product was recovered following reversed phase HPLC. Unlabeled IVaraU was prepared in five steps from arabinosyluridine via an organotin intermediate with an overall yield of 22%. An exchange radioiodination was also identified, based on accessible BrVara U in the presence of water and a cuprous ion catalyst. [123I]NaI (up to 40 mCi) or alternatively [125I]NaI reacted under exchange conditions to give no-carrier-added [123,125I]IVaraU in a radiolabeling yield of 93%; the product was recovered following reversed phase HPLC.

Antiviral Agents↗

Additive effect of allopurinol and deferoxamine in the prevention of spinal cord injury caused by aortic crossclamping.

Fourteen domestic swine were divided into two groups. Group A (n = 7) was the control group, in which no pharmacologic intervention was applied. In group B (n = 7), the ischemic-reperfused spinal cord was treated with the combination of allopurinol (50 mg/kg/day for 3 days before the day of operation) and deferoxamine (Desferal, 50 mg/kg administered intravenously over 3 to 4 hours). The administration of deferoxamine was completed 1 hour before crossclamping. The crossclamp was placed on the descending aorta just distal to the left subclavian artery for 30 minutes. Proximal hypertension was controlled with sodium nitroprusside and volume depletion. Methods of assessment included an evaluation of the neurologic status of the animals by quantitative Tarlov criteria, blood flow by radiolabeled microspheres, and histologic examination of the spinal cord. All animals in the control group, group A, were completely paraplegic with 0% recovery by Tarlov criteria at 24 hours after the removal of the crossclamp. In contrast, all animals in group B, in which the combination of allopurinol and deferoxamine was used, completely recovered (100% recovery by Tarlov criteria), and at 24 hours after the ischemic episode they were able to walk with no difficulty and had intact sensation. Functional parameters of these animals fully correlated with the morphologic findings. Widespread acute neuronal injury and vacuolation of neuropil were observed in the control group of animals. In contrast, animals in group B showed much less pronounced morphologic changes after the same period of ischemia. In summary, the combined use of these agents significantly (p < 0.001) reduced the incidence of paraplegia induced by aortic crossclamping with 82% additivity.

Allopurinol↗

Potential 99mTc radiopharmaceuticals for renal imaging: tris(N-substituted-3-hydroxy-2-methyl-4-pyridinonato)technetium(IV) cations.

A series of monocationic complexes of N-substituted-3-hydroxy-2-methyl-4-pyridinones labeled with technetium(IV)-99m have been evaluated in vivo as potential radiopharmaceuticals. The pyridinones have different substituents at the ring nitrogen atom: ethyl, i-propyl, i-butyl, benzyl, phenyl, p-methoxyphenyl, 3-butoxypropyl and cyclohexyl. Biodistribution studies of the 99mTc complexes have been carried out in rabbits and mice. High kidney uptake and retention of the radionuclide has been shown in rabbits and mice with the cationic complexes of 3-hydroxy-1-(p-methoxyphenyl)-2-methyl-4-pyridinone and 1-(cyclohexyl)-3-hydroxy-2-methyl-4-pyridinone. These 99mTcL3+ compounds appear to be morphologic renal agents.

Animals↗

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↗