Donald M. Lyster

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

Abstract 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.

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.

Evaluation of DNA aptamers directed to thrombin as potential thrombus imaging agents

Two DNA aptamers directed against two separate exosites on human alpha-thrombin were evaluated for thrombus-imaging potential. Aptamer ODN 1 is directed to the thrombin substrate binding site (exosite 1). Our finding that ODN 1 competes with fibrin for binding to exosite 1 on thrombin suggests that ODN 1 will not be useful for thrombus imaging. Aptamer ODN 2 is directed against the thrombin heparin binding site (exosite 2). ODN 2 bound to model thrombi that were formed either by clotting purified fibrinogen with thrombin, or by recalcifying citrated plasma. As the thrombin content of thrombi was increased the rate of ODN 2 uptake into preformed thrombi increased, whereas the rate of release of ODN 2 out of preformed thrombi decreased. This in vitro data suggested that ODN 2 might be useful for thrombus imaging because it can bind to exosite 2 on fibrin-bound thrombin. However, in a rabbit jugular vein model using thrombus supplemented with human thrombin, ODN 2 uptake was equal to the ovalbumin control, and did not reflect thrombin content. While the in vitro results with ODN 2 were consistent with thrombus imaging, the rapid clearance of ODN 2 from circulation, combined with slow mass transfer in the clot, seem to work against in vivo thrombin-dependent imaging or washout analysis.

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.

Radioimmunoimaging with 99mTc monoclonal antibodies: Clinical studies

Abstract A technetium-99 m ( 99m Tc) mouse monoclonal anti-hCGbeta antibody fragment labeled according to a novel pretinning method is shown in the present studies to be suitable for the in vivo detection of hCG-secreting and certain non-hCG-secreting human tumours. The advantages of this radiopharmaceutical over other radiolabeled antibody compositions previously described for in vivo tumor detection relate to its improved image quality, lower radiation exposure, and earlier scanning times.

Interstitial Lymphoscintigraphy for Lymphatic Mapping in Surgical Practice and Research

Lymphoscintigraphy is a nuclear medicine technique that gives morphologic and functional information about the lymphatic system. The size of radiopharmaceutical used is a critical factor for it to have acceptable characteristics of uptake by the lymphatics and migration to lymph nodes. A small particle (10-100 nm) with opsonins or a unique surface is required for uptake by lymph-node macrophages. It can be prepared for application with a simple filtering process producing a predictable size distribution and number of particles for the scan. The radiation dose is safe for the patient and staff. Technetium-99m sulfur colloid is readily available and approved for use. The injection can be performed by anyone with certification in handling radiopharmaceuticals. Imaging is done with standard gamma cameras available in any nuclear medicine department. The addition of the hand-held gamma probe adds a new dimension to application of the technique of lymphatic mapping and identification of areas that retain radiopharmaceuticals. Its use is simple and reproducible. The application of lymphoscintigraphy and gamma-probe localization techniques in clinical medicine is best exemplified with the now commonly used sentinel node approach to staging and treating intermediate-thickness malignant melanoma. A number of other malignant diseases such as breast cancer may have their treatments altered with these techniques as well. As a research and diagnostic tool, the creative application of interstitial lymphoscintigraphy can give important qualitative information regarding the morphology and physiology of the lymphatic system. The development of these techniques for surgical research and practice is reviewed.

Animal Model for Investigation of Spinal Cord Injury Caused by Aortic Cross-Clamping

The objective of this experimental protocol was to design a large animal model that could simulate the ischemic condition caused by aortic cross-clamping during the operation for intrathoracic and thoraco-abdominal aneurysm. Domestic swine weighing 25 to 30 kg were used for this model. The thoracic cavity was opened through the fourth intercostal space. Cross-clamp was applied below the left subclavian artery. Duration of cross-clamp was 30 min and the reperfusion period was 24 h. Methods of assessment included Tarlovs criteria, histology transmission electron microscopy, and spinal cord perfusion with microspheres. This model is reproducible. The results of experimental protocols completed using this model are referenced. This article discusses the details of the experimental protocol with steps toward reproduction of the model and rationalization. This animal model can be used for the evaluation of the pathophysiology of spinal cord injury and sensory- and motor-evoked potentials, and most importantly it can also be used for the examination of pharmacological interventions for prevention and treatment of ischemia reperfusion injury caused by aortic cross-clamping.

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.

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.

15-(Para-[123I] iodophenyl) pentadecanoic acid obtained using mercuration and subsequent [123I] radioiodination

In an ongoing effort to obtain quantitative, rapid kit type labelling of [123I] radiopharmaceuticals, we have examined organomercury precursors of [123I] 15-(para-iodophenyl)-pentadecanoic acid (IPPA). Chloromercuri derivatives of phenyl pentadecanoic acid (PPA) and the PPA ethyl ester were obtained by mercuration utilizing mercuric trifluoroacetate in trifluoroacetic acid followed by treatment with acetic acid and hydrochloric acid. The most simple compound, chloromercuri PPA, proved insoluble at room temperature in the common solvents useful for radioiodination and purification. The study was extended in a systematic way to chloromercuri PPA ethyl ester and the acetoxy mercuri PPA ethyl ester. As expected, these two compounds posessed successively more useful ranges of solvent compatibility. Iodination and [123I] radioiodination were carried out with the three compounds of PPA. Chloromercuri PPA was dissolved with difficulty in acetic acid at 70°C and 71% radiochemical yield of [123I] IPPA was obtained during the course of a 5 minute reaction utilizing chloramine T. The chloromercuri PPA ethyl ester was dissolved in ethyl acetate/acetic acid (2/1 v/v) at room temperature and 87% radiochemical yield of [123I] IPPA was obtained following 10 minutes reaction. With the acetoxy mercuri PPA ethyl ester it was possible to conduct the radioiodination in ethanol again using chloramine T. A modest radiochemical yield (r. y.) (51%) of [123I] IPPA ethyl ester was obtained after 60 min. It was possible to enhance the radiochemical yield in the presence of lithium acetate (84% r. y.). The isomeric purity of the [123I] IPPA ethyl ester was unexpectedly high (99.9% para) when the radioiodination was conducted at room temperature.