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Biomedical subjects

R A Holmes

Publications and source records attributed to R A Holmes.

At least 19 recordsLinked to original sources
PubMed1992

The effect of ligand structure on glutathione-mediated decomposition of propylene amine oxime derivatives.

Tetramethylpropyleneamine oxime (TMPAO) was synthesized and complexed to 99mTc. 99mTc-TMPAO samples, when challenged with reduced glutathione (GSH), were shown to have two GSH sensitive components, similar to a mixture of d,l and meso 99mTc-HMPAO. One component had a GSH-induced second-order dissociation rate constant (K2) similar to 99mTc-meso-HMPAO. Despite the presence of a large fraction of this component in these samples, brain uptake and autoradiographic studies with 99mTc-TMPAO were equivalent to 99mTc-d,l-HMPAO suggesting that both the d,l and meso 99mTc-TMPAO isomers are efficiently trapped in brain.

Animals↗
PubMed1992

[153Sm]EDTMP: a potential therapy for bone cancer pain.

Reactor-produced samarium-153 (153Sm) is both a beta and gamma emitter with a physical half-life of 46.3 hours. When complexed with EDTMP, more than 50% of the administered dose localizes in bone. A therapeutic trial on patients with painful bone metastases performed at the University of Missouri produced relief in 65.4% of the patients who were evaluable. Myelotoxicity was mild and transient. For [153Sm]EDTMP to attain clinical utility, studies demonstrating its efficacy as an analgesic must be performed to exclude a "ligand analgesic effect".

Animals↗
PubMed1992

Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer.

Samarium-153 emits medium-energy beta particles and an imageable gamma photon with a physical half-life of 46.3 hr. When chelated to ethylenediaminetetramethylenephosphonic acid (EDTMP), it is remarkably stable in vitro and in vivo. In this study, we administered escalating amounts of 153Sm-EDTMP, from 0.1 to 1.0 mCi/kg (3.7-37 MBq/kg), to 22 patients with painful metastatic bone cancer. A complete concordance was found when the scintigrams of 153Sm-EDTMP were compared qualitatively to 99mTc-HDP bone images. Moreover, the skeletal uptake of the 153Sm-EDTMP related to the number of metastatic sites (r = 0.65; p = 0.001) showed an inverse proportion to the plasma radioactivity at 30 min following injection (r = -0.79; p = 0.0001) and was unaffected by the administered (mCi/kg), (r = 0.33; p = 0.13). Myelotoxicity was observed in 10 of the 29 treatment courses and leukopenia occurred in two. Thrombocytopenia occurred in patients who had low pretreatment platelet counts, albeit within the normal range (p = 0.001), most suffered from prostate cancer (p = 0.007) and retained a higher percentage of the 153Sm-EDTMP in their skeleton (p = 0.057). In four patients an exacerbation of the pre-existing pain ("flare reaction") was recorded. Pain palliation occurred in 65% of the treated patients (mean: 3.8 mo, range: 1-11 mo). Retreatment in first time responder patients was quite effective. Our preliminary results indicate that 153Sm-EDTMP is a promising radiotherapeutic agent for palliative treatment of metastatic bone cancer pain, and further study is necessary to ascertain its optimal dose, efficacy and toxicity.

Adult↗
PubMed1992

Electrocardiographic and echocardiographic features of trypanosomiasis in dogs inoculated with North American Trypanosoma cruzi isolates.

Purebred Beagles were inoculated with Trypanosoma cruzi isolates from a North American opossum or armadillo (Tc-W), and dog (Tc-D). Although Tc-D established infection in dogs, the dogs did not develop cardiac abnormalities. Dogs inoculated with Tc-W developed acute myocarditis associated with increases in P-R interval, atrioventricular block, depression of R wave amplitude and shifts in mean electrical axis. Echocardiograms were normal during this stage. Three Tc-W-inoculated dogs died during the acute stage. Following the acute stage, 5 of 8 Tc-W-inoculated dogs entered an indeterminate stage in which ECG changes were minor and echocardiograms were normal. Progression to the chronic stage in 5 of the 8 Tc-W-inoculated dogs was indicated by development of ventricular-based arrhythmias, mainly ventricular premature contractions, between postinoculation days 60 and 170. In some dogs, ventricular premature contractions were multifocal. Electrocardiographic abnormalities progressively degenerated to various forms of ventricular tachycardia. Worsening ECG coincided with loss of left ventricular function as measured by echocardiography. Mean percent ejection fraction and percentage of fractional shortening decreased to 63% and 52% of control values, respectively. The left ventricular free wall (LVFW) thickness decreased and % septal: % LVFW thickening ratio increased, indicating a relative preservation of septal wall motion and LVFW hypokinesis.

Acute Disease↗
PubMed1992

Radiographic and neuro-SPECT imaging in an immature third ventricle teratoma: case report.

We report a case of an immature teratoma of the third ventricle, which was preoperatively thought to be a choroid plexus papilloma. The diagnosis was made by biopsy since the radiographic (CT, MRI), angiographic and scintigraphic findings ([99mTc]pertechnetate, 99mTc-DTPA, 99mTc-HMPAO brain SPECT) were nonspecific. Disruption of the blood-brain barrier is the mechanism for radionuclidic and contrast tumoral uptake and is demonstrated by marked contrast enhancement on CT and focal concentration on [99mTc]pertechnetate and 99mTc-DTPA images. No suppression of [99mTc]pertechnetate tumor uptake was observed following the administration of potassium perchlorate. Increased concentration of tumor protein is suggested by the increased signal on the T1-weighted magnetic resonance images and high [99mTc]pertechnetate uptake. The tumor's detection on the 99mTc-HMPAO brain SPECT was due to its intraventricular location. A number of potential mechanisms for brain tumor localization of 99mTc-HMPAO are discussed.

Cerebral Ventricle Neoplasms↗
PubMed1991

Biolocalization and cell labeling properties of neutral-lipophilic 99mTc-amine-phenol chelates.

99mTc-diamine-diphenol chelates are neutral lipophilic chelates exhibiting good stability in aqueous solutions. The cell labeling and biolocalization properties of four different 99mTc-amine-phenol complexes were determined. All four chelates readily labeled leukocytes and RCBs in high yields. Even though 99mTc was retained by the cells, the elution rate of 99mTc from the labeled cells in plasma at 37 degrees C was unacceptably high for potential utility in scintigraphic imaging. The uptake of 99mTc in brain or heart following i.v. injection of the chelates in rats was low and clearance of activity from the blood was slow.

Animals↗
PubMed1991

Determination of lesion to normal bone uptake ratios of skeletal radiopharmaceuticals by QARG (quantitative autoradiography).

An animal model was developed to determine the ratio of uptake of different bone seeking radiotracers in skeletal lesions relative to normal bone in rats by dual tracer quantitative autoradiography (QARG). The lesion to normal bone uptake ratios (L/NB ratios) of 99mTc-MDP, 99mTc-HDP and 99mTc-DMAD were compared using 153Sm-EDTMP as an internal standard. The results from these studies demonstrated that the L/NB ratio of 99mTc-DMAD was an average of 54 and 71% higher than 99mTc-MDP and 99mTc-HDP, respectively and 79% higher than measured for 153Sm-EDTMP.

Animals↗
PubMed1991

Radiographic techniques for early detection of osteoporosis.

Sequelae of osteoporosis such as fracture and deformities usually occur when the bone mass has been severely reduced. Since the lost bone mass cannot be replaced, management of osteoporosis is aimed at preventing, halting, or retarding its progression. Early detection of osteoporosis and the identification of individuals at high risk for the disease are crucial if therapy is to be effective. Several radiographic techniques are currently available for osteoporosis screening, including dual photon absorptiometry (DPA), quantitative computed tomography (QCT), and dual-energy radiographic absorptiometry (DRA). This paper discusses the relative value and limitations of these techniques.

Absorptiometry, Photon↗
PubMed1991

Sensitivity of technetium-99m-d,1-HMPAO to radiolysis in aqueous solutions.

The sensitivity of technetium-99m- (99mTc) d,l-HMPAO to radiolytically induced dissociation in aqueous solutions was investigated. It was found that cobalt-60 (60Co) gamma irradiation of solutions containing 99mTc-d,l-HMPAO with only 1600 cGy reduced the lipophilic chelates' radiochemical purity (RCP) to 50%-60%. The radiolytic sensitivity of 99mTc-meso-HMPAO is significantly lower. The results indicate that radiolytically produced intermediates limit the in vitro stability of 99mTc-d,l-HMPAO.

Cobalt Radioisotopes↗
PubMed1990

Reverse radioaerosol/radioperfusion distribution in pulmonary endobronchial obstruction.

A characteristic image pattern of diminished radioaerosol penetration and reduced radioparticle perfusion has been observed in endobronchial obstruction. This reverse mismatch has a variety of etiologies, with the most common being mucus plugging. The regional hypoxia created by the obstruction causes the blood to shunt from the affected lung. Eleven patients from a group of 178 patients referred with a working diagnosis of pulmonary embolism showed the reversed mismatch. All presented with sudden dyspenea, chest pain and hypoxia. Bronchoscopy was recommended from the image results and nine patients demonstrated mucus plugs that were subsequently aspirated, one patient had a partially obstructing endobronchial carcinoma and one patient had a traumatic fractured bronchus that became occluded with healing granulation tissue. All improved following bronchoscopy. The incompleteness of the airway obstruction accounted for the variations of the perfusion images. Because of the radioaerosol's ability to sharply image the pulmonary airway distribution in contrast to the poor resolution of the radiogases such as xenon-133, it is recommended that radioaerosol lung imaging be substituted for radiogas ventilation imaging since it can accurately detect endobronchial obstruction as well as pulmonary embolism.

Adolescent↗
PubMed1990

Effects of repeated Strongylus vulgaris inoculations and concurrent ivermectin treatments on mesenteric arterial lesions in pony foals.

Eight of 10 pony foals reared under helminth-free conditions were inoculated PO with 50 Strongylus vulgaris infective larvae/week for 4 weeks, at which time 1 foal died of acute verminous arteritis. Inoculation of 7 remaining foals continued at 2-week intervals for 20 weeks. Of the 7 foals, 3 were treated with ivermectin (0.2 mg/kg of body weight) in an oral paste formulation at experiment weeks 8, 16, 24; 4 foals were not treated. Two foals were not inoculated or treated and served as controls. After the first ivermectin treatment, ivermectin-treated foals had fewer days (12 +/- 2.9) with rectal temperatures greater than 38.6 C than did nontreated foals (23.3 +/- 3.8). Mean baseline rectal temperatures were 38 +/- 0.2 C. Adverse clinical reactions to ivermectin treatment were not observed in foals. Foals were euthanatized and necropsied 3 weeks after the last ivermectin treatment (week 24). Ivermectin was effective in reducing S vulgaris arterial larval and intestinal adult parasite numbers by 100% in 3 treated foals. Strongylus vulgaris arterial larvae and/or adults were recovered from all 4 nontreated inoculated foals. One nontreated inoculated foal lacked arterial larvae or active arterial lesions, indicating that protective resistance had developed in this individual. Marked gross and histopathologic lesions typical of chronic S vulgaris infection were observed in the 3 nontreated inoculated foals with arterial larvae. Repeated killing of intra-arterial S vulgaris fourth-stage larvae in ivermectin-treated foals did not exacerbate lesions associated with verminous arteritis or induce unique lesions associated with repeated destruction of arterial larvae.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Sequential mesenteric arteriography in pony foals during repeated inoculations of Strongylus vulgaris and treatments with ivermectin.

Semiselective mesenteric arteriography was performed at regular intervals (inoculation weeks [IW] 0, 11, 18, and 24) in 9 of 10 pony foals raised to be free of parasites. Fifty infective larvae (L3) of Strongylus vulgaris were administered weekly for 4 weeks, then every 2 weeks through the 20th week. Three ponies were given ivermectin (oral paste, 0.2 mg/kg of body weight) treatment at IW 8, 16 and 24. Four ponies were inoculated, but did not receive ivermectin, and a third group of 2 ponies acted as uninoculated controls. Control ponies did not have gross or arteriographic lesions, whereas the inoculated untreated ponies had gross and progressive arteriographic lesions typical of verminous arteritis. Arteriographic lesions in the ivermectin-treated inoculated ponies were not as severe those in the untreated inoculated group, and there was either a partial resolution or a lack of progression of arteriographic lesions in all treated ponies. One untreated inoculated pony did not have progressive arterial lesions as did the 3 others in the group, and may develop resistance to the parasite.

Angiography↗
PubMed1989

Diagnosis of a liver abscess with Ga-67 and radiocolloid tomography.

A 46 year-old white male with fever of unknown origin demonstrated a multiloculated hepatic cyst on abdominal CT. Persistent fever and leukocytosis prompted Tc-99m Sulfur colloid liver-spleen and gallium-67 citrate imaging to identify a possible liver abscess. SPECT imaging provided pertinent clinical information that allowed the diagnosis of abscess to be made.

Citrates↗
PubMed1989

Discordant radioaerosol/radioperfusion in drug-induced maternal pulmonary edema.

A case of pulmonary edema in a 34-year-old pregnant woman on corticosteroids and beta adrenergics yielded an unusual radioaerosol/radioperfusion lung image. The image showed normal perfusion but multiple bilateral penetration defects on the radioaerosol study. Factors contributing to this unique pattern include the combined action of corticosteroids and beta-adrenergic agonists, local airway irritation caused by the drying effect of nebulized oxygen, sepsis, or a combination of these factors.

Adult↗