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Biomedical subjects

R E Boyd

Publications and source records attributed to R E Boyd.

At least 19 recordsLinked to original sources
PubMed2001

Alpha(2) adrenoceptor agonists as potential analgesic agents. 3. Imidazolylmethylthiophenes.

A series of imidazolylmethylthiophenes has been prepared and evaluated as ligands for the alpha(2) adrenoceptor. These compounds were tested in two animal models that are predictive of analgesic activity in humans. The 3-thienyl compounds were generally the most potent, particularly those with substitution in the 4-position. A subset of the most active compounds was further evaluated for adverse cardiovascular effects in the anesthetized rat model. In addition to excellent binding at the alpha(2D) adrenoceptor, the 4-bromo analogues 20e and 21e were very active in the rat abdominal irritant test (RAIT) with ED(50) doses of 0.38 and 0.31 mg/kg, respectively. We constructed a pharmacophore model based on the biological activity of the present series, dexmedetomidine (1), and conformationally restrained analogues 3 and 4.

Adrenergic alpha-Agonists↗
PubMed2001

Alpha2-adrenergic receptor agonists as analgesics.

Alpha2-adrenergic receptor agonists are analgesic agents, and the alpha2-adrenergic agonist clonidine has been used in clinical studies for regional analgesia after intrathecal administration. We review here recent developments concerning the structure activity relationships of a new class of potent alpha2-adrenergic agonists and their use as analgesic agents. The effect of structure upon cardiovascular side-effects is also monitored, such as the prolongation of the QT portion of the cardiac action potential.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1999

Alpha(2) adrenoceptor agonists as potential analgesic agents. 1. (Imidazolylmethyl)oxazoles and -thiazoles.

A series of (imidazolylmethyl)oxazoles and -thiazoles were prepared and evaluated as alpha(2) adrenoceptor agonists. These compounds were also tested in in vivo paradigms that are predictive of analgesic activity. Variations in both the imidazole and thiazole portions of the molecule were investigated. Some of the more potent compounds such as 22, 26, 45, and 53 displayed alpha(2) receptor binding in the 10-20 nM range and also had significant antinociceptive activity in the mouse abdominal irritant test (MAIT).

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1999

Treatment of osteoarthritis pain with controlled release oxycodone or fixed combination oxycodone plus acetaminophen added to nonsteroidal antiinflammatory drugs: a double blind, randomized, multicenter, placebo controlled trial.

OBJECTIVE: To compare the efficacy and safety of controlled release oxycodone given every 12 h around the clock with immediate release oxycodone-acetaminophen (APAP) given 4 times daily for osteoarthritis (OA) pain. METHODS: Adults (n=167) with moderate to severe OA pain despite regular use of nonsteroidal antiinflammatory drugs (NSAID) entered open label titration for 30 days with immediate release oxycodone qid; 107 qualified for randomization to double blind, parallel group treatment for 30 days with placebo, controlled release oxycodone, or immediate release oxycodone-APAP. RESULTS: Following titration with immediate release oxycodone, mean (SE) pain intensity (0, none to 3, severe) decreased from 2.44 (0.04) to 1.38 (0.05) (p=0.0001), and quality of sleep (1, very poor; 5, excellent) improved from 2.58 (0.08) to 3.57 (0.07) (p=0.0001). Mean dose was about 40 mg/day. Pain intensity and quality of sleep were significantly improved in both active groups compared with the placebo group (p< or =0.05) during the double blind trial. Pain intensity and sleep scores were comparable in both active groups during double blind treatment. Nausea (p=0.03) and dry mouth (p=0.09) were less common with controlled release oxycodone than immediate release oxycodone-APAP. CONCLUSION: Controlled release oxycodone q12h and immediate release oxycodone-APAP qid, added to NSAID, were superior to placebo for reducing OA pain and improving quality of sleep. The active treatments provided comparable pain control and sleep quality. Controlled release oxycodone was associated with a lower incidence of some side effects.

Acetaminophen↗
PubMed1995

Piperazinylalkyl heterocycles as potential antipsychotic agents.

We recently reported on a series of pyrrole Mannich bases orally active in inhibiting the conditioned avoidance response (CAR) in rats. These compounds exhibit affinity for both D2 and 5-HT1A receptors, and some are noncataleptogenic. Such a profile suggests that they may be potential antipsychotic agents which lack the propensity for causing extrapyramidal side effects and tardive dyskinesias in humans. One of these compounds, 1-[[1-methyl-5-[[4-[2-(1-methylethoxy)phenyl]- 1-piperazinyl]methyl]-1H-pyrrol-2-yl]methyl]-2-piperidinone (RWJ 25730, 1), was chosen for further development but found to be unstable in dilute acid. In order to improve stability, we replaced the pyrrole methylene linkage to the piperazine ring with ethylene, employed ethylene and dicarbonyl as linkers between the lactam and the pyrrole ring, placed electron-withdrawing groups on the pyrrole ring, and substituted acyclic amide for lactam. In addition, we replaced the pyrrole segment with other heterocycles including thiophene, furan, isoxazole, isoxazoline, and pyridine. Generally, replacement of the N-methylpyrrole segment with thiophene, furan, isoxazoline, or pyridine afforded compounds equipotent with 1 in CAR, which were more stable in dilute acid. In the case of side chain or lactam modifications, CAR activity was significantly decreased or abolished, with the exception of 6. For the most part, the modifications to 1 resulted in the decrease or loss of D2 receptor binding. However, within this series, 5-HT1A receptor binding was greatly increased, with thiophene 40 exhibiting an IC50 of 0.07 nM. The CAR activities of pyrroles 6 and 12, thiophene 40, furans 44-47, isoxazolines 49 and 50, and pyridine 54 coupled with their weak or nonexistent D2 binding and strong 5-HT1A binding suggest that they may be acting via a nondopaminergic mechanism or that dopaminergic active metabolites are responsible. Pyrrole 6 and furans 44 and 47 show promise as antipsychotic agents based on their CAR activity, receptor-binding profile, and solution stability.

Animals↗
PubMed1993

Gout: modern management of an ancient malady.

If Dr. Sydenham could have benefited from today's therapy, he likely would not have had to endure thirty years of "violent ... torture" that gave birth to his most elegant and classic description of acute gout. The five key points to remember in management of the gouty spectrum are: (1) Establish the diagnosis as clearly as possible or as clearly as seems necessary under the clinical circumstances (i.e. arthrocentesis with crystal analysis to establish diagnosis is not always necessary with reliable patients when septic joint seems highly unlikely). (2) Treat acute attacks with NSAIDs alone or perhaps steroids--or rarely IV colchicine under special circumstances. (3) DO NOT START ALLOPURINOL OR PROBENECID DURING AN ACUTE FLARE OF GOUT--IT MAY MAKE THE EPISODE WORSE. (4) The pattern of disease over time (frequency and severity of attacks) determines whether or not one decides to use an agent such as allopurinol, probenecid, or prophylactic colchicine chronically once a patient is over the acute attack--the mere presence of increased uric acid and a single or rare gouty attack would not usually require any other than the appropriate acute therapy. (5) The presence of visible tophi, uric acid renal calculi and destructive gouty arthritis nearly always warrant uric acid lowering therapy.

Allopurinol↗
PubMed1992

Physiological modeling of disposition of potential tumor-imaging radiopharmaceuticals in tumor-bearing mice.

Radiopharmaceuticals have great potential in the early detection of human tumors. Three potential 99mTc-labeled platinum compounds based on cisplatin have been synthesized and tested in tumored mice. This report presents the analysis of the disposition data obtained after a single intravenous injection with an empirical, physiologically based pharmacokinetic model. The radioactivity of each radiopharmaceutical after administration was measured in blood, urine, and 15 tissues, including tumor. Parameters included in the model were tissue volumes (experimentally determined), tissue blood flows (determined from literature values), tissue:blood extraction ratios (determined by nonlinear least-squares regression with MULTI-FORTE), and clearance terms (also determined by nonlinear least-squares regression). Data were weighted by the reciprocal of the square of the observed values. Good fits to the experimental data were obtained. As expected, the compound producing the best tumor:blood profile (3) also had the highest tumor extraction ratio (6.2 versus 2.0 and 1.3 for 1 and 2, respectively). Total body clearance values for the radioactivity associated with the three compounds 1-3 were calculated to be 0.09, 0.04, and 0.016 mL/min, respectively. Analysis of data with such an empirical, physiologically based model may assist future development of suitable tumor-imaging agents.

Animals↗
PubMed1987

Samarium-153 chelate localization in malignant melanoma.

153Sm, a radiolanthanide of half life 46.27 h, has a gamma emission of 0.103 MeV which is well suited to imaging, it is also a moderate energy beta emitter and tumour localization of various 153Sm chelates was evaluated in B16 murine melanoma to assess their endoradiotherapeutic potential. 153Sm was prepared from enriched 152Sm in the Australian Nuclear Science and Technology Organization reactor. 153Sm chelates were prepared from 153Sm-chloride and their chromatographic behaviour characterized. Tumour and organ uptake of 153Sm-chloride, 153Sm-citrate and the 153Sm chelates, DTPA, HEDTA, HIDA, BZ, PBH, PIH and NTA were measured at 1, 6, 24 and 48 h after intravenous administration to C57 black mice bearing either melanotic or amelanotic B16 melanoma of mean size 0.75 cm3. Histopathological examination of the tumours at each passaging assured comparability of the degree of melanogenesis and the absence of necrosis. 153Sm-chloride was immobile on chromatography and the rapid hepatic accumulation of both 153Sm-chloride and 153Sm-citrate was attributed to in vivo formation of a colloid. In contrast, 153Sm-DTPA, moving at the solvent front on chromatography, showed no reticuloendothelial accumulation in vivo and was rapidly excreted by the kidneys without tumour uptake. The other 153Sm chelates were of intermediate stability and all localized in both melanotic and amelanotic tumours, although to a significantly lesser degree than 67Ga-citrate. The relatively high 153Sm-HIDA activity in liver and 153Sm-NTA activity in bone impaired tumour definition, but on imaging of all the 153Sm chelates only 153Sm-DTPA failed to demonstrate the B16 melanoma and the best tumour delineation was obtained using 153Sm-HEDTA.

Animals↗
PubMed1987

Synthesis and characterization of potential tumor scintigraphic agents.

Potential tumor imaging radiopharmaceutical agents have been prepared by attaching a cisplatin derivative to a ligand capable of forming a stable complex with 99mTc. Three new organometallic compounds, with iminodiacetic acid as the 99mTc chelating group and 2,3-diaminopropionamide as the platinum complexing group, have been prepared and characterized. Preliminary biodistribution studies in tumor bearing mice support the utility of this approach.

Animals↗
PubMed1985

The medical case for an Australian national cyclotron facility.

Both a national cyclotron and a reactor are necessary to provide Australia with the complete range of radioisotopes. For the last 17 years, Australia has been well supplied with reactor radioisotopes by the Australian Atomic Energy Commission which provides a daily nationwide distribution service, but, to be self-sufficient, Australia also needs a national cyclotron. Many cyclotron radioisotopes are too short-lived for importation, and the demand can be met only by domestic production. Despite the availability of the necessary expertise and instrumentation, Australian patients are being denied a wide range of important clinical investigations because of the lack of suitable radioisotopes, for example, krypton-81m and iodine-123. An Australian medical cyclotron is overdue. Australia and New Zealand are the only developed countries that do not possess at least one medical cyclotron. The historical events in Australia's quest for a medical cyclotron are summarized, and the medical reasons why the writers believe that Australia should now acquire its own medical cyclotron are reviewed.

Australia↗
PubMed1985

Systemic lupus erythematosus: a review of clinico-laboratory features and immunogenetic markers in 150 patients with emphasis on demographic subsets.

Clinical and laboratory features as well as immunogenetic markers were analyzed in 150 patients with SLE to determine if demographic factors--age at diagnosis, sex and race--influenced the expression of disease. The overall series included 103 white females, 35 black females, 10 white males and 2 black males; the mean age at diagnosis was 32.5 years. Males had a significantly older mean age at diagnosis than females (40.4 versus 31.8 years) and a significantly higher frequency of peripheral neuropathy (50% versus 18.8%). No other differences in clinical or laboratory features or HLA-DR or DQ phenotype frequencies were noted. Blacks had a significant younger mean age at diagnosis than whites (26.9 versus 33.4 years) as well as significantly higher frequencies of nephritis, hypertension, acute lupus pneumonitis, discoid rash, hyperglobulinemia and hypocomplementemia. There were no differences in autoantibody frequencies between race-specific subgroups. HLA-DR2, DRw52 and DQ1 were significantly associated with SLE in whites compared to controls; no HLA-DR or DQ associations were found with SLE in blacks. In whites, HLA-DR2 was associated with the presence of anti-Ro(SS-A) antibody while HLA-DR3 was associated with the presence of both anti-Ro(SS-A) and anti-La(SS-B) antibody. In blacks, HLA-DR2 was associated with the presence of anti-nDNA antibody. In whites, patients with late-onset SLE (age at diagnosis greater than or equal to 50 years) had significantly lower frequencies of nephritis and mesenteric vasculitis but, on the other hand, a higher frequency of secondary Sjögren syndrome than patients with age at diagnosis less than or equal to 22 years. Similar findings were noted when blacks aged 35 and above were compared to those aged 17 and below at diagnosis. In whites, the frequency of both anti-Ro(SS-A) and La(SS-B) antibodies increased with increasing age as did that of HLA-DR3; HLA-DR2, however, was more frequent in those with younger age at diagnosis. These data suggest the existence of two serologic-genetic subsets of SLE with different age at diagnosis.

Adolescent↗
PubMed1983

Acute effects of steroids on immune complex profile of patients with systemic lupus erythematosus. Correlation of profile with development of target organ involvement.

Eleven patients with active systemic lupus erythematosus, previously untreated, were studied to 1) determine the acute effect of corticosteroids on circulating immune complex (CIC) levels and 2) correlate the initial CIC profile with the development of organ system involvement. Using serial measurements of CIC as detected by assays for cryoglobulins and binding to C1q, Raji cells, and rheumatoid factor, we found that levels of CIC change little during the first month of high dose daily steroid therapy, but they uniformly decrease to near normal by 6 to 12 months. High levels of CIC detected by Raji cell assay early in the course of systemic lupus erythematosus and before steroid therapy appear to be predictive of the development of chronic lupus nephritis (P less than 0.005).

Adult↗
PubMed1983

Strychnine poisoning. Recovery from profound lactic acidosis, hyperthermia, and rhabdomyolysis.

Strychnine poisoning results in a predictable and treatable sequence of events involving blockade of the inhibitory neurotransmitter, extensor muscle spasms, seizures, and respiratory paralysis. These spasms may lead to hyperthermia, profound lactic acidosis, and rhabdomyolysis. Acidosis is primarily attributable to lactate, as indicated by the correlation between arterial pH and log of lactic acid concentration (r = -0.878). Interruption of the strychnine blockade is the primary therapy for strychnine poisoning. Phenobarbital in moderate doses should be the first intervention and anesthetic doses should be used if necessary. Suppression of convulsions will permit successful management of the complications of strychnine poisoning. Our patient survived, even though at one point he had a pH of 6.55, a lactate level of 32 mM/liter, a temperature of 43 degrees C, and rhabdomyolysis with an increased creatine phosphokinase level of 359,000 mU/ml (5,983 mumol/s/liter).

Acidosis↗
PubMed1982

Technetium-99m generators--the available options.

The review describes the three most commonly used methods of separating 99mTc from 99Mo, namely chromatography, sublimation and solvent extraction. General comparisons are made between the various generator systems and their respective advantages and weaknesses. The method of producing the parent radionuclide 99Mo often dictates which of the generator options is more appropriate to a particular 99mTc user. Although the use of fission-produced 99Mo is widespread, this technique is not ideal since it requires considerable capital investment and gives rise to large quantities of long-lived radioactive waste. In certain countries such resources cannot be presumed and as a result alternative methods of producing 99mTc from neutron-activation-produced 99Mo are attractive. Recent advances in generator technology indicate that neutron-activation-produced 99Mo may eventually replace the need for fission-produced 99Mo. The review mentions one method of achieving this goal.

Kinetics↗