PubMed Health⌕ Search

Biomedical subjects

David W Robertson

Publications and source records attributed to David W Robertson.

10 recordsLinked to original sources
PubMed2006

Interstitial temperature mapping during Prolieve transurethral microwave treatment: imaging reveals thermotherapy temperatures resulting in tissue necrosis and patent prostatic urethra.

OBJECTIVES: Temperature mapping of the prostate during transurethral microwave thermotherapy and imaging of the resultant zones of tissue necrosis have been previously performed using several commercial systems. This study was performed using the Prolieve Thermodilatation System, which simultaneously compresses the prostate with a 46F balloon circulating heated fluid and delivering microwave energy into the prostate. METHODS: Interstitial temperature mapping during Prolieve treatment was performed on 10 patients with benign prostatic hyperplasia using 24 temperature sensors arrayed throughout the prostate. Voiding cystourethrograms were performed on 3 additional patients treated without temperature mapping to document the patency of the prostatic urethra 1 hour after treatment. Gadolinium-enhanced magnetic resonance imaging studies were performed on all patients 1 week after treatment to determine the extent and pattern of tissue necrosis resulting from transurethral microwave thermotherapy. RESULTS: Interstitial temperature mapping found that the heating pattern generated by the Prolieve system created average peak temperatures of 51.8 degrees C an average of 7 mm away from the prostatic urethra. These temperatures were greater near the bladder neck and mid-gland than toward the prostatic apex. Subtherapeutic temperatures were seen adjacent to the urethra, consistent with the viable tissue seen on gadolinium-enhanced magnetic resonance imaging sequences. Magnetic resonance imaging also revealed necrotic zones that were consistent with sustained temperatures greater than 45 degrees C. Voiding cystourethrograms showed widely patent prostatic urethras 1 hour after treatment. CONCLUSIONS: Transurethral microwave thermotherapy with the Prolieve Thermodilatation System produced sustained therapeutic temperatures that resulted in tissue necrosis while maintaining viable tissue surrounding a temporarily dilated prostatic urethra.

Body Temperature↗
PubMed2006

Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors.

The synthesis, evaluation, and structure-activity relationships of a series of succinoyl lactam inhibitors of the Alzheimer's disease gamma-secretase are described. Beginning with a screening hit with broad proteinase activity, optimization provided compounds with both high selectivity for inhibition of gamma-secretase and high potency in cellular assays of A beta reduction. The SAR and early in vivo properties of this series of inhibitors will be presented.

Alzheimer Disease↗
PubMed2004

Anxiolytic-like effects of the corticotropin-releasing factor1 (CRF1) antagonist DMP904 [4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine] administered acutely or chronically at doses occupying central CRF1 receptors in rats.

Corticotropin-releasing factor(1) (CRF(1)) antagonists may be effective in the treatment of anxiety disorders with fewer side effects compared with classic benzodiazepines. The behavioral effects of DMP904 [4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine] and its effects on the hypothalamic-pituitary-adrenal (HPA) axis were related to its levels in plasma and estimated occupancy of central CRF(1) receptors. DMP904 (10-30 mg/kg, p.o.) and alprazolam (10 mg/kg, p.o.) increased time spent in open arms of an elevated-plus maze. In addition, acutely or chronically (14 days) administered DMP904 (1.0-30 mg/kg, p.o.) and acute alprazolam (1.0-3.0 mg/kg, p.o.) significantly reduced exit latency in the defensive withdrawal model of anxiety in rats, suggesting that tolerance may not develop to the anxiolytic-like effects of DMP904 in this model of anxiety. Acutely, DMP904 reversed the stress-induced increase in plasma corticosterone levels in defensive withdrawal at doses of 3.0 mg/kg and higher. These doses also resulted in levels of DMP904 in plasma similar to (for anxiolytic-like effects) or 4-fold higher (for effects on the HPA axis) than the in vitro IC(50) value for binding affinity at CRF(1) receptors and greater than 50% occupancy of CRF(1) receptors. Unlike alprazolam, DMP904 did not produce sedation, ataxia, or chlordiazepoxide-like subjective effects (as measured by locomotor activity, rotorod performance, and chlordiazepoxide discrimination assays, respectively) at doses at least 3-fold higher than anxiolytic-like doses. In conclusion, anxiolytic-like effects and effects on the stress-activated HPA axis of DMP904 in the defensive withdrawal model of anxiety required 50% or greater occupancy of central CRF(1) receptors. This level of CRF(1) receptor occupancy resulted in fewer motoric side effects compared with classic benzodiazepines.

Animals↗
PubMed2003

Interdisciplinary research: putting the methods under the microscope.

BACKGROUND: While the desirability of interdisciplinary inquiry has been widely acknowledged, indeed has become 'the mantra of science policy', the methods of interdisciplinary collaboration are opaque to outsiders and generally remain undescribed. DISCUSSION: Many have analysed interdisciplinarity, especially in relation to the creation of new disciplines and institutions. These analyses are briefly outlined. Still, there currently persists a silence about the methods of interdisciplinary collaboration itself, and the core of this paper proposes a template for such methods. SUMMARY: Breaking this silence--by making the methods of interdisciplinary projects transparent--could further invigorate interdisciplinary research.

Academies and Institutes↗
PubMed2003

Novel, highly potent, selective 5-HT2A/D2 receptor antagonists as potential atypical antipsychotics.

The discovery of N-substituted-pyridoindolines and their binding affinities at the 5-HT(2A), 5-HT(2C) and D(2) receptors, and in vivo efficacy as 5-HT(2A) antagonists is described. The structure-activity relationship of a series of core tetracyclic derivatives with varying butyrophenone sidechains is also discussed. This study has led to the identification of potent, orally bioavailable 5-HT(2A)/D(2) receptor dual antagonists as potential atypical antipsychotics.

Animals↗
PubMed2003

Imidazo[4,5-b]pyridines as corticotropin releasing factor receptor ligands.

A series of high affinity CRF receptor ligands with an imidazo[4,5-b]pyridine core is described. Individual analogues were synthesized and tested in a rat CRF receptor binding assay. The best compounds were further tested in the dog N-in-1 pharmacokinetic model to assess plasma levels at 1mg/kg (po) and in the rat situational anxiety model to assess anxiolytic efficacy at 3mg/kg (po). The structure-activity relationships for good receptor binding affinity are described herein.

Animals↗
PubMed2003

Imidazo[4,5-c]pyridines as corticotropin releasing factor receptor ligands.

A series of high affinity CRF receptor ligands with an imidazo[4,5-c]pyridine core is described. Individual analogues were synthesized and tested in vitro in rat brain receptors to determine binding affinity. The best compound was further tested in the dog N-in-1 pharmacokinetic model to assess oral bioavailability at 1 mg/kg po.

Administration, Oral↗
PubMedDate not supplied

Solid-phase synthesis of alkyl aryl ethers via the Ullmann condensation.

Alkyl aryl ether formation is a frequently employed reaction in organic synthesis. Ullmann condensation is an alternative method to the widely used Mitsunobu reaction and is very useful in situations where application of the Mitsunobu reaction is limited. By application of this reaction to solid-phase synthesis of a series of alkyl aryl ethers, reaction conditions (catalyst, solvent, temperature, time, etc.) for a sterically hindered class of alcohols were investigated and optimized. A range of aryl halides was used to explore the scope of the reaction in solid phase.

Journal Article↗