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Biomedical subjects

Douglas Brown

Publications and source records attributed to Douglas Brown.

12 recordsLinked to original sources
PubMed2006

Refusals by pharmacists to dispense emergency contraception: a critique.

Over the past several months, numerous instances have been reported in the United States media of pharmacists refusing to fill prescriptions written for emergency postcoital contraceptives. These pharmacists have asserted a "professional right of conscience" not to participate in what they interpret as an immoral act. In this commentary, we examine this assertion and conclude that it is not justifiable, for the following reasons: 1) postcoital contraception does not interfere with an implanted pregnancy and, therefore, does not cause an abortion; 2) because pharmacists do not control the therapeutic decision to prescribe medication but only exercise supervisory control over its dispensation, they do not possess the "professional right" to refuse to fill a legitimate prescription; 3) even if one were to grant pharmacists the "professional right" not to dispense prescriptions based on their own personal values and opinions, pharmacists "at the counter" lack the fundamental prerequisites necessary for making clinically sound ethical decisions, that is, they do not have access to the patient's complete medical background or the patient's own ethical preferences, have not discussed relevant quality-of-life issues with the patient, and do not understand the context in which the patient's clinical problem is occurring. We conclude that a policy that allows pharmacists to dispense or not dispense medications to patients on the basis of their personal values and opinions is inimical to the public welfare and should not be permitted.

Adolescent↗
PubMed2006

Regarding zygotes as persons: implications for public policy.

In this paper, we examine the notion put forward by certain groups (largely as a consequence of their opposition to elective abortion) that the immediate post-fertilization cellular entity - the zygote - is a person and should be given full moral status. Because the zygote has none of the inherent characteristics necessary to be regarded as a person in the traditional philosophical sense (e.g., John Locke or Immanuel Kant), some advocates of this position attempt to advance their case with arguments based on the genetic potential of the human zygote to develop into a person. We argue that this position represents a flawed use of human genetics and ignores the extraordinarily inefficient and wasteful nature of human reproduction. We then explore the public policy consequences that would follow from granting the zygote full moral status. We conclude that the logical consequences of granting the zygote full moral status would require a revolutionary restructuring of many basic social institutions, especially the health care system. The social, political, and economic changes that would be required if the zygote is enshrined as a person in law constitute a convincing reductio ad absurdum that demonstrates the danger in taking this position seriously.

Beginning of Human Life↗
PubMed2005

Identification of unique reciprocal and non reciprocal cross packaging relationships between HIV-1, HIV-2 and SIV reveals an efficient SIV/HIV-2 lentiviral vector system with highly favourable features for in vivo testing and clinical usage.

BACKGROUND: Lentiviral vectors have shown immense promise as vehicles for gene delivery to non-dividing cells particularly to cells of the central nervous system (CNS). Improvements in the biosafety of viral vectors are paramount as lentiviral vectors move into human clinical trials. This study investigates the packaging relationship between gene transfer (vector) and Gag-Pol expression constructs of HIV-1, HIV-2 and SIV. Cross-packaged vectors expressing GFP were assessed for RNA packaging, viral vector titre and their ability to transduce rat primary glial cell cultures and human neural stem cells. RESULTS: HIV-1 Gag-Pol demonstrated the ability to cross package both HIV-2 and SIV gene transfer vectors. However both HIV-2 and SIV Gag-Pol showed a reduced ability to package HIV-1 vector RNA with no significant gene transfer to target cells. An unexpected packaging relationship was found to exist between HIV-2 and SIV with SIV Gag-Pol able to package HIV-2 vector RNA and transduce dividing SV2T cells and CNS cell cultures with an efficiency equivalent to the homologous HIV-1 vector however HIV-2 was unable to deliver SIV based vectors. CONCLUSION: This new non-reciprocal cross packaging relationship between SIV and HIV-2 provides a novel way of significantly increasing bio-safety with a reduced sequence homology between the HIV-2 gene transfer vector and the SIV Gag-Pol construct thus ensuring that vector RNA packaging is unidirectional.

Animals↗
PubMed2005

'PACLIMS': a component LIM system for high-throughput functional genomic analysis.

BACKGROUND: Recent advances in sequencing techniques leading to cost reduction have resulted in the generation of a growing number of sequenced eukaryotic genomes. Computational tools greatly assist in defining open reading frames and assigning tentative annotations. However, gene functions cannot be asserted without biological support through, among other things, mutational analysis. In taking a genome-wide approach to functionally annotate an entire organism, in this application the approximately 11,000 predicted genes in the rice blast fungus (Magnaporthe grisea), an effective platform for tracking and storing both the biological materials created and the data produced across several participating institutions was required. RESULTS: The platform designed, named PACLIMS, was built to support our high throughput pipeline for generating 50,000 random insertion mutants of Magnaporthe grisea. To be a useful tool for materials and data tracking and storage, PACLIMS was designed to be simple to use, modifiable to accommodate refinement of research protocols, and cost-efficient. Data entry into PACLIMS was simplified through the use of barcodes and scanners, thus reducing the potential human error, time constraints, and labor. This platform was designed in concert with our experimental protocol so that it leads the researchers through each step of the process from mutant generation through phenotypic assays, thus ensuring that every mutant produced is handled in an identical manner and all necessary data is captured. CONCLUSION: Many sequenced eukaryotes have reached the point where computational analyses are no longer sufficient and require biological support for their predicted genes. Consequently, there is an increasing need for platforms that support high throughput genome-wide mutational analyses. While PACLIMS was designed specifically for this project, the source and ideas present in its implementation can be used as a model for other high throughput mutational endeavors.

Algorithms↗
PubMed2005

Antiviral activity of steric-block oligonucleotides targeting the HIV-1 trans-activation response and packaging signal stem-loop RNAs.

Mixmer oligonucleotides consisting of residues of both 2'-O-methylnucleosides (OMe) and locked nucleic acids (LNA) were designed targeting two stem-loops in the 5'-UTR of HIV-1 RNA, the transactivation response region (TAR), which is the site of binding of the Tat protein, and the SL3 loop, which is the primary packaging element that binds the Gag polyprotein. These oligonucleotides were found to inhibit syncitia formation dose- and sequence-dependently when delivered to HeLa T4 LTR beta-Gal cells and subsequently infected with HIV-1.

5' Untranslated Regions↗
PubMed2005

Databases and information integration for the Medicago truncatula genome and transcriptome.

An international consortium is sequencing the euchromatic genespace of Medicago truncatula. Extensive bioinformatic and database resources support the marker-anchored bacterial artificial chromosome (BAC) sequencing strategy. Existing physical and genetic maps and deep BAC-end sequencing help to guide the sequencing effort, while EST databases provide essential resources for genome annotation as well as transcriptome characterization and microarray design. Finished BAC sequences are joined into overlapping sequence assemblies and undergo an automated annotation process that integrates ab initio predictions with EST, protein, and other recognizable features. Because of the sequencing project's international and collaborative nature, data production, storage, and visualization tools are broadly distributed. This paper describes databases and Web resources for the project, which provide support for physical and genetic maps, genome sequence assembly, gene prediction, and integration of EST data. A central project Web site at medicago.org/genome provides access to genome viewers and other resources project-wide, including an Ensembl implementation at medicago.org, physical map and marker resources at mtgenome.ucdavis.edu, and genome viewers at the University of Oklahoma (www.genome.ou.edu), the Institute for Genomic Research (www.tigr.org), and Munich Information for Protein Sequences Center (mips.gsf.de).

Base Sequence↗
PubMed2004

Terminal vanadium-neopentylidyne complexes and intramolecular cross-metathesis reactions to generate azametalacyclohexatrienes.

Four-coordinate vanadium complexes containing a terminal neopentylidyne functionality have been prepared by two consecutive alpha-hydrogen abstraction reactions both of which were induced by one-electron oxidations. Among these vanadium-alkylidyne complexes are the neutral and the cation (Nacnac)VCtBu(OTf) and [(Nacnac)VCtBu(THF)]+, respectively (Nacnac- = [Ar]NC(CH3)CHC(CH3)N[Ar], Ar = 2,6-(CHMe2)2C6H3). The vanadium-alkylidynes have been characterized by 1H, 13C, 51V NMR spectroscopy and single-crystal X-ray diffraction and are consistent with a short VC bond. These alkylidynes were found to transform to azametalacyclohexatriene systems via an intramolecular cross-metathesis reaction. Kinetic studies of the transformation of (Nacnac)VCtBu(OTf) in C7D8 reveal the formation of the azametalacyclohexatriene to be independent of solvent (toluene vs THF) and the reaction to be first order in vanadium (k = 3.30(5) x 10-5 s-1 at 80 degrees C, with activation parameters DeltaH= 25.4(3) kcal/mol, DeltaS = -6(3) cal/molK). High-level DFT calculations on the full model suggest an intramolecular mechanism invoking only one transition state. The overall thermodynamic driving force for the reaction (DeltaG) in solution phase was estimated to be -21.3 kcal/mol.

Journal Article↗
PubMed2004

Ethical issues arising from the performance of pelvic examinations by medical students on anesthetized patients.

Anesthetized women are frequently examined by medical students before gynecologic surgery is performed. We argue that the key element in determining the appropriateness of such examinations is whether there is benefit to the patient as a result. Because every member of a surgical team needs a clear understanding of the nature, goals, and technical steps to be used in carrying out any operation, it is appropriate for a medical student to examine those patients in whose surgery he or she is going to participate as an active member of the surgical team. However, if pelvic examinations are carried out "solely for educational purposes" by students who are not actual members of the operating team, such actions are not appropriate unless specific permission has been obtained from the patient by the surgeon in charge of the case.

Education, Medical↗
PubMed2004

Recurrent Mycobacterium xenopi infection in a patient with rheumatoid arthritis receiving etanercept.

A case of recurrent Mycobacterium xenopi infection presenting as Pott's disease in a patient receiving etanercept for severe rheumatoid arthritis is described. A 49-y-old Caucasian male had received a total of 11 months of anti-mycobacterial therapy for hip infection acquired 15 months earlier; he presented with progressive back pain, which was diagnosed as Pott's disease. He had been treated with etanercept in addition to his prior immunosuppressive agents after the diagnosis of hip infection.

Arthritis, Rheumatoid↗
PubMed2002

Pharmaceutical sales representatives and the doctor/patient relationship.

As marketing efforts by drug companies become more aggressive, physicians are being asked to provide clinical "preceptorships" to pharmaceutical sales representatives. During a "preceptorship" of this type, the company representative spends a day with the physician seeing patients "as an educational experience," and the physician receives an "honorarium" from the drug company in return. We explore the implications of this practice. First, we examine the nature of the doctor/patient relationship and the fiduciary obligations incumbent upon physicians in their role as healers. Second, we examine four interlocking ethical principles-nonmaleficence, beneficence, respect for patient autonomy, and justice-that should govern doctor/patient encounters. Third, we critique several hypothetical scenarios involving individuals who might put forth a claim to enter the doctor/patient relationship (ie, a pharmacist, a social scientist, the husband of the patient, and a pharmaceutical sales representative). We conclude that the practice of providing clinical "preceptorships" to pharmaceutical sales representatives is unjustifiable, is unethical, and should not be permitted.

Beneficence↗
PubMed2002

The ascending pharyngeal artery: branches, anastomoses, and clinical significance.

Neuroradiologists generally do not fully appreciate the importance of the territory of the ascending pharyngeal artery. The ascending pharyngeal artery is a small but important artery that supplies multiple cranial nerves and anastomotic channels to the anterior and posterior cerebral circulations. Several disease processes in the head and neck involve the ascending pharyngeal artery. To evaluate and treat such diseases, it is necessary for neuroradiologists not only to know selective angiography and embolization techniques, but also the territory of the ascending pharyngeal artery, anastomoses, and vascular supply to the vasa nervorum of lower cranial nerves. Herein, the normal angiographic anatomy of the ascending pharyngeal artery, its relationship with neighboring territories, its importance in clinical situations, and research models are reviewed.

Arteries↗