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Biomedical subjects

D Morrow

Publications and source records attributed to D Morrow.

At least 19 recordsLinked to original sources

Paralogues of porcine aromatase cytochrome P450: a novel hydroxylase activity is associated with the survival of a duplicated gene.

The gonadal and placental paralogues of porcine aromatase cytochrome P450 (P450arom) were examined for novel catalytic properties to shed light on the evolutionary survival of duplicated copies of an enzyme critical to reproduction. Recombinant gonadal P450arom catalyzed the formation of a novel metabolite from testosterone, identified by gas chromatography/mass spectrometry and biochemical analyses as 1 beta-hydroxytestosterone (1 beta OH-T), in almost equal proportion to 17beta-estradiol (E(2)). This activity was absent in reactions with the porcine placental paralogue (or other orthologues) of P450arom and was minimal with androstenedione. Incubations with both porcine enzymes and with bovine and human P450arom demonstrated that 1 beta OH-T was not aromatizable, and 1 beta OH-T activated the androgen receptor of prostate cancer cells in vitro. Porcine testicular and follicular granulosa tissues synthesized 1 beta OH-T, which was also detected in testicular venous plasma. These results constitute the first of identification of a novel, perhaps potent, nonaromatizable metabolite of testosterone, whose synthesis (paradoxically) can be definitively ascribed to the activity of the gonadal paralogue of porcine P450arom. It probably represents an evolutionary gain of function associated with fixation and the survival of the genes after CYP19 duplication. Novel activities and adaptive functions may exist among other duplicated vertebrate aromatases.

Animals↗

Surgical therapy for tremor in multiple sclerosis: an evaluation of outcome measures.

OBJECTIVE: To assess the reliability, validity, and sensitivity of outcome measures that might be used in a clinical trial of surgery for the treatment of severe tremor associated with MS (MS tremor). METHODS: Nine patients with MS tremor were evaluated before and 3 and 12 months after thalamic surgery (six thalamotomy, three deep brain stimulation). A clinical tremor rating scale (CTRS), a novel quantitative movement analysis technique (QMA), and a variety of measures of disability, neurologic impairment, and quality of life was utilized. RESULTS: Both the CTRS and QMA were reliable measures of tremor and both were sensitive to the improvement in tremor following surgery. However, QMA correlated with disability measures and corresponded better to patient and examiner assessment of surgical results. The disability scales used were insensitive to functional improvements that may follow surgery. The box and blocks test clearly separated three patients who had excellent results from three who had poor results. Baseline QMA values predicted improvement on the box and blocks test. CONCLUSIONS: 1) QMA is a reliable, objective and valid measure of MS tremor that could be used in a clinical trial. 2) The box and blocks test can detect the improvement in prehensile function that follows surgery, but standard disability scales are poorly responsive to this change. 3) Preoperative QMA values may predict which patients are most amenable to functional improvement after surgery.

Adult↗

Methyl-substituted diindolylmethanes as inhibitors of estrogen-induced growth of T47D cells and mammary tumors in rats.

Diindolylmethane (DIM) is formed by acid catalyzed dimerization of the phytochemical indole-3-carbinol, and both compounds inhibit formation and/or growth of mammary tumors in rodents. In this study, we have investigated the aryl hydrocarbon receptor (AhR) agonist activity and inhibitory AhR-estrogen receptor crosstalk induced by the following methyl-substituted DIMs: 1,1'-dimethyl-, 2,2'-dimethyl-, 5,5'-dimethyl-, 6,6'-dimethyl-, and 7,7'-dimethylDIM and 1,1',2,2'-tetramethylDIM. The six compounds bound to the rat cytosolic AhR in a transformation assay but, at concentrations < or = 10 microM, exhibited minimal to non-detectable AhR agonist or antagonist activities associated with CYP1A1 induction. In contrast, the methyl-substituted DIMs inhibited estrogen-induced T47D human breast cancer cell growth and the four most active compounds (1,1'-, 2,2'-, 5,5'-dimethylDIM and 1,1',2,2'-tetramethylDIM) inhibited one or more estrogen-induced responses in the 21-day-old female B6C3F1 mice at a dose of 100 mg/kg/day (X3). Induction of hepatic CYP1A1-dependent activity was not observed at this high dose. The antitumorigenic activity of these compounds was examined in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor model in which the DIM analogs were orally administered (by gavage in corn oil) at a dose of 1 mg/kg/day (X10). 1,1'-DimethylDIM, 5,5'-dimethylDIM and 1,1',2,2'-tetramethylDIM significantly inhibited mammary tumor growth, and this was not accompanied by changes in organ/body weights or histopathology. These studies demonstrate that methyl-substituted DIMs are selective AhR modulators (SAhRMs) with potential for clinical treatment of breast cancer.

Animals↗

Development of a bioassay for phytochemicals using Daphnia pulex.

The freshwater cladoceran Daphnia pulex was explored as an alternative to Artemia salina for the biological screening of phytochemicals. This paper reports on the results of screening 27 compounds, and comparisons are made with screens using Artemia salina. The effect of miniaturisation of the assay system was investigated. Petri-dish based tests were performed for the 27 compounds using 10 daphnids at each of 5 concentrations (1 - 1000 mg l(-1)). Potassium dichromate was used as a control and the number immobile after 24 hours were counted. Results were expressed as EC(50) values. The active compounds (EC(50) < 25 mg l(-1)) comprised mainly adrenoceptor agonist alkaloids, while the cytotoxins vincristine and colchicine, and several antibiotics were relatively non-toxic towards Daphnia. The method was validated by comparative bioassay of A. belladonna fractions. Overall, this screen compared favourably with those based on Artemia. Daphnia were sensitive to a wide range of biologically active molecules including CNS-stimulants, anti-malarials, narcotics and anti-spasmodics, and the sensitivity was broader than previously seen with Artemia. The screen is perhaps limited by the lack of sensitivity to cytotoxins, but this might be overcome by altering the test criteria.

Animals↗

Medication schemas and memory for automated telephone messages.

The present study investigated whether older and younger adults use a schema to organize and remember spoken reminder messages for taking medication. Previous research has shown that older and younger adults share preferences for organizing printed instructions for taking medication, suggesting a shared schema. Older and younger participants in Experiment 1 of the present study used a similar schema to organize medication reminder messages. This finding suggests that the medication schema generalizes across communication purpose (to remind or to instruct) as well as across patient age. Medication reminder messages were better understood and remembered when organized to match this schema, whether the reminders were presented as automated telephone messages (Experiment 2) or in printed form (Experiment 3). Schema-compatible organization especially helped people draw inferences from the messages, suggesting that organization helps older and younger adults construct a situation model of the medication-taking task from the messages. Potential applications of organized messages include increasing the impact of automated systems for delivering health services.

Adult↗

Asymptomatic occlusion of the left main coronary artery by an aortic pseudoaneurysm.

Extrinsic compression of the left main coronary artery is a rare cause of coronary ischemia. We describe a 35-year-old Asian woman with complete asymptomatic occlusion of the left main coronary artery by a large aortic pseudoaneurysm. She underwent repair of the pseudoaneurysm and coronary artery bypass grafting at the Mayo Clinic in Rochester, Minn. The differential diagnosis is discussed. Based on this patient's age and associated vascular lesions, we conclude that Takayasu arteritis was the most likely cause of her condition.

Adult↗

High-resolution comparative physical mapping of mouse chromosome 10 in the region of homology with human chromosome 21.

Comparative mapping of human and mouse chromosomes can be used to predict locations of homologous loci between the species, provides the substrate to examine the process of chromosomal evolution, and facilitates the continuing development of mouse genetic models for human disorders. A YAC contig of the region of mouse Chromosome (Chr) 10 (MMU10) that demonstrates conserved linkage with the distal portion of human Chr 21 (HSA21) has been constructed. The contig contains all known genes mapped in both species, defines the proximal region of homology between MMU10 and HSA22, and contains the evolutionary junction between HSA21 and HSA22 on MMU10. It consists of 23 YACs and 2 PACs, and covers 3.2 Mb of MMU10. The average marker density for this region is 1 marker/69 kb. Nine of 22 expressed sequences are mapped here for the first time in mouse, and two are newly characterized expressed sequences. The contig also contains 12 simple sequence repeats (SSRs) and 16 YAC and PAC endclone markers. YAC fragmentation analysis was used to create a physical map for the proximal 2.2 Mb of the contig. Cloning of the corresponding region of HSA21 has proven difficult, and the mouse contig includes segments absent from previously described sequence ready maps of HSA21.

Animals↗

Repetition improves older and younger adult memory for automated appointment messages.

Automated telephone messaging systems have dramatically expanded communication about health service appointments, but few studies have directly investigated these messages. The present study investigated whether message repetition (1, 2, or 3 presentations) and listener age (mean age = 71 or 19 years) improved memory for automated appointment messages. Repetition improved older and younger adult memory for appointment information. Moreover, 2 presentations reduced age differences in accuracy of answering questions about the messages. This was not the case for free recall, suggesting that older adults differentially benefited from repetition only when provided with additional retrieval support. These findings show that older as well as younger adults benefit from at least 1 repetition of appointment messages. Actual or potential applications of this research include the use of repetition to improve comprehension of automated telephone messages.

Adult↗

The endoscopic forehead lift.

Endoscopic techniques are being successfully applied to address eyebrow and forehead ptosis. The methods rely on extensive subperiosteal and subgaleal release of the forehead and scalp flap, allowing the elevation of soft tissues. Ablation of the depressor supercilli and procerus can be performed to address skin folding in the glabellar region. The mobilized frontotemporal flap is then elevated to the desired level and fixated with microscrews to the outer table of the skull. Laterally, the flap is fixed to the deep temporalis fascia. The technique relies upon a solid knowledge of the regional anatomy and the use of specialized instruments now available for dissecting under the flap. The endoscopic forehead lift can achieve results comparable to those obtained by the open coronal forehead lift while minimizing the incidence and extent of postoperative cutaneous anesthesia and telogenic hair loss, which frequently follows open coronal forehead surgery. In addition, the endoscopic technique is able to address eyebrow ptosis in the balding male without causing disfiguring scarring.

Adult↗

Dentistry at the top of the world.

This report provides a brief description of the Khumbu region of Nepal, its people, and the availability of dental treatment in this remote area. It also highlights Canadian involvement in the training of dental staff who provide treatment in a new clinic in the region.

Canada↗

Improving consultations between health-care professionals and older clients: implications for pharmacists.

Consultations between pharmacists and many clients are now federally mandated in the United States, but guidelines have not been developed for communication in this context. This article reviews research on communication between clients and health-care professionals in order to help develop recommendations for consultations between pharmacists and older clients. The review is organized around a collaborative approach to health communication, which identifies strategies by which speakers and listeners work together to achieve mutually defined goals. This approach is used to analyze cognitive processes underlying communication during pharmacist consultations. This review suggests that miscommunication often reflects a break-down in collaboration between health-care professional and clients. Recommendations are developed to improve collaboration, including suggestions for initiating consultations, presenting easy to understand messages, and monitoring to ensure that the messages are mutually understood. Most important, successful collaboration requires tailoring strategies to individual clients rather than basing communication on general assumptions about clients.

Aged↗

Relationship of other joint problems and anterior disc position in symptomatic TMD patients and in asymptomatic volunteers.

Anterior disc position has been highly correlated with temporomandibular disorders (TMD). It was hypothesized that internal derangement of the temporomandibular joint may be a part of a joint phenotype that imparts an increased risk for joint disorders. If this hypothesis is true, an increased prevalence of joint disorders in individuals diagnosed with displaced discs should be expected. A total of 263 symptomatic TMD patients and 82 asymptomatic volunteers was examined. Asymptomatic volunteers with anteriorly displaced discs were twice as likely as asymptomatic volunteers without disc displacements to report pain/dysfunction in other joints. Symptomatic patients with and without displaced discs reported an increase in other joint problems three to four times greater than in asymptomatic subjects. Compared to symptomatic TMD patients without disc displacement, symptomatic TMD patients with anteriorly displaced discs were also twice as likely to report other family members as being affected by TMD. Familial aggregation of TMD and an increased prevalence of other joint problems in these individuals may represent more than a serendipitous occurrence.

Adolescent↗

When expertise reduces age differences in performance.

The authors examined whether aviation expertise reduces age differences in a laboratory task that was similar to routine air traffic control (ATC) communication. In Experiment 1, older and younger pilots and nonpilots read typical ATC messages (e.g., commands to change aircraft heading). After each message, they read back (repeated) the commands, which is a routine ATC procedure requiring short-term memory. Ss also performed less domain-relevant tasks. Expertise eliminated age differences in repeating heading commands, but did not reduce age differences for the less relevant tasks. In Experiment 2, expertise reduced but did not eliminate age differences in repeating heading commands from spoken messages. The results suggest that expertise compensates age declines in resources when the task is highly domain relevant.

Adult↗

Acute and 8-hour effects of alcohol (0.08% BAC) on younger and older pilots' simulator performance.

This preliminary study examined the acute and 8-hour effects of alcohol at a target peak BAC of 0.08% on pilot performance. Fourteen younger (mean age 27.6 years) and fourteen older (mean age 60.3 years) pilots flew a Frasca 141 simulator in a scenario that included ATC communications and emergencies. Plots were tested during an alcohol and placebo condition at three timepoints: predrink, acute intoxication, and 8 h postdrink. Of eight performance measures, two showed statistically significant effects related to alcohol. First, cockpit monitoring was poorer when pilots were intoxicated, with recovery at 8 h. Second, younger pilots made more communication errors under the influence and there was no significant recovery at 8 h. Older pilots made more communication errors than younger pilots, but possibly because of methodological problems, older pilots' communication performance was not significantly impaired by alcohol. These results provide direction for future research.

Adult↗

Intrathecal cholinergic agonists lessen bupivacaine spinal-block-induced hypotension in rats.

Hypotension is an important side effect of spinal anesthesia. Intrathecal (IT) cholinergic agonists, including neostigmine (NEO), increase arterial blood pressure by stimulating spinal sympathetic neurons. Therefore, we tested the ability of IT cholinergic agonists to prevent the hypotensive effect of IT bupivacaine (BUP) (430 nmol) in rats instrumented with IT and arterial catheters. The mean arterial pressure (MAP) decreased 35 +/- 4 mm Hg (n = 10) after IT-BUP alone. In contrast, MAP did not significantly change after IT-BUP + IT-NEO (12.5 and 25 nmol; n = 5 for each dose). Intramuscular (IM) NEO was not effective, and MAP decreased 38 +/- 4 mm Hg after IT-BUP + IM-NEO (25 nmol; n = 5). Three additional cholinesterase inhibitors, physostigmine, edrophonium, and ambenonium, as well as the direct-acting cholinergic agonists carbachol, oxotremorine, and arecoline, each lessened the hypotension seen after IT-BUP. Furthermore, the nonselective muscarinic antagonist, atropine, as well as the M2 receptor selective antagonist, methoctramine, prevented the vasopressor effect of IT-NEO in our model. Finally, the nicotinic antagonist, mecamylamine, and the M1 selective antagonist, pirenzepine, did not affect the pressor effects of NEO in our model. In conclusion, IT cholinergic agonists lessen BUP spinal-block-induced hypotension in rats by a muscarinic dependent pathway.

Anesthesia, Spinal↗