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Biomedical subjects

A Pope

Publications and source records attributed to A Pope.

At least 19 recordsLinked to original sources

A digital 3-dimensional method for computing great artery flows: in vitro validation studies.

BACKGROUND: Conventional 2-dimensional Doppler large vessels are prone to inaccuracy. Three-dimensional (3D) volume imaging provides the opportunity to make cross-sectional flow calculations through digital spatiotemporal integration of flow velocity, area, and profile. METHODS: A new digital 3D color Doppler reconstruction method was used to generate radially acquired flow data sets. Raw scanline data with digital velocity assignments, obtained by scanning parallel to flow, were transferred from a specially programmed but otherwise conventional ultrasonographic system, which controlled a multiplane transesophageal probe, to a computer workstation via an Ethernet link for assimilation into color 3D data sets. This configuration was used to study 20 pulsatile laminar flows (stroke volumes 30 to 70 mL and peak flow rates 65 to 205 mL/s) in a curved tube model with an oval cross-sectional geometry. After generation of the color 3D data set, flow velocity values from cross sections perpendicular to the tubes were analyzed to determine flow rate and stroke volume. RESULTS: The flows from 3D digital velocity profiles showed close correlation with peak instantaneous flow rates (r = 0.99, y = 1.01x-0.9, standard error of estimate 4.1 mL/s). When interpreted with pulsed wave Doppler data obtained through the cardiac cycle, they also allowed computation of stroke volume (r = 0.98, y = 1.44x-2.5, standard error of estimate 3.8 mL). CONCLUSION: The ability to compute laminar flows from 3D digital data sets obtained parallel to the direction of flow and without the need for geometric assumptions represents an important opportunity for and advantage of 3D color Doppler echocardiography.

Coronary Vessels↗

Rapid caspase-3 activation during apoptosis revealed using fluorescence-resonance energy transfer.

Caspase-3 is a crucial component of the apoptotic machinery in many cell types. Here, we report the timescale of caspase-3 activation in single living cells undergoing apoptosis. This was achieved by measuring the extent of fluorescence resonance energy transfer within a recombinant substrate containing cyan fluorescent protein (CFP) linked by a short peptide possessing the caspase-3 cleavage sequence, DEVD, to yellow fluorescent protein (YFP; i.e. CFP-DEVD-YFP). We demonstrate that, once initiated, the activation of caspase-3 is a very rapid process, taking 5 min or less to reach completion. Furthermore, this process occurs almost simultaneously with a depolarization of the mitochondrial membrane potential. These events occur just prior to the characteristic morphological changes associated with apoptosis. Our results clearly demonstrate that, once initiated, the commitment of cells to apoptosis is a remarkably rapid event when visualized at the single cell level.

Animals↗

Umpire needed

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Journal Article↗

Observation of a paradoxical temperature increase during cognitive stress in some chronic pain patients.

A total of 224 chronic pain somatoform disorder patients without obvious pathophysiology or psychopathology were found to have colder hands than nonpatients. A paradoxical temperature increase (PTI) in response to a cognitive stressor (mental arithmetic) was noted in a subset of these chronic pain patients. Patients were defined as "PTI" responders if, during cognitive stress, an increase in digital temperature occurred over a prior eyes closed resting condition. It was found that 49.4% of males and 42.6% of females in a total sample of 224 patients demonstrated PTI. The PTI patients had significantly colder hands than non-PTI patients prior to stress. A concurrent SCL measure of sympathetic activation found no difference between the PTI and non-PTI groups either at baseline or during cognitive stress. It appears from this data that PTI is specific to the peripheral vascular system of these patients and may be a marker of psychophysiological dissociation or trauma blocked from consciousness.

Adult↗

Association between PM10 and decrements in peak expiratory flow rates in children: reanalysis of data from five panel studies.

Panel studies have found 1-3% increases in reports of acute respiratory symptoms associated with each 10 microg x m(-3) increase in ambient concentrations of particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10). Statistically significant decrements in population mean peak expiratory flow (PEF) have also been observed but their magnitude is only about 0.1% for the same exposure. This study evaluated whether this difference is due to the different measurement scales used for the expression of the effects of air pollution on PEF and respiratory symptoms. The association between the prevalence of large decrements in PEF (more than 10% or 20% below the median) and PM10 concentrations was analysed using data from five recent panel studies. The effect estimates were compared to the effect estimates from original studies based on the population mean PEF. The decrement in the population mean PEF for an increase of 10 microg x m(-3) of the same-day PM10 concentration was 0.07%, averaged over all panels. A significant relative increase of 2.7% (95% confidence interval 1.6-3.8) in the prevalence of PEF decrements greater than 10% was associated with the same exposure. In conclusion, defining the peak expiratory flow response by the prevalence of large decrements provides effect estimates of a comparable magnitude to effect estimates for the prevalence of reports of acute lower respiratory symptoms.

Air Pollutants↗

Identifying the need for curriculum change. When a rural training program needs reform.

OBJECTIVE: To identify what changes should be made in the University of British Columbia's rural family practice training program curriculum to help graduates be better prepared to practice. DESIGN: Two cross-sectional surveys via mailed questionnaires: one designed to measure physicians' self-reported preparedness for practice and the other to measure the importance of various rural family medicine components. SETTING: Rural training program graduates and preceptors representing rural communities in British Columbia. PARTICIPANTS: Thirty-nine graduates of the rural training program between 1982 and 1991 and 14 community-based rural training program preceptors representing eight communities throughout the province participated in this study. MAIN OUTCOME MEASURES: Percentage of graduates of the rural program who reported themselves to be underprepared on each family practice item and preceptors' mean scores for the attributed importance to rural practice of each item on this questionnaire. RESULTS: A list of curriculum areas most in need of reform was created. This list included trauma, counseling skills, radiology, vacuum extraction, fracture care, exercising community leadership, cost-effective use of diagnostic tests, using community health resources, obtaining hospital privileges, ophthalmology, dermatology, otolaryngology, personal and professional growth, relationships with other physicians, and personnel issues. CONCLUSIONS: Using both the level of graduates' self-reported underpreparedness and the attributed importance of elements of rural practice, as indicated by the preceptor survey, we developed a list of the areas of the rural training program curriculum most in need of reform.

Adult↗

The chemistry of pseudomonic acid. 17. Dual-action C-1 oxazole derivatives of pseudomonic acid having an extended spectrum of antibacterial activity.

A series of C-1 oxazole isosteres of pseudomonic acid A (mupirocin) bearing a nitroheterocycle have been synthesized, and significant differences in both spectrum of activity and potency were found between these derivatives and mupirocin. Additionally, the antibacterial potency of two members of this class of compounds against mupirocin-resistant staphylococci could not be accounted for solely by inhibition of the target enzyme isoleucyl-tRNA synthetase (IRS), indicating an additional mode of action. The most potent compound, the nitrofuran 3f (SB 205952), was the most electron affinic derivative prepared and was transformed by NAD(P)H-dependent bacterial reductases at a rate similar to that for nitrofurantoin. The second mode of action of this compound may therefore arise from its reduction to a species with cellular targets other than IRS. In in vivo studies, 3f was shown to be a very effective agent by both the subcutaneous and oral routes of administration.

Anti-Bacterial Agents↗

In vitro selection of a high affinity antibody to oestradiol using a phage display human antibody library.

We have isolated a monoclonal antibody binding to oestradiol with high affinity (3.7 nM), and exhibiting a better than 1000-fold selectivity in binding to other steroids. A high affinity antibody with good specificity is essential for the accurate determination of circulating oestradiol levels. To date, conventional hybridoma technology has not yielded a reagent of sufficiently high affinity and specificity for this ligand. The aim of this study was to investigate whether such a reagent was accessible through the engineering of antibodies on the surface of filamentous phage. Antibodies were isolated from a large repertoire of single chain Fv fragments (scFv) derived from non-immunised human donors, with selection and screening procedures biased to favour those binding to free oestradiol. This resulted in an antibody with nanomolar affinity for oestradiol, while affinities for related steroids are in the micromolar range. The relative lack of reactivity for steroids substituted at either end of the molecule suggests that this antibody is unique among anti-steroid monoclonal antibodies in lacking a 'blind-spot'. Our results demonstrate that phage display can provide solutions to problems that have so far proved intractable using conventional hybridoma technology.

Antibodies, Monoclonal↗

The holmium: YAG laser for ureteric stones.

OBJECTIVE: To assess the efficacy of the pulsed holmium: YAG laser for the fragmentation of ureteric stones. PATIENTS AND METHODS: One hundred patients (72 males and 28 females, age range 14 months-85 years) underwent 114 ureteroscopic procedures using either a 7.2 F semi-rigid or 9.5 F flexible ureteroscope. A holmium: YAG laser (Sunrise Technologies. Fremont, Ca, USA) was used for laser lithotripsy at a maximum energy of 1.0 J/pulse at 5 Hz. Most of the stones (46%) were located in the upper third of the ureter. The mean size of the stones was 9 x 8 mm and the mean duration of the procedure was 73 min (including anaesthesia) with a mean hospital stay of 2.7 days. RESULTS: All the stones were accessed successfully using miniaturized endoscopes either retrogradely or antegradely. The holmium laser effectively fragmented all types of stones. Total clearance of all stones fragments was achieved in 87% of cases, with the best results obtained for stones in the lower third of the ureter (96%). The complications attributed directly to the laser included three strictures and three perforations of the ureteric wall. CONCLUSION: The holmium: YAG laser was effective in fragmenting ureteric stones irrespective of their hardness. However, it has the potential to damage the ureteric wall and must be used with caution.

Adolescent↗

Recovery from experimental parkinsonism in primates with GM1 ganglioside treatment.

A parkinsonian syndrome can be produced in nonhuman primates by administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Parkinsonian-like symptoms induced acutely by MPTP were ameliorated after treatment with GM1 ganglioside, a substance shown to have neurotrophic effects on the damaged dopamine system in rodents. Treatment with GM1 ganglioside also increased striatal dopamine and metabolite levels and enhanced the dopaminergic innervation of the striatum as demonstrated by tyrosine hydroxylase immunohistochemistry. These results suggest that GM1 ganglioside may hold promise as a therapeutic agent for the treatment of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Diaphragm metabolism during supramaximal phrenic nerve stimulation.

The metabolic changes accompanying diaphragm fatigue caused by supramaximal stimulation of the phrenic nerves are incompletely described. In particular, we wished to determine whether the occurrence of anaerobic metabolism correlated with fatigue as defined by decline in force generation. In 10 anesthetized mechanically ventilated mongrel dogs we measured arterial pressure, transdiaphragmatic pressure (Pdi), phrenic arterial flow (Qdi-Doppler flow probe), arterial and phrenic venous blood gases, and lactate levels. From these we derived indexes of diaphragm O2 consumption (VO2) and lactate production. Bilateral phrenic nerve pacing was carried out (50 Hz, duty cycle 0.4, 24 contractions/min) for two 15-min pacing periods separated by a 45-min rest period. Over each pacing period Pdi decreased from approximately 16 to approximately 10 cmH2O (P less than 0.01, no significant difference between periods). Initially, during pacing, Qdi and VO2 each increased fivefold over prepacing base line. Qdi remained elevated at this level whereas VO2 decreased over the pacing period by approximately 25%. Hence, the change in VO2 over the pacing period was due primarily to changes in O2 extraction. During the first pacing period lactate production was observed early and declined throughout the pacing period. No lactate production was observed during the second pacing period, although Pdi, VO2, and Qdi responses were the same for both pacing periods. Phrenic venous PO2 remained greater than 30 Torr throughout both pacing periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗