Search PubMed⌕ Search

Biomedical subjects

D Hall

Publications and source records attributed to D Hall.

At least 55 records · Page 3Linked to original sources
PubMed1998

Determination of prestenotic flow volume using an automated method based on colour Doppler imaging for evaluating orifice area by the continuity equation: validation in a pulsatile flow model.

OBJECTIVE: To evaluate, in a pulsatile flow model simulating flow conditions in valvar stenoses, whether accurate determination of orifice area can be achieved by the continuity equation using automated determination of flow volumes based on spatiotemporal integration of digital colour Doppler flow velocities. METHODS: A method for automated determination of flow volumes which takes into account the velocity distribution across a region of interest was examined using flow through a tube and various restrictive outlet orifices with areas ranging between 0.2 and 3.1 cm2. The sampling rectangle of the Doppler method was positioned proximal to the obstructions within the flow convergence zone for evaluating prestenotic flow volume. Stenotic jet velocities were recorded by continuous wave Doppler to obtain the integral under the velocity curve. Prestenotic flow volume was then divided by the velocity integral to calculate functional orifice area according to the continuity equation. RESULTS: The presence of parabolically shaped velocity profiles across the prestenotic region was demonstrated by the Doppler method. Excellent agreement was found between prestenotic flow volumes measured by the Doppler technique and actual values (r = 0.99, SEE = 1.35 ml, y = 0.99x-0.24). Use of the continuity equation led to a close correlation, with a systematic underestimation of geometric orifice sizes. Correction of Doppler data for flow contraction yielded an excellent agreement with actual orifice areas. CONCLUSIONS: The study validated the accuracy of a Doppler method for automated determination of flow volumes for quantifying orifice area by the continuity equation. Prestenotic flow volume and functional orifice area could be evaluated reliably in the presence of non-flat velocity profiles. Thus the method contributes to the non-invasive assessment of valvar stenoses.

Echocardiography, Doppler, Color↗
PubMed1998

Arachidonic acid potentiates the feedback response of mesangial BKCa channels to angiotensin II.

The influence of arachidonic acid (AA) on the feedback regulation of mesangial contraction by large Ca(2+)-activated K+ channels (BKCa) was determined through single-channel analysis using the patch clamp method. The mesangial BKCa is a low-gain negative feedback inhibitor of contraction that is activated in response to agonist-induced Ca2+ transients and membrane depolarization. AA activated BKCa in cell-attached patches in a dose-dependent manner with a maximal effect at 400 nM and a half-maximal response at 49 nM. In inside-out patches, AA directly activated BKCa with a maximal effect at 400 nM. BKCa was activated significantly in response to addition of 100 nM ANG II in the presence but not the absence of AA. Since it was shown previously that fatty acids stimulated both soluble and membrane-bound guanylyl cyclase, we determined whether AA activated BKCa by interfering with cGMP-mediated signal transduction pathways. It was previously shown that 10 microM cGMP, via cGMP-dependent protein kinase, activated BKCa in a biphasic manner with an early increase in probability of a channel existing in an open state (Po) and a subsequent inactivation mediated by protein phosphatase 2A (PP2A). We found that 10 microM dibutyryl-cGMP enhanced BKCa activity in an additive manner with saturating concentrations (400 nM) of AA. Moreover, the inactivation phase mediated by PP2A was not abolished. Thus AA does not affect the phosphorylation/dephosphorylation regulatory cycle for BKCa. It is concluded that AA potentiates the ANG II feedback response of BKCa by a mechanism that is independent of the phosphorylation cycle.

Angiotensin II↗
PubMed1998

Golf related head injuries in children: the little tigers.

Head injury is a major cause of morbidity in Western society and sport related incidents account for approximately 11% of all head injured patients attending Accident and Emergency Departments. Golf was shown to be one of the sports most commonly associated with head injury requiring referral to a regional neurosurgical centre. Previous studies have demonstrated that it is predominantly children who sustain golf related head injuries which present either to an accident and emergency department or a regional neurosurgical centre. This study examines the number and pattern of golf related head injuries in children presenting to an accident and emergency department or requiring admission to the regional neurosurgical centre, over a three month period.

Age Distribution↗
PubMed1997

Planning for learning.

Explore the source record for details and available documents.

Education, Nursing, Continuing↗
PubMed1997

Lesson-planning.

Explore the source record for details and available documents.

Curriculum↗
PubMed1997

Regulation of large calcium-activated potassium channels by protein phosphatase 2A.

Vasodilating agents induce relaxation of mesangial cells, in part through cGMP-mediated activation of large calcium-activated potassium channels (BKCa). Normally quiescent in cell-attached patches, the response of BKCa to nitric oxide, atrial natriuretic peptide, and dibutyryl cGMP (Bt2cGMP) is characterized by a biphasic increase and then decrease ("rundown") in open probability. Using the patch-clamp method in conjunction with phosphatase inhibitors, we investigated whether the run-down phase was the result of dephosphorylation by an endogenous protein phosphatase. In cell-attached patches, cantharidic acid (500 nM), okadaic acid (100 nM), and calyculin A (100 nM), nondiscriminant inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A) at these concentrations, caused a significantly greater and sustained response of BKCa to Bt2cGMP. Within 2 min, the response of BKCa to the combination of cantharidic acid and Bt2cGMP was greater than the response to these agents added separately. Incubation of mesangial cells with okadaic acid for 20 min at a concentration (5 nM) specific for PP2A increased the basal open probability of BKCa and completely inhibited rundown after activation by Bt2cGMP. Incubation with calyculin A (10 nM), a more potent inhibitor of PP1, did not affect BKCa activity. In inside-out patches, Bt2cGMP plus MgATP caused a sustained activation of BKCa that was inhibited by exogenous PP2A but not PP1. It is concluded that either BKCa or a tightly associated regulator of BKCa is a common substrate for endogenous cGMP-activated protein kinase, which activates BKCa, and PP2A, which inactivates BKCa, in human mesangial cells.

Cell Adhesion↗
PubMed1997

Child development teams: are they fulfilling their purpose?

Child development teams (CDTs) have been in existence for a quarter of a century, yet little is known of how they function or what they do. This paper originated in a national seminar on how CDTs function and what they seek to achieve. It discusses the wide range of practice in CDTs across Britain and the apparent deficiencies in service provision for certain types of disability. Since each child has a unique set of needs, the composition of the team must be flexible and responsive to the changing circumstances of each child. The need for a philosophical shift to take account of changing parental expectations is stressed. There is a need for further research on a number of topics, including: the patterns of service provision and the differences between districts; the implementation of what is already known about standards of good practice; the possible role of a charter for disabled children and their families; the training needs of future CDT professionals.

Caregivers↗
PubMed1997

The relationship between audit, research and policy: lessons from a community paediatric audiology service.

The pace of medical change is in danger of paralysing the process of decision making, particularly in services where clinical improvements occur more slowly than the introduction of new interventions. Audit within an individual district enables staff to monitor progress towards desired goals and standards but rarely generates sufficient data to inform decision making about major policy changes. The paper describes how the findings from nine audits of a community paediatric audiology service over a 13-year period were combined with reviews of the literature, resulting in a series of changes to a children's audiological service. The interest and commitment of all the staff involved were maintained by involving them in the process and using them as a valuable source of qualitative data. Audit must be thorough and should be based on precise case definition and comprehensive casefinding if the results are to be meaningful. It is a more powerful means of achieving improvements in systems if it is combined with research evidence, and a readiness to change the system if the agreed goals are not being attained.

Cohort Effect↗
PubMed1997

High-dose nevirapine in previously untreated human immunodeficiency virus type 1-infected persons does not result in sustained suppression of viral replication.

High-dose nevirapine treatment has been reported to confer sustained antiretroviral effects, despite a rapid development of resistance. The use of this strategy was evaluated in 20 previously untreated human immunodeficiency virus type 1 (HIV-1) p24 antigenemic persons with CD4 cell counts between 100 and 500/mm3. Treatment consisted of 400 mg of nevirapine, after a 2-week lead-in dose of 200 mg. Rash was the most frequently reported adverse event, occurring in 25%. While sustained declines in p24 antigen levels were observed in the majority, serum HIV-1 RNA load and CD4 cell counts returned to baseline values within 12 weeks in virtually all subjects. The resistance-conferring tyrosine-to-cysteine substitution at reverse transcriptase position 181 was detected after 4 weeks in most subjects. These observations suggest that plasma drug levels attained with high-dose nevirapine were not sufficient to inhibit nevirapine-resistant virus, although they were approximately 2-fold higher than reported IC50 values of resistant virus.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Lichen sclerosus: early diagnosis is the key to treatment.

Lichen sclerosus of the vulvar is an often misdiagnosed and chronic gynecologic disease. Women of any age can be affected, but it is most common in the perimenopausal and postmenopausal years. The treatment for lichen sclerosus is limited with no cure. The current treatment is a lifelong procedure and may not prevent the progression of the disease. The primary treatment for lichen sclerosus is testosterone ointment, which may cause unwanted side effects. Complications arising from vulvar lichen sclerosus include loss of vulvar structure and fusing of labia which causes covering of the clitoris. Vulvar lichen sclerosus may also cause painful intercourse and defecation. Due to the intense pruritus, excoriation of the area occurs. This information can help the clinician to detect the disease early and start treatment before serious complications begin. Diagnostic and treatment information is provided in this article to help the clinician understand the nature of this disease.

Biopsy↗
PubMed1995

Three-dimensional structure of a mutant HIV-1 protease displaying cross-resistance to all protease inhibitors in clinical trials.

Analysis of mutational effects in the human immunodeficiency virus type-1 (HIV-1) provirus has revealed that as few as four amino acid side-chain substitutions in the HIV-1 protease (M46I/L63P/V82T/I84V) suffice to yield viral variants cross-resistant to a panel of protease inhibitors either in or being considered for clinical trials (Condra, J. H., Schleif, W. A., Blahy, O. M., Gadryelski, L. J., Graham, D. J., Quintero, J. C., Rhodes, A., Robbins, H. L., Roth, E., Shivaprakash, M., Titus, D., Yang, T., Teppler, H., Squires, K. E., Deutsch, P. J., and Emini, E. A. (1995) Nature 374, 569-571). As an initial effort toward elucidation of the molecular mechanism of drug resistance in AIDS therapies, the three-dimensional structure of the HIV-1 protease mutant containing the four substitutions has been determined to 2.4-A resolution with an R factor of 17.1%. The structure of its complex with MK639, a protease inhibitor of the hydroxyaminopentane amide class of peptidomimetics currently in Phase III clinical trials, has been resolved at 2.0 A with an R factor of 17.0%. These structures are compared with those of the wild-type enzyme and its complex with MK639 (Chen, Z., Li, Y., Chen, E., Hall, D. L., Darke, P. L., Culberson, C., Shafer, J., and Kuo, L. C. (1994) J. Biol. Chem. 269, 26344-26348). There is no gross structural alteration of the protease due to the site-specific mutations. The C alpha tracings of the two native structures are identical with a root-mean-square deviation of 0.5 A, and the four substituted side chains are clearly revealed in the electron density map. In the MK639-bound form, the V82T substitution introduces an unfavorable hydrophilic moiety for binding in the active site and the I84V substitution creates a cavity (unoccupied by water) that should lead to a decrease in van der Waals contacts with the inhibitor. These changes are consistent with the observed 70-fold increase in the Ki value (approximately 2.5 kcal/mol) for MK639 as a result of the mutations in the HIV-1 protease. The role of the M46I and L63P substitutions in drug resistance is not obvious from the crystallographic data, but they induce conformational perturbations (0.9-1.1 A) in the flap domain of the native enzyme and may affect the stability and/or activity of the enzyme unrelated directly to binding.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Identification of the cis-elements mediating the autogenous control of ribosomal protein L2 mRNA stability in yeast.

The ribosomal protein L2 (rpL2) of Saccharomyces cerevisiae regulates the accumulation of its own mRNA by a feedback mechanism. An RNA sequence is responsible for this control, initially characterized as a 360 nucleotide-long region, localized at the 5' end of the transcript. This region, fused to an unrelated coding sequence, is able to down-regulate the accumulation of the chimeric transcript when increased levels of rpL2 are induced in the cell. The target regulatory region also responds to regulation when inserted inside an intron, demonstrating that the control process can take place inside the nucleus. Deletion analysis from the 5' and 3' borders have restricted the responsive region to approximately 200 nt. The insertion of a poly-G cassette downstream of the regulatory region allowed the identification of truncated 3' cut-off poly(A)+ RNA molecules. The parallel identification of cut-off molecules containing the 5' portion of the transcript allowed us to deduce that the truncated products originate by endonucleolytic cleavage. Altogether, these results are consistent with a mechanism by which the presence of excess amounts of rpL2 in the cell triggers its own mRNA to a degradative pathway; this involves an initial endonucleolytic cleavage that is followed by exonucleolytic trimming. Such a regulatory mechanism shows interesting analogies with the translational regulation of r-proteins in Escherichia coli.

Base Sequence↗