External beam radiation therapy for CNV.
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Choroidal Neovascularization↗
Biomedical subjects
P Hart
Publications and source records attributed to P Hart.
A microbiological investigation following the disinfection of alginate and addition cured silicone rubber impression materials.
The antimicrobial efficacy of four commercially available disinfectants (Haz-tabs, chlorhexidine, Virkon and C&J Algisept Spray) was investigated. It was shown that all were effective in decontaminating the impressions whilst those placed only in sterile water, used as a control, showed variable levels of bacterial growth. Moreover, alginate appeared to carry significantly higher numbers of bacteria than addition cured silicone rubber.
Adult↗
Development of a sedation scoring protocol.
The creation of a research and development post within the Intensive Therapy Unit (ITU) environment at St Helier has provided the opportunity to review all aspects of practice to ensure that the care delivered is evidence-based and not merely rooted in routines and rituals. The first aspect of care to be examined was our sedation practice. It was felt that sedation procedures varied at times and that a research-based protocol was necessary to ensure that patients receive optimal levels of sedation consistently. A 'sedation scoring group' was set up in order to achieve this. Questionnaires were sent to all members of staff and the resulting data used to formulate a sedation scoring system and algorithm as well as a protocol which included information on sedative drugs and the effects of over- and under-sedating patients.
Algorithms↗
Cystic fibrosis gene encodes a cAMP-dependent chloride channel in heart.
cAMP-dependent chloride channels in heart contribute to autonomic regulation of action potential duration and membrane potential and have been inferred to be due to cardiac expression of the epithelial cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. In this report, a cDNA from rabbit ventricle was isolated and sequenced, which encodes an exon 5 splice variant (exon 5-) of CFTR, with >90% identity to human CFTR cDNA present in epithelial cells. Expression of this cDNA in Xenopus oocytes gave rise to robust cAMP-activated chloride currents that were absent in control water-injected oocytes. Antisense oligodeoxynucleotides directed against CFTR significantly reduced the density of cAMP-dependent chloride currents in acutely cultured myocytes, thereby establishing a direct functional link between cardiac expression of CFTR protein and an endogenous chloride channel in native cardiac myocytes.
Alternative Splicing↗
Women in medical research: headaches and hurdles.
Very few women have professorial status in Australian medical schools. However, there are approximately equal numbers of male and female PhD students in biomedical research at Australian universities. At Flinders University of South Australia, females comprise approximately 25% of academics in the School of Medicine, with 75% of general staff (including research staff without academic status, e.g. research assistants, research officers) being female. Females comprise 29% of Fellows in the highly competitive Career Awards Scheme of the National Health and Medical Research Council of Australia (NHMRC; 26% excluding those of the lowest rank, namely RD Wright Fellows). In both systems, a higher percentage of women are appointed to the lower levels. The statistics suggest that the main hurdle for women in medical research is the inability to progress in the postdoctoral ranks (e.g. appointment to, or promotion from, academic Level A/B positions (Tutor/Lecturer) or appointment to the NHMRC Research Fellowships Scheme). This may reflect the conflicts that women face in their debate of the priorities of family (children and partner) versus career, or research versus teaching and professional activities. All medical research is time-demanding and continuing research funds are difficult to obtain. Women and men have similar success rates for obtaining funds from the NHMRC. However, a greater percentage of women academics do not apply for grants. Why? Can women be helped to play a larger role in medical research?
Australia↗
CFTR chloride channels in human and simian heart.
OBJECTIVES: The cAMP-dependent Cl- conductance in heart is believed to be due to cardiac expression of the cystic fibrosis transmembrane conductance regulator (CFTR). While CFTR expressed in rabbit and guinea-pig heart (CFTRcardiac) is an alternatively spliced isoform of the epithelial gene product, little information is known regarding possible expression of CFTR in primate heart. In this study, we examined molecular expression of CFTR in human and simian atrium and ventricle and functional expression of cAMP-dependent Cl- currents in isolated human atrial and simian ventricular cells. METHODS: The reverse transcription polymerase chain reaction (RT-PCR) was performed on human and simian atrial and ventricular mRNA using primers designed to border regions of the CFTR gene product corresponding to transmembrane segments I-VI (TSI-VI), the first nucleotide binding domain (NBD1), transmembrane segments VII-XII (TSVII-XII), and the large cytoplasmic domain which includes the regulatory (R) domain and NBD1. Functional expression of CFTR Cl- channels in human atrial and simian ventricular myocytes was determined using whole-cell and giant inside-out patch-clamp techniques. RESULTS: Southern blot analysis of these RT-PCR products demonstrated expression of CFTR transcripts in human and simian atrial and ventricular tissue and revealed a novel pattern of expression compared to most animal species studies: both the exon 5 plus (unspliced) and exon 5 minus (spliced) CFTR transcripts are co-expressed in human and simian atrium and ventricle. Whole-cell experiments demonstrated a Cl- sensitive time-independent background conductance in both human atrial and simian ventricular myocytes that was activated by forskolin (FSK) and insensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). In inside-out patches utilizing the giant patch technique on human atrial myocytes, unitary Cl- sensitive channels resembling CFTR Cl- channels (approximately 14 pS conductance) were activated by the catalytic subunit of protein kinase A (PKA) in 3/12 patches examined. CONCLUSIONS: These results clearly demonstrate the molecular expression of CFTR Cl- channels and provide electrophysiological evidence consistent with functional expression of these channels in human atrial and simian ventricular myocardium.
Aged↗
The magnitude and time course of vecuronium potentiation by desflurane versus isoflurane.
BACKGROUND: Preliminary studies suggest that desflurane and isoflurane potentiate the action of muscle relaxants equally. However, variability between subjects may confound these comparisons. A crossover study was performed in volunteers on the ability of desflurane and isoflurane to potentiate the neuromuscular effect of vecuronium, to influence its duration of action, and on the magnitude and time course of reversal of potentiation when anesthesia was withdrawn. METHODS: Adductor pollicis twitch tension was monitored in 16 volunteers given 1.25 MAC desflurane on one occasion, and 1.25 MAC isoflurane on another. In eight subjects, vecuronium bolus dose potency was determined using a two-dose dose-response technique; the vecuronium infusion dose requirement to achieve 85% twitch depression also was determined. Also in these subjects, the magnitude and time course of spontaneous neuromuscular recovery were determined when the anesthetic was withdrawn while maintaining a constant vecuronium infusion. In the other eight subjects, the time course of action of 100 micrograms/kg vecuronium was determined. RESULTS: Vecuronium's ED50 and infusion requirement to maintain 85% twitch depression were 20% less during desflurane, compared to isoflurane, anesthesia; vecuronium plasma clearance was similar during the two anesthetics. After 100 micrograms/kg vecuronium, onset was faster and recovery was longer during desflurane anesthesia. When the end-tidal anesthetic concentration was abruptly reduced from 1.25 to 0.75 MAC, twitch tension increased similarly (approximately 15% of control), and time for the twitch tension to reach 90% of the final change was similar (approximately 30 min) with both anesthetics. Decreasing anesthetic concentration from 0.75 to 0.25 MAC increased twitch tension by 46 +/- 10% and 25 +/- 7% of control (mean +/- SD, P < 0.001) with desflurane and isoflurane, respectively; 90% response times for these changes were 31 +/- 10 min and 18 +/- 7 min (P < 0.05), respectively. CONCLUSIONS: Desflurane potentiates the effect of vecuronium approximately 20% more than does an equipotent dose of isoflurane.
Adult↗
Angiography and the aetiology of heart failure.
The diagnosis of idiopathic dilated cardiomyopathy should not be made without first performing a coronary angiogram. If the cause of heart failure is unknown this should be stated rather than attributing the cause to dilated cardiomyopathy. Severe ventricular dysfunction may improve dramatically after revascularisation in some cases of coronary disease. Preservation of R waves on the surface electrocardiogram suggests the presence of hibernating myocardium but thallium scintigraphy or positron emission tomography scanning should be employed to investigate this further.
Cardiomyopathy, Dilated↗
Neuropeptide Y attenuates satiety: evidence from a detailed analysis of patterns ingestion.
Centrally injected neuropeptide Y (NPY) is a potent stimulant of ingestive behavior capable of augmenting both food and fluid intake in fully satiated animals. To gain further insight into NPY's mechanism of action, we recorded patterns of licking behavior in rats drinking sweetened condensed milk solutions immediately after lateral ventricular injection of NPY (10 micrograms) or vehicle. In a separate study, we examined licking patterns after 23 h food deprivation (FD) that produced approximately the same total intake as NPY. Consistent with previous reports, we found NPY stimulated intake by increasing total ingestion time and total volume consumed during a 1-h test. Although NPY increased the number of bouts of licking and shortened pauses between bouts, it also decreased mean bout size, bout duration and within-bout lick rate (local rate). It had no significant effect on start latency or lick efficiency (licks/ml). Further analyses revealed that NPY attenuated satiety (reduced slope of lick-rate functions with session time) but had no significant effect on the beginning lick rate, a measure related to orosensory excitation. In contrast to NPY, FD increased both the beginning lick rate and individual bout size without changing either the mean number of bouts or the pause between bouts. In general, NPY stimulated an intermittent pattern of licking and delayed satiation whereas FD increased the initial rate of licking and the size of individual bouts without changing the basic licking pattern. The increase in initial lick rate suggests that FD, unlike NPY, enhances orosensory stimulation. These data compliment previous results showing that NPY increases the motivation to eat.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Molecular physiology of CFTR Cl- channels in heart.
Recent electrophysiological data suggests a number of similarities in the properties of cAMP-dependent Cl- channels in heart and cAMP-dependent Cl- channels encoded by the cystic fibrosis transmembrane conductance regulator (CFTR) gene product in various epithelial cells. We tested the hypothesis that cAMP-dependent Cl- channels in heart may be due to cardiac expression of CFTR by amplification and sequencing of several regions of CFTR from myocardial tissue derived from various species and areas of the heart. Regions corresponding to the first nucleotide binding domain (NBD1), transmembrane segments I-VI (TS I-VI), transmembrane segments VII-XII (TS VII-XII), and the regulatory domain (R domain) were amplified and sequenced from rabbit ventricle (see Fig. 1). Comparison of the known amino acid sequence of human epithelial CFTR with the deduced sequence from rabbit heart indicated deletion of exon 5 in the first cytoplasmic loop of TS I-VI suggesting that CFTR is an alternatively spliced isoform in rabbit ventricle. Outside of the alternatively spliced region, the heart CFTR Cl- channel isoform displayed greater than 95% identity to human epithelial CFTR Cl- channels. We have also compared the molecular distribution of the CFTR gene product to the distribution of cAMP-dependent Cl- channels in native cardiac myocytes derived from various species and areas of the heart. Amplification of regions corresponding to NBD1, R domain, and TS VII-XII from atrium and ventricle of guinea pigs, rabbit, and dog hearts exhibited a distribution which closely matched the distribution of cAMP-dependent Cl- channels assessed using electrophysiological techniques.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Cumulative characteristics of atracurium and vecuronium. A simultaneous clinical and pharmacokinetic study.
BACKGROUND: Cumulative effects (increased 25-75% recovery time with increasing dose) are evident with vecuronium but not with atracurium. Pharmacokinetic simulations suggest that vecuronium's cumulation occurs as recovery shifts from distribution to elimination whereas atracurium's recovery always occurs during elimination. The purpose of this study was to examine this pharmacokinetic explanation. METHODS: We assigned 12 volunteers to receive atracurium of vecuronium on three occasions during nitrous oxide-isoflurane anesthesia. Evoked adductor pollicis twitch tension was monitored. On occasion 1, the dose expected to produce 95% block (ED95) was estimated for each subject. On occasions 2 and 3, 1.2 or 3.0 multiples of ED95 were given as a bolus. Plasma was sampled for 128 min to determine muscle relaxant concentrations; pharmacodynamic modeling was used to determine effect-compartment drug concentrations (Ce). For each drug, recovery time, recovery phase half-life (rate of decrease in Ce during recovery), and Ce at 25% and 75% recovery were compared between doses. RESULTS: Atracurium's recovery time increased 2.4 +/- 2.2 min (mean +/- SD) with the larger dose, less than the increase with vecuronium (8.2 +/- 3.8 min). Atracurium's recovery phase half-life was 14.6 +/- 1.7 and 20.1 +/- 2.3 min with the small and large doses (P < 0.05); vecuronium's recovery phase half-life increased similarly from 13.5 +/- 2.3 to 18.5 +/- 5.0 min (P < 0.05). At 75% recovery, vecuronium's Ce decreased from 65 +/- 18 ng/ml with the small dose to 55 +/- 15 ng/ml with the large dose (P < 0.05). Assuming that neuromuscular junction sensitivity was constant, this difference could be explained by considering neuromuscular effects of vecuronium's metabolite, 3-desacetylvecuronium. CONCLUSIONS: Although vecuronium was cumulative (as predicted), atracurium was also slightly cumulative. Inconsistent with our hypothesis, recovery phase half-lives for both drugs increased similarly between doses; therefore, differences in cumulation were not solely explained by pharmacokinetics of the muscle relaxant. It appears that 3-desacetylvecuronium contributes to vecuronium's cumulative effect, even after usual clinical doses.
Adult↗
Changes in the oral microflora during cytotoxic chemotherapy in children being treated for acute leukemia.
Thirty-four children with diagnosed cases of acute leukemias and being treated with cytotoxic chemotherapy at St James' Hospital, Leeds, were followed for between 6 months and 1 year to determine the changes in their oral microflora. They were examined before treatment commenced and then at monthly intervals. Swabs were taken from the oral cavity to test for the presence or absence of bacteria and Candida. Saliva samples were also used to assess the levels of Streptococcus mutans in the mouth. Sensitivity tests were carried out to assess the effect of the cytotoxic agents on the oral flora. All children received prophylactic nystatin and chlorhexidine gluconate mouthrinses four times daily for the whole period of the study. There was significant difference (p < 0.0001) for counts of S. mutans at different treatment stages. Sensitivity tests showed that S. mutans was sensitive to the cytotoxic drug daunorubicin, and this drug was probably responsible for the fall in S. mutans counts. A significant difference was also found in the types of bacteria isolated between the study and reference groups, but there was no change in the composition of the flora in the study group during treatment. These bacteria were also found to mirror those cultured from routine blood samples in children with acute leukemia.
Adolescent↗
Alternative splicing of CFTR Cl- channels in heart.
We have previously demonstrated that cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels are expressed in heart (Levesque et al., Circ. Res. 71: 1002-1007, 1992). However, the structural identity between this cardiac protein and CFTR in epithelial cells is unknown. We amplified cDNA from rabbit ventricle and cloned fragments corresponding to the 12 transmembrane spanning domains of the epithelial CFTR transcript. The deduced sequence from rabbit heart indicated deletion of a 30-amino acid segment in the first cytoplasmic loop of CFTR, which corresponds to known locations of intron-exon junctions bordering exon 5 in the CFTR gene, suggesting that CFTR is alternatively spliced in heart. Outside this region, the heart CFTR isoform displayed > 95% identity to human epithelial CFTR. Molecular analysis demonstrated CFTR expression only in cardiac tissues that exhibited a adenosine 3',5'-cyclic monophosphate-dependent Cl- conductance in native cells. The expression of a specific isoform of CFTR Cl- channels in mammalian heart may have functional and clinical significance.
Animals↗
Changes in the leucocyte count during and after brief intense exercise.
Twelve healthy male volunteers exercised at 200 W on a cycle ergometer for 8 min or until exhausted, if sooner. Retrospectively, subjects fell into two groups. During the last minute of exercise at 200 W, those in group 1 (n = 5) had a mean respiratory exchange ratio (R) of 1.06 (SD 0.01) and were working at a mean of 79% (SD 4%) of their maximum oxygen consumption (VO2max) as measured in a separate incremental load test. For subjects in group 2 (n = 7), R was 1.31 (SD 0.08) and their VO2 was maximal (mean 101%. SD 3%). Plasma lactate, and adrenaline concentrations rose to higher levels during exercise in subjects in group 2 than in those in group 1. At the finish of exercise, the leucocyte count and the plasma lactate concentration immediately began to fall in subjects in group 1 whereas in group 2 subjects both rose for several minutes before falling. Plasma catecholamine concentrations fell rapidly in both groups during recovery.
Adult↗
The role of the retinoblastoma gene in tumour pathogenesis.
Retinoblastoma is a rare tumour. The gene involved in the formation of retinoblastoma has been identified, and it has since been shown to be implicated in many other tumour types. In addition, patients with the familial form of retinoblastoma are known to be at an increased risk of developing second primary, non-ocular, malignancies. Retinoblastoma provides us with an important insight into the genetic mechanisms involved in tumorigenesis, to the extent that the retinoblastoma gene has now become the archetype of the 'tumour-suppressor' genes. The importance of this class of genes in tumorigenesis may come to exceed that of the oncogenes.
Child↗
The cyclopean ternus display and the perception of element versus group movement.
This study investigated the perception of bistable stroboscopic motion (Ternus display) with cyclopean stimuli created from retinal disparity embedded in dynamic random-element stereograms, the responses to which arise at binocular-integration levels of the visual system. To provide comparison data, observers were also tested with luminance-domain stimuli matched as closely as possible to their cyclopean counterparts. The results showed that the perception of element vs group movement was similar for both stimulus domains: element movement predominated at short interstimulus intervals (ISIs) while group movement predominated at long ISIs, and there was a tendency for a greater percentage of group movement to occur with a longer frame duration. These results cast suspicion on the interpretation of bistable motion that assumes element movement is a signature of a lower-level, short-range motion system whereas group movement is a signature of a higher-level, long-range system; both percepts are engendered at binocular-integration levels of vision.
Depth Perception↗
Cross-infection hazards associated with the use of pumice in dental laboratories.
The bacteriological contamination of pumice slurry in polishing units in a dental clinical area (high risk), a production laboratory (medium risk), and a non-clinical teaching laboratory (low risk), was investigated. Slurry samples taken from all three areas were found to be heavily contaminated with pathogenic organisms. The investigations were repeated following the addition of a disinfectant with both bacteriocidal and virucidal properties to the pumice. Lower bacterial counts were obtained indicating that routine disinfection of pumice slurries is desirable.
Bacteroides↗
Relatively few clinicians in medical research in Australia: a problem?
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Australia↗