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Biomedical subjects

A Watt

Publications and source records attributed to A Watt.

At least 19 recordsLinked to original sources
PubMed2001

Maximising health gain within available resources in the New Zealand public health system.

OBJECTIVE: to obtain intervention-condition-specific investment and disinvestment recommendations which optimise the potential for health gain from existing respiratory diseases resource expenditure; and to trial a health economics technique for this purpose, assessing its usefulness as a means of prioritising health services resource allocation. DESIGN: a programme budgeting and marginal analysis (PBMA) exercise drawing upon the expertise of an advisory group of clinicians, managers and consumer advocates, supported by health authority staff. SETTING: the Southern and Midland health regions in New Zealand which have populations of one million and seven hundred thousand respectively. HEALTH SYSTEM CONTEXT: publicly funded secondary care sector in which regional health authority (RHA) purchasers contract for services with health care providers. METHODS: available evidence on the marginal costs and benefits of services for respiratory diseases was examined by an advisory group who produced investment and disinvestment recommendations by consensus using agreed prioritisation criteria. RESULTS: A list of specific investment and disinvestment proposals. Implementation plans for a number of investments formed part of the business plans for both RHAs in 1997/1998. No disinvestments were planned. CONCLUSIONS: prioritisation methods like PBMA, which are explicit and rational, can produce defensible evidence-based recommendations with the additional benefit of the credibility and support of an expert advisory group. The process encourages co-operative working and may itself have enduring benefits. However, preparation and conduct of such exercises is resource intensive and requires careful planning. This exercise has provided valuable lessons for the conduct of future prioritisation work.

Delivery of Health Care↗
PubMed2000

Corpus cavernosum as an alternative means of intravenous access in the emergency setting.

BACKGROUND: The present study was designed to investigate the feasibility of using the corpus cavernosum as an alternative means of intravenous access in the emergency setting. METHODS: The feasibility of achieving the infusion flow rates was first ascertained using direct intracavernous infusion of normal saline. The effect of atropine and adrenaline when given via this route was then studied. Hypovolaemic shock was then induced in dogs who were then actively resuscitated via this route using normal saline, Haemaccel and whole blood. RESULTS: Infusion flow rates were achieved for normal saline of 32.3, 50.3 and 67.3 mL per min at 100, 200 and 300 mmHg pressure, respectively. The peak effects of atropine and adrenaline via this route were seen at approximately 1 min after injection. Resuscitation using this method was uniformly successful in all dogs via the corpus cavernosum, with all reaching or exceeding their premorbid central venous pressure (CVP), and approaching or reaching their premorbid mean arterial pressure (MAP). In comparison the control dog's CVP and MAP did not rise during the period of observation after it was bled. CONCLUSIONS: The corpus cavernosum is a practical alternative means of intravenous access in the emergency setting in the dog model.

Adrenergic Agonists↗
PubMed2000

Randomized trial of graded compression stockings for prevention of deep-vein thrombosis after acute stroke.

Graded compression stockings are commonly used to prevent deep-vein thrombosis (DVT) after stroke, but their efficacy in this setting has not been evaluated. Extrapolation of effectiveness from trials in patients undergoing elective surgery may be inappropriate. We undertook a randomized, controlled trial, with blinded data review, in a University hospital Acute Stroke Unit. Patients were allocated to graded compression stockings or to standard care alone. DVT incidence was determined at baseline and at day 7+/-2 by colour-flow Doppler ultrasound. Ninety-eight patients with acute, immobilizing stroke were randomized; 97 had full outcome data. One patient had clinically manifest DVT, and no patient had pulmonary thromboembolism. DVT was detected in 7/65 patients allocated stockings, and 7/32 controls (odds ratio 0.43, 95% CI 0.14-1.36); DVT involving femoral veins was detected in 3/65 and 2/32. In the first week after stroke, radiologically-detected DVT remains common, but is usually clinically silent. Proximal DVT is less common. Graded compression stockings produced a reduction in DVT incidence comparable to that in other patient groups, but the reduction was not statistically significant, and the magnitude of effect size requires confirmation. There is greater doubt over efficacy in early prevention of proximal DVT.

Aged↗
PubMed1999

Cooperation of Sp1 and p300 in the induction of the CDK inhibitor p21WAF1/CIP1 during NGF-mediated neuronal differentiation.

Addition of nerve growth factor (NGF) to PC12 cells promotes neuronal differentiation while inhibiting cell proliferation. In order to understand how NGF exerts its antimitogenic effect during differentiation, we have studied the mechanism by which this factor activates the promoter of the CDK inhibitor p21W4F1/CIP1. The minimal region of the p21 promoter required for the NGF-induction was mapped to a contiguous stretch of 10 bp located 83 bases upstream of the transcription initiation site. This GC-rich region was shown to interact specifically with the transcription factor Sp1 and the related protein Sp3, in either exponentially-growing or NGF-treated PC12 cells. The addition of NGF resulted in an accumulation of the transcriptional co-activator p300 in complexes associated with the NGF-responsive region. Transcriptional activity of Sp1, Sp3 and p300 was specifically induced by NGF in a Gal4-fusion assay, indicating that induction of p21 during neuronal differentiation may involve regulation of the activity of these factors by NGF. Furthermore, p300 was able to act as a co-activator for Sp1-mediated transcriptional activation in PC12 cells, suggesting that p300 and Sp1 may cooperate in activating p21 transcription during the withdrawal of neuronal precursors from the cell cycle. This hypothesis is supported by experiments showing that p300 and Sp1 form complexes in PC12 cells.

Animals↗
PubMed1998

Hippocampal lesions disrupt an associative mismatch process.

Novel assays were used to assess inter alia whether the hippocampus is involved in detecting novelty per se or in an associative mismatch process. During training, rats received two audiovisual sequences (tone-left constant light and click-left flashing light). In both sham-operated control rats and those with excitotoxic hippocampal lesions, novel visual targets provoked an orienting response that habituated during training. Moreover, like sham-operated rats, rats with hippocampal lesions acquired associations between the elements of two audiovisual sequences. However, subsequent test trials in which the auditory stimuli preceding the visual targets were switched (click-left constant light and tone-left flashing light) provoked renewed orienting to the visual targets in sham-operated rats but not in hippocampal rats. These results support the view that hippocampal damage results in a failure to detect (or act on) mismatches that are generated when an auditory stimulus associatively evokes the memory of one visual stimulus and a different (familiar) visual stimulus is present in the environment.

Animals↗
PubMed1998

Cdm1, the smallest subunit of DNA polymerase d in the fission yeast Schizosaccharomyces pombe, is non-essential for growth and division.

Highly purified DNA polymerase delta from the fission yeast Schizosaccharomyces pombe is a complex of at least four distinct subunits. Genes encoding three of these (pol3+/cdc6+, cdc1+ and cdc27+) have been characterised previously. Here we describe the isolation and characterisation of cdm1+, the gene encoding the smallest (22kDa) subunit of the Pol delta complex. Over-expression of cdm1+, which encodes a 160 amino-acid protein with no significant sequence similarity to proteins in current databases, is able to rescue cells carrying temperature-sensitive mutations in either pol3+/cdc6+, cdc1+ or cdc27+. Cells deleted for cdm1+ are viable, indicating that cdm1+ is non-essential for mitotic growth, and are no more sensitive to a variety of DNA replication inhibitors and DNA damaging agents than are wild-type cells. In addition, over-expression of cdm1+ suppresses the temperature-sensitive cdc24-M38 mutant suggesting that cdc24+ may also have a role in DNA polymerase delta function.

Amino Acid Sequence↗
PubMed1998

Acquired relational equivalence: implications for the nature of associative structures.

In 2 experiments, rats received discrimination training in which separate presentations of A and B signaled a common pair of relationships or associations (X-->food and Y-->no food), whereas presentations of C and D signaled a different pair of relationships (X-->no food and Y->food). To assess the nature of the associative structures acquired during this training, rats then received 2 types of reevaluation procedure: In Experiment 1, A was paired with shock and C was not. In Experiment 2, the relationships that A and B had previously signaled (X-->food and Y-->no food) were paired with shock, whereas those that C and D had signaled (Y-->food and X-->no food) were not. After both types of reevaluation treatment, rats showed greater generalized conditioned suppression in the presence of B than D. These results indicate that A, B, C, and D come to evoke memories of the relationship or associations that they have signaled.

Animals↗
PubMed1998

A comparison of the effects of mibefradil and atenolol on regression of left ventricular hypertrophy in hypertensive patients.

OBJECTIVE: This study was designed to compare the effect of mibefradil, a selective T-type calcium channel antagonist, with the beta-blocker atenolol on regression of left ventricular (LV) hypertrophy in hypertensive patients. METHODS: In this multicenter, double-blind, active-controlled, randomized, parallel-group comparison, 66 patients with mild-to-moderate hypertension (sitting diastolic blood pressure, SDBP, 95-114 mm Hg) and LV mass index > 102 g/m2 for males and > 88 g/m2 for females were randomized to an initial treatment with 50 mg of either mibefradil or atenolol for 4 weeks. Doses were increased to 100 mg/day if blood pressure was not normalized to < or = 90 mm Hg, and, if needed, 25 mg of hydrochlorothiazide was added. Treatment continued for a total of 24 weeks. LV hypertrophy was assessed by echocardiography, and trough SDBP and adverse events were recorded. RESULTS: Treatment with mibefradil or atenolol resulted in decreases from baseline in LV mass index of 11.1% (p < 0.001) and 9.1% (p < 0.001), respectively. The treatment difference (mibefradil vs. atenolol) was not statistically significant. Reductions in SDBP with mibefradil and atenolol were 14.3 and 10.7 mm Hg, respectively, again not statistically significant. Both drugs were well tolerated; however, overall there were more potentially drug-related adverse events reported with atenolol (48.5%) than with mibefradil (24.2%). CONCLUSIONS: The reductions in LV hypertrophy and blood pressure achieved with mibefradil were larger but statistically equivalent to those with atenolol, but a lower overall incidence of treatment-related adverse events was seen in the mibefradil-treated patients.

Adrenergic beta-Antagonists↗
PubMed1997

Familial glucocorticoid deficiency: one syndrome, but more than one gene.

Familial glucocorticoid deficiency is a rare autosomal recessive disease characterised by resistance to the action of ACTH. A number of mutations in the ACTH receptor have been demonstrated in patients with this disorder which are likely to lead to loss of receptor function and thus would account for the syndrome. Several patients, however, do not have mutations in the ACTH receptor gene coding region, and it can be demonstrated by segregation analysis that another distant gene must account for the disease in some of these cases. The nature of several candidate genes for this normal receptor form of the disease is discussed.

Animals↗
PubMed1997

Combining CSs associated with the same or different USs.

In three experiments, hungry rats received appetitive training with four stimuli, A, B, X, and Y. In each Experiment, A and B were paired with one unconditioned stimulus (US; e.g. food pellets) whereas X and Y were paired with a second US (e.g. sucrose). Subsequently, rats responded more vigorously to combinations of stimuli associated with different USs (A-Y & X-B) than to combinations of stimuli associated with the same US (A-B & X-Y; Experiments 1, 2, & 3). This effect was observed when the stimuli were presented simultaneously and during the second elements of serial compounds (Experiments 2 & 3). Moreover, combining CSs associated with different USs resulted in a more marked CR than combining CSs that had each been paired with both US1 and US2 (Experiment 3). These results suggest that the sensory properties of appetitive reinforcers have an important influence on performance.

Analysis of Variance↗
PubMed1996

Three-dimensional stylization of structures of interest from computed tomography images applied to radiotherapy planning.

PURPOSE: Techniques to detect structures of interest and model them as simple geometric shapes to enhance their visualization are presented. METHODS AND MATERIALS: Three-dimensional visualization techniques can be used to enhance the detection of critical structures by enclosing them in a readily perceived bounding volume. This article describes stylization techniques that define three-dimensional shapes that conform to the real shape of the structures in the case of the spinal cord and the eyeballs. The term stylization can, thus, be defined as a combination of segmentation and the production of a tight bounding volume. The stylization techniques attempt to minimize the region that belongs to the solid produced and does not belong to the real structure, but they also attempt to ensure that the solid produced is a bounding volume to the real structure. RESULTS: The results produced by these techniques proved to be efficient and, thus, provide a means of easily visualizing the critical regions. CONCLUSION: The stylization technique can be seen as an adaptive volumetric contour. With potential use in clinical practice, it also provides a platform for further investigations of the geometric stylization concept.

Eye↗
PubMed1996

An induction gene trap screen in embryonic stem cells: Identification of genes that respond to retinoic acid in vitro.

We have developed a novel induction gene trap approach that preselects in vitro for integrations into genes that lie downstream of receptor/ligand-mediated signaling pathways. Using this approach, we have identified 20 gene trap integrations in embryonic stem cells, 9 of which were induced and 11 of which were repressed after exposure to exogenous retinoic acid (RA). All but one of these integrations showed unique spatially restricted or tissue-specific patterns of expression between 8.5 and 11.5 days of embryogenesis. Interestingly, expression was observed in tissues that are affected by alterations in RA levels during embryogenesis. Sequence analysis of fusion transcripts from six integrations revealed five novel gene sequences and the previously identified protooncogene c-fyn. To date, germ-line transmission and breeding has uncovered one homozygous embryonic lethal and three homozygous viable insertions. These studies demonstrate the potential of this induction gene trap approach for identifying and mutating genes downstream of signal transduction pathways.

Animals↗
PubMed1996

Computer morphing of scanning electron micrographs: an adjunct to embryology teaching.

Traditional embryology courses demand considerable expenditure of time and effort from students to master the spatial awareness skills necessary to create three-dimensional mental images from two-dimensional serial sections. Then students must imagine a movie sequence of the changes which take place during normal development. Further steps are required to relate this information to the clinical situation. As more medical and dental schools move towards problem-based curricula, more efficient methods of improving understanding of embryology are needed. The development of many organs can be studied using scanning electron micrographs of embryos at different ages. These high quality images are more easily interpreted by our students than histological sections and the understanding achieved more readily applied to clinical problems. Still more beneficial would be the provision of moving images showing the actual changes happening. We decided to use computer morphing techniques to prepare movie sequences showing development of the face and plate. For each, four scanning electron micrographs of appropriately-sized sheep embryo heads were taken at the same magnification and orientation to use as start and end points of morphing sequences. After using retouching techniques to colour the separate processes, further sequences were prepared. The discipline of maintaining the same magnification throughout and the possibility of directly observing changes between stages revealed some surprising growth patterns. This technique is adaptable to any area of biological development where pre- and post-illustrations are available. Animations can be presented on computer or on video and incorporated into programs. Student feedback has been very favourable.

Animals↗
PubMed1996

First steps in building ACME--an admission case-mix system for the elderly.

In the United Kingdom, specialists in Geriatric Medicine usually have a major role in treating acute medical problems of elderly people, in addition to running rehabilitation services and continuing care. The proportion of the different types of patients varies widely from service to service, however, making it difficult for clinicians to compare their performance with that of colleagues. Existing casemix measurement systems are usually designed to deal with a more homogeneous patient group (e.g. rehabilitation, long-stay care) and/or are too detailed for day-to-day use. We describe our attempts to devise a simple casemix system which would be of practical day-to-day use for individual specialists in Geriatric Medicine. We have classified patients according to (1) the acuteness and potential for recovery of their presenting illness and (2) their functional status (based on simple measures of mobility and cognitive impairment). These factors have been incorporated into a three-point score, CMIX, which was capable of explaining 19.5% of the variability in duration of stay in a prospective study of 400 new admissions in two centres. In contrast, age and sex explained only 1% of variability in these patients. The pattern of patient outcome also differed significantly between the three CMIX categories. We also propose a simple graphical method of classifying outcome which should prove useful for audit purposes even when our casemix system is not employed.

Activities of Daily Living↗
PubMed1994

Quality of life as an indicator of outcome in the treatment of cancer patients: the purchaser perspectives.

Evaluation of treatment can be seen as part of a wider concern to measure quality of care, as well as about the need to monitor and improve the effectiveness of services. Quality of life issues will be of increasing interest to those involved in the commissioning of health-care services. Cancer is used to illustrate how the quality of life of patients, both during and after treatment, can be measured and the information used by purchasers to consider the relative effectiveness of different methods of treatment. This in turn can inform the overall purchasing strategy of commissioning agencies.

Health Knowledge, Attitudes, Practice↗
PubMed1993

Made in heaven?

Explore the source record for details and available documents.

Health Care Coalitions↗
PubMed1992

The effect of auxiliary conditions on intestinal unstirred layer diffusion modelled by numerical simulation.

Estimation of intestinal unstirred layer thickness usually involves inducing transmural potential difference changes by altering the content of the solution used to perfuse the small intestine. Osmotically active solutes, such as mannitol, when added to the luminal solution diffuse across the unstirred water layer (UWL) and induce osmotically dependent changes in potential difference. As an alternative procedure, the sodium ion in the luminal fluid can be replaced by another ion. As the sodium ion diffuses out of the UWL, the change in concentration next to the intestinal membrane alters the transmural potential difference. In both cases, UWL thickness is calculated from the time course of the potential difference changes, using a solution to the diffusion equation. The diffusion equation solution which allows the calculation of intestinal unstirred layer thickness was examined by simulation, using the method of numerical solutions. This process readily allows examination of the time course of diffusion under various imposed circumstances. The existing model for diffusion across the unstirred layer is based on auxiliary conditions which are unlikely to be fulfilled in the same intestine. The present simulation additionally incorporated the effects of membrane permeability, fluid absorption and less than instantaneous bulk phase concentration change. Simulation indicated that changes within the physiologically relevant range in the chosen auxiliary conditions (with the real unstirred layer length kept constant) can alter estimates of the apparent half-time. Consequently, changes in parameters unassociated with the unstirred layer would be misconstrued as alterations in unstirred layer thickness.

Gastrointestinal Contents↗