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Biomedical subjects

A Watt

Publications and source records attributed to A Watt.

At least 19 recordsLinked to original sources
PubMed2003

Early perfluorodecalin lung distension in infants with congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Pulmonary hypoplasia contributes to mortality in infants with severe congenital diaphragmatic hernia (CDH). Accelerated postnatal lung growth with perfluorocarbon lung distension has been demonstrated in animals. The authors present a study measuring perfluorodecalin distension in neonates with severe CDH on extracorporeal membrane oxygenation (ECMO) support. METHODS: Six consecutive neonates with CDH requiring ECMO support were recruited. The lungs were filled with perfluorodecalin, and continuous positive airway pressure was applied for 6 to 10 days (mean, 7.7 days +/- 0.7). The perfluorodecalin was exchanged 4 times a day. Radiographic lung projections were measured, and from 2-dimensional measurements an estimated lung volume was calculated using the ECMO cannula as reference. RESULTS: Perfluorodecalin instillation started soon after starting ECMO support (mean, 13.5 +/- 5.3 hours). The volume required to fill the lungs increased significantly (P <.02). The radiographic dimension of the affected lung increased significantly (mean percentage increase, 272%; P <.02). The contralateral lung dimension also increased (mean percentage increase 51%; P <.02). CDH repair was undertaken on ECMO in all cases. All patients survived (follow-up, 3 to 42 months). CONCLUSIONS: This protocol of early perfluorodecalin lung distension in infants with severe CDH on ECMO support resulted in significant radiographic lung enlargement. Clinical outcomes are encouraging. Possible mechanisms include alveolar recruitment, alveolar dilatation, and accelerated postnatal lung growth.

Extracorporeal Membrane Oxygenation↗
PubMed2003

P-Glycoprotein efflux reduces the brain concentration of the substance P (NK1 receptor) antagonists SR140333 and GR205171: a comparative study using mdr1a-/- and mdr1a+/+ mice.

Investigation of the antidepressant-like actions of substance P (NK1 receptor) antagonists has been hindered by the few available compounds that bind with high affinity to the rat and mouse NK1 receptor, as these are the most commonly used preclinical species. The best available compounds for such studies are SR140333 and GR205171. However, SR140333 does not penetrate the central nervous system (CNS) after systemic administration, and GR205171 is active only at high doses, where unspecific pharmacological effects occur, so that changes in behaviour cannot be attributed to selective NK1 receptor blockade. These compounds may be substrates for P-glycoprotein (P-gp) and hence are actively excluded from the brain. The present studies used mdr1a-/- mice, a spontaneously occurring mutant that is deficient in P-gp, to examine the CNS penetration of SR140333 and GR205171. Following systemic administration of SR140333 and GR205171 (0.01-10 mg/kg i.v.), considerably higher drug concentrations were achieved in the brains of mdr1a-/- than in mdr1a+/+ mice, and this corresponded with a greater ability to inhibit NK1-agonist-induced behaviours in the mdr1a-/- mutants. Moreover, an NK1-receptor-specific inhibition of aggressive behaviour by GR205171 (10 mg/kg) could be demonstrated in mdr1a-/-, but not mdr1a+/+, mice. These findings suggest that P-gp deficient mice may have useful applications in behavioural pharmacology studies, especially when highly brain-penetrant compounds are not yet available.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

The role of follow-up imaging in paediatric blunt abdominal trauma.

AIM: To assess the role of follow-up imaging in paediatric blunt abdominal trauma. METHOD: All children who underwent CT scanning of their abdomen at our institution following acute blunt injury between January 1997 and December 2000 were included in the study. Case notes where researched for details regarding mechanism of injury, initial clinical presentation, acute management, complications and follow-up until discharge. Reports of imaging investigations were retrieved from the RIS database. RESULTS: In the study period 75 children underwent CT scanning of their abdomen as a primary investigation for acute blunt abdominal trauma. Of these, 12 were normal, 52 showed evidence of intra-abdominal organ injury and 11 showed findings other than abdominal organ injury. Of the 52 children that sustained intra-abdominal organ injury, 48 (92 percent) were treated conservatively. 4 (8 percent) underwent emergency surgery, 3 for bowel injury and 1 for renal trauma. Of the 48 that were treated conservatively, 9 had a complicated clinical course with 7 showing complications on follow-up imaging. The remaining 39 children had an uneventful clinical course with follow-up imaging by CT or US in 34. None showed complications that required a change in management. CONCLUSION: In our series, follow-up imaging did not contribute to further management in children with an uncomplicated clinical course following blunt abdominal trauma.

Abdominal Injuries↗
PubMed2001

Peptide nucleic acids are potent modulators of endogenous pre-mRNA splicing of the murine interleukin-5 receptor-alpha chain.

Antisense oligonucleotides (ASOs) that bind target pre-mRNA with high affinity have been shown to alter splicing patterns and offer promise as therapeutics. Previous studies have shown that ASOs fully modified with 2'-O-methoxyethyl (2'-O-MOE) sugar residues redirect constitutive and alternative splicing of the murine interleukin-5 receptor-alpha (IL-5Ralpha) chain pre-mRNA in cells, resulting in inhibition of the membrane-bound isoform and enhanced expression of the soluble isoform. Here, we show that antisense peptide nucleic acids (PNAs) alter splicing of the IL-5Ralpha pre-mRNA in a fashion similar to their 2'-O-MOE-modified counterparts of the same sequence. Moreover, using PNA as the splicing modulator, the length of the antisense oligomer could be shortened from 20 to 15 nucleobase units to obtain a comparable effect. Treatment of cells with antisense PNA resulted in dose-dependent, specific downregulation of IL-5Ralpha membrane isoform mRNA expression and enhanced levels of the soluble IL-5Ralpha isoform transcript, with an EC50 equivalent to that observed in parallel with the corresponding 2'-O-MOE ASO. The pronounced activity of antisense PNAs in modulating IL-5Ralpha mRNA splicing observed in our study identifies these compounds as a promising new class of lower molecular weight splicing modulators.

Alternative Splicing↗
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↗
PubMed2001

Caring for patients with phantom limb sensation.

Phantom limb pain is increasingly perceived as a complex condition that is likely to have multifactorial causes. Although acknowledgement of the existence of the condition is more prevalent than it was, its treatment remains elusive. Nurses caring for people with phantom limb pain have a unique role to play in the overall holistic therapy of the amputee.

Female↗
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↗