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Biomedical subjects

M Wilkinson

Publications and source records attributed to M Wilkinson.

At least 37 records · Page 2Linked to original sources

"Hospital at home" versus hospital care in patients with exacerbations of chronic obstructive pulmonary disease: prospective randomised controlled trial.

OBJECTIVES: To compare "hospital at home" and hospital care as an inpatient in acute exacerbations of chronic obstructive pulmonary disease. DESIGN: Prospective randomised controlled trial with three months' follow up. SETTING: University teaching hospital offering secondary care service to 350 000 patients. PATIENTS: Selected patients with an exacerbation of chronic obstructive pulmonary disease where hospital admission had been recommended after medical assessment. INTERVENTIONS: Nurse administered home care was provided as an alternative to inpatient admission. MAIN OUTCOME MEASURES: Readmission rates at two weeks and three months, changes in forced expiratory volume in one second (FEV(1)) from baseline at these times and mortality. RESULTS: 583 patients with chronic obstructive pulmonary disease referred for admission were assessed. 192 met the criteria for home care, and 42 refused to enter the trial. 100 were randomised to home care and 50 to hospital care. On admission, FEV(1) after use of a bronchodilator was 36.1% (95% confidence interval 2.4% to 69.8%) predicted in home care and 35.1% (6.3% to 63. 9%) predicted in hospital care. No significant difference was found in FEV(1 )after use of a bronchodilator at two weeks (42.6%, 3.4% to 81.8% versus 42.1%, 5.1% to 79.1%) or three months (41.5%, 8.2% to 74.8% versus 41.9%, 6.2% to 77.6%) between the groups. 37% of patients receiving home care and 34% receiving hospital care were readmitted at three months. No significant difference was found in mortality between the groups at three months (9% versus 8%). CONCLUSIONS: Hospital at home care is a practical alternative to emergency admission in selected patients with exacerbations of chronic obstructive pulmonary disease.

Aged↗

The regulation of leptin gene expression in the C6 glioblastoma cell line.

The hormone leptin is implicated in the regulation of appetite and body weight in rodents, primates and humans. We reported that the leptin gene (ob) is expressed in the brain, but the factors which control ob expression in the central nervous system are not known. We previously showed that brain-derived rat C6 glioblastoma cells express ob mRNA and protein. In the present study we examined the regulation of ob expression in C6 cells. Leptin and leptin receptor immunoreactivity was detected in C6 cells, suggesting a possible autocrine role for leptin. The identity of the leptin immunoreactivity (OB-ir) in C6 cells was confirmed by immunoprecipitation and Western blotting using two leptin specific polyclonal antibodies. Using RT-PCR analysis a product of the expected size for the short, but not the long, leptin receptor isoform was detected in C6 cells. Cells were maintained in serum-free (SF) media for 0-24 h in the presence of various regulators of leptin expression. Leptin mRNA levels were significantly higher in cells treated with dbcAMP (1 mM), IGF 1 (100 ng/ml) or insulin (5 microg/ml) compared to SF controls. In contrast, corticosterone (10(-7)M) reduced leptin mRNA. In the presence of dbcAMP, C6 cells undergo a dramatic alteration in morphology which is coincident with an apparent increase in the number of leptin-ir nuclei and an increase in leptin immunoreactivity. In contrast to C6 cells, glucocorticoids are reported to increase leptin levels in adipocytes/adipose tissue, while increases in intracellular cAMP levels are reported to reduce leptin levels. Overall, our in vitro data suggest that the regulation of leptin gene expression in C6 glioblastoma cells is different from that in adipocytes.

Animals↗

The heart reinnervates after transplantation.

BACKGROUND: Whether cardiac reinnervation occurs after transplantation remains controversial. If reinnervation does occur, how sympathetic and parasympathetic efferent neurons do this remains unknown. METHODS: Power spectral analysis of heart rate variability was assessed for 1 year after cardiac autotransplantation in 9 dogs. After induction of anesthesia 13 months after transplantation, cardiac and intrinsic cardiac neuronal responses elicited by both electrical stimulation of parasympathetic or sympathetic efferent neurons and systemic or local coronary artery administration of nicotine (5 microg/kg), angiotensin II (0.75 microg/kg), and tyramine (1.2 microg/kg) were studied. The transmembrane electrical properties of intrinsic cardiac neurons were studied in vitro. Ventricular tissue catecholamine content, alpha-tubulin expression, and beta-adrenergic receptor density and affinity were studied. The presence of axons crossing suture lines was sought histologically. RESULTS: Nerves were identified crossing suture lines. Electrical or chemical (ie, nicotine or angiotensin II) activation of sympathetic efferent neurons enhanced cardiodynamics, as did tyramine. Stimulating vagal efferent preganglionic axons induced bradycardia in half of the dogs. Functional reinnervation did not correlate with specific power spectra derived from rate variability in the conscious state. Responding to nicotine and angiotensin II in situ, transplanted intrinsic cardiac neurons generated spontaneous activity. These neurons displayed nicotine-dependent synaptic inputs in vitro. Ventricular tissue had normal beta-adrenergic receptor affinity and density but reduced catecholamine and alpha-tubulin contents. CONCLUSIONS: The intrinsic cardiac nervous system receives reduced input from extracardiac sympathetic efferent neurons after transplantation and inconsistent input from parasympathetic efferent preganglionic neurons. These heterogeneous neuronal inputs are not reflected in heart rate variability or ventricular beta-adrenergic receptor function. Transplanted angiotensin II-sensitive intrinsic cardiac neurons exert greater cardiac control than do nicotine-sensitive ones. The intrinsic cardiac nervous system remodels itself after cardiac transplantation, and this indicates that direct assessment of extracardiac and intrinsic cardiac neuronal behavior is required to fully understand cardiac control after transplantation.

Animals↗

Stabilization of neurites in cerebellar granule cells by transglutaminase activity: identification of midkine and galectin-3 as substrates.

The formation of covalent isopeptide cross-links between cell surface protein molecules by the enzyme transglutaminase C influences cell adhesion and morphology. Retinoid-inducible cross-linking activity associated with this enzyme is present in the developing rat cerebellar cortex [Perry M. J. M. et al. (1995) Neuroscience 65, 1063-1076]. A monoclonal antibody was used to localize transglutaminase C to granule neurons in the developing cerebellar cortex. The enzyme was inducible by retinoic acid both in granule neurons cultured from postnatal rat cerebellar cortex and in cells of the embryonic dorsal rhombic lip, which contain granule neuron precursors. A possible biological function for transglutaminase activity was investigated in living granule neurons, cultured on a biomatrix substratum, studied by time-lapse cinematographic analysis using the transglutaminase inactivator RS-48373-007. Inhibition of cross-linking activity did not influence the number of neurites formed by granule neurons, but caused the destabilization of neurites during the initial outgrowth period, seen as an increase in the number of growth cone retractions and the onset of premature axon collateral formation (bifurcation). Inactivation of cross-linking activity prevented the formation of fascicles between neurites only when cells were cultured on a biomatrix surface. Two glial proteins involved in cell-extracellular matrix interactions, midkine and galectin-3, were identified as putative substrates for granule neuron transglutaminase. The results suggest that covalent cross-link formation by transglutaminase C or a related enzyme generates multimeric molecular forms of glial-derived proteins, and plays a role in stabilizing newly formed neurites. A possible non-pathological role for transglutaminase in the control of axon collateral branching by developing granule neurons in the cerebellar cortex is discussed.

Animals↗

A chain is no stronger than its weakest link: double decay analysis of phylogenetic hypotheses.

In decay analyses the support for a particular split in most-parsimonious trees is its decay index, that is, the extra steps required of the shortest trees that do not include the split. By focusing solely on the support for splits, traditional decay analysis may provide an incomplete and potentially misleading summary of the support for phylogenetic relationships common to the most-parsimonious tree or trees. Here, we introduce double decay analysis, a new approach to assessing support for phylogenetic relationships. Double decay analysis is the determination of the decay indices of all n-taxon statements/partitions common to the most-parsimonious tree. The results of double decay analyses are presented in a partition table, but various approaches to graphical representation of the results, including the use of reduced consensus support trees, are also discussed. Double decay analysis provides a more comprehensive summary and facilitates a better understanding of the strengths and weaknesses of complex phylogenetic hypotheses than does traditional decay analysis. The limitations of traditional decay analyses and the utility of double decay analyses are illustrated with both contrived data and real data for sauropod dinosaurs.

Animals↗

Routine parathyroid autotransplantation during total thyroidectomy: the influence of technique.

OBJECTIVE: To find out whether injecting a suspension of finely minced parathyroid tissue into the muscle bed had any adverse outcomes as it is simpler and potentially safer than implanting parathyroid tissue into muscle pockets. DESIGN: Prospective, randomised, controlled clinical trial. SETTING: University hospital, Australia. PATIENTS: 50 patients who were to have total thyroidectomy and routine parathyroid autotransplantation. INTERVENTIONS: Patients were randomised to either the injection technique or the implantation technique. MAIN OUTCOME MEASURES: Clinical assessment; corrected serum calcium and intact parathyroid hormone concentrations (PTH) measured immediately before, and at 1 day, 2 weeks, and 3 months after operation. RESULTS: Calcium was reduced significantly in both groups immediately after thyroidectomy. Although mean PTH concentrations decreased immediately after thyroidectomy and parathyroid autotransplantation in both groups, these changes were significant only in the implantation group. By 2 weeks and again by 3 months, calcium and intact parathyroid hormone concentrations had returned to baseline in both groups. At 3 months, 2 patients in each group still required some form of calcium supplement. At 6 months, no patients in the injection group required supplement. CONCLUSIONS: Injection of a suspension of parathyroid tissue is a simple, safe, and rapid technique for parathyroid autotransplantation during total thyroidectomy and is not associated with any more adverse outcome than is the standard technique.

Adolescent↗

CHORIPETALA and DESPENTEADO: general regulators during plant development and potential floral targets of FIMBRIATA-mediated degradation.

Two Antirrhinum majus mutants, choripetala (cho) and despenteado (desp), exhibit identical highly pleiotropic phenotypes including petaloid transformation of first whorl floral organs, narrowing of both vegetative and floral organs, reduction in carpel size and fertility and delayed germination. The petaloid first whorl results from ectopic expression of the class B genes DEFICIENS and GLOBOSA and is correlated with the ectopic expression of the proposed class B/C gene regulator FIMBRIATA (FIM). Ectopic class B gene expression is apparent from the earliest point at which class B gene transcription can be detected in the wild type, indicating that the pre-patterning of the class B domain has been disrupted in these mutants. Single and double mutant analyses indicate that CHO and DESP also play a role in regulation of the class C domain. Interestingly, the cho and desp mutations partially suppress the phenotype of fim null mutants, suggesting that the F-box protein FIM may target a member of the CHO/DESP pathway for degradation. We propose that CHO and DESP are members of a 'basal regulatory function' influencing many processes throughout plant development and in particular are directly or indirectly required for the repression of class B and C genes during early stages of flower development.

Gene Expression Regulation, Developmental↗

Microsystems: small structures, big impact.

Microsystems are devices that incorporate a combination of microfluidic, micromechanical, microoptical and microelectronic components. This is the first in a series of articles looking at the major impact the technology is likely to have on medical products during the next 10 years and how companies can profit from the opportunities it offers.

Diagnostic Equipment↗

Microsystems: applications in catheters and endoscopes.

Microsystems are devices that incorporate a combination of microfluidic, micromechanical, microoptical and microelectronic components. This is the second article in a series that investigates the impact the technology is likely to have on medical products during the next 10 years. This article describes how that technology is being used to construct pressure sensors, temperature sensors, microsurgical instruments, ultrasound transducers and imaging devices.

Catheterization↗

Microsystems: how to access the technology.

Microsystems are devices that incorporate a combination of microfluidic, micromechanical, micro-optical and microelectronic components. This users' guide provides information on how to access the technology and find the resources needed for design, prototyping and manufacture in Europe.

Computer-Aided Design↗

Estrogen stimulates expression of adenine nucleotide translocator ANT1 messenger RNA in female rat hearts.

The identification of estrogen-responsive genes in the heart, is necessary to understand estrogen-induced changes in cardiac function. Using Delta RNA fingerprinting, we demonstrate that a single injection of estradiol benzoate (50 microg, s.c.) revealed mRNA species that were elevated, down-regulated, or were unaffected in the heart tissue of ovariectomized female rats. One of the upregulated genes was identified, by cloning and sequencing, to have 95.8% (230/240) identity with the 3' end of the rat ant1 gene encoding the mitochondrial adenine nucleotide translocator, ANT1. Using the isolated ANT1 cDNA (280 bp) as a probe in Northern analysis, estrogen was shown to upregulate the expression of cardiac ANT1, by at least 3-fold in female rats, from as early as 1 h to as long as 24 h. In contrast, estrogen treatment had no effect on ANT1 expression in heart tissue from male rats. RNA yields were low in rat atria and no transcript was detectable by Northern analysis. Using primers specific to the known rat ANT1 gene, the estrogen upregulation of the cardiac ANT1 transcript in female rat was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR); a predicted product of 249 bp was obtained and this was stimulated by at least 3-fold upon estrogen treatment for 24 h.

Animals↗

Intelligence patterns among children with high-functioning autism, phenylketonuria, and childhood head injury.

High-functioning children with autistic-spectrum disorder show the typical pattern of lower Comprehension relative to their own scores on Block Design. This profile is shared, almost exactly, by age- and IQ-matched children with poorer control PKU. Quite distinct profiles are shown by children with better control PKU, who show no difference between Block Design and Comprehension, and by children with head injury involving frontal lobe contusion, who show slightly better Comprehension that Block Design. The data bear on several questions: the relation between Comprehension deficits and language functions measured by Vocabulary; the limits of the advantages conveyed by higher IQ to autistic individuals; whether impaired Comprehension in autism indexes persisting symptoms and/or impairments on theory of mind tasks; the possibility that dopamine deficiency is common to autism and poorer control PKU; and the need for future research aimed at understanding the relations among neurodevelopmental disorders.

Analysis of Variance↗