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Biomedical subjects

Robert Kelly

Publications and source records attributed to Robert Kelly.

10 recordsLinked to original sources

Metal slits and liquid crystals at microwave frequencies.

While the use of liquid crystals (LCs) over the visible region is ubiquitous in flat-screen displays, there has been little by the way of applications at other wavelengths. Specifically, notwithstanding the continuing permittivity anisotropy to be found at longer wavelengths, there has been virtually no development in the microwave domain. This is largely due to the fact that scaling up the micrometer-thick LC layers used for visible radiation to millimetre dimensions is seen as impractical. In this study, it is shown how, using thin slits in metal structures, a completely new generation of LC devices for use at microwaves may be realized. Such structures include slatted metal Fabry-Perot resonators, beam-steering devices, thin flexible voltage tunable filters and even cascade structures with strongly enhanced and reshaped microwave fields.

Journal Article↗

Detection of cervical spine injuries in alert, asymptomatic geriatric blunt trauma patients: who benefits from radiologic imaging?

There are differing recommendations in the literature regarding cervical spine imaging in alert, asymptomatic geriatric patients. Previous studies also have not used computed tomography routinely. Given that cervical radiographs may miss up to 60 per cent of fractures, the incidence of cervical spine injuries in this population and its implications for clinical management are unclear. We conducted a retrospective study of blunt trauma patients 65 years and older who were alert, asymptomatic, hemodynamically stable, and had normal neurologic examinations. For inclusion, patients were required to have undergone computed tomography and plain radiographs. The presence and anatomic location of potentially distracting injuries or pain were recorded. Two hundred seventy-four patients were included, with a mean age of 76 +/- 10 years. The main mechanisms of injury were falls (51%) and motor vehicle crashes (41%). Nine of 274 (3%) patients had cervical spine injuries. The presence of potentially distracting injuries above the clavicles was associated with cervical injury when compared with patients with distracting injuries in other anatomic locations or no distracting injuries (8/115 vs 1/159, P = 0.03). There was no association of cervical spine injury with age greater or less than 75 years or with mechanism of injury. The overall incidence of cervical spine injury in the alert, asymptomatic geriatric population is low. The risk is increased with a potentially distracting injury above the clavicles. Patients with distracting injuries in other anatomic locations or no distracting injuries may not need routine cervical imaging.

Accidental Falls↗

Effectiveness of harm reduction programmes for injecting drug users in Dhaka city.

This paper provides a brief overview of the harm reduction programme for injecting drug users (IDU) of CARE, Bangladesh in Dhaka city and uses data from surveillance and a focussed research study on a cohort of IDU, to evaluate the programme. The harm reduction programme in Dhaka is run by CARE, Bangladesh and includes needle/syringe exchange, awareness raising on HIV/STI, abscess management, condom distribution and advocacy with different groups of people. The needle/syringe exchange programme (NEP) has been in place since 1998, the 2nd Generation Surveillance in Bangladesh is being conducted since 1998, and an in-depth cohort study, started in 2002, is being conducted in two areas of Dhaka city with approximately 500 IDU under CARE's NEP who are being followed bi-annually to assess risk behaviour, incidence of HIV, hepatitis C and syphilis. As the surveillance and the cohort study are both closely associated with the NEP of CARE, Bangladesh, these data can be used to monitor the NEP.

Journal Article↗

Fgf10 expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineage.

Lineage formation in the lung mesenchyme is poorly understood. Using a transgenic mouse line expressing LacZ under the control of Fgf10 regulatory sequences, we show that the pool of Fgf10-positive cells in the distal lung mesenchyme contains progenitors of the parabronchial smooth muscle cells. Fgf10 gene expression is slightly repressed in this transgenic line. This allowed us to create a hypomorphic Fgf10 phenotype by expressing the LacZ transgene in a heterozygous Fgf10 background. Hypomorphic Fgf10 mutant lungs display a decrease in beta-galactosidase-positive cells around the bronchial epithelium associated with an accumulation of beta-galactosidase-expressing cells in the distal mesenchyme. This correlates with a marked reduction of alpha smooth muscle actin expression, thereby demonstrating that FGF10 is mostly required for the entry of mesenchymal cells into the parabronchial smooth muscle cell lineage. The failure of exogenous FGF10 to phosphorylate its known downstream targets ERK and AKT in lung mesenchymal cultures strongly suggests that FGF10 acts indirectly on the progenitor population via an epithelial intermediate. We provide support for a role of epithelial BMP4 in mediating the formation of parabronchial smooth muscle cells.

Actins↗

Pyoderma gangrenosum complicated by herpes simplex virus infection.

High-dose immunosuppression used in the treatment of pyoderma gangrenosum predisposes patients to opportunistic infections. A 66-year-old man presented with recalcitrant pyoderma gangrenosum in which the ulcer itself became infected with herpes simplex virus type 1. This patient was immunosuppressed with multiple agents including topical and oral corticosteroids, cyclosporin, mycophenolate mofetil, intravenous immunoglobulin and infliximab. However, the patient's ulcer continued to extend despite this. It was not until the presence of this virus was detected using polymerase chain reaction on a viral swab of the lesion and oral aciclovir was commenced that the ulcer began to heal. In addition, a fungal granuloma developed on this patient's left forearm as a complication of the potent immunosuppression, which was resolved following treatment with oral voriconazole.

Acyclovir↗

Six1 and Eya1 expression can reprogram adult muscle from the slow-twitch phenotype into the fast-twitch phenotype.

Muscle fibers show great differences in their contractile and metabolic properties. This diversity enables skeletal muscles to fulfill and adapt to different tasks. In this report, we show that the Six/Eya pathway is implicated in the establishment and maintenance of the fast-twitch skeletal muscle phenotype. We demonstrate that the MEF3/Six DNA binding element present in the aldolase A pM promoter mediates the high level of activation of this promoter in fast-twitch glycolytic (but not in slow-twitch) muscle fibers. We also show that among the Six and Eya gene products expressed in mouse skeletal muscle, Six1 and Eya1 proteins accumulate preferentially in the nuclei of fast-twitch muscles. The forced expression of Six1 and Eya1 together in the slow-twitch soleus muscle induced a fiber-type transition characterized by the replacement of myosin heavy chain I and IIA isoforms by the faster IIB and/or IIX isoforms, the activation of fast-twitch fiber-specific genes, and a switch toward glycolytic metabolism. Collectively, these data identify Six1 and Eya1 as the first transcriptional complex that is able to reprogram adult slow-twitch oxidative fibers toward a fast-twitch glycolytic phenotype.

Animals↗

[The mouse as a model of heart morphogenesis in mammals: origin and lineage of myocytes].

In order to follow cardiac precursor cells, we have adopted a retrospective clonal approach, based on the nlaacZ genetic label. Random clones were generated and observed at different developmental stages in murine myocardium. The distribution of these clones in clusters suggest for the first time that cells fated to form myocardium proliferate in two steps. The first growth phase, before E8.5, is dispersive and polarised along the axis of the primitive cardiac tube, contributing to its elongation. The second growth phase is coherent and polarised differentially in different cardiac subregions. Interestingly, this can be correlated with production of geometrical forms (dilatation of a sphere, enlargement of a tube), showing the relation between heart morphogenesis and the controlled proliferation of myocardial cells. The restricted distribution of clones to the right or left ventricule was also investigated with the goal of establishing the time at which cardiac chamber identity emerges. Right and left ventricular lineages appear to segregate early, in agreement with the existence of two populations of cardiac precursors, the so-called primary (or posterior) and secondary (or anterior) heart fields.

Animals↗

[The mouse as a model for heart morphogenesis in mammals: the origin of myocytes and studies with cardiac explants].

The heart is one of the first organs to form during embryogenesis since its circulatory function is critical from early stages for embryo survival. In man, morphological events are affected by molecular perturbations, which can lead to a congenital heart defect. It is important therefore to understand not only the molecular signals, but also the morphological events, which govern myocardial cell identity. The study of transgenic mouse lines, Mlc1v-nlacZ-24 and Mlc3f-nlacZ-2, has led to the identification of a new precardiac territory, the anterior heart field, which has also been described recently in birds, and which contributes to the myocardium of the arterial pole of the heart. The use of explant cultures also indicates that pharyngeal mesoderm participates in the formation of the outflow tract and right ventricle and shows that the primitive heart tube has a predominantly left ventricular identity. We have also shown that Fgf-10 is expressed in the anterior heart field, where a role for FGF signaling in arterial pole morphogenesis is suggested by inhibitor experiments. Finally explant cultures have been employed to examine the acquisition of left-right atrial identity. The Mlc3f-nlacZ-2 line, which marks the right atrium, allowed us to determine the time window during which left-right signaling confers left-right atrial identity.

Animals↗

The prevalence of treatable left ventricular systolic dysfunction in patients who present with noncardiac vascular episodes: a case-control study.

OBJECTIVES: We sought to determine the prevalence of treatable left ventricular (LV) systolic dysfunction (LVSD) in patients who present with their first noncardiac vascular episode. BACKGROUND: Screening for LV dysfunction in patients who present with their first stroke (cerebrovascular accident), their first transient ischemic attack (TIA) or their first manifestation of peripheral vascular disease (PVD) may represent a golden opportunity to identify treatable LV dysfunction, and so their known high incidence of sudden cardiac death may be reduced. METHODS: Participating in this study were 522 (75%) of 700 consecutive patients (302 patients with stroke, TIA or PVD and 220 age- and gender-matched control subjects). Each underwent a full clinical assessment, 12-lead electrocardiography and two-dimensional echocardiography. Left ventricular dysfunction was defined as LV ejection fraction < or = 40%. RESULTS: Seventy-two (28%) patients with vascular disease and 11 (5.5%) control subjects were found to have LVSD. Twenty-six (28%) stroke patients, 22 (26%) patients with TIA and 24 (31%) patients with PVD had LVSD. Left ventricular systolic dysfunction was symptomatic in 44% of patients and in 35% of control subjects. CONCLUSIONS: Left ventricular systolic dysfunction is five times more common among patients with stroke, TIA and PVD than among age- and gender-matched control subjects. Asymptomatic LVSD is more common than symptomatic LVSD in these patients. These findings suggest that routine screening of all patients with noncardiac vascular episodes for LVSD should now be considered. Future studies should investigate whether identifying and treating LVSD in these patients would reduce their known high rate of cardiac death.

Aged↗