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Biomedical subjects

G O'Reilly

Publications and source records attributed to G O'Reilly.

At least 19 recordsLinked to original sources

Commissioning and quality assurance protocol for dual energy X-ray absorptiometry (DEXA) systems.

This study reports on the development and evaluation of a protocol for testing DEXA systems, which can be incorporated into a routine medical physics/engineering service. Methodologies are reported for (1) scatter measurement, (2) estimation of reference dose and (3) enquiry into potential sources of overexposure. Results show that fan-beam and cone-beam systems require shielding if the walls or operator are within 1 m of the table. Patient reference dose was estimated using the dose-area product (DAP). This varied over an order of magnitude from 2 to 36 mGy cm2 in the range of systems studied. The inquiry into potential sources of overexposure revealed some weaknesses in current practise including a design which prevents the inclusion of DAP metres; beam non-uniformity; incorrect specification of patient dose and the risk of overexposure when tube operates during patient positioning.

Absorptiometry, Photon↗

Exposure variations under error conditions in automatic exposure controlled film-screen projection radiography.

Improper automatic exposure control (AEC) termination may result in high overexposures on some radiographic systems. Under AEC, X-ray factors are adjusted automatically to compensate for differences in patient thickness and density. In radiography, AEC is implemented using ionization chambers placed in the film bucky. In this study we deliberately chose incorrect set-up conditions and assessed the response of the AEC system. Two types of incorrect set-up were studied: (1) incorrect selection of bucky radiation detector and (2) simulated misalignment between the X-ray field and light field. The systems tested varied in age from 1 year to in excess of 10 years. In the first test, overexposures of 90 mGy were recorded. Two systems did not meet EC guidelines for improper AEC termination. The second test, misalignment of the X-ray field, was observed to affect the exposure delivered by approximately +/-22%. The maximum dose increase observed, with a chest phantom in the beam, was 165 microGy. Misalignments also resulted in reduced exposures, which may impact on image quality.

Humans↗

Percutaneous endoscopic gastrostomy in patients with ventriculoperitoneal shunts.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) may be required in neurosurgical patients with a persistently depressed neurological status or severe lower cranial nerve palsies. Such patients may have a coexisting hydrocephalus requiring cerebrospinal fluid (CSF) diversion. Despite the risk of infection resulting from exposure to oropharyngeal flora by the pull-through PEG technique and the secondary pneumoperitoneum seen in one-third of patients, simultaneous peritoneal placement of CSF shunt catheters with PEG is the current practice. The aim of the study was to determine the frequency of CSF diversionary procedures in neurosurgical patients undergoing PEG insertion and the occurrence of infective complications in patients with simultaneous placement of a PEG and a ventriculoperitoneal (VP) shunt. METHODS: This was a retrospective review of all neurosurgical patients undergoing PEG. The presence of hydrocephalus, mode of CSF diversion and the development of subsequent infection in those having coexistent distal peritoneal catheter placement and PEG were determined. RESULTS: PEGs were placed in 42 neurosurgical patients (9.3 per cent of all PEGs inserted), of whom 21 had a coexisting hydrocephalus. Eight of 16 shunts with distal catheter placement in the peritoneal cavity developed infection requiring revision. Infections occurred with greater frequency in patients with a tracheostomy. There were no shunt infections requiring revision in a second group of 21 patients who had a coexisting shunt and tracheostomy without PEG. CONCLUSION: Simultaneous placement of a PEG and a VP shunt should be avoided in the acute phase of a patient's hospital admission.

Adolescent↗

Malignant eccrine poroma with spinal and cerebrospinal fluid metastases: case report.

OBJECTIVE AND IMPORTANCE: A rare case of metastasizing malignant eccrine poroma (porocarcinoma) is described. This case is unique because metastasis resulted in hydrocephalus in the cerebrospinal fluid and spinal cord compression in the lumbar spine. CLINICAL PRESENTATION: A 57-year-old man presented with acute confusion, lower limb weakness, and urinary concerns. Investigation revealed acute hydrocephalus and extradural cord compression of the lumbar spine. INTERVENTION: The acute hydrocephalous was treated with a ventriculoperitoneal shunt. The spinal cord and conus were decompressed by laminectomy and supplemented with pedicular screw fixation. CONCLUSION: The case reported here is the first with metastases from a malignant eccrine poroma causing spinal cord compression and acute hydrocephalus. Our observation is compared with a review of the literature.

Acrospiroma↗

Quality assurance programme applied to mobile C-arm fluoroscopy systems.

The importance of quality assurance (QA) of X-ray equipment in diagnostic imaging departments is well recognised. However, practically no attention has been paid in the literature to the application of QA programmes to mobile C-arm fluoroscopy systems. This equipment is sometimes omitted from these programmes because it is often "off-site" from the main radiological facility and suitable QA protocols are unavailable. The need for QA can be substantiated by the fact that these systems are finding greater clinical use in orthopaedic, vascular and cardiac applications. Hence, there is a growing awareness among users for the need of good image quality and low patient radiation dose. In view of this, the objective of this study was to review the existing literature, design a suitable QA protocol for this equipment and use it to survey 10 C-arms in clinical use. The protocol was designed to address mechanical and electrical safety in addition to radiation safety and image quality. Results indicate substantial performance differences between systems with significant variations in input air kerma rate to the image receptor. The authors believe that such a protocol is necessary with a view to establishing optimal performance levels and assist in the development of suitable "write-off" criteria for such systems.

Equipment Safety↗

Expression of endothelin peptides and mRNA in the human heart.

1. We have examined the expression of endothelin isoforms and their precursors in the human heart using RIA, HPLC, immunocytochemistry and reverse transcriptase-polymerase chain reaction assays. 2. Highly specific RIAs were used to measure the levels of mature endothelin and big endothelin-1 immunoreactivity in extracts of human right ventricle. There was no significant difference between samples from patients with ischaemic heart disease and idiopathic dilated cardiomyopathy. 3. HPLC coupled with RIAs allowed the separation and identification of the three mature isoforms of endothelin, big endothelin-1 and the C-terminal fragment of big endothelin-1. In extracts of human endocardial endothelial cells, peaks of immunoreactivity that co-eluted with authentic endothelin-1, big endothelin-1 and C-terminal fragment were found. 4. Intense immunocytochemical staining of mature endothelin immunoreactivity was detected in the cytoplasm of endothelial cells of all regions of the heart tested. Big endothelin-1 immunoreactivity mirrored that of the mature peptide and, in two of three individuals tested, big endothelin-2 immunoreactivity was also detected. No big endothelin-3 immunoreactivity was detected in any of the tissues examined. 5. Reverse transcriptase-polymerase chain reaction assays demonstrated endothelin-1 and endothelin-2 mRNA in all three samples of human left ventricle tested. In two of the individuals, additional bands were also detected with the endothelin-2 primers which corresponded to splice variants. There was no evidence for the expression of endothelin-3 mRNA. 6. These data suggest that endothelin-1 is the predominant isoform of endothelin in the human heart and is probably largely synthesized by the endothelial cells within the heart. If released from the endothelial cells in vivo, this potent cardiotonic peptide may play an important paracrine role in human cardiovascular function.

Adult↗

Intradural lipoma presenting in pregnancy.

Progressive peripheral neuropathy is an unusual condition in pregnancy requiring specialist opinion to identify the possible underlying pathology. The case presented is that of a patient with cervical intradural lipoma and worsening neurological symptoms, treated surgically at the time of caesarean section. This rare disease and its management are discussed.

Adolescent↗

Endothelin ETA and ETB mRNA and receptors expressed by smooth muscle in the human vasculature: majority of the ETA sub-type.

1. We measured the ratio of ETA and ETB sub-types in the media (containing mainly smooth muscle) of human cardiac arteries (aorta, pulmonary and coronary), internal mammary arteries and saphenous veins. 2. In saturation experiments, [125I]-endothelin-1 ([125I]-ET-1) bound with high affinity to the media of each vessel (n = 3 individuals or homogenate preparations +/- s.e. mean): coronary artery, KD = 0.14 +/- 0.02 nM, Bmax = 71.0 +/- 21.0 fmol mg-1 protein; pulmonary artery, KD = 0.85 +/- 0.25 nM, Bmax = 15.2 +/- 10.3 fmol mg-1 protein; aorta, KD = 0.51 +/- 0.02 nM, Bmax = 9.4 +/- 4.4 fmol mg-1 protein; internal mammary artery. KD = 0.34 +/- 0.31 nM, Bmax = 2.0 +/- 0.5 fmol mg-1 protein and saphenous vein, KD = 0.28 +/- 0.05 nM, Bmax = 52.8 +/- 1.0 fmol mg-1 protein. In each vessel, over the concentration-range tested, Hill slopes were close to unity and a one site fit was preferred to a two site model. 3. In competition binding assays, the ETA selective ligand, BQ123 inhibited the binding of 0.1 nM [125I]-ET-1 to the media in a biphasic manner. In each case, a two site fit was preferred to a one or three site model: coronary artery, KDETA = 0.85 +/- 0.03 nM, KDETB = 7.58 +/- 2.27 microM, ratio = 89:11%; pulmonary artery, KDETA = 0.27 +/- 0.05 nM, KDETB = 24.60 +/- 5.34 microM, ratio = 92:8%; aorta, KDETA = 0.80 +/- 0.40 nM, KDETB = 2.67 +/- 2.60 microM ratio = 89:11%; saphenous vein, KDETA = 0.55 +/- 0.17 nM, KDETB = 14.4 +/- 0.26 microM, 85:15% (n = 3 individuals or homogenate preparations +/- s.e. mean). BQ123 showed up to 18000 fold selectivity for the ETA over the ETB sub-type. The ETA-selective ligand, [125I]-PD151242 labelled 85% of the receptors detected by a fixed concentration of [125I]-ET-1 in media of internal mammary artery, measured by quantitative autoradiography. In contrast, the density of ETB receptors detected with [125I]-BQ3020 was 7.0 +/- 1.5 amol mm-2, representing about 8% of [125I]-ET-1. 4. A single band corresponding to the expected position for mRNA encoding the ETA receptor (299 base pairs) was found in the media in each of the five vessels (n = 3 individuals) using reverse transcript as epolymerase chain reaction assays. A single band corresponding to the ETB sub-type (428 base pairs) was also always detected.5. 35S-labelled antisense probes to ETA and ETB hybridised to the media of epicardial coronary arteries as well as intramyocardial vessels, confirming the presence of mRNA encoding both sub-types in the vascular smooth muscle of the vessel wall.6 Although mRNA for both receptors was detected, competition binding using BQ123 demonstrated that the majority (at least 85%) of ET receptors present in smooth muscle are the ETA sub-type. These results provide further support for the hypothesis that the ETA sub-type is the receptor that must be blocked in humans to produce a beneficial vasodilatation in pathophysiological conditions where there is an increase in peptide concentration or receptor density.

Adult↗

The Sophy valve and the el-Shafei shunt system for adult hydrocephalus.

A selected series of 22 adult patients with hydrocephalus were treated by a shunt system incorporating a variable pressure Sophy valve or by ventriculojugular shunting against the direction of blood flow using the El-Shafei system. One patient had insertion of two Sophy valves and an El-Shafei shunt. Patient selection was reserved to those with hydrocephalus thought to be at high risk when shunted with systems containing a conventional unipressure valve. None of the eight patients who had ventriculojugular shunting by the El-Shafei method demonstrated any notable clinical or radiological improvement subsequent to shunt insertion. Of the 16 Sophy devices inserted only seven produced a satisfactory result. The current evaluation of shunt malfunction could be improved by support for a national register.

Adolescent↗

ETA and ETB endothelin receptors in human myometrium characterized by the subtype selective ligands BQ123, BQ3020, FR139317 and PD151242.

ETA selective (BQ123, FR139317, PD151242) and ETB selective (BQ3020) ligands were used to define the binding characteristics and contractile function of endothelin receptor subtypes in human myometrium. In saturation binding assays with 10 microns-thick tissue sections [125I]endothelin-1 (ET-1) bound with a single affinity to receptors in the myometrium (Kd, 1.19 +/- 0.17 nM) and adjacent endometrium (Kd, 1.39 +/- 0.51 nM). Competition binding assays in myometrium revealed a heterogeneous population of receptors with BQ123 (Kd ETA, 1.43 +/- 0.33 nM; Kd ETB, 39.91 +/- 9.06 microM), FR139317 (Kd ETA, 2.54 +/- 0.87 nM; Kd ETB, 89.79 +/- 24.34 microM) and BQ3020 (Kd ETA, 4.57 +/- 0.58 microM; Kd ETB, 90.07 +/- 19.53 nM). The presence of these receptors in myometrium was confirmed by saturation assays with the new ETA selective ligand [125I]PD151242 (Kd, 0.93 +/- 0.08 nM; Bmax 138.7 +/- 1.0 fmol/mg protein) and the ETB selective [125I]BQ3020 (Kd, 0.62 +/- 0.07; Bmax 44.5 +/- 1.1 fmol/mg protein). Reverse-transcriptase PCR assays detected mRNA encoding both receptor subtypes in myometrium. Autoradiography with radiolabelled PD151242 and BQ3020 demonstrated that ETA receptors were the predominant subtype in the myometrium and identified a population of ETB receptors in the endometrium. In tissue bath experiments, an ET-1-induced increase in contractility of myometrial strips was antagonized by 10 microM FR139317 but not by BQ123 at the same concentration. The ETB agonist BQ3020, which is a potent agonist in animal tissue, did not increase contractility when tested at concentrations up to 2 microM.

Azepines↗

Quantification of mRNA in human tissue using fluorescent nested reverse-transcriptase polymerase chain reaction.

We report the development of a quantitative nested reverse-transcriptase polymerase chain reaction which utilizes a fluorescence detection system. Using specific primer pairs to study mRNA for endothelin receptors in the human kidney, we synthesized a cRNA construct containing the same sequences but yielding a PCR product some 300 base pairs larger than native mRNA. Inclusion of a known amount of construct as internal standard with tissue RNA prior to cDNA synthesis allowed all reactions to occur under the same conditions in the same tube. In the nested PCR reaction, serial dilutions made before the second round enabled construction of a standard curve for each assay, and confirmation that standard and sample curves remained parallel. This indicates that both cDNAs amplified at the same rate. One internal primer was fluorescently labeled. Quantification of products using an ABI 373A sequencer with Genescan software gave sensitive and reproducible results. Analysis of a needle biopsy (10 mg) of histologically normal cortex gave 0.4 amol ETA mRNA and 1.6 amol ETB mRNA/micrograms total RNA. In medulla these values were 0.46 and 1.16 amol/micrograms, respectively. Ratios of ETB to ETA message were 74:26 in cortex and 77:23 in medulla, agreeing with previous ligand binding studies of receptor protein. Intra- and interassay coefficients of variation were 4.5 and 5.3%. This new method has potential for widespread application to the study of low copy-number mRNA or where only very small amounts of tissue are available, such as biopsy specimens.

Base Sequence↗

Vasoconstrictor endothelin receptors characterized in human renal artery and vein in vitro.

1. We have identified the endothelin receptors present in the media of human main stem renal artery and vein and characterized the subtypes mediating vasoconstriction in these blood vessels in vitro. 2. Messenger RNA encoding both ETA and ETB receptors was identified in the smooth muscle layer of human renal artery and vein by reverse transcriptase-polymerase chain reaction assay. In cryostat-cut cross-sections of both vessels autoradiographical visualisation suggested a majority of ETA receptors. Intense binding was obtained to the non-selective ligand [125I]-ET-1 and the ETA-selective [125I]-PD151242 but only weak labelling of sites by the ETB-selective [125I]-BQ3020. 3. ET-1 potently constricted renal artery and vein preparations with EC50 values of 4.06 nM and 1.00 nM, respectively. Sarafotoxin 6b was approximately ten times less potent than ET-1 with EC50 values of 36.3 nM and 13.8 nM respectively. In the renal artery, ET-3 and sarafotoxin 6c showed little or no activity up to 300 nM. Responses to these peptides were more variable in the renal vein. Preparations from three individuals did not respond to ET-3 but in three further cases, although ET-3 was much less potent than ET-1, full dose-response curves were obtained. S6c elicited dose-related contractions in vein preparations from 5/6 individuals and although more potent than ET-1, the maximum response was 30-60% of that obtained to ET-1. 4. ET-1-induced vasoconstriction of renal artery and vein was antagonized by the ETA-selective, BQ123 (3-10 microM). The dose-response curves to ET-1 were displaced in a parallel rightward fashion with no attenuation of the maximum responses. pA2 values were estimated to be 6.8 +/- 0.1 and 6.8 +/- 0.4 for artery and vein respectively.5. These data suggest that mRNA encoding both ETA and ETB receptors is present in the media of human main stem renal artery and vein. However, autoradiographical studies indicate that the majority of ET receptors expressed are of the ETA subtype. The relative potencies of ET-1 and ET-3 as vasoconstrictors of renal blood vessels in vitro is consistent with this being an ETA-mediated response,and therefore whilst responses to S6c indicate that constrictor ETB receptors may be present in renal veins from some individuals these are likely to be of less importance in these blood vessels.

Adult↗

Trochlear nerve schwannomas: a case report and literature review.

Trochlear nerve sheath tumours are extremely uncommon, only six cases diagnosed during life having been presented previously. In none of these earlier cases were magnetic resonance imaging studies obtained. We report here upon the clinical presentation, surgical management and post-operative course of a case where the diagnosis was suspected pre-operatively from MRI studies. The radiological appearances are described, together with a review of all previously published accounts of this rare tumour.

Adult↗

Alternatively spliced mRNAs for human endothelin-2 and their tissue distribution.

The cDNA for Endothelin-2 (ET-2) has been previously cloned and characterised; however, ET-2 remains the least studied of the endothelin isopeptides and little is known of its function and location. In the present study reverse transcriptase-polymerase chain reaction revealed the presence of seven alternatively spliced mRNA variants encoding ET-2, with a specific pattern of distribution in various human tissues. Computer alignment and analysis of the DNA sequences demonstrated alternative splicing of five exons of 52, 169, 123, 99 and 174 base pairs, in the carboxy terminal region of the mRNA encoding preproET-2. This region contains sites for the post-transcriptional processing of preproET-2 into mature ET-2, therefore we postulate that post-transcriptional processing may be disrupted or altered in these variants.

Alternative Splicing↗

Identification of an actin binding region in aldolase.

Fragmentation of the actin binding glycolytic enzyme, aldolase, with cyanogen bromide yields an 18K actin binding fragment which corresponds to residues 1-164 of the aldolase sequence. Within this fragment there is a region of sequence (residues 32-52) which is highly homologous to a region of sequence near the C-terminus of actin itself and which is also found in the actin binding domains of a number of other actin binding proteins. A synthetic peptide corresponding to the aldolase sequence 32-52 encompassing this region of homology binds to F-actin and specifically competes with native aldolase for binding to this cytoskeletal protein.

Actins↗

Endothelin-2 mRNA splice variants detected by RT-PCR in cultured human vascular smooth muscle and endothelial cells.

Our aim was to examine the hypothesis that vascular smooth-muscle cells (VSMCs) express only ETA mRNA and endothelial cells express only ETB mRNA and to determine which ET mRNA isoforms are expressed in these cell cultures. Using the reverse transcriptase polymerase chain reaction, we were able to detect ETB, ET-1 and splice variant ET-2 mRNA in cultured human umbilical vein endothelial cells (HUVECs) and ETA and splice variant ET-2 mRNA in cultured aortic smooth-muscle cells. The presence of ET-2 mRNA in cultured VSMCs has not been previously reported. These results agree with the hypothesis that ET-1 may be released from vascular endothelial cells to act predominantly on ETA receptors on VSMCs to stimulate contraction of the underlying smooth-muscle cells, and that endothelium-derived relaxing factor release may be mediated predominantly via the ETB receptors on HUVECs. The role of ET-2 expression from HUVECs and VSMCs is less clear.

Base Sequence↗