Search PubMed⌕ Search

Biomedical subjects

J G Houston

Publications and source records attributed to J G Houston.

At least 19 recordsLinked to original sources

Evaluation of MR angiographic technique in the assessment of thoracic outlet syndrome.

AIM: To evaluate two-dimensional time of flight (2D TOF) and three-dimensional contrast-enhanced magnetic resonance angiographic (3DCE MRA) techniques in the assessment of patients with suspected thoracic outlet syndrome (TOS) of vascular origin. MATERIALS AND METHODS: Fifty-five consecutive examinations, in 51 patients with suspected TOS of vascular origin, were examined using either a 1T or 1.5T Siemens magnetic resonance imaging (MRI) unit, using either 2D TOF (n=13) or 3DCE MRA (n=42). Examinations were performed with the arms abducted (n=27) or both abducted and adducted (n=28). The source images and MIPs were reviewed retrospectively and assessed for image quality and the presence of significant persistent stenosis or impingement (a >60% reduction in the diameter of the subclavian vessels at the thoracic outlet or evidence of post-stenotic dilatation). When significant impingement was identified, the images were reformatted with multiplanar reconstruction to determine the cause. RESULTS: Images were sub-optimal in 53% 2D TOF and 10% 3DCE MRA examinations. 3DCE MRA offered vessel coverage from the aortic arch to the distal axilliary arteries, whereas, 2D TOF sequences gave more limited coverage. Eight patients were found to have significant impingement (n=7) or stenosis (n=1) of the subclavian artery attributable to TOS. 3DCE MRA also demonstrated other relevant significant stenoses not attributable to TOS (n=5). All cases of impingement were either seen only, or more prominently, on sequences with the arms abducted. Reformatting the 3DCE MRA studies demonstrated the cause of impingement. CONCLUSIONS: Both 2D TOF and 3DCE MRA may demonstrate TOS with significant arterial impingement. In comparison with 2D TOF sequences, 3DCE MRA offers extensive vessel coverage, is less prone to artefact and frequently demonstrates the underlying cause of TOS when studies are reformatted. Evidence of impingement should be sought from sequences performed with the arms abducted and venous phase sequences may show corroborative venous impingement.

Adolescent↗

Non spiral and spiral (helical) flow patterns in stenoses. In vitro observations using spin and gradient echo magnetic resonance imaging (MRI) and computational fluid dynamic modeling.

AIM: Physiological blood flow patterns are themselves poorly understood despite their impact on arterial disease. Stable spiral (helical) laminar flow (SLF) has been observed in normal subjects. The purpose of the present study is to develop a method of magnetic resonance (MR) flow pattern visualization and to analyze spiral and non-spiral flow patterns with and without luminal narrowing in vitro. The flow conditions were then modeled using computational fluid dynamics (Star-CD). METHODS: Laminar integrity was examined in a flow-rig using spin and gradient echo magnetic resonance imaging (MRI) in non-stenosed and stenosed conduits in the presence of non-spiral and spiral flow. RESULTS: No difference was observed in a non-stenosed conduit between non-spiral and spiral flow. In the presence of a stenosis spiral flow preserves flow velocity coherence whereas non-spiral flow increasingly lost coherence beginning proximal to the stenosis. Computational fluid dynamic modeling of the in vitro experiment showed marked differences between the 2 flow patterns. Non-spiral flow produced greater inwardly directed forces just beyond the stenosis and greater outward pressures at more distal sites. The near wall turbulent energy was up to 700% less with spiral flow over non-spiral flow beyond the stenosis. CONCLUSIONS: Spiral flow appears to offer clear flow profile stabilizing advantages over non-spiral flow, by significantly reducing the turbulence caused by a stenosis. Spiral flow also produces lower forces acting on the vessel wall.

Blood Flow Velocity↗

Ethnomedicinally selected plants as sources of potential analgesic compounds: indication of in vitro biological activity in receptor binding assays.

A number of plant species used in traditional medicine for the relief of pain have been selected from the medicinal and scientific literature of China, South America, Asia and West Africa. Extracts were prepared and tested in three in vitro receptor radioligand binding assays to determine whether there was an indication of biological activity, in particular their selectivity to a single receptor implicated in the mediation of pain. The three neuropeptide receptors chosen were Bradykinin (BK II), expressed in Chinese hamster ovary cells (CHO), neurokinin 1 (NK 1) expressed in astrocytoma cells, and calcitonin gene related peptide (CGRP) which were all implicated in the mediation of acute pain in the mammaliancentral nervous system. The plant species chosen to investigate were Ageratum conyzoides, Barringtonia edulis, Croton tiglium, Ipomea pes-caprae, Panax ginseng, Physostigma venenosum, Sinomenium acutum, Solidago virgaurea, Symplocos leptophylla and Typhonium giganteum. The results showed that there was a strong indication of biological activity for some of the plants which are used ethnomedicinally to treat pain, in the three in vitro receptor binding assays used, and particular plant extracts exhibited selective action to a single receptor.

Analgesics, Non-Narcotic↗

The chemical-biological interface: developments in automated and miniaturised screening technology.

The rapidly changing developments in genomics and combinatorial chemistry, generating new drug targets and large numbers of compounds, have caused a revolution in high-throughput screening technologies. Key to this revolution has been the introduction of robotics and automation, together with new biological assay technologies (e.g., homogeneous time resolved fluorescence). With ever increasing workloads, together with economic and logistical constraints, miniaturisation is rapidly becoming essential for the future of high-throughput screening and combinatorial chemistry. This is evident from the introduction of high-density microtitre plates, small volume liquid handling robots and associated detection technology.

Automation↗

High-throughput RT-PCR analysis of multiple transcripts using a microplate RNA isolation procedure.

We have developed a high-throughput, multiplex reverse transcription PCR (RTPCR) assay that is suitable for the analysis of medium-to low-copy cellular RNA transcripts from small numbers of cells (10(4)). High throughput was attained by utilizing microplate-based RNA extraction and RTPCR protocols, followed by PCR product visualization of a multiwelled agarose gel, stained with SYBR Green I dye. The transcriptional assay was unaffected by solvents (dimethyl sulfoxide and methanol) routinely used in high-throughput drug screens at concentrations required for compound solubilization. Furthermore, it has been used successfully for the investigation of differential mRNA expression levels of tumor necrosis factor alpha (TNF-alpha) and Interleukin-1 beta (IL-1 beta) in lipopolysaccharide (LPS)-stimulated THP-1 cells (a human monocytic cell line) and the identification of specific IL-1 beta transcriptional inhibitors.

Benzothiazoles↗

Comparison of two-dimensional time-of-flight dynamic magnetic resonance angiography with digital subtraction angiography in popliteal artery entrapment syndrome.

OBJECTIVE: To assess dynamic magnetic resonance angiography (MRA) as an alternative to catheter angiography in patients with popliteal artery entrapment syndrome (PAES). PATIENTS AND METHODS: Nine patients with surgically proven PAES underwent provocation digital subtraction angiography (DSA) and 2-dimensional time-of-flight dynamic MRA of the popliteal fossae (total of 17 limbs). Eight normal volunteers also underwent dynamic MRA (total of 16 limbs). Two observers blinded to the surgical findings and the results of DSA independently evaluated the 33 limbs of the 17 subjects on the basis of maximum-intensity projection images and transverse MRA source images. The degree of stenosis was graded and compared with that indicated by DSA. RESULTS: Among the 17 limbs of patients with surgically proven PAES, dynamic MRA suggested the correct diagnosis in 13 (76%) by indicating stenosis greater than 50%. Dynamic MRA indicated stenosis of 1% to 50% for 4 (25%) of the 16 normal limbs and no stenosis in the other 12 normal limbs (i.e., no false positive results). CONCLUSION: Catheter angiography is not necessary if dynamic MRA indicates stenosis of greater than 50% in patients with clinical suspicion of PAES, but is recommended if dynamic MRA indicates stenosis of 1% to 50%.

Adolescent↗

Comparison of ultrasound with fluoroscopy in the assessment of suspected hemidiaphragmatic movement abnormality.

A comparative study of quantitative hemidiaphragmatic ultrasound with fluoroscopy was undertaken in 30 patients referred for investigation of suspected hemidiaphragmatic movement abnormality. The aim of this study was to determine whether assessment with ultrasound or fluoroscopy differed, and which technique appeared more suitable in the investigation of hemidiaphragmatic movement disorder. There were four technical failures using fluoroscopy (13%), compared with none using ultrasound. Using the normal ranges of right to left ratio of maximal excursion (0.5-2.0 for fluoroscopy and 0.5-1.6 for ultrasound) there was concordance in 21 out of 26 (81%) patients. All cases of abnormality on fluoroscopy were seen on ultrasound. Four of the discordant cases had excursions on the lesser side in the normal range on ultrasound suggesting a milder movement abnormality detected by ultrasound than by fluoroscopy. Sniff testing conferred no advantage over quantitative testing. Ultrasound has technical, qualitative and quantitative advantages over fluoroscopy and should be the method of choice in the investigation of suspected hemidiaphragmatic movement abnormality.

Adult↗

Ultrasonic evaluation of movement of the diaphragm after acute cerebral infarction.

Respiratory dysfunction is an important complication of acute stroke but its mechanisms are poorly understood. Previous indirect assessments suggest that paralysis of the diaphragm occurs contralateral to the cerebral lesion. Diaphragmatic excursion was studied with real time ultrasound during quiet and deep breathing in 50 patients within 72 hours of acute stroke and 40 controls. During quiet breathing, hemidiaphragmatic movements were not significantly different between right hemispheric stroke, left hemispheric stroke, and controls. During deep inspiration, there was a significant bilateral reduction in hemi-diaphragmatic excursion in patients with stroke, for both right hemispheric stroke and left hemispheric stroke when compared with controls (both P < 0.001). Thus isolated hemidiaphragmatic paresis does not occur but maximal excursion of the diaphragm is reduced bilaterally in patients with acute stroke. This is a likely contributor to the respiratory dysfunction after acute stroke.

Acute Disease↗

Ultrasonic assessment of hemidiaphragmatic movement: an indirect method of evaluating mediastinal invasion in non-small cell lung cancer.

This preliminary study aimed to assess the potential value of diaphragmatic ultrasound (DUS) in evaluating phrenic nerve involvement indirectly, in the non-invasive pre-operative staging of mediastinal invasion in non-small cell lung cancer (NSCLC). A prospective study of 30 patients with NSCLC comparing the findings of diaphragmatic ultrasound, chest radiograph, computed tomography (CT) thorax and mediastinoscopy was performed. In all cases adequate quantitiative assessment of hemidiaphragmatic excursion was obtained. There was discordance in four of 30 patients between DUS and chest radiograph. Three of nine patients with extensive mediastinal disease on CT had abnormal DUS, and two of eight patients with indeterminate mediastinal disease on CT had abnormal DUS and were later found to be non-resectable. No abnormal cases of DUS were found in those cases with normal mediastinal CT. There was no clear relationship between the site, size and side of the primary tumour on CT, or its pleural or diaphragmatic contiguity, and hemidiaphragmatic excursion. There was concordance between DUS and mediastinoscopy in 17 of 21 patients. Two patients had normal mediastinoscopy and abnormal DUS but were not resectable at thoracotomy. No patient with abnormal DUS was resectable. DUS may be of potential value in the pre-operative staging of NSCLC and is therefore worthy of further evaluation.

Aged↗

The squalestatins: novel inhibitors of squalene synthase. Enzyme inhibitory activities and in vivo evaluation of C1-modified analogues.

Squalestatin analogues modified in the C1 side chain were prepared and evaluated for their ability to inhibit rat liver microsomal and Candida squalene synthase (SQS) in vitro. While maintaining the 4,6-dimethyloctenoate or 4,6-dimethyloctanoate ester groups at C6, a number of modifications to the C1 side chain were well tolerated. However, in the absence of the C6 ester group, similar modifications to the C1 side chain caused substantial loss of activity. Compounds were also evaluated for their ability to inhibit cholesterol biosynthesis in vivo in rats and to reduce serum cholesterol levels in marmosets. These studies revealed that compounds with similar SQS inhibitory activities can possess different in vivo durations of action and lipid-lowering abilities.

Animals↗

Ultrasound assessment of normal hemidiaphragmatic movement: relation to inspiratory volume.

BACKGROUND: Traditionally the radiological assessment of diaphragmatic movement has relied on fluoroscopy. Ultrasound scanning has recently been shown to be a sensitive and reproducible method of assessing hemidiaphragmatic movement in normal subjects. A study was undertaken to examine how movement of the diaphragm measured by ultrasound scanning relates to inspired lung volumes measured by spirometric testing. METHODS: Ultrasound examinations were performed on 14 normal volunteers using a 3.5 MHz sector transducer (Acuson 128). A fixed skin position on each lateral chest wall between the anterior clavicular and midaxillary line was selected symmetrically to obtain a longitudinal plane of each hemidiaphragm including the maximal renal bipolar length, allowing identification of the adjacent posterior aspect of the diaphragm. Craniocaudal excursions of the posterior part of each hemidiaphragm on successive respiratory cycles were recorded on videotape and compared with spirometric measurements recorded simultaneously on a water bath spirometer. Measurements were made in the sitting and supine position and were repeated on a separate occasion (at least two weeks apart) in 10 subjects by the same operator to assess reproducibility. RESULTS: The relation between inspired volume and hemidiaphragmatic movement was found to be linear. The gradient of these observed linear relations (hemidiaphragmatic excursion (mm)/inspired volume (1)) was calculated and their distribution for each hemidiaphragm followed a normal distribution irrespective of position. The 95% confidence limits of the right to left ratio of these gradients in the supine position were 0.53 and 1.7. Change of posture from the supine to the sitting position reduced the gradient. The technique had acceptable reproducibility with coefficients of variation for the supine position of 7.5% and 11.7% for right and left hemidiaphragm respectively. CONCLUSION: Ultrasound scanning is a simple, non-invasive and reproducible means of assessing hemidiaphragmatic movement, yielding quantitative information which relates to inspired lung volumes.

Adult↗

Interaction of Candida albicans with neutrophils: effect of phenotypic changes in yeast cell-surface composition.

The susceptibility of four strains of Candida albicans to phagocytosis and intracellular killing by rabbit peritoneal neutrophils was investigated. Two of the strains, isolated from active infections, were known to synthesize a surface layer of mannoprotein fibrils in response to growth on 500 mm-galactose; the other strains, from asymptomatic carriers, lacked this capability. The presence of serum opsonins greatly enhanced phagocytosis of all four strains and, following opsonization, phagocytosis of an infective strain was equally rapid after growth on either 500 mm-galactose or 50 mm-glucose. In the absence of opsonins, galactose-grown infective strains were phagocytosed faster than either glucose-grown infective strains or galactose-grown carrier strains. These differences in phagocytic uptake were paralleled by differences in neutrophil chemiluminescence response. Intracellular killing of galactose-grown infective strains was only half that of glucose-grown infective strains or galactose-grown carrier strains after incubation for 60 min. Pretreatment of neutrophils with extracellular polymeric material, which contains the surface fibrils, completely inhibited intracellular killing. These results indicate that production of the fibrillar layer promotes yeast virulence by increasing resistance to intracellular killing, although it may enhance phagocytosis in locations where opsonic activity is poor.

Animals↗

Isolation and study of an acquired inhibitor of human coagulation factor V.

A coagulation Factor V inhibitor developed in a man 75 yr of age in association with an anaplastic malignancy and drug treatment (including the aminoglycoside antibiotic, gentamicin). The patient did not bleed abnormally, despite both surgical challenge and plasma Factor V activity of less than 1%. The inhibited plasma had grossly prolonged prothrombin and activated partial thromboplastin times, but a normal thrombin time. Mixing studies indicated progressive coagulation inhibition with normal plasma, but not with Factor V-deficient plasma, and reversal of coagulation inhibition by the addition of bovine Factor V to the patient's plasma. 1 ml of patient plasma inhibited the Factor V activity of 90 ml of normal human plasma. The inhibitor was isolated by sequential affinity chromatography on protein A-Sepharose and Factor V-Sepharose. The IgG isolate markedly inhibits the activity of prothrombinase assembled from purified Factors Xa and Va, calcium ion, and phospholipid vesicles, and partially inhibits prothrombinase assembled from purified Factor Xa, calcium ion, and normal platelets. The Factor V of platelets, however, appears relatively inaccessible to the antibody, inasmuch as platelets isolated from whole blood supplemented for 8 h with the antibody functioned normally with respect to platelet Factor V-mediated prothrombinase function. The absence of obvious hemorrhagic difficulties in the patient, the total inhibition of plasma Factor V by the inhibitor, and the apparent inaccessibility of platelet Factor V to the inhibitor specifically implicate platelet Factor V in the maintenance of hemostasis.

Aged↗