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Biomedical subjects

I Young

Publications and source records attributed to I Young.

At least 19 recordsLinked to original sources
PubMed2002

Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating capacity in hypopituitary adults with GH deficiency.

OBJECTIVES: Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro-atherogenic state associated with adult GHD. DESIGN AND PATIENTS: In a randomized, double-blind, placebo-controlled study we investigated the effects of GH replacement on low-density lipoprotein (LDL) oxidation and neutrophil superoxide (O(-)(2)) generating capacity in 32 GHD adults (19 males, 13 females; age range 19-64 years) over 3 months. Thirty age- and sex-matched healthy controls were also studied. MEASUREMENTS: Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper-catalysed lag phase of LDL oxidation. Neutrophil O(-)(2)- generating capacity was assessed by a lucigenin-based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis. RESULTS: Compared to controls, GHD subjects had higher LDL cholesterol (4.0 +/- 0.8 vs. 3.5 +/- 0.9 mmol/l, P < 0.01) and higher triglyceride concentrations (2.3 +/- 1.5 vs. 1.1 +/- 0.7 mmol/l, P < 0.001) but lower HDL cholesterol (1.1 +/- 0.3 mmol/l vs. 1.4 +/- 0.4 mmol/l, P < 0.01), lower levels of HPOs (0.72 +/- 0.35 vs. 0.92 +/- 0.20 microm, P < 0.01) and lower basal (2.5 +/- 1.5 vs. 4.5 +/- 2.3 mV/5 x 10(5) neutrophils, P < 0.01) and peak post-activation levels (23.2 +/- 11.1 vs. 34.4 +/- 15.6 mV/5 x 10(5) neutrophils, P < 0.01) of neutrophil O(-)(2)- generation. GH replacement resulted in an increase in HPOs from 0.70 +/- 0.39 to 0.86 +/- 0.19 microm (P < 0.05), although there was no change in the lag time of LDL oxidation. Neutrophil O(-)(2)- generating capacity was enhanced with a rise in basal O(-)(2)- generation from 2.8 +/- 1.4 to 5.4 +/- 4.6 mV/5 x 10(5) neutrophils (P < 0.05) and in peak post-activation O(-)(2)- generation from 21.9 +/- 9.5 to 35.8 +/- 21.7 mV/5 x 10(5) neutrophils (P < 0.05). LDL cholesterol was reduced from 4.1 +/- 0.8 mmol/l to 3.5 +/- 0.8 mmol/l (P < 0.01). No significant changes in measured parameters occurred in the placebo group. CONCLUSIONS: Adult GHD is associated with reduced lipid peroxidation and impaired neutrophil O(-)(2)- generating capacity, both of which are reversible with GH replacement. Our data suggest that: (i) that oxidative stress is not a major feature of the pro-atherogenic state in hypopituitary adults with GHD and (ii) a role for GH in modulating neutrophil function and leucocyte-lipoprotein interactions.

Adult↗
PubMed2001

Aerosol deposition and clearance measurement: a novel technique using dynamic SPET.

Planar gamma camera scintigraphy is a well-established technique for characterising the deposition and clearance of radiolabelled aerosols. While single-photon emission tomography (SPET) can offer superior assessment of radioaerosol deposition and better differentiation between peripheral and central deposition, the long acquisition times of single-headed SPET have largely prevented its use for measuring clearance or deposition of fast-clearing radioaerosols. This study investigated the feasibility of fast dynamic SPET imaging (1 min/frame) using a three-headed gamma camera to assess the regional and total deposition and clearance of different radioaerosols over a period of 26 min. Six subjects inhaled nebulised technetium-99m diethylene triamine penta-acetic acid radiolabelled aerosols with small and large droplet sizes [mass median aerodynamic diameter (MMAD) 3.2 +/- 0.2 and 6.5 +/- 0.2 microm, span 1.8 and 1.7, respectively] and in normal (0.9%) or hypertonic (7%) saline with controlled breathing on four separate occasions. The penetration indices (PIs) calculated from the SPET data for normal saline were 0.50 +/- 0.04 and 0.36 +/- 0.02 for the small and large droplet sizes, respectively. Consistent with the hygroscopic growth of the hypertonic aerosols, the PIs for hypertonic saline were lower, at 0.43 +/- 0.02 and 0.34 +/- 0.02 for the small and large droplet sizes, respectively. PIs calculated from the planar data showed similar trends, but failed to detect the significant difference seen with SPET between small normal and small hypertonic saline radioaerosols. In conclusion, the feasibility of using fast dynamic SPET for imaging radioaerosol deposition and associated radiolabel clearance in the lung has been successfully demonstrated. The fast SPET was able to reveal important differences in aerosol deposition that were not detected by planar imaging.

Administration, Inhalation↗
PubMed2001

'Settings' based health promotion: a review.

Over the past 10 years, 'settings' based health promotion has become a central feature of efforts to promote health that recognize the significance of context. Emerging in part from a perception of an over-reliance on individualistic methods, the approach was built on a profound belief in its value and deployed a range of novel theoretical resources, mainly from organizational sociology and psychology. This initial enthusiasm has been maintained within policy directives, in the published literature and, from our own experience, amongst health promotion practitioners. At the same time, with the maturing of the approach, has come a healthy element of critical review. Drawing upon the literature and based upon our experiences within the Health Education Board for Scotland, this paper seeks to bring together a range of perspectives, casting a critical yet constructive eye on current settings theory and practice. The paper first reviews the nature of settings based work, highlighting the varied bases and expectations that underpin it. Similarly, the many factors that influence the ability of health promoters to deliver such activities are considered. In relation to the construction and delivery of such activity, the paper suggests that there needs to be an explicit and detailed assessment of the nature of the setting, the skills of the health promoter and the associated expectations.

Health Promotion↗
PubMed2000

Phages will out: strategies of host cell lysis.

Most phages accomplish host lysis using a muralytic enzyme, or endolysin, and a holin, which permeabilizes the membrane at a programmed time and thus controls the length of the vegetative cycle. By contrast, lytic single-stranded RNA and DNA phages accomplish lysis by producing a single lysis protein without muralytic activity.

Amino Acid Sequence↗
PubMed1999

Deposition of aqueous aerosol of technetium-99m diethylene triamine penta-acetic acid generated and delivered by a novel system (AERx) in healthy subjects.

Deposition of technetium-99m diethylene triamine penta-acetic acid aqueous radioaerosols generated by a novel aerosol delivery system (AERx) was studied in six healthy subjects using both planar and single-photon emission tomography (SPET) imaging. AERx is a microprocessor-controlled, bolus inhalation device that is actuated at pre-programmed values of inspiratory flow rate and volume. The aims of the study were to determine the effects of posture and inhaled volume upon deposition of the aerosol in the lungs. Each subject inhaled the radioaerosol in two positions (supine vs sitting) and with two inspiratory manoeuvres [vital capacity (VC) vs "fixed volume" of 1 l above functional residual capacity]. Simultaneous transmission-emission planar and tomographic images were acquired. The results showed diffuse deposition of the aerosol in the lung. Neither the breathing manoeuvre nor the posture was found to affect the distribution of the aerosol as measured by the ratio of the activity (counts per pixel) in the peripheral:central (penetration index, PI) or in the apex:base regions of the planar lung images (P>0.1). A small, albeit statistically significant, difference in PI (P<0.03) was found between VC and fixed volume sitting manoeuvres with SPET only. The PI values themselves indicate that the radioaerosol was well distributed in the lung, with the periphery having 45%-64% of the activity of the central region. Superposition of transmission SPET lung outline on emission SPET visually confirmed the excellent peripheral deposition of the aerosol. The AERx system showed high efficiency of delivery, with approximately 50% of the extruded dose in the device depositing in the lung. The uniformity of radioactivity distributed throughout the lung is attributed to the fine particle size (mass median aerodynamic diameter of 2 microm) of the aerosol and the electronic control of aerosol inhalation by the device. In conclusion, the AERx system can be ideal for diffuse aerosol deposition of therapeutic or diagnostic agents and is largely unaffected by inhaled volume and posture. The efficiency of the device device can limit the total radiation exposure of patients and staff administering the radioaerosols, and can make it suitable for delivery of expensive drugs.

Adult↗
PubMed1999

Asymptomatic inflammation and/or infection in benign prostatic hyperplasia.

OBJECTIVE: To determine the extent, pattern and clinical significance of asymptomatic histological inflammation and latent infection (National Institute of Health Category IV prostatitis) in benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study included 80 patients (from a cohort of 100 consecutive potentially eligible subjects) with a diagnosis of BPH, but no history or symptoms of prostatitis. Histological sections were obtained from specimens collected prospectively at transurethral resection of the prostate (TURP), immunostained for leukocyte common antigen and scanned using a computerized image-analysis system. Foci of inflammation were categorized as glandular, periglandular, stromal or peri-urethral, and the inflammatory cell density graded from 1 to 3. Relationships and correlations were calculated between the volume, degree and type of inflammation, presence and type of bacteria (culture of deep prostatic biopsies), the use of catheters and prostate specific antigen (PSA) levels. RESULTS: Inflammation was identified in all patients but the mean tissue surface area involved was only 1.1% of the total specimen, with periglandular inflammation being the predominant pattern (0.5%). Of the prostate specimens, 44% showed bacterial growth (in 67% of the catheterized patients and 28% of those uncatheterized; 42% of patients were catheterized before TURP). There was no significant difference between any combination of inflammation pattern, volume or grade of inflammation in those catheterized or not (P=0.15) or culture-positive (pathogenic or not) and culture-negative cases (P=0.06). Neither total PSA or PSA density was significantly correlated (P>0.05) with the amount, degree or distribution of inflammation. CONCLUSION: Prostatic inflammation is an extremely common histological finding in patients with symptoms of BPH who have no symptoms of prostatitis. There was no correlation between the degree and pattern of inflammation, catheterization, presence of bacteria, serum PSA or PSA density. The clinical significance of asymptomatic Category IV chronic prostatitis associated with BPH has yet to be determined.

Bacterial Infections↗
PubMed1999

Diagnosis and risk stratification of patients with anginal pain and non-diagnostic electrocardiograms.

Patients with acute chest pain suggestive of myocardial ischaemia, and normal or non-diagnostic electrocardiograms, form a difficult subgroup for diagnosis and early risk stratification. We prospectively evaluated the role of troponin T (cTnT), troponin I (cTnI), CKMB mass and myoglobin, in the diagnosis and risk stratification of 214 patients with acute chest pain of < or = 24 h and non-diagnostic or normal ECGs admitted directly to the Cardiac Unit of the Royal Victoria Hospital Belfast from the Mobile Coronary Care Unit or the Accident/Emergency Department. This was a single-centre prospective study, and follow-up (3 months) was complete for all patients. Blood was assessed for quantitative cTnT, cTnI, CKMB mass and myoglobin, and qualitative cTnT on admission and at 12 h. Diagnosis of index event and incidence of new cardiac events (death, non-fatal myocardial infarction, revascularization, or readmission for unstable angina) over 3 months were assessed. Based on standard criteria, myocardial infarction occurred in 37/214 (17%), and unstable angina in 72/214 (34%). At 12 h from admission, cardiac troponins had higher sensitivity for the diagnosis of acute coronary syndromes (myocardial infarction and unstable angina) than conventional markers (cTnI 48%, cTnT 38%, CKMB mass 30% or myoglobin 27%). At 3 months, a new cardiac event had occurred in 42/214 (20%). Significantly higher event rates occurred when any of the biochemical markers was elevated, but the statistical significance was highest for patients with elevated cTnI (p < 0.0001). Whilst gender, history of ischaemic heart disease (IHD), stress test response, cTnT, cTnI, CKMB mass and myoglobin were univariate predictors, cTnI at 12 h and stress test response were the only two independent significant predictors for a subsequent cardiac event at 3 months. Raised cTnI at 12 h after admission had the highest sensitivity for the diagnosis of acute coronary syndromes, and was independently associated with a 2-3 times increased risk of future cardiac events within 3 months among patients with acute chest pain suggestive of myocardial ischaemia but with normal or non-diagnostic ECGs.

Aged↗
PubMed1997

The effect of tramadol on dento-alveolar surgical pain.

The aim of the study was to assess the analgesic effect of tramadol in the relief of pain after dentoalveolar operations that involve the removal of bone and suturing. Four-hundred and fifty-two patients over the age of 18 years who were to undergo removal of impacted teeth (n = 362), removal of root (n = 79), or alveolectomy, enucleation of cysts, or removal of soft tissue (n = 11) under local anesthesia were studied. Patients were randomly allocated to receive tramadol 100 mg or 50 mg four times daily, or 50 mg twice daily, or placebo. Median pain scores on the day of operation in the three tramadol groups were similar (2 in each group, ranges 1-5, 1-4.8, and 1-5 respectively) and were all significantly lower than that in the placebo group (2.3 range 1-4.2). The median number of Paracetamol tablets taken by patients in the three tramadol groups was 2 (ranges 0-8, 0-12 and 0-8 respectively), and were all significantly less than in the placebo group (4, range 0-12). More patients given tramadol reported complete pain relief than the placebo group. The advantages of tramadol continued over the next 2 days. There were no serious or unexpected adverse effects. It is concluded that tramadol is an effective analgesic after dentoalveolar operations.

Acetaminophen↗
PubMed1997

Dentato-olivary dysplasia in sibs: an autosomal recessive disorder?

The cases of a brother and sister with dentato-olivary dysplasia are described. Both had severe developmental delay, severe epilepsy of early onset, evolving hypertonic quadriplegia, and death in early childhood. Postmortem examination of the brain in one child showed a particular form of dentato-olivary dysplasia. These children show many features in common with previously described cases of this condition, but this is the first report of occurrence in sibs.

Dentate Gyrus↗
PubMed1997

Molecular-cytogenetic detection of a deletion of 1p36.3.

We report a deletion of 1p36.3 in a child with microcephaly, mental retardation, broad forehead, deep set eyes, depressed nasal bridge, flat midface, relative prognathism, and abnormal ears. The phenotype is consistent with that described for partial monosomy for 1p36.3. Reverse chromosome painting and microsatellite and Southern blot analyses were used to map the extent of the deletion. Fluorescence in situ hybridisation (FISH) analysis using probes from every telomere indicates that the rearrangement is likely to be a chromosomal truncation or rearrangement involving subtelomeric repetitive DNA. The deletion was identified by screening a sample of children and adults with idiopathic mental retardation. In conjunction with previous work on this sample, we estimate that 7.4% of the group have subtelomeric rearrangements.

Adolescent↗
PubMed1996

Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome.

The Coffin-Lowry syndrome (CLS), an X-linked disorder, is characterized by severe psychomotor retardation, facial and digital dysmorphisms, and progressive skeletal deformations. Genetic linkage analysis mapped the CLS locus to an interval of 2-3 megabases at Xp22.2. The gene coding for Rsk-2, a member of the growth-factor-regulated protein kinases, maps within the candidate interval, and was tested as a candidate gene for CLS. Initial screening for mutations in the gene for Rsk-2 in 76 unrelated CLS patients revealed one intragenic deletion, a nonsense, two splice site, and two missense mutations. The two missenses affect sites critical for the function of Rsk-2. The mutated Rsk-2 proteins were found to be inactive in a S6 kinase assay. These findings provide direct evidence that abnormalities in the MAPK/RSK signalling pathway cause Coffin-Lowry syndrome.

Abnormalities, Multiple↗
PubMed1996

Incorporation of the Arden Syntax within the reimplementation of a closed-loop decision support system.

The initial implementation of a clinical decision support system, although extremely successful and popular with users, suffered from response time and operational support difficulties. As part of the redesign of the system, which uses closed-loop rules to propose laboratory and other investigations, the decision was taken to move to Arden Syntax for the expression of such rules, although in some areas the current standard was felt to be either inadequate or inelegant. Such limitations have been overcome by the development of local extensions to the Arden Syntax, which are described and where appropriate proposed as possible enhancements of the standard. The use of common UNIX tools in the creation of a compiler which converts Arden Medical Logic Modules to M (MUMPS) code is also discussed.

Decision Making, Computer-Assisted↗
PubMed1996

An ELISA for the detection of antibody to the core antigen of hepatitis C virus: use in diagnosis and analysis of indeterminate samples.

AIMS: In order to examine more carefully the natural history of hepatitis C virus infection and to determine a role for anti-core in the discrimination of indeterminate samples, a solid phase ELISA to detect antibody of the immunoglobulin G class to the hepatitis C virus core antigen was developed using purified protein expressed in Escherichia coli from a major portion of the core antigen coding region. METHODS/RESULTS: In a study which examined 651 samples submitted for routine testing by a commercial ELISA (Ortho), only 11 samples showed discrepant results; of these, 10 were Ortho ELISA positive, anti-core negative and one was Ortho ELISA negative anticore positive. Supplemental tests showed that 5/10 of these samples were anti-HCV negative by RIBA and the reciprocal 5 were negative for anti-C22 but positive for anti-C100 and anti-C33. The Ortho ELISA negative, anticore positive sample was weakly positive for anti-C22. The anti-core ELISA was then used to examine 67 indeterminate samples from the blood bank; 11/11 samples which were HCV-RNA positive were anti-core positive and 7/56 samples which were HCV-RNA negative were anti-core positive. The anti-core titre was then examined in two groups of indeterminate samples; group 1, polymerase chain reaction-positive, anti-core positive and group 2, polymerase chain reaction-negative, anti-core positive. The geometric mean anti-core titres in these groups were 1 x 10(-3.6) and 1 x 10(-2.3), respectively. Thus in this group of indeterminate samples, all samples (except one) with an anti-core titre > or = 1/200 were polymerase chain reaction-positive, confirming a close correlation between anti-core levels and hepatitis C viraemia. Anti-core was detected with equal efficiency in patients infected with genotypes which differed to that used to express the recombinant core antigen.

Antibody Specificity↗