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Biomedical subjects

J Andrews

Publications and source records attributed to J Andrews.

At least 19 recordsLinked to original sources

Takayasu's arteritis--recent advances in imaging offer promise.

Takayasu's arteritis (TA), a rare large vessel vasculitis of unknown aetiology, remains a difficult disease to manage with diagnosis often delayed until the late occlusive stage when irreversible vascular damage has occurred. Recent studies suggest that non-invasive imaging modalities including magnetic resonance imaging, ultrasound and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) allow diagnosis of TA earlier in the disease course than standard angiography and provide a means for monitoring disease activity. Choice of appropriate therapy for TA is limited by a lack of evidence and a combination of corticosteroids and immunosuppressive drugs is most commonly used. Novel therapeutic approaches such as the use of anti-tumour necrosis factor alpha (TNF-alpha) inhibitors and drug-eluting arterial stents show promise for improving the prognosis in severe disease. In addition, strict management of traditional cardiovascular risk factors such as dyslipidaemia, hypertension and lifestyle factors is mandatory to minimize secondary cardiovascular complications, which are the major cause of death in this disease.

Angiography↗

Identification and mapping of SNPs from ESTs in sunflower.

More than 67,000 expressed sequence tags (ESTs) have recently been generated for sunflower (Helianthus), including 44,000 from cultivated confectionery (RHA280) and oilseed (RHA801) lines of Helianthus annuus and 23,000 from drought- and salt-tolerant wild sunflowers, H. argophyllus and H. paradoxus, respectively. To create a transcript map for sunflower, we identified 605 ESTs that displayed small insertion-deletion polymorphism (SNP) variation in silico, had apparent tissue-specific expression patterns, and/or were ESTs with candidate functions in traits such as development, cell transport, metabolism, plant defense, and tolerance to abiotic stress. Primer pairs for 535 of the loci were designed from the ESTs and screened for polymorphism in recombinant inbred lines derived from a cross between the same cultivars (RHA280 x RHA801) employed for sequencing. In total, 273 of the loci amplified polymorphic products, of which 243 mapped to the 17 linkage groups previously identified for sunflower. Comparisons with previously mapped QTL revealed some cases where ESTs with putatively related functions mapped near QTLs identified in other crosses for salt tolerance and for domestication traits such as stem diameter, shattering, flowering time, and achene size.

Chromosome Mapping↗

Managing waiting time for radiotherapy: a single machine unit experience.

Waiting time (WT) for radiotherapy (RT) is a significant clinical problem. This paper examines various strategies for managing WT for patients treated with radical and palliative intent in the new setting of a rural single machine unit in Australia. Cohorts of patients undergoing both radical and palliative RT in Bendigo had their WT prospectively recorded. Matched cohorts from the hub centre (Peter MacCallum Cancer Centre, Melbourne) treated with palliative intent were also collated. Strategies implemented included a devoted priority meeting, palliative points system, and reallocation of appointment times. The audit was to continue until best practice guidelines were bettered. Three cohorts of patients were compared. There is a significant trend for increasing numbers of patients treated per month since the centre opened (P < 0.0001). The ratio of palliative to radical intent patients remained stable between 46 and 52%. Mean WT for palliative RT reduced from 25 days in the first cohort to 7 days in the final cohort (P < 0.0005). Waiting time for palliative RT was initially longer at Bendigo than the hub centre (P < 0.0005), but by the final cohort there was a non-significant difference favouring the Bendigo cohort (P = 0.26). Waiting time for radical treatment also improved throughout the three cohorts in Bendigo (P < 0.0005). A number of new strategies have successfully resulted in the abolition of lengthy WT for RT in Bendigo despite the increasing demand for the RT service.

Analysis of Variance↗

Randomized, double-blind comparison of growth in infants receiving goat milk formula versus cow milk infant formula.

OBJECTIVE: To compare growth of infants fed goat milk infant formula (GMF) or cow milk infant formula (CMF) and to compare tolerability and safety of the two formulas. METHODS: The study was conducted in Auckland, New Zealand. This was a double-blind randomized controlled trial. Newborn term infants were randomized within 72 h of birth to GMF or CMF. Milk formula powder in single serve sachets were reconstituted and fed to infants from trial commencement until age 168 days. No other formula given from randomization until age 168 days. Infant weight, length and head circumference were measured at birth and age 14, 28, 56, 84, 112, 140 and 168 days. Bowel motion frequency and consistency, sleeping and crying patterns and adverse events were also measured. RESULTS: Seventy-two infants were randomized, 36 each to GMF or CMF, with 62 infants completing the intervention. At enrollment the average weight of infants in the GMF group (mean +/- SD) was 3.33 +/- 0.43 kg and in the CMF group 3.43 +/- 0.47 kg; and at study completion 8.07 +/- 0.90 kg (GMF) and 7.87 +/- 0.99 kg (CMF). The difference in average weight gain over the study period for the GMF group versus the CMF group was not significant (+309 g; 95% CI = -49 to +668, P = 0.09). Median daily bowel motion frequency was greater in the GMF group than the CMF group (2.4 vs 1.7, P = 0.01). There were no group differences in bowel motion consistency, duration of crying, ease of settling, or frequency of adverse events. CONCLUSION: Growth of infants fed GMF is not different to that of infants-fed CMF.

Animals↗

Breath condensate ammonium is lower in children with chronic asthma.

Exhaled breath condensate pH and ammonium reflect asthmatic status and acute exacerbations in adults. The aim of this study was to assess whether pH and ammonium could reflect asthma and its severity in children. The current study comprised two parts: 1) a cross-section of 74 children with asthma (median age 10.5 yrs) compared with 47 healthy controls (median age 10 yrs); and 2) longitudinal assessment of eight children (mean age 8.5 yrs) admitted with asthma exacerbation. Condensate pH and ammonium were compared with clinical observations. In the cross-sectional part of the study, lower per cent forced expiratory volume in one second was associated with more symptoms and treatment. There was no significant difference between median pH in children with stable asthma (6.05) compared with controls (5.90). Ammonium was significantly lower in children with asthma (median 258 microM) compared with controls (median 428 microM). No association was found between ammonium or pH and lung function or symptom-free days. In the longitudinal study, significant improvements in oxygen saturation and respiratory rate with treatment of an acute exacerbation were not reflected by changes in pH or ammonium. In conclusion, pH does not appear to reflect disease or severity in children with asthma. Ammonium was significantly lower in children with asthma when compared with controls.

Adolescent↗

An evaluation of the cell-dyn 3200 for counting cells in cerebrospinal and other body fluids.

This study compared the white blood cell (WBC) and red blood cell (RBC) counts obtained with the Cell-Dyn 3200 (CD 3200) with results obtained by hemocytometer, the reference method for counting cerebrospinal fluid (CSF) and other body fluid specimens. Ninety-six CSF and 65 body fluid specimens were evaluated. Background counts were maintained on the CD 3200 at 0.001 x 10(9)/L and 0.00 x 10(12)/L for WBC and RBC counts, respectively. Linearity and precision were acceptable for both the total nucleated cell (TNC) count and the RBC count. The CD 3200 WBC optical count was correlated with the TNC count obtained by the manual reference method for CSF specimens across the range of 0 x 10(9 )/L to 7.863 x 10(9)/L (r2 = 0.9867) and for body fluid specimens across the range of 0 x 10(9)/L to 14.0 x 10(9)/L (r2 = 0.9955). An r2 value of 0.9016 was obtained for the 82 CSF specimens with manual TNC counts of <0.200 x 10(9)/L. Analysis of the CSF and body fluid specimens indicated that automated RBC counts could be reported at > or = 0.003 x 10(12)/L. In this study, 7 CSF and 30 body fluid specimens had RBC counts of >0.003 x 10(12)/L, and there was good agreement with manual RBC counts, with r2 values of 0.9893 and 0.9960 obtained for CSF and other body fluids, respectively. The CD 3200 in our experience has a lower reportable range than the ranges of most automated cell counters reported in the literature. In contrast to the only other instrument with comparable reportable ranges, the CD 3200 requires a smaller sample volume without any special sample preparation, reagents, or software. By using the CD 3200 with our laboratory-specific rules for agreement between duplicate counts, we would be able to reduce our manual CSF specimen counts from 192 TNC and 192 RBC counts to 2 TNC and 178 RBC counts. For body fluid specimens, our manual counts would be reduced from 130 TNC and 130 RBC counts to 10 TNC and 4 RBC counts.

Blood Cell Count↗

Tissue kinetics of telithromycin, the first ketolide antibacterial.

The potential efficacy of an antibacterial depends not only on its spectrum of activity but also on its concentration at the site of infection. The tissue kinetics of telithromycin-the first ketolide antibacterial-are reviewed here. Telithromycin accumulates rapidly in white blood cells, inflammatory fluid, and cells and tissues of the upper and lower respiratory tract, with mean concentrations above the MICs of key respiratory pathogens. Tissue kinetics of telithromycin support facilitated delivery to the site of infection, good efficacy against intracellular respiratory pathogens and respiratory pathogens at extracellular sites in the airways, and effectiveness in the treatment of upper and lower respiratory tract infections (RTIs). The tissue kinetics profile of telithromycin, together with its microbiological profile, makes it a promising new antibacterial for the treatment of community-acquired RTIs.

Anti-Bacterial Agents↗

Non-invasive imaging in the diagnosis and management of Takayasu's arteritis.

OBJECTIVES: Takayasu's arteritis (TA) is a rare disease, in which early diagnosis and assessment of treatment efficacy remain a problem. Signs and symptoms may be non-specific and conventional blood tests unreliable, with vascular inflammation often persisting in the face of a normal acute phase response. The current "gold standard" investigation, x ray angiography, is invasive and only identifies late, structural changes in vessels. Recently, non-invasive imaging methods have shown promise in the assessment of patients with TA. METHODS: The invasive and non-invasive imaging performed on all patients in the rheumatology department at the Hammersmith Hospital between May 1996 and May 2002 who fulfilled the ACR criteria for TA were reviewed. All patients were clinically active at diagnosis and were treated with high dose oral prednisolone and additional oral or intravenous immunosuppression. RESULTS: Non-invasive imaging methods ([(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) and magnetic resonance imaging (MRI)) provided important additional information about disease activity ([(18)F]FDG-PET) and progression of vessel wall thickening (MRI) when compared with x ray angiography. CONCLUSIONS: Non-invasive imaging methods provide useful additional information towards the diagnosis and management of TA. Such techniques may allow earlier diagnosis and more accurate assessment of response to treatment than conventional clinical assessment and/or angiography. Non-invasive imaging is likely to be useful in the management of other large vessel vasculitides.

Adult↗

Concentrations of garenoxacin in plasma, bronchial mucosa, alveolar macrophages and epithelial lining fluid following a single oral 600 mg dose in healthy adult subjects.

A microbiological assay was used to measure concentrations of garenoxacin (BMS-284756) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF), following a single 600 mg oral dose. Twenty-four healthy subjects were allocated into four nominal time intervals after the dose, 2.5-3.5, 4.5-5.5, 10.5-11.5 and 23.5-24.5 h. Mean concentrations in plasma, BM, AM and ELF, respectively, for the four nominal time windows were for 2.5-3.5 h 10.0 mg/L (S.D. 2.8), 7.0 mg/kg (S.D. 1.3), 106.1 mg/L (S.D. 60.3) and 9.2 mg/L (S.D. 3.6); 4.5-5.5 h 8.7 mg/L (S.D. 2.2), 6.0 mg/kg (S.D. 1.9), 158.6 mg/L (S.D. 137.4) and 14.3 mg/L (S.D. 8.2); 10.5-11.5 h 6.1 mg/L (S.D. 1.9), 4.0 mg/kg (S.D. 1.4), 76.0 mg/L (S.D. 47.7) and 7.9 mg/L (S.D. 4.6); and 23.5-24.5 h 2.1 mg/L (S.D. 0.5), 1.7 mg/kg (S.D. 0.7), 30.7 mg/L (S.D. 12.9) and 3.3 mg/L (S.D. 2.3). Concentrations at all sites exceeded MIC(90)s for the common respiratory pathogens Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.015 mg/L) and Streptococcus pneumoniae (0.06 mg/L). These data suggest that garenoxacin should be effective in the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

Administration, Oral↗

Comparison of three stool antigen tests for Helicobacter pylori detection.

BACKGROUND: Active Helicobacter pylori infection can be diagnosed by invasive (biopsy based) or non-invasive methods, such as stool antigen testing. AIMS: To compare three stool antigen enzyme immunoassay kits--Premier Platinum Hp SA, FemtoLab Cnx, and Hp Ag--with biopsy based methods for the detection of H pylori in previously undiagnosed patients. METHODS: One hundred and eleven adults with dyspepsia referred for endoscopy provided a stool sample for testing and had biopsies taken. Patients were considered H pylori positive if two out of three invasive tests were positive or if culture alone was positive. RESULTS: The sensitivities and specificities of the Premier Platinum Hp SA, FemtoLab Cnx, and Hp Ag stool antigen kits when compared with biopsy based diagnosis were, 63.6%, 88.0%, and 56.0% and 92.6%, 97.6%, and 97.6%, respectively. CONCLUSIONS: FemtoLab Cnx may be considered as an alternative to urea breath testing in the initial diagnosis of patients with dyspepsia who do not require immediate endoscopy. Stool testing has the potential advantages of being simple to perform, relatively cheap, and samples can be submitted directly from primary care.

Adult↗

Discrepancies in volume calculations between different radiotherapy treatment planning systems.

It has been determined that, contrary to expectation, there is a clinically significant variation in the volume calculations of different RTPS (Radiotherapy Treatment Planning System) for identical contours. The situation was investigated prior to a multi-centre trial to determine whether tumour volume is an independent prognostic factor in NSCLC (non-small cell lung cancer) and included four of the commercially available RTPS. The four RTPS tested were, Theraplan Plus V3.0, Cadplan V6.2, Focus V2.6 and ADAC V3.0. Five randomly chosen clinical target related volumes (3 GTVs, one PTV and one CTV) from the trial database originally marked on the Cadplan system were transferred to the other four systems and the resulting volumes were calculated. It was found that Cadplan consistently underestimated the volume relative to the other three systems by 6-12%. This systematic underestimation was found to be caused by different assumptions made by the Cadplan system about the axial outer slice extension of the volume. Cadplan truncates the volume, while the other three systems extrapolate it by half the slice thickness at each end. A short program was written to apply the same method of volume extension to the Cadplan volume that is utilised by the other systems. This produced calculated volumes that were within +/- 1.0% of the average of the volumes calculated by the other three planning systems, and the maximum deviation from the average for any planning system was then reduced to 1.5%. This program was implemented at all participating trial centres utilising Cadplan, thus reducing the intersystem variability to a negligible factor in comparison to the estimates of inter-physician variation. This unexpected finding has significant implications for the validity of multi-centre trials using dose volume histograms, and indeed the adoption of any clinical protocol employing dose volume histogram constraints derived from experience at another centre employing a different RTPS.

Carcinoma, Non-Small-Cell Lung↗

Display of positron emission tomography with Cadplan.

Recent clinical experience at Peter MacCallum Cancer Institute (PMCI) with the use of unregistered Positron Emission Tomography (PET) images for radiotherapy target marking in the lung suggests that co-registered PET images would be invaluable. PMCI has three radiotherapy treatment planning systems but none of them currently is able to display or co-register PET images with Computed Tomography (CT) images. This paper details the approach taken to display co-registered PET images with the CADPLAN treatment planning system. CT Image files are normally transferred to Cadplan by DICOM transfer, but the Cadplan DICOM server will not receive (has no presentation context for) PET images. The fundamental design of the CADPLAN system envisages display of only a single image dataset, which must be a CT scan for planning reasons. The problem of data transfer is crudely solved by File Transfer Protocol (FTP) over the network. Fortunately the multislice format of the PET image files makes individual transfer manageable. A menu based C program running at the same time as Cadplan is invoked to sample the DICOM PET Image and create multiple Cadplan CART image format files that are co-registered with each existing transverse CT slice. With the Cadplan in contour mode, the program allows the co-registered PET images to be swapped in and out of the image section of the CART files promptly, while keeping the contour information. This allows radiotherapy target volumes to be marked using transverse PET emission images, and effectively circumvents the design constraints prohibiting the display of more than one image set. Contours can be over-laid for review on reconstructed sagittal or coronal views of CT or PET images constructed using the standard Cadplan tools. Co-registration is facilitated by identical positioning with the aid of lasers and FDG loaded fiducial markers on the PET scanner and CT couch. A polyurethane cast fixed with EFFILOCK is used to ensure identical patient orientation on the CT and PET couches. Since both imaging modalities are without significant geometric distortion the co-registration is then simply a translation. PET transmission images can be used for co-registration verification. The practical implementation of display of PET images with CADPLAN has enabled us to begin a trial of 10 patients, the results of which will be reported separately.

Data Display↗

Usefulness of the presenting electrocardiogram in predicting myocardial salvage with thrombolytic therapy in patients with a first acute myocardial infarction.

AIMS: Patients with Q waves and T-wave inversion are generally at a later stage of the infarction process than patients without these changes. Our aim was to investigate whether a single assessment of electrocardiographic parameters at presentation would predict the proportion of myocardium salvageable by thrombolytic therapy. METHODS AND RESULTS: Electrocardiographic algorithms to calculate the potential and final infarct size have been developed and allow the proportion of myocardium salvageable with therapy to be calculated. This was measured in 146 patients with acute myocardial infarction who had angiography at a median of 91 min after streptokinase. The relationship between myocardial salvage and the electrocardiographic parameters at presentation (Q waves, T-wave inversion, quantitative ST segment changes, and the initial QRS score), was examined together with the 90-min angiographic parameters (TIMI flow grade and collateral grade), clinical parameters (haemodynamics and age), and time to therapy. Parameters that correlated with myocardial salvage included the initial QRS score (r=-0.56, P<0.0001), Q wave grade (r=-0.36, P<0.0001), number of leads with ST depression (r=0.28, P<0.001), maximum ST depression (r=0.27, P<0.01), T-inversion grade (r=-0.26, P<0.01), and TIMI flow grade at 90 min (r=0.21, P<0.02). The time from symptom onset to thrombolytic therapy did not correlate with salvage (r=-0.09). On multivariate analysis, only the initial QRS score and T-inversion grade on the initial electrocardiogram were independent predictors of salvage (multivariate r using both variables combined=0.57, P<0.001). CONCLUSIONS: The QRS score and T-wave inversion grade on the presenting electrocardiogram provide important information in predicting myocardial salvage. These parameters may help triage patients to appropriate therapies.

Angiography↗

Comparative study of the metabolism of drug substrates by human cytochrome P450 3A4 expressed in bacterial, yeast and human lymphoblastoid cells.

1. The aim was to compare the metabolic activity of human CYP3A4 expressed in bacteria (E. coli), yeast (S. cerevisiae) and human lymphoblastoid cells (hBl), with the native CYP3A4 activity observed in a panel of human livers. 2. Three CYP3A4 substrates were selected for study: dextromethorphan (DEM), midazolam (MDZ) and diazepam (DZ). The substrate metabolism in each of the four systems was characterized by deriving the kinetic parameters K(m) or S(50), V(max) and intrinsic clearance (CL(int)) or maximum clearance (CL(max)) from the kinetic profiles; the latter differing by 100-fold across the three substrates. 3. The K(m) or S(50) for the formation of metabolites 3-methoxymorphinan (MEM), 1'-hydroxymidazolam (1'-OH MDZ) and 3-hydroxydiazepam (3HDZ) compared well in all systems. For CYP3A4-mediated metabolism of DEM, MDZ and DZ, the V(max) for hBl microsomes were generally 2-9-fold higher than the respective yeast and human liver microsomes and E. coli membrane preparations, resulting in greater CL(int) or CL(max). In the case of 3HDZ formation, non-linear kinetics were observed for E. coli, hBl microsomes and human liver microsomes, whereas the kinetics observed for S. cerevisiae were linear. 4. The use of native human liver microsomes for drug metabolic studies will always be preferable. However, owing to the limited availability of human tissues, we find it is reasonable to use any of the recombinant systems described herein, since all three recombinant systems gave good predictions of the native human liver enzyme activities.

Adult↗

Subcellular localization of peroxidase in tomato fruit skin and the possible implications for the regulation of fruit growth.

The cessation of tomato fruit growth has been associated with the appearance of three 'wall-bound' peroxidase isozymes in the skin of tomato fruit. However, the presence of these isozymes in the ionically eluted 'wall-bound' fraction may be an artefact of either non-specific binding of symplastic peroxidase to the cell wall, or isozymes bound to membranes included in the 'wall-bound' fraction. Therefore, subcellular localization of peroxidase in both immature and mature tomato fruit skins was studied. Immature fruits showed intense peroxidase activity associated with the tonoplast and pro-vacuolar membranes, but little or no activity associated with the cell wall. However, the presence of peroxidase activity within the cell wall of mature green fruits was confirmed. Furthermore, peroxidase activity was also observed associated with the plasma membrane and large vesicles allied to the plasma membrane. While cross-linking in cell wall components was previously assumed to be the mechanism by which peroxidase might control fruit growth, the incorporation of 'lignin-like' phenolics may also play a part. Isoelectric focusing (IEF) of both symplastic and apoplastic peroxidase extracted from immature and mature tomato fruit skin showed that all peroxidase isozymes present were highly anionic. In this current study, histochemical techniques are used to demonstrate a developmental increase in 'lignin-like' phenolics within the sub-cuticular cell walls of the fruit skin. The localization of peroxidase within tomato fruit skin is discussed in relation to its potential role in the regulation of tomato fruit growth.

Cell Wall↗

Partial purification of tomato fruit peroxidase and its effect on the mechanical properties of tomato fruit skin.

Peroxidase (EC 1.11.1.7)-mediated stiffening of cell walls within the fruit skin of tomato is hypothesized to regulate fruit growth. However, to date, there is no experimental evidence demonstrating that peroxidase affects the mechanical properties of skin tissue. Here, the mechanical properties of skin strips excised from a range of fruits at different ages were determined using an 'Instron' universal material testing instrument. The stiffness of tomato fruit skin strips increases 3-fold with increasing fruit age. Application of partially-purified peroxidase from the cell walls of mature tomato fruit skin significantly increased the stiffness of fruit skin irrespective of the age of fruit. Furthermore, the application of hydrogen peroxide significantly increased the stiffness of skin strips excised from fruit of an age when endogenous peroxidase isozymes associated with the termination of growth are first detected. The results support the hypothesis that the tomato fruit skin plays an integral role in the regulation of tomato fruit growth, and that changes in its mechanical properties may be mediated by peroxidase. As far as is known, this is the first demonstration that peroxidases alter the mechanical properties of the plant cell wall.

Electrophoresis, Polyacrylamide Gel↗