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Biomedical subjects

A Ross

Publications and source records attributed to A Ross.

At least 19 recordsLinked to original sources
PubMed2006

In vivo micro-CT lung imaging via a computer-controlled intermittent iso-pressure breath hold (IIBH) technique.

Respiratory research with mice using micro-computed tomography (micro-CT) has been predominantly hindered by the limited resolution and signal-to-noise ratio (SNR) as a result of respiratory motion artefacts. In this study, we develop a novel technique for capturing the lung microstructure in vivo using micro-CT, through a computer-controlled intermittent iso-pressure breath hold (IIBH), to reduce respiratory motion, increasing resolution and SNR of reconstructed images. We compare four gating techniques, i.e. no gating, late expiratory (LE) gating, late inspiratory (LI) gating and finally intermittent iso-pressure breath hold (IIBH) gating. Quantitatively, we compare several common image analysis methods used to extract valuable physiologic and anatomic information from the respiratory system, and show that the IIBH technique produces the most representative and repeatable results.

Animals↗
PubMed2006

Clinical determinants of dementia and mild cognitive impairment following ischaemic stroke: the Sydney Stroke Study.

BACKGROUND: Dementia following stroke is common but its determinants are still incompletely understood. METHODS: In the Sydney Stroke Study, we performed detailed neuropsychological and medical-psychiatric assessments on 169 patients aged 50-85 years, 3-6 months after a stroke, and 103 controls with a majority of both groups undergoing MRI brain scans. Stroke subjects were diagnosed as having vascular mild cognitive impairment (VaMCI) or vascular dementia (VaD) or no cognitive impairment by consensus. Demographic, functional, cerebrovascular risk factors and neuroimaging parameters were examined as determinants of dementia using planned logistic regression. RESULTS: 21.3% of subjects were diagnosed with VaD, with one case in those aged 50-59 years, 24% in those aged 60-69 years and 23% in those 70-79 years. There was no difference by sex. The prevalence of VaMCI was 36.7%. VaD subjects had lower premorbid intellectual functioning and had 0.9 years less education than controls. The VaD and VaMCI groups did not differ from the no cognitive impairment group on any specific cerebrovascular risk factor, however overall those with impairment had a greater number of risk factors. They did not differ consistently on depression severity, homocysteine levels and neuroimaging parameters (atrophy, infarct volume and number of infarcts) except for an excess of white matter lesions on MRI and greater number of infarcts in the VaD and VaMCI groups. On a series of logistic regression analyses, stroke volume and premorbid function were significant determinants of cognitive impairment in stroke patients. CONCLUSION: Post-stroke dementia and MCI are common, especially in older individuals. Cerebrovascular risk factors are not independent risk factors for VaD, but stroke volume is a significant determinant of dementia. Premorbid functioning is a determinant of post- stroke impairment.

Aged↗
PubMed2005

Comparison of axillary, rectal and tympanic temperature measurements in children admitted with malaria.

We compared axillary, rectal and tympanic temperatures in children admitted with severe malaria. The axillary temperatures were 0.74 degrees C (95% limits of agreement -0.85 to 2.33 degrees C) less than rectal temperatures and tympanic temperatures 0.42 degrees C (95% limits of agreement -0.16 to 2.44 degrees C) less than rectal temperatures. The difference was greater on admission than 24 hours later. These differences may be important in defining criteria for clinical syndromes.

Axilla↗
PubMed2004

Optimised fermentation strategy for 13C/15N recombinant protein labelling in Escherichia coli for NMR-structure analysis.

A widely applicable cultivation strategy, which reduces the costs of expensive isotopes, is designed for maximal (98-100%) incorporation of [13C] and [15N] into labelled recombinant protein expressed in Escherichia coli, allowing better assignment of the resonances for NMR studies. Isotope labelling of the culture was performed throughout the complete process, starting from preculture. Sufficient biomass is first generated in a batch phase. Upon consumption of glucose, identified by a sharp drop of on-line monitored oxygen consumption, expression is induced and cultivation is continued under glucose-limited conditions as fed-batch process. Thereby a quantitative utilisation of the most expensive component [13C]-glucose is achieved, while the approximate amount of the [15N]-ammonium chloride to be incorporated is calculated from the scheduled biomass. The usefulness of the strategy is demonstrated with production of uniformly [13C/15N]-labelled tryparedoxin of Crithidia fasciculata. Ideal isotope incorporation and product quality is documented by MALDI-TOF mass spectrometry and two- and three-dimensional NMR spectra.

Carbon Isotopes↗
PubMed2004

Improving malaria home treatment by training drug retailers in rural Kenya.

Recent global malaria control initiatives highlight the potential role of drug retailers to improve access to early effective malaria treatment. We report on the findings and discuss the implications of an educational programme for rural drug retailers and communities in Kenya between 1998 and 2001 in a study population of 70,000. Impact was evaluated through annual household surveys of over-the-counter (OTC) drug use and simulated retail client surveys in an early (1999) and a late (2000) implementation area. The programme achieved major improvements in drug selling practices. The proportion of OTC anti-malarial drug users receiving an adequate dose rose from 8% (n = 98) to 33% (n = 121) between 1998 and 1999 in the early implementation area. By 2001, and with the introduction of sulphadoxine pyrimethamine group drugs in accordance with national policy, this proportion rose to 64% (n = 441) across the early and late implementation areas. Overall, the proportion of shop-treated childhood fevers receiving an adequate dose of a recommended anti-malarial drug within 24 h rose from 1% (n = 681) to 28% (n = 919) by 2001. These findings strongly support the inclusion of private drug retailers in control strategies aiming to improve prompt effective treatment of malaria.

Antimalarials↗
PubMed2004

A randomised, controlled trial of once daily and multi-dose daily gentamicin in young Kenyan infants.

AIMS: To test the suitability of a simple once daily (OD) gentamicin regimen for use in young infants where routine therapeutic drug monitoring is not possible. METHODS: In an open, randomised, controlled trial, infants with suspected severe sepsis admitted to a Kenyan, rural district hospital received a novel, OD gentamicin regimen or routine multi-dose (MD) regimens. RESULTS: A total of 297 infants (over 40% < or =7 days) were randomised per protocol; 292 contributed at least some data for analysis of pharmacological endpoints. One hour after the first dose, 5% (7/136) and 28% (35/123) of infants in OD and MD arms respectively had plasma gentamicin concentrations <4 microg/ml (a surrogate of treatment inadequacy). Geometric mean gentamicin concentrations at this time were 9.0 microg/ml (95% CI 8.3 to 9.9) and 4.7 microg/ml (95% CI 4.2 to 5.3) respectively. By the fourth day, pre-dose concentrations > or =2 microg/ml (a surrogate of potential treatment toxicity) were found in 6% (5/89) and 24% (21/86) of infants respectively. Mortality was similar in both groups and clinically insignificant, although potential gentamicin induced renal toxicity was observed in <2% infants. CONCLUSIONS: A "two, four, six, eight" OD gentamicin regime, appropriate for premature infants and those in the first days and weeks of life, seems a suitable, safe prescribing guide in resource poor settings.

Anti-Bacterial Agents↗
PubMed2004

Steroid signalling in human ovarian surface epithelial cells: the response to interleukin-1alpha determined by microarray analysis.

The human ovarian surface epithelium (HOSE) is a common site of gynaecological disease including endometriosis and ovarian cancer, probably due to serial injury-repair events associated with successive ovulations. To comprehend the importance of steroid signalling in the regulation of the HOSE, we used a custom microarray to catalogue the expression of over 250 genes involved in the synthesis and reception of steroid hormones, sterols and retinoids. The array included a subset of non-steroidogenic genes commonly involved in pro-/anti-inflammatory signalling. HOSE cells donated by five patients undergoing surgery for non-malignant gynaecological conditions were cultured for 48 h in the presence and absence of 500 pg/ml interleukin-1alpha (IL-1alpha). Total RNA was reverse-transcribed into biotin-labelled cDNA, which was hybridised to the array and visualised by gold-particle resonance light scattering and charge-coupled device (CCD) camera detection. Results for selected genes were verified by quantitative reverse-transcription PCR. In five out of five cases, untreated HOSE cells expressed genes encoding enzymes required for de novo biosynthesis of cholesterol from acetate and subsequent formation of C21-pregnane and C19-androstane steroids. Consistent with the inability of HOSE cells to synthesise glucocorticoids, oestrogens or 5alpha-reduced androgens de novo, CYP21, CYP19 and 5alpha-reductase were not detected. The only steroidogenic gene significantly up-regulated by IL-1alpha was 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1). Other cytokine-induced genes were IL-6, IL-8, nuclear factor kappaB (NFkappaB) inhibitor alpha, metallothionein-IIA and lysyl oxidase: inflammation-associated genes that respond to glucocorticoids. The only steroidogenic gene significantly suppressed by IL-1alpha was 3betaHSD1. Other genes suppressed by IL-1alpha were aldehyde dehydrogenase (ALDH) 1, ALDH 10, gonadotrophin hormone-releasing hormone receptor, peroxisome proliferation-activated receptor-binding protein (PPAR-bp) and nuclear receptor subfamily 2 group F member 2. These results define a steroidogenic phenotype of cultured HOSE cells and provide a limited expression profile for genes with associated signalling functions. IL-1alpha co-ordinately induces 11betaHSD1 and a panel of glucocorticoid-regulated, inflammation-associated genes in HOSE cells, providing further evidence that cortisol generated by 11betaHSD1 could participate in the local resolution of inflammation associated with ovulation.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2004

Invasive group A streptococcal disease in North Queensland (1996 - 2001).

BACKGROUND & OBJECTIVES: The incidence of group A streptococcal (GAS) invasive infections have been increasing worldwide. The aim of this study was to characterize clinical and microbiological features of isolates obtained from invasive GAS infections in North Queensland, Australia between 1996 and 2001. METHODS: Clinical and demographic data were collected prospectively. Isolates were biotyped, emm sequenced, M typed and tested for antibiotic sensitivity using E-test. Detection of the presence of the streptococcal pyrogenic exotoxin (spe) and fibronectin binding protein (prtF1) genes was also carried out. RESULTS: There were 109 isolates from blood and sterile sites. All isolates were sensitive to penicillin. Tetracycline and erythromycin resistance was seen in 11 and 2.7 per cent of isolates respectively. The isolates were evenly distributed by age and sex. The overall mortality was 7 per cent and there were 18 cases of streptococcal toxic shock syndrome (STSS) in which the mortality was 22 per cent. Indigenous patients had a crude incidence rate of 82.5 per 100,000 per year compared with 10.3 per 100,000 per year in the non-indigenous patients. There was no predominance of emm / M type or association of spe type with STSS. There was also no relationship between the presence of the prtF1 gene and invasive disease. INTERPRETATION & CONCLUSION: Invasive group A streptococci from North Queensland are similar to those from the Northern Territory of Australia in that no single strain is predominant. The indigenous population is overrepresented. Invasiveness and the development of streptococcal toxic shock is not related to the presence of the prtF1 gene or spe a or c.

Adhesins, Bacterial↗
PubMed2003

Prognostic indicators of early and late death in children admitted to district hospital in Kenya: cohort study.

OBJECTIVES: To identify clinical indicators of immediate, early, and late mortality in children at admission to a sub-Saharan district hospital and to develop prognostic scores. DESIGN: Prospective cohort study. SETTING: One district hospital in Kenya. PARTICIPANTS: Children aged over 90 days admitted to hospital from 1 July 1998 to 30 June 2001. MAIN OUTCOME MEASURES: Prognostic indicators of mortality. RESULTS: Of 8091 children admitted up to 1 June 2000, 436 (5%) died. Sixty (14%) died within four hours after admission (immediate), 193 (44%) after 4-48 hours (early), and 183 (42%) after 48 hours (late). There were marked differences in the clinical features associated with immediate, early, and late death. Seven indicators (neurological status, respiratory distress (subcostal indrawing or deep breathing), nutritional status (wasting or kwashiorkor), severe anaemia, jaundice, axillary temperature, and length of history) were included in simplified prognostic scores. Data from 4802 children admitted from 1 July 2000 to 30 June 2001 were used to validate the scores. For simplified prognostic scores the areas under the receiver operating characteristic curves were 0.93 (95% confidence interval 0.92 to 0.94), 0.82 (0.80 to 0.83), and 0.82 (0.81 to 0.84) for immediate, early, and late death, respectively. CONCLUSION: In children admitted to a sub-Saharan hospital, the prognostic indicators of early and late deaths differ but a small number of simple clinical signs predict outcome well.

Cause of Death↗
PubMed2003

Abnormal blood glucose concentrations on admission to a rural Kenyan district hospital: prevalence and outcome.

AIMS: To determine the prevalence, clinical characteristics, and outcome of hypoglycaemia on admission in children at a rural Kenyan district hospital. METHODS: Observational study of 3742 children (including 280 neonates) in Kilifi District Hospital, Kenya. MAIN OUTCOME MEASURES: hypoglycaemia (blood glucose <2.2 mmol/l) and hyperglycaemia (blood glucose >10.0 mmol/l). RESULTS: Non-neonates: the prevalence of hypoglycaemia on admission was 7.3%. Severe illness, malnutrition, last meal >12 hours ago, and a positive malaria slide were independently associated with hypoglycaemia. Overall, mortality in hypoglycaemic children was 20.2% compared to 3.8% in normoglycaemic children (p < 0.001). The brunt of mortality in hypoglycaemic children was borne by those who were severely ill or malnourished (31.8%) as opposed to those who were neither severely ill nor malnourished (9.0%). Neonates: 23.0% of neonates were hypoglycaemic on admission. Inability to breast feed and weight <2500 g were independently associated with hypoglycaemia. Mortality was 45.2% compared to 19.6% in normoglycaemic neonates (p < 0.001). Hyperglycaemia was present in 2.7% of children and was associated with a higher mortality than normoglycaemia, 14.0% versus 3.8% respectively (p < 0.001). CONCLUSIONS: Hypoglycaemia is common in children admitted to a rural Kenyan district hospital and is associated with an increased mortality. Apart from features of severe illness and poor feeding, clinical signs have a low sensitivity and specificity for hypoglycaemia. Where diagnostic facilities are lacking, presumptive treatment of severely ill children is recommended. For other children, the continuation of feeding (by nasogastric tube if necessary) should be part of standard management.

Age Distribution↗
PubMed2002

Frequency of postoperative nausea and vomiting in patients undergoing laparoscopic foregut surgery.

BACKGROUND: Wrap disruption or intrathoracic herniation of a fundoplication is a dreaded complication of laparoscopic foregut surgery. This problem may often be related to postoperative nausea and vomiting (PONV). This study aimed to investigate the occurrence of PONV and its management in patients undergoing laparoscopic foregut procedures. METHODS: Between January 31 and May 23, 2000, 104 patients undergoing laparoscopic foregut procedures (fundoplication, myotomy, or paraesophageal hernia repair) were followed prospectively. Their postoperative course was documented along with the occurrence and management of PONV. All laparoscopic foregut surgery patients are managed postoperatively with a uniform clinical pathway, and their care is focused on a nursing unit with skill and experience in postoperative management. RESULTS: Nausea was documented in the postanesthesia care unit (PACU) for 30.1% of the patients, and for 59.6% of the patients during their nursing unit stay. Antiemetics were given to all the patients with documented nausea. Emesis was noted in 1.9% of the patients in the PACU, as compared with 3.8% of the patients on the floor. In one of the patients with nursing unit emesis, an acute wrap herniation into the chest occurred, necessitating a return to the operating room for correction. The patients with a history of postoperative nausea did not have a higher rate of PONV than in those with no history of postoperative nausea. The use of preoperative or intraoperative antiemetics did not appear to alter the occurrence of PONV. Postoperative nausea occurred in 60% of the patients administered preoperative antiemetic, as compared with 64% of the patients who received no preoperative antiemetic. The average length of hospital stay was longer in those with PONV than in those with no PONV (2.6 vs 1.8 days). CONCLUSION: Nausea after laparoscopic foregut procedures is common, occurring twice as often on the nursing unit as in the PACU. The occurrence of PONV leads to a longer hospital stay, and can result in significant sequelae requiring reoperation. The use of preoperative or intraoperative antiemetics does not alter the frequency of postoperative nausea, suggesting the need to develop effective preemptive regimens for patients undergoing laparoscopic foregut procedures. The high rate of PONV and its potential risk of damage to a fundoplication and hiatal hernia repair should lead surgeons to consider whether laparoscopic foregut procedures should ever be performed on an outpatient basis.

Antiemetics↗
PubMed2002

Genetic diversity of Plasmodium falciparum parasites from Kenya is not affected by antifolate drug selection.

The genotypes of merozoite surface protein-1, merozoite surface protein-2 and glutamine rich protein are frequently used to distinguish recrudescence from reinfection when parasitaemia reappears after antimalarial drug treatment. However, none of the previous reports has clearly assessed the change of genetic diversity following drug treatment. In the present study, we have assessed the impact of pyrimethamine/sulfadoxine and chlorproguanil/dapsone on the genetic diversity of isolates and the multiplicity of infection in patient isolates from Kilifi, Kenya. We have analysed the length polymorphism of merozoite surface protein-1, merozoite surface protein-2 and glutamine rich protein and the data clearly show that treatment with pyrimethamine/sulfadoxine and chlorproguanil/dapsone did not change the multiplicity of infection found in patients, in contrast to the selection that these drugs exert on the genes encoded by the target enzymes. In addition, we report that children of less than 2 years tend to have fewer numbers of clones per isolate when compared with older children. Overall, this study shows that the selection for genes that confer drug resistance is not a factor in reducing the genetic diversity of parasite clones in a patient.

Age Distribution↗
PubMed2002

Report of the Tumor Evaluation Committee workshops at ISHAGE 2001.

Multiple factors impact polymerase chain reaction (PCR) detection of tumor cells ranging from the fundamental, such as selection of targets for amplification, to the practical, including the timing of sample processing, granulocyte contamination and anticoagulant used. Much more work, including standardization studies, remains to be performed. Tumor enrichment can be achieved either by positive selection, generally by use of antibodies or by depletion of (CD45(+)) hematopoietic cells. Both approaches work and each has advantages and disadvantages. Enriched tumor cells can be further analyzed for expression of prognostic markers. A future area of emphasis should be to establish a dialogue between practitioners of tumor detection and developers of new therapies who are in search of surrogate markers of outcomes.

Biomarkers, Tumor↗
PubMed2002

Partial rescue of the Dazl knockout mouse by the human DAZL gene.

Y-chromosomal DAZ (deleted in azoospermia) and autosomal DAZ-like (DAZL) comprise a gene family involved in gametogenesis. Y-chromosomal and autosomal genes only co-exist in humans and old world monkeys, indicating that DAZ genes are a recent acquisition of the Y chromosome. In most mammals, the ancestral Dazl alone is sufficient to complete gametogenesis. It is not yet understood why humans and old world monkeys have a second set of genes that are apparently necessary for spermatogenesis, since deletions removing the Y-chromosomal DAZ are often associated with azoo- or oligospermia. We used transgenic mice carrying either human DAZL or human DAZ on a mouse Dazl null background to investigate the functions of the human homologues. Both transgenes enabled prophase spermatocytes to be produced, mainly of the leptonema/zygonema stage, but failed to promote differentiation into mid- to late pachytenes. The presence of human DAZL resulted in a larger amount of early germ cells compared with that observed in DAZ. The degree of rescue was independent of copy number, integration site or presence of the DAZ repeat region for the DAZ transgenes. These findings confirm that DAZL and DAZ can only substitute for early functions of the murine homologue resulting in the establishment of the germ cell population and partial progression into meiosis.

Animals↗
PubMed2002

Scrapie epidemic in a fully PrP-genotyped sheep flock.

In scrapie-affected sheep flocks, host PrP genotype plays a vital role in determining which sheep will succumb to scrapie and the incubation period. Consequently, within-flock scrapie dynamics is best understood within the context of the genotype profile of the flock. Here we describe a 17 month epidemic of scrapie in a commercially farmed flock of 230 genotyped Texel sheep. At the start of the study, 70% of the sheep were of three genotypes only: ARR/ARQ, ARH/ARQ and ARQ/ARQ. Only 15% of sheep encoded the disease-associated VRQ allele and only a single sheep (0.4%) was of the most susceptible VRQ/VRQ genotype. For susceptible genotypes there was a marked deficit (P<0.025) of older animals (> or =3 years), implying that some cases of scrapie had occurred previously. In the ensuing 17 months, 18 sheep of known genotype were confirmed positive for the disease: seven VRQ/ARQ, six VRQ/ARH, two VRQ/ARR, three ARQ/ARQ. Median ages at death were 2.7, 2.8, 4.2 and 3.8 years respectively. Mortality rates were 55, 86, 13 and 3% respectively. Survival analysis revealed a highly significant effect of genotype on survivorship, but no difference between VRQ/ARQ and VRQ/ARH, or between VRQ/ARR and ARQ/ARQ. There was no difference in the survivorship of middle- and older-age cohorts of susceptible sheep. Scrapie risk group (as defined by PrP genotype) was not associated with submission as a scrapie suspect but later found to be negative, or with dying of unknown causes on the farm.

Age Factors↗
PubMed2001

Peripheral blood dendritic cells in children with acute Plasmodium falciparum malaria.

The importance of dendritic cells (DCs) for the initiation and regulation of immune responses not only to foreign organisms but also to the self has raised considerable interest in the qualitative and quantitative analysis of these cells in various human diseases. Plasmodium falciparum malaria is characterized by the poor induction of long-lasting protective immune responses. This study, therefore, investigated the percentage of peripheral blood DCs as lineage marker-negative and HLA-DR(+) or CD83(+) cells in healthy children and in children suffering from acute malaria in Kilifi, Kenya. Comparable percentages of CD83(+) DCs were found in peripheral blood of healthy children and children with malaria. However, the percentage of HLA-DR(+) peripheral blood DCs was significantly reduced in children with malaria. The results suggest that a proportion of peripheral blood DCs may be functionally impaired due to the low expression of HLA-DR on their surface.

Acute Disease↗
PubMed2001

Stable gene expression from a mammalian artificial chromosome.

We have investigated the potential of PAC-based vectors as a route to the incorporation of a gene in a mammalian artificial chromosome (MAC). Previously we demonstrated that a PAC (PAC7c5) containing alpha-satellite DNA generated mitotically stable MACs in human cells. To determine whether a functional HPRT gene could be assembled in a MAC, PAC7c5 was co-transfected with a second PAC containing a 140 kb human HPRT gene into HPRT-deficient HT1080 cells. Lines were isolated containing a MAC hybridizing with both alpha-satellite and HPRT probes. The MACs segregated efficiently, associated with kinetochore proteins and stably expressed HPRT message after 60 days without selection. Complementation of the parental HPRT deficiency was confirmed phenotypically by growth on HAT selection. These results suggest that MACs could be further developed for delivering a range of genomic copies of genes into cells and that stable transgene expression can be achieved.

Blotting, Northern↗