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Biomedical subjects

A Morris

Publications and source records attributed to A Morris.

At least 37 records · Page 2Linked to original sources
PubMed2004

Segregation of QTL for production traits in commercial meat-type chickens.

This study investigated whether quantitative trait loci (QTL) identified in experimental crosses of chickens provide a short cut to the identification of QTL in commercial populations. A commercial population of broilers was targeted for chromosomal regions in which QTL for traits associated with meat production have previously been detected in extreme crosses. A three-generation design, consisting of 15 grandsires, 608 half-sib hens and over 15 000 third-generation offspring, was implemented within the existing breeding scheme of a broiler breeding company. The first two generations were typed for 52 microsatellite markers spanning regions of nine chicken chromosomes and covering a total of 730 cM, approximately one-fifth of the chicken genome. Using half-sib analyses with a multiple QTL model, linkage was studied between these regions and 17 growth and carcass traits. Out of 153 trait x region comparisons, 53 QTL exceeded the threshold for genome-wide significance while an additional 23 QTL were significant at the nominal 1% level. Many of the QTL affect the carcass proportions and feed intake, for which there are few published studies. Given intensive selection for efficient growth in broilers for more than 50 generations it is surprising that many QTL affecting these traits are still segregating. Future fine-mapping efforts could elucidate whether ancestral mutations are still segregating as a result of pleiotropic effects on fitness traits or whether this variation is due to new mutations.

Analysis of Variance↗
PubMed2004

A study of association between genetic markers in candidate genes and reproductive traits in one generation of a commercial broiler breeder hen population.

Markers of alleles for three physiological candidate genes for reproductive traits, growth hormone (GHR), gonadotropin-releasing hormone receptor (GNRHR) and neuropeptide Y (NPY) were assessed for the association with the total egg production, number of double-yolked eggs and age at first egg in a single generation of a broiler breeder (Gallus gallus) pedigree dam line. Single-nucleotide polymorphisms and deletions were detected in the GHR, GNRHR and NPY genes. Genotypes were identified using a PCR-RFLP assay. The frequency of restriction enzyme+/-alleles in the population was for GHR 0.68 (NspI-) and 0.32 (NspI+), for NPY 0.78 (DraI+) and 0.22 (DraI-) and for GNRHR 0.54 (Bpu1102I+) and 0.46 (Bpu1102I-). Trait data from a total of 772 hens in 67 sire families from one generation of the pedigree dam line were recorded. However, the analysis used only the offspring of heterozygous sires to reduce the influence of selection and genetic background (n=33 sire families for GHR; n=14 sire families for NPY; n=36 sire families for GNRHR). A dominance effect of NPY on age at first egg and an additive effect of GNRHR on the number of double-yolked eggs were found (P<0.05).

Animals↗
PubMed2004

The effects of selective cytokine inhibitory drugs (CC-10004 and CC-1088) on VEGF and IL-6 expression and apoptosis in myeloma and endothelial cell co-cultures.

Myeloma cells and human umbilical vein endothelial cells (HUVECs) were co-cultured to model in vitro the interactions between myeloma and endothelium, and treated with thalidomide and two selective cytokine inhibitory drugs (SelCIDs, phosphodiesterase-4 inhibitors). Flow cytometry and enzyme-linked immunosorbent assay were used to assess production of two key cytokines--vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6)--and apoptosis in co-cultured HUVECs and myeloma cells. VEGF was produced by both myeloma cells and HUVECs, while IL-6 was almost exclusively produced by endothelial cells. In co-culture, there was significant up-regulation of VEGF and IL-6 production compared with the sum of separate myeloma and endothelial cell cultures. SelCIDs markedly inhibited production of both cytokines in co-cultures, with CC-10004 being more potent than CC-1088. In addition, SelCIDs induced myeloma cell apoptosis. Apoptosis in co-cultured myeloma cells was significantly lower than in those cultured separately, suggesting that co-culture partially protected myeloma cells from drug-induced apoptosis. This protective effect was probably due to IL-6 produced by endothelial cells in co-culture as addition of anti-IL-6 neutralizing antibody, but not anti-VEGF antibody, abrogated it. In conclusion, SelCIDs can exert their anti-myeloma activity through two mechanisms, i.e. inhibition of VEGF and IL-6 production by interacting myeloma and endothelium and induction of myeloma cell apoptosis.

Angiogenesis Inhibitors↗
PubMed2004

A primary field compensation scheme for planar array magnetic induction tomography.

In biomedical magnetic induction tomography (MIT), measurement precision may be improved by incorporating some form of primary field compensation/cancellation scheme. Schemes which have been described previously include gradiometric approaches and the use of 'back-off' coils. In each of these methods, however, the primary field cancellation was achieved only for a single transmitter/receiver combination. For the purpose of imaging, it would be desirable for a fully electronically scanned MIT system to provide a complete set of measurements, all with the primary field cancelled. A single channel suitable for incorporation into an MIT system with planar-array geometry is described. The transmitter is a 6-turn coil of wire 5 cm in diameter. The receiver is a surface mount inductor, of inductance 10 microH, mounted such that, in principle, no net primary field flux threads it. The results of measurements carried out with the single channel system suggest that the signal due to the primary excitation field can be reduced on average by a factor of 298 by the sensor geometry over the operating frequency range 1-10 MHz. The standard deviation and drift of the signal with the system adjusted for maximum primary field cancellation, expressed as a percentage of the signal when the receiver coil was rotated until its axis of sensitivity lay along the primary field, were 0.0009% and 0.009%, respectively. The filter time constant used was 30 ms.

Artifacts↗
PubMed2003

Intravenous nicardipine for treatment of postcoarctectomy hypertension in children.

Our objective was to evaluate the efficacy of intravenous (IV) nicardipine for the treatment of postcoarctectomy hypertension in children with coarctation of the aorta. We carried out a retrospective review in a pediatric intensive care unit at a tertiary care children's hospital. The patients were children with coarctation of the aorta treated for postcoarctectomy hypertension. Children with postcoarctectomy hypertension defined as a systolic blood pressure >95th percentile for age measured by indwelling arterial catheter were treated with IV nicardipine. We measured change in mean arterial blood pressure (MAP), mean systolic and diastolic blood pressure, and mean heart rate (HR) from baseline after initiating treatment with IV nicardipine. The outcome measure was a reduction in MAP and mean systolic and diastolic blood pressure after treatment with IV nicardipine. During a 4-year period, 10 children met the study criteria. Median age was 3.25 months (range, 0.25 to 180 months). Initial median treatment dose of IV nicardipine was 1.0 micro g/kg/min (range, 0.5 to 6 micro g/kg/min); median dose used to control hypertension was 1.5 micro g/kg/min (range, 0.25 to 6 micro g/kg/min). Median duration of therapy was 26.3 h (range, 13 to 49 h). Treatment with IV nicardipine resulted in a 26.5% decrease in MAP from baseline during the first hour of treatment ( p = 0.0006). Mean systolic blood pressure decreased from 133 to 105 mmHg ( p = 0.005), and mean diastolic blood pressure decreased from 75 to 52.5 mmHg ( p = 0.001) during the first hour of therapy with nicardipine. There was a significant reduction ( p = 0.0005) in MAP during continued treatment with IV nicardipine. The mean HR of 150 remained unchanged during the first hour of therapy with nicardipine, and no significant change in mean HR or adverse effects was noted during continued therapy. Two children receiving other antihypertensive therapy demonstrated further reduction in their blood pressure when IV nicardipine was initiated. Tachycardia and hypotension were not observed in any child treated with IV nicardipine. We concluded that IV nicardipine reduced MAP with no significant change in mean HR and no adverse effects in patients with postcoarctectomy hypertension. Nicardipine produced a further reduction in MAP in children receiving other antihypertensive agents. Nicardipine is an effective agent for treatment of postcoarctectomy hypertension in children with coarctation of the aorta.

Antihypertensive Agents↗
PubMed2003

Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes.

AIMS/HYPOTHESIS: Although ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1 diabetes. The Diabetes UK cohort, essentially one of patients with Type 1 diabetes, now has sufficient follow-up to report all heart disease, and specifically ischaemic heart disease, mortality rates by age. METHODS: A cohort of 23,751 patients with insulin-treated diabetes, diagnosed under the age of 30 years and from throughout the United Kingdom, was identified during the period 1972 to 1993 and followed for mortality until December 2000. Age- and sex-specific heart disease mortality rates and standardised mortality ratios were calculated. RESULTS: There were 1437 deaths during the follow-up, 536 from cardiovascular disease, and of those, 369 from ischaemic heart disease. At all ages the ischaemic heart disease mortality rates in the cohort were higher than in the general population. Mortality rates within the cohort were similar for men and women under the age of 40. The standardised mortality ratios were higher in women than men at all ages, and in women were 44.8 (95%CI 20.5-85.0) at ages 20-29 and 41.6 (26.7-61.9) at ages 30-39. CONCLUSIONS/INTERPRETATION: The risk of mortality from ischaemic heart disease is exceptionally high in young adult women with Type 1 diabetes, with rates similar to those in men with Type 1 diabetes under the age of 40. These observations emphasise the need to identify and treat coronary risk factors in these young patients.

Adolescent↗
PubMed2003

Surgical management of intracranial gliomas--does radical resection improve outcome?

UNLABELLED: This paper discusses the arguments for and against radical tumor resection as a strategy for treatment of cerebral gliomas. METHOD: Data from the Glioma Outcome Project were analyzed to determine whether survival could be related to extent of resection in 666 patients treated by biopsy or resection for malignant cerebral gliomas. FINDINGS: Consistent survival advantages were noted for those patients treated with resection. INTERPRETATION: This observational study, although undoubtedly reflecting selection bias, provides data that support resection as a major factor in survival after surgery for malignant gliomas.

Adult↗
PubMed2003

Magnetic induction tomography: phase versus vector-voltmeter measurement techniques.

In magnetic induction tomography (MIT) the in-quadrature component, and hence the phase, of the received signal contains information about the conductivity of the tissue. The quality of imaging will depend on the precision with which phase can be measured. Preliminary studies suggest that a precision of 10 m degrees may be required for a practical biomedical MIT system operating at 10 MHz. This paper describes the results of measurements carried out with a 16-channel, downconverting, 10 MHz, MIT system utilizing two types of data extraction techniques: direct-phase measurement and measurement of the in-phase and in-quadrature components of the signal with a vector voltmeter. The basic precision provided by each technique was 50 m degrees, with thermal drift representing the major limiting factor. Preliminary measurements of average conductivity and permittivity for a human thigh in vivo are given.

Artifacts↗
PubMed2003

Systemic exposure, tolerability, and efficacy of pimecrolimus cream 1% in atopic dermatitis patients.

AIMS: To measure pimecrolimus blood concentrations and to evaluate tolerability and efficacy in children and infants treated topically for atopic dermatitis with pimecrolimus cream 1% for three weeks. METHODS: Three open label, non-controlled, multiple topical dose studies were conducted in children aged 8-14 years (study A, ten patients), and in infants aged 8-30 months (study B, eight patients) and 4-11 months (study C, eight patients). Pimecrolimus blood concentrations were determined on days 4 and 22 of treatment, and at end of study. Efficacy was assessed using the Eczema Area and Severity Index (EASI). RESULTS: Pimecrolimus blood concentrations were consistently low, typically (81%) below 1 ng/ml, with more than half of the measurements below the assay limit of quantitation (0.5 ng/ml) in studies A and B. The highest blood concentration measured throughout the three studies was 2.6 ng/ml. The cream was well tolerated, locally and systemically. The most common adverse event suspected to be related to study medication was a transient mild to moderate stinging sensation at the application site in 5/26 patients. There was no indication of any systemic adverse effect. The patients responded well to therapy with a rapid onset of action, usually within four days. Median reductions of EASI from baseline at day 22 were 55% (study A), 63% (study B), and 83% (study C). CONCLUSION: Three weeks treatment of children and infants with extensive atopic dermatitis, using pimecrolimus cream 1% twice daily, is well tolerated and results in minimal systemic exposure, at which no systemic effect is expected.

Adolescent↗
PubMed2003

Quantitative trait locus detection in commercial broiler lines using candidate regions.

A QTL that explained a large proportion of the phenotypic difference between broiler and layer chickens in an experimental cross was evaluated in a commercial broiler line. A three-generation design, consisting of 15 grandsires, 608 half-sib hens, and more than 50,000 third-generation offspring, was implemented within the existing breeding scheme of a broiler breeding company. Four markers from a candidate region on chicken chromosome 4 were selected for their informativeness in the grandsires and used to genotype the first two generations. Using half-sib analyses, linkage was studied between these markers and 13 growth and carcass traits. The QTL analyses confirmed the presence of significant QTL for body weight (P < 0.01) and residual feed intake (P < 0.05) on chicken chromosome 4. Furthermore, evidence was found for QTL affecting the relative weight of bone and muscle in the thigh. Four more markers were added to increase resolution of the QTL positions. This increased the significance of the QTL for body weight (P < 0.001) and residual feed intake (P < 0.01) and showed evidence (P < 0.05) for additional QTL affecting carcass weight and conformation score. This study showed for the first time that a QTL that explains differences between broilers and layers was segregating in lines that have been selected for body weight over 50 generations. A possible explanation could be a pleiotropic or closely linked effect on fitness-related traits that are not part of the present study. The results demonstrate the feasibility of QTL detection and the potential for marker-assisted selection within a commercial broiler line without altering the existing breeding scheme.

Animals↗
PubMed2002

Australian Paediatric Surveillance Unit : progress report.

The Australian Paediatric Surveillance Unit (APSU), through active surveillance, collects information on the epidemiology of rare or uncommon childhood conditions. This research resource allows paediatricians to collaborate at State, national and international levels. The APSU sends a monthly report card to all (currently 971) paediatricians in Australia, who in turn indicate whether or not they have seen a patient in the last month with any of the conditions listed (98% response rate in 1999). Study investigators, notified by the APSU of positive case reports, obtain demographic and clinical data on the patient from the reporting doctor by postal questionnaire (90% response rate in 1999). Since 1993, the APSU has monitored 27 conditions, including conditions that are vaccine-preventable, otherwise infectious, genetic, congenital and non-communicable. Information collected is disseminated to paediatricians and other health professionals via an annual report, newsletters and publications and is made available to the International Network of Paediatric Surveillance Units. Information provided by the APSU has raised awareness among paediatricians of rare and uncommon childhood conditions, and has been used by health authorities for planning of prevention and intervention strategies and allocation of health resources.

Australia↗
PubMed2002

Telomerase expression of malignant epithelial cells correlates with Dukes' stage in colorectal cancer.

BACKGROUND: The ribonucleoprotein telomerase has been proposed as a potential prognostic marker for malignancy. Whether telomerase activity of clinical specimens correlates with other clinico-pathological variables, however, remains controversial. This is at least in part due to the varying contribution that nonmalignant cells will make to the net activity when extracts are assayed for telomerase activity. We therefore designed experiments to assay telomerase activity of isolated malignant cells of primary colorectal cancers. METHODS: Thirty colorectal cancer and 20 corresponding specimen taken from macroscopically normal regions of the colon were mechanically disaggregated and digested with collagenase, DNase and hyaluronidase. The epithelial cell population was separated using Ber-EP4 pan-epithelial antibody and Magnetic Activated Cell Sorting technique. Haematoxylin and eosin staining was used to assess the proportion of recovered epithelial cells which were malignant. Telomerase activity was assayed by the Telomeric Repeat Amplification Protocol, which was quantified by PhosphorImager with Image Quant software. RESULTS: Epithelial cells of three of 20 normal mucosa specimens were telomerase positive with weak activity (mean 3.7 TPGs, Total Product Generated, range 1.4-5.1TPGs). In the cancer group the vast majority (>95%) of the epithelial cells recovered were malignant by cytological criteria. Epithelial cells were telomerase positive in all the cancers, with a wide range of telomerase activity values (mean 22.7 TPGs, range 0.19-308 TPGs). Telomerase activity correlated with Dukes' stage (r = 0.52, P=0.004, Spearman's rank). CONCLUSIONS: Pathological stage correlates with telomerase activity of the malignant cell population of the primary tumour in colorectal cancer. This suggests that telomerase activity increases during the progression of a cancer and may have implications for the design of anticancer (antitelomerase) agents.

Journal Article↗
PubMed2002

Frequency downconversion and phase noise in MIT.

High-frequency (3-30 MHz) operation of MIT systems offers advantages in terms of the larger induced signal amplitudes compared to systems operating in the low- or medium-frequency ranges. Signal distribution at HF, however, presents difficulties, in particular with isolation and phase stability. It is therefore valuable to translate received signals to a lower frequency range through heterodyne downconversion, a process in which relative signal amplitude and phase information is in theory retained. Measurement of signal amplitude and phase is also simplified at lower frequencies. The paper presents details of measurements on a direct phase measurement system utilizing heterodyne downconversion and compares the relative performance of three circuit configurations. The 100-sample average precision of a circuit suitable for use as a receiver within an MIT system was 0.008 degrees for input amplitude -21 dBV. As the input amplitude was reduced from -21 to -72 dBV variation in the measured phase offset was observed, with the offset varying by 1.8 degrees. The precision of the circuit deteriorated with decreasing input amplitude, but was found to provide a 100-sample average precision of <0.022 degrees down to an input amplitude of -60 dBV. The characteristics of phase noise within the system are discussed.

Amplifiers, Electronic↗
PubMed2002

Cross-cultural differences in the management of children and adolescents with diabetes.

Glycaemic control deteriorates frequently in adolescents with diabetes. There is a considerable body of work on the effect of psychological aspects of management in this age group, but few randomized controlled trials of the effect of specific behavioural therapy and lifestyle modification on the improvement of glycaemic control. Of recent interest have been the observations from the Hvidøre Study Group on cross-cultural differences in glycaemic control. The average glycosylated haemoglobin in 22 centres, across 18 countries, varied in young people, with HbA1c levels ranging from 7.6 to 10.2%. No obvious differences in management were identified in this survey that could account for the disparities in glycaemic control. Data from the Scottish Study Group demonstrated similar variation in average glycaemic control in centres across a single culture. Using the qualitative methodology of anthropological research, some specific factors were identified that appear to influence young people's response to diabetes management and strategies employed by health professionals in their advice and care of the diabetes, particularly in relation to intensive insulin regimens. The main cultural factors influencing glycaemic control appear to be communication, reciprocal support between young people and professional heart carers and family structure within an individualistic, as against an egalitarian, society. Shared beliefs about teenage risk behaviour together with the medicalization of adolescence within medical culture also appears to be highly influential. The aim of this educational discussion group was to explore how a variety of health care professionals from distinctive cultures approach diabetes care delivery in this age group. The specific success and difficulties in different cultures in managing the young person with diabetes were investigated. Also discussed was how qualitative research methodology may generate further research in this area.

Adolescent↗