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Biomedical subjects

D Millar

Publications and source records attributed to D Millar.

At least 19 recordsLinked to original sources
PubMed2006

IL-7R alpha versus CCR7 and CD45 as markers of virus-specific CD8+ T cell differentiation: contrasting pictures in blood and tonsillar lymphoid tissue.

In humans, circulating CD8(+) memory T cells to a nonpersistent virus (influenza) lie within CCR7(+)CD45RA(-) central memory, whereas memory to Epstein-Barr virus (EBV) latent, EBV lytic, and cytomegalovirus (CMV) antigens are progressively larger in size and are more biased toward CCR7(-)CD45RA(-) effector memory and CCR7(-)CD45RA(+) terminally differentiated compartments. We found that these populations are also distinguished by progressively lower expression of the interleukin-7 receptor (IL-7R alpha) and by lower IL-7 responsiveness; indeed, percentage IL-7R alpha -positive values showed a tight inverse correlation with population size. However, these relationships among size, differentiation phenotype, and IL-7R alpha status in blood did not hold in tonsillar tissue. In tonsil tissue, although EBV reactivities outnumbered their CMV and influenza counterparts, the distinct CCR7/CD45 isoform signatures of the different virus-specific populations were retained. Moreover, all detectable reactivities showed high levels of IL-7R alpha expression. As a discriminator between different virus-specific populations, IL-7R alpha therefore appears to be more susceptible to tissue location than the classical CCR7/CD45 markers.

CD8-Positive T-Lymphocytes↗
PubMed2006

Antithrombin for respiratory distress syndrome in preterm infants.

BACKGROUND: Acquired Antithrombin (AT) deficiency is a common and prognostically important finding in sick preterm infants with respiratory distress syndrome (RDS). It has been hypothesised that AT concentrate may improve clinical outcomes in preterm infants with RDS. OBJECTIVES: To determine whether the administration of AT concentrate decreases mortality in preterm infants with RDS compared with placebo or no treatment. SEARCH STRATEGY: An electronic literature search in the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE in August 2006 was performed. No language restriction was applied. References from identified studies were cross-checked for possible additional studies. Experts in the field and pharmaceutical companies were contacted for unpublished data. Abstracts of the American Society of Pediatric Research and European Society of Pediatric Research meetings (1983-2005) were searched and authors of relevant studies were contacted to obtain additional information. SELECTION CRITERIA: Randomized controlled trials comparing any dose and duration of AT therapy with placebo or no treatment in preterm infants with RDS. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data from included studies regarding mortality, intraventricular hemorrhage, mechanical ventilation, and other reported events in the clinical course of the patients. Data for similar outcomes were combined where appropriate, using a fixed-effects model in MetaView 4.2 (Update Software). MAIN RESULTS: Two trials consisting of 182 preterm infants, fulfilled the inclusion criteria. Mean gestational age of patients included was 28 weeks. In one trial, patients had to be intubated and ventilated for RDS to be eligible for the study. In the other trial, RDS was not mentioned as an inclusion criteria, however the vast majority of infants in the study received surfactant. No individual trial showed a significant difference in mortality. One of the trials was stopped early because of an increase in deaths in the AT group. The pooled analysis for mortality within the first week of life showed a typical relative risk of 2.67 (95% CI 0.72-9.83) in favour of the control group. Only the trial that was stopped early followed the infants long enough to report neonatal mortality. This trial reported 7 deaths (11.5%) in the AT group and two deaths (3.3%) in the placebo group within 28 days of life. Secondary outcomes included days of mechanical ventilation and supplemental oxygen which were only reported in 1 trial. Both outcomes were in favour of the control group and statistically significant (p < 0.05). AUTHORS' CONCLUSIONS: Preterm infants with RDS are unlikely to benefit from AT treatment and may be harmed.

Anticoagulants↗
PubMed2004

Factors influencing time from presentation to treatment of colorectal and breast cancer in urban and rural areas.

Stage at diagnosis and survival from cancer vary according to where people live, suggesting some may have delays in diagnosis. The aim of this study was to determine if time from presentation to treatment was longer for colorectal and breast cancer patients living further from cancer centres, and identify other important factors in delay. Data were collected on 1097 patients with breast and 1223 with colorectal cancer in north and northeast Scotland. Women with breast cancer who lived further from cancer centres were treated more quickly than those living closer to cancer centres (P=0.011). Multilevel modelling found that this was largely due to them receiving earlier treatment at hospitals other than cancer centres. Breast lump, change in skin contour, lymphadenopathy, more symptoms and signs, and increasing age predicted faster treatment. Screen detected cancers and private referrals were treated more quickly. For colorectal cancer, time to treatment was similar for people in rural and urban areas. Quicker treatment was associated with palpable rectal or abdominal masses, tenesmus, abdominal pain, frequent GP consultations, age between 50 and 74 years, tumours of the transverse colon, and iron medication at presentation. Delay was associated with past anxiety or depression. There was variation between general practices and treatment appeared quicker at practices with more female general practitioners.

Adult↗
PubMed2004

Benefits of non invasive ventilation.

Mechanical ventilation of the newborn infant has increased neonatal survival. However, this increased survival has come at the expense of increased morbidity, in the form of bronchopulmonary dysplasia, and at the cost of an expensive technology. Continuous positive airway pressure (CPAP) is accepted as conferring clinical benefit in supporting the recently extubated preterm infant and in the management of apnea of prematurity. Attention is now being drawn to physiologic and clinical evidence to support CPAP use, with or without early surfactant, as a primary treatment of hyaline membrane disease. The purpose of this review is to explore these proposed benefits of non invasive ventilation and place them in the context of current clinical evidence.

Bronchopulmonary Dysplasia↗
PubMed2003

Kakadumycins, novel antibiotics from Streptomyces sp NRRL 30566, an endophyte of Grevillea pteridifolia.

An endophytic streptomycete (NRRL 30566) is described and partially characterized from a fern-leaved grevillea (Grevillea pteridifolia) tree growing in the Northern Territory of Australia. This endophytic streptomycete produces, in culture, novel antibiotics - the kakadumycins. Methods are outlined for the production and chemical characterization of kakadumycin A and related compounds. This antibiotic is structurally related to a quinoxaline antibiotic, echinomycin. Each contains, by virtue of their amino acid compositions, alanine, serine and an unknown amino acid. Other biological, spectral and chromatographic differences between these two compounds occur and are given. Kakadumycin A has wide spectrum antibiotic activity, especially against Gram-positive bacteria, and it generally displays better bioactivity than echinomycin. For instance, against Bacillus anthracis strains, kakadumycin A has minimum inhibitory concentrations of 0.2-0.3 microg x ml(-1) in contrast to echinomycin at 1.0-1.2 microg x ml(-1). Both echinomycin and kakadumycin A have impressive activity against the malarial parasite Plasmodium falciparum with LD(50)s in the range of 7-10 ng x ml(-1). In macromolecular synthesis assays both kakadumycin A and echinomycin have similar effects on the inhibition of RNA synthesis. It appears that the endophytic Streptomyces sp. offer some promise for the discovery of novel antibiotics with pharmacological potential.

Anti-Bacterial Agents↗
PubMed2001

Educational opportunities in palliative care: what do general practitioners want?

It is important to support general practitioners (GPs) in maintaining and developing their palliative care skills as most of the final year of a patient's life is spent at home under the care of the primary health care team. The training needs and uptake of GPs have been explored, but little is known about how GP educational preferences vary. The aim of this study was to explore the current educational preferences of GPs in different geographical locations as part of an evaluation of an educational intervention. The methods used included postal questionnaires sent to 1061 GPs. Results from 640 (60%) of GPs revealed that half (51%) wanted education in symptom control for non-cancer patients. More inner-city GPs wanted education in opiate prescribing (43%), controlling nausea and vomiting (45%), and using a syringe driver (38%) than their urban and rural colleagues (26%, 29% and 21%, respectively). Increased educational preference and increased difficulty in accessing information was associated with reduced confidence in symptom control. To maximize educational uptake it will be important for educational strategies to be developed and targeted according to variations in demand, and in particular to respond to the need for palliative care education in symptom control for patients suffering from advanced non-malignant disease.

Adult↗
PubMed2001

A psychoanalytic view of Biblical myth.

The author looks at some ways in which certain biblical myths tell a story, a story about loss--loss of freedom, of the homeland, of God's favour, ultimately loss of the good object--and about guilt for these losses. He describes in the post-exilic myth of the Old Testament and the Jesus myth of the New Testament a pattern in which, he argues, there is a 'retreat' from the depressive anxieties that seem to be troubling the group, with loss and guilt becoming mediated through a rigidified defensive organisation that holds out the promise that it will make this loss and guilt easier to bear. Guilt, worthlessness, badness and fallibility are split off and projected into a near foreign group blamed for loss, while within the group's own boundary there is an identification with righteousness and power. The author describes the post-exilic myth and the Jesus myth as what he terms 'hardened myths' that embody a belief in an idealized privileged identity in which exclusive group possession of the good object is asserted. The analysis of such hardened myths reveals a shared belief in the efficacy of group idealization. The author links the formation of these hardened myths with what we know about how individuals manage actual loss, and argues that (for the group as for the individual) the myths express collusion with the moral authority of an idealized and very punitive superego. The paper ends with a very brief suggestion that, analogously, hardened myths may be relevant in other cultural and social millieux, especially, perhaps, the troubled relations of some psychoanalytic groups to one another.

Anxiety↗
PubMed2000

Methylation of a CpG island within the promoter region of the KAI1 metastasis suppressor gene is not responsible for down-regulation of KAI1 expression in invasive cancers or cancer cell lines.

The molecular basis for downregulation of the KAI1 metastasis suppressor gene in invasive and metastatic human cancers is unknown. We have used bisulphite methylation analysis of DNA from paraffin-embedded invasive bladder tumour samples and from bladder cancer cell lines to determine if hypermethylation of a CpG island within the KAI1 promoter is responsible for this effect. Representative invasive tumour cell lines were also exposed to 5-aza-2-deoxycytidine. We found no evidence for hypermethylation of the CpG island and suggest that mechanisms other than promoter hypermethylation are responsible for reduced KAI1 expression in invasive bladder tumours and tumour cell lines.

Antigens, CD↗
PubMed2000

Quality control and optimized procedure of hybridization capture-PCR for the identification of Mycobacterium avium subsp. paratuberculosis in faeces.

Nucleic acid sequence capture techniques are used to improve both the sensitivity and specificity of PCR for the diagnosis of plant, animal and human diseases. Hybridization capture-PCR (HC-PCR) was first reported as a method for the detection of Mycobacterium avium subsp. paratuberculosis in 1995 and was successfully trialed on a small number of faecal samples from cattle with Johne's disease. A locally optimized HC-PCR method was evaluated on faeces from infected and non-infected animals. However, sample to sample cross contamination during the DNA purification step highlighted that the original format of the test was unsuitable for routine diagnostic use. Here, we report modifications and optimization of HC-PCR, particularly with respect to DNA purification from faeces, hybridization and capture steps. We also identified procedurally sensitive critical points in the test during capture and washing of magnetic beads. Southern blotting was omitted from the protocol to preserve specificity but this resulted in analytical sensitivity of 5000 organisms per 200 mg faecal sample. Nevertheless, HC-PCR detected M.paratuberculosis in pellets from infected sheep diluted at rates of up to 1 in 100 in normal faeces, suggesting that the technique should be evaluated further for low-cost diagnosis in flocks/herds using pooled samples.

Animals↗
PubMed2000

Providing palliative care in primary care: how satisfied are GPs and district nurses with current out-of-hours arrangements?

The complex needs of palliative care patients require an informed, expert, and swift response from out-of-hours general medical services, particularly if hospital admission is to be avoided. Few general practitioners (GPs) reported routinely handing over information on their palliative care patients, particularly to GP co-operatives. District nurses and inner-city GPs were least satisfied with aspects of out-of-hours care. Most responders wanted 24-hour availability of specialist palliative care. This indicates a need to develop and evaluate out-of-hours palliative care procedures and protocols, particularly for GP co-operatives, and to improve inter-agency collaboration.

Adult↗
PubMed1996

IS900 PCR to detect Mycobacterium paratuberculosis in retail supplies of whole pasteurized cows' milk in England and Wales.

IS900 PCR for Mycobacterium paratuberculosis was applied to cream, whey, and pellet fractions of centrifuged whole cows' milk. The test and simultaneous control reactions gave correct results for spiked milk and for native milk samples obtained directly from M. paratuberculosis-free, subclinically infected, and clinically infected cows. The test was then applied to units of whole pasteurized cows' milk widely obtained from retail outlets throughout central and southern England from September 1991 to March 1993. With peak periods in January to March and in September to November, when up to 25% of units were affected, an overall 22 of 312 samples (7%) tested positive for M. paratuberculosis. In 18 of the 22 positive samples (81%), the PCR signal segregated to the cream or pellet fractions or both, consistent with the presence of intact mycobacteria. Nine of 18 PCR-positive milk samples (50%) and 6 of 36 PCR-negative milk samples (16%) yielded long-term liquid cultures which tested positive for M. paratuberculosis after 13 to 40 months of incubation, despite overgrowth by other organisms. Taken together with data on the prevalence of M. paratuberculosis infection in herds in the United Kingdom, the known secretion of M. paratuberculosis in milk from subclinically infected animals, and the inability of laboratory conditions simulating pasteurization to ensure the killing of all these slowly growing or unculturable organisms, there is a high risk, particularly at peak times, that residual M. paratuberculosis will be present in retail pasteurized cows' milk in England.

Animals↗
PubMed1995

Engineering proteins without primary sequence tryptophan residues: mutant trp repressors with aliphatic substitutions for tryptophan side chains.

Combinatorial mismatch-primer mutagenesis was used to make simultaneous changes of codons for residues Trp19 and Trp99 of the Escherichia coli trp aporepressor (TrpR protein) to codons for other residues. Among 21 different single- and double-mutant repressors obtained from this round of mutagenesis, proteins with Trp-->Leu and Trp-->Met changes at one or both positions were found to be nearly as active as the wild type (wt). Genes encoding repressors with each of the eight possible combinations of single- and double-mutant changes of Trp19 and Trp99 to Leu and Met were constructed by recombination in vitro. Whereas three of these eight mutant repressors are unstable in E. coli, all are made at similar steady-state levels in Salmonella typhimurium. Three of the eight mutant holorepressors are lethal when overproduced in S. typhimurium, because they confer an induced auxotrophy. Two different activity assays in vivo show that one of the four double-mutant repressors (Trp19-->Leu; Trp99-->Met) is similar to wt TrpR in its interactions with both Trp and DNA. These results show that more general approaches to engineering active proteins with fewer Trp residues may give rise to functional mutants without aromatic substitutions, and that aliphatic changes should be considered in cases where engineered changes of Trp to Phe or Tyr do not work.

Amino Acid Sequence↗
PubMed1993

Planned sexual behaviour of young Australian visitors to Thailand.

OBJECTIVE: To research the knowledge of AIDS and other sexually transmitted diseases among young Australian tourists to Thailand, and their intended sexual behaviour. DESIGN AND SETTING: A cross-sectional survey by anonymous, self-administered questionnaire, of persons seeking pre-travel medical advice in private clinics in five Australian cities. PARTICIPANTS: 213 consecutive patients travelling to Thailand without a spouse or partner. RESULTS: Only 34% of the sample reported a definite intention not to have sex in Thailand. Regarding choice of potential partners: 24.5% more men than women said they would have sex with a Thai national; 13.7% of men said they would have sex with a "bar girl"; and 21.7% more women than men said they would choose a fellow Australian traveller. Eighty-two per cent of the sample reported that they would use condoms 100% of the time, and there was no significant difference between the number of men and women who expressed this intention. CONCLUSIONS: Although not obviously "sex tourists", many young Australian travellers are likely to have sex while visiting Thailand. These data have important implications for education and prevention programs to control the spread of human immunodeficiency virus (HIV) and other sexually transmitted diseases.

Acquired Immunodeficiency Syndrome↗