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J Sims

Publications and source records attributed to J Sims.

At least 19 recordsLinked to original sources
PubMed2006

Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis.

Discrepant findings have been reported regarding an association of the apolipoprotein E (APOE) gene with the clinical course of multiple sclerosis (MS). To resolve these discrepancies, we examined common sequence variation in six candidate genes residing in a 380-kb genomic region surrounding and including the APOE locus for an association with MS severity. We genotyped at least three polymorphisms in each of six candidate genes in 1,540 Caucasian MS families (729 single-case and multiple-case families from the United States, 811 single-case families from the UK). By applying the quantitative transmission/disequilibrium test to a recently proposed MS severity score, the only statistically significant (P=0.003) association with MS severity was found for an intronic variant in the Herpes Virus Entry Mediator-B Gene PVRL2. Additional genotyping extended the association to a 16.6 kb block spanning intron 1 to intron 2 of the gene. Sequencing of PVRL2 failed to identify variants with an obvious functional role. In conclusion, the analysis of a very large data set suggests that genetic polymorphisms in PVRL2 may influence MS severity and supports the possibility that viral factors may contribute to the clinical course of MS, consistent with previous reports.

3' Untranslated Regions↗
PubMed2006

Isolation of salmonella bacteriophages from swine effluent lagoons.

Bacteriophages (phages) associated with Salmonella were collected from nine swine manure lagoons in Mississippi. Phages were isolated by an enrichment protocol or directly from effluent. For enrichment, chloroform-treated samples were filtered (0.22 mum) and selectively enriched by adding a cocktail of Salmonella strains in trypticase soy broth. After overnight incubation at 35 degrees C, chloroform was added and samples stored at 5 degrees C. Enriched samples were tested by double agar layer (DAL) plaque assay against individual Salmonella isolates. Phage titers of 2.9 x 10(8) to 2.1 x 10(9) plaque forming units (pfu) per mL were produced, but estimation of phage titers in lagoons was not possible. For direct isolation, effluent was clarified by centrifugation, filtered (0.22 microm), and used in DAL plaque assays to select single-plaque isolates for 15 Salmonella strains. Plaque counts varied among Salmonella strains and lagoons. The most sensitive strain for direct phage recovery was ATCC 13311. Phage titers estimated by direct isolation with ATCC 13311 ranged among lagoons from 12 to 148 pfu per mL. In limited host range tests, 66 isolates recovered by the enrichment protocol produced plaques only on Enteritidis and Typhimurium strains of Salmonella and none produced plaques on lagoon isolates of Citrobacter, Escherichia, Proteus, Providencia, or Serratia. Electron microscopy (EM) showed purified enrichment isolates had Podoviridae morphology (tailless 50-nm icosahedral heads with tail spikes). Electron microscopy of clarified concentrated effluent showed 5.5:1 tailless to tailed phages. The isolated phages have potential as typing reagents, specific indicators, and biocontrol agents of Salmonella.

Animals↗
PubMed2006

11 IL-1 family members in inflammatory skin disease.

The cytokines IL-1alpha and IL-1beta have long been known to play a profound role in inflammation, and in the past decade another cytokine, IL-18 (originally known as IGIF), has also been realized to be an IL-1 family member and to possess significant inflammatory activity. Half a dozen additional members of the IL-1 family have been identified in recent years, and given their relatedness to IL-I and IL-18, it is tempting to speculate that they too might possess inflammatory potential. We have demonstrated that certain of these cytokines can activate MAP kinases and the pathway leading to NFkappaB, via known IL-1R family members. Moreover, when overexpressed in skin, they are capable of causing an inflammatory skin condition resembling that seen in human disease.

Animals↗
PubMed2006

Proliferating trichilemmal cysts of the scalp on CT.

Proliferating trichilemmal cysts, also known as pilar tumors, are slow-growing lobulated masses most commonly found on the scalp of elderly women. We present the case of a 69-year-old woman with a 25-year history of multiple enlarging scalp masses. The patient was evaluated for surgical consultation after the dominant mass presented with malignant degeneration. A CT of the head revealed multiple large, subcutaneous, cystic masses with calcifications.

Aged↗
PubMed2004

The Victorian Active Script Programme: promising signs for general practitioners, population health, and the promotion of physical activity.

BACKGROUND: The Active Script Programme (ASP) aimed to increase the number of general practitioners (GPs) in Victoria, Australia who deliver appropriate, consistent, and effective advice on physical activity to patients. To maximise GP participation, a capacity building strategy within Divisions of General Practice (DGPs) was used. The objectives of the programme were to (a) train and support GPs in advising sedentary patients, and (b) develop tools and resources to assist GPs. OBJECTIVE: To evaluate the effectiveness of the ASP. METHODS: A systems approach was used to promote capacity in Victorian general practice. Economic analyses were incorporated into the programme's evaluation. Participants were selected DGPs and their GP members. The programme worked with DGPs to train GPs and provide relevant resources. The main outcome measures were (a) changes in GP knowledge and behaviour and (b) cost effectiveness, based on modelled estimates of numbers of patients advised and adopting physical activity and gaining the associated health benefits. RESULTS: GP awareness and provision of physical activity advice increased. Although the programme's reach was modest, based on actual GP involvement, the cost effectiveness figures (138 Australian dollars per patient to become sufficiently active to gain health benefits, and 3647 Australian dollars per disability adjusted life year saved) are persuasive. CONCLUSIONS: The ASP increased DGPs' capacity to support GPs to promote physical activity. There is a strong economic argument for governments to invest in such programmes. However, caution is warranted about the maintenance of patients' activity levels. Programme refinement to encourage GPs to use community supports more effectively will guide future development. Further research on long term patient adherence through a multisectorial approach is warranted.

Adult↗
PubMed2003

Spatial resolution of phospholipid scramblase 1 (PLSCR1), caspase-3 activation and DNA-fragmentation in the human hippocampus after cerebral ischemia.

Reports on non-neural cells have shown that enhanced activity of the Ca(2+)-dependent/ATP-independent phospholipid scramblase (PLSCR1) is, at least in part, responsible for surface exposure of phosphatidylserine and the collapse of plasma membrane asymmetry in injured or apoptotic cells. To shed some light on mechanisms with a potential to lead to apoptotic death of human neurones following ischemic/hypoxic injury, we examined the immunoreactivity of hippocampal neurones for PLSCR1, caspase-3, cytochrome c and DNA-fragmentation in 22 individuals with clinically symptomatic cerebral ischemia after cardiac arrest or severe hypotension. WE FOUND: (1) significant differences in the percentage of PLSCR1-immunoreactive neurones between controls and short survivors; statistically strong differences between the frequency of immunoreactive neurones among the subfields studied with lowest levels in the CA3; preferential distribution of immunoreactive neurones in controls within the regio entorhinalis, subfield CA1, and hilum. Additionally, these areas exhibited staining of fibre bundles which probably correspond to perforant path, alvear path and collateral's of Schaffer, (2) caspase-3 was upregulated in a region-specific manner with marked activation in the selectively vulnerable hippocampal areas, (3) cytochrome c was redistributed, (4) DNA-fragmentation represented by scattered TUNEL-positive cells increased predominantly during the first 3 days after ischemia, and particularly in the regions of greatest susceptibility to hypoxic injury. This study presents the first evidence that PLSCR1, and probably remodelling of plasma membrane phospholipids (PL), plays a role in ischemic injury in the human hippocampus.

Adult↗
PubMed2001

Assessment of biotechnology products for therapeutic use.

Biotechnology products for therapeutic use include a very diverse range of products, including growth factors, cytokines, hormones, receptors, enzymes, clotting factors, monoclonal antibodies, vaccines, DNA vaccines, gene transfer products, cell therapies and tissue/organ grafts. While some of these products are regulated as medicinal products, the regulatory status of others such as some cell therapies and tissue/organ-based products differs globally and falls within the borderline between the practice of medicine, medical devices and medicinal products. The unclear regulatory status of some products can add to the complexity of the safety assessment of such products. Conventional non-clinical testing paradigms and guidelines for small molecule development are often not relevant for biotechnology products. Guidelines relating to the non-clinical safety evaluation of biotechnology products, gene transfer products and cell therapy products are available and represent a set of general guiding principals to be applied on a case-by-case basis. The quality, safety and efficacy of biotechnology products for therapeutic use are intricately linked, far more so than for conventional medicinal products, leading to the need for increased communication between those responsible for ensuring product quality and those responsible for non-clinical safety testing. Safety issues include microbiological safety (due to the use of biological materials either during the manufacturing process or as an integral part of the products), pharmacological/ biological toxicity (due to excessive primary pharmacology or undesirable secondary pharmacology), immunogenicity and potential tumourigenicity (for example, for growth factors, immunosuppressive monoclonal antibodies and cell therapy products). Genotoxicity and intrinsic chemical toxicity are less of a problem for biotechnology products.

Biotechnology↗
PubMed2001

Early discharge revisited: problems encountered with the home visit follow-up after the liberalization of eligibility criteria.

OBJECTIVE: To determine how changes in eligibility criteria for early discharge affected quality and costs of home nursing follow-up care for Medicaid patients. METHODS: A nurse screened women delivering vaginally to determine eligibility for discharge at 24-47 h. Maternal criteria were a vaginal delivery, no serious medical problems, > or = 8 h after bilateral tubal ligation and, if 24 h postpartum, by 21.00 on day of discharge. Newborn criteria were 36 weeks' gestation or more, 2000 g or greater and a normal examination at 24 h of age. By 48 h after discharge, a nursing visit was ordered for each mother and newborn. Nursing consultations were tracked and later entered into a database linked to hospital financial data. RESULTS: Of 3133 vaginal deliveries occurring from 1 August 1997 to 31 January 1999, eligibility criteria allowed 1799 mothers (58%) and 1587 newborns (51%) to be discharged early. Medical problems were rarely detected at follow-up (1% mothers, 2% newborns). To perform the increased number of visits, more personnel were hired and home nursing costs rose 150%. Despite the increased staff and costs, 19 mothers (1%) and ten newborns (0.6%) were lost to follow-up and 25 mothers (1%) and 20 newborns (1%) were visited beyond 72 h after discharge. CONCLUSIONS: Liberal changes in maternal and newborn eligibility criteria did not adversely affect the quality of home nursing follow-up care following early discharge. For hospitals performing a large number of early discharges, follow-up care using only a home nursing visit may be too expensive and difficult to organize. Alternative follow-up plans, such as clinic visits or phone calls, may also need to be utilized.

Adolescent↗
PubMed2001

Rural interprofessional education: promoting teamwork in primary health care education and practice.

In a climate of increasing incentives to work effectively within a primary health care team, the ability of various health care professionals to collaborate comes into focus. The principles of effective teamwork can be learned and this learning is most effectively achieved in the field under the supervision of experienced preceptors. It is also enhanced if learners have the opportunity to participate actively in the team and do so from undergraduate level. A 3 year project is underway in Victoria involving rural primary care placements for mixed groups of nursing and medical students. The students are educated in the field by medical and nursing tutors and preceptors who are currently working closely together. The learning objectives include understanding the principles of collaboration, teamwork and various roles in the health care team within a primary health care framework. The present paper describes the context for an evolving interprofessional education project in rural primary care, designed to promote collaboration. It outlines the policy underpinning the project's development. It provides a brief review of the associated evidence base, highlighting barriers to and enablers of interprofessional education. Lessons learnt during the implementation and evaluation of this project will guide efforts to extend the reach of interprofessional education across the primary health care sector.

Allied Health Personnel↗
PubMed2000

Sucralose metabolism and pharmacokinetics in man.

The metabolic and pharmacokinetic profile of sucralose was studied in human volunteers. Following a single oral dose of (14)C-sucralose (1mg/kg, 100 microCi) to eight male subjects, a mean of 14.5% (range 8.9 to 21.8%) of the radioactivity was excreted in urine and 78.3% (range 69.4 to 89.6%) in the faeces, within 5 days. The total recovery of radioactivity averaged 92.8%. Plasma concentrations of radioactivity were maximal at about 2 hours after dosing. The mean residence time (MRT) for sucralose was 18.8hr, while the effective half-life for the decline of plasma radioactivity was 13hr. Two volunteers given a higher oral dose (10mg/kg, 22.7 microCi) excreted a mean of 11.2% (9.6 and 12.7%) of the radioactivity in urine, and 85.5% (84.1 and 86.8%) in faeces over 5 days. The total recovery of radioactivity was 96.7%. The radiolabelled material present in faeces was essentially unchanged sucralose. Sucralose was the principal component in the urine together with two more polar components which accounted for only 2.6% of the administered dose (range 1.5 to 5.1% of dose); both metabolites possessed characteristics of glucuronide conjugates of sucralose.

Adult↗
PubMed2000

The metabolic fate of sucralose in rats.

The fate of sucralose was investigated in rats following single intravenous or oral doses of 2-1000mg/kg. Following intravenous administration (2-20mg/kg) approximately 80% of the dose was eliminated in urine with 9-16% in the faeces. In contrast, only about 5% of oral doses (10-1000mg/kg) was recovered in the urine, indicating that sucralose is poorly absorbed from the intestinal tract. After both intravenous and oral administration, the radioactivity excreted in urine and faeces was mainly unchanged sucralose. Two minor radioactive urinary components were observed, which together accounted for less than 1% of the administered dose. Rats which had been given high concentrations of sucralose (3%) in the diet for more than 18 months showed a similar metabolic profile, demonstrating that metabolic adaptation of the gut microflora or mammalian enzymes had not occurred during the treatment period.

Administration, Oral↗
PubMed2000

The industry view on long-term toxicology testing in drug development of human pharmaceuticals.

The approach to chronic toxicity testing over the past decade is reviewed and assessed in the light of developing ICH guidelines. The 1990's have seen a general acceptance that studies with a maximal duration of 6 months in rodents are all that is required for adequate safety assessment of developmental pharmaceutical agents. However, controversy has arisen concerning the most appropriate duration for chronic toxicity testing in non-rodents. Initial suggestions that 6 months duration was sufficient have been countered by findings noted in 12-month studies that were not seen in shorter-term studies. Retrospective analysis of available data eventually lead to a subsequent ICH recommendation that studies of 9 months duration would be now acceptable. However, until recently the FDA position on this recommendation was unclear and an analysis of industry practices since the ICH recommendation was made in 1997 has shown that the 9-month guideline is not widely applied. Recent clarification by the FDA will probably result in a continued but limited use of this alternative. An industry view on the future of chronic toxicology testing in rodents and non-rodents is presented.

Animals↗
PubMed2000

Cognitive impairment among methadone maintenance patients.

AIMS: To compare the cognitive performance of methadone maintenance patients (MMPs) and a matched sample of non-heroin-using control subjects, and to ascertain risk factors for poorer cognitive performance. DESIGN: Matched control study. SETTING: Sydney, Australia. PARTICIPANTS: Thirty MMPs and 30 non-heroin using controls, matched for age, gender and education. FINDINGS: The MMP group had significantly higher rates than controls of alcohol dependence, heroin overdose and head injury. There was no difference between the groups on pre-morbid functioning. The MMP group performed significantly poorer than controls on all of the neuropsychological domains measured: information processing, attention, short-term visual memory, delayed visual memory, short-term verbal memory, long-term verbal memory and problem solving. A life-time diagnosis of alcohol dependence and the number of non-fatal heroin overdoses were independent significant predictors of poorer cognitive performance. CONCLUSIONS: In addition to high rates of psychiatric morbidity, MMPs also show cognitive deficits compared to matched controls. A history of alcohol dependence and repeated exposure to overdose increase the likelihood of cognitive impairment. The current study does not rule out the possibility of other factors, that were not measured, that may contribute to cognitive impairment among this MMPs.

Adult↗
PubMed2000

Health promotion and older people: the role of the general practitioner in Australia in promoting healthy ageing.

OBJECTIVE: The Commonwealth Government's Enhanced Primary Care initiative supports measures to enhance the role of general practitioners (GPs) in promoting healthy ageing as part of a population health approach. This paper comments on how the health assessments can be conducted to best effect, to strengthen the role of GPs in primary care and to promote autonomy and independence in older people. METHOD: The relevant literature was collated to produce a review of public health and health promotion approaches and to ascertain the effectiveness of health promotion interventions for older people. A broad definition of health promotion including primary, secondary and tertiary prevention was adopted. RESULTS: The evidence base suggests there is scope for greater targeting of health promotion activities towards older people. The rationale for the Australian GP to assume a major health promotion role with their older patients is provided. Associated barriers and enablers are discussed. CONCLUSIONS: Prevention of disability is a key public health issue. The new MBS items may enable systematic evaluation of function and assist healthy ageing for all older people, including the frail aged. An increase in the preventive advice given to older patients has the potential to increase healthy behaviours and alter health outcomes. IMPLICATIONS: The annual health assessment items on the Medicare Benefits Schedule, by enabling the GP to focus on prevention and coordination of care, have the potential to improve the health, physical, psychological and social function of older Australians.

Aged↗
PubMed1999

What influences a patient's desire to participate in the management of their hypertension?

There are potential benefits to giving the patient a more active role in the management of his or her care. This study explored the characteristics which influence a preference for participation and the extent to which hypertensive patients wish to participate in the management of their condition. A cross-sectional study with in-depth, face-to-face interviews was conducted with 49 hypertensive patients from one health centre. Interview themes were identified using content analysis. Characteristics predictive of participation desire were detected via quantitative analyses. Half of those interviewed were interested in participating in hypertension management. Those who had been hypertensive longer were less inclined to favour participation. Those with negative views of their 'disease' status and with higher blood pressure were more likely to want to participate. Patients needed further information and advice before decisions about future level of participation could be properly considered.

Adult↗
PubMed1999

The vagaries of self-reports of physical activity: a problem revisited and addressed in a study of exercise promotion in the over 65s in general practice.

BACKGROUND: The assessment of levels of physical activity relies upon suitable measurement tools. OBJECTIVE: We aimed to investigate whether a practice nurse, using a motivational interview technique, could encourage older patients to increase their physical activity. METHODS: Health and well-being were monitored at baseline and 8 weeks following intervention. Physical activity levels were ascertained using both a self-report measure and ambulatory heart-rate monitoring. RESULTS: Whilst patients reported higher levels of physical activity at follow-up, this finding was not confirmed by the heart-rate data. CONCLUSION: The study concludes that patients tend to overestimate the amount of physical activity undertaken and that ambulatory heart-rate monitoring may be more useful for verifying actual behaviour.

Aged↗