Sustained gene expression in transplanted skin fibroblasts in rats

Retrovirus-mediated gene transfer into adult skin fibroblasts has provided measurable amounts of therapeutic proteins in animal models. However, the major problem emerging from these experiments was a limited time of vector encoded gene expression once transduced cells were engrafted We hypothesized that sustained transduced gene expression in quiescent fibroblasts in vivo might be obtained by using a fibronectin (Fn) promoter. Fibronectin plays a key role in cell adhesion, migration and wound healing and is up-regulated in quiescent fibroblasts. Retroviral vectors containing human adenosine deaminase (ADA) cDNA linked to rat fibronectin promoter (LNFnA) or viral LTR promoter (LASN) were compared for their ability to express ADA from transduced primary rat skin fibroblasts in vivo. Skin grafts formed from fibroblasts transduced with LNFnA showed strong human ADA enzyme activity from 1 week to 3 months. In contrast, skin grafts containing LASN-transduced fibroblasts tested positive for human ADA for weeks 1 and 2, were faintly positive at week 3 and showed no human ADA expression at 1, 2 and 3 months. Thus, a fibronectin promoter provided sustained transduced gene expression at high levels for at least 3 months in transplanted rat skin fibroblasts, perhaps permitting the targeting of this tissue for human gene therapy.

Diabetes detection in Australian general practice: a comparison of diagnostic criteria

Objectives: To study the influence of different diagnostic criteria on the prevalence of diabetes mellitus and characteristics of those diagnosed. Design and setting: Retrospective analysis of data from the general-practice-based Australian Diabetes Screening Study (January 1994 to June 1995). Participants: 5911 people with no previous diagnosis of diabetes, two or more symptoms or risk factors for diabetes, a random venous plasma glucose (PG) level > 5.5 mmol/L and a subsequent oral glucose tolerance test (OGTT) result. Main outcome measure: Prevalence of undiagnosed diabetes based on each of three sets of criteria: 1997 criteria of the American Diabetes Association (ADA), 1996 two-step screening strategy of the Australian Diabetes Society (ADS) (modified according to ADA recommendations about lowered diagnostic fasting PG level), and 1999 definition of the World Health Organization (WHO). Results: Prevalence estimates for undiagnosed diabetes using the American (ADA), Australian (ADS) and WHO criteria (95% CI) were 9.4% (8.7%-10.1%), 16.0% (15.3%-16.7%) and 18.1% (17.1%-19.1%), respectively. People diagnosed with diabetes by fasting PG level (common to all sets of criteria) were more likely to be male and younger than those diagnosed only by 2 h glucose challenge PG level (Australian and WHO criteria only). The Australian (ADS) stepwise screening strategy detected 88% of those who met the WHO criteria for diabetes, including about three-quarters of those with isolated post-challenge hyperglycaemia. Conclusion: The WHO criteria (which include an OGTT result) are preferable to the American (ADA) criteria (which rely totally on fasting PG level), as the latter underestimated the prevalence of undiagnosed diabetes by almost a half. The Australian (ADS) strategy identified most of those diagnosed with diabetes by WHO criteria.

Redox active macrocyclic receptors for neutral guests

A novel series of triazine-appended macrocyclic complexes has been investigated as potential hydrogen bonding receptors for complementarily disposed heterocycles. Cocrystallization of a melamine-appended azacyclam complex of Cull has been achieved with barbitone, the barbiturate anion and thymine. In each case, a complementary DAD/ADA hydrogen bonding motif between the melamine group and the heterocycle has been identified by X-ray crystallography. Electrochemical studies of the copper macrocycles in both nonaqueous and aqueous solution show anodic shifts of the CuII/I redox couple of more than 60 mV upon addition of guest molecules with matching H-bonding motifs. The Zn-II analogues have been synthesized via transmetalation of the Cull complex, and their guest binding properties investigated by NMR spectroscopy. H-1 NMR shifts of up to 0.8 ppm were observed upon addition of guest, and stability constants are similar to those obtained electrochemically.

Disorders of breathing and continence have a stronger association with back pain than obesity and physical activity

Although obesity and physical activity have been argued to predict back pain, these factors are also related to incontinence and breathing difficulties. Breathing and continence mechanisms may interfere with the physiology of spinal control, and may provide a link to back pain. The aim of this study was to establish the association between back pain and disorders of continence and respiration in women. We conducted a cross-sectional analysis of self-report, postal survey data from the Australian Longitudinal Study on Women's Health. We used multinomial logistic regression to model four levels of back pain in relation to both the traditional risk factors of body mass index and activity level, and the potential risk factors of incontinence, breathing difficulties, and allergy. A total of 38 050 women were included from three age-cohorts. When incontinence and breathing difficulties were considered, obesity and physical activity were not consistently associated with back pain. In contrast, odds ratios (OR) for often having back pain were higher for women often having incontinence compared to women without incontinence (OR were 2.5, 2.3 and 2.3 for young, mid-age! and older women, respectively). Similarly, mid-aged and older women had higher odds of having back pain often when they experienced breathing difficulties often compared to women with no breathing problems (OR of 2.0 and 1.9, respectively). Unlike obesity and physical activity, disorders of continence and respiration were strongly related to frequent back pain. This relationship may be explained by physiological limitations of co-ordination of postural, respiratory and continence functions of trunk muscles.

Routine physiotherapy does not induce cardiorespiratory training effect post-stroke

Background and Purpose. Cardiorespiratory fitness is increasingly being recognized as an impairment requiring physiotherapy intervention after stroke. The present study seeks to investigate if routine physiotherapy treatment is capable of inducing a cardiorespiratory training effect and if stroke patients attending physiotherapy who are unable to walk experience less cardiorespiratory stress during physiotherapy when compared to those who are able to walk. Method. A descriptive, observational study, with heart rate monitoring and video-recording of physiotherapy rehabilitation, was conducted. Thirty consecutive stroke patients from a geriatric and rehabilitation unit of a tertiary metropolitan hospital, admitted for rehabilitation, and requiring physiotherapy were included in the study. The main measures of the study were duration (time) and intensity (percentage of heart rate reserve) of standing and walking activities during physiotherapy rehabilitation for non-walking and walking stroke patients. Results. Stroke patients spent an average of 21 minutes participating in standing and walking activities that were capable of inducing a cardiorespiratory training effect. Stroke patients who were able to walk spent longer in these activities during physiotherapy rehabilitation than non-walking stroke patients (p < 0.05). An average intensity of 24% heart rate reserve (HRR) during standing and walking activities was insufficient to result in a cardiorespiratory training effect, with a maximum of 35% achieved for the stroke patients able to walk and 30% for those unable to walk. Conclusions. Routine physiotherapy rehabilitation had insufficient duration and intensity to result in a cardiorespiratory training effect in our group of stroke patients. Copyright © 2006 John Wiley & Sons, Ltd.

A paralysis in public health policy: water fluoridation in Queensland (1996-2006)

By focusing on developments between 1996 and 2006, this paper explains the reasons for one of Australia’s public health inconsistencies, the comparatively low adoption of adjusted water fluoridation in Queensland. As such, this work involved literature review and traditional historical method. In Queensland, parliamentary support for water fluoridation is conditional on community approval. Political ambivalence and the constraints of the “Fluoridation of Public Water Supplies Act (1963)” Qld have hindered the advocacy of water fluoridation. The political circumstance surrounding the “Lord Mayor’s Taskforce on Fluoridation Report” (1997) influenced its findings and confirms that Australia’s biggest local authority, the Brisbane City Council, failed to authoritatively analyse water fluoridation. In 2004, a private member’s bill to mandate fluoridation failed in a spectacular fashion. In 2005, an official systems review of Queensland Health recommended public debate about water fluoridation. Our principal conclusion is that without mandatory legislation, widespread implementationof water fluoridation in Queensland is most unlikely.