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Biomedical subjects

C Anderson

Publications and source records attributed to C Anderson.

At least 37 records · Page 2Linked to original sources

Progressive resistance strength training for physical disability in older people.

BACKGROUND: Muscle weakness in old age, is associated with physical disability and an increased risk of falls. Progressive resistance strength (PRT) training exercises (i.e. movements performed against a specific external force that is regularly increased during training) are designed to increase strength in older people. OBJECTIVES: To assess the effect of PRT on measures of physical disability, functional limitation and impairment in older people, and identify adverse events. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialized register (to August 2002), CENTRAL/CCTR (The Cochrane Library Issue 2, 2002), MEDLINE (1966 to February 1, 2002), EMBASE (1980 to February 1, 2002), CINAHL (1982 to February 1, 2002), Sports Discus (1948 to February 1, 2002), PEDro - The Physiotherapy Evidence Database (accessed February 1, 2002) and Digital Dissertations (accessed February 1, 2002). We also searched reference lists of articles, reviewed conference abstracts and contacted authors. SELECTION CRITERIA: Randomised trials of PRT alone for older people (i.e. mean age of 60 or over) were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Weighted mean differences (WMD) were obtained using fixed or random effect models as appropriate. When measures with different units were pooled, standardised mean differences (SMD) were calculated. Relative risks were calculated for dichotomous outcomes. MAIN RESULTS: Sixty-six trials with 3783 participants were included. Most studies were small and of poor quality. PRT had a large positive effect on strength (41 trials, 1955 participants), but there was statistical heterogeneity that was not explained by differences in study quality, participant characteristics or the exercise program. Some functional limitation measures showed modest improvements (i.e. gait speed, 14 trials, 798 participants, WMD 0.07 m/s, 95% CI 0.04 to 0.09). However, there was no evidence that PRT had an effect on physical disability when activity measures or health related quality of life measures (HRQOL) were assessed (10 trials, 798 participants, SMD 0.01, 95% CI -0.14 to 0.16 ). Adverse events were poorly recorded, but musculoskeletal injuries were detected in most of the studies that prospectively defined and monitored these events. REVIEWER'S CONCLUSIONS: PRT appears to be an effective intervention to increase strength in older people and has a positive effect on some functional limitations. However, the effect of this intervention on more substantive outcomes such as measures of disability or HRQOL remains unclear. It is difficult to determine the balance of risks and benefits of PRT because adverse events have generally been poorly collected and recorded.

Aged↗

A comparison of photodynamic therapy using topical methyl aminolevulinate (Metvix) with single cycle cryotherapy in patients with actinic keratosis: a prospective, randomized study.

BACKGROUND: Actinic keratosis (AK) is a very common condition, which has the potential of progressing to squamous cell carcinoma. The present study is a prospective, randomized study comparing the lesion response, cosmetic outcome, patient satisfaction and tolerability of a new treatment modality, photodynamic therapy (PDT), using topical methyl aminolevulinate (Metvix), with the most commonly used standard therapy for AK, cryotherapy. METHODS: A total of 204 patients with clinically diagnosed AK were randomized to either cryotherapy or PDT. The PDT patients were further assigned to an active or placebo group in a random, double-blind manner. Cryotherapy was performed using liquid nitrogen spray in a single freeze-thaw cycle. PDT was performed using 160 mg/g methyl aminolevulinate cream or placebo, a 3-hour application time, red light (570-670 nm) and a total light dose of 75 J/cm(2). PDT was repeated after 7 days. Two sessions of PDT were undertaken, as a previous study had shown a single session had similar efficacy to cryotherapy. Lesion response was assessed clinically after 3 months (complete response or non-complete response). RESULTS: The lesion response rate was 91% in the methyl aminolevulinate PDT group, 68% in the cryotherapy group and 30% in the placebo PDT group. Methyl aminolevulinate PDT was statistically significantly better than both cryotherapy and placebo PDT in terms of response rates and cosmetic outcome. Most patients preferred PDT to other treatments. CONCLUSIONS: PDT with methyl aminolevulinate is an excellent treatment option, particularly for patients with widespread damage or AK lesions in cosmetically sensitive areas.

Administration, Cutaneous↗

Cytokine production, lymphocyte proliferation and T-cell receptor Vbeta expression in primary peripheral blood mononuclear cell cultures from nickel-allergic individuals.

BACKGROUND: Clinical history and patch test constitute the two cornerstones in the diagnosis of nickel (Ni) allergy. Due to technical and interpretative limits of the patch test, the in vitro lymphocyte transformation test (LTT) has been developed for confirming contact allergy; however, most studies show an overlap in lymphocyte proliferation between Ni-allergic and nonallergic subjects using the LTT. The aim of this study was to see if the secretion of cytokines, especially interleukin (IL)-10 and IL-17, or the use of T-cell receptor (TCR) Vbeta families in Ni-stimulated primary peripheral blood mononuclear cell (PBMC) cultures might be more useful for discriminating between allergic and nonallergic subjects. METHODS: Ni(2+)-stimulated primary PBMC cultures derived from female subjects diagnosed as Ni-allergic (n = 5) or nonallergic (n = 5) on the basis of a positive or negative patch test were assessed for cell proliferation by tritiated thymidine incorporation and for production of interferon-gamma, IL-4, IL-10 and IL-17 in the culture supernatant by ELISA. The immunophenotype and TCR-Vbeta family affiliation of the Ni(2+)-induced lymphoblasts were determined by flow cytometry. RESULTS: Lymphocytes from Ni-allergic individuals challenged with a high and a low concentration of Ni showed significantly higher cell proliferation than lymphocytes from nonallergic individuals, but all subjects showed a positive LTT result (stimulation index >2). We found a significantly higher release of IL-10 in Ni(2+)-treated cultures from Ni-allergic compared with nonallergic subjects that provided better separation between individuals in the two groups than did lymphocyte proliferation. The proliferating lymphoblasts were predominantly CD4+, and in 2 of the 5 Ni-allergic subjects, but in none of the 5 nonallergic subjects, the CD4+ lymphoblasts showed a dominance of TCR-Vbeta17. CONCLUSIONS: Determination of IL-10 production in primary PBMC cultures is a potentially promising in vitro method for discrimination of Ni allergy in females, as compared with cell proliferation.

Adult↗

The socio-economic impact of telehealth: a systematic review.

We reviewed the socio-economic impact of telehealth, focusing on nine main areas: paediatrics, geriatrics, First Nations (i.e. indigenous peoples), home care, mental health, radiology, renal dialysis, rural/remote health services and rehabilitation. A systematic search led to the identification of 4646 citations or abstracts; from these, 306 sources were analysed. A central finding was that telehealth studies to date have not used socio-economic indicators consistently. However, specific telehealth applications have been shown to offer significant socio-economic benefit, to patients and families, health-care providers and the health-care system. The main benefits identified were: increased access to health services, cost-effectiveness, enhanced educational opportunities, improved health outcomes, better quality of care, better quality of life and enhanced social support. Although the review found a number of areas of socio-economic benefit, there is the continuing problem of limited generalizability.

Bias↗

The neurochemical characterisation of hypothalamic pathways projecting polysynaptically to brown adipose tissue in the rat.

The identification of leptin and a range of novel anorectic and orexigenic peptides has focussed attention on the neural circuitry involved in the genesis of food intake and the reflex control of thermogenesis. Here, the neurotropic virus pseudorabies has been utilised in conjunction with the immunocytochemical localisation of a variety of neuroactive peptides and receptors to better define the pathways in the rat hypothalamus directed polysynaptically to the major thermogenic endpoint, brown adipose tissue. Infected neurones were detected initially in the stellate ganglion, then in the spinal cord followed by the appearance of third-order premotor neurones in the brainstem and hypothalamus. Within the hypothalamus these were present in the paraventricular nucleus, lateral hypothalamus, perifornical region, and retrochiasmatic nucleus. At slightly longer survival times virus-infected neurones appeared in the arcuate nucleus and dorsomedial hypothalamus. Neurones in the retrochiasmatic nucleus and in the adjacent lateral arcuate nucleus which project to the brown adipose tissue express cocaine- and amphetamine-regulated transcript, pro-opiomelanocortin and leptin receptors. Neurones in the lateral hypothalamus, a site traditionally associated with the promotion of feeding, project to brown adipose tissue and large numbers of these contained melanin-concentrating hormone and orexin A and B. These data provide part of an anatomical framework which subserves the regulation of energy expenditure.

Adipose Tissue, Brown↗

Guidelines for visualization of cutaneous blood flow by laser Doppler perfusion imaging. A report from the Standardization Group of the European Society of Contact Dermatitis based upon the HIRELADO European community project.

This report reviews how to set up a laser Doppler perfusion imaging system intended for visualization of skin blood perfusion, capture images and evaluate the results obtained. A brief summary of related papers published in the literature within the areas of skin irritant and allergy patch testing, microdialysis and skin tumour circulation is presented, as well as early applications within other fields such as diabetology, wound healing and microvascular research.

Humans↗

Technical prerequisites for in vivo microdialysis determination of interleukin-6 in human dermis.

BACKGROUND: Cutaneous microdialysis in vivo in human skin is demonstrably of use in the study of skin metabolism, percutaneous absorption and skin inflammation. A promising area for cutaneous microdialysis is the measurement of cytokines. This requires catheters equipped with membranes permeable to molecules of high molecular weight. OBJECTIVES: To address technical problems of poor sample volume retrieval and analysis sensitivity in the simplest model of provocation, namely the insertion of the catheter itself in vivo into human dermis. METHODS: Use of a polyethylenesulphone membrane, with a cut-off value of 100,000 Da, allowed measurement of target molecules of large molecular weight. Using an adaptation of a commercially available high sensitivity enzyme-linked immunosorbent assay, the ubiquitous proinflammatory cytokine interleukin (IL)-6 was measured in the normal skin of six healthy volunteers after insertion of the microdialysis catheter. RESULTS: Reliable sample volumes and high analyte recovery were achieved either by push-pull pumping or by standard pumping using a perfusate consisting of Ringers Dextran 60 Braun. No IL-6 was detected in 25 of 26 samples taken during the first 100 min after catheter insertion. The IL-6 concentration then increased and remained elevated for the duration of the experiments. CONCLUSIONS: Technical and analytical modifications in the microdialysis technique have allowed the measurement of IL-6 in vivo in human dermis. It is suggested that the cytokine production is the result of the dermal trauma caused by catheter insertion, but the cellular source of the IL-6 is at present unknown.

Adult↗

2-Methoxyestradiol induces G2/M arrest and apoptosis in prostate cancer.

Few therapeutic treatment options are available for patients suffering from metastatic androgen-independent prostate cancer. We investigated the ability of the estrogen metabolite 2-methoxyestradiol to inhibit the proliferation of a variety of human prostate cancer cell lines in vitro and to inhibit the growth of androgen-independent prostate cancer in a transgenic mouse model in vivo. Our results showed that 2-methoxyestradiol is a powerful growth inhibitor of LNCaP, DU 145, PC-3, and ALVA-31 prostate cancer cells. Cell flow cytometry of 2-methoxyestradiol-treated DU 145 cells showed a marked accumulation of cells in the G2/M phase of the cell cycle and an increase in the sub-G1 fraction (apoptotic). In addition, staining for annexin V, changes in nuclear morphology, and inhibition of caspase activity support a role for apoptosis. More importantly, we showed that 2-methoxyestradiol inhibits prostate tumor progression in the Ggamma/T-15 transgenic mouse model of androgen-independent prostate cancer without toxic side effects. These results in cell culture and an animal model support investigations into the clinical use of 2-methoxyestradiol in patients with androgen-independent prostate cancer.

2-Methoxyestradiol↗

Three double-blind, randomized trials evaluating the safety and tolerance of different formulations of the saponin adjuvant QS-21.

The effects of the adjuvant QS-21 in various formulations on immediate pain on injection after intramuscular injection were evaluated in three Phase I clinical trials in healthy adults. Each trial was designed as a double-blind, randomized, four-way or five-way cross-over study with each subject acting as his/her own control. In the first trial, four formulations designed to evaluate the effect of QS-21 or pH (over a range of 6--7.2) were evaluated: phosphate-buffered saline at pH 6.0 or 7.2, and 50 microg of QS-21 in phosphate-buffered saline at pH 6.0 or 7.2. Thirty-three volunteers received each of the four intramuscular injections in random order separated by approximately 1 week. The volunteers assessed the immediate injection pain from 0 to 10 (none to most pain). The data indicate that the presence of QS-21, but not pH, is associated with transient injection site pain. The second trial, which utilized the same design as the first trial, evaluated formulations of QS-21 in various excipients. Fifteen volunteers received phosphate-buffered saline, QS-21/PBS, QS-21/aluminum hydroxide, and QS-21/4 mg/ml of polysorbate 80. Polysorbate 80, but not aluminum hydroxide, reduced the mean pain score compared to QS-21/PBS. The third trial evaluated formulations of QS-21 in additional excipients. Fifteen volunteers received aluminum hydroxide (without QS-21), QS-21/PBS, QS-21/0.72% benzyl alcohol, QS-21/30 mg/ml of hydroxypropyl-beta-cyclodextrin, and QS-21/8-mg/ml of polysorbate 80. Benzyl alcohol, cyclodextrin, and the higher concentration of polysorbate 80 reduced the pain scores associated with QS-21. Hence, QS-21 is associated with injection pain in simple buffer formulations, but it is possible to improve the acceptability of QS-21-containing formulations through reformulation with certain excipients.

2-Hydroxypropyl-beta-cyclodextrin↗

Oxidative damage induced by the injection of HIV-1 Tat protein in the rat striatum.

Oxidative stress has been hypothesized to play a role in the pathogenesis of different neurodegenerative disorders, including HIV-related dementia. Tat, a nonstructural protein of HIV, is implicated in potentiation of neuronal apoptosis by mechanisms involving the disruption of calcium homeostasis and oxidative stress. The injection of Tat caused an increase of protein carbonyl formation in the rat striatum. Increased oxidative modification of proteins occurred early after Tat injection and preceded Tat-mediated astrogliosis. Immunostaining of brain sections demonstrated that an area of prominent protein carbonyl immunoreactivity surrounded an injection site in the striatum of Tat-injected rats. Intense protein carbonyl immunoreactivity was localized in cell bodies. Our study suggests that increased protein oxidation may be an important part of the mechanism of Tat neurotoxicity.

Animals↗

Estrogen protects against the synergistic toxicity by HIV proteins, methamphetamine and cocaine.

BACKGROUND: Human immunodeficiency virus (HIV) infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness. To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat. RESULTS: Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by changes in mitochondrial membrane potential and neuronal cell death. Neurotoxicity occurred in a sub-population of neurons. Importantly, the presence of 17beta-estradiol prevented these synergistic neurotoxicities and the neuroprotective effects were partly mediated by estrogen receptors. CONCLUSION: Our observations suggest that methamphetamine and cocaine may affect the course of HIV dementia, and additionally suggest that estrogens modify the HIV-drug interactions.

Cells, Cultured↗

Regional brain and ventricular volumes in Tourette syndrome.

BACKGROUND: The pathophysiology of Tourette syndrome (TS) is thought to involve disturbances in cortico-striato-thalamo-cortical circuitry. The morphological characteristics of the cortical and associated white matter portions of these circuits have not been previously examined in TS subjects. METHODS: High-resolution anatomical magnetic resonance images were acquired in 155 TS and 131 healthy children and adults. The cerebrums and ventricles were isolated and then parcellated into subregions using standard anatomical landmarks. RESULTS: For analyses that included both children and adults, TS subjects were found to have larger volumes in dorsal prefrontal regions, larger volumes in parieto-occipital regions, and smaller inferior occipital volumes. Significant inverse associations of cerebral volumes with age were seen in TS subjects that were not seen in healthy controls. Sex differences in the parieto-occipital regions of healthy subjects were diminished in the TS group. The age-related findings were most prominent in TS children, whereas the diminished sex differences were most prominent in TS adults. Group differences in regional ventricular volumes were less prominent than in the cerebrum. Regional cerebral volumes were significantly associated with the severity of tic symptoms in orbitofrontal, midtemporal, and parieto-occipital regions. CONCLUSIONS: Broadly distributed cortical systems are involved in the pathophysiology of TS. Developmental processes, sexual dimorphisms, and compensatory responses in these cortical regions may help to modulate the course and severity of tic symptoms.

Adolescent↗

Elimination of active tad elements during the sexual phase of the Neurospora crassa life cycle.

Tad is an active LINE-like retrotransposon isolated from the Adiopodoumé strain of Neurospora crassa. Extensive analysis of other Neurospora strains has revealed no other strain with active Tad, but all strains tested have multiple copies of defective Tad elements. We have examined the ability of Tad to survive during the sexual cycle of Neurospora and find that active Tad is rapidly eliminated. The characteristics of this elimination suggest that the repeat-induced point mutation (RIP) mechanism was responsible. By the use of transformation to switch the mating type of the Adiopodoumé strain we concluded that this strain is not defective in the RIP process. Analysis of defective Tad elements isolated from a variety of strains indicates that the major difference between these elements and active Tad is due to the presence of a large number of G-C to A-T transition mutations. This would be expected if the changes were due primarily to the RIP process. Mapping of a selection of defective Tad elements reveals that they are present on all of the chromosomes; however, many of the elements are not widely shared among strains. This suggests that repeated introduction and elimination of Tad elements has occurred. Mechanisms that might be responsible for this repeated introduction are discussed.

Blotting, Southern↗

Success and failure of biphasic shocks: results of bidomain simulations.

The mechanisms behind the superiority of optimal biphasic defibrillation shocks over monophasic are not fully understood. This simulation study examines how the shock polarity and second-phase magnitude of biphasic shocks influence the virtual electrode polarization (VEP) pattern, and thus the outcome of the shock in a bidomain model representation of ventricular myocardium. A single spiral wave is initiated in a two-dimensional sheet of myocardium that measures 2 x 2 cm(2). The model incorporates non-uniform fiber curvature, membrane kinetics suitable for high strength shocks, and electroporation. Line electrodes deliver a spatially uniform extracellular field. The shocks are biphasic, each phase lasting 10 ms. Two different polarities of biphasic shocks are examined as the first-phase configuration is held constant and the second-phase magnitude is varied between 1 and 10 V/cm. The results show that for each polarity, varying the second-phase magnitude reverses the VEP induced by the first phase in an asymmetric fashion. Further, the size of the post-shock excitable gap is dependent upon the second-phase magnitude and is a factor in determining the success or failure of the shock. The maximum size of a post-shock excitable gap that results in defibrillation success depends on the polarity of the shock, indicating that the refractoriness of the tissue surrounding the gap also contributes to the outcome of the shock.

Animals↗