Biomedical subjects
Publications and source records attributed to A Miller.
The mechanism of chest pain in spontaneous pneumothorax has never been discussed in the literature. It is proposed that this is due to acute parietal pleural irritation secondary to leakage of inflammatory material following bleb rupture, rather than the presence of interpleural air.
Glucagon-like peptide-2 (GLP-2) is an enteroendocrine hormone which is uniquely trophic for the intestine; a physiological role in regulating nutrient absorptive capacity is becoming apparent. GLP-2, independent of enteral feeding, stimulates a classical pattern of intestinal adaptation in terminal ileum following resection. Herein we investigate the effects of GLP-2 on the jejunal remant using a rat model of short bowel syndrome (SBS). Juvenile 250- to 275-g SD rats underwent 80% distal small bowel resection, leaving 20 cm of proximal jejunum and venous catheterization. Animals were maintained with total parenteral nutrition (TPN) or TPN+10 microg/kg/hr GLP-2 (n=8 per group). After 7 days, intestinal permeability was assessed by urinary recovery of gavaged carbohydrate probes. Animals were euthanized, and the intestines taken for analysis of morphology, crypt cell proliferation, apoptosis, and expression of SGLT-1 and GLUT-5 transport proteins. GLP-2 treatment reduced intestinal permeability and increased in vivo glucose absorption, small intestinal weight, surface area, villus height, crypt depth, and microvillus height. Intestinal mucosal DNA and protein content per unit length of the small bowel were increased (P < 0.05 for all comparisons). However, in contrast to previous studies examining GLP-2's effects on remnant ileum, the jejunal crypt apoptotic index was increased in GLP-2-treated animals, with no increase in SGLT-1 or GLUT 5 expression. These results show that exogenous GLP-2 treatment of animals with jejunal remnant reduces intestinal permeability, increases glucose absorption, and stimulates morphological features of intestinal adaptation including increased micovillus height and surface area. However, the pattern of changes seen is different from that in remnant ileum. This suggests that GLP-2's effects are specific to different regions of the bowel. Nonetheless, remnant jejunum is responsive to GLP-2 in the absence of enteral nutrition. Further studies are warranted to establish the mechanisms of action and therapeutic potential of GLP-2 in modulating nutrient absorptive capacity.
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Very large and complex incisional hernias, especially those with loss of abdominal wall, can be a very interesting and perplexing problem, which present a particular challenge to the surgeon. The reported technique was developed and refined by one of our surgeons, between 1998 and 1999 for the repair of incisional hernias in a selected group of patients with large defects, often with a major loss of abdominal wall, overweight and previous attempts for incisional hernia repair. The technique involves a modified preperitoneal approach and was used on 43 eligible patients between 1999 and 2002. There were 30 females and 13 males at a mean age of 61 years. The median ASA score of the group was 2, with a mean BMI of 30.4 and a mean hernia surface area of 162 cm(2). One-third of the patients had one or more previous incisional hernia repair. Mean operating time was 190 min with an average hospital stay of 5.7 days. Postoperative complications occurred in 28% of the patients, most of which were minor and did not necessitate admission to the intensive care unit. None of the patients died. Wound infections occurred in 9.3%, was associated with an increased risk for cutaneous sinus formation, but not for mesh removal or hernia recurrence. A recurrence rate of 12.5% was found after a mean follow-up period of 46 months. We advocate this procedure for the repair of large, complex incisional hernias with loss of abdominal domain in patients with significant risk factors for recurrence.
OBJECTIVE: To describe the infant feeding practices and attitudes of women who used prevention of mother-to-child transmission of HIV (PMTCT) services in rural Zimbabwe. DESIGN: A cross-sectional study including structured interviews and focus group discussions was conducted between June 2003 and February 2004. SETTING: The study took place in Murambinda Mission Hospital (Buhera District, Manicaland Province), the first site offering PMTCT services in rural Zimbabwe. SUBJECTS: The interviews targeted HIV-infected and HIV-negative women who received prenatal HIV counselling and testing and minimal infant feeding counselling, and who delivered between 15 August 2001 and 15 February 2003. The focus groups were conducted among young and elderly men and women. RESULTS: Overall, 71 HIV-infected and 93 HIV-negative mothers were interviewed in clinics or at home. Most infants (97%) had ever been breast-fed. HIV-negative mothers introduced fluids/foods other than breast milk significantly sooner than HIV-infected mothers (median 4.0 vs. 6.0 months, P = 0.005). Infants born to HIV-negative mothers were weaned significantly later than HIV-exposed infants (median 19.0 vs. 6.0 months, P = 10(-5)). More than 90% of mothers reported that breast-feeding their infant was a personal decision, a third of whom also mentioned having taken into account health workers' messages. CONCLUSION: The HIV-infected mothers interviewed were gradually implementing infant feeding practices recommended in the context of HIV. Increased infant feeding support capacity in resource-limited rural populations is required, i.e. training of counselling staff, decentralised follow-up and weaning support.
BACKGROUND: There is little information in the research literature of agreement between parent and child in reports of child quality of life (QOL) for a sample of children diagnosed with attention-deficit/hyperactivity disorder (ADHD). The aim of our study was to determine whether parent and child concordance is greater for physical domains of QOL than for psychosocial domains; whether parents rate their child's QOL better or poorer than their child's ratings; and whether concordance is related to demographic, socioeconomic or clinical factors. METHODS: The study was a questionnaire survey of children aged 10-17 referred to the ADHD clinic and diagnosed with ADHD in the province of British Columbia (Canada) between November 2001 and October 2002 and their parent. RESULTS: Fifty-eight children diagnosed with ADHD and their parents completed our study questionnaire. The main outcome measure was the Child Health Questionnaire, which permitted comparisons on eight QOL domains and one single item. Intraclass correlation coefficients were moderate for five domains (range from 0.40 to 0.51), and good for three domains (range from 0.60 to 0.75). Children rated their QOL significantly better than their parents in four areas and poorer in one. Standardized Response Means indicated clinically important differences in mean scores for Behaviour and Self-esteem. Compared with population norms, across most domains, children with ADHD reported comparable health. Discrepancies between parent-child ratings were related to the presence of a comorbid oppositional/defiant disorder, a psychosocial stressor and increased ADHD symptoms. CONCLUSIONS: Although self-report is an important means of eliciting QOL data, in children with ADHD, given the discrepancies in this study between parent and child report, measuring both perspectives seems appropriate.
OBJECTIVE: To evaluate the influence of a prevention of mother-to-child transmission of HIV advocacy and mobilization campaign on awareness and knowledge levels within the community. METHOD: We used a knowledge, attitudes and practices survey to collect baseline data in November 2002 and again in July 2004 for evaluation purposes. RESULTS: A total of 351 women attending healthcare services were interviewed each time. The proportion of women aware of the service increased from 48.0% in 2002 to 82.8% in 2004 (OR = 4.9, 95% CI 3.3-7.3, P = 0.001). Exclusive breastfeeding was identified as a mother-to-child transmission risk factor by 27.1% in 2002 and by 55.8% of respondents in 2004 (OR = 2.9, CI 2.1-4.2, P = 0.001). Although most interviewees agreed that the prevention of sexual transmission of HIV was the best strategy for prevention of mother-to-child transmission of HIV (88.3% in 2002 and 96.4% in 2004), few reported having ever used a male condom (24.8% in 2002 vs. 29.8% in 2004, P = 0.16). DISCUSSION: Prevention of mother-to-child transmission of HIV strategies at both individual and community level were still insufficiently understood and applied. Targeted educational messages and communication for social change need to be combined. Knowledge, attitudes and practices surveys can be used to monitor programme progress.
An International Working Group for Treatment Optimization in MS met to recommend evidence-based therapeutic options for the management of suboptimal responses or intolerable side-effects in patients treated with disease-modifying drugs (DMDs) for multiple sclerosis (MS). Several DMDs are now available for the treatment of MS that have been shown to alter the clinical course of the disease by decreasing disease activity and delaying the progression of disability. Nevertheless, many patients continue to experience disease activity whilst on treatment, and recommendations have been made on how the success of therapy in an individual patient can be assessed. However, even after having identified criteria for a suboptimal response to current treatments, clinicians require guidance on how to improve the outcomes. This report summarizes the conclusions from a workshop at which this issue was addressed. We suggest treatment pathways for optimizing therapy for those patients with suboptimal responses to DMDs, and therapeutic options for patients with unacceptable side-effects on their current therapy.
OBJECTIVE: To examine the efficacy of two preparatory interventions on one mile run performance in 90 high school long distance runners. METHOD: After participants had completed a one mile baseline run, they were randomly assigned to participate in either one of two interventions (brief yoga exercises, motivational shouting exercises) or a no intervention control condition. Experimental conditions were implemented one week after the baseline run about 20 minutes before a second one mile trial. RESULTS: Participants assigned to the motivational intervention improved their running performance significantly more than those assigned to the other two conditions. Although the magnitude of the effect was small, participants assigned to yoga exercises showed significant improvements in running performance relative to control condition participants. Consumer satisfaction ratings indicated that participants who were assigned to the motivational and yoga exercise groups liked their interventions more than those assigned to the control group. CONCLUSION: Motivational and yoga interventions designed to improve long distance running performance were equally acceptable to the participants, but the former had a greater effect.
The continuing medical education (CME) needs of anaesthetists within Australia, New Zealand, Hong Kong, Malaysia and Singapore have been largely unknown. The aim of this study was to undertake a comprehensive survey of the attitude to CME, learning preferences, attitudes and abilities relating to self-paced material, literature and information searching, preferred content and preferred approach to CME of anaesthetists within these countries. A survey tool was developed and refined for ease of use by pilot-testing. The survey was mailed to 3,156 anaesthetists throughout Australia, New Zealand, Hong Kong, Malaysia and Singapore. Three options for data return were offered; postal reply, facsimile and a data entry web-page. There were 1,800 responses, which represented a response rate of 57%. The demographics of the respondents were similar to the overall demographics of Fellows of the Australian and New Zealand College of Anaesthetists. A large majority of respondents (92%) stated that their involvement in CME improved patient care. However, almost half the respondents reported that they have difficulty either in participating in current CME activities (31%) or implementing new knowledge into their workplace (14%). Anaesthetists within this region appear to be motivated by the need to make better decisions based on independent standards of practice. While Australia is a world leader in flexible education, it is still emerging as a discipline. Flexible education may be used to facilitate anaesthetists' participation in CME activities and in implementation of new knowledge in their workplace.
The discovery of tetrahydrogestrinone (THG) abuse by several elite athletes led the U.S. Congress to declare it a controlled substance, although conclusive evidence of its anabolic/androgenic activity is lacking. We determined whether THG affects myogenic differentiation and androgen receptor (AR)-mediated signaling, whether it binds to AR, and whether it has androgenic and anabolic effects in vivo. Accordingly, we measured the dissociation constant for THG with a fluorescence anisotropy assay using recombinant AR-ligand binding domain. The AR nuclear translocation and myogenic activity of androstenedione were evaluated in mesenchymal, multipotent C3H10T1/2 cells. We performed molecular modeling of the THG:AR interaction. The androgenic/anabolic activity was evaluated in orchidectomized rats. THG bound to AR with an affinity similar to that of dihydrotestosterone. In multipotent C3H10T1/2 cells, THG upregulated AR expression, induced AR nuclear translocation, dose dependently increased the area of myosin heavy chain type II-positive myotubes, and up-regulated myogenic determination and myosin heavy chain type II protein expression. The interaction between AR and the A ring of THG was similar to that between AR and the A ring of dihydrotestosterone, but the C17 and C18 substituents in THG had a unique stabilizing interaction with AR. THG administration prevented the castration-induced atrophy of levator ani, prostate gland, and seminal vesicles and loss of fat-free mass in orchidectomized rats. We conclude that THG is an anabolic steroid that binds to AR, activates AR-mediated signaling, promotes myogenesis in mesenchymal multipotent cells, and has anabolic and androgenic activity in vivo. This mechanism-based approach should be useful for rapid screening of anabolic/androgenic agents.
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Patient and/or resident handling is a major cause of injury to healthcare workers. The effectiveness of an overhead ceiling lift programme at mitigating the risk of injury from resident handling was evaluated by comparing injury data and staff perceptions before and after implementation of the programme, and by comparison with a similar unit that did not implement an overhead ceiling lift programme. A questionnaire was used to assess perceived risk of injury and discomfort, preferred resident handling methods, frequency of performing designated resident handling tasks, perceived physical demands, work organization, and staff satisfaction. Staff preferred overhead ceiling lifts to other methods of transfer (manual or floor lifts) when lifting or transferring residents. A significant reduction was observed in the perceived risk of injury and discomfort to the neck, shoulders, back, hands, and arms of care staff. Compensation costs due to lifting and transferring tasks were reduced by 68% for the intervention unit and increased by 68% for the comparison unit. Overhead ceiling lifts were not beneficial in reducing the perceived risk of injury, pain or discomfort, or compensation costs when used to reposition residents. The study demonstrated an overall cost-savings associated with the installation of the overhead lifts, and highlighted areas for further improvement.
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Screening people for serious diseases is receiving increasing attention as studies demonstrates the potential benefits of early detection and early intervention in preventing morbidity and mortality. Screening tests are available for some of the most important noncommunicable diseases, including cardiovascular disease, type 2 diabetes and several site-specific cancers. However, screening guidelines for cardiovascular disease, cancers and diabetes vary within and between countries because many national and international organizations are developing their own guidelines. There is a need to address the issue of screening for disease, with an emphasis on providing accurate and practical information relevant to all countries. This report arose from a Consultation Group meeting held at WHO headquarters in Geneva. It presents an examination of the principles of screening with an emphasis on noncommunicable disease prevention and control policy.
Data in the Caribbean documenting the speciation of yeast associated with vulvovaginitis are lacking. The widespread use of antibiotics and increased availability of antimycotic agents, both prescribed and over-the-counter, predisposes both to a change in the epidemiologic patterns and the possible development of secondary resistance among previously susceptible yeast. This study was conducted to evaluate the aetiologic agents associated with mycotic vulvovaginitis and to review the appropriateness of prescribed antifungal therapy. Of 134 positive isolates, the most frequent yeast isolate was C. albicans accounting for 78%, C. tropicalis 10%, Prototheca wickerhamii (P. wickerhamii) 5%, C. glabrata 4%, Cryptococcus albidus (C. albidus) 2% and C. lusitaniae (1%) were also isolated. Of the positive cases, 75% were treated with antifungals, 17% with antibiotics and 8% were not treated. The azole group was the most frequently prescribed antifungal (71%). Of cases with negative yeast cultures, 83% were treated with antifungals. The presence of non-albicans Candida species and other opportunistic fungi is an important finding and combined with the pattern of therapy, represents a major challenge for future empirical therapeutic and prophylactic strategies in the treatment of mycotic vulvovaginitis.
Autoimmune diseases seem to have strong genetic attributes, and are affected to some extent by shared susceptibility loci. The latter potentially amount to hundreds of candidate genes (CG), creating the need for a prioritization strategy in genetic association studies. To form such a strategy, 26 autoimmune-related CG were genotyped for a total of 72 single nucleotide polymorphisms (SNPs) in three distinct Israeli ethnic populations: Ashkenazi Jews, Sephardic Jews and Arabs. Four quantitative criteria reflecting population stratification were analyzed: allele frequencies, haplotype frequencies, the Fst statistic for homozygotes distribution and linkage disequilibrium extents. According to the consequent interpopulation genomic diversity profiles, the genes were classified into conserved, intermediate and diversified gene groups. Our results demonstrate a correlation between the biological role of autoimmune-related CG and their interpopulation diversity profiles as classified by the different analyses. Annotation analysis suggests that genes more readily influenced by environmental conditions, such as immunological mediators, are 'population specific'. Conversely, genes showing genetic conservation across all populations are characterized by apoptotic and cleaving functions. We suggest a research strategy by which CG association studies should focus first on likely conserved gene categories, to increase the likelihood of attaining significant results and promote the development of gene-based therapies.
BACKGROUND: Analysis of the bispectrum of EEG waveforms is a component of the proprietary BIS index-a commonly used commercial monitor of depth of anaesthesia. Does the use of the bispectrum give more information about depth of anaesthesia than the power spectrum? METHODS: We collected and analysed EEG waveforms during induction of general anaesthesia in 39 patients, comparing the changes in bispectral parameter (SynchFastSlow), with an analogous power spectrum-based parameter (PowerFastSlow). Both compare the logarithmic ratio of high frequency components (40-47 Hz) with the total (1-47 Hz). Because the changes in bispectrum are affected by signal amplitude, we also calculated a third parameter (SFSbicoh) from the bicoherence, which is an amplitude-independent statistic. RESULTS: The SynchFastSlow and PowerFastSlow were correlated (r=0.84) and neither was superior in predicting the awake or anaesthetized state (area under receiver operating characteristic curves = 0.85 vs 0.93). There was no change in the SFSbicoh over the induction period, and it did not correlate with SynchFastSlow (r=0.07). CONCLUSIONS: We could not show that bispectral analysis gave more information than power spectral-based analysis. Most of the changes in the bispectral values result from decreases in the relative high frequency content of the EEG caused by anaesthesia.