Biomedical subjects
Publications and source records attributed to P Holt.
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BACKGROUND: The incidence of Staphylococcus aureus (S. aureus) colonization on the skin of patients with atopic eczema/dermatitis syndrome (AEDS) is approximately 90% and a variety of evidence implicates epidermal staphylococcal infection as a pathogenic factor in atopic dermatitis. However, the mechanism(s) underlying the effects of this organism in the disease process are unclear. The cellular responses of AEDS suffers and asymptomatic atopic individuals to bacterial superantigens (SAg) were investigated in an attempt to elucidate the role of staphylococcal enterotoxin B (SEB) in atopic disease. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from normal nonatopic adults, asymptomatic atopic individuals, patients with active AEDS and patients with active allergic asthma. The cells were cultured for 24 or 96 h with house dust mite (HDM), SEB and phytohaemagluttinin (PHA), and the supernatants were assayed for cytokine levels. RESULTS: Staphylococcal enterotoxin B selectively stimulates the production of interleukin (IL)-5 in AEDS sufferers but not in asymptomatic atopics or nonatopics. Additionally, we observed comparable susceptibility to the IL-5-stimulatory effects of SEB in allergic asthmatics. CONCLUSIONS: Given the central role of IL-5-driven eosinophilia in progression from mild atopy to severe disease, these findings provide a plausible mechanism for the AEDS-promoting effects of staphylococcal SAg. Staphylococcal enterotoxin B may also have a similar role in atopic respiratory disease.
Inflammation is homeostatic process associated with a variety of cellular injuries resulting from infections, toxicosis, and physical trauma. The studies on inflammation in avian species are limited. To understand the inflammation-induced changes, 4-wk-old male broiler chickens were subjected to experimental inflammation by a subcutaneous injection of croton oil (inflammatory) with changes in serum measured over time and were compared with birds treated similarly with olive oil (injected control). Croton oil treatment significantly elevated serum interleukin (IL)-6 concentrations and heterophil counts by 6 and 16 h postinjection, respectively, which returned to the basal levels of controls at 16 and 24 h, respectively. Croton oil treatment affected the serum protein profiles of chickens as assessed by SDS-PAGE and densitometric analyses. Compared with olive oil-injected or noninjected chicken sera, there were increases in the density of protein bands corresponding to molecular weights (MW) of 42, 65, 200, and 219 kDa and decreases in bands corresponding to 49 kDa (serum albumin) and a 56-kDa protein in chickens treated with croton oil. Most of these changes were evident at 24 h and lasted through 48 h. The protein band corresponding to 65 kDa was further characterized using two-dimensional gel electrophoresis and N-terminal sequence analyses. A sequence similarity search in the Genbank database using the first 22 amino acids yielded a complete homology with chicken ovotransferrin. Western blot analysis using antichicken serum transferrin or antichicken ovotransferrin antibodies also confirmed the 65-kDa protein band to be ovotransferrin. Under nonreducing conditions, the ovotransferrin standard also showed an apparent MW corresponding to 65 kDa, like the serum transferrin. The serum ovotransferrin was found to be glycosylated using a glycoprotein stain. Although the significance of ovotransferrin in avian inflammation is not clear, these results show that it is a major acute phase protein (APP) in chickens.
AIMS: To evaluate whether a single decapolar electrode is a reliable and cost-effective substitute for the 'Halo' catheter to map the circuit and detect bidirectional isthmus block during atrial flutter (AFL) ablation. METHODS AND RESULTS: Twenty-four patients underwent AFL ablation by using the decapolar electrode in the infero-lateral wall of right atrium (group A) while a 'Halo' catheter was used in 11 patients (group B). Both groups had similar clinical characteristics. Anti-clockwise rotation (20 patients), clockwise (3 patients) or both forms of AFL (1 patient) were detected in group A. All patients in group B had anti-clockwise AFL. Bidirectional isthmus block was completed in 22 patients of group A and in 9 of group B (P=NS) while incomplete isthmus block was detected in 2 patients in each group (P=NS). Mean fluoroscopy and procedure time was 27 +/- 47 min, 107 +/- 36 min in group A and 14 +/- 19 min, 114 +/- 65 min in group B (P=NS). AFL relapsed in 3 patients of group A (follow-up 7 +/- 4 months) and in 2 of group B (4 +/- 2 months). CONCLUSION: A single decapolar electrode is a reliable method to map the circuit and demonstrate bidirectional isthmus block during AFL ablation. The cost of the decapolar electrode is a quarter of that of the 'Halo' catheter. This represents a significant saving particularly for centres with a substantial number of AFL ablations.
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OBJECTIVE: To compare the clinical efficacy of rofecoxib, a specific inhibitor of cyclooxygenase 2 (COX-2), with that of diclofenac in patients with osteoarthritis (OA) and to evaluate the safety and tolerability of rofecoxib. METHODS: We performed a randomized, double-blind, active comparator-controlled trial in 784 adults with OA of the knee or hip. Patients were randomized to 1 of 3 treatment groups: 12.5 mg of rofecoxib once daily, 25 mg of rofecoxib once daily, and 50 mg of diclofenac 3 times daily. Clinical efficacy and safety were evaluated over a 1-year continuous treatment period. RESULTS: Rofecoxib at dosages of 12.5 and 25 mg demonstrated efficacy that was clinically comparable to that of diclofenac, as assessed by all 3 primary end points according to predefined comparability criteria. Results from secondary end points were consistent with those of the primary end points. There were small statistical differences favoring diclofenac for 2 of the end points. All treatments were well tolerated. CONCLUSION: Rofecoxib was well tolerated and provided efficacy that was clinically comparable, according to predefined statistical criteria, to that of 150 mg of diclofenac per day in this 1-year study. Specific inhibition of COX-2 provided therapeutic efficacy in OA.
BACKGROUND: Most health care executives see outcome measurement as a technical or tactical matter rather than as a strategic tool. Accordingly, provider investment in outcome measurement and management is relatively small. Nevertheless, outcome information can be key to achieving an organization's strategic objectives. Advances in risk adjustment and improvements in technology for data collection and analysis have made outcome measurement a practical tool for individual hospital use. CASE STUDIES: Strategically integrated outcome measurement efforts can give providers a competitive advantage over organizations that only use outcomes tactically. One of the best examples of an acute care provider that has used outcome information for strategic advantage is Intermountain Health Care (IHC; Salt Lake City). In 1997 IHC made clinical quality and outcomes the primary focus of its five-year strategic plan. To support the new strategy IHC's board of trustees approved the development of an outcome information system that generated data along clinical processes of care and the creation of a new management structure to use these data to hold professionals accountable and to set and achieve clinical improvement goals. From 1996 to 1999, IHC's share of the commercial health care market in Utah increased from roughly 50% to about 62% of the market, with the result that it has stopped actively marketing its services. DISCUSSION: Health care executives will not willingly invest in outcomes until they believe that they have business value. Therefore, making the business case for outcomes can help improve the quality of health care and the lives of individuals.
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Procedures have been developed to identify the chromatographic binding domains of horse heart cytochrome c (Cyt c) and bovine growth hormone (bGH) during their interaction with reversed-phase sorbent materials. The procedure involves adsorption of the protein solute to the chromatographic sorbent, followed by proteolytic cleavage. Comparison of the proteolytic map obtained for Cyt c and bGH in free solution with the corresponding map obtained when these proteins are adsorbed to the chromatographic sorbent revealed significant differences in the digestion pattern. Following characterization of the peptides generated in both maps, the results indicated that specific regions on the surface of both Cyt c and bGH are inaccessible to tryptic cleavage when adsorbed to the hydrophobic surface of both a C-4 and a C-18 sorbent. Based on the assumption that the region of the protein surface that is in contact with the sorbent remains intact and bound to the sorbent during the digestion step, while the protein surface that is exposed to the solvent is accessible to proteolysis, the regions that were inaccessible to tryptic digestion were found to correspond to hydrophobic domains on the protein surface. These results also suggest that the three-dimensional structures of these proteins remain largely intact upon adsorption to the hydrophobic surface.
OBJECTIVE: To determine current beliefs and knowledge about, and use of, two screening tests for breast cancer (mammography and clinical breast examination [CBE]) among general practitioners (GPs). DESIGN, PARTICIPANTS AND SETTING: National postal survey of randomly selected GPs from throughout Australia in May 1996. MAIN OUTCOME MEASURES: Belief in the effectiveness of each screening test in reducing premature deaths from breast cancer; recommended age group and screening interval for each test; likelihood of including each opportunistically or in a health check-up. Predictors were determined by regression analyses. RESULTS: The response rate was 67% (855/1271). Significantly more respondents believed in the effectiveness of mammography than of CBE (92% v. 66%). About half identified women 50 years and over as the appropriate target group for mammography. Only 40% indicated they would be "highly likely" to discuss mammography opportunistically, although 82% would be "highly likely" to discuss it in a health check-up. After adjusting for confounders, female GPs were more likely to discuss mammographic screening and to advocate a biennial frequency. Older GPs and those from New South Wales were least likely to recommend mammography (consistent with the national policy). Significantly more respondents were "highly likely" to discuss CBE than mammography in a health check-up. CONCLUSIONS: GPs are convinced of the effectiveness of mammography, but as respondents were more likely to screen by CBE than to recommend mammography in a dedicated health check-up a consistent national policy about CBE would be highly desirable.
An explicit focus on health outcomes has the potential to improve health if applied at the local level. However, clinical services require clear and practical support in the measurement and analysis of health outcome indicators. This paper suggests 12 steps for departments or services to take in promoting an outcomes orientation, based on our experiences in the Central Sydney Area Health Service. These include determining commitment at the service level, setting up a working group, specifying service consumers, their health problems and intervention processes, specifying desired health changes, consulting the literature and peers, identifying existing resources, pilot-testing and refining outcome measures, collecting data and responding to sub-optimal results with evidence-based interventions. The paper also reviews common criticisms of the health outcomes approach and key issues which have arisen in the course of applying these steps at the local level.
This cross-sectional survey of cancer screening in May 1996 used a national random sample of a specified group of general practitioners (GPs). The survey included items to assess the impact of the Organised Approach to the Prevention of Cervical Cancer (OAPCC). Of the 1,271 GPs who satisfied the eligibility criteria, 855 (67%) returned a completed questionnaire. Fifty-two per cent indicated they would be 'highly' likely to introduce a discussion about cervical smears to a 58-year-old woman who was in good health and had come for a non-gynaecological consultation. Female sex, RACGP affiliation, practising in a metropolitan area and awareness of the OAPCC booklet were independent predictors of an opportunistic orientation. By contrast, 91% indicated that they would be 'highly' likely to include a Pap smear in a general health checkup. Thirty-eight per cent reported that they had found the booklet about the 1991 screening policy 'very' useful, while 38% found the NHMRC guidelines for the management of women with screen detected abnormalities 'very' useful. Around one-fifth of the GPs were not aware of these documents. Overall, 19% still recommended annual or more frequent screening. GPs from NSW and Queensland were less likely to support biennial screening than GPs from other states. Overall, 26% of GPs did not indicate that they would refer a woman who had tested positive for any grade of CIN for colposcopic assessment. Female GPs were more likely to refer women with CIN for colposcopic assessment while older doctors were less likely to do so.
To evaluate response-aiding strategies feasible in large surveys, we randomly allocated general practitioners (GPs) to one of four intervention groups: Group 1 received 'exhaustive' telephone prompts by a medical peer in advance of a questionnaire; Group 2, inclusion of an embossed pen with the questionnaire; Group 3, an advance letter prompt; and Group 4, a 'single attempt' advance telephone prompt by a non-medical research assistant. Follow-up procedures were identical. Response rates by group were not significantly different overall (chi 2 = 4.59, df = 3, p = 0.20) although advance prompts by a medical peer were significantly more effective than other strategies for male GPs. The difference in overall response rates between males (63%) and females (74%) was significant (chi 2 = 15.40, df = 1, p < 0.01). No other response bias was evident. Our demonstration of a significant interaction between respondent sex and response-aiding strategy invites further research.
For the first time the complete cDNA encoding a major allergen and novel protein of the yeast Malassezia furfur, Mal f 1, has been sequenced and expressed. The amino acid sequences of nine tryptic peptides of the protein were determined. Oligonucleotides were designed from these amino acid sequences. The cDNA sequence was obtained by hybridizing these primers to mRNA and enhancement by reverse-transcriptase PCR techniques. The cDNA is 1176 bp in length. It shows an open reading frame of 1050 bp coding for a protein of 38178 Da and a deduced amino acid sequence containing 350 residues. The hydropathy plot and the tryptic digest indicate that the first 22 amino acids represent a leader sequence determining a mature protein of 35 988 Da. The complete encoding cDNA was expressed as a maltose-binding protein fusion protein in Escherichia coli. The recombinant fusion protein reacted with our specific monoclonal antibody and with IgE from patients with atopic dermatitis.
Although the molecular genetic changes that take place during carcinogenesis in the large bowel have been well elucidated, very little work has been done on the carcinogenesis process in the small bowel where this phenomenon is much rarer. The few studies that have been done to suggest that certain oncogenes, i.e., erbB2, K-ras, cyclin D1, and p53, are all altered in ways and in frequency similar to these phenomena in large bowel cancer. Some tumor markers have been noted to occur in malignant carcinoid tumours as well. Given the overall similarities in the epidemiology and the role of the adenoma-carcinoma sequence for both small bowel adenocarcinoma and colorectal adenocarcinoma, it is highly likely that the same molecular genetic changes play a major role. Further work is needed to confirm this. If true, a potentially important are of future research would be to determine why these molecular genetic changes occur so much less frequently in the small bowel as compared to the large bowel.
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In a telephone survey of 455 of the top 600 companies in Australia, around three-quarters reported the existence of restrictions on both smoking and alcohol in the workplace. Forty-six percent of companies had a total ban on smoking at work, 31% had designated limited areas where employees were permitted to smoke, and 23% had no policy on smoking. Seventy-seven percent of companies encouraged a total alcohol-free work environment. The larger the company, the more likely it was to have restrictions on smoking in the work-place, but there was no relationship between the size of the company and alcohol restrictions. Government organizations were more likely to have restrictions on smoking than non-government organizations, but this difference was not apparent for alcohol restrictions. The major reasons given for smoking restrictions were related to health and comfort, while those for alcohol were related to work productivity and safety.
This article presents findings from a survey of programmes available for tobacco and alcohol users working in 455 of Australia's top 600 companies. Companies were twice as likely to have programmes for smokers (43%) as for problem drinkers (24%) and these programmes were more apparent in large companies. The majority of programmes for smoking were delivered within a health promotion context which included other life-style issues, such as nutrition, exercise, weight management and stress management. Although Employee Assistance Programs (EAPs) were the most commonly available type of work-place programme for excessive drinkers and other drug users, followed by Alcoholics Anonymous and local hospital clinics, only 6% had an EAP for alcohol. Only 21% of programmes for smokers and 12% for excessive alcohol users were evaluated. Around one-quarter of companies knew the costs of smoking programmes, and 9% reported costs of conducting programmes for excessive alcohol consumers.