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Biomedical subjects

A Fraser

Publications and source records attributed to A Fraser.

At least 55 records · Page 3Linked to original sources
PubMed2001

Matrix metalloproteinase 9, apoptosis, and vascular morphology in early arthritis.

OBJECTIVE: To examine matrix metalloproteinase 9 (MMP-9) in the synovial fluid (SF) and synovial membrane (SM) in relation to vascular endothelial cell (EC) apoptosis, vascular endothelial growth factor (VEGF), and SM vascular pattern. METHODS: Thirty-four patients underwent needle arthroscopy of the knee joint; 12 had early rheumatoid arthritis (RA), 12 had early psoriatic arthritis (PsA), and 10 had osteoarthritis (OA). The early RA and early PsA patients were matched for disease activity. SF levels of MMP-9 and VEGF were measured by an enzyme-linked immunosorbent assay, and EC apoptosis was measured by TUNEL assay. MMP-9 expression was examined in SM by immunohistochemistry. Synovial tissue explants were stimulated with VEGF, and MMP-9 levels were measured in the supernatants. The synovial vascular pattern was recorded. RESULTS: SF MMP-9 levels were significantly higher in early PsA patients than in early RA patients; OA patients had minimal levels. MMP-9 levels correlated with blood vessel morphology and SF VEGF levels. MMP-9 expression was greater in early PsA SM than in early RA SM, but the difference was not significant. In contrast however, EC apoptosis was greater in early RA SM than in early PsA SM. MMP-9 levels increased 2-fold and 9-fold, respectively, in SM explant culture supernatants on day 7 in response to stimulation with 25 ng/ml and 50 ng/ml of VEGF. CONCLUSION: SF MMP-9 levels correlate with the pattern of SM neovascularization and SF VEGF levels in early inflammatory arthritis, and VEGF increases MMP-9 production by SM. Endothelial cell apoptosis, however, appears to be more prevalent in early RA. This combination of factors may explain the pattern of differential angiogenesis in these arthritides.

Adult↗
PubMed2001

The clinical features, risk factors and outcome of thrombotic thrombocytopenic purpura occurring after bone marrow transplantation.

In this study, we retrospectively analysed the clinical features, risk factors and outcome of 22 patients with thrombotic thrombocytopenic purpura (TTP) occurring after allogeneic stem cell transplantation. All but two of these patients received stem cells from unrelated donors (UDs), two-thirds were female, three-quarters were adults and leukaemia was the major reason for transplant. The incidence of TTP was 20 out of 332 patients (6%) with UD transplants and two out of 104 recipients (2%) of matched sibling allografts (P = 0.16). In order to ascertain basic demographic risk factors for the development of TTP, we compared the 22 patients with 434 patients who did not develop TTP. Compared with patients who did not develop TTP, patients with TTP were nearly three times older (P < 0.001) and were more than twice as likely to be female (P = 0.001). Because > 90% of patients were recipients of UD marrow, we then compared the 20 UD-bone marrow transplantation (BMT) patients with 60 randomly selected UD-BMT patients who did not develop TTP. On univariate analysis, age and female gender were again significant risk factors, as was grade II-IV acute graft-versus-host disease (GvHD) (P = 0.002), and there was a trend towards an association with chronic GvHD (P = 0.083). However, after logistic regression analysis, only age and sex remained significant (P < 0.001 and 0.009 respectively). We report an 86% mortality with only three survivors out of 22 patients, and one of these remains thrombocytopenic and red cell transfusion dependent, possibly in part because of graft hypoplasia. Six out of 17 patients responded to plasmapheresis, but the majority of them ultimately succumbed because of TTP, often in association with GvHD or fungal infection.

Adolescent↗
PubMed2001

Are people with learning disabilities able to contribute to focus groups on health promotion?

AIM: This paper shows the differences between the success of three focus groups in promoting group discussion on health promotion and also the detailed effects of individual members with speech and language difficulties in participating. BACKGROUND: Conducting focus groups with people with learning disabilities can promote their social inclusion. CONCLUSIONS: We conclude that focus groups are an effective method of conducting exploratory research with adults with learning disabilities in the community, however, ability to participate with other members may be a limiting factor. Furthermore, special arrangements may need to be made for groups to be successful, including the use of an interpreter. The preparation of the moderator is also an important factor in group success.

Adult↗
PubMed2001

Hydrogen peroxide has opposing effects on IKK activity and IkappaBalpha breakdown in airway epithelial cells.

Recent studies have advanced our knowledge about the signal transduction cascade involved in the activation of nuclear factor (NF) kappaB, including the identification and characterization of IkappaB kinases (IKKs). Although exposure to hydrogen peroxide (H2O2) in vitro can activate NF-kappaB, this response is not universal and depends on the cell type and transformation state. In this study, we examined the effects of H2O2 on IKKs and activation of NF-kappaB in primary normal human bronchial epithelial (NHBE) cells. Our results demonstrate that treatment with H2O2 increased IKK activity, phosphorylation, and ubiquitination of IkappaBalpha in NHBE cells. However, there was no significant proteolytic degradation of IkappaBalpha, nuclear translocation of p65, or NF-kappaB DNA binding activity in cells treated with H2O2. Treatment with H2O2 also inhibited tumor necrosis factor (TNF)-alpha-induced IkappaBalpha breakdown, NF-kappaB DNA binding activity, and NF-kappaB-dependent transcription but had no effect on TNF-alpha-induced IkappaBalpha phosphorylation or ubiquitination. Furthermore, treatment with H2O2 alone or in combination with TNF-alpha increased the levels of other ubiquitinated proteins in NHBE cells, suggesting general inhibition of proteasomal activity by H2O2. Taken together, these results demonstrate that in airway epithelial cells treatment with H2O2 has opposing effects on IKK activity and proteasomal degradation of IkappaBalpha, and suggest that H2O2 may suppress TNF-alpha-induced NF-kappaB- dependent gene expression.

Bronchi↗
PubMed2000

Randomised controlled trial of nurse practitioner versus general practitioner care for patients requesting "same day" consultations in primary care.

OBJECTIVE: To ascertain any differences between care from nurse practitioners and that from general practitioners for patients seeking "same day" consultations in primary care. DESIGN: Randomised controlled trial with patients allocated by one of two randomisation schemes (by day or within day). SETTING: 10 general practices in south Wales and south west England. SUBJECTS: 1368 patients requesting same day consultations. MAIN OUTCOME MEASURES: Patient satisfaction, resolution of symptoms and concerns, care provided (prescriptions, investigations, referrals, recall, and length of consultation), information provided to patients, and patients' intentions for seeking care in the future. RESULTS: Generally patients consulting nurse practitioners were significantly more satisfied with their care, although for adults this difference was not observed in all practices. For children, the mean difference between general and nurse practitioner in percentage satisfaction score was -4.8 (95% confidence interval -6.8 to -2.8), and for adults the differences ranged from -8.8 (-13.6 to -3.9) to 3.8 (-3.3 to 10.8) across the practices. Resolution of symptoms and concerns did not differ between the two groups (odds ratio 1.2 (95% confidence interval 0.8 to 1.8) for symptoms and 1.03 (0.8 to 1.4) for concerns). The number of prescriptions issued, investigations ordered, referrals to secondary care, and reattendances were similar between the two groups. However, patients managed by nurse practitioners reported receiving significantly more information about their illnesses and, in all but one practice, their consultations were significantly longer. CONCLUSION: This study supports the wider acceptance of the role of nurse practitioners in providing care to patients requesting same day consultations.

Acute Disease↗
PubMed2000

Kenneth Mellanby Review Award. Bioaccumulation of persistent organic chemicals: mechanisms and models.

A review is presented of bioaccumulation of organic substances in organisms, especially fish, including the incentives for developing a tiered predictive approach for addressing the large number of chemicals of commerce. From a review of the existing estimation methods it is suggested that the simplest Tier 1 approach is an empirical correlation for bioconcentration factor as a function of the octanol-water partition coefficient. For more detailed Tier 2 evaluation, the bioaccumulation factor is best predicted using a mechanistic mass balance model applied to the organism at steady state in which relevant uptake and loss processes are quantified. The equivalence of rate constant and fugacity models is demonstrated and methods of obtaining parameter values are discussed. Such a model reveals the relative significance of gill ventilation, food uptake, egestion, and metabolism. The most detailed Tier 3 evaluation should involve prediction of the potential for biomagnification in a food chain involving both fish and air-breathing animals. Research needs are discussed with a view to understanding the mechanisms more fully and developing more accurate quantitative descriptions or models of bioaccumulation phenomena.

Journal Article↗
PubMed2000

What practical skills do rheumatologists of the future need?

In this chapter, we consider future practical skills required for rheumatologists. While difficult to predict against a background of rapid technological advance and successive changes to health-care provision world wide, a number of questions are examined. The first question is what core skills are essential in the curriculum? This has been addressed in at least one joint European effort by UEMS. Great diversity in both clinical practice and training was found across Europe; clearly, the difference across continents may prove even more significant. Second, the role of arthroscopy is considered, the evidence for its therapeutic benefit in clinical rheumatology practice being inconclusive. Issues concerning diagnostic methods including electrophysiology and ultrasound (US) are also discussed in this chapter. There is evidence to support the use of electrophysiology in routine diagnosis for specific diseases. US has become popular as technology improves. It is cheap but highly operator dependent, and the feasibility of rheumatologists using US in the clinic remains to be proved. In conclusion, health care is changing rapidly, and training must adapt, and is adapting, to meet its challenges. A number of opportunities will present to the rheumatologist of the future, but the feasibility of these in routine clinical practice remains to be seen.

Education, Medical↗
PubMed2000

Detection of Echinococcus granulosus coproantigens in Australian canids with natural or experimental infection.

Coproparasitological and purging methods for diagnosing canids infected with the intestinal helminth Echinococcus granulosus, an important zoonotic parasite, are unreliable. Detection of coproantigens in feces of infected dogs by enzyme-linked immunosorbent assay (ELISA) is suitable for detecting patent and prepatent infections with a high degree of sensitivity and specificity. In the present study, natural and experimental infections in domestic and wild Australian canids were investigated using a coproantigen capture ELISA. Experimental infection of dogs with E. granulosus was detected at between 14 and 22 days postinfection (PI), and optical density (OD) values remained high until termination of experiments 35 days PI. After chemotherapy, coproantigen levels in infected dogs dropped rapidly, becoming negative 2-4 days after treatment. In experimentally infected red foxes (Vulpes vulpes), the coproantigen excretion profile was different, with ELISA OD levels peaking 15-17 days PI, then falling to low or undetectable levels by 30 days PI. Coproantigens were detected in the feces of naturally infected Australian wild dogs (dingoes, dingo/domestic dog hybrids) with infection levels ranging between 2 worms and 42,600. Preliminary data on the stability of coproantigen in dog feces exposed to environmental conditions indicated that there was no change in antigenicity over 6 days. The results suggest the coproantigen ELISA could be successfully used to monitor E. granulosus prevalence rates in Australian domestic dogs, foxes, and wild dogs.

Animals↗
PubMed1999

The anatomy and cell biology of peripheral myelin protein-22.

The gain of function phenotypes exhibited by the heterozygous Tr, Tr-J, and CMT1A mutations indicate that these mutations interfere with more than the function of a single PMP22 allele. The identification of proteins that interact with PMP22 and that are sensitive both to stoichiometry and the effects of the mutations could provide important leads to a unified hypothesis to explain the riddle of the PMP22-related neuropathies.

Animals↗
PubMed1999

Community prevalence study of taeniasis and cysticerosis in Bail, Indonesia.

Taenia solium, a human cestode parasite endemic throughout most of South-east Asia, causes a number of public health and economic problems. The parasite is endemic in Bali due to a mix of cultural and religious practices. Immunoepidemiological investigation of three rural communities revealed a taeniasis prevalence of 0.72% (3/415). One of the three cases was due to Taenia solium, the other two to Taenia saginata. A further nine cases of Taenia infection were identified from patients from villages surrounding the chosen communities, suggesting that prevalence levels may be higher in other areas. Seroprevalence of human cysticercosis by immunoblot was 1.65% (6/363), though all cases were detected within a single community (6/115; prevalence 5.22%). Several other cases of subcutaneous cysticercosis were identified from local clinics, suggesting continued transmission of Taenia solium in the region. Other intestinal helminth parasites identified within the communities were Ascaris lumbricoides (29.9%), Trichuris trichiuria (33.9%) and hookworm (8.2%).

Adult↗
PubMed1999

Epidemiological study of Taenia solium taeniasis/cysticercosis in a rural village in Yucatan state, Mexico.

A survey to detect human taeniasis and cysticercosis was conducted in a community in Yucatan state, Mexico, an area endemic for Taenia solium. Information on the environmental, demographic and risk factors associated with transmission of T. solium within the community was recorded on questionnaires. Although no Taenia eggs or proglottides were found in the initial faecal samples collected from each of the 475 subjects, the results of a capture-ELISA for T. solium coproantigen were positive for 10 of the subjects (of both genders and various ages). After treatment with niclosamide, proglottides were detected in purge samples from seven of these 10 subjects. The prevalence of parasitologically confirmed taeniasis was therefore 1.5% (seven in 475). The other three ELISA-positive cases delayed supplying faecal material post-treatment, and it is nuclear whether they had expelled proglottides before providing the samples. All 10 ELISA-positive subjects became ELISA-negative after treatment. Seroprevalence of human cysticercosis, based on the detection in immunoblots of antibodies to antigens of 8- and 26-kDa from a crude saline extract of T. solium metacestodes, was 3.7% (i.e. five positives out of 134 subjects). None of the seropositive cases demonstrated clinical symptoms of infection. Again, the positive cases were of both genders and various ages. Although tongue palpation indicated that 17 (23%) of 75 pigs kept within the community had T. solium cysticercosis, the results of immunoblotting demonstrated antibodies to the 8- and/or 26-kDa antigens of T. solium in 26 (35%). The pigs allowed to roam throughout the community were far more likely to have cysticercosis than those kept in pens (odds ratio = 42, with a 95% confidence interval of 5.05-920.2; P < 0.00001). Not surprisingly, the risk factors associated with human taeniasis and cysticercosis included the eating of infected pork and close proximity to a carrier of T. solium. The main risk factor identified for porcine cysticercosis was free-range husbandry, permitting access to human faeces. This is the first comprehensive report of taeniasis and cysticercosis in a rural population from the Yucatan peninsula of Mexico.

Adolescent↗
PubMed1999

A 6-year experience demonstrates the utility of screening for both cytogenetic and FMR-1 abnormalities in patients with mental retardation.

Cytogenetic abnormalities were found in 81 of 2,757 cases (2.93%) screened for both cytogenetic and FMR-1 mutations because of mental retardation from 1992 to 1997. Of these, 38 (46.9%) were unbalanced autosomal abnormalities, 23 (28.4%) sex chromosomal abnormalities, and 20 (24.7%) balanced autosomal rearrangements. Five subtle deletions were found, of which three involved the long arm of chromosome 7 (7q22-q31.1). Although a high-resolution banding method was used for screening, we concluded that a banding level of 450-550, generally achieved in routine analysis, was sufficient to detect all of these abnormalities. Fragile-X DNA studies revealed CGG expansion mutations in 72 other cases (2.61%). Of the abnormals, 36 (50%) were males and 8 (11.1%) females with full mutations, and 12 (16.7%) were males and 16 (22.2%) females with premutations. Together, our cytogenetic and DNA screening gave 5.5% abnormal results. In this report, these findings are compared with similar surveys of 3,940 subjects from five previous studies. From the combined data of 6,697 cases, this testing approach should reveal nearly equal numbers of cytogenetic and fragile X abnormalities in approximately 6-7% of subjects. It is productive, cost-effective, and consistent with American College of Medical Genetics (ACMG) guidelines for screening of mentally handicapped individuals.

Blotting, Southern↗
PubMed1999

Predicting 'normal' grip strength for rheumatoid arthritis patients.

OBJECTIVE: An ability to predict accurately 'normal' grip strength in rheumatoid arthritis (RA) patients would facilitate a more accurate assessment of the degree of their functional loss. This, in turn, would allow the setting of more meaningful treatment goals aimed at restoring hand function towards normal. This study carefully measures three modalities of hand grip strength and their correlation with multiple simple anthropometric parameters in normal subjects. We aim to determine which of these parameters are best correlated to grip strength, and whether this correlation is strong enough to allow the accurate prediction of what normal grip strength should be in RA patients. METHODS: In 81 normal subjects (67 female), power, pinch and tripod grip strength measurements were made using an MIE digital pinch grip analyser. These strength data were correlated with specific local forearm anthropometric measurements: forearm circumference, forearm length, forearm volume, hand circumference, hand length, hand volume, hand and forearm volume, and various general anthropometric parameters (weight, height and age). These normal subjects had been chosen so as to be age and sex matched with 83 RA patients (67 female) in whom the same strength and anthropometric parameters were assessed and correlated. In patients, the grip strength results were additionally correlated with two markers of disease activity: a modified Ritchie Articular Index local to the hand and forearm (mRAI) and a visual analogue scale (VAS) assessing subjective pain severity. RESULTS: In normal subjects, clear correlations were demonstrated between hand grip strengths and all specific anthropometric variables, the strongest correlation being with forearm and hand volume (r = 0.729 and 0.638 for dominant and non-dominant hands, respectively; P < 0.01 for both). The patients were considerably weaker than normal subjects. Markers of disease activity showed a negative correlation with grip strength. In normal subjects, the dominant hand was significantly stronger than the non-dominant hand, and on average by 8%, while the opposite was true in patients, who were 20% weaker on the dominant side. CONCLUSION: Simple anthropometric measurements, and forearm and hand volume in particular, would be useful at baseline for predicting 'normal' hand grip strength in RA patients, both in the clinical setting and in research trials aimed at improving grip strength and hand function.

Aged↗
PubMed1999

Digital information evolution: the AIDS Library experience.

The AIDS Library evolved out of consumer health activism in response to the need for the latest HIV information, materials, and technology. In 1998, staff implemented a microcomputer-based integrated automated library system with Web publishing capability to link catalogs, databases of Philadelphia regional services, online publications, and fact sheets. The Web site, , became "live" December 1, 1998. History leading to its development and future plans are presented.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Fermenting debate: do yeast undergo apoptosis?

Apoptosis is a common feature of multicellular organisms. However, the recent observations of non-metazoan cell deaths displaying morphology reminiscent of apoptosis has suggested the existence of an ancestral cell death machinery. We discuss this possibility and its implications for the use of yeast in the dissection of the metazoan apoptotic process.

Animals↗