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C Steele

Publications and source records attributed to C Steele.

At least 19 recordsLinked to original sources

Managing 'suspicious glaucomatous discs' identified during digital-photography-based diabetic retinopathy screening.

PURPOSE: An audit to demonstrate the outcome of patients identified with suspicious glaucomatous discs within a digital-photography-based diabetic retinopathy screening programme. METHODS: Primary care based digital photographic screening was performed utilising mydriasis and two-field digital photography for all patients with diabetes. Patients identified with discs suspicious of glaucomatous optic neuropathy (GON) were initially referred to an accredited community-based optometrist for further assessment. Some patients were then referred to secondary care where appropriate. RESULTS: From 1st April 2002 to 31st March 2003 a total of 3868 patients were screened for diabetic retinopathy. This audit revealed that 55 subjects were identified by retinal screeners as having discs suspicious of glaucoma. A total of 29 were already under glaucoma clinic review. A total of 23/26 remaining were referred for an assessment by an accredited optometrist. Of these 13 were normal, 6 were referred to secondary care and 4 failed to attend. The three remaining were referred directly to secondary care. CONCLUSIONS: All nine referrals to secondary care were deemed appropriate by a glaucoma specialist. This suggests that the system described does not lead to over-referral of suspicious discs - although the issue of how many glaucomatous discs are missed during screening (false negatives) will only be answered in the longer term.

Aged↗

Association between cyclooxygenase-2-expressing macrophages, ulceration and microvessel density in colorectal cancer.

AIM: In colorectal carcinomas, cyclooxygenase-2 (COX-2) is expressed predominantly by epithelial cells and is implicated in tumour progression. Tumour-associated macrophages may influence tumour growth, proliferative rate and angiogenesis and also express COX-2 when activated. Thus they may play an important stromal-epithelial role in carcinogenesis. Tauhe aim of this study was to define the relationship between microvessel density (MVD), tumour COX-2 and macrophage COX-2 expression. METHODS AND RESULTS: Sixty-five cases of formalin-fixed paraffin-embedded colorectal cancer were included in the study. Tissues were immunostained for COX-2, CD68 (macrophage marker) and CD34 (endothelial marker to assess MVD). Thirty-six cases were grossly ulcerated cancers and 29 cases showed focal/microscopic ulceration. Macrophages were in high concentration at the base of ulcerated areas, and were also diffusely dispersed within tumoral stroma. However, the pattern of macrophage COX-2 expression revealed two populations of macrophages--those deep within the tumour (negative for COX-2) and those at the base of ulcers (positive for COX-2). In all cases, the tumour epithelial cells expressed COX-2. MVD was higher at the base of ulcers, adjacent to COX-2+ macrophages, and was lower deep within the tumour. CONCLUSIONS: In colorectal cancers, macrophages may have a dual role. Those concentrated at the base of the ulcers, where there is an associated high MVD, may induce angiogenesis, but their function may be in a healing/repair process. The lack of COX-2+ macrophages and lower MVD deep within the tumour suggests that it may be the epithelial COX-2 component that is important in tumour progression.

Antigens, CD↗

Oral and vaginal epithelial cell anti-Candida activity is acid labile and does not require live epithelial cells.

BACKGROUND: Candida albicans is the causative agent of oral and vaginal candidiasis. Innate host defenses against C. albicans are important against each infection. Among these are oral and vaginal epithelial cells that have anti-Candida activity. The mechanism of action includes a requirement for cell contact with no role for soluble factors, and a putative role for carbohydrates based on the sensitivity of the activity to periodic acid. METHODS: Periodic acid treatment of epithelial cells as well as the property of partial resistance of antifungal activity to fixation was used to further dissect the mechanism of action. RESULTS: The results herein effectively now challenge a role for carbohydrates alone. Firstly, the putative carbohydrate(s) released into supernatants of periodic acid-treated epithelial cells could not compete with fresh epithelial cells for activity, and equivalent abrogation of activity was observed by periodic acid-treated cells irrespective of the amount of carbohydrate released. Instead, the similar abrogation of activity following treatment with other acids or when cocultured under acidic conditions suggests that the activity is acid-labile. Finally, while activity requires intact epithelial cells, it does not require live cells; activity was minimally affected by fixing epithelial cells prior to coculture where the majority of cells remained impermeable to Trypan blue but were defined as non-viable by positive nuclear staining with propidium iodide. CONCLUSION: These results suggest that antifungal activity is dependent on contact by intact, but not necessarily live, epithelial cells through an acid-labile mechanism.

Adolescent↗

Cyclooxygenase-2 expression in primary human colorectal cancers and bone marrow micrometastases.

BACKGROUND: Both the expressions of the inducible form of cyclooxygenase-2 and the presence of bone marrow micrometastases are poor prognostic markers in patients with colorectal carcinoma. AIMS: As cyclooxygenase-2 expression in these tumours is associated with increased metastatic potential in vitro, our objectives were to determine the relationship between cyclooxygenase-2 and haematogenous spread to bone marrow. PATIENTS AND METHODS: Thirty-two patients with resection of colorectal carcinoma were evaluated (median age: 69.5 years). Bone marrow was obtained from all patients from both iliac crests before manipulation of the primary tumour. The tumours were of varying stages at diagnosis (5 Dukes' A, 14 Dukes' B, 11 Dukes' C and 2 Dukes' D). Tumour sections were stained for cyclooxygenase-2 using the avidin-biotin immunohistochemical technique. Extent of staining was graded depending on the percentage of epithelial cells staining positive for cyclooxygenase-2. Micrometastases were detected by staining contaminant cytokeratin-18 positive cells in the bone marrow aspirates by either immunohistochemical (ARAAP) or immunological (flow cytometry) methods. Fisher's exact probability test was used to calculate statistical significance. RESULTS: Cyclooxygenase-2 expression in the primary tumour was detected in 72% of the patients. Twelve (38%) patients had bone marrow micrometastases detected by either immunohistochemistry or flow cytometry. Of the 12 patients who had bone marrow micrometastases, 8 tumours demonstrated increased expression of cyclooxygenase-2 protein (66.6%). In contrast, 9 out of the 20 (45%) patients in whom micrometastases were not detected expressed increased levels of cyclooxygenase-2 (P = 0.29). When dividing the patients into subgroups of localised (Dukes' A and B) versus disseminated (Dukes' C and D) disease, there was no further association between cyclooxygenase-2 expression and bone marrow micrometastases (P = 0.179 and 1.0). CONCLUSION: In this pilot study, there was no association between cyclooxygenase-2 expression and bone marrow micrometastases in patients with otherwise localised or disseminated disease.

Aged↗

Salivary cytokine profiles in the immunocompetent individual with Candida-associated denture stomatitis.

Cell-mediated immunity conferred by CD4+ T helper cells is considered the predominant host defense against mucosal Candida infections, with Thelper (Th1)-type responses associated with resistance to infection and Th2-type responses associated with susceptibility to infection. Oropharyngeal candidiasis, the most common oral opportunistic infection in HIV-infected persons, is associated with a Th2-type cytokine profile in saliva. To obtain more direct evidence for a role of salivary cytokines in susceptibility to oropharyngeal candidiasis during immunosuppression, we evaluated Th1/Th2-type cytokines in the saliva of those with denture stomatitis, a form of oropharyngeal candidiasis not related to immunosuppression. Results showed that HIV-negative denture wearers with and without denture stomatitis demonstrated a mixed Th1/Th2 cytokine profile with no significant differences found between the groups. These results suggest that a local Th cytokine dichotomy in saliva is not associated with susceptibility to denture stomatitis in immunocompetent persons.

Adult↗

An audit of nutritional care delivered to elderly inpatients in community hospitals.

BACKGROUND: There is continuing concern over the lack of attention to the nutritional needs of older people in hospitals. A 2-year audit project was undertaken to examine the nutritional care of inpatients in Leicestershire Community Hospitals. METHOD: The methods used included analysis of menu cycles; observation of meal and drink provision, wastage, supplement usage and portion sizes; and patient satisfaction questionnaire examination. RESULTS: Patient menus were nutritionally inadequate for energy, fibre and vitamin D, and protein levels were variable. The percentage of meal wastage and inadequate portion sizes were of concern. Patient satisfaction results were overall positive. CONCLUSION: Patient energy intakes are a major concern with low calorie provision from menus exacerbated by a deficit in recommended portion sizes and a high percentage of meal wastage. Routine audits need to be implemented to monitor both portion size and meal wastage, and to address patient satisfaction issues to improve the overall intakes of patients. Multidisciplinary team input is required to address the above issues and additional recommendations to promote nutrition as a key component in clinical care.

Aged↗

Partial protection against experimental vaginal candidiasis after mucosal vaccination with heat-killed Candida albicans and the mucosal adjuvant LT(R192G).

The effectiveness of a mucosal vaccine composed of heat-killed Candida albicans (HK-CA) or C. albicans culture filtrate (CaCF) in conjunction with the mucosal adjuvant LT(R192G) against vulvovaginal candidiasis was examined in an estrogen-dependent murine model. Mice vaccinated intranasally with HK-CA + LT(R192G) exhibited a significant but short-lived protection accompanied by a vigorous delayed-type hypersensitivity response as well as high titers of circulating C. albicans-specific antibodies. Surprisingly, the levels of antigen-specific antibodies in the vaginal secretions of protected mice were negligible and no correlates of vaginal-associated Type 1 or Type 2 cytokines were observed. Vaginal priming with C. albicans before vaccination did not alter the protective outcome. Immunization with CaCF + LT(R192G) induced a discrete level of protection when administered intrarectally but not intranasally. These results suggest that mucosal vaccination can afford partial protection against vulvovaginal candidiasis, but the precise immune mechanisms responsible for protection are complex and as yet, not well understood.

Adjuvants, Immunologic↗

Growth inhibition of Candida albicans by human vaginal epithelial cells.

Vulvovaginal candidiasis (VVC) is a common mucosal infection caused by Candida species in women of childbearing age. Although acute VVC affects a large number of women and is often precipitated by hormonal fluctuations involving high estrogen levels, recurrent VVC (RVVC) affects another 5%-10% of women without any known predisposing factors. We have recently reported that vaginal epithelial cells from nonhuman primates and mice inhibit the growth of Candida albicans in vitro, which may represent an innate host defense mechanism against C. albicans at the vaginal mucosa. In the present study, we show that vaginal epithelial cells collected from healthy women with no history of VVC also exhibit anti-Candida activity, with no differences in activity at various stages of the menstrual cycle. Women diagnosed with RVVC, on the other hand, have reduced epithelial cell anti-Candida activity. These results are further evidence that vaginal epithelial cells provide an innate host resistance mechanism against Candida and that reduced activity may contribute to RVVC.

Adult↗

Botulinum toxin type A injections in the spastic upper extremity of children with hemiplegia: child characteristics that predict a positive outcome.

Evidence is increasing to suggest that botulinum toxin type A (BTX-A) plays a role in the management of upper extremity spasticity in the paediatric population. However, little information is available on the clinical characteristics of the child that predict a response to this intervention. Our research group previously published a randomized controlled trial demonstrating that BTX-A injection improves function of the upper extremity of children with spastic hemiplegia. In the present paper, we evaluate the child characteristics that predict a positive response to the BTX-A injections in the randomized treatment group. The treatment group was divided into positive functional responders and nonresponders using a cut score of a change of 10 points on the Quality of Upper Extremity Skills Test (QUEST). A two-way analysis of variance procedure was done comparing the following baseline characteristics: function as scored on the QUEST and the Pediatric Evaluation of Disability Inventory (PEDI) self-care domain, grip strength, upper extremity spasticity and age. Grip strength was significantly higher in responders with a P-value of 0.001. Young age approached significance with a P-value of 0.05. Correlation of change scores on the QUEST with baseline characteristics in the treatment group yielded similar results. BTX-A causes a reduction in spasticity and strength; we postulate that if the hand is weak initially, BTX-A can decrease hand function. Two case reports are presented that highlight the importance of grip strength and age.

Activities of Daily Living↗

Predictor index of mortality in dementia patients upon entry into long-term care.

BACKGROUND: The purpose of this study was to develop an algorithm that predicts survival in patients with dementia upon entry into long-term care. There are, as yet, no predictive equations developed for those in the late stages of Alzheimer's disease (AD). METHODS: This was a prospective, observational study of 132 patients with dementia (61% with AD) followed for up to 5.0 years (median of 41.0 months) after admission to a long-term care facility for dementia patients. Information on demographic characteristics, physical health, and cognitive, emotional, and behavioral characteristics was collected shortly after admission and entered as predictors of time until death in Cox regressions. Findings were used to derive an index predicting mortality. RESULTS: There were 60 deaths among the 132 patients (45.4% mortality), with an average survival of 22.4 months in those who died. Better physical health and the presence of delusions were associated with longer survival. These two variables were aggregated into the Copper Ridge Index (CRI). Each one-point increase on the CRI was associated with a four-fold greater likelihood of death over 5 years. CONCLUSIONS: A predictive equation incorporating measures of general physical health and delusions accurately predicted time to death in dementia patients in long-term care.

Aged↗

Acute upper gastrointestinal haemorrhage and colitis: an unusual presentation of Wegener's granulomatosis.

Wegener's granulomatosis is a rare necrotizing vasculitis usually affecting the respiratory tract and kidneys. The aetiology is unknown and it usually occurs in patients over the age of 40. Involvement of the gastrointestinal tract in Wegener's granulomatosis is relatively rare and usually occurs long after the onset of initial symptoms. Acute colitis as a presenting feature of Wegener's granulomatosis is very rare with only a few reports in the literature. We describe a young woman who presented initially to hospital with gastrointestinal features and then developed a severe colitis and severe gastrointestinal haemorrhage. This preceded the development of respiratory tract features with severe pulmonary haemorrhage, haemoptysis and the development of rapidly progressive renal failure and nasal septal perforation. Following treatment with intravenous steroids and cyclophosphamide, gastrointestinal symptoms and signs improved dramatically, as did her pulmonary disease. She still remains dialysis dependent, due to end-stage renal disease secondary to glomerulonephritis.

Acute Disease↗

African Americans and high blood pressure: the role of stereotype threat.

We examined the effect of stereotype threat on blood pressure reactivity. Compared with European Americans, and African Americans under little or no stereotype threat, African Americans under stereotype threat exhibited larger increases in mean arterial blood pressure during an academic test, and performed more poorly on difficult test items. We discuss the significance of these findings for understanding the incidence of hypertension among African Americans.

Adult↗

Potential role for a carbohydrate moiety in anti-Candida activity of human oral epithelial cells.

Candida albicans is both a commensal and a pathogen at the oral mucosa. Although an intricate network of host defense mechanisms are expected for protection against oropharyngeal candidiasis, anti-Candida host defense mechanisms at the oral mucosa are poorly understood. Our laboratory recently showed that primary epithelial cells from human oral mucosa, as well as an oral epithelial cell line, inhibit the growth of blastoconidia and/or hyphal phases of several Candida species in vitro with a requirement for cell contact and with no demonstrable role for soluble factors. In the present study, we show that oral epithelial cell-mediated anti-Candida activity is resistant to gamma-irradiation and is not mediated by phagocytosis, nitric oxide, hydrogen peroxide, and superoxide oxidative inhibitory pathways or by nonoxidative components such as soluble defensin and calprotectin peptides. In contrast, epithelial cell-mediated anti-Candida activity was sensitive to heat, paraformaldehyde fixation, and detergents, but these treatments were accompanied by a significant loss in epithelial cell viability. Treatments that removed existing membrane protein or lipid moieties in the presence or absence of protein synthesis inhibitors had no effect on epithelial cell inhibitory activity. In contrast, the epithelial cell-mediated anti-Candida activity was abrogated after treatment of the epithelial cells with periodic acid, suggesting a role for carbohydrates. Adherence of C. albicans to oral epithelial cells was unaffected, indicating that the carbohydrate moiety is exclusively associated with the growth inhibition activity. Subsequent studies that evaluated specific membrane carbohydrate moieties, however, showed no role for sulfated polysaccharides, sialic acid residues, or glucose- and mannose-containing carbohydrates. These results suggest that oral epithelial cell-mediated anti-Candida activity occurs exclusively with viable epithelial cells through contact with C. albicans by an as-yet-undefined carbohydrate moiety.

Adult↗

Resistance of T-cell receptor delta-chain-deficient mice to experimental Candida albicans vaginitis.

Conditions consistent with tolerance or immunoregulation have been observed in experimental Candida albicans vaginal infections. The present study investigated the role of gamma/delta T cells in experimental vaginal candidiasis. Results showed that T-cell receptor delta-chain-knockout mice had significantly less vaginal fungal burden when compared to wild-type mice, suggesting an immunoregulatory role for gamma/delta T cells in Candida vaginitis.

Animals↗

Growth inhibition of Candida by human oral epithelial cells.

Oropharyngeal candidiasis (OPC) caused by Candida albicans is a significant problem in human immunodeficiency virus (HIV)-infected persons. Recognizing the paucity of information on innate and/or adaptive mucosal host defenses against C. albicans, we recently reported that human and nonhuman primate and mouse vaginal epithelial cells inhibit the growth of C. albicans in vitro. In the present study, oral epithelial cells collected from saliva of healthy volunteers and a purified oral epithelial cell line were found to inhibit blastoconidia and/or hyphal growth of several Candida species. Cell contact was a strict requirement for the epithelial cell anti-Candida activity; neither saliva nor culture supernatants alone inhibited Candida growth, and addition of saliva to the coculture did not modulate the epithelial cell activity. Finally, epithelial cell anti-Candida activity was significantly lower in HIV-infected persons with OPC. Together, these results suggest that oral epithelial cells may play a role in innate resistance against OPC.

Adult↗

Quality of life in dementia patients in long-term care.

OBJECTIVE: To evaluate variables associated with quality of life (QOL) in dementia residents in a long-term care facility using a recently standardized and validated dementia-specific QOL scale (ADRQL). METHOD: A cross-sectional, case-control design was employed using validated scales to assess dementia-related symptomatology. Thirty-two facility staff members were interviewed to assess the QOL of 120 patients meeting DSM-IV for dementia criteria residing in long-term care. RESULTS: ADRQL scores were higher in assisted living residents than in skilled nursing facility residents. In univariate analyses, worse orientation, greater physical dependency, depression, and treatment with anxiolytics were associated with lower ADRQL scores. In multivariate analyses, lower scores were associated with worse orientation, greater physical dependency, depression, and anxiolytic treatment. CONCLUSIONS: Residents exhibited better QOL than expected. Future longitudinal studies should address if reorientation, activity therapy, treatment of depression, and avoidance of benzodiazepines might improve QOL in this population. Interventions that might improve orientation and physical abilities, such as cholinomimetic therapies, psychosocial interventions, or behavioral strategies, should also be studied in future research on QOL.

Activities of Daily Living↗

Islet autoimmunity in infants with a Type I diabetic relative is common but is frequently restricted to one autoantibody.

AIMS/HYPOTHESIS: To determine the sequence of development of islet autoantibodies and their relation to HLA genes in infants at risk for Type I diabetes followed from birth. METHODS: We followed 357 (189 male, 168 female) infants, with a first degree relative with Type I diabetes for a mean of 3 years from birth. Human leukocyte antigen typing and assays for insulin autoantibodies (IAA), glutamic acid decarboxylase antibodies (GADAb) and tyrosine phosphatase IA2 (IA2Ab) antibodies were done on cord blood, and venous blood was sampled every 6 months for IAA, GADAb and IA2Ab. RESULTS: We did not find any antibodies in 263 (73%) infants; 50 (14%) were positive for a single antibody once, 19 (5%) for a single antibody more than once and 25 (7%) for two or more antibodies. Of the latter, 10 (2.8% overall) were persistently positive; they had higher frequencies of HLA DR4 (p < 0.01) and HLA DR3, 4 (p < 0.05). Of the group persistently positive for two or more antibodies four infants developed diabetes. Insulin autoantibodies were the first ones to develop in 64% of infants with two or more antibodies. CONCLUSION/INTERPRETATION: Infants with high risk HLA-DR alleles and multiple antibodies at high risk for diabetes were identified. A much larger group of infants had transient low level increases usually of a single antibody. Whereas transient low level positivity could be attributed to difficulties with assay technique and cut off levels for normality, the results overall support the phenomenon of transient 'self limited' islet autoimmunity in at risk infants.

Aging↗

An evaluation of botulinum-A toxin injections to improve upper extremity function in children with hemiplegic cerebral palsy.

OBJECTIVE: In a randomized, controlled, single-blind trial, to test the hypothesis that botulinum-A toxin (BTA) injections into the upper extremity of children with spastic hemiplegia improve upper extremity function. STUDY DESIGN: Thirty children with hemiplegia, aged 2.5 to 10 years, were randomly assigned to receive: (1) a BTA injection into 1 or more of 3 muscle groups (biceps, volar forearm muscles, adductor pollicis) plus occupational therapy or (2) occupational therapy alone. Blinded outcomes obtained at baseline and at 1, 3, and 6 months included the Quality of Upper Extremity Skills Test (QUEST), goniometry measurements, grip strength, and Ashworth scores. The caregiver completed the self-care domain of the Pediatric Evaluation of Disability Inventory. RESULTS: Twenty-nine subjects completed the study. The QUEST demonstrated a significant improvement favoring the treatment group on a 2-way analysis of variance (F = 4.69, df = 1,83; P =.039). BTA treatment was also associated with an improvement in score on the self-care domain of the Pediatric Evaluation of Disability Inventory (F = 4.68, df = 1,82; P =.04). CONCLUSIONS: This study supports the effectiveness of BTA injections to improve upper extremity function of children with hemiplegia who have at least moderate spasticity.

Analysis of Variance↗