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Biomedical subjects

B Kirby

Publications and source records attributed to B Kirby.

At least 19 recordsLinked to original sources
PubMed2005

Recognition, diagnosis and management of obesity after myocardial infarction.

OBJECTIVE: We investigated the documentation of obesity as a medical problem, and subsequent management recommendations, in patients after myocardial infarction (MI). DESIGN: We performed a cross-sectional analysis of a randomly selected sample of 627 patients discharged after an MI, from five US teaching hospitals between 1/1/01 and 12/31/02. Information was extracted from clinical notes using standardized definitions. RESULTS: Mean body mass index (BMI) was 31+/-13 kg/m2, which was documented in only 14% of patients and had to be calculated post hoc in the rest. Waist circumference and waist/hip ratio were not documented at all; 83% of patients were overweight, 55% obese, and 8% morbidly obese. In only 20% of patients with BMI> or =30 kg/m2 was the diagnosis of obesity documented either as a current medical problem, as part of past medical history or as a final diagnosis. A dietary counseling was carried out in 61% of patients with BMI> or =25 kg/m2 and in 61% of patients with BMI<25 kg/m2, P=0.96. Weight loss was described as part of the goals/plan at discharge in 7% of overweight and 9% of obese patients. There was no change in either the level of recognition of obesity (22 vs 19%, P=0.3) or in the proportion of obese patients for whom weight loss was described as part of the goals/plan at discharge (8 vs 10%, P=0.7) before (n=301) compared to after (n=326) the Call to Action in Obesity by the Surgeon General in December 2001. CONCLUSION: Obesity is underecognized, underdiagnosed and undertreated in persons with acute MI.

Aged↗
PubMed2005

Gene expression profiles in psoriasis: analysis of impact of body site location and clinical severity.

BACKGROUND: Psoriasis is characterized by symmetry of plaques and modulation of multiple genes within those plaques. OBJECTIVES: We compared gene expression profiles of plaques of psoriasis at different anatomical sites for both symmetrical and asymmetrical disease to ascertain whether the same genes were expressed. METHODS: Gene expression profiles were analysed in biopsies from lesional and uninvolved skin from two groups of patients with either predominantly symmetrical or truncal plaques of psoriasis vulgaris, and from normal skin of healthy volunteers. Genomic analyses were performed using cDNA array and kinetically monitored reverse transcriptase-initiated polymerase chain reaction (kRT-PCR) approaches. A cluster of genes upregulated in involved psoriasis skin as compared with normal skin was identified using each of these two technologies. RESULTS: Clustering of patients based on their gene expression profile did not reveal any correlation with family history of psoriasis, age at onset or association of psoriasis with arthritis. There was no difference in gene expression profile between the type (symmetrical vs. truncal) or location (left vs. right side of body) of psoriatic plaques. Gene expression profiles of involved psoriatic skin analysed by kRT-PCR analysis did correlate with both global (Psoriasis Area and Severity Index) and local (erythema, desquamation and plaque elevation) clinical severity. CONCLUSIONS: These results indicate that it may be feasible to analyse the molecular effects of pharmacological agents on psoriatic skin in 'minizone' protocols, that the obtained data can be correlated with clinical severity and that plaques of psoriasis in the same individual express the same genes.

Adult↗
PubMed2005

Replacement of routine liver biopsy by procollagen III aminopeptide for monitoring patients with psoriasis receiving long-term methotrexate: a multicentre audit and health economic analysis.

BACKGROUND: Patients receiving long-term methotrexate for psoriasis are at risk of developing hepatic fibrosis. Repeated liver biopsy has long been regarded as the only reliable method of detecting this and it is still recommended by the American Academy of Dermatology (AAD). More recently, monitoring by serum procollagen III aminopeptide (PIIINP) measurement (Orion Diagnostica, Espoo, Finland) has been advocated as a means of significantly reducing the need for liver biopsy. OBJECTIVES: To assess the validity of guidelines developed in Manchester for the use of PIIINP to monitor patients with psoriasis receiving long-term methotrexate; to assess the anticipated benefits to patients of introducing this change in practice, including reduction in requirement for liver biopsy; and to determine the impact of its introduction on healthcare costs. METHODS: A multicentre audit was conducted over a 24-month period to compare the healthcare costs and outcomes of two intervention groups from centres where serial PIIINP measurement was employed with those of two control groups from centres in which AAD guidelines were followed. RESULTS: A sevenfold reduction in the need for liver biopsy was observed in the two intervention groups (n = 166; 0.04 and 0.02 biopsies/patient/year, respectively) compared with the two control groups (n = 87; 0.26 and 0.30 biopsies/patient/year, respectively). Abnormalities of sufficient severity to influence management were identified in one in five patients biopsied in the main intervention group compared with one in 16 in the control groups. The overwhelming majority of patients surveyed expressed a preference for being monitored by methods that would minimize the need for liver biopsy. The adoption of PIIINP for monitoring would result in significant cost savings. CONCLUSIONS: This audit has shown that patients managed by the Manchester protocol using serial PIIINP measurement and selective liver biopsy were not disadvantaged in comparison with those managed according to AAD guidelines; they were subjected to sevenfold fewer liver biopsies without evidence that important liver toxicity was missed in the process. If PIIINP monitoring were widely adopted, methotrexate would become a more acceptable option for many patients who are dissuaded from considering it because of the threat of repeated liver biopsy; it would also result in significant savings to the healthcare budget.

Adult↗
PubMed2005

Response of the hypothalamic-pituitary-adrenal axis to psychological stress in patients with psoriasis.

BACKGROUND: Psoriasis may, in some patients, be triggered and/or exacerbated by stress. OBJECTIVES: As activation of the hypothalamic-pituitary-adrenal (HPA) axis is critical to a successful stress response we investigated this in patients with psoriasis. METHODS: Forty patients with chronic plaque psoriasis and 40 age-matched normal controls experienced three randomly presented acute psychological stressors (cognitive, emotional and social). Serial serum cortisol, pulse rate and blood pressure assessments were undertaken at baseline and following each of the stressors. Salivary cortisol samples were collected at 09.00 h on the day of testing. RESULTS: In control subjects there was a significant (r = 0.38; P < 0.05) correlation between pulse rate and serum cortisol level following the social performance stressor; this was not evident in the psoriasis group (r = 0.07; not significant). Patients who believed that their psoriasis was highly stress responsive had significantly lower salivary cortisol levels at baseline (P < 0.01) and lower serum cortisol levels following the social performance stressor (P = 0.016) than patients with nonstress-responsive disease who believed that stress had no impact. In contrast, there was no difference between the groups for change in pulse rate poststressor. CONCLUSIONS: This study shows that patients with psoriasis, and in particular those whose disease appears to be stress responsive, exhibit an altered HPA response to acute social stress. The implication is that such patients may perhaps be primed to flares of their psoriasis. Whether this is genetically predetermined and/or a consequence of the distress of living with psoriasis remains to be determined.

Adolescent↗
PubMed2004

Successful treatment of psoriasis improves psoriasis-specific but not more general aspects of patients' well-being.

BACKGROUND: Psoriasis has a detrimental effect on patients' quality of life. However, there is a relative dearth of information on which aspects of a patient's well-being are affected by successful treatment. OBJECTIVES: To investigate whether, and to what extent, improvement in the clinical severity of psoriasis induced by photochemotherapy with psoralen plus ultraviolet A (PUVA) translates into meaningful changes in beliefs about psoriasis, coping, stress, distress or disability. METHODS: In a prospective study, 72 patients were assessed before PUVA therapy and again when they had achieved clearance of their psoriasis. RESULTS: Patients demonstrated significant reductions in psoriasis-related disability, psoriasis-related stress or daily hassles and in the frequency of psoriasis-related symptoms. By comparison, there were no significant differences in levels of anxiety, depression or worrying. Similarly, patients' perceptions about cure, potential chronicity, causes, consequences and coping also remained unchanged. CONCLUSIONS: These results suggest that while clearance of psoriasis produces a significant reduction in factors specific to psoriasis (disability and stress), it does not impact upon psychological distress, on patients' beliefs about psoriasis or on coping. This observation highlights the complex features of patients' psychological experience of psoriasis and may provide further impetus for integration of psychological interventions into standard care protocols.

Adaptation, Psychological↗
PubMed2003

Differentiated chondrocytes for cartilage tissue engineering.

Trauma to the articular cartilage surface of the joint represents a challenging clinical problem due to the very limited ability of this tissue to self-repair. Moreover, repair techniques such as microfracture, which introduce cells into the joint, have unpredictable clinical outcomes as they produce a fibrocartilage tissue that degenerates with time. Alternative treatments include tissue reconstruction with autograft and allograft tissue. However, these procedures are restricted by the availability of suitable donor tissue. These limitations have been the driving force behind the emerging field of articular cartilage tissue engineering. This paper will highlight and contrast the key challenges associated with the tissue engineering of this neo-tissue using differentiated adult cells. The various components of the tissue engineering process will be described including the choice of donor cell/tissue type and the selection of scaffolds that guide the formation of tissue. The ability of the tissue engineered implants to stimulate the repair of defects in vivo will also be discussed. Tissue engineering approaches may, in the future, provide an ideal alternative to the current surgical treatments for cartilage repair.

Adult↗
PubMed2003

A Crohn's disease-associated insertion polymorphism (3020insC) in the NOD2 gene is not associated with psoriasis vulgaris, palmo-plantar pustular psoriasis or guttate psoriasis.

A C-insertion polymorphism in the NOD2 gene (3020insC) on chromosome 16 is a rare mutation associated with Crohn's disease. Crohn's disease and psoriasis are more commonly observed together than expected by chance. Furthermore a susceptibility locus for psoriasis has been identified on chromosome 16q which overlaps the recently identified susceptibility locus for Crohn's disease. Thus, NOD2 may potentially be important as a candidate susceptibility gene for psoriasis. We tested this hypothesis by genotyping psoriasis patients for the C-insertion polymorphism using the Taqman ABI 7700 sequencing system. No statistically significant differences were observed between psoriasis vulgaris (n = 216), palmo-plantar pustular psoriasis (PPP) (n = 100), guttate psoriasis (n = 118) and the control group (n = 283). In both patient and control groups, no mutant homozygotes were observed and approximately 4% were heterozygotes. This particular insertion mutation in the NOD2 gene does not appear to contribute to the genetic susceptibility of psoriasis vulgaris, PPP or guttate psoriasis. However, other mutations exist in the NOD2 gene, which may potentially have a role in psoriasis susceptibility.

Adolescent↗
PubMed2003

Circulating natural killer cells in psoriasis.

BACKGROUND: Psoriasis is an immunologically mediated, probably autoimmune, disease in which T-helper type 1 cytokines play an important role. Established autoimmune diseases, with similar mechanistic characteristics to psoriasis, include multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus and systemic lupus erythematosus. Natural killer (NK) and natural killer-T (NK-T) cells are considered key to the pathogenesis of these conditions, which are characterized by reduced numbers of NK cells in peripheral blood. NK and NK-T cells have been implicated in the pathogenesis of psoriasis and are present in plaques of psoriasis. OBJECTIVES: To investigate whether levels of NK and NK-T cells are reduced in the peripheral blood of patients with psoriasis. METHODS: Fourteen patients with untreated psoriasis, mean +/- SD age 46 +/- 13 years, and 13 healthy volunteers, mean +/- SD age 34 +/- 9 years, were venesected and peripheral blood mononuclear cells isolated, labelled with a panel of antibodies to T-cells and NK cells including CD3, CD56, CD57, CD16, CD94, CD158a, CD69 and cutaneous lymphocyte-associated antigen (CLA) and analysed using triple-colour flow cytometry. RESULTS: There were significantly fewer cells expressing the NK-cell markers CD16 (P < 0.001), CD56 (P < 0.003), CD94 (P < 0.001) and CD158a (P < 0.02) in patients with psoriasis compared with normal controls. However, circulating numbers of NK-T cells (CD3+ CD56+ CD57+), T-cells (CD3+), activated lymphocytes (CD69+) or CLA+ cells were not significantly different between patients with psoriasis and controls. CONCLUSIONS: Circulating NK cells are reduced in psoriasis. This finding is similar to those in established autoimmune diseases such as rheumatoid arthritis. This observation provides some evidence that psoriasis may be an autoimmune disease in which NK cells play a role.

Adult↗
PubMed2002

Natural killer and natural killer-T cells in psoriasis.

Psoriasis is characterized by a dermal and epidermal infiltrate comprised predominantly of CD4(+) and CD8(+) T cells, respectively. These cells behave in an antigen-dependent manner, which suggests that psoriasis may be a T-cell-mediated autoimmune disease. Psoriasis shares certain immunological features with recognized autoimmune conditions such as type I diabetes mellitus and multiple sclerosis, in both of which a pathogenic role is postulated for natural killer (NK) cells and natural killer-like T (NK-T) cells. However, there are few studies assessing the role of NK and NK-T cells in psoriasis. We sought to determine whether NK and NK-T cells are present in psoriasis. Skin biopsies were taken from the active edge of a psoriasis plaque and from uninvolved skin at least 5 cm away from involved skin of ten patients with chronic plaque psoriasis. Skin from four normal subjects was used as controls. Using an immunoperoxidase technique, cryostat sections were stained using antibodies to T-cell markers CD2, CD3, CD4 and CD8; cutaneous leucocyte associated antigen; NK cell markers CD16, CD56, CD57, CD94 and CD158a; and the NK-T cell marker CD161. There were significantly more cells expressing T cell markers, NK cell markers CD16, CD57, CD94 and CD158a and NK-T cell marker CD161 in involved skin than in uninvolved or normal skin ( P<0.01). There was no difference in the number of cells expressing CD56. Cells expressing NK markers were found most commonly in the papillary dermis immediately subjacent to the dermoepidermal junction. Cells expressing CD57 were found in significantly higher numbers in the epidermis and reticular dermis of involved skin. This study demonstrates that cells expressing NK markers and NK-T cell markers are present in plaques of psoriasis. The exact roles of NK and NK-T cells in psoriasis are unclear, although they may modulate autoimmune inflammation and act as a source of Th(1) cytokines important in the psoriatic process.

Adult↗
PubMed2002

A cognitive-behavioural symptom management programme as an adjunct in psoriasis therapy.

BACKGROUND: Patients with psoriasis may experience significant psychological and social disabilities. Stress or distress are proposed aggravators of the disease process in psoriasis. Preliminary studies to date have suggested that adjunctive psychological therapies may be effective in the clinical management of psoriasis. OBJECTIVES: To examine whether a 6-week multidisciplinary management approach, the Psoriasis Symptom Management Programme (PSMP) for patients with psoriasis improves clinical severity of psoriasis and its associated psychological distress and disability. METHODS: In a case-control study, patients with psoriasis attending an out-patient psoriasis specialty clinic chose to receive standard psoriasis treatment alone (n = 53) or to enter the PSMP as an adjunct to standard therapy (n = 40). They were assessed at baseline, at the end of the 6-week PSMP and after 6 months follow-up. RESULTS: As compared with standard treatment alone, analysis of covariance indicated that participation in the PSMP resulted in a greater reduction in clinical severity of psoriasis (P = 0.001), anxiety (P = 0.001), depression (P = 0.001), psoriasis-related stress (P = 0.001) and disability (P = 0.04) at 6 weeks and 6 months follow-up. CONCLUSIONS: The management of the physical aspects of psoriasis and its psychological effects are significantly improved for patients who opt for a 6-week integrated multidisciplinary approach. Furthermore, the techniques learnt by participation in the PSMP facilitate continued control of psoriasis for at least 6 months.

Administration, Topical↗
PubMed2002

Novel immune-based therapies for psoriasis.

The primacy of the immune system in the pathogenesis of psoriasis is a well-established concept to the extent that psoriasis has been classified as a T-cell-mediated, autoimmune disease. An explosion of knowledge concerning immunological events in psoriasis and the clinical efficacy of immunologically directed therapies, such as cyclosporin, support this concept. Armed with this understanding and modern biotechnology, novel interventions have been developed to treat psoriasis. The aim of these therapies is to provide selective, immunologically directed intervention with the hope that such specificity will result in fewer side-effects than traditional therapies. Of interest and importance, these pharmaceutical interventions also act as a form of investigational tool in psoriasis. Their relative efficacy in the psoriatic process provides useful insights into the hierarchial importance of immune events in the disease process and recent evidence suggests that innate rather than acquired immunity has a key role. This article reviews recent developments in immune-based therapies for psoriasis.

Cytokines↗
PubMed2002

Downregulation and altered spatial pattern of caveolin-1 in chronic plaque psoriasis.

BACKGROUND: Caveolin-1 is a key structural and functional protein for plasmalemmal invaginations termed caveolae. Caveolin-1 is known to modulate multiple signal-transducing pathways involved in cell differentiation and proliferation. Psoriasis is viewed as a multifactorial pathology characterized by keratinocyte hyperproliferation and abnormal cell maturation. We hypothesized that loss of caveolin-1 within epidermal keratinocytes may contribute to the development and/or progression of the psoriatic phenotype. OBJECTIVES: To examine the expression and spatial distribution of caveolin-1 in skin biopsies from normal subjects and in patients with psoriasis. METHODS: Using immunohistochemical methods caveolin-1 protein expression was assayed in two independent patient groups. Firstly, a retrospective analysis was conducted on archival skin samples obtained from nine normal subjects and from involved tissue of 12 patients with psoriasis. Following this, a prospectively designed study was conducted in 10 further patients with active psoriasis and involving caveolin-1 staining of biopsy tissue from the uninvolved, advancing edge and lesional skin tissue from within the same subject. RESULTS: In normal skin or uninvolved skin from psoriasis patients intense caveolin-1 staining was present throughout full-thickness epidermis. In 20 of the 22 patient cases (combined retrospective and prospective samples) caveolin-1 protein was significantly reduced and consistently showed very weak or absent staining within the hyperproliferative basal cell layers of the psoriatic plaque (P < 0.002 for retrospective archival study and P < 0.01 for prospectively designed study). Comparisons between caveolin-1 staining in uninvolved tissue and at the advancing edge of a migrating plaque were more equivocal (P > 0.05). CONCLUSIONS: The findings of this study are consistent with a downregulation of caveolin-1 that may serve as an aetiological factor in the development and/or progression of psoriasis. Further mechanistic investigations are required with the potential that caveolin-1 protein may be a novel target for therapy of psoriasis.

Adolescent↗
PubMed2001

Monocyte chemoattractant protein (MCP)-1 is rapidly expressed by sympathetic ganglion neurons following axonal injury.

EDI-immunoreactive macrophages, absent from the superior cervical ganglia (SCG) of normal rats, appear in these ganglia within 48h after postganglionic axotomy. Further, resident macrophages show changes after axotomy. Since chemokines function as chemoattractants and activators of leukocytes, the effects of axotomy on chemokine expression in the SCG were examined. Within 6 h after nerve transection, increases were seen in mRNA levels for monocyte chemoattractant protein (MCP)-1. MCP-1 mRNA was concentrated in a population of neurons, while MCP-1 protein was localized to endothelial cells. This axotomy-induced neuronal MCP-1 expression may trigger the infiltration and/or activation of macrophages in SCG after injury.

Animals↗