Atorvastatin as adjunctive therapy for chronic plaque type psoriasis versus betamethasone valerate alone: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Psoriasis is a T helper 1 cell-mediated chronic inflammation. Statins have been found to have anti-inflammatory and immunomodulatory effects targeting T helper 1 cells and thus, are being investigated as treatments for psoriasis. AIMS: To investigate the efficacy and safety of atorvastatin as adjunctive treatment for mild to moderate chronic plaque psoriasis; and the impact of atorvastatin on quality of life. The study also aimed to correlate the beneficial effects of atorvastatin with its lipid-lowering effects. METHODS: Twenty-eight (19-65 year old) mild-moderate chronic plaque psoriasis patients were randomly assigned to two groups (treatment group: atorvastatin 40 mg OD; control group: placebo OD) and followed up for 6 months. All were allowed to use betamethasone valerate 0.1% ointment twice a day for a maximum of 3 weeks continuous application with 1-week rest periods in between. Primary outcome measures were the mean percentage reduction in Psoriasis Area and Severity Index (PASI) scores and percentage of patients achieving PASI-50. RESULTS: Fourteen patients (treatment: 6, control: 8) completed the trial. Mean reductions in PASI scores between the treatment (2.15 ± 2.17) and control (1.69 ± 2.36) groups were not statistically significant (P = 0.636). Intention-to-treat analysis of PASI-50 showed increased risk of treatment failure with atorvastatin as adjunct but estimates were not significant. Changes in Dermatology Life Quality Index (DLQI) scores (P = 0.214) and high-sensitivity C-reactive protein (P = 0.884) were likewise not statistically significant. Reductions in PASI scores were not linearly correlated with reductions in total cholesterol (P = 0.924), triglycerides (P = 0.274), low-density lipoprotein-cholesterol (P = 0.636), high-density lipoprotein-cholesterol (P = 0.584), or high-sensitivity C-reactive protein levels (P = 0.906). Adverse effects in the treatment group were transient elevated transaminases (n = 1) and mild myalgia (n = 1). LIMITATIONS: A 50% dropout rate was experienced. This remarkably high dropout rate decreases the robustness of the study results. CONCLUSIONS: Although atorvastatin exhibited earlier percentage reduction in PASI scores, it was not able to produce an additional benefit compared to psoriatic patients applying steroid alone.

Validation of a Filipino version of the cardiff acne disability index

@#<p style="text-align: justify;"><strong>OBJECTIVE:</strong> This study assessed the reliability and validity of a Filipino version of the Cardiff Acne Disability Index.<br /><strong>METHODS:</strong> In Phase 1, the Cardiff Acne Disability Index (CADI) was translated into Filipino as the Cardiff Indeks ng Kapansanan ng may Tigyawat (CIKT) following international guidelines on translation and cultural adaptation, and passed a cognitive debriefing test (a form of face validity testing). In Phase 2, the CIKT was administered to 400 public high school students (11-18 years old). Cronbach's ? was used to measure reliability while construct validity was determined by comparing 1) the CIKT scores of adolescents with acne and those without acne and 2) the CIKT scores with the scores of the Taluntunan ng Kalidad ng Buhay na Hinggil sa Dermatolohiya (TKBD), which is a validated Filipino version of the Dermatology Life Quality Index.<br /><strong>RESULTS:</strong> Cronbach's ? showed an adequate internal consistency of 0.7. The linear regression coefficient for those with and without acne was 0.98 (CI 0.59, 1.37) (p = 0.00) while the Spearman correlation showed a positive correlation between the CIKT and the TKBD (0.58, p=0.00), both indicating validity.<br /><strong>CONCLUSION:</strong> The CIKT is a reliable and valid Filipino translation of the CADI.</p>

Validation of a Filipino version of the cardiff acne disability index

OBJECTIVE: This study assessed the reliability and validity of a Filipino version of the Cardiff Acne Disability Index.METHODS: In Phase 1, the Cardiff Acne Disability Index (CADI) was translated into Filipino as the Cardiff Indeks ng Kapansanan ng may Tigyawat (CIKT) following international guidelines on translation and cultural adaptation, and passed a cognitive debriefing test (a form of face validity testing). In Phase 2, the CIKT was administered to 400 public high school students (11-18 years old). Cronbach's ? was used to measure reliability while construct validity was determined by comparing 1) the CIKT scores of adolescents with acne and those without acne and 2) the CIKT scores with the scores of the Taluntunan ng Kalidad ng Buhay na Hinggil sa Dermatolohiya (TKBD), which is a validated Filipino version of the Dermatology Life Quality Index.RESULTS: Cronbach's ? showed an adequate internal consistency of 0.7. The linear regression coefficient for those with and without acne was 0.98 (CI 0.59, 1.37) (p = 0.00) while the Spearman correlation showed a positive correlation between the CIKT and the TKBD (0.58, p=0.00), both indicating validity.CONCLUSION: The CIKT is a reliable and valid Filipino translation of the CADI.

Is anatomical failure following anterior vaginal repair associated with weak native vaginal tissues? A biomechanical and immunohistochemical study.

INTRODUCTION AND HYPOTHESIS: This study was performed to determine whether anatomical recurrence of cystocoele 1 year after anterior vaginal repair is related to biomechanical properties and/or the content of collagen in the vaginal wall and epithelial tissues. METHODS: In this prospective, observational study in a UK teaching hospital, we assessed women undergoing surgery for symptomatic anterior compartment prolapse. Outcome measures were anatomical recurrence, biomechanical strength and collagen content in vaginal tissues. In part one of the study, 42 women underwent biomechanical testing of full-thickness anterior vaginal wall tissue samples to determine the elastic moduli and yield stress. In part two, 59 women underwent immunohistochemical testing of anterior vaginal wall tissue samples to determine tissue content of procollagen I; collagen types I, III, V; and matrix metalloproteinases 1 and 2 (MMP-1 and 2). Results were then compared with anatomical outcome at 1 year postsurgery. RESULTS: Differences in yield strain in all outcome groups (optimal, satisfactory and unsatisfactory) were not statistically significant. Considerable variation was found in collagen type I in both satisfactory and unsatisfactory groups. There was no difference or correlation with procollagen, collagen types III and V, and MMP-1 and recurrence of pelvic organ prolapse (POP) between groups. There was a weak correlation between collagen type I and higher yield stress in both groups. CONCLUSIONS: Anatomical failure of anterior repair does not appear to be related to the biomechanical strength or collagen content of the anterior vaginal wall.

VEGF release is associated with reduced oxygen tensions in experimental inflammatory arthritis.

OBJECTIVE: The contribution of local VEGF production and subsequent angiogenesis within the synovial membrane to the propagation of arthritis is unclear. The relationship between synovial oxygenation and blood flow in the development of arthritic disease is unknown. We have therefore measured oxygen levels and perfusion rates in the synovial space in a murine model of arthritis. METHODS: Arthritis was induced in DBA/1 mice by immunisation with type II collagen. Oxygen and perfusion levels were measured polarographically using silver needle microelectrodes within the knee joints prior to and 10 days after the onset of arthritis. In addition, synovial cells were isolated from knee joints of naive, pre-arthritic and arthritic mice. RESULTS: Onset of arthritis was associated with a marked reduction in synovial oxygen tensions (pO2). The perfusion rates in naive and arthritic animals were not significantly different: in naive mice, the rate was 0.58 +/- 0.11 ml/min/g and in arthritic joints, 0.64 +/- 0.17 ml/min/g. Furthermore, synovial cells isolated from the knee joints of naive animals did not express mRNA for VEGF, but significant levels were detected in cells from non-arthritic mice immunised with collagen. The onset of arthritis was associated with expression of VEGF mRNA and protein, and correlated negatively with pO2 levels. CONCLUSION: These data demonstrate that decreases in intra-articular pO2 occur in established arthritic conditions and may be the stimulus for local VEGF production. However, perfusion was not increased in arthritic animals and vascular density was unaltered, suggesting that the neovascularisation associated with inflammatory arthritis, is insufficient to restore oxygen homeostasis in the joint.

Imaging erythrocytes under physiological conditions by atomic force microscopy.

Since its invention in the mid 1980s atomic force microscopy has revolutionised the way in which surfaces can be imaged. Close to atomic resolution has been achieved for some materials and numerous images of molecules on surfaces have been recorded. Atomic force microscopy has also been of benefit to biology where protein molecules on surfaces have been studied and even whole cells have been investigated. Here we report a study of red blood cells which have been imaged in a physiological medium. At high resolution, the underlying cytoskeleton of the blood cell has been resolved and flaws in the cytoskeleton structure may be observed. Comparison of the normal 'doughnut' shaped cells with swollen cells has been undertaken. Differences in both the global properties of the cells and in the local features in cytoskeleton structure have been observed.

The synovial lining: a paradigm for connective tissue research?

It is to be expected that the extensive researches of Professor Levick and his group on the exchange of water and solutes between synovial fluid and the microcirculation of the synovial lining will advance understanding of the nutrition and lubrication of the synovial joint and of the ways in which disturbances in these processes are involved in joint disease. What is less expected is the way in which this work has raised, and often definitively answered, questions that are pertinent to many other areas of physiology and biophysics.

Comparison of three solid phase supports for promoting three-dimensional growth and function of human liver cell lines.

An extracorporeal liver support system will require that liver cells maintain their normal differentiated function. This is more likely to be achieved utilizing a three-dimensional culture configuration rather than a simple monolayer culture. We present data on a human liver cell line attached and maintained on different three-dimensional supports, porous glass (Siran), silicon (Immobasil), and calcium-alginate beads. Albumin, fibrinogen, prothrombin, alpha1-acid glycoprotein and alpha1-antitrypsin secretions were measured. Proliferation was slower on each of the three-dimensional supports than on the monolayer culture. The protein secretion of all 5 proteins was highest in cells encapsulated in alginate; silicon beads supported greater protein secretion than glass. Cells on silicon or within alginate were rounded; those on glass grew in 2 configurations as flattened monolayers and as rounded colonies. Cells in alginate secreted as much protein as the whole liver (e.g., albumin, 14.88 g/10(12) cells/day compared to the whole liver, approximately 12 g/day). Three-dimensional culture of a human liver cell line leads to both proliferation and a high synthetic capacity, an important feature of cells suitable for an extracorporeal liver support system.

Growth factors for human fibroblasts in the solute remaining after clot formation.

Fibroblasts adhere to, and readily grow into, fibrin clots that form as a result of the cleavage of fibrinogen by thrombin. Subsequent fibroblast replication is believed to be stimulated by mitogens released by entrapped platelets, such as platelet-derived growth factor. We suggest that the supernatant remaining after the fibrinogen-thrombin reaction could stimulate fibroblast replication, even in the absence of other blood components. To examine this hypothesis we expressed liquid from a fibrin clot and measured its mitogenic activity on human lung fibroblasts, in serum-free conditions, using a colorimetric assay based on uptake and subsequent release of Methylene Blue. The clot supernatant caused a mitogenic response of 51 +/- 6% above control and was equivalent to about half that elicited by medium containing 10% newborn calf serum. On their own, both thrombin and fibrinopeptides A and B (small molecular weight cleavage products released from fibrinogen) showed some mitogenic activity, but there was also activity in higher molecular weight cleavage products, suggesting the presence of uncharacterized mitogens. It is proposed that these agents may play important roles in wound healing and diseases associated with vascular leakage and fibrosis, by stimulating fibroblast replication.

Unilateral lung disease detected by radioisotopic scanning in children thought to have asthma.

The clinical courses of three children are described. They were initially thought to have troublesome asthma alone or in association with other diseases. The children had radioactive gas lung scans using 13N for studies of ventilation and perfusion which in each case revealed one entirely healthy lung and one disordered lung. The technique of 13N gamma scanning is described and its clinical value in such patients is discussed.