Interleukin 4 and interferon-gamma expression of the dermal infiltrate in patients with erythroderma and mycosis fungoides. An immuno-histochemical study

BACKGROUND: Erythroderma, or generalized erythema of the skin, may result from different causes. At present it is unclear whether the underlying patho-mechanisms that lead to erythroderma are identical or different depending on the original disease. The aim of this study was to investigate the dermal cytokine profile in different types of erythroderma and mycosis fungoides. METHODS: Snap-frozen skin biopsy specimens from 33 patients with erythroderma were studied. Thirteen had idiopathic erythroderma, 7 erythrodermic atopic dermatitis, 5 Sézary syndrome and 8 had erythroderma from miscellaneous causes. We also studied 6 patients with mycosis fungoides (5 plaques and 1 tumor) and 5 healthy non-atopic volunteers. The biopsies were immunohistochemically stained for interleukin 4 (IL-4) and interferon gamma (IFN-gamma). All positive cells for IL-4 and IFN-gamma in the dermis were counted and the number of positive cells was calculated per mm2. IL-4/IFN-gamma ratio was calculated for each biopsy. RESULTS: The patients with idiopathic erythroderma, atopic dermatitis and miscellaneous erythroderma, all showed more IFN-gamma-positive cells than IL-4-positive cells in the dermis. The median IL-4/ IFN-gamma ratio for these three groups was 0.6, 0.9 and 0.45, respectively. These differences were not statistically significant. All patients with Sézary syndrome however, showed more IL-4-positive cells than IFN-gamma-positive cells. The median IL-4/IFN-gamma ratio was 1.8, which is significantly higher than in the other groups p<0.05). In mycosis fungoides roughly the same number of cells expressed IL-4 and IFN-gamma. The median IL-4/IFN-gamma ratio was 1.0, which is significantly lower than in Sézary syndrome (p<0.05). CONCLUSIONS: The dermal infiltrate in patients with Sezary syndrome mainly shows a T-helper 2 (Th2) cytokine profile, this in contrast to T-helper 1 (Th1) cytokine profile in benign reactive erythroderma. This indicates that although a relative uniform clinical picture of erythroderma is obvious, a different patho-mechanisms may be underlying.     

Expression of VCAM-1, ICAM-1, E-selectin, and P-selectin on endothelium in situ in patients with erythroderma, mycosis fungoides and atopic dermatitis

BACKGROUND: Erythroderma may result from different causes. At present it is unclear whether the patho-mechanisms that lead to these different types of erythroderma are identical or different. Adhesion molecules and their ligands play a major role in endothelial-leukocyte interactions, which affect the binding, transmigration and infiltration of lymphocytes and mononuclear cells during inflammation, injury, or immunological stimulation. The aim of this study was to investigate the adhesion molecule expression on endothelial cells in erythroderma in situ. METHODS: Snap-frozen skin biopsy specimens from 23 patients with erythroderma were studied. Eight had idiopathic erythroderma, 5 erythrodermic atopic dermatitis, 4 Sézary syndrome and 6 had erythroderma from miscellaneous causes. As a control we studied skin specimens from 10 patients with mycosis fungoides, 5 patients with atopic dermatitis and 5 healthy non-atopic volunteers. To determine adhesion molecule expression on endothelial cells in situ, sections were immuno-histochemically double stained with biotinylated Ulex Europaeus agglutinin 1 as a pan-endothelial cell marker, and for the adhesion molecules VCAM-1, ICAM-1, E-, and P-selectin. All double- and single-stained blood vessels in the dermis were counted. RESULTS: Mean endothelial expression in erythroderma was as follows: VCAM-1 51.4%, ICAM-1 70.1%, E-selectin 43.5%, and P-selectin 52.6%. There was no statistical difference between different groups of erythroderma. Mean expression of all adhesion molecules tested, was in Sézary syndrome higher than in mycosis fungoides albeit not significant. In erythrodermic atopic dermatitis only VCAM-1 expression was significantly higher than in lesional skin of atopic dermatitis. No differences were observed in expression of the other three adhesion molecules. CONCLUSIONS: There is no difference regarding adhesion molecule expression on endothelial cells between different types of erythroderma.     

Does root surface conditioning with citric acid delay healing?

Abstract Effects of topical citric acid application on tissue maturation was studied in standardized periodontal defects in 6 beagle dogs. Following elevation of facial mucoperiosteal flaps, fenestration defects, 3 mm in diameter, were made through the cortical bone and recessed 0.5 mm into the dentin of maxillary canines. 1 defect in each dog was conditioned with a saturated solution of citric acid for 3 min and then rinsed with saline. Control defects in contralateral teeth were treated with saline only for the same length of time. The defects were covered with an expanded polytetrafluoroethylene membrane and the flaps re-positioned and sutured. 14 days postsurgery, healing appeared more advanced along the defect walls and floor than in the center of the defect in all instances. Histometrically, citric acid-conditioned defects exhibited a higher density of collagen fibers along the defect walls and floor and adjacent to the barrier membrane as well as more advanced resolution of the residual blood clot than the surgical controls. Differences in fibroblast density within specimen pairs were non-significant. All control defects but none of the acid-conditioned defects showed an artifactual split between the dentin walls and the granulation tissue. This study failed to support the contention that topical application of citric acid to root surfaces may delay healing following periodontal surgery.     

Intracanal placement of Ca(OH)2: a comparison of techniques.

Ten extracted human maxillary first molars were selected with a variety of root curvatures. The distofacial roots were resected and the mesiofacial canals were instrumented to a size #25 K file. Three techniques were used to introduce Ca(OH)2 paste into the instrumented canals. These techniques were evaluated for their ability to carry the Ca(OH)2 to working length and also to produce a dense fill. The Lentulo spiral was most effective in carrying the paste to working length. The Lentulo spiral also produced the highest quality fill. The Calasept injection system followed by a #25 finger plugger was the second most effective technique. Counterclockwise rotation of a #25 K file was the least effective of the techniques tested.     

ERBB2 amplification in breast cancer with a high rate of proliferation.

The ERBB2 proto-oncogene was studied in 539 invasive primary breast tumors and was found amplified (2- greater than 30 copies) in 19%. Amplification was correlated to most known risk factors, including; large tumor size, lymph node positivity and many tumor involved nodes, advanced stage, low patient age (less than 40 years), non-diploidy and hypertetraploidy, and most significantly (P less than 0.00001) to the absence of steroid receptors and to a high rate of proliferation (flow cytometric determined S phase fraction). ERBB2 amplification was strongly associated (P less than 0.0001) with early recurrence and death in breast cancer among node-positive patients. This connection did not, however, remain in multivariate analyses. No correlations to clinical outcome were seen among node-negative patients. Similarly, non-diploid, but not diploid, amplified tumors were particularly aggressive. Furthermore, ERBB2 amplification was associated with a high rate of proliferation and poor prognosis in steroid receptor positive, but not receptor negative tumors. In progesterone receptor positive breast cancer, amplification was an independent and with node status equally powerful (P less than 0.0001) predictor of poor survival. It is concluded that ERBB2 activity is related to an increased tumor growth rate but not directly to metastasizing ability. Its clinical relevance as a prognostic factor may be in selecting a high risk subgroup of breast cancer, in general considered as being of good prognosis.     

Serum osteoprotegerin and its relationship with bone mineral density and markers of bone turnover

Introduction: The purpose of this study was to compare age-related differences in osteoprotegerin (OPG) in relationship with BMD and the serum bone markers osteocalcin (OC), collagen crosslinks (CTX), and tartrate-resistant acid phosphatase 5b (TRACP-5b). Methods: Data were derived from a cross-sectional study on bone health in a random sample of community-dwelling adults aged 30 to 85 years in the Reykjavik area in Iceland. All subjects had whole body, hip, and lumbar spine BMD measured (by DXA), gave blood samples, and answered a thorough questionnaire on medications and medical history. We assessed relationships using the Spearman correlation coefficient, partial correlation, and multivariable linear regression. Men and women were analyzed separately. Results: Of 2,310 subjects invited over 2 years, 1,630 participated. After excluding individuals with diseases and medications affecting bone metabolism, 517 women (age 56.1 ± 16.9 years) and 491 men (age 58.7 ± 14.9 years) remained for analysis. OPG increased steadily with age in both genders without a gender difference. In women, BMD at all sites declined steadily after age 50. In men, BMD remained relatively stable until age 70, after which it declined significantly. After controlling for age, BMI, and other confounding variables, OPG showed only a borderline positive relationship with whole body BMD in men (P=0.10), but the relationship was nonsignificant in women. In multivariable models, OPG was inversely related to TRACP-5b (P=0.002) and positively with OC (P=0.007), the OC/TRACP-5b (P=0.001) and OC/CTX (P=0.02) ratios in women. Among men, multivariable models showed a positive association between OPG and OC (P=0.05) and OC/TRACP-5b (P<0.009). Conclusions: We conclude that serum OPG levels are associated with a profile of bone turnover markers favoring bone formation, suggesting that OPG may be protective against age-related bone loss. Longitudinal studies are needed to address that issue.     

Use of X-rays in family practice A multicentre study

Practising physicians, faced with pressure to control healthcare costs, are increasingly being asked to incorporate considerationsof cost into their decisions regarding the care they offer theirpatients. Accordingly, it is of importance to know how the moneyis spent. The use and cost of X-rays in family practice, andwhat factors influence it, is not well known. The aim of thisstudy is to analyse the use and the cost of X-ray requests infamily practice. A prospective practice study from 16 Icelandiccommunity health centres (HC) with computerised contact dataand their target populations, 12 rural and four urban, was carriedout. The X-ray requests, numbers, types and cost were analysed.Patient and practice characteristics were used to assess variationin X-ray practices. A total of 5173 X-ray requests were recorded,which comprised 3.2% of all office visits. The mean number ofX-ray requests was 24.7 and 14.7/1000 contacts in rural andurban HCs respectively, and 123.1/1000 inhabitants in ruralHCs. The X-ray request rate per individual increased with age,but per contact it was highest among young males. Extremityand chest X-rays were the most common requests. For every 1000individuals added to a practice population, the likelihood ofhaving an X-ray requested decreased by 18%. The use of X-rayexaminations in family practices represents approximately 17%of all ambulatory X-ray use in Iceland. The calculated costof X-rays requested in this study was $6157/1000 inhabitantsper year as of October 1993. The rate of X-rays requested differsgreatly among doctors, which indicates potential for savingsin the health care system, through radiology guidelines. Thisstudy indicates that the rate and the cost of X-rays are lowin general practice in Iceland. X-ray facilities should be adequateand accessible to each practice. The results of this study areuseful in quality control, organisation and in the analysisof cost in the health care system. Training of family doctorsneeds to take this information into account.     

Support for involvement of the AHI1 locus in schizophrenia

Recently, markers in the Abelson Helper Integration Site 1 (AHI1) region were shown to be associated with schizophrenia in a family sample of Israeli-Arabs. Here, we report a study evaluating the relevance of the AHI1 region to schizophrenia in an Icelandic sample. Seven markers shown to confer risk in the previous report were typed in 608 patients diagnosed with broad schizophrenia and 1,504 controls. Odds ratios for the overtransmitted alleles in the Israeli-Arab families ranged from 1.15 to 1.29 in the Icelandic sample. After Bonferroni correction for the seven markers tested, two markers were significantly associated with schizophrenia. Thus, our results are in general agreement with the previous report, with the strongest association signal observed in a region upstream of the AHI1 gene.     

Patient-reported outcomes helped predict survival in multiple myeloma using partial least squares analysis

OBJECTIVE: The prognostic value of Patient-Reported Outcomes (PRO) in predicting mortality during treatment of multiple myeloma (MM) patients was assessed using partial least square (PLS) regression, a statistical method that is well-adapted for highly correlated data. STUDY DESIGN AND SETTING: Four PRO measures, The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, the EORTC QLQ-MY24, the FACIT-Fatigue scale, and the FACT/GOG-Ntx scale, were administered during a trial designed to evaluate the efficacy and safety of bortezomib (VELCADE 1.3mg/m(2)) in MM patients (N=202). Clinical and PRO data were analyzed for predictive value by univariate and multivariate logistic regression methods and then by PLS regression. RESULTS: Fifteen baseline PRO parameters were significant in predicting mortality during treatment when univariate logistic regression was used. In contrast, only two variables were retained in the multivariate analysis, as correlated variables were excluded from the model. Using PLS regression, 14 of the 21 PRO predictors were significant in predicting mortality. Clinical and PRO data used together increased the predictive power of all models compared to clinical data alone. CONCLUSION: The prognostic value of PRO was established and was more informative using PLS regression. PLS regression may therefore be a valuable method for analyzing PRO data.